Lower respiratory infections (LRI), upper respiratory infections (URI), and nutritional deficiency (ND) in under-5 children from low-middle-income countries has been at a high level for decades, despite efforts that have been realized in some countries. The study used data extracted from the global burden of diseases (GBD) to analyze the trends behavior between 1990 and 2019, and evaluate their association with maternal factors. Between 1990 and 2019, the incidence of LRI decreased between 1.2 percent and 1.3 percent (1.2-1.3%) in different female age groups, and by nearly 1 to 1.3% in those of the male gender. The incidence of URI did not decrease (0.0%) in any of their age groups. ND incidence declined around 0.7 to 4.9% in the under-5 children. LRI declined mostly in the female age groups (1.2 to 1.3%), while ND decreased more in the male gender (0.9 to 4.9%). Maternal risk factors were strongly associated to the incidence of the three conditions with over 90 percent. Maternal prevalence of HIV/AIDS and tuberculosis positively impacted the incidence of LRI, URI, and ND in Chadian under-5 children. Although the incidence of LRI and ND declined, URI incidence remained steady between 1990 and 2019 in Chadian under-5 children. To improve the health and provide a healthy growth of under-5 children, the maternal prevalence of HIV/AIDS and tuberculosis infection should be strongly addressed for a prompt accomplishment of the sustainable development goals.

ADHD is a neurodevelopmental disorder that children and also adults can develop. A complex interplay of genetic and environmental factors may underlie interindividual variability in ADHD and potentially related aggressive behavior. Using high-resolution molecular biology techniques, we investigated the impact of some MAOA and SLC6A4 variations on ADHD and aggressive behavior in a group of 80 Italian children with ADHD and in 80 healthy controls.We found that homozygous genotypes of MAOA rs6323 and rs1137070 were associated with an increased risk of ADHD (p=0.02 and p=0.03, respectively), instead the heterozygous genotypes (GT of rs6323 and CT of rs1137030) (p=0.0002 and p=0.0006) were strongly linked to a lower risk of developing this disorder. In patients with aggressive behavior, we highligted only a weak negative association of both MAOA polymorphisms (heterozygous genotypes) with aggressiveness then, suggesting that these genotypes maybe protective towards specific changes in behavior (p=0.05). Interestingly, an increase of the GG genotype of rs6323 (p=0.01) and a decrease of GT genotype (p=0.0005) was also found in patients without aggressive behavior compared with controls. Regarding 5HTT gene genotyping, no allele and genotype differences have been detected among patients and controls. Our work shows that defining a genetic profile of ADHD may help to early detect those patients who are more vulnerable to ADHD and/or antisocial and aggressive behavior and to design precision-targeted therapies.

Studies shows that, normal to high serum 25(OH)D status appears to have some beneficial influence on the incidence and severity of some, though not all, types of infections. However, studies with vitamin D supplementation on young children produced conflicting results with respect to the level of vitamin D deficiency among common medical illnesses among children. Method: A systematic review of literatures from PubMed, CINAHL, Web of science, global health and Google scholar electronic databases was conducted to assess the pooled prevalence of vitamin D deficiency among healthy and sick children in sub-Saharan Africa. The data was extracted by two authors independently using standard data extraction format and STATA Version 14 was used for analysis. The heterogeneity of the studies was assessed by using I2 test. A random-effects model was used to estimate the pooled prevalence among both healthy and sick children. Presence of publication bias was checked using Funnel plot and Egger's test. Result: A total of 1212 articles were identified by the total search of utilized data bases of which 13 papers fulfilled the inclusion criteria and accessible with full document. The meta-analysis revealed that the pooled prevalence of vitamin D deficiency among healthy children in this study was 50.06% (95%CI 33.46%, 66.67%) with mean serum vitamin D level of 41.06 nm/L (CI range from 23.82nm/L to 58.31nm/L). The pooled prevalence among the sick children was 39.36% (CI 20.57%, 57.96%) with 66.96nm/L (95% CI 54.81nm/L, 79.11nm/L) mean concentration of vitamin D. Comparing the two level of the pooled prevalence, the prevalence among the healthy children was significantly higher compared to those who have common medical illnesses and the pooled mean concentration among the sick was much higher than the mean concentration among healthy children. Conclusion: The level of pooled prevalence among both group of population was significantly of public health concern and the prevalence among the healthy children was much higher among the sick children implying the need for reconsideration of available recommendations for the prevention of vitamin D deficiency

Introduction: Child stunting remains a public health concern. It is characterized as poor cognitive and physical development in children due to inadequate nutrition during the first 1,000 days of life. Across South Asia, Pakistan has the second-highest prevalence of stunting. This study has assessed the most recent nationally representative data, the National Nutrition Survey (NNS) 2018, to identify the stunting prevalence and determinants among Pakistani children under five. Methods: The NNS 2018, a cross-sectional household-level survey, was used to conduct a secondary analysis. Data on malnutrition, dietary practices, and food insecurity was used to identify the prevalence of stunting among children under five years by demographic, socioeconomic, and geographic characteristics. The prevalence of stunting was calculated using the World Health Organization (WHO) height for age z-score references. Univariate and multivariable logistic regressions were conducted to identify factors associated with child stunting. Results: Analysis showed that out % of 52,602 children under five, 40.0% were found stunted. Male children living in rural areas were more susceptible to stunting. Furthermore, stunting was more prevalent among children whose mothers had no education, were between 20 and 34, and were employed. In the multivariable logistic regression, male children (AOR=1.08, 95% CI[1.04-1.14], P<0.001) from rural areas (AOR=1.07, 95% CI [1.01-1.14], P=0.014), with the presence of diarrhea in the last two weeks (AOR=1.15, 95% CI [1.06-1.25], P<0.001), with mothers who have no education (AOR=1.57, 95% CI [1.42-1.73], P<0.001) or lower levels of education (Primary: AOR=1.35, 95% CI [1.21-1.51], P<0.001; Middle: AOR=1.29, 95% CI [1.15-1.45], P<0.001) had higher odds of stunting. Younger children aged <6 months (AOR=0.53, 95% CI [0.48-0.58], P<0.001) and 6-23 months (AOR=0.89, 95% CI [0.84-0.94], P<0.001), with mothers aged 35-49 years (AOR=0.78, 95% CI [0.66-0.92], P=0.003) had lower odds of stunting. At the household level, the odds of child stunting were higher in the poorest households (AOR=1.64, 95% CI [1.46-1.83], P<0.001), with ≥7 members (AOR=1.09, 95% CI [1.04-1.15], P<0.001), with no access to improved sanitation facilities (AOR=1.14, 95% CI [1.06-1.22], P<0.001) and experiencing severe food insecurity (AOR=1.07, 95% CI [1.01-1.14], P=0.02). Conclusion: Child stunting in Pakistan is strongly associated with various factors, including gender, age, diarrhea, residence, maternal age and education, household size, food and wealth status, and access to sanitation. To address this, interventions must be introduced to make locally available food and nutritious supplements more affordable, improve access to safe water and sanitation, and promote female education for long-term reduction in stunting rates.

Background- In India, 26 million children are born every year. These Children (0-6 years) comprise 13% of the country's population. Undernutrition is fallout of malnutrition, malabsorption, and nutritional imbalance which causes problem of underweight in children. It can affect child’s brain development and other developmental milestones. Methods- We used anonymized, publicly available secondary data from the India National Family Health Survey (NFHS-5). Descriptive statistical analysis, correlation coefficient analysis, and regression analysis of the data have been done. Results- Multiple linear regression for independent variables, operational AWCs (%) and women with Internet access (%), and dependent variable underweight children per state (%) developed the model, Underweight children (%) = 37.1607 + 0.5659. operational AWCs (%) – 0.2907. women with Internet Access (%). It shows Ꞵ0= 37.1607, Ꞵ1= 0.5659, and Ꞵ2= -0.2907 as well as R squared value as 0.5709. This shows independent variables have a significant influence on the number of underweight children in the state. Results of the Pearson correlation indicated that there is a significant large positive relationship between operational AWCs (%) and the percentage of underweight children in the state, (r(34) = .58, p < .001). Whereas there is a significant large negative relationship between Internet access to women (%) and the percentage of underweight children in the state, (r(34) = .733/-0.733, p < .001). Conclusion- The study clearly shows that when compared, community daycare centers (AWCs) have a limited role in the child's nutrition, but Internet access to the mothers can be a determinant of the child's nutrition. The internet access to women can help to reduce the number of underweight children under five years and improve overall maternal and child health as well as public health.

This study aimed to assess knowledge and practice of caregivers and its relationship to the disease and nutritional status of children under five years of age in rural areas of Sylhet, Bangladesh. A total of 110 households having 6 to 59 months aged children was selected by simple random method from ten rural communities of three Upazila of Sylhet during September 2019 to February 2020. Descriptive statistics were used to assess the WASH knowledge & practice and multivariate chi-square analyses were performed to assess associations among diseases & nutritional status with WASH following a structured questionnaire. The study found a significant association of WASH with childhood disease and nutritional status, and 65% of children were found to be in a diseased state and 35% of children were found to be in a disease-free state within the last six months. The findings sketched that mother with poor wash knowledge and practice was at greater risk for disease outbreaks, disease frequency and duration. The highest incidence of diarrhea was 17% in children aged 12 to 23 months. Significant effect of WASH was also found in children nutrition status, that was reflected in the ratio of stunted, underweight and wasted children. Integrated convergent work focusing on the provision of clean water within the household, stop open defecation, promotion of hand washing, behavior change and poverty alleviation is needed to improve the situation. Health, nutrition and livelihood programs should be uninterrupted, and mothers or caregivers should be encouraged to participate in these programs.

This survey of research literature is an overview of the current state of science addressing DSM-5 diagnostic criteria as it relates to identifying Autism Spectrum Disorder (ASD) in young children. Selected sources are of high quality and have been published since 2020 in peer-reviewed journals relevant to children’s health. The narrative is organized from the earliest to the most recent publications and is divided into sections around categories and themes that highlight the main arguments, findings, and controversies identified by researchers. There are indications in the literature that while ASD can be identified and differentiated from other developmental disorders in young children, doing so requires that clinicians who have relied on the DSM-5 should also use multiple measures, including other formalized screening tools as assessments that gather observational input from parents and caregivers, as well as findings from physical examinations, laboratory investigations, and magnetic resonance imagining (MRI). This high level of corroboration points to an emerging diagnosis paradigm through which transdiagnostic approaches to early diagnosis and intervention may exist.

The 5-hydroxymethylfurfural (HMF) is a six-carbon heterocyclic organic compound with two substituents an aldehyde group and an alcohol group. It is formed from saccharides as a result of two reactions: the Maillard reaction and the caramelization of saccharides. It has both a negative and a positive effect on the human body, which makes it, even more, an attractive research object. The objective of the study was to determine HMF content in honey samples available on the Polish market using three varied methods and compare the results obtained. The methodology used included: two spectrophotometric methods (by White and Winkler) and the HMF determination method based on the LC-MS/MS technique developed uniquely for this study. The determined HMF content in all tested honey samples did not exceed the applicable standard. All results are within the scope of the European Council Directive 2001/110/EC of 20 December 2001, i.e. they do not exceed HMF content in honey, which is 40 mg/kg.

Background/Purpose: Over the last two decades, malaria has remained a major worldwide public health concern, especially in the developing countries leading to high morbidity and mortality among children. Nigeria is the world most burdened malaria endemic nation, contributing more than a quarter of global malaria cases. This study determined the prevalence of malaria among children 6-59 months in Nigeria, and the effects of individual and contextual factors. Methods: The study utilized data from 2018 Nigeria Demographic and Health Survey (NDHS) involving a weighted sample size of 10,185 children who were tested for malaria using rapid diagnostic test (RDT). Given the hierarchical structure of the data set, such that children at level-1 are nested in community at level-2, and nested in states and Federal Capital Territory (FCT) at level-3, multilevel mixed effect logistic regression models were used for the analysis. Results: The proportion of children 6-59 months of age in Nigeria that had malaria fever positive as assessed by RDTs was 35.5% (3,418/10185), (CI: 33.9-37.1). Kebbi State had the highest proportion of children 6-59 months who were malaria positive, 77.6%, (CI: 70.2-83.5), followed by Katsina State, 55.5%, (CI: 47.7-63.1). The Federal Capital Territory (FCT), Abuja had the proportion of 29.6%, (CI: 21.6-39.0), malaria positive children of 6-59 months of age. Children between the age of 48 and 59 months were 2.68 times more likely to have malaria fever than children 6-11 months of age (AOR=2.68, 95% CI: 2.03-3.54). Also, children from the rural area (AOR= 2.12, 95% CI: 1.75-2.57), were more likely to suffer from malaria infection compare with children from urban area. Conclusion: The study identified some individual and contextual predictors of malaria among children in Nigeria. These factors are areas that need to be considered for policy designs and implementations toward control and total elimination of malaria-related morbidity and mortality among children in Nigeria.

Autism has been described as a gastrointestinal and neurological condition that is represented by impairments in language and social situations. Recently reported increases in the occurrence of Autism Spectrum Disorder (ASD) have resulted in increased research into the environmental differences between areas with a high occurrence, as in the “Western” diet populations, and a more locally derived diet population, wherein the rate appears to be significantly less. Thirty autistic children (USA) ages 6 to 21, were sampled at three different intervals: prior to any intervention, post-xylitol intervention, and post-probiotic intervention. The sampling consisted of buccal swabs for MITOSWAB testing, and saliva for metatranscriptomics to determine the entire range of microorganisms and the metabolome. In addition, a “Blue Zone” subject component that included 30 Colombian children, ages 6-16, and who were healthy and within normal behavior standards, also had buccal swabbing and salivary sampling performed for comparison along with 30 healthy (no history medications, illnesses, or behavior issues) USA children matched for age and gender. Saliva samples were analyzed metatranscriptomically and artificial intelligence was utilized to discern important differences in the microbiome that included bacteria, archaea, fungi, and viruses, and microbial functions. Significant differences were noted, and seen in the temporal data, demonstrating shifts that may have been precipitated by the interventions, with both the probiotics and the polyols. Particular bacterial strains were significantly more prevalent in the autism subject group including a strain that reduces neurotransmitters by enzymatic degradation. This provided supporting evidence to the hypothesis that the occurrence of autism may also be influenced by low Gamma Amino Butyric Acid (GABA) levels during development. Also, of interest was the un-expected finding that verbal skills dramatically increased in 6 of the 30 ASD subjects following xylitol supplementation.

Reducing under-five mortality is a key indicator of a country's overall development, yet in Angola, understanding the factors contributing to hospital deaths in this vulnerable demographic remains incomplete despite improvements in healthcare infrastructure and public health policies. With one of the highest under-five mortality rates in Sub-Saharan Africa, Angola grapples with significant challenges, including malaria, malnutrition, pneumonia, neonatal conditions, and intestinal infectious diseases, as leading causes of death among children. This study aimed to identify factors associated with these hospital deaths in children aged 28 days to five years admitted to DBPH in Luanda between May 2022 and June 2023. Utilizing a hospital-based case-control design, a total of 1020 children were studied, with 340 cases of hospital deaths. Notably, distal and intermediate determinants emerged as primary predictors of hospital mortality, revealing significant associations with maternal education status, maternal alcohol consumption during pregnancy, short hospital stays (≤24h), poor nutritional status, short interbirth intervals, maternal age ≤19 years, and maternal age ≥35 years. These findings underscore the preventable nature of most under-five hospital deaths and emphasize the urgent need to address social inequities and enhance the quality of primary healthcare services to effectively mitigate child mortality.

Background: Low-income families often depend on fuels such as wood, coal, and animal dung for cooking. Such solid fuels are highly polluting and are a primary source of indoor air pollutants (IAP). We examined the association between solid fuel use (SFU) and acute respiratory infection (ARI) among under-five children in Afghanistan and the extent to which this association varies by socioeconomic status (SES) and gender. Materials and Methods: This is a cross-sectional study based on de-identified data from Afghanistan’s first standard Demographic and Health Survey conducted in 2015. The sample consists of ever-married mothers with under-five children in the household (n=27,565). We used mixed-effect Poisson regression models with robust error variance accounting for clustering to examine the associations between SFU and ARI among under-five children after adjusting for potential confounders. We also investigated potential effect modification by SES and sex. Additional analyses were conducted using an augmented measure of the exposure to IAP accounting for both SFU and the location of cooking/kitchen (High Exposure, Moderate, and No Exposure). Results: Around 70% of households reported SFU, whereas the prevalence of ARI was 17.6%. The prevalence of ARI was higher in children living in households with SFU compared to children living in households with no SFU (adjusted prevalence ratio [aPR]= 1.10; 95%CI: 0.98, 1.23). We did not observe any effect modification by SES or child sex. When using the augmented measure of exposure incorporating the kitchen’s location, children highly exposed to IAP had a higher prevalence of ARI compared to unexposed children (aPR 1.17; 95% CI: 1.03, 1.32). SES modified this association with the strongest associations observed among children from the middle wealth quintile. Conclusion: The findings have significant policy implications and suggest that ARI risk in children may be reduced by ensuring clean cookstove as well as clean fuels and acting on the socio-environmental pathways.

Background/Purpose: Multimorbidity of malaria, anaemia, and malnutrition (MAMM) is a condition in which an individual cohabits with two or more of these health outcomes and is becoming an emergent public health concern in sub-Saharan African countries. The independent associations of a child’s demographic variables and socioeconomic disparities with a child’s health outcomes have been established in literature. However, the effects of the intersection of these factors on MAMM, while accounting for other covariates have not been studied. Therefore, this study aimed to determine how children’s sex, age and socioeconomic status interact to explain the variations in MAMM among children aged 6-59 months in Nigeria. Methods: Data from the 2018 Nigeria Demographic and Health Survey and the 2018 National Human Development Report (NHDR) were used. The study includes weighted samples of 10,184 children aged 6-59 months in Nigeria. A three-level multilevel mixed effect ordinal logistic regression model such that individual characteristics at level 1 are nested in communities at level 2 and nested in states at level 3 was used. Subsequently, predictive probability charts and average adjusted probability tables were used to interpret the intersectional effects. Five models were created in this scenario. Model 1 is the interaction between the child's sex and wealth status; model 2, child's sex and age; model 3 is between child's age and wealth status; model 4 has the three 2-way interactions of child's sex, age, and household wealth status, and model 5 includes model 4 and the 3-way interactions between a child's sex, age, and wealth quintiles. Results: The prevalence of children with ‘none of the three diseases’ outcomes was 17.3% (1767/10,184), while, 34.4% (3499/10,184) had ‘only one of the diseases’, and 48.3% (4,918/10,184) cohabit with ‘two or more’ of MAMM. However, in the multivariate analyses, model 3 was the best fit compared with other models, so, that the two-way interaction effects of a child's age and wealth status are significant predictors in the model. Children aged 36-47 months living in the poorest households have the probability of 0.11, 0.18, and 0.32 of contracting MAMM above the probability of children of the same age and live in the middle, more prosperous and richest households, respectively, while all other covariates are held constant. Thus, the variation in MAMM over a child's age differs depending on the household wealth quintile. In other words, as the children grow older, variations in MAMM become more evident between the rich and the poor household. Conclusion: Therefore, it is recommended that policies that are geared toward economic redistribution will help bridged the disparities observed in multiple diseases among children aged 6-59 months in Nigeria

Background/Purpose: In recent times, Sub-Sahara Africa (SSA) had been rated by the World Health Organization, (WHO), as the most malaria endemic region in the world. Evidence synthesis of the risk factors associated with malaria among children aged under-five in SSA is urgently needed. This would help to inform decisions that policy makers and executors in the region need to make for the effective distribution of scare palliative resources to curb the spread of the illness. This scoping review is aimed to identify studies that have used multivariate classical regression analysis to determine risk factors associated with malaria among children under-five years old in SSA. Methods/Design: The search terms followed PICOTS, (Population, Intervention, Comparator, Outcome, Timing, Setting), and were used in searching through the following databases: PubMed, MEDLINE, Web of Science, Cumulative Index of Nursing and Allied Health Literature (CINAHL), Scopus, and MeasureDHS. The databases were searched for published articles from January 1990 to December 2020. Results: Among the 1154 studies identified, only thirteen (13) studies met the study’s inclusion/exclusion criteria. Narrative syntheses were performed on the selected papers to synchronise the various risk factors identified. Factors ranging from child-related, (age, birth order and use of bed net), parental/household-related, (maternal age and education status, household wealth index) and community-related variables, (community wealth status, free bed net distribution), were some of the identified significant risk factors. Conclusion: It is timely to have a synthesis of risk factors that influence the malaria status of children under-five in SSA. The outcome of the review will increase the knowledge of the epidemiology of morbidity that will form the basis for designing efficient and cost-effective distribution of palliatives and controls of malaria in SSA.

This is a SARS-CoV-2 seroepidemiological study in pediatric population(0-16 years) during BA.5 Omicron predominance period in Athens metropolitan area. Serum samples were tested for SARS-CoV-2 nucleocapsid antibodies(Abs-N), representing natural infection during three sub-periods of BA.5 predominance: 01/05/2022-31/08/2022(period A), 01/09/2022-31/12/2022(period B) and July 2023(period C) and epidemiological data were collected. Additionally in period C Abs-N seronegative samples were tested for SARS-CoV-2 spike antibodies(Abs-S). A total of 878 children were tested (males:51.3%) with median age(IQR): 108(36-156) months and seropositivity during the 3 subperiods was: A:292/417(70%), B:288/356(80.9%), C:89/105(84.8%), P-value<0.001. SARS-CoV-2 seropositivity increased for from period A to C for 0-1-year (P-value: 0.044), 1-4 years (P-value: 0.028) and 6-12 years children (P-value: 0.003). Children 6-12y had the highest seroposi-tivity rates in all subperiods (A: 77.3%, B: 91.4% and C: 95.8%). A significant correlation of monthly SARS-CoV-2 median antibody titers with monthly seropositivity rates was detected (rs:0.812, P-value:0.008). During period C, an additional 12/105 (11.4%) Abs-S seropositive and Abs-N ser-onegative samples were detected and total seropositivity was estimated at 96.2% (101/105). The increased SARS-CoV-2 seropositivity detected in current seroepidemiology study illustrates a high exposure rate during BA.5 predominance period. These data could guide public health decisions regarding immunization strategies and protection measures.

(1) Background: The aim of study was to investigate the salt consumption by children and adolescents from the Silesian Province (Poland), taking into account the region’s dietary traditions and number of years of school education. (2) Methods : 300 students aged 10–18 from different types of schools, were enrolled in the study and divided into groups in terms of: school, sex, the state of nutrition. The survey questionnaire about dietary habits, including the frequency and serving size with respect to 12 salty products was used. On the basis of the frequency and the amount of consumed products, as well as the data on salt content, the amount of total daily intake of salt was estimated.; (3) Results: The mean daily intake of salt by children and adolescents was 1.083 g ( 0.433 g of sodium); children aged 10–12 consumed the highest amount of salt (1.296 g/day) compared to pupils aged 13–15 (1.131 g of sodium) and adolescents aged 16–18 (0.863 g/day); (4) Conclusions: With age, as a result of various factors, the consumption of salt declines. The parents impact and the familial socio-environmental factors begin to wane, and other factors start to have influence, e.g. school education of healthy lifestyle, health behavior of peers.

This study investigates the therapeutic potential of new compound, potassium 2-[2-(2-oxo-4-phenylpyrrolidin-1-yl) acetamido]ethanesulfonate (Compound I), in depression. Willner's chronic unpredictable mild stress model of depression in 48 male Wistar rats was used a depression model. The rats were randomized into four groups, including an intact group, a Compound I group, a Fluoxetine group, and a control group receiving saline. Behavioral tests, such as the Porsolt forced swim test, hole-board test, elevated plus maze test, and light-dark box, were used to assess the animals' conditions. Our results demonstrated that Compound I effectively reduced the immobilization time of rats in the forced swim test, increased orientation and exploratory behavior, and decreased the latency period of going into the dark compartment compared to the control group. Hippocampal and striatal serotonin concentrations were increased in the Compound I group, and the compound also reduced the level of corticosterone in the blood plasma of rats compared to intact animals. These results suggest that Compound I has a reliable antidepressant activity, comparable to that of the reference antidepressant Fluoxetine.

Background and Objectives: Acute lung injury (ALI) is an inflammatory response in the lung caused by bacteria, viruses, trauma and other factors that results in lack of alveolar surfactant and subsequently respiratory distress. Endothelial-to-mesenchymal transition (EndoMT) is closely related to ALI-induced pulmonary fibrosis development and progression. This study examined the effect of milk fat globulin factor 8 (MFGE8) knockdown and overexpression on lipopolysaccharide (LPS)-induced EndoMT. Methods: Total MFGE8 activity in patients with acute respiratory distress syndrome (ARDS) and healthy volunteers was assessed using a colorimetric kit. In vitro, cell morphology was observed by microscopy, and invasion and migration were tested by Transwell and scratch assays. Specific siRNAs were transfected into HLMECs to downregulate MFGE8, and CD31 and α-SMA protein expression was detected by fluorescence microscopy and FCM. MFGE8, BMP, Smad 1, Smad4, Smad5, Snail, CD31 and α-SMA protein and gene expression was assessed by western blotting (WB) and qRT‒PCR. In vivo, the changes in cell morphology and alveolar septum in the lung of mice (C57BL/6, aged 7-8 weeks, male) were observed by H&E staining. In addition, ECM deposition in lung tissue was detected by Masson staining. CD31 and α-SMA protein expression in lung tissue was measured by WB. Results: The serum level of MFGE8 was lower in the ARDS group than in the control group. MFGE8 was identified as a protective factor associated with hospital survival. In vitro, the treatment of human lung microvascular endothelial cells (HLMECs) with LPS for 96 h clearly changed the cells from the typical cobblestone shape of ECs to spindle-like fibroblasts. The scratch and Transwell assay results indicated that endothelial cell migration and invasion were enhanced in the LPS group compared with the control group. Fluorescence microscopy, FCM, WB and PCR showed that LPS greatly inhibited CD31 (endothelial marker) expression and increased α-SMA (mesenchymal marker) expression. These data showed that LPS could induce EndoMT in HLMECs. Notably, siRNA-treated HLMECs yielded the same results. The administration of rhMFGE8 to HLMECs in the LPS or LPS+siRNA group ameliorated the changes in cell morphology and decreased cell migration and invasion. rhMFGE8 attenuated the effect of LPS or LPS+siRNA on EndoMT induction by increasing CD31 and decreasing α-SMA protein and gene expression. Moreover, activation of BMP/Smad1/5-Smad4 signalling in response to LPS and Snail (related to EndoMT transcription factors) expression were increased by MFGE8 knockdown but inhibited by rhMFGE8. In vivo, H&E staining revealed a thickened alveolar septum in the LPS group, and the thickness increased over time; in contrast, rhMFGE8 reversed this effect. ECM deposition occurred early in ALI induced by LPS and increased over time, and the administration of rhMFGE8 reversed this effect. WB showed that LPS inhibited CD31 protein expression and increased α-SMA protein expression in lung tissue. Conclusions: rhMFGE8 exerts a protective effect early in LPS-induced EndoMT through BMP/Smad1/5/Smad4 signalling and could be a therapeutic target in ALI.

Memory and emotion, fundamental components of our mental existence, are highly vulnerable to psychiatric disorders like post-traumatic stress disorder (PTSD). This condition has been linked to serotonin (5-HT) metabolism disruptions. Over 95% of the 5-HT precursor tryptophan (Trp) is metabolized through the Trp-kynurenine (KYN) metabolic pathway, but little is known about its role in behavior. Kynurenine aminotransferases are responsible for the production of the Trp-KYN metabolite kynurenic acid. The gene aadat codes for mitochondrial kynurenine aminotransferase isotype 2. We generated CRISPR/Cas9-induced aadat knockout (kat2−/−) mice to examine the consequence of the gene deletion on negative valence in emotion, memory, and motor function in males 8 weeks of age and compared them to their wild-type counterparts. The forced swim test showed increased depression-like behaviors in transgenic mice. Anxiety and memory tests showed no significant differences. The transgenic mice had fewer center field and corner entries, shorter ambulation distances, and fewer jumping counts in the open field test. Overall, the transgenic mice exhibit depression-like behavior in a learned helplessness model, emotional indifference, and motor deficits. Here we present the first evidence that the deletion of the aadat gene triggers depression-like behaviors, uniquely associated with despair experience rather than adverse-conditioned memory. These findings have profound implications, opening avenues for further exploration into the main causes of experience-based depression linked to despair. This investigation has the potential to advance our understanding of these complex conditions and pave the way for improved therapeutic strategies by elucidating the relationship between Trp metabolism and the pathogenesis of PTSD.

Introduction: In the year 2022, 4.9 million children died worldwide before five years of age. United Nations General Assembly has set the target of bringing down under-five child mortality to 25 deaths per 1000 live births by 2030. However, the United Nations Inter-Agency Group for Child Mortality Estimation highlights, that without rapid action many low and Lower Middle-Income Countries (LMICs) will not be able to achieve this target and 35 million under-five children will die before 2030. In such a scenario understanding the determinants that bring down preventable deaths in children is important. Design: Anonymized, publicly available data from the India National Family Health Survey (NFHS-5) is collected. The sample consisted of 724,115 women in the age group of 15-49 years has been sub-grouped as urban and rural women. Data on the number of Anganwadi centers per state has been collected from the Ministry of Women and Child Development. For better analysis of data, the country is divided into regions. Union territories are grouped in these regions as per their geographical locations. Descriptive statistical analysis, correlation coefficient analysis, and linear regression analysis were done. Results: Results of the Pearson correlation indicated that there is a significantly large positive relationship between operational AWCs (%) and U5MR (r = 0.542, p < .001) whereas there is a significantly large negative relationship between women with Internet access (%) and U5MR, (r = -0.738, p < .001). For our data, the multiple regression equation for y is U5MR (per 1000 live births) = 0.77266. AWCs (%) - 0.58788. women with Internet access (%) + 53.68073. Conclusion: Compared to NFHS-4 (2015-16) U5MR has reduced in almost all states of the country. The study shows more urban women have access to the Internet as compared to rural women. Child mortality is higher in rural areas in every state as compared to urban areas. Urban women have more access to health information because of internet access which may be the reason for lesser child mortality in urban areas compared to rural areas. Internet access for women (individual level) is far more effective in bringing down U5MR if compared to the community-level approach of Daycare centers.

On entering higher education, students from disadvantaged schools seem unable to cope with new academic demands and all too often the need for adjustment is attributed to under-preparedness. The purpose of this paper is to identify the factors contributing to and mitigating the alienation of students in institutions of higher learning. The narrative inquiry with a qualitative method was employed to obtain the perceptions of 51 selected first-level science university students on their experiences. This is a case of the University of Venda first-year level students registered in the 2023 academic year. The findings of this paper build on and contribute to the literature on understanding alienation in higher education. In particular, the key findings of this paper reveal that the students failed to quickly adapt to a different culture of teaching and learning; the academic workload was overwhelming, and lecturers were unapproachable Students from previously disadvantaged backgrounds especially struggled to assimilate into the new university culture of teaching and learning. This paper concludes by recommending that there is a serious need to take cognisance of the influx of previously disadvantaged students into institutions that were not created with them in mind. Universities and their teaching staff should recognise the culturally diverse nature of the student body and thereby restructure teaching and assessment to foster social justice to promote student success.

A Robust Optimization framework with original concepts and fundamentals also admitting a fusion of ideals from relative regret models and static robust optimization, containing conservatism concepts is disclosed. The algorithm uses a fine-tune strategy to tune the model so the robustness and a target ideality can be mutually achieved with a specified risk. The framework comprises original concepts, a mathematical approach and an algorithm. The statistical treatment of the data with the original concepts from the framework make it able to make short, middle or long-term decision-making setting. The framework has high tractability since the algorithm forces the creation of a setting that makes a robust optimization with the specified risk. The framework can be applied in linear and nonlinear mathematical models since that the objective function is monotonic in the domain of the active convex region. Several examples are solved to best understand the framework and all results demonstrated high tractability and performance. There is a wide range of applications. Along all the text, there is a profound discussion about its philosophy, objective, original concepts, fields of application, statistical and probabilistic fundamentals.

Looking for effective synthetic methods for 1H-pyrazolo[3,4-b]quinolines preparation, we came across a procedure where in a three component reaction catalyzed by L-proline, 4-aryl-4,9-dihydro-1H-pyrazolo[3,4-b]quinolines are formed. These compounds can be easily oxidized to a fully aromatic system, which gave hope for a synthetic method that could replace e.g. Friedländer condensation, often used for this purpose, although severely limited by the availability of suitable substrates. However, after careful repetition of the procedures described in the publication, it turned out that the compounds described therein do not form at all. The actual compounds turned out to be 4,4-(phenylmethylene)-bis-(3-methyl-1-phenylpyrazol-5-oles). 4-Aryl-4,9-dihydro-1H-pyrazolo[3,4-b]quinolines were prepared by another method and used as standards to compare the products formed in the original procedure.

Introduction: Over decades, much have been said and done regarding under-five mortality in Ethiopia. The country has been following the lead of sustainable development goals and UNICEF with its transformation plan targets. However, unless the efforts supported by status assessing studies, it might be difficult for the country to progress. Thus, the current study was directed to identify the prevalence and associated factors of under-five mortality in 2019. Methods: According to the study criteria, we extract and cleaned data in STATA v. 15.0. The data then weighted as per the sampling weight, primary sampling unit, and strata before analyzing in STATA 15.0. Data management consisted of descriptive (mean, standard deviation, and proportion or percent) and association statistics. We deliberated binary logistic regression for this analysis and we checked each variable at 0.25 p-values to include in the model. The final p-value to declare association was p <0.05 and AOR with 95% CI was also applied to describe the results. The data source was the Ethiopian Mini Demographic Health Survey (EMDHS) 2019. EMDHS collected the data from 8,885 in a face-to-face manner with a 99% response rate. Results: From 5,527 numbers of weighted women with under-five analysed in this study, the proportion of under-five mortality was 277.23(5.02%). Factors like 2nd birth order 0.52(0.35, 0.79), 3rd-4th 0.49(0.28, 0.84), 1-2 ANC visits 0.24(0.12, 0.49, ANC visit three’ 0.14(0.07, 0.28), ANC visit four and above 0.22(0.14, 0.36), in marriage mother 0.43(0.19, 0.96), ‘1-2 under-five children 0.02(0.011, 0.03), and greater than three under-five children 0.007(0.0007, 0.004) were all negatively associated with under-five mortality rate. Conclusion: To obtain the exalted outcome out of this study, the government might need to increase antenatal care, women education, institutional delivery, and the modern contraceptive methods use through enhanced community mobilization, health education using community health workers, increasing access to essential cares of mothers and children, and the policy commitment for the issues related to family size, birth order, and birth interval.

This paper introduces an alternative method to design the path following controller of an under-actuated spherical mobile robot, which has a single pendulum structure its inside as a driving mechanism. The mechanism has an under-actuated problem; two inputs for the roll and pitch but no direct input for the yaw. In order to overcome this problem, the proposed method defines a virtual reference input for the heading direction. The virtual reference input works as a control input since it can be arbitrarily designed just like the reference input of a conventional system. The control scheme using the defined virtual reference input achieves the stabilization and path following control of the under-actuated spherical mobile robot without any additional control technique. The stability of the proposed control scheme is guaranteed by Lyapunov stability analysis, and simulation results are given to demonstrate its performance.

The accumulation of high levels of lead or lead ions in a human body is harmful, particularly to children. Its neurotoxic effect is profound, damaging the central and peripheral nervous systems, resulting in stunted growth, behavioral problems and learning disabilities. The major source of lead or lead ions comes from the drinking water and tap water. The assessment of the water quality, including lead or lead ion content, is usually completed by a regional water department professional. This assessment is time-consuming and requires expensive instruments and skilled operators. Therefore, there is a need to produce a simple-use and relatively inexpensive method to detect lead or lead ions in water samples. This research has developed a simple-use, cost effective sensor system for the detection of lead ions in tap water. An under-potential deposited bismuth sub-layer on a thin gold film based electrochemical sensor was designed, manufactured and evaluated. Differential pulse voltammetry (DPV) measurement technique was employed in this detection. Tap water from the Cleveland, Ohio, USA regional water district was the test medium. Concentrations of lead ion in the range of 8 X 10^-8 M to 8 x 10^-4 M were evaluated. This DPV detection system required 3 -6 minutes to complete the detection measurement. A longer measurement time of 6 minutes was used for the lower lead ion concentration. The selectivity of this lead ion sensor was very good, and Fe III, Cu II, Ni II and Mg II at a concentration level of 5×10^-4 M did not interfere with the lead ion measurement.

Etiological factors involved in myelodysplastic syndrome (MDS) include immunologic, oxidative stress, and inflammatory factors, among others, and these are targets for microRNAs (miRNs). Here, we evaluated whether some miRNs may affect the tumor development comparing untreated and 5-azacitidine (5-AZA) MDS-treated patients. Peripheral blood samples were collected from 20 controls and 24 MDS patients, and selected miRNs related to redox balance and inflammation, including miR-18a, miR-21, miR-34a and miR-146a, were isolated and measured by quantitative real-time polymerase chain reaction (qRTPCR). A differential expression profile of miRNs was detected in untreated MDS patients and 5-AZA group. MiR-18a, miR-21, miR-34a and miR-146a were significantly overexpressed in untreated MDS, compared to controls. However, we did not observe any miRNs profile alteration during the progression of the disease. On the other hand, 5-AZA treatment tends to restore miRNs expression levels. Relating to prognostic risk factors, high risk MDS groups (high IPSS-R, high cytogenetic risk, high molecular risk (HMR) mutations tended to be related with higher expression levels of miR-18a and miR-34a. Higher miRNs expression is correlated with lower glutathione peroxidase activity, while they are related with a higher profile of pro-inflammatory cytokines (IL-2, IL-6, IL-8, TNF-α). Although our study was limited by the low number of MDS patients included, we identified miRNs deregulation involved in the MDS development, that could regulate redox sensors and inflammatory responses. Finally, 5-AZA treatment is related with lower miRNs expression levels in MDS patients.

Pathophysiology of depression is related with reduced volume of the hippocampus and amygdala and hypertrophy of the nucleus accumbens. The mechanism of these changes is not well under-stood, but clinical studies have shown that administration of the fast-acting antidepressant keta-mine reversed the decrease in hippocampus and amygdala volume in depressed patients, and the magnitude of this effect correlated with the reduction of depressive symptoms. In the present study, we attempted to find out whether the psychedelic substance psilocybin affects neurotransmission in the limbic system in comparison to ketamine. Psilocybin and ketamine increased the release of dopamine (DA) and serotonin (5-HT) in the nucleus accumbens of naive rats as demonstrated using microdialysis. Both drugs influenced glutamate and GABA release in the nucleus accumbens, hippocampus and amygdala and increased ACh levels in the hippocampus. The changes in D2, 5-HT1A and 5-HT2A receptor density in the nucleus accumbens and hippocampus was observed as a long-lasting effect. A marked anxiolytic effect of psilocybin in acute phase and 24 h post-treatment was shown in the open field test. These data provide the neurobiological background for psilocybin effect on stress, anxiety and structural changes in the limbic system and translate into antidepres-sant effect of psilocybin in depressed patients.

The CAALA (Complex Augmentation of ALA) regimen was developed with the goal of redressing some of the weaknesses of 5-aminolevulinic acid (5-ALA) use in glioblastoma treatment as it now stands. 5-ALA is approved for use prior to glioblastoma surgery to better demarcate tumor from brain tissue. 5-ALA is also used in intraoperative photodynamic treatment of glioblastoma by virtue of uptake of 5-ALA and its selective conversion to protoporphyrin IX in glioblastoma cells. Protoporphyrin IX becomes cytotoxic after exposure to 410 nm or 635 nm light. CAALA uses four currently marketed drugs - the antibiotic ciprofloxacin, the iron chelator deferiprone, the antimetabolite 5-FU, and the xanthine oxidase inhibitor febuxostat - that all have evidence of ability to both increase 5-ALA mediated intraoperative glioblastoma demarcation and photodynamic cytotoxicity of in situ glioblastoma cells. Data from testing the full CAALA on living minipigs xenotransplanted with human glioblastoma cells will determine safety and potential for benefit in advancing CAALA to a clinical trial.

DNA methylation is one of the epigenetic mechanisms which have been implicated in cellular differentiation, ageing and disease development. The effect of hypomethylating drug 5-aza-2´deoxycytidine (5-aza dC) on the biosynthetic profile of caudal region chondrocytes from chick sternum was studied in detail. The chondrocytes in culture were treated with varying doses of 5-aza dC for 48h and maintained subsequently without the treatment and harvested at selected time points for analysis of growth and differentiation status. 15µg/ml of 5-aza dC showed optimum Concentration at which there was a significant increase in DNA synthesis and RNA synthesis as per cell basis. There was also a significant increase in total protein synthesis and collagen synthesis as per cell basis at this concentration. This optimal concentration also showed to up regulate the gene expression of Type X collagen and alkaline phosphatase, which are the marker of hypertrophic chondrocyte expression. These results further support the notion that methylation is the major epigenetic factor controlling the differentiation and maturation of chondrocytes.

Malnutrition is the main cause of child mortality in developing nations, especially in Sub-Saharan Africa and South Asian countries. This undernutrition status is predominantly higher among primitive tribal (ST) children under 5 years of age. The nutritional status of tribal children is a serious concern in India. For this, there should be intends to examine the prevalence and determinants of primitive tribal children's nutritional status. To investigate the effect of household, child’s & maternal characteristics on biological children under 5 years of age. The study aims to find out the association between some selected determinants on scheduled tribe child’s nutritional status. The study used some selected variable of scheduled tribe mothers, household characteristics and their children anthropometric indices from DHS datasets of India, which was published by the NFHS datasets of India. In this study People datasets and Children (Under 5 years of age) of interviewed women file datasets of NFHS-IV & V is taken. The datasets of West Bengal, ST mothers, and their child into consideration as per the research interest. Then to analyze the determinants of ST children (U5 age) nutritional status, some determinant factors are taken from mothers, children and household characteristics. Children’s stunting, wasting and underweight as dependent variable and the mothers, child’s and household’s characteristics as independent variable. The statistical analysis was done by using Pearson Chi square test used to analyze the association between dependent and independent variables. The study results shows that the mother’s educational status, child’s age, birth order, size of child at birth, type of residence had significant associations with stunting. Mother's anemia status and mother age had significant associations with wasting. Mother education, currently breastfeeding, child age, sex of the child, birth order, size of child at birth, type of residence, wealth, toilet facility, and cooking fuel shows a significant association with underweight. The results found that many determinant factors had a significant role among ST children's (U5 age) nutritional status. Thus, the findings will help to achieve tentative resource allocation, and utilization through various programs and policies to improve the ST children (U5 age) nutritional status. There is a need to take a multisectoral and multidimensional approach to develop for those primitive tribal children.

Among many research areas to which Ron Yager contributed are decision making under uncertainty (in particular, under interval and fuzzy uncertainty) and aggregation – where he proposed, analyzed, and utilized the use of Ordered Weighted Averaging (OWA). The OWA algorithm itself provides only a specific type of data aggregation. However, it turns out that if we allows several OWA stages one after another, we get a scheme with a universal approximation property – moreover, a scheme which is perfectly equivalent to deep neural networks. In this sense, Ron Yager can be viewed as a (grand)father of deep learning. We also show that the existing schemes for decision making under uncertainty are also naturally interpretable in OWA terms.

Abstract: Turmeric is a plant with multiple medicinal attributes. One of them being its analgesic effect. In this project the analgesic effect of the plant was evaluated with an inflammatory pain model: the 5% formalin model. Turmeric was administered to 250 g male Wistar rats (6 ± 2) provided by the Health Science department’s vivarium. The dose-response curve of the plant was per-formed observing the analgesic effect. Once the dose was selected, they were administrated within different turmeric protocols. 400 mg orally every 24 h for two weeks, another group with turmeric ad libitum for two weeks, the control group with 0.9% saline solution for two weeks, and a group with administration of metamizole prior to evaluation with 5% formalin. Subsequently, each rat was evaluated by 5% formalin intraplantarly and the number of rat paw twitches per 1 h was observed. The analysis of the data generated through the obtained results was carried out. The dose of 400 mg of oral turmeric was administered for two weeks without observing any collateral effects. An excellent analgesic effect was found in this protocol, as well as, in the ad libitum administration for two weeks compared to the control group. Likewise, turmeric presents a milder effect than metamizole, a well-known analgesic.

Introduction: Guardians play a pivotal role in the management of childhood illness. Their responsibilities include home managing childhood illnesses and supporting continuity of care following healthcare facility treatment. Evidence has shown that guardians' negative experience in health care facilities when accessing under-five childcare services impacts their utilization of such facilities. Exploration of guardians' experiences is important in providing the evidence base necessary for quality childcare and reducing under-five morbidity and mortality. The study aimed to explore the experiences of guardians of children under five regarding the care received in Vhembe healthcare facilities. Methods: A qualitative approach using an interpretative phenomenology analysis (IPA) was used for this study. The study was conducted in eight primary healthcare facilities in the Vhembe district, with the highest headcount for children under five. Sixteen guardians were purposefully sampled for the study. Data analysis was done following the IPA steps of data analysis. Trustworthiness criteria were followed: credibility, confirmability, dependability, authenticity, and transferability. Ethical approval was obtained from the university and the province, followed by permission from the district and the operational managers before data collection. Results: The three emerging themes are associated with participants' positive experiences as they interfaced within the healthcare system: quality care, healthcare environment, support, and empowerment. The ten sub-themes were: timely service provision, availability of medicines, perceived nursing competence and professionalism, person-centred care, welcoming environment, effective communication, positive attitude of healthcare providers, guardians’ satisfaction with care received, guardians' involvement in childcare and community support. Conclusion: It is indeed not always bad. The participants in this study had positive care experiences, which is crucial in the optimal utilization of health care services, resulting in improved health outcomes.

Background. COVID-19 efforts were often ineffective in controlling the spread of the pandemic. Identifying ineffective controls during a pandemic is thus vital. Method. Utilizing publicly available data on COVID deaths in the counties of US states, we create an index to capture and interpret ineffectiveness in the efforts to reduce the spread of the pandemic in US counties. This index is based on the Intervened Poisson Distribution (IPD) introduced originally by Shanmugam. Motivation for the research idea occurred while we noticed the data dispersion of the COVID deaths is smaller than the average only in some counties. Under-dispersed data is common in statistical modeling. A novel approach we adapted in this article includes the estimation of an intervention parameter estimated through iterative non-linear optimization. Results. Twenty-five counties in California, Idaho, Minnesota, Mississippi, Montana, Nebraska, North Carolina, North Dakota, Texas, and Utah were found to be ineffective in controlling for fatalities based on the expected probability distribution. A review of the policies enacted in these areas would provide insight into ineffective prevention efforts, and some of these issues are documented in current literature. Conclusion. The IPD index an innovate way to document efficacy of interventions during pandemics. The IPD may identify ineffective efforts prior to statistical models intended to evaluate efficacy of efforts.

As mental health problems tend to increase during adolescence and is a serious public health issue in the Republic of Kazakhstan. Early detection is necessary and monitoring at the population level can be used to evaluate the progress of national programmes promoting positive well-being. Physical activity (PA) can be protective whereas increased screen time behaviours (STB) can be a risk for low levels of well-being. A national representative sample (n=4,731) of young adolescents aged 11y, 13y, and 15y from the Republic of Kazakhstan took part in the WHO collaborative Health Behaviour in School-aged Children (HBSC) study. Respondents completed the WHO-5 Well-being scale, and items in on PA and STB. Internationally recognised, recommended cut-offs were used for analyses. Two models of binary logistic regressions were performed to examine the associations with PA (Model 1) and PA with STB (Model 2) after stratification by gender and controlling for age, locality and family affluence. Three quarters of young adolescents in the Republic of Kazakhstan have good overall well-being, despite the proportion reduces as adolescents age from 11y to 15y (boys, OR=0.66 CI=0.49-0.80; girls, OR=0.55, CI=0.43-0.71). The odds ratio for positive well-being were more than twice for boys and more than 3.5 for girls who reported daily PA than not being active daily. Spending less time on STB for girls was associated with positive well-being than spending more STB time (OR=1.28, CI=1.04-1.59). Well-being among young adolescents drops dramatically between the ages of 11y and 15y and is higher among rural schools attendees than in urban schools. The recommended amounts of PA can be protective of low well-being for both boys and girls. However, meeting reporting STB recommendations was only protective for girls and not boys. Designing and implementing positive well-being programmes require consideration of locality and amounts of PA and STB

The string of bacteria, Vibrio. sp. QD-5 utilizing alginate, was separated from rotten kelp. The results of genome sequencing showed that the strain QD-5 contained four alginate lyase genes.One of the alginate genes Aly-IV was cloned and linked to the plasmid pET-22b (+). The heterologous expressed alginate lyase aly-IVwas characterized，which possessed the theoretical molecular mass of 62 kDa, and theoretical isoelectric point (pI) of 5.12. - The enzyme aly-IV was purified and the activity reached 1256.78 U/mg, with optimal temperature of 35 ^oC and pH value of 8.9. Nurtured in the temperature below 25 ^oC for 30 minutes, the activity was almost stable. The result also suggested that the activity of enzyme was strongly affected by - NaCl whose optimal concentration was 15 mM in a lab environment The TLC and ESI-TOF-MS analysis suggested that the enzyme aly-IV could degrade sodium alginate and polyG in endo-lytic type, producing monomer, dimer and trimmer. So, aly-IV can also be widely applied to make large scale preparation of alginate oligosaccharides with low degree of polymerization (DP).

The main challenges in oil platforms are how to define optimal setpoints and decision-making for controlling variables due to many existing dynamical production uncertainties while conceding safe operation and minimizing discharge to sea and atmosphere without killing plantwide inventory. A novel scheduling model to optimize the whole essential units of an oil platform production gathering topside and subsea variables is disclosed. A proper topside and subsea scheduling model enables and creates harmony between optimal production, supply chain, costs, and market dynamics, satisfying demands, environmental and operations constraints leading to stability. The interest of the present research lies in determining the optimal topside and subsea operational settings and decision-making, establishing maximum E&P performance and production control setpoints while predicting and manipulating reservoir lifespan and its revitalization. This objective is attained through a novel multiperiod large-scale model for the planning and operational production scheduling and model predictive control (MPC) in oil platforms complying with sustainability, profitability, platform design capacities, and offloading of oil and gas to supply chains or to pipeline exportation. The present model details heat and mass transfer, PVT, flow profiles along a planning horizon and can be used to any oil platform since comprises all the essential unit operations for oil, gas, CO₂, H₂S and water. The model maximizes the total oil production over any planning horizon. The model is versatile, and decision-making can be either linear or nonlinear but rather a MILP or LP as best choice on optimizing large-scale systems. If the model is applied with auto rescheduling on site within variable hours or minutes, it becomes a real-time optimization schedule approach. Due to its high-velocity performance and robustness, a novel multi-objective function strategy, acting as an LP generic plantwide MPC with industrial scope to maximize production while controlling the process is presented, and as an example is here used to control slug flow to avoid equipment trips and inventory instability, at the same time production is maximized. The output from the decision-making was compared to actual plant data, and the results proved compliance to the design capacity with process safety and sustainability. Comparing to official Brazil's government data for oil, the case study showed superiority to the same size platforms, like FPSOs P-75 and MV32, e.g., more than 101.5% more capacity to produce oil in beginning of campaign after first oil, and 10.5% during campaign. The present work indicates that: 1) the production of millions of barrels is being delayed or left aside; 2) not scheduling production harms the environment and diminish process safety; 3) not scheduling production can create stochastic supply chain deliveries instead of organizing it by deterministic offloading days; 4) scheduling is essential to manipulate, revitalize and monitor reservoir's pressure and content under uncertainty; 5) the oil platform can be automatic optimized by a plantwide MPC reducing human activity/dependency; 6) scheduling gives more transparency to stakeholders and contractors by forecasting business data and capability, and can design, develop or enable new businesses.

Background: COVID-19 has impacted Indian engineering institutions (EIs) enormously. It has tightened its knot around EIs that forced their previous half-shut shades completely down to prevent the risk of spreading COVID-19. In such a situation, fetching new enrollments on EI campuses is a difficult and challenging task, as students’ behavior and family preferences have changed drastically due to mental stress and emotions attached to them. Historically, during crisis situations, institutions have struggled to return to the normal track. Consequently, it becomes a prerequisite to examine the choice characteristics influencing the selection of EI during the COVID-19 pandemic to make it ‘normal’ for ‘new’ enrollments. The purpose of this study is to critically examine choice characteristics that affect students’ choice for EI and consequently to explore relationships between institutions’ characteristics and the suitability of EI during the COVID-19 pandemic across students’ characteristics. Quantitative research, conducted through a self-reported survey composed of a closed-ended structured questionnaire, was purposefully incorporated into the students who recently were enrolled in EIs (batch years 2020-2021) belonging to the North Maharashtra region of India. Results:The findings of this study revealed dissimilarities across students’ characteristics regarding the suitability of EIs under pandemic conditions. Regression analysis revealed that EI characteristics such as proximity, image and reputation, quality education and curriculum delivery have significantly contributed to suitability under COVID-19. At the micro level, multiple relationships were noted between EI characteristics and the suitability of EI under the pandemic across students’ characteristics. Conclusion:Bringing ‘normality’ to ‘new’ enrollments totally depends on EI’s resilience in meeting the needs of diversity in the COVID-19 pandemic situation, which repositions themselves to govern student-centric strategies instituted for the overall suitability of EI under pandemic conditions. The study has successfully demonstrated how choice characteristics can be executed to regulate the ‘suitability’ of EI under the COVID-19 pandemic for the inclusion of diversity. It is useful for policy makers and academicians to reposition EIs that fetch diversity during the pandemic. This study is the first to provide insights into the performance of choice characteristics and their relationship with the suitability of EIs under a pandemic and can be a yardstick in administering new enrollments.

Drought stress at the reproductive stage in rice is one of the most important cause for yield reduction, affecting both productivity and quality. All Basmati rice varieties, including the popular cultivar ‘Pusa Basmati 1 (PB1)’ is highly sensitive to reproductive stage drought stress (RSDS). We report for the first time, improvement of a Basmati cultivar for RSDS tolerance, with the introgression of a major quantitative trait locus (QTL), ‘qDTY1.1’ into PB1. The QTL donor was sourced from an aus variety, Nagina 22 (N22). A QTL linked microsatellite (SSR) marker ‘RM 431’ was employed for foreground selection for qDTY1.1 in the marker assisted backcross breeding process. A set of 113 SSR markers polymorphic between N22 and PB1 were utilized for background selection to ensure higher genome recovery. After three backcrosses followed by five generations of selfing, eighteen near isogenic lines (NILs) were developed, through combinatory selection for agro-morphological, grain and cooking superiority traits. The NILs were evaluated for three consecutive Kharif seasons, 2017, 2018 and 2019 under well-watered and drought stress conditions. RSDS tolerance and yield stability indicated that NIL3, NIL5, NIL6, NIL7, NIL12, NIL15 and NIL17 were best in terms of overall agronomic and grain quality under RSDS. Additionally, NILs exhibited high yield potential under normal condition as well. The RSDS tolerant Basmati NILs with high resilience to water stress, is a valuable resource for sustaining Basmati rice production under water limiting production environments.

This paper considers the problem of quantifying the quality of a model selection problem for a graphical model. The model selection problem often uses a distance measure such as the Kulback-Leibler (KL) distance to quantify the quality of the approximation between the original distribution and the model distribution. We extend this work by formulating the problem as a detection problem between the original distribution and the model distribution. In particular, we focus on the covariance selection problem by Dempster, [1], and consider the cases where the distributions are Gaussian distributions. Previous work showed that if the approximation model is a tree, that the optimal tree that minimizes the KL divergence can be found by using the Chow-Liu algorithm [2]. While the algorithm minimizes the KL divergence it does not minimize other measures such as other divergences and the area under the curve (AUC). These measures all depend on the eigenvalues of the correlation approximation measure (CAM). We find expressions for KL divergence, log-likelihood ratio, and AUC as a function of the CAM. Easily computable upper and lower bounds are also found for the AUC. The paper concludes by computing these measures for real and synthetic simulation data.

The considerable biological and medicinal activities of pyridazines has stimulated considerable research on efficient syntheses of these derivatives. In the last decade, microwave irradiation has generally been used for the energy source. As demonstrated in recent studies, pressure reactor “Q-tubes” may be used to accelerate several of these reactions in a more optimal and safer manner (compared to microwaves). In these studies there has been postulated a pathway for the formation of pyridazino[5,4,3-de][1,6]naphthyridine derivatives . In this paper we consider this pathway, and an alternate pathway, for several reactions. Contrary to the suggestion in these studies the pathway in which initial dimerization of malononitrile was postulated could be excluded based on chemical evidence. The reactions performed were the reaction of arylhydrazonals 1a,b with benzylidinemalononitrile which afforded in Q-tube the 3-acyl-4-aryl-1-phenyl-6-amino-1,4-dihydropyridazines, and the reaction of arylhydrazonals 1a,b, malononitrile 9 and aromatic aldehydes 10a-g in Q-tubes which afforded the tricyclic systems 12a-n whose structure could be established by X-ray crystal structure determination. In conclusion, we have added to the work of the recent studies by excluding a reaction pathway for one of their reaction products.

Background: Glioma surgery was remarkably renewed in the past 2 decades, with improved safety and limited but yet improved life expectations. Fluorescence-guided resection of high-grade gliomas (HGG) plays a central role in this sense, by allowing higher degrees of extent of resection (EOR). The introduction of the exoscopic guided surgery may be considered an implementation for fluorescence techniques over the traditional microscopes. We present the application and the advantages of the exoscopic guided surgery compared to the microscopic surgery in tumor resection guided by 5-ALA fluorescence in patients with HGG. Methods: ten consecutive patients underwent a surgery for HGG resection. The surgery was performed via an exoscopic-guided procedure (Olympus Orbeye) and after oral administration of Gliolan 5 hours before the procedure. During surgery, the procedure was shifted to microscope (Kinevo 900, Zeiss) view. The intensity of the fluorescence under the two different was subjectively measured in different picture samples during the surgery in a 1 to 5 (from minimum to maximum) scale. The brightness of the surgical field and the detailing of the anatomy were also analyzed comparatively. Results: among the ten patients the histopathological diagnosis was an high grade glioma in all cases. In 9 cases was possible to achieve the gross total resection. There was no perioperative mortality. The median fluorescence intensity, on a scale of 1–5, was 4.5 in the exoscope group and 3.5 in the microscope group (p<0.01). Conclusions: The exoscopic guided surgery adds advantages to the traditional fluorescence- guided surgery with 5-aminolevulinic acid. Beyond the important advantage of low cost and the possibility to perform collaborative surgeries, it adds a plain and continuous visualization of the tumor and the surgical field in the fluorescence guided glioma surgery compared to the microscopic guided one.

Fetal growth restriction (FGR) is a major concern in perinatal care. Various medications have been proposed as potential treatments for this serious condition. Nonetheless, there is still no definitive treatment. We studied tadalafil, a phosphodiesterase-5 inhibitor, as a therapeutic agent for FGR in clinical studies and animal experiments. In this review, we summarize our preclinical and clinical data on the use of tadalafil for FGR. Our studies in mouse models indicated that tadalafil improved FGR and hypertensive disorders of pregnancy. In addition, tadalafil protected cerebral nerve development in FGR offspring. The clinical trials we have conducted to date, including a case–control study, a phase I trial, and a phase II trial, have indicated the efficacy of tadalafil in prolonging pregnancy, as well as a good safety profile for fetuses and neonates. The number of fetal, neonatal, and infant deaths was significantly lower in those receiving tadalafil treatment group than that in controls, and no severe adverse maternal events associated with tadalafil were observed. Although further studies are needed to establish the usefulness of tadalafil in FGR treatment, our research indicates that the use of tadalafil in FGR treatment may be a paradigm shift in perinatal care.

As one of toxic Volatile Organic Pollutant (TVOCs), formaldehyde has a toxic effect on microorganisms, and then inhibits the biochemical process of formaldehyde wastewater treatment. Therefore, the selective degradation of formaldehyde is of great significance to achieve formaldehyde wastewater high-efficiency and low-cost treatment. This study constructed a heterogeneous Fe-ZSM-5/H2O2 Fenton system for selective degradation to target compounds. By bonding Fe3+ onto the surface of ZSM-5 molecular sieve, Fe-ZSM-5 was prepared successfully. XRD, BET and FT-IR spectral studies shown the prepared Fe-ZSM-5 was mainly composed of micropores. The influences of different variables on formaldehyde selective heterogeneous Fenton degradation performance were studied. The 93.72% formaldehyde degradation and the 98.15% selectivity of formaldehyde compared with glucose had demonstrated in the optimized Fenton system after 360 min. Notably, the resultant selective Fenton oxidation system had a wide range of pH suitability from 3.0 to 10.0. Also, the Fe-ZSM-5 was used in 5 consecutive cycles, while the degradation efficiency of formaldehyde did not drop dramatically. Using reactive oxygen species scavengers, hydroxyl radical was the main active substance to degrade formaldehyde. Furthermore, the great degradation performance of this system to high concentration of formaldehyde was acquired, and the degrading efficiency was more than 95%.

Rice blast fungus (Magnaporthe oryzae) causes massive yield losses annually worldwide. The fungus secreted bunch of effector proteins target different rice cellular compartments to facilitate its infection. However, most of intensively studied effectors are small secreted proteins with high presence/absence polymorphism in the fungus, and effectors conserved among different species were rarely investigated. In this study, we identified MoPce1, a CAP/PR domain containing protein common in different species, as an important virulence factor from a screening of 145 putative core effectors (PCE). MoPCE1 is required for pathogenicity but not the asexual development. Ectopic expression of MoPCE1sp in ZH11 background compromised the plant resistance. We also found that MoPce1 lacks the conserved cysteine residuals in CAP domain, and is BIC-localized in invasive hyphae and nuclei-localized when ectopically expressed in tobacco leaves and rice protoplasts. These results suggested that MoPce1 may bind novel ligand(s) rather than sterol. Indeed, we found that MoPce1 could interact with OsDi19-5, a transcription factor in rice. We inferred from these results that MoPce1 is required for pathogenicity by suppressing the immune response in rice, likely through the interaction with OsDi19-5.

Serotonergic neurons constitute one of the main systems of neuromodulators, whose diffuse projections regulate the functions of the cerebral cortex. Serotonin (5-HT) is known to play a crucial role in the differential modulation of cortical activity related to behavioral contexts. Certain aspects of the 5-HT signaling framework hint at its potential role as a modulator of activity-dependent synaptic changes within the critical period of the primary visual cortex (V1). Cells of the serotonergic system are among the first neurons to differentiate and operate. During postnatal development, ramifications from raphe nuclei become massively distributed in the visual cortical area, remarkably increasing the availability of 5-HT for the regulation of excitatory and inhibitory synaptic activity. A substantial amount of evidence has demonstrated that synaptic plasticity at pyramidal neurons of the superficial layers of V1 critically depends on a fine regulation of the balance between excitation and inhibition (E/I). Therefore, 5-HT could play an important role in controlling this balance, providing the appropriate excitability conditions that favor synaptic modifications. In order to explore this possibility, the present work used in vitro intracellular electrophysiological recording techniques to study the effects of 5-HT on the E/I balance of V1 layer 2/3 neurons, during the critical period. Serotonergic modulation of the E/I balance has been analyzed on spontaneous activity, evoked synaptic responses, and long-term depression (LTD). Our results pointed out that the predominant action of 5-HT implies a reduction of the E/I balance. 5-HT promoted LTD at excitatory synapses while blocking LTD at inhibitory synaptic sites, thus shifting the Hebbian alterations of synaptic strength towards lower levels of E/I balance.

Autophagy, an alternative cell death mechanism, is also termed programmed cell death type II. Autophagy in cancer treatment needs to be regulated. In our study, autophagy inhibition by desipramine or the autophagy inhibitor chloroquine (CQ) enhanced tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor-2 [death receptor (DR5)] expression and subsequently TRAIL-induced apoptosis in TRAIL-resistant A549 lung cancer cells. Genetic inhibition of DR5 substantially reduced desipramine-enhanced TRAIL-mediated apoptosis, proving that DR5 was required to increase TRAIL sensitivity in TRAIL-resistant cancer cells. Desipramine treatment upregulated p62 expression and promoted conversion of light chain 3 (LC3)-I to its lipid-conjugated form, LC3-II, indicating that autophagy inhibition occurred at the final stages of autophagic flux. Transmission electron microscopy analysis showed the presence of condensed autophagosomes, which resulted from the late stages of autophagy inhibition by desipramine. TRAIL, in combination with desipramine or CQ, augmented the expression of apoptosis-related proteins cleaved caspase-8 and cleaved caspase-3. Our results contributed to the understanding of the mechanism underlying the synergistic anti-cancer effect of desipramine and TRAIL and presented a novel mechanism of DR5 upregulation. These findings demonstrated that autophagic flux inhibition by desipramine potentiated TRAIL-induced apoptosis, suggesting that appropriate regulation of autophagy is required for sensitizing TRAIL-resistant cancer cells to TRAIL-mediated apoptosis.

This study contextualises the background of Japan’s “carbon neutrality and net-zero” (CNN) policy announced in October 2020, thereby identifying important changes in the country’s climate policy between 1990 and 2020. Using four research questions, four main findings were extracted from a narrative technique-based analysis of Japan’s policy documents related to CNN. The following are the findings: [i] the framing of climate change as a “climate crisis” by influential Japanese climate stakeholders was a key motivation for Japan to formally announce its CNN policy in October 2020, [ii] pressure from the international community and the political leadership of the Yoshihide Suga administration are essential factors that led the Japanese government to change its stance and announced this policy, [iii] Japan unintentionally delayed announcement of the policy until 2020 due to the concern among Japanese climate stakeholders about the problem of fairness in Kyoto Protocol’s emission reduction targets, and [iv] this delay was also due to Keidanren’s (or business sector) consistent opposition to the introduction of regulatory schemes. These results emerge for the first time in a study of Japan’s CNN politics, particularly in terms of the broader context of climate politics. Finally, we offer a possible explanation for Suga’s deliberate announcement of the CNN policy. This opens up space for future research to complement our study by providing important indicators on the trajectory of this important policy.

Abstract. Babies born to severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) infected mothers are at greater risk for perinatal morbidity and more likely to receive a neurodevelopmental diagnosis in the first year of life. However, the effect of maternal infection on placental function and neonatal outcomes varies depending upon the patient population. We set out to test our hypothesis that maternal SARS-CoV-2 infection in our underserved, socioeconomically disadvantaged, predominantly African American and Latina population in the Bronx, NY would have effects evident at birth. Fifty-five SARS-CoV-2 positive and 61 negative third trimester patients were randomly selected from Montefiore Medical Center (MMC), Bronx, NY. In addition, two positive cases from Yale New Haven Hospital, CT were included as controls. All 55 placentas delivered by SARS-CoV-2 positive mothers were uninfected by the virus, based on immunohistochemistry, in-situ hybridization, and qPCR analysis. However, placental villous infarcts, mild preeclampsia, shortened gestational periods and lower Apgar scores were observed in the infected cases. These findings suggest that even without entering the placenta, SARS-CoV-2 can affect various systemic pathways culminating in altered placental development and function, which may adversely affect the fetus, especially in a high-risk patient population such as ours. These results underline the importance of vaccination among pregnant women, particularly in low resource areas.

The terms 'open' and 'openness' are widely used across the current higher education environment particularly in the areas of repository services and scholarly communications. Open-access licensing and open-source licensing are two prevalent manifestations of open culture within higher education research environments. As theoretical ideals, open-licensing models aim at openness and academic freedom. But operating as they do within the context of global neoliberalism, to what extent are these models constructed by, sustained by, and co-opted by neoliberalism? In this paper, we interrogate the use of open-licensing within scholarly communications and within the larger societal context of neoliberalism. Through synthesis of various sources, we will examine how open access licensing models have been constrained by neoliberal or otherwise corporate agendas, how open access and open scholarship have been reframed within discourses of compliance, how open-source software models and software are co-opted by politico-economic forces, and how the language of 'openness' is widely misused in higher education and repository services circles to drive agendas that run counter to actually increasing openness. We will finish by suggesting ways to resist this trend and use open-licensing models to resist neoliberal agendas in open scholarship.

Similarly to a phoenix, SARS-CoV-2 has appeared periodically in waves. The new variants that appeared through mutations have during the 4 years of the pandemic suppressed earlier variants, causing new waves of the pandemic. The Omicron BA.2.86 Pirola variant is the latest in the sequence of SARS-CoV-2 variants, which appeared in 2023. The BA.2.86 variant has started to spread rapidly and we are witnesses of a new epidemic wave. In this short period, an increased infectivity was noticed, which results in rapid spreading and decreased pathogenicity, which results in a lower number of severe cases. However, in the public there is a fear of further development of the epidemic. This analysis was made with the goal to assess the risks in the period of late 2023. Mutations that were developed by the BA.2.86 variant have led to a change in empirical formula and thermodynamic properties. It seems that there is no ground for fear of an extensive spreading of severe forms, but there are reasons for caution and monitoring of the spreading of the epidemic and potential appearance of new mutations.

This study investigates the cyclic load application impact on fly ash-based geopolymer composites that are reinforced with a low amount of fibre reinforcement. For reinforcement purposes, PVA and steel fibres are used. For testing purposes, four geopolymer composite mixes were made, 3 of which had fibre reinforcement. Simultaneously specimens were tested for shrinkage, static load-induced creep, and cyclic load-induced creep. For static and cyclic creep testing, specimens were loaded with 20% of their strength. For cyclic creep testing, load application and release cycles were seven days long. When each cycle was introduced, the load was added in steps. In 5 minutes, by 25% steps of the necessary load, the specimens were loaded or unloaded. Only plain specimens show that static creep strains are within cyclic creep strains. For all the other specimens, the static load is higher than the cyclic load-induced creep amplitude. Also, 1% PVA fibre-reinforced specimens show the most elastic characteristics under cyclic load, and 1% steel fibre-reinforced specimens appear to be the most resistant to the cyclic load introduction.

Both bacteria product flagellin and macrophages are implicated in HIV infection/disease progression. However, the impact of their interaction on HIV infection and the associated mechanisms remain to be determined. We thus examined the effect of the flagellins on HIV infection of primary human macrophages. We observed that the pretreatment of macrophages with the flagellins from the different bacteria significantly inhibited HIV infection. The mechanistic investigation showed that the flagellin treatment of macrophages downregulated the major HIV entry receptors (CD4 and CCR5) and upregulated the CC chemokines (MIP-1α, MIP-1β, and RANTES), the ligands of CCR5. These effects of the flagellin could be compromised by a toll like receptor 5 (TLR5) antagonist. Given the important role of flagellin as a vaccine adjuvant in TLR5 activation-mediated immune regulation and in HIV infection of macrophages, future investigations are necessary to determine the in vivo impact of flagellin-TLR5 interaction on macrophage-mediated innate immunity against HIV infection and the effectiveness of flagellin adjuvant-based vaccines studies.

Anderson – Fabry disease (AFD) is a rare, X-linked lysosomal storage disorder caused by a mutation in the α-Galactosidase A gene resulting in α-Galactosidase A enzyme (α-Gal A) deficiency. The metabolic defect leads to progressive accumulation of glycosphingolipids and structural and functional impairment of affected organs. Due to the inheritance pattern, male patients are hemizygous with more severe manifestations of the disease as compared to females who in most cases are heterozygous with delayed and variable clinical presentation caused by uneven X – chromosome inactivation. Fabry disease cases are often identified by targeted screening programs in high-risk groups, such as in patients with end-stage renal disease, premature stroke or unexplained cardiomyopathy. Here we describe a unique case of homozygous female patient identified by a nationwide screening program in hypertrophic cardiomyopathy patients. Before the systematic screening, the patient had a diagnosis of hypertrophic obstructive cardiomyopathy and was treated accordingly including alcohol septal ablation to reduce the obstructive gradient. The confirmation of Fabry disease has led to discovery of the same variant in several members of her family. The identified variant was c.644A>G, p.Asn215Ser (N2015S) known to cause predominant cardiac involvement with late onset of the disease. The variant is amenable for an oral therapy by the small molecular chaperone migalastat which was started, then interrupted for recurrence of patient´s migraine and then re-initiated again after two years. During this period the patient received enzyme replacement therapy by agalsidase beta but developed a progressively worsening venous access. Our case illustrates the importance of systematic screening of patients with clinical evidence of hypertrophic cardiomyopathy in whom routine diagnostic process fails to discover Fabry disease, in particular variants with late onset cardiac manifestations. Many of the late onset variants are amenable for orally active therapy by migalastat which significantly improves the comfort of the treatment. Its long term results are analysed by a large international “Follow-me” registry which was designed to verify the validity of pivotal trials with migalastat in Fabry disease.

Viruses pose a great threat to people’s lives. Enterovirus A71 (EV-A71) infects children and infants all over the world with no FDA-approved treatment to date. Understanding the basic mechanisms of viral processes aids in selecting more efficient drug targets and designing more effective antivirals to thwart this virus. The 5´-untranslated region (5’-UTR) of the viral RNA genome is composed of a cloverleaf structure and an internal ribosome entry site (IRES). Cellular proteins that bind to the cloverleaf structure regulate viral replication, while those that bind to the IRES also known as IRES trans-acting factors (ITAFs) regulate viral translation. In this review, we survey the cellular proteins currently known to bind the 5’-UTR and influence viral translation and replication with emphasis on comparing proteins’ functions and localizations pre- and post-(EV-A71) infection. Comprehensive understanding of how the host cell’s machinery is hijacked and reprogrammed by the virus to facilitate its replication is crucial for developing effective antivirals.

The search for a continuous continental record of interglacial periods in semi-arid regions is problematic due to the absence of stable and continuous sedimentary systems over time in this type of climate. In this work, a relatively stable basin is described and analyzed during the last interglacial in a semi-arid region of the western Mediterranean. For this purpose a geomorphological, stratigraphic and sedimentological study has been carried out, with dating through 230Th. A semi-endorrheic Pleistocene basin has been identified, with two units that correspond to a fluvial-lacustrine system (unit P1) and an alluvial system (unit P2). Unit P1 has been dated in the MIS 5e interglacial episode. A framework is described in which the Aljezares Quaternary basin can be considered as a possible source of paleoenvironmental and paleoclimatic information in semi-arid regions from the last interglacial period in future studies.

Reduced glutathione (GSH) is an antioxidant in plants and is one of the important ways for plants to combat low-temperature stress. In this paper, Eriobotrya japonica Lindl. cv. Zaozhong No. 6 seedlings were used to study the effects of exogenous 5-aminolevulinic acid (ALA) application on glutathione synthesis and cyclic metabolism of loquat seedlings under low-temperature stress and to explore the regulatory mechanism of ALA on loquat cold tolerance. The results showed that ALA treatment could increase the content of GSH and the reduced glutathione/oxidized glutathione (GSH/GSSG) ratio in loquat leaf slices under low-temperature stress; reduce the electrolyte leakage rate and GSSG, H₂O₂ and MDA contents in leaf tissues; and alleviate the peroxidation damage caused by low temperature. ALA treatment increased the activity of γ-glutamine synthetase (γ-ECS) in loquat leaf slices under low-temperature stress and promoted the biosynthesis of reduced glutathione, thereby increasing the GSH content in leaf tissues. On the other hand, ALA treatment could also improve the activities of glutathione reductase (GR), glutathione S-transferase (GST) and glutathione peroxidase (GPX) and promote the cyclic regeneration of GSH, accordingly maintaining a high GSH/GSSG ratio, promoting the removal of reactive oxygen species (ROS), and enhancing the antioxidant capacity of leaves. The regulatory effect of ALA on enhancing the antioxidant capacity of loquat seedlings under low-temperature stress can be inhibited by L-buthionine-sulfoximine (BSO, GSH biosynthesis inhibitor). The results showed that ALA improved the antioxidant capacity of loquat seedlings under low-temperature stress, and GSH was involved in the regulation of the antioxidant effect of ALA on loquat seedlings under low-temperature stress.

Trace amine-associated receptor 5 (TAAR5) is a G protein-coupled receptor that belongs to the TAARs family (TAAR1-TAAR9). TAAR5 is expressed in the olfactory epithelium and is responsible for sensing 3-methylamine (TMA). However, recent studies showed that TAAR5 is also expressed in the limbic brain regions and is involved in the regulation of emotional behaviour and adult neurogenesis, suggesting that TAAR5 antagonism may represent a novel therapeutic strategy for anxiety and depression. We used the AtomNet® model, the first deep learning neural network for structure-based drug discovery, to identify putative TAAR5 ligands and tested them in an in vitro BRET assay. We found two mTAAR5 antagonists with low to submicromolar activity that are able to inhibit the cAMP production induced by TMA. Moreover, these two compounds also inhibited the mTAAR5 downstream signalling, such as the phosphorylation of CREB and ERK. These two hits exhibit drug-like properties and could be used to develop further more potent TAAR5 ligands with putative anxiolytic and antidepressant activity.

Enhanced permeation retention (EPR) was a significant milestone discovery by Maeda et al. paving the road for the emerging nanomedicine as a powerful tool in the fight against cancer. Sildenafil is a potent inhibitor of phosphodiesterase 5 (PDE-5) used for treatment of erectile dysfunction (ED) through the relaxation of smooth muscles and the modulation of vascular endothelial permeability. Overexpression of PDE-5 was reported in lung, colon, metastatic breast cancers and bladder squamous carcinoma. Accordingly, there has been a growing interest in using sildenafil as monotherapy or chemoadjuvant in EPR augmentation and management of different types of cancer. Sildenafil had been reported to increase the sensitivity of tumor cells of different origins to the cytotoxic effect of chemotherapeutic agents with augmented apoptosis mediated through inducing the expression of Bad and Bax proapoptotic proteins. It was also reported that the use of sildenafil prior to the administration of Doxorubicin (DOX) increased its EPR-related concentration in breast cancer tissues by 2 folds. Further, a substantial reason of anticancer chemotherapeutic failure is due to multidrug resistance (MDR), exacerbated by the overexpression of ATP-binding cassette (ABC) transporters such as ABCB1 and ABCCs. Sildenafil has demonstrated inhibitory effects on the efflux activity of ABCC4, ABCC5, ABCB1, and ABCG2, ultimately reversing MDR caused by these transporters. In this review, we critically examine the overall potential of sildenafil in enhancing EPR-based anticancer drug delivery pointing up the outcome of the most important related preclinical and clinical studies.

In this article we report the first investigation over time of the atmospheric conditions around TGFs occurrence, using GPS sensors in combination with geostationary satellite observations and ERA5 reanalyses data. The goal is to understand which characteristics are favourable to the development of these events and to investigate if any precursor signals can be expected. A total of 9 TGFs, occurred at a distance lower than 45 km from a GPS sensor, were analysed and two of them are shown here as an example analysis. Moreover, the lightning activity, collected by the World Wide Lightning Location Network (WWLLN) was used in order to identify any links and correlations with TGF occurrence and PWV trends. The combined use of GPS and the stroke rate trends identified, for all cases, a recurred pattern in which an increase of PWV is observed on a timescale of about two hours before the TGF occurrence that can be placed within the lightning peak. The temporal relation between the PWV trend and TGF occurrence is strictly related to the position of GPS sensors in relation to TGF coordinates. The life cycle of these storms observed by geostationary sensors, described TGFs producing clouds as intense with a wide range of extensions and, in all cases, the TGF is located at the edge of the convective cell. Furthermore, the satellite data give an added value in associating the GPS water vapor trend to the convective cell generating the TGF. The investigation with ERA5 reanalyses data showed that TGFs mainly occur in convective environment with not exceptional values with respect to the monthly average value of parameters measured in the same location. Moreover the analysis showed the strong potential of the use of GPS data for the troposphere characterization in areas with complex territorial morphology. This study provided indications on the dynamics of convective systems linked to TGFs and will certainly help refine our understanding on their production highlights a potential approach through the use of GPS data to explore the lightning activity trend and the TGFs occurrence.

Ten-eleven translocation (TET) enzymes are implicated in DNA demethylation through dioxygenase activity, which converts 5-methylcytosine to 5-hydroxymethylcytosine (5-hmC). However, the specific roles of TET enzymes and 5-hmC levels in head and neck squamous cell carcinoma (HNSCC) have not yet been evaluated. In this study, we analyzed 5-hmC levels and TET mRNA expression in a well-characterized dataset of 117 matched pairs of HNSCC tissues and normal tissues. 5-hmC levels and TET mRNA expression were examined via enzyme-linked immunosorbent assay and quantitative real-time PCR, respectively. 5-hmC levels were evaluated according to various clinical characteristics and prognostic implications. Notably, we found that 5-hmC levels were significantly correlated with tumor stage (P = 0.032) and recurrence (P = 0.018). Univariate analysis revealed that low levels of 5-hmC were correlated with poor disease-free survival (DFS; log-rank test, P = 0.038). The expression of TET family genes was not associated with outcomes. In multivariate analysis, low levels of 5-hmC were evaluated as a significant independent prognostic factor of DFS (hazard ratio: 2.352, 95% confidence interval: 1.136–4.896; P = 0.021). Taken together, our findings showed that reduction of TET family gene expression and subsequent low levels of 5-hmC may affect the development of HNSCC.

The three heat-induced coffee contaminants acrylamide, furfuryl alcohol (FA) and 5-hydroxymethylfurfural (HMF) were analyzed in a collective of commercial samples as well as in Coffea arabica seeds roasted under controlled conditions from very light Scandinavian style to very dark Neapolitan style profiles. Regarding acrylamide, average contents in commercial samples were lower than in a previous study in 2002 (196 compared to 303 µg/kg). The roasting experiment confirmed the inverse relationship between roasting degree and acrylamide content, i.e. the lighter the coffee the higher the acrylamide content. However, FA and HMF were inversely related to acrylamide and found in higher contents in darker roasts. Therefore, mitigation measures must consider all contaminants and not be focused isolatedly on acrylamide, specifically since FA and HMF are contained in much higher contents with lower margins of exposure compared to acrylamide.

Enzymes reliant on pyridoxal 5'-phosphate (PLP), the metabolically active form of vitamin B6, hold significant importance in both biology and medicine. They facilitate various biochemical reactions, particularly in amino acid and neurotransmitter metabolisms. Vitamin B6 is absorbed by organisms in its non-phosphorylated form and phosphorylated within cells by pyridoxal kinase (PLK) and pyridox-(am)-ine 5'-phosphate oxidase (PNPOx). The flavin mononucleotide dependent PNPOx enzyme converts pyridoxine 5'-phosphate and pyridoxamine 5'-phosphate into PLP. PNPOx is vital for both biosynthesis and salvage pathways in organisms producing B6 vitamers. However, for those depending on vitamin B6 as nutrient, PNPOx participates only in the salvage pathway. Transferring PLP produced by PNPOx to client apo-enzymes is indispensable for their catalytic function, proper folding and targeting to specific organelles. PNPOx activity deficiencies due to inborn errors lead to severe neurological pathologies, particularly neonatal epileptic encephalopathy. PNPOx enzymes from different organisms maintain PLP homeostasis through highly regulated mechanisms, including structural alterations throughout the catalytic cycle and allosteric PLP binding influencing substrate transformation at the active site. Despite shared features, species-specific regulations are evident among PNPOx enzymes.

This study aimed to use remote sensing and GIS to detect changes in surface water and wetlands in the Kumasi Metropolis over a period of 20 years (2002-2022). Landsat images were processed using the QGIS software, and the Maximum Likelihood Algorithm was used to perform supervised classification of land use land cover, while raster calculator aided in detecting wetlands by calculation for NDWI, MNDWI, and AWEI. The results showed that the majority of the landscape in the Kumasi metropolis was made up of built-up areas (79.4%), followed by agricultural lands (13.3%) and wetlands (7.3%). Over the 20-year period, built-up areas had gained 20.7% of the total landscape, while agricultural lands and wetlands had lost 16.7% and 4.0%, respectively. All water index methods recorded an increase in non-water cover and a loss of water cover over the period, with surface water decreasing by 5% and non-water land cover increasing by 5%. The study concludes that there have been significant changes in wetlands and surface water land use and land cover within the Kumasi Metropolis over the past 20 years, and recommends the enforcement of legislation on surface water protection in the area to protect wetlands

China is rich in coal resources under water bodies. However, for a long time, the safety prediction of high-intensity mining under water bodies is one of the problems encountered by the coal industry. It is of great significance to realize safe mining under water bodies, improve the recovery rate of coal resources and protect reservoir resources. Therefore, this article takes the No. 5 coal seam and No. 11 mining area of Wangwa Coal Mine as the research object, and integrates physical simulation, numerical simulation, theoretical analysis and other methods to study the development height of water-conducting fracture zones in fully mechanized top coal caving mining. Solid-liquid coupling physical simulation test reveals the failure characteristics of overlying strata in goaf and the seepage law of reservoir water under the influence of mining. By comparing the monitoring data of borehole leakage, the measured data obtained by borehole peeping with the height data of water-conducting fracture zone obtained by the traditional empirical formula of three-under standard, the error between the two is as high as -29.39 %. In this case, the variance correction coefficient is used to correct the empirical formula, and on this basis, in order to effectively protect the surface water dam and water body, the mining height of coal seam in the working face with limited height mining is inversely derived. The research results provide a basis for the safety prediction of high-intensity mining under the reservoir dam in the ecologically fragile areas of western China and provide a scientific guarantee for the formulation of safety measures under such conditions.

Since the 21st century, China's urbanization process has been rapid development, the concept and function of urban public space in the city has been gradually paid attention to. In order to guarantee life and water, most urban construction relies on rivers, and Bridges are the most important way to communicate between urban areas. The main functional part of the bridge is the span structure, that is, the bearing structure of the bridge, and the lower part of the "gray" space formed by the bridge structure. Considering the social level, with the economic growth and urbanization development, people have brought a better living environment and quality of life, and also improved the requirements for urban public environment. In the increasingly tense urban space, how to use and transform the space under the bridge is a problem that needs to be considered and solved. In view of this problem, in this study, we try to solve the micro-transformation of space under Bridges in cities through public art from the perspective of "regional culture" and "art for all". This paper analyzes the micro-transformation of space art under Bridges in two large cities of Shanghai and Foshan, namely, the space under Bridges under Songhong Road in Shanghai, the space under Bridges under Central Of Suzhou River and the space under Bridges under Pingsheng Bridge in Foshan. This paper discusses the cultural intervention of "regional culture" in the micro-transformation of the space under the bridge, and the influence and effect of "art for all" on the public art space under the bridge after the transformation to the community and the public.

Cholangiocarcinoma is an aggressive cancer with limited treatment options. Current therapies, such as cisplatin and 5-fluorouracil (5-FU), often cause side effects and drug resistance. This study investigated a potential new approach by combining a peanut skin extract (KK4-PSE) with these drugs. The extract effectively inhibited the growth of cholangiocarcinoma cells in laboratory studies and showed even greater selectivity for cancer cells compared to healthy cells. When combined with cisplatin or 5-FU, KK4-PSE enhanced the drugs' effects, leading to cell cycle arrest and increased cell death. These combined treatments also reduced levels of proteins that promote cancer cell survival. In animal models, KK4-PSE combined with 5-FU showed superior tumor suppression compared to the combination with cisplatin. Overall, these findings suggest that KK4-PSE may be a promising synergistic agent to improve the effectiveness of chemotherapy for cholangiocarcinoma, warranting further clinical investigation.

The construction industry has a notable negative impact on the environment; thus, the promotion of the use of timber structures is an alternative to mitigate its effects. The research develops an artificial intelligence-based decision approach in the calculation of timber structures focused on the enhancement of the sustainability of roof structures. Based on the optimization carried out through genetic algorithms and the framework established in Eurocode 5, a general set of equations has been proposed for a laminated timber roof structure. The tool, which determines the most suitable roof structure for each strength class of laminated timber, allows for the determination of the dimensions of beams and purlins and their respective separations in order to minimize wood consumption. The ultimate goal is to offer multiple solutions regarding strength classes and structural designs in order to foster informed sustainable choices that promote efficient use of resources in construction.

Wood is poised to become a material of choice for future construction. When appropriately managed, it is a renewable material with unique mechanical properties. Beyond its inherent sustainability, the use of wood has a crucial role in addressing climate change concerns due a significantly lower energy consumption and emissions during manufacturing and transportation, while simultaneously acting as a carbon sink. Thus, there has been a growing demand for hardwoods for structural applications, including Castanea sativa Mill., the focal point of this investigation. Albeit in a limited capacity, Eurocode 5-2 offers friction coefficients for softwoods, but it falls short for hardwoods which it is a gap to bridge with this research. These coefficients play a critical role in numerical simulations involving friction, enabling the optimization of joints and, by extension, the overall structural integrity. Test samples were evaluated at 18% moisture content, which is typical of Service Class 2, for various orientations of timber-to-timber and timber-to-steel friction. Considering previous friction coefficients at 12% moisture content, the linear variation was evaluated at an intermediate value of 15%. The results provide an experimental database for numerical simulations and highlight the influence of moisture content on the coefficients, which increase linearly along moisture percentages.

Cancer being a multi-factorial disease, a multi-target approach is needed to treat it with minimal side-effects. Therefore, combined use of a proven herbal formula with chemo-therapy could be the better therapeutic. It may maintain homeostasis by synergistically targeting multiple signaling pathways involved in tumorigenesis, thus circumventing recurrence, resistance, and immunosuppression. Here we aim to determine the effectiveness and safety of an FDA-approved herbal formula, SR033 in combination with 5-fluorouracil (5FU) and paclitaxel (PTX). We report chemo-sensitization and chemo-synergy in HeLa and MCF-7 cell lines, immunomodulation of COX-2, PD-L1, VEGF and TGFβ and overall survival in-vitro and in-vivo via oral and topical delivery of SR033. In-vitro, SR033/5FU significantly reverses 5FU and PTX-resistance, lower COX-2, and PD-L1, resulting in TGFβ/ VEGF axis modulation. Furthermore, the study suggests that due to anti-oxidative potential of SR033, oral administration exerts chemo-preventive activity and restores cellular compartment in solid tumor and ascites-bearing mice models. Furthermore, the topical application, SR033L with low-dose 5FU increases survival rate, reduces tumor growth, and completely restores local and peripheral neutrophil-lymphocyte ratio in solid tumor mice model. The study indicates that SR033 could be a strong candidate in combination with low-dose 5FU and PTX for a holistic approach to cancer management.

The described data set contains features from the machine control of a five-axis milling machine. The features were recorded during thirteen series productions. Each series production includes a changeover process in which the machine was set up for the production of a different product. In addition to the timestamps and the twenty recorded features derived from Numerical Control (NC) control variables, the data set also contains labels for the different production phases. For this purpose, up to 23 phases were assigned, which are based on a generalized milling process. The data set consists of thirteen .csv files, each representing a series production. The data set was recorded in a production company in the contract manufacturing sector for components with real series orders in ongoing industrial production.

Toxoplasma gondii is a widespread protozoan parasite that infects most warm-blooded animals, and felids can serve as intermediate and definitive hosts. Pathological diagnosis and serological and etiological investigations were conducted on a captive caracal (Caracal caracal) carcass collected from China in 2022. Pathological diagnosis revealed that cardiac insufficiency, pulmonary edema, hepatic failure, and renal insufficiency were the causes of the caracal’s death. A modified agglutination test (cut-off: 1:25) revealed that IgG antibodies against T. gondii were present in the myocardium juice, hydroperitoneum, and hydropericardium (≥1:800). A viable T. gondii (TgCaracalCHn2) strain was isolated from the tissue samples (heart, brain, spleen, and skeletal muscle) of this caracal using a mouse bioassay. The genotype of TgCaracalCHn2 was ToxoDB#5 (Type II variant), as determined by RFLP-PCR. The strain was avirulent in Swiss mice and matched the prediction of ROP18 and ROP5 gene alleles of TgCaracalCHn2 (2/2). Many tissue cysts (203 ± 265) were observed in mice brains after inoculation with TgCaracalCHn2 tachyzoites. ToxoDB#5 is the dominant genotype in North American wildlife, and this is the first documented isolation of T. gondii ToxoDB#5 from China. This indicates that caracals can accelerate the transmission of T. gondii genotypes.

Inosine 5'-monophoaphate (IMP) allows animals to sense umami. Intake of IMP in C57/KsJ-db/db (db/db) mice induced lipohyperplasia causing the liver cirrhosis, however, how to that of in normal mammals injure health is still unclear. Thus, we had investigated that intake of IMP in C57BL/6J mice effected its metabolic functions. We found that intake of 255 M/d IMP in C57BL/6J mice for 4 months induced hyperlipidemia and body fat rate raised. In mechanism, the expressions of ACC1 and phosphorylated ACC2 in hepatocytes were increased though IMP promoting phosphorylation of AMPK. The increased ACC1 promoted the conversion of acetyl-CoA into TG. These TG were transported out of hepatocytes to avoid NAFLD, causing a deficiency of acetyl-CoA in liver, and then the increased phosphorylated ACC2 promoted cytoplasm fatty acids into mitochondria to convert into acetyl-CoA though the fatty acids β-oxidation pathway, causing a deficiency of fatty acids. Therefore, liver enhanced the absorption of exogenous fatty acids, which were converted into TG caused lipohyperplasia. Moreover, intake of IMP in normal mice induced complement system weaken in liver causing mild inflammation. Our data not only alerted that humans avoid excessive intake of IMP, but also provided novel insights into the adipose of metabolic dysfunctions.

Dehydroaromatization of methane (MDA) is of great interest as a promising process for processing natural and associated petroleum gases, the main component of which is methane. The rapid loss of catalyst activity because of coke formation hinders the introduction of the DHA methane process into industry. Therefore, the aim of the research was to find ways to improve Mo/ZSM-5 catalysts for MDA. The paper presents the results of the synthesis of high-silica zeolites of the ZSM-5 type with a microporous and micro-mesoporous structure, the preparation of Mo/ZSM-5 catalysts based on them, and the study of the physicochemical and catalytic properties of the obtained samples during the non-oxidative conversion of methane into aromatic hydrocarbons. Zeolite catalysts were investigated by IR spectroscopy, X-ray diffraction, TPD-NH3, SEM, HR-TEM, N2-adsorption. It was found that the addition of carbon black at the stage of synthesis of zeolite type ZSM-5 does not lead to structural changes, the obtained samples have a crystallinity equal to 100%. The creation of the micro-mesoporous structure in Mo/ZSM-5 catalysts lead to an increase in their activity and stability in the process of methane dehydroaromatization. The highest conversion of methane is observed on a 4.0%Mo/ZSM-5 catalyst prepared based on of zeolite synthesized using 1.0% carbon black, and is 13.0% in 20 minutes of reaction, while the benzene yield reaches 7.0%. It has been shown by HR-TEM that a more uniform distribution of the active metal component is observed in a zeolite catalyst with a micro-mesoporous structure than in a microporous zeolite.

Pancreatic cancer exhibits a poor prognosis due to the lack of early diagnostic biomarkers and the resistance to conventional chemotherapy. CD44 has been known as a cancer stem cell marker, and plays tumor promotion and drug resistance in various cancers. Especially, the splicing variants are overexpressed in many carcinomas, and play essential roles in the cancer stemness, invasiveness or metastasis, and resistance to treatments. Therefore, the understanding of each CD44 variant (CD44v) function and distribution in carcinomas is essential for the establishment of CD44-targeting tumor therapy. In this study, we immunized mice with CD44v3–10-overexpressed Chinese hamster ovary-K1 (CHO) cells, and established various anti-CD44 monoclonal antibodies (mAbs). One of the established clones (C44Mab-3; IgG1, kappa) recognized peptides of the variant 5-encoded region, indicating that C44Mab-3 is a specific mAb for CD44v5. Moreover, C44Mab-3 reacted with CHO/CD44v3–10 cells or pancreatic cancer cell lines (PK-1 and PK-8) by flow cytometry. The apparent KD of C44Mab-3 for CHO/CD44v3–10 and PK-1 was 7.1 × 10−10 M and 1.9 × 10−9 M, respectively. C44Mab-3 could detect the exogenous CD44v3–10 and endogenous CD44v5 in western blotting, and stained the formalin-fixed paraffin-embedded pancreatic cancer cells, but not normal pancreatic epithelial cells in immunohistochemistry. These results indicate that C44Mab-3 is useful for detecting CD44v5 in various applications, and expected for the application of pancreatic cancer diagnosis and therapy.

Pancreatic cancer is projected to be the second leading cause of cancer-related death by 2030 in the US. The benefits of the most common systemic therapy for various pancreatic cancer have been masked by high drug toxicities, adverse reactions, and resistance. Using nanocarriers like liposomes to overcome these unwanted effects has become very popular. This study aimed to formulate 1,3-bis tetrahydrofuran-2yl-5FU (MFU)-loaded liposomal nanoparticles (Zhubech) and evaluate the stability, MFU release kinetics, in vitro and in vivo anticancer activities, and biodistribution. Particle size and zeta potential were determined using a particle size analyzer, while cellular uptake of rhodamine-entrapped liposomal nanoparticle (Rh0-LnP) was determined by confocal microscopy. Gadolinium hexanoate (Gd-Hex) was synthesized and entrapped into the liposomal nanoparticle (LnP) (Gd-Hex-LnP) as a model contrast agent, to evaluate gadolinium biodistribution and accumulation by LnP in vivo using inductively coupled plasma mass spec-trometry (ICP-MS). The mean hydrodynamic diameters of the blank LnP and Zhubech were 90.0 ± 0.65 nm and 124.9 ± 3.2 nm, respectively. The hydrodynamic diameter of Zhubech was found to be highly stable at 4o C and 25oC for 30 days in solution. In vitro drug release of MFU from Zhubech formulation exhibited the Higuchi model (R2 value = 0.95). Both Miapaca-2 and Panc-1 treated with Zhubech showed reduced viability, two- or four-fold lower than that of MFU-treated cells in 3D spheroids (IC50Zhubech = 3.4 ± 1.0μM vs IC50MFU = 6.8 ± 1.1μM) and organoids (IC50Zhubech = 9.8 ± 1.4μM vs IC50MFU = 42.3 ± 1.0μM) culture models. Confocal imaging confirmed high uptake of rhodamine-entrapped LnP by Panc-1 cells in a time-dependent manner. Tumor efficacy studies in PDX bearing mouse model revealed more than 9-fold decrease in mean tumor volumes in Zhu-bech treated (108 ± 13.5 mm3) compared to 5-FU treated (1,107 ± 116.2 mm3) animals respectively. This study demonstrates that Zhubech may be a potential candidate for delivering drugs for pancreatic cancer treatment.

Single-stand selective monofunctional uracil DNA glycosylase 1 (SMUG1) works to remove uracil and certain oxidized bases from DNA during base excision repair (BER). This review provides a historical characterization of SMUG1 and 5-hydroxymethyl-2'-deoxyuridine (5-hmdU) one important substrate of this enzyme. Biochemical and structural analyses provide remarkable insight into the mechanism of this glycosylase revealing SMUG1 has a unique helical wedge which influences damage recognition during repair. Rodent studies suggest that, while SMUG1 shares substrate specificity with another uracil glycosylase UNG2, loss of SMUG1 can have unique cellular phenotypes. This review highlights the multiple roles SMUG1 may play in preserving genome stability, and how the loss of SMUG1 activity may promote cancer. Finally, we discuss recent studies indicating SMUG1 has moonlighting functions beyond BER, playing a critical role in RNA processing including the RNA component of telomerase.

Multiple studies have shown that hospital settings are poorly cleaned during terminal cleaning. The adequacy of these cleaning methods has been undermined by presence of multi drug resistant bacteria on hospital surfaces. This case is even more serious in developing countries leading to health care- associated infections that pose a great threat to patients, visitors and health care providers in hospital settings.This study used various microbiological techniques to test for antibiotic susceptibility profiles of bacteria present at Thika Level 5 Hospital surfaces, Kenya. A simple random cross sectional study was performed, with a total of 85 samples being collected from five different sites. The sites included male and female wards, health care personnel offices, latrine, and kitchen surfaces. Samples were collected using sterile swabs, dipped in normal saline, and transported to the laboratory within 2Hours for processing.Of the 85 plates cultured, 47 plates showed bacterial growth (55%) on selective media with a significant P value of 0.0357. Seven different species of bacteria were identified biochemically from all sites, Escherichia coli was the most abundant species (28%), and the least was Salmonella typhii (5%). Multiple drug resistance was common in the different bacteria identified. All isolates were resistant to chloramphenical and susceptible to gentamycin. The most resistant microorganism was Staphylococcus aureus (50%), and the least resistant microorganism was Klebsiella pneumoniae (12.5%). The antimicrobial resistant bacterial species identified in this study have been documented to cause serious health care associated infections. These results present a significant public health concern because there is a possibility of patients, staff and visitors contacting nosocomial infections when they come into contact with surfaces at Thika Level 5 Hospital surfaces, Kenya.

Anxiety disorders manifest in women more than in men by almost twofold. This narrative review aims to summarize the sex-related biological factors, which underpin anxiety, focusing on the interactions of sex and tryptophan/serotonin with anxiety.A literature search was conducted using Google Scholar, PubMed/MEDLINE, Scopus, and EMBASE databases from inception until December 31, 2017. This review shows that sex may interact with many serotonin functions thereby modulating anxiety, including 5-HT1A and 5-HT2C receptors, 5-HT transporter and central 5-HT concentrations and metabolism. Sex-steroids modulate the expression of serotonin transporter genes, creating a difference in serotonin availability. Sex and estrous cycle phases lead to varying anxiety responses to tryptophan depletion. Testosterone, progesterone and estrogen are important factors in mediating sex differences in serotonin responses to anxiety-generating behavioral tests. At prenatal levels, there are sex-related differences in the reciprocal relationships between serotonin and the HPA-axis, which modulate anxiety-like behaviors. Activated immune-inflammatory pathways induce indoleamine-2,3-dioxynease (IDO) and the tryptophan catabolite (TRYCAT) pathway thereby increasing tryptophan degradation and increasing the production of TRYCATs including kynurenine and quinolinic acid, which may create an overall anxiogenic effect. The effects of immune activation on IDO are significantly more pronounced in women than men and therefore females may show increased levels of anxiogenic TRYCAT following immune challenge. Aberrations in the IDO-activated TRYCAT pathway are found in pregnant females and parturients and are associated with increased anxiety levels in the postnatal period. The results of this review underscore the necessity of studying the associations between serotonin and anxiety in both sexes taking into account the effects of immune activation on IDO and production of anxiogenic TRYCATs. Future anxiety research should focus on the interactions between serotonin/tryptophan and sex, sex hormones, the menstrual cycle, pregnancy, the HPA axis and the immune system through production of anxiogenic TRYCATs.

The objective is to describe infant feeding practices and the nutritional status of infants under six months among Syrian refugees in Greater Beirut, Lebanon. A cross-sectional study was conducted among Syrian refugee mothers with children under five years (July-October 2018), mothers with infants under six months were included in the analysis (n=114). Additionally, eleven focus groups discussions were conducted to explore supportive factors and barriers associated with early breastfeeding practices. The prevalence of pre-lacteal feeding was high (62.5%), whereas early initiation of breastfeeding (EIBF) was low (31%), and exclusive breastfeeding (EBF) very low (24.6%). About one-fifth of the infants were suffering from anemia (20.5%) and 9.6% were wasted. Supporting factors of adequate infant feeding practices comprised knowledge on maternal nutrition and EBF, in addition to receiving support from healthcare professionals and family members. Identified barriers included preterm delivery, pre-lacteal feeding, an at-risk waist circumference and moderate to severe depression among mothers, bottle feeding, early introduction of food, maternal health reasons, breastmilk substitutes’ distribution, and misinformation offered by mothers-in-law. To address sub-optimal feeding practices documented among Syrian refugees in our study, existing infant and young child feeding policies and programs need to be strengthened and revised to tackle the identified gaps.

Automation of forest field reference data collection has been an intensive research objective for laser scanning scientists ever since the invention of terrestrial laser scanning more than two decades ago. Recently, it has been proposed that such automated data collection providing both the tree heights and stem curves would require a combination of above-canopy UAV point clouds and terrestrial point clouds. In this study, we demonstrate that an under-canopy UAV laser scanning system utilizing a rotating laser scanner can alone provide accurate estimates of the canopy height and the stem volume for the majority of the trees in a boreal forest. To this end, we mounted a rotating laser scanner based on a Velodyne VLP-16 sensor onboard a manually piloted UAV. The UAV was commanded with the help of a live video feed from the onboard camera of the UAV. Since the system was based on a rotating laser scanner providing varying view angles, all important elements such as treetops, branches, trunks, and ground could be recorded with laser hits. In an experiment including two different forest structures, namely sparse and obstructed canopy, we showed that our system can measure the heights of individual trees with a bias of -20 cm and a standard error of 40 cm in the sparse forest and with a bias of -65 cm and a standard error of 1 m in the obstructed forest. The accuracy of the obtained tree height estimates was equivalent to airborne above-canopy UAV surveys conducted in similar forest conditions. The higher underestimation and higher inaccuracy in the obstructed site can be attributed to three trees with a height exceeding 25 m and the applied laser scanning system VLP-16 that had a limited height measurement capacity when it comes to trees taller than 25 m. Additionally, we used our system to estimate the stem volumes of individual trees with a standard error at the level of 10%. This level of error is equivalent to the error obtained when merging above-canopy UAV laser scanner data with terrestrial point cloud data. Future research is needed for testing new sensors, for implementing autonomous operation inside canopies through collision avoidance and navigation through canopies, and for developing robust methods that work also with more complex forest structure. The results show that we do not necessarily need a combination of terrestrial point clouds and point clouds collected using above-canopy UAV systems in order to accurately estimate the heights and the volumes of individual trees.

Since the beginning, humans advanced their civilization by making better tools to improve their lives. Tools and products were designed for better living considering manufacturing issues, cost and time as predominant criteria. It has become clear that not considering environment and society, both at local/global levels, has now become a major impediment affecting living conditions on a large portion of the Earth and in many societies. Design methodologies should lead to creative solutions with consideration to engineering and economics for practicality but also to environmental and social constraints for sustainability. We propose a comprehensive design methodology based on multidisciplinary design to include the knowledge of humanities, environmentalists, science and engineering, and allowing for experts’ inputs from these areas to provide a holistic approach to engineering design . For example, experts in humanities are expected to interact with stakeholders to evaluate their value systems to provide guidance for the design. The methodology that we synthesize is new and combines (i) Societal level impacts at all scales, (ii) Environmental impacts and (iii) Engineering design with economic impacts, including uncertainty considerations. The proposed design methodology is called Social-Environmental-Economical-Engineering Framework (SEEEF). It can utilize concepts and tools such as Circular Design, Doughnut Economics, design based on environmental life cycle analysis, among others. SEEEF is quantity based and provides steps for evaluating any project or product in an objective manner and will help train engineers in design for sustainability. It also provides non-engineers with a significant role in design to increase their understanding of the hard constraints of engineering. Ultimately, SEEEF allows society to take an informed decision considering short/long term and local/global impacts of the design and the pertinent uncertainties.

The impacts of climate change on precipitation and drought characteristics over Bangladesh were examined by using the daily precipitation outputs from 29 bias-corrected general circulation models (GCMs) under the representative concentration pathway (RCP) 4.5 and 8.5 scenarios. A precipitation-based drought estimator, namely, the Effective Drought Index (EDI), was applied to quantify the characteristics of drought events in terms of the severity and duration. The changes in drought characteristics were assessed for the beginning (2010–2039), middle (2040–2069), and end of this century (2070–2099) relative to the 1976–2005 baseline. The GCMs were limited in regard to forecasting the occurrence of future extreme droughts. Overall, the findings showed that the annual precipitation will increase in the 21st century over Bangladesh; the increasing rate was comparatively higher under the RCP8.5 scenario. The highest increase of rainfall is expected to happen over the drought-prone northern region. The general trends of drought frequency, duration, and intensity are likely to decrease in the 21st century over Bangladesh under both RCP scenarios, except for the maximum drought intensity during the beginning of the century, which is projected to increase over the country. The extreme and medium-term drought events did not show any significant changes in the future under both scenarios except for the medium-term droughts, which decreased by 55% compared to the base period during the 2070s under RCP8.5. However, extreme drought days will likely increase in most of the cropping seasons for the different future periods under both scenarios. The spatial distribution of changes in drought characteristics indicates that the drought-vulnerable areas are expected to shift from the northwestern region to the central and the southern region in the future under both scenarios due to the effects of climate change.

This work studied the corrosion of welded pipes and how welding destroyed surface film of pipes. Surface reaction of a welded pipe is key to understanding phenomena and important factors during the corrosion. This paper presents experiment and CFD modeling approaches of a welded pipe corrosion under salt vapor condition. The pipes were welded at currents of 60 A,70 A and 80 A to observe the effect of welding current on corrosion. A welded pipe is a stainless-steel ASTM A312 grade 304L and period of experiment about 0-600 hours that they are tested in vertical and horizontal alignments. In CFD software, there is not direct model of corrosion but it can use surface reaction and create add-on species and chemical reaction technique for imitating the corrosion mechanism. The modeling approaches of corrosion have presented in 3-dimensional transient times in CFD simulation. Surface reactions were performed by Species Model which involve site species. Site species in Species Model took place at gas-solid interfaces and in this case are salt vapor and surface pipe. Chemical reaction rate on the surface controls lost weight of a welded pipe and the model can be validated with experiment. In conclusion, in period 0-600 hours error between CFD modeling and experiment have error trend decreased. The error at 600 hours is 6% both of vertical pipe and horizontal pipe test. The modeling approaches closely with the performed experiment and can be accepted. Moreover, the model is able to predict corrosion of a welded pipe of different sizes and their lost weight after 600 hours without experiment. Also the model can predict lifetime of pipe.

L-17 is a thiadiazine derivative with putative anti-inflammatory, neuroprotective, and antidepressant-like properties. In this study, we applied combined in silico and in vivo electrophysiology techniques to reveal the potential mechanism of action of L-17. PASS 10.4 Professional Extended software suggested that L-17 might have pro-cognitive, antidepressant, and antipsychotic effects. Docking energy assessment with AutoDockVina predicted that the binding affinities of L-17 to the serotonin transporter (SERT) and serotonin receptors 3 and 1A (5-HT3 and 5-HT1A) are compatible to the selective serotonin reuptake inhibitor (SSRI) fluoxetine and selective antagonists of 5-HT3 and 5-HT1A receptors, granisetron and WAY100135, respectively. However, while the binding mechanisms of L-17 to the SERT and 5-HT1A receptor were similar to fluoxetine and WAY100135, its interacting with 5-HT3 receptor might be substantially different from this of granisetron. Acute administration of L-17 led to dose-dependent inhibition of firing activity of 5-HT neurons of the dorsal raphe nucleus. This inhibition was partially reversed by subsequent administration of WAY100135. Based on both in silico and in vivo electrophysiology assessments, we suggest that L-17 is a potent 5-HT reuptake inhibitor and a putative partial agonist of 5-HT1A receptors. As such, L-17 in particular and thiadiazine derivatives, in general, might be a representative of a new class of antidepressant drugs. Since L-17 also possesses neuro- and cardioprotective properties, it can be useful in affective illness developing due to the general medical condition, such as post-stroke and post-myocardial infarction (MI) depression.

Even with 100% certainty of a complete cure for breast cancer (BC), there is still a long way to go toward more efficient treatment. This requires sensitive and timely detection and accurate pre/post-clinical characterizations. Despite the availability of advanced diagnostic tools, many cancer patients lack access to efficient diagnostics that are both highly reliable and affordable. The fluorescence-based optical technique aims to make another significant leap forward in improving patient safety. It offers a convenient operation that reduces healthcare costs compared to visual examination tools (VETs). The primary and metastatic stages of BC consider different cancerous cell lines (MDAs), meaning the highest number of cells in this research (up to 300,000) represents the metastatic stages of BC, and 50,000 represents the primary level of BC developments have been studied based on fluorescence-enhanced photodynamic characterizations. The ability to characterize the fluorescence caused by MDA with 50,000 cells compared to the dominant radiation of MDA with 300,000 cells is emphatic proof of the high potential of fluorescence technique in timely BC detections, specifically before it spreads to the axillary lymph nodes. The specific cell numbers of 50,000 and 300,000 were chosen arbitrarily based on the cultivation of common biological limitations. Comparing the outcomes between 50,000 and 300,000 cells allows for evaluating the fluorescence technique’s diagnostic capability across various stages of breast cancer. This assessment provides valuable insights into the effectiveness of the fluorescence-based characterizing approach in detecting cancerous cells at different stages of the disease. Here, we have assessed fluorescence’s spectral shift and intensity difference as a diagnostic approach to distinguish between cancerous and normal breast cells. This study also presents a two-way structure of the 5-aminolevulinic acid (5-ALA) prodrug and Fluorescein Sodium (FS) effect in BC cell characterization from the perspective of photodynamical procedures and the detection side. 5-ALA induces an accumulation of protoporphyrin IX (PpIX) photosensitizer through a biosynthetic pathway, leading to red radiation of fluorescence measurements depending on different factors, such as temperature, incubation time, added glucose of the culturing medium, as well as photosynthesis processes. The presence and progression of breast cancer can be indicated by elevated levels of Reactive Oxygen Species (ROS), which are associated with the production of PpIX in cells following the administration of 5-ALA. Also, nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) fluorophores are recognized as the main factors for fluorescence emissions at around 420-580 nm emission intervals. Considering the MDA’s high metastatic potential, the impact of 5-ALA on MDA’s cellular morphology and viability has been investigated. The molecular fluorophores are the primary probes to MDA’s cellular photodynamic considerations, allowing this widespread pre/post-clinical approach. The fluorescence signal reduction due to decreased cell viability and increased MDA’s cellular death rate after 24 hours of the 5-ALA-induced staining corresponds to the changes in lipid metabolism enzymes of MDAs cultured at different doses, which could be known as a cell death inducer function. Furthermore, statistical concerns have been studied using PCA multivariate component analysis to differentiate MDA cell lines administrated by 5-ALA.

Methylation is a biochemical process involving the addition of a methyl group (-CH3) to various chemical compounds. It plays a crucial role in maintaining the homeostasis of the endothelium, which lines the interior surface of blood vessels and has been linked, among other conditions, to coronary artery disease (CAD). Despite significant progress in CAD diagnosis and treatment, intensive research continues into genotypic and phenotypic CAD biomarkers. This review explores the significance of the methylation pathway and folate metabolism in CAD pathogenesis, with a focus on endothelial dysfunction resulting from deficiency in the active form of folate (5-MTHF). We discuss emerging areas of research into CAD biomarkers and factors influencing the methylation process. By highlighting genetically determined methylation disorders, particularly the MTHFR polymorphism, we propose the potential use of the active form of folic acid (5-MTHF) as a novel CAD biomarker and personalized pharmaceutical for selected patient groups. Our aim is to improve the identification of individuals at high risk of CAD and enhance their prognosis.

Although migraine belongs to the main causes of disability worldwide the mechanisms of its pathogenesis are poorly known, which is among the reasons that this disease is underdiagnosed and undertreated. As migraine diagnosis is based on the subjective assessment of symptoms, there is a need to establish objective markers of its occurrence and severity. Tryptophan (TRP) metabolism has been associated with the pathogenesis of neurological and psychiatric disorders. In the present work, we investigated an association between migraine and the urine concentration of TRP and its metabolites 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QA) in 21 low-frequency episodic migraine patients and 32 controls. Migraine patients displayed lower urinary levels of 5-HIAA and KYNA, but KYN and QA were enhanced as compared with the controls. Consequently, the patients were characterized by different values of the 5-HIAA/TRP, KYN/TRP, KYNA/KYN, and KYNA/QA ratios. Furthermore, urinary concentration of 5-HIAA was negatively correlated with Migraine Disability Assessment score, monthly migraine, and monthly headache days. A negative correlation between Patient Health Questionnaire 9 scores assessing depression. In conclusion, the urinary 5-HIAA level may be an easy-to-determine marker of migraine occurrence and severity and may contribute to the identification of migraine patients with depression.

Objective: to retrospectively evaluate the incidence rate (IR) of echocardiographic signs suspected for pulmonary hypertension (PH) in Systemic sclerosis (SSc) patients after the introduction of a combination therapy with bosentan and sildenafil for treatment or prevention of digital ulcers. Methods: patients attending the Scleroderma Unit of the Universital Hospital of Careggi from July 2010 to July 2023 were enrolled. Patients older than 18 years old, with an history of digital ulcers, treated with bosentan and sildenafil in combination for at least 12 months were included. Patients with a diagnosis of PH preceding the introduction of the therapy were excluded. Demographical data, disease duration, laboratoristic and instrumental data (pulmonary function tests, echocardiographic estimation of pulmonary artery pressure (PAPs) and ultrasonographic value of renal resistive index) were collected. The IR of echocardiographic signs suspected for pulmonary hypertension and their 95% confidence interval were calculated in events/1000 patients-years.Results: forty-seven patients were enrolled; mean disease duration was 12,14 years (SD 5,87). Mean duration of the combination treatment was 78.33 (SD 41.37) months and total at-risk time was 3525 months. Two patients (4,2%) presented echocardiographic signs of PH (sPAP 50 mmHg and 40 mmHg); the IR was calculated to be 6.8/1000 patients-years (95% CI 6,02-7,7). In one of the 2 patients RHC excluded PAH, while the other patient refused to undergo to RHC and PAH could not be confirmed/excluded. A stability of PFTs and echocardiografic PAPs was observed during the observation time. Conclusions: the results of this retrospective study suggest that combination therapy with endothelin receptor antagonist and Phosphodiesterase-5 (PDE5) inhibitors could help in preventing PAH in SSc; prospective case-control studies on larger population are needed to improve knowledge in this field.

In May 2022, WHO reported an outbreak of Mpox in several European countries which were previously Mpox free. Mpox (formerly known as monkeypox) is a zoonotic viral disease endemic in Central and West Africa. The sudden emergence of Mpox outside Africa and its subsequent rapid spread lead the WHO to declare the outbreak as Public Health Emergency of International Concern. As of May 15, 2023, a total of 87,704 confirmed cases and 140 deaths had been reported from 111 countries and territories worldwide. Looking back on this outbreak one year later, several important questions have arisen. Here, we address these questions using the classic five Ws: What, When, Where, Who and Why? We discuss these questions and outline what needs to be done to prevent, or at least minimize, outbreaks from emerging and re-emerging viral infection.

In this work, polyacrylic acid-functionalized MCM-41 was synthesized, which was further interacted with calcium ions, to realize enhanced pH-responsive nanocarrier for sustained drug release. First, mesoporous silica nanoparticles (MSNs) were prepared by the sol-gel method. Afterward, (3-trimethoxysilyl)propyl methacrylate (TMSPM) modified surface was prepared by using the post-grafting method, then polymerization of acrylic acid was proceeded. After adding calcium chloride solution, polyacrylic acid-functionalized MSNs with calcium-carboxyl ionic bonds in the polymeric layer, which can prevent the cargo from leaking out of the mesopore, were prepared. The structure and morphology of the modified nanoparticles (PAA-MSNs) were characterized by X-ray diffraction (XRD), Fourier-transform infrared (FT-IR) spectroscopy, transmission electron microscopy (TEM), and N2 adsorption-desorption analysis, etc. The controlled release of guest molecules was studied by using 5-fluorouracil (5-FU). The drug molecules-incorporated nanoparticles showed different releasing rates under different pH conditions. It is considered that our current materials have the potential as pH-responsive targeted nanocarriers in the field of medical treatment.

Trace amine-associated receptors (TAARs) are a family of G protein-coupled receptors present in mammals in the brain and in several peripheral organs. Apart from its olfactory role, TAAR5 is expressed in the major limbic brain areas and regulates brain serotonin functions and emotional behaviors. However, most of its functions remain undiscovered. Given the role of serotonin and limbic regions in some aspects of cognition, we used a temporal decision-making task to unveil a possible role of TAAR5 in cognitive processes. We found that TAAR5 knock-out (KO) mice showed a generally better performance due to a reduced number of errors and displayed a greater rate of improvement at the task than WT littermates. However, task-related parameters, such as time accuracy and uncertainty have not changed significantly. Overall, we show that TAAR5 modulates specific domains of cognition, highlighting a new role in brain physiology.

To characterize the mechanisms by which the highly-conserved exocyst trafficking complex regulates eye physiology in zebrafish and mice, we focused on exoc5 (aka sec10), a central exocyst component. We analyzed both exoc5 zebrafish mutants and retinal pigmented epithelium (RPE)-specific Exoc5 knockout mice. Exoc5 is present in both the non-pigmented epithelium of the ciliary body and in the RPE. In this study we set out to establish an animal model to study the mechanisms underlying the ocular phenotype and to establish if loss of visual function is induced by postnatal RPE Exoc5-deficiency. Exoc5-/- zebrafish showed smaller eyes, with decreased number of melanocytes in the RPE and shorter photoreceptor outer segments. At 3.5 days post fertilization, loss of rod and cone opsins were observed in zebrafish Tg:exoc5 mutants. Mice with postnatal RPE-specific loss of Exoc5 showed retinal thinning associated with compromised visual function, and loss of visual photoreceptor pigments. This retinal phenotype in Exoc5-/- mice was present at 20-weeks, and the phenotype was more severe at 27-weeks, indicating progressive disease phenotype. We previously showed that the exocyst is necessary for photoreceptor ciliogenesis and retinal development. Here, we report that exoc5 mutant zebrafish and mice with RPE-specific genetic ablation of Exoc5 develop abnormal RPE pigmentation, resulting in retinal cell dystrophy and loss of visual pigments associated with compromised vision. As RPE cells are “downstream” of photoreceptor cells in the visual process, these data suggest exocyst-mediated retrograde communication and dependence between the RPE and photoreceptors.

Erectile dysfunction (ED) due to diabetes mellitus remains difficult to treat despite advances in pharmacotherapeutic approaches in the field. Therefore, this study investigated the erectogenic effect of the methanolic extract of Maytenus procumbens roots on type 2 diabetes in rats. The fructose-streptozotocin model was used to induce type 2 diabetes-linked ED in male rats. The sexually active male Sprague Dawley rats were randomly divided into two major groups; normal group and high fructose fed group for 120 days. After 120 days, the high fructose fed group rats were given a single intraperitoneal injection of a freshly prepared streptozotocin solution (30 mg/kg). The diabetic ED rats were orally administered with the extract at 250 mg/kg, daily for 28 days. The serum, brain and penile tissues were removed for biochemical analysis and protein expression. Increased testosterone level, mounting frequency, reduced blood glucose level and serum fructosamine content was observed after 28 days of treatment in diabetic rats. Methanolic extract also exhibited an inhibitory effect on arginase, AChE, and ACE activities. The crude extract further downregulated proteins PDE-5, RhoA and increased expression of eNOS in the diabetic ED treated rats. The results obtained indicate that the methanolic extract of Maytenus procumbens roots ameliorates erectile dysfunction in type 2 diabetes-induced erectile dysfunction in rats.

Liver receptor homolog-1 (LRH-1) has emerged as a regulator of hepatic glucose, bile acid, and mitochondrial metabolism. However, the functional mechanism underlying the effect of LRH-1 on lipid mobilization has not been addressed. This study investigated the regulatory function of LRH-1 in lipid metabolism during fasting. The wild-type (WT) and LRH-1 liver-specific knockout (LKO) mice were either fed or fasted for 24 h, and the liver and serum were isolated. During fasting, the LRH-1 LKO mice showed greater accumulation of triglycerides in the liver compared to that in WT mice. Interestingly, LRH-1 LKO liver decreased the perilipin 5 (PLIN5) expression and genes involved in β-oxidation. Additionally, the LRH-1 agonist dialauroylphosphatidylcholine also enhanced PLIN5 expression in human cultured HepG2 cells. To identify new target genes of LRH-1, these findings directed to analyze the PLIN5 promoter sequence, which revealed −1620/−1614 to be a putative binding site for LRH-1. This was confirmed by promoter activity and chromatin immuno-precipitation assays. Moreover, fasted WT primary hepatocytes showed increased co-localization of PLIN5 in lipid droplets (LDs) compared to that in fasted LRH-1 LKO primary hepatocytes. Overall, these findings suggest that PLIN5 might be a novel target of LRH-1 to mobilize LDs and manage the cellular needs.

A single dose of psilocybin, a psychedelic and serotonin 2A receptor (5-HT2AR) agonist, may be associated with antidepressant effects. The mechanism behind its antidepressive action is unknown but could be linked to increased synaptogenesis and down-regulation of cerebral 5-HT2AR. Here, we investigate if a single psychedelic dose of psilocybin changes synaptic vesicle protein 2A (SV2A) and 5-HT2AR density in the pig brain. Twenty-four awake pigs received either 0.08 mg/kg psilocybin or saline intravenously. Twelve pigs (n=6/intervention) were euthanized one day post-injection, while the remaining twelve pigs were euthanized seven days post-injection (n=6/intervention). We performed autoradiography on hippocampus and prefrontal cortex (PFC) sections with [3H]UCB-J (SV2A), [3H]MDL100907 (5-HT2AR antagonist) and [3H]Cimbi-36 (5-HT2AR agonist). One day post psilocybin injection, we observed 4.4% higher hippocampal SV2A density and lowered hippocampal and PFC 5-HT2AR density (-15.21% to -50.19%). These differences were statistically significant in the hippocampus for all radioligands and in PFC for [3H]Cimbi-36 only. Seven days post-intervention, there was still significantly higher SV2A density in hippocampus (+9.24%) and PFC (+6.1%) whereas there were no longer any differences in 5-HT2AR density. Our findings suggest that psilocybin’s antidepressive actions are linked to increased persistent synaptogenesis and possibly also to an acute decrease in 5-HT2AR density.

After the increasing number of SARS-CoV-2 infections all over the world, researchers and clinicians are struggling to find a vaccine or innovative therapeutic strategies to treat this viral infection. The SARS-CoV infection that occurred in 2002, MERS and other more common infectious diseases such as HCV, led to the discovery of many RNA-based drugs. Among them, siRNAs and antisense LNAs have been demonstrated to have effective antiviral effects both in animal models and humans. Owing to the high genomic homology of SARS-CoV-2 and SARS-CoV (80-82%) the use of these molecules could be employed successfully also to target this emerging coronavirus. Trying to translate this approach to treat COVID-19, we analyzed the common structural features of viral 5’UTR regions that can be targeted by non-coding RNAs and we also identified miRNAs binding sites suitable for designing RNA-based drugs to be employed successfully against SARS-CoV-2.

CrHZSM-5 was placed in an electric field with appropriate strength in a quartz packed bed reactor with CO2 as oxidant to analyze its catalytic activity. Olefin yield increases with decrease in band gap since lattice oxygen mobility increases by reducing band gap. Fermi level change at the catalyst surface affects the catalytic activity. One way to change Fermi level is use electric field. In high voltage electric field, energy band was curved, bending of the energy band promoted the activity and Fermi level position is increasing. The CCD experiments were carried out with Design-Expert 7.3 software to determine the interaction between four operating variables, namely: temperature, electrical current, gap distance and metal loading. The levels of the independent variables were: temperature (550-700 °C), electrical current (0-12 mA), gap distance (6-14 mm), metal loading (0.5-7.5 %wt.). The conversion of LPG (Liquefied petroleum gas) was greatly increased by weak and effective application of an electric field to the catalyst bed. The obtained results indicated that the maximum yield value (46.94%) can be achieved under 673.66 °C, input electrical current of 11.01 mA, gap distance of 6.55 mm and metal loading of 3.98 wt.%.

Lung cancer is almost the most common cause of cancer death in the world. Clinically, the conventional therapy to eradicate the cancer cells is chemotherapy but a better drug remains required. In this study, the effects of three bufadienolides, kalantuboside B, kalantuboside A and bryotoxin C, isolated from Kalanchoe tubiflora (Harvey) were evaluated and characterized in CL1-5 highly metastatic human lung cancer cells. Contrary to the apoptosis-promoting activity in other cancer cells, these three bufadienolides did not induce apoptosis in CL1-5 cancer cells. Instead, they activated an autophagy pathway, as indicated by the increase of autophagosomes formation. The induction of autophagy by these three bufadienolides was demonstrated to link to down-regulation of p-mTOR as well as up-regulation of LC3-II, ATG5, ATG7, Beclin-1. Moreover, among these three compounds, kalantuboside B in which a monosaccharide is attached at the bufadienolide aglycon, exhibited a better autophagy induction. Our findings revealed an alternative mechanism of drug action by bufadienolides in lung cancer cells and provided evidence for the possibility of treating highly metastatic human lung cancer through an autophagy pathway.