Subsoil tillage loosens compacted soil for better plant growth, but promotes water loss, which is a concern in areas commonly irrigated. Therefore, our objective was to determine the physiological responses of high yield spring corn (Zea mays L.) to Subsoil tillage depth when grown in the western plain irrigation area of Inner Mongolia that leads to the best water use efficiency. The experiment during 2014 and 2015 used Zhengdan958 and Xianyu335 with three differing subsoil tillage depths (30, 40, or 50 cm) as trial factor and shallow rotary as a control. Subsoil tillage increased shoot dry matter accumulation, leading to a greater shoot/root ratio. Subsoil tillage helped retain greater leaf area index in each growth stage, increase the leaf area duration, net assimilation rate, and relative growth rate, with greater effects as tillage was deeper, effectively delaying the aging of the blade. Grain yields were increased by 0.7%–8.9% on average in subsoil tillage treatments compared to conventional soil treatment shallow rotary, Water use efficiency were increased by 1.93%–18.49% on average in subsoil tillage treatment compared to shallow rotary, resulting in net income increases by 2.24% to 6.97% compared to shallow rotary. Among the three different subsoil tillage depth treatment, the grain yield, water use efficiency, and net income is the best under the treatment of subsoil tillage depth of 50 cm.

The interest on the use of renewable energy resources is increasing, especially towards wind and hydro powers, which should be efficiently converted into electric energy via suitable technology tools. To this aim, self--tuning control techniques represent viable strategies that can be employed for this purpose, due to the features of these nonlinear dynamic processes working over a wide range of operating conditions, driven by stochastic inputs, excitations and disturbances. Some of the considered methods were already verified on wind turbine systems, and important advantages may thus derive from the appropriate implementation of the same control schemes for hydroelectric plants. This represents the key point of the work, which provides some guidelines on the design and the application of these control strategies to these energy conversion systems. In fact, it seems that investigations related with both wind and hydraulic energies present a reduced number of common aspects, thus leading to little exchange and share of possible common points. This consideration is particularly valid with reference to the more established wind area when compared to hydroelectric systems. In this way, this work recalls the models of wind turbine and hydroelectric system, and investigates the application of different control solutions. The scope is to analyse common points in the control objectives and the achievable results from the application of different solutions. Another important point of this investigation regards the analysis of the exploited benchmark models, their control objectives, and the development of the control solutions. The working conditions of these energy conversion systems will be also taken into account in order to highlight the reliability and robustness characteristics of the developed control strategies, especially interesting for remote and relatively inaccessible location of many installations.

Technology has transformed aeroponics, providing numerous advantages over traditional soil-based agriculture. However, there remains a need for comprehensive information on the types of technology employed in aeroponics and their impact on the growing process. This paper presents a literature review of 47 studies published between 2012 and 2023 in peer-reviewed journals and conference proceedings. As a result, it identifies the status and tendencies in the usage of technology in aeroponics as well as the main opportunities and challenges. Furthermore, this paper introduces the Technology Adoption and Integration in Sustainable Agriculture (TAISA) model. TAISA is a model that identifies the degree of technology integration in any sustainable agriculture system to determine how technology affects production and quality. Overall, the systematic review suggests that technology can play a vital role in improving the efficiency and sustainability of aeroponic farming. However, careful consideration must be given to the costs and technical requirements associated with using these technologies. Moreover, the TAISA model reveals that technology has primarily been employed in creating new processes that are not possible to implement without the help of technology. Therefore, we conclude that technology use has taken root in aeroponics and can be promoted to improve sustainable agriculture.

Abstract: The trend of fasting until noon (omission or delayed breakfast) is increasingly prevalent in modern society. This eating pattern triggers discordance between endogenous circadian clock rhythms and the feeding/fasting cycle and is associated with an increased incidence of obesity and T2D. Although the underlying mechanism of this association is not well understood, growing evidence suggests that fasting until noon, also known as an “extended postabsorptive state,” has the potential to cause a deleterious effect on clock gene expression and disrupted regulation of body weight, postprandial and overall glycemia, skeletal muscle protein synthesis, appetite and may also lead to lower energy expenditure. This manuscript overviews the clock gene-controlled glucose metabolism during the active and resting phases. The consequences of postponing until noon the transition from postabsorptive to fed state on glucose metabolism, weight control, and energy expenditure. Finally, we will discuss the metabolic advantage of shifting more energy, carbohydrates (CH), and proteins to the early hours of the day.

Currently, there is an increase in the aging of the population, which represents a risk factor for many diseases, including sarcopenia. Sarcopenia involves progressive loss of mass, strength, and function of the skeletal muscle. Some mechanisms include alterations in muscle structure, reduced regenerative capacity, oxidative stress, mitochondrial dysfunction, and inflammation. The zebrafish has emerged as a new model for studying skeletal muscle aging because of its numerous advantages, including histological and molecular similarity to human skeletal muscle. In this study, we used fish of 2, 10, 30, and 60 months of age. The older fish showed a higher frailty index because of reduced locomotor activity and alterations in biometric measurements. We observed changes in muscle structure with a decreased number of myocytes and an increase in collagen with aging, corresponding to alterations in the synthesis, degradation, and differentiation pathways. These changes were accompanied by mitochondrial alterations, such as a decrease in intermyofibrillar mitochondria, increased mitochondrial damage, and reduced mitochondrial dynamics. Overall, we demonstrated a similarity in the aging processes of muscle aging between zebrafish and mammals.

Melanin is extensively distributed in organisms and believed to be synthetized by tyrosinase (TYR), leading to aberrant coloring and skin conditions when over-produced. Loquat (Eriobotrya japonica (Thunb.) Lindl.) flowers contain large amounts of bioactive substances currently few studied on their suppressive capabilities to melanin synthesis. Its isolate product (LFP) was obtained by ethanol solution extraction and resin purification, of which the inhibitory mechanism on TYR activity was elaborated by enzyme kinetics and multi-spectroscopy determinations and the impact on related proteins’ expression in mouse melanoma B16 cells was analyzed with Western blotting. HPLC-MS analysis indicated that LFP was identified into 137 compounds, with 12 including flavonoids (quercetin, isorhamnoin, p-coumaric acid, etc.), cinnamic acid and its derivatives as well as benzene and its derivatives owning TYR inhibitory activities. LFP inhibited TYR activity in a concentration-dependent manner with its IC50 value being 2.8 mg/mL and an anti-competitive mechanism involved altering the enzyme's conformation. LFP reduced the expression of TYR, TRP1, and TRP2 in melanoma B16 cells, hence inhibiting the synthesis of melanin. Considered collectively, LFP would be a viable option for treating hyperpigmentation caused by tyrosinase, providing a theoretical basis for the value-added utilization of loquat flower resource in beauty and aging related functional products.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, with septic cardiomyopathy being a common and severe complication. Despite its significant clinical impact, the molecular mechanisms underlying sepsis-induced cardiomyopathy (SICM) remain incompletely understood. In this study, we performed a comparative analysis of whole transcriptome profiles in two widely used mouse models of septic cardiomyopathy, the cecal ligation and puncture (CLP) model and the lipopolysaccharide (LPS) model. Our aim was to identify key genes and pathways involved in the development of septic cardiomyopathy and to evaluate the similarities and differences between the two models. Our findings suggested that 1) both methods can induce septic heart dysfunction within 24 hours; 2) distinct whole transcriptome expression profiles are revealed; 3) potentially different pathways are involved in causing heart failure in sepsis. The comprehensive comparison provides valuable insights into the molecular basis of septic cardiomyopathy and contributes to the ongoing search for effective treatment strategies, triggered by different factors for SICM.

The zebrafish is now an important model organism for cancer biology studies and provides some unique and complementary opportunities in comparison to the mammalian equivalent. The translucency of zebrafish has allowed in vivo live imaging studies of tumour initiation and progression at the cellular level thus providing novel insights into our understanding of cancer. Here we summarise and discuss available transgenic zebrafish tumour models and what we have gleaned from them with respect to cancer inflammation. In particular, we focus on the host inflammatory response toward transformed cells during the pre-neoplastic stage of tumour development. We discuss features of tumour associated macrophages and neutrophils in mammalian models and present evidence which supports the idea that these inflammatory cells promote early stage tumour development and progression. Direct live imaging of tumour initiation in zebrafish models has shown that the intrinsic inflammation induced by pre-neoplastic cells is tumour promoting. Signals mediating leukocyte recruitment to pre-neoplastic cells in zebrafish correspond to signals mediating leukocyte recruitment in mammalian tumours. The activation state of macrophages and neutrophils recruited to pre-neoplastic cells appears to be heterogenous, as seen in mammalian models, which provides an opportunity to study the plasticity of innate immune cells during tumour initiation. Although several potential mechanisms are described that might mediate the trophic function of innate immune cells during tumour initiation in zebrafish, there are several unknowns that are yet to be resolved. Rapid advancement of genetic tools and imaging technologies for zebrafish will facilitate research into the mechanisms that modulate leukocyte function during tumour initiation and identify targets for cancer prevention.

Hypoxic-ischemic encephalopathy (HIE) is one of the most common causes of childhood disability. Hypothermic therapy is currently the only approved neuroprotective approach. However, early diagnosis of HIE can be challenging, especially in the first hours after birth when the decision to treat with hypothermic therapy is critical. Differentiating HIE from other neonatal conditions, such as sepsis, further complicates the diagnosis. This study investigated the utility of a metabolomic-based approach using the NeoBase 2 MSMS kit to diagnose HIE using dry blood stains in a Rice-Vannucci model of HIE in rats. We evaluated the diagnostic accuracy of this method between 3 and 6 hours after the onset of HIE, including in the context of systemic inflammation and concomitant hypothermic therapy. Discriminant analysis revealed several metabolite patterns associated with HIE. A logistic regression model using glycine levels achieved high diagnostic accuracy with areas under the curve (AUC) of 0.94 at 3 hours and 0.96 at 6 hours after the onset of HIE. In addition, orthogonal partial least squares discriminant analysis, which included five metabolites, achieved 100% sensitivity and 80% specificity within 3 hours of HIE. These results highlight the significant potential of the NeoBase 2 MSMS kit for the early diagnosis of HIE and could improve patient management and outcomes in this serious illness.

In this paper, we consider the one-dimensional Ising model (shortly, 1D-MSIM) having mixed spin-(s,(2t−1)/2) with nearest neighbors and the external magnetic field. We establish the partition function of the model by means of the transfer matrix. Under a null boundary condition, we compute certain thermodynamic quantities for the 1D-MSIM. We find some precise formulas to determine the model’s free energy, entropy, magnetization, and susceptibility. By examining the model’s associated iterative equations, we use the cavity approach to investigate the phase transition problem. We numerically determine the model’s periodicity.

Prevalence studies of current smoking among hospitalized COVID-19 patients demonstrated an unexpectedly low prevalence of current smoking among patients with COVID-19. The aim of the present proposal was to evaluate the effect of smoke from cigarettes on ACE-2 in bronchial epithelial cells. Normal bronchial epithelial cells (H292) were exposed to smoke by an air-liquid-interface (ALI) system and ACE-2 membrane protein expression was evaluated after 24 hours from exposure. Our transcriptomics data analysis showed a significant selective reduction of membrane ACE-2 expression (about 25%) following smoking exposure. Interestingly, we observed a positive direct correlation between ACE-2 reduction and nicotine delivery. Furthermore, by stratifying GSE52237 as a function of ACE-2 gene expression levels, we highlighted 1012 genes related to ACE-2 in smokers and 855 in non-smokers. Furthermore, we showed that 161 genes involved in the endocytosis process were highlighted using the online pathway tool KEGG. Finally, 11 genes were in common between the ACE-2 pathway in smokers and the genes regulated during endocytosis, while 12 genes with non-smokers. Interestingly, six in non-smokers and four genes in smokers were closely involved during the viral internalization process. Our data may offer a pharmaceutical role of nicotine as potential treatment option in COVID-19.

The aim of this study was to evaluate the effect of two different insertion speeds at 8 different insertion torque values ranging from 25-60 during implantation in a dense polyurethane D1 bone model on the placement status and removal torque of dental implants. In this study, 50 pcf single layer polyurethane plates were used. In the study, a total of 320 implant sockets were divided into 2 groups as Group 1 (30 rpm) and Group 2 (50 rpm) in terms of insertion speed. Group 1 and Group 2 were divided into 8 subgroups as 25, 30, 35, 40, 45, 50, 55 and 60 torques. There were 20 implant sockets in each subgroup. During the implantations, implant placement status and removal torque values were assessed. There was a statistically significant difference between the 30 and 50 RPM groups in terms of overall implant placement status (p<0.01). It was found that the removal torque values at 50 RPM were statistically significantly higher than those at 30 RPM (p<0.01). This study showed that in dense D1 bone, the minimum parameters at which all implants could be placed at bone level were 50 torque at 30 rpm and 40 torque at 50 rpm.

Safe water is a global public health concern amid increasing scarcity and pollution. Bottled water production and consumption contribute to these problems. This study examines tap water consumption in Italy, assessing associated sociodemographic factors and related health outcomes such as obesity and self-perceived health status. Data from the Italian National Statistics Institute's "Aspects of daily life" survey (N=45,597) were analyzed. Covariates included education, age, gender, economic status, region, concerns about waste and climate change, consumption of carbonated drinks excluding water, alcohol consumption, consumption of vegetables, consumption of snacks, body mass index, and self-perceived health status. Bivariate analyses and mixed-effect logistic regression models explored the associations. People who drink tap water were 19,674 with a higher prevalence in people aged 45 to 59 old, people with a graduate/post-graduate degree diploma, with optimal economic resources, and concerned about waste production and climate change, coming from the North-East regions of Italy. Underweight people showed a higher prevalence of TW assumption as well as those who drink less than occasionally carbonated drinks, drink alcohol, consume vegetables more than once a day, and snacks less than once a week with a satisfying level perceived health status. Regressions showed that all age classes are less likely to drink tap water than people younger than 20 years old. The category with “inadequate” economic resources is more likely to consume tap water. Low educational classes show a low likelihood of consuming tap water as well as Islands. A concern about waste production and climate change is associated with an increased likelihood of assuming tap water. Tap water consumption was negatively associate with obesity but not with a satisfactory Self-perceived health status. Insights from this study can inform public health strategies.

Evaluation of drug permeability using cell monolayers is an important in vitro assay in the process of drug development, to identify compounds with favourable pharmacokinetics that may proceed to in vivo studies. When allowed to differentiate on permeable filters for at least 21 days, monolayers of Caco-2 cells develop morphological and functional properties similar to those of the intestinal epithelium. Permeability through Caco-2 monolayers is thus particularly relevant to assess drug absorption after oral administration. The major drawback of this assay is its very low throughput, with the cell monolayers being used in a single permeability assay. We have previously proposed a protocol to allow the re-use of the Caco-2 monolayer on additional permeability assays during the stable period and shown that cell monolayer integrity is maintained. In this work we evaluate the effect of re-use on the permeability of several reference compounds that permeate through passive pathways and show that the cell monolayers can be re-used twice in additional permeability assays. Preliminary results were also obtained regarding active transport pathways, and a new methodology is proposed to quantify the contribution from passive and active transport. This is a major step towards the full validation of the re-use methodology proposed, which at least triplicates the throughput of this important in vitro assay.

Evidence regarding the role of oral antibiotics (oA) alone or combined with mechanical bowel preparation (MoABP) for elective colorectal surgery remains controversial. A prospective database of 8,359 colorectal resections gathered over a 32-month period in 78 Italian surgical units (the iCral 2 and 3 studies), reporting patient-, disease-, and procedure-related variables together with 60-day adverse events, was re-analyzed to identify a subgroup of 1,013 cases (12.1%) that received either oA or MoABP. This dataset was analyzed using a 1:1 propensity score-matching model including 20 covariates. Two well-balanced groups of 243 patients each were obtained: group A (oA), and group B (MoABP). The primary endpoints were anastomotic leakage (AL) and surgical site infections (SSIs) rates. Group A vs. group B showed a significantly higher AL risk [14 (5.8%) vs 6 (2.5%) events; OR 3.77; 95%CI 1.22-11.67; p = .021], while no significant difference was recorded between the two groups regarding SSIs. These results strongly support the use of MoABP for elective colorectal resections.

In economics, especially econometrics, fixed-effects are widely recognized as powerful tools for heterogeneity analysis of longitudinal data sets. However, the existing research pays more attention to such as the variable selection, parameter estimation and dimension reduction on linear relationships with too many assumptions while nonlinear relationships are ubiquitous. In this paper, an extension fixed-effects model is proposed on the curve_fit nonlinear least squares. First, with the help of expert knowledge, the series regressions between independent variables including time and dependent variable is estimated on each series data, and the parameters are estimated by curve_fit. Similarly, the coeffection between independent variables including time and dependent variable is also initially estimated on the whole panel data. Second, the distance between regressions is defined, and then the coeffect function between the series regressions is obtained on the initial co-effect with curve_fit. Third, the time-effects and individual fixed-effects for each series data in the panel data are estimated on the differences of series regressions and co-effect function. Additionally, the effectiveness of the proposed method is varified on the synthetic data.

Gelephu, located in the Himalayan region, has experienced one of the strongest development activities due to the suitable topography and geographic location, which has led to rapid urbanization. The main objective of the study is to perform land use land cover (LULC) mapping for Gelephu for 2016 and 2023 by a Random Forest (RF) classifier, using the Semi-automatic Classification Plugin (SCP) in QGIS and identify LULC changes. Furthermore, the study assessed the vegetation change dynamics within the study area by analysing the Normalized Difference Vegetation Index (NDVI) for 2016 and 2023. Additionally, the study characterized the resulting LULC change for Gelephu Thromde, a sub-administrative municipal entity, as a result of the notable intensity of the infrastructure development activities. The current study used a framework to collect Sentiniel-2 satellite data, which was then used for pre- and post-processing to create LULC and NDVI maps. The classification model achieved high accuracy, with an area under the curve (AUC) of up to 0.89. The corresponding LULC and NDVI statistics were analysed to determine the current status of the LULC and vegetation indices, respectively. The LULC change analysis reveals urban growth of 5.65% and 15.05% for Gelephu and Gelephu Thromde, respectively. The NDVI assessment shows significant deterioration in vegetation health with a 75.11% loss of healthy vegetation in Gelephu between 2016 and 2023. This research provides the first version of LULC and NDVI maps of Gelephu. The analysis results indicate possible future implications on sustainable development management in Gelephu Bhutan.

3,4-Dihydroquinolin-2(1H)-ones represent a class of valuable bioactive compounds with six-membered nitrogen-containing heterocyclic structures. The development of simple, mild and efficient synthetic methods has been widely concerned by synthetic chemists. In this review, we have summarized a series of different synthetic strategies for the synthesis of dihydroquinoline-2(1H)-ones via catalytic annulation of α,β-unsaturated N-arylamides in the past decade, including covering electrophilic cyclization, radical initiated cyclization and photochemical cyclization reactions. Besides, the substrate scope and mechanistic details are also discussed. This paper will provide a useful reference for the development of diverse synthesis methodologies of 3,4-dihydroquinolin-2(1H)-ones.

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.

One aspect of reproducibility in preclinical research that is frequently overlooked is the physical condition in which physiological, pharmacological, or behavioural recordings are conducted. In this study, the physical conditions of mice were altered through the attachments of wireless electrophysiological recording devices (Neural Activity Tracker-1, NAT-1). NAT-1 devices are miniaturised multichannel devices with on-board memory for direct high-resolution recording of brain activity for >48 hrs. Such devices may limit the mobility of animals and affect their behavioural performance due to the added weight (total weight of approximately 3.4 g). Mice were additionally treated with saline (control), N-methyl-D-aspartate (NMDA) receptor antagonist MK801 (0.85 mg/kg), or the muscarinic acetylcholine receptor blocker scopolamine (0.65 mg/kg) to allow exploration of the effect of NAT-1 attachments in pharmacologically treated mice. We found only minimal differences in behavioural outcomes with NAT-1 attachments in standard parameters of locomotor activity widely reported for the open field test between drug-treatments. Hypoactivity was globally observed as a consistent outcome in MK801-treated subjects and hyperactivity in scopolamine groups regardless of NAT-1 attachments. These data collectively confirm the reproducibility for combined behavioural, pharmacological and physiological endpoints even in the presence of lightweight wireless data loggers. The NAT-1 therefore constitutes a pertinent tool for investigating brain activity in e.g. drug discovery, models of neuropsychiatric and/or neurodegenerative diseases with minimal effects on pharmacological and behavioural outcomes.

Inflammation is the body’s response to infection, injury, or other stimuli. Acute inflammation is a crucial component of the immune system’s defense, aimed at eliminating infected or damaged cells and halting disease progression. A subtle interaction between pro- and anti-inflammatory processes determines its progression to inflammation resolution or to chronic inflammation. In this study, we propose a generic model of inflammation through a system of reaction-diffusion equations involving various inflammatory and anti-inflammatory cells and cytokines. We investigate the formation of patterns, determined by the emergence of Turing structures, through linear stability analysis and numerical simulations. These theoretical findings are further supported by observations of similar patterns in skin diseases.

Abstract: Safety issues related to the electrification of more electric aircraft (MEA) need to be addressed because of the increasing complexity of aircraft electrical power systems and the growing number of safety-critical sub-systems that need to be powered. Managing the energy storage systems and the flexibility in the load-side plays an important role in preserving the system’s safety when facing an energy shortage. This paper presents a system-level centralized operation management strategy based on model predictive control (MPC) for MEA to schedule battery systems and exploit flexibility in the demand-side while satisfying time-varying operational requirements. The proposed online control strategy aims to maintain energy storage (ES) and prolong the battery life cycle, while minimizing load shedding, with fewer switching activities to improve devices lifetime and to avoid unnecessary transients. Using a mixed-integer linear programming (MILP) formulation, different objective functions are proposed to realize the control targets, with soft constraints improving the robustness of the model. Besides, an evaluation framework is proposed to analyze the effects of various objective functions and the prediction horizon on system performance, which provides the designers and users of MEA and other complex systems with new insights into operation management problem formulation.

Background: The objectives were to evaluate: the safety and immunogenicity of nonavalent human papillomavirus (nHPV) vaccine in adult Spanish women living with HIV (WLHIV); the prevalence of anal and cervical dysplasia and nHPV vaccine genotypes in anus and cervix; and risk factors for high-risk HPV (HR-HPV) infection in anal mucosa. Methods In this single-center, open-arm, non-randomized clinical trial, nHPV vaccine was administered at 0, 2, and 6 months to WLHIV enrolled between February 2020 and November 2023, measuring vaccine antibody titers pre-vaccination and at 2, 6, and 7 months after the first dose. Cervical and anal cytology and HPV PCR genotyping studies were performed. Women with abnormal cytology and/or anal or cervical HPV infection at baseline underwent high-resolution anoscopy and/or colposcopy. Results: 122 participants were included with mean age of 49.6 years: 52.5% smoked; 10.7% had anal-genital condylomatosis; 38.5% infection by HR-HPV in anus and 25.4% in cervix, most frequently HPV-16; 19.1% had AIN1 and 3.1% CIN1 and CIN2. Vaccine administration did not modify viral-immunological status (CD4 [809±226.8 cells/uL vs. 792.35 ±349.95; p=0.357]) or plasma HIV load (3.38±4.41 vs. 1.62±2.55 cop/uL [log]; p=0.125). Anti-HPV antibodies ([IQR: 0-0] vs. 7.63 nm [IQR: 3.46-19.7]; p=0.0001) and seroconversion rate (8.2% vs. 96.7% [p=0.0001]) were increased at 7 versus 0 months. There were no severe vaccine-related adverse reactions; injection-site pain was reported by around half of participants. HR-HPV infection in anus was solely associated with concomitant cervix infection (HR 5.027; 95% CI: 1.009-25.042). Conclusions: nHPV vaccine in adult WLHIV is immunogenic and safe.

The human immunodeficiency virus (HIV) continues to pose a significant global health challenge, with millions of people affected and new cases emerging each year. While various treatment and prevention methods exist, including antiretroviral therapy and non-vaccine approaches, developing an effective vaccine remains the most crucial and cost-effective solution to combat the HIV epidemic. Despite significant advancements in HIV research, the HIV vaccine field has faced numerous challenges, and only one clinical trial has demonstrated a modest level of efficacy. This review delves into the history of HIV vaccines and the current efforts in HIV prevention, emphasizing pre-clinical vaccine development using the non-human primate model (NHP) of HIV infection. NHP models offer valuable insights into potential preventive strategies for combating HIV, and they play a vital role in informing and guiding the development of novel vaccine candidates before they can proceed to human clinical trials.

Lutein, a plant-derived xanthophyl-carotenoid, is an exceptional antioxidant and anti-inflammatory constituent found in food. Elevated concentrations of lutein found in human blood and plasma, due to high dietary intake, are beneficial against eye disease and improve cardiometabolic health. Lutein plays an important protective role against the development of neurological disorders, including Alzheimer’s disease (AD), multiple sclerosis (MS) and Parkinson’s disease (PD). It has also been shown to be beneficial for liver, kidney and respiratory health. Lutein, acting as a very strong antioxidant, can alleviate oxidative stress and downgrade reactive oxygen species (ROS). Oxidative stress is one of the key pathogenic mechanisms in post-COVID and mRNA vaccine injury syndromes. Recent in silico studies suggest that lutein and other naturally derived antioxidants, by docking at the site where the SARS-CoV-2 spike protein (SP) binds to the angiotensin enzyme type 2 (ACE2) receptor, may neutralize the SP-ACE2 interactions. Lutein can be added to a detoxification regimen to aid in clearing Spike protein and relieving symptoms. In agreement with Hippocrates’ dictum to “Let food be thy medicine,” this review establishes dietary lutein as a valuable therapy in the treatment of post-COVID syndrome, mRNA vaccine injury syndromes, and a wide range of other chronic illnesses.

The COVID-19 pandemic made it harder to communicate accurate information about vaccines because of the spread of misinformation. The European Medicines Agency (EMA) tried to reas-sure the public by communicating about the development and approval of COVID-19 vaccines. They surveyed patients/consumers, healthcare professional organizations, and individual stake-holders to see if their core information materials were informative and well understood. They also asked about the public's preferred communication channels. The surveys showed that indi-vidual patients/consumers generally prefer to get information about COVID-19 vaccines from the internet or mass media. Organizations and individual healthcare professionals prefer to get in-formation from national and international health authorities' sources. This supports EMA's ap-proach of using media, stakeholder engagement, and web-based formats to communicate about COVID-19 vaccines. Both at the EU and local levels, participants had a good understanding of the key messages from regulators and found the materials useful and relevant. However, some im-provements were recommended to the visuals, texts, and dissemination formats. These recom-mendations were generally consistent in both contexts. User-testing of proactive communication materials aimed at prebunking misinformation during a public health crisis helps to ensure that users understand the development and safety safeguards of novel vaccine technologies. This in-formation can then be used as a basis for evidence-based communication activities by regulators and public health bodies in an emergency context.

More than 3 years have passed since the emergence of COVID-19. On May 8, 2023, COVID-19 in Japan was downgraded to Category 5 by the Infectious Disease Control Law. In Japan, at the beginning of the COVID-19 pandemic in 2020, cases of infection and deaths from severe disease were few compared with those of Western countries. However, in the medical field, screening for COVID-19 was given top priority, resulting in confusion and proving disadvantageous for many patients, also the overreaction to COVID-19 as the most important issue in society can be attributed largely to statements by infectious disease experts. In addition, the mRNA vaccine emerged in 2021, and most of the population was vaccinated up to two times within a short period of less than 1 year because infectious disease experts strongly promoted vaccination. After 2022, when vaccination progressed, and the Omicron strain, which is an attenuated strain, became the mainstay of the SARS-CoV-2, the number of severe cases of COVID-19 decreased significantly; however, the number of infected people increased dramatically instead. A significant portion of the population is thought to have hybrid immunity due to vaccination plus natural infection and maintains high antibody titers. Henceforth, additional vaccination should be given preferentially to those who will benefit most from it. Conversely, measures against COVID-19 caused serious damage to the economy and society. Policies that not only address countermeasures against infection, but also those that encompass the economy and society as a whole are necessary.

Live attenuated vaccines have through history proved themselves as safe and efficient. Pasteur has developed a vaccine against rabies, through a long process of passage of the virus wild type through rabbits. The result was one of the most efficient attenuated live-virus vaccines. This paper suggests a method based on calculations of biothermodynamic properties of potential tissues for vaccine application, predilected host tissue and virus wild type. Gibbs energy of biosynthesis represents the thermodynamic driving force for virus multiplication. The attenuated strain of the virus should possess Gibbs energy of biosynthesis, which is less negative than the predilected target tissue, but more negative than the vaccine portal tissue. In that way, the attenuated virus strain should be able to multiply in the vaccine portal of entry tissue and cause an immune response, making it efficient. On the other hand, the attenuated strain cannot multiply in the predilected host tissue, making it safe. The attenuation is achieved by adding a gene to the virus, which encodes a ballast protein. Production of the ballast protein would make virus multiplication less favorable, since it would require energy, but be useless to the virus.

Background and Objectives: In the current Covid-19 pandemic, children below the age of 12 could manifest Covid-19 symptoms and serve as a reservoir for the virus in the community. The present study was conducted to evaluate the reactogenicity, and immunogenicity of BBIBP-CorV, prior to involving this age group in the vaccination program in the kingdom of Bahrain. Subjects and Methods: The study included 582 children from 3 to 12 years old of Bahraini and non-Bahraini nationality, all of which contributed to the reactogenicity study. Of those, 401 contributed to the immunogenicity study. All children received 2 doses of BBIBP-CorV inactivated virus 3 weeks apart. To assess reactogenicity, children were followed up for 5 weeks to evaluate any vaccine-related adverse events (AE). To assess immunogenicity, blood was collected on day 0 and day 35 to assess antibody titer against S, N, and neutralizing antibody. Results: Of the 582 participants, (45.4%) were female, (54.61%) were male, with 49% in 9-12 age group. Of the 401 children contributing to the immunogenicity study, 274 (68.3%) had no prior exposure to Covid-19. The overall incidence of AE was 27.7%. No significant difference was found among different age groups. The most frequent AE was local (at the injection site) and occurred in 16% of children, followed by fever in 9.3%. No serious adverse events were reported. The Seroconversion rate was 100% among children with no prior exposure to Covid-19. Children with previous Covid-19 exposure had higher averages of anti-S (2379 U/ml compared to 409.1), anti-N (177.6 U/ml compared to 30.9) and neutralizing antibody (93.7 U/ml compared to 77.1) than children with no prior exposure at day 35. Conclusions: Two doses of COVID-19 BBIBP-CorV on the subjects aged between 3 to 12 has good safety and tolerance and can induce an effective immune response and neutralizing antibody titer.

Increasing evidence points to host Th17 inflammatory responses as contributing to the severe lung pathology and mortality of lower respiratory tract infections from coronaviruses. This includes host inflammatory and cytokine responses to COVID-19 caused by the SARS-2 coronavirus (SARS CoV2). From studies conducted in laboratory animals, there are additional concerns about immune enhancement and the role of potential host immunopathology resulting from experimental human COVID-19 vaccines. Here we summarize evidence suggesting there may be partial overlap between the underlying immunopathologic processes linked to both coronavirus infection and vaccination, and a role for Th17 in immune enhancement and eosinophilic pulmonary immunopathology. Such findings help explain the link between viral-vectored coronavirus vaccines and immune enhancement and its reduction through alum adjuvants. Additional research may also clarify links between COVID-19 pulmonary immunopathology and heart disease.

Lassa virus (LASV) is responsible for a type of acute viral haemorrhagic fever referred to as Lassa fever. Lack of adequate treatment and preventive measures against LASV resulted in a high mortality rate in its endemic regions. In this study, a multi-epitope vaccine was designed using immunoinformatics as a prophylactic agent against the virus. Following a rigorous assessment, the vaccine was built using T-cell (N_CTL=8 and N_HTL=6) and B-cell (N_LBL=4) epitopes from each LASV-derived protein with suitable linkers and adjuvant. The physicochemistry, immunogenic potency and safeness of the designed vaccine (~68 kDa) were assessed. In addition, chosen CTL and HTL epitopes of our vaccine showed 97.37% worldwide population coverage. Besides, disulphide engineering also improved the stability of the chimeric vaccine. Molecular docking of our vaccine protein with toll-like receptor (TLR2) showed binding efficiency followed by dynamic simulation for stable interaction. Furthermore, higher levels of cell-mediated immunity and rapid antigen clearance were suggested by immune simulation and repeated-exposure simulation, respectively. Finally, the optimized codons were used in in silico cloning to ensure higher expression within E. coli K12 bacterium. With further assessment both in vitro and in vivo, we believe that our proposed peptide-vaccine would be potential immunogen against Lassa fever.

Proteins are considered to be the main carriers of antigenic properties of Mycobacterium tuberculosis and Mycobacterium bovis, the causative agents of tuberculosis, the most serious infectious disease. Neutrophils, following resident macrophages, are among the first to attack the mycobacteria in defense of the organism. Neutrophils themselves are also the target of mycobacterial products; and their effect on neutrophil functions has been less studied. We have obtained about 70 protein fractions from M. bovis lysate; among them four protein fractions (10, 22, 24, and 40 kDa) had high serological activity against the serum of a rabbit immunized with M. bovis cells. We studied the effect of the serologically active proteins isolated from M. bovis on the generation of reactive oxygen species by bone marrow granulocytes of the Balb/c mouse, evaluated by luminol-dependent chemiluminescence. For comparison, two synthetic peptides (both 3 kDa) carrying immunogenic epitopes of MPB 70 protein (M. bovis) were taken. Proteins of 10, 22, and 24 kDa at concentrations of 83, 80, and 59 ng/mL, respectively, were found to activate ROS generation by mouse granulocytes. The 10- and 40-kDa antigens inhibited the receptor-mediated respiratory responses to opsonized zymosan (OZ) and N-formyl-MLF peptide (fMLF) but significantly enhanced the response to the phorbol ester PMA, which directly activates protein kinase C. Antigens with molecular weights of 22 and 24 kDa enhanced the fMLF-induced response and had no effect on the response activated by PMA. The response to OZ was suppressed in the presence of the 22 kDa protein. Synthetic peptides over a wide range of concentrations showed no activity in any case. All M. bovis proteins examined did not affect both proliferation and cell viability of the A549 and THP-1 cells; therefore, they have no cytotoxic or proliferative effects. Thus, serologically active proteins with molecular weights of 10, 22, 24, and 40 kDa isolated from M. bovis modulated the respiratory responses of mouse granulocytes induced by the formyl peptide, while proteins of 10, 22, and 40 kDa inhibited the responses induced by OZ.

Cell autonomous circadian oscillation is present in central and various peripheral tissues. The intrinsic tissue clock and various extrinsic cues drive gene expression rhythms. Transcription regulation is thought to be the main driving force for gene rhythms. However, how transcription rhythms arise remains to be fully characterized, due to the fact that transcription is regulated at multiple steps. In particular, Pol II recruitment and pause release are two critical regulatory steps that determine the status of Pol II pausing. Recently, we showed that Pol II pausing exhibits genomewide changes during daily transcription in mouse liver. In this article, we review historical as well as recent findings on the regulation of transcription rhythms. We also discuss the possible mechanisms for daily changes in Pol II pausing and the critical involvement of Pol II pausing regulation in generating rhythmic transcription output.

The signal transducer and activator of transcription 3 (Stat3) is activated in response to the phosphorylation of Y705 (pStat3) and has the dual function of signal transduction and activation of transcription. Our previous study suggested that pStat3 is functional during oocyte maturation when transcription is silenced. Therefore, we speculated that pStat3 may have another function. Immunocytochemical analysis revealed that pStat3 emerges at the microtubule asters and spindle and then localizes at the spindle poles concomitant with a Pericentrin during mouse oocyte maturation. When we examined conditionally knocked out Stat3−/− oocytes, we detected Stat3 and pStat3 proteins. The localization of the pStat3 was the same as that of Stat3+/+ oocytes, and the oocyte maturation proceeded normally, suggesting that pStat3 was still functioning. The oocytes were treated either with the Stat3 specific inhibitors, Stattic and BP-1-102, or anti-pStat3 antibody injection. This caused significant abnormal spindle assembly and chromosome mis-location in a dose-dependent manner, in which the pStat3 was either negative or localized improperly. Moreover, development of pre-implantation stage embryos derived from inhibitor-treated oocytes was also hampered significantly after in vitro fertilization. These findings indicate a novel function of pStat3 involved in spindle assembly.

Backround: Thoracic trauma causes life-threatening organ injuries, ranging from simple abrasions to contusions of intrathoracic organs. In this study, we aimed to investigate the effects of bosentan on endothelin-1 (ET-1), hypoxia-inducible factor-1 (HIF-1), nuclear factor-kappa B (NF-κB), tumor necrosis factor (TNF)-α as inflammation markers, pro-oxidant antioxidant balance (PAB) and total antioxidant capacity (TAC) levels as oxidative stress parameters in lung tissues of rats in experimental model of pulmonary contusion (PC) induced by blunt thoracic trauma. Methods: Thirty-seven animals male Sprague-Dawley rats were divided into 5 groups. All 4 groups, except for the control group, were performed to PC. In the first group, C: control group (n=6) consisted of unprocessed and untreated. The second group, PC3 (n=8) underwent of 3 days PC performed. The third group, PC-B3 (n=8) received 100 mg/kg bosentan was given orally once a day for 3 days. The fourth group, PC7 group (n=7) underwent of 7 days PC performed, and the fifth group PC-B7 (n=8) received 100 mg/kg bosentan was given orally once a day for 7 days. While ET-1, NF-B, TNF-, and HIF-1 was measured by ELISA method, TAC and PAB by spectrophotometric in lung tissue samples. Results: ET-1, NF-B, TNF-, HIF-1, and PAB levels were higher, while TAC activities were lower in all groups compared with the control (p < 0.05). There was no significant difference in ET-1 and TNF-- levels between the PC-B3 and PC-B7 groups and the control group (p < 0.05) while NF-B, HIF-1, and PAB levels were still higher in both the PC-B3 and PC-B7 groups than in the control group. Bosentan treatment causes decreased ET-1, NF-B, TNF-, HIF-1, and PAB and increased TAC levels in comparison to the nontreated groups (p < 0.05). Conclusions: We found that the use of bosentan decreased the severity of oxidative stress in the lung and reduced the inflammatory reaction in rats with PC induced by blunt thoracic trauma. This suggests that bosentan may have protective effects on lung injury mechanisms by reducing hypoxia, inflammation and oxidative stress. If supported by similar studies, bosentan can be used in both pulmonary and emergency clinics to reduce ischemic complications, inflammation, oxidative stress in some diseases that may be accompanied by ischemia.

Significant efforts are being made across academia and industry to better characterize lithium-ion battery cells as reliance on the technology for applications ranging from green energy storage to electric mobility increases. The measurement of short-term and long-term volume expansion in lithium-ion battery cells is relevant for several reasons. For instance, it provides information about the quality and homogeneity of battery cells during charge and discharge cycles, as well as aging over it’s lifetime. The expansion measurements are useful for the evaluation of new materials and the improvement of end-of-line quality tests during cell production. These measurements may also indicate the safety of battery cells by aiding in predicting state of charge and state of health over the lifetime of the cell. Expansion measurements can also assess inhomogeneities on the electrodes and defects such as gas accumulation and lithium plating. In this review, we first establish the known mechanisms through which short term and long term volume expansion in lithium-ion battery cells occurs. We then explore the current state-of-the-art for both contact and non-contact measurements of volume expansion. This review compiles existing literature to outline the various options available to researchers aiming to make ex situ volume expansion measurements by doing post mortem analyses on individual components and in operando measurements on entire battery cells. Finally, we discuss the different considerations when selecting an appropriate measurement technique. The selection of the optimal method for measuring battery cell expansion depends on the objective of the characterization, duration, required resolution, and repeatability of results. Costs and required space for the measurement equipment are also considered.

Melatonin, a naturally occurring chemical, has pleiotropic effects across various species. It plays a vital role in animals by regulating the body clock, while in plants, it is known to resist aging. Melatonin is associated with various plant physiological processes, including stress response, plant growth, and flowering time. It has prospects in enhancing and promoting plant growth and development, as well as in strengthening crop yield and increasing sustainability in agriculture. This review summarized the potential roles of melatonin in several plant species, as well as its biosynthetic modes. In addition, we described the recently uncovered melatonin features in plants, summarized the issues and challenges facing plant melatonin research and some feasible solution ideas are proposed.

Twining stems are an important form of plant stems. Twining stems can exhibit two different chiralities: right-handed and left-handed, with right-handed twining stems being much more common than left-handed ones. The determination of chirality in twining stems has always been a fascinating topic. Many people believe that the direction of twining stems in a given species is fixed, but this is not the case. Some species have twining stems that exhibit both chirality types, i.e. the chirality is variable. Moreover, such species or genera are not rare and can be commonly encountered in everyday life. Here, we report the presence of variable-chirality twining stems (VCTS) in several species or genera within the Asteraceae, Campanulaceae, Rubiaceae, Lamiaceae, Polygonaceae, Santalaceae, and Ranunculaceae families, including common plants such as Mikania micrantha and Pleuropterus multiflorus. VCTS is an objectively existing phenomenon, but often overlooked. Understanding and accepting this concept will greatly assist future research in this field.

In the last two decades, plant taxonomy has bloomed, following the development of a novel technique, namely DNA Barcoding. DNA barcodes are standardized sequences, ideally unique, coding or non-coding, either from the genome of the organism or from its organelles, that are used to identify/classify an organismal group; in short the method includes amplification of the DNA barcode, sequencing and comparison with a reference database containing the relevant sequences from different species. In plants, the use a universal DNA barcode, such as COI which is used in animals, has not been achieved so far. Several DNA barcodes from single loci as well as combinations of barcodes have been successfully used in various settings; additionally, as next generation sequencing becomes affordable, very long sequences- super barcodes, such as the chloroplast genome are being used successfully especially to distinguish between close species. In this review we summarize the work done on DNA barcoding in plants and discuss different approaches used so far.

Transposons are mobile DNA sequences that contribute large fractions of many plant genomes. They provide exclusive resources for tracking gene and genome evolution and for developing molecular tools for basic and applied research. Despite extensive efforts, it is still challenging to accurately annotate transposons, especially for the beginners as transposon prediction requires necessary expertise in both transposon biology and bioinformatics. Moreover, the complexity of plant genomes and the dynamic evolution of transposons also bring difficulties for genome-wide transposon discovery. This review summarizes the three major strategies for transposon detections including repeat-based, structure-based, and homology-based annotation, and introduces the transposon superfamilies identified in plants thus far, and some related bioinformatics resources for detecting plant transposons. Furthermore, it describes the transposon classification and explains why the terms of ‘autonomous’ and ‘non-autonomous’ cannot be used to classify the superfamilies of transposons. Last, this review also discusses how to identify misannotated transposons and improve the quality of transposon database. This review provides helpful information about plant transposons and a beginner’s guide on annotating these repetitive sequences.

In recent years, the ecological and economic values of forest plants have been gradually recognized worldwide. However, the growing global demand for new forest plant varieties with higher wood production capacity and better stress tolerance cannot be satisfied by conventional phenotype-based breeding, marker-assisted selection, and genomic selection. In the recent past, diverse omics technologies, including genomics, transcriptomics, epigenomics, proteomics, and metabolomics, have been developed rapidly, providing powerful tools for the precision genetic breeding of forest plants. Genomics lays a solid foundation for understanding complex biological regulatory networks, while other omics technologies provide different perspectives at different levels. Multi-omics integration has combined the different omics technologies, becoming a powerful tool for genome-wide functional element identification in forest plant breeding. This review summarizes the recent progress of omics technologies and their applications in the genetic studies of forest plants. It will provide forest plant breeders with an elementary knowledge of multi-omics techniques for future breeding programs.

Advances in computing technology provide an opportunity to grow and develop an effective crop protection system. This study is a new way of diagnosing plant diseases using a deep and convolutional neural network. Deep learning is the strengthened method of machine learning. It uses a neural network that imitates like a human brain and gains certain information. Although powerful, its training process necessitates millions of tagged data points. The study's Methodology consists of three key stages: data acquisition, pre-processing, and Model Building.

Plant geneticists and breeders have used marker technology since the 1980s in quantitative trait locus (QTL) identification. Marker-assisted selection is effective for large-effect QTL but has been challenging to use with quantitative traits controlled by multiple minor effect alleles. Therefore, genomic selection (GS) was proposed to estimate all markers simultaneously, thereby capturing all their effects. However, breeding programs are still struggling to identify the best strategy to implement it into their programs. Traditional breeding programs need to be optimized to implement GS effectively. This review explores the optimization of breeding programs for variety release based on aspects of the breeder’s equation. Optimizations include reorganizing field designs, training populations, increasing the number of lines evaluated, and leveraging the large amount of genomic and phenotypic data collected across different growing seasons and environments to increase heritability estimates, selection intensity, and selection accuracy. Breeding programs can leverage their phenotypic and genotypic data to maximize genetic gain and selection accuracy through GS methods utilizing multi-trait and, multi-environment models, high-throughput phenotyping, and deep learning approaches. Overall, this review describes various methods that plant breeders can utilize to increase genetic gains and effectively implement GS in breeding .

Water deficit caused by drought is a significant threat to crop growth and production. Nitric oxide (NO), a water- and lipid-soluble free radical, plays an important role in cytoprotection. Apart from a few studies supporting the role of NO in drought responses, little is known about this pivotal molecular amendment in the regulation of abiotic stress signaling. In this review, we highlight the knowledge gaps in NO roles under drought stress and the technical challenges underlying NO detection and measurements, and we provide recommendations regarding potential avenues for future investigation. The modulation of NO production to alleviate abiotic stress disturbances in higher plants highlights the potential of genetic manipulation to influence NO metabolism as a tool with which plant fitness can be improved under adverse growth conditions.

This research paper is part of the wider project concerning the very first detailed mapping of the overall Taiwanese hydro-power plants that took place from 2013 up to 2015 and it is currently in evaluation and finalization stage. The case of Shanping hydro-power plant has been carefully studied, photographed, documented and mapped in situ. It was one of the isolated hydro-power plant projects originally built to supply the remote area with the specific designation. Shanping hydro-power plant, as well as the other units from the early hydro-power generation era in Taiwan, are considered to be the technological heritage of civil and mechanical engineering that reflects later in all the further projects up to nowadays modern Taiwanese hydro-power plants. Unfortunately, most of the hydro-power houses from the older periods were severely damaged or destroyed by natural causes which were also the case of Shanping unit. The research is trying to reconstruct the original location of the powerhouse and its supporting structures based on available historical documents, previous studies, comparative methodology, and the current on-site observation.

B chromosomes are supernumerary chromosomes which are found in addition to the normal standard chromosomes (A chromosomes). B chromosomes are well known to accumulate several types of repeats. Although the evolution of B chromosomes has been subject of numerous studies, the mechanisms of accumulation and evolution of repetitive sequences is not fully understood. Recently, new genomic approaches have shed light on the origin and accumulation of different classes of repetitive sequences in the process of B chromosome formation and evolution. Here we discuss the impact of repetitive sequences accumulation on the evolution of plant B chromosomes.

The increase in the rate and prevalence of diseases associated with the localized and general loss of bone mass calls for an investigation into therapeutic alternatives that largely involve the de-velopment of new biomaterials and cell therapy, converting tissue bioengineering into a prom-ising option. An experimental model of a critical mandibular lesion in rats has been used to study bone re-generation by treating the ostectomy with the biomaterials Evolution® and Gen-Os® (OsteoBiol®, Italy) combined, or not, with dental pulp stem cells (DP-MSC). The results obtained through the Micro-CT and histological study reveal the almost complete re-covery of the lesion in the group with DP-MSC. These results are supported by increases in endoglin, TGF-β, protocollagen I, parathormone, and calcitonin, generating an environment of bone generation and development when combining Evolution® and Gen-Os® (OsteoBiol®, Italy) with DP-MSC. These promising results confirm the transcendental role of DP-MSC in combina-tion with osteogenic biomaterials for bone regeneration, and warrant further studies, including its assessment in clinical trials.

A new two-step method for developing a nanocomposite of polypropylene (PP) decorated with photocatalytically active TiO2 nanoparticles (nTiO2) is proposed. This method involves low-temperature plasma functionalization of polypropylene followed by ultrasound-assisted anchoring of nTiO2. The nanoparticles, polymeric substrate, and resultant nanocomposite were thoroughly characterized using nanoparticle tracking analysis (NTA), microscopic observations (SEM, TEM, EDX), spectroscopic investigations (XPS, FTIR), thermogravimetric analysis (TG/DTA), and water contact angle (WCA) measurements. The photocatalytic activity of the nanocomposites was evaluated through the degradation of methyl orange. The individual TiO2 nanoparticles ranged from 2-6 nm in size. Oxygen plasma treatment of PP generated surface functional groups (mainly -OH and -C=O), transforming the surface from hydrophobic to hydrophilic, which facilitated efficient deposition of nTiO2. Optimized plasma treatment and sonochemical deposition parameters resulted in an active photocatalytic nTiO2/PP system, degrading 80% of methyl orange under UVA irradiation in 200 minutes. The proposed approach is considered versatile for the functionalization of polymeric materials with photoactive nanoparticles and, in a broader perspective, can be utilized for the fabrication of self-cleaning surfaces.

The leaves of Nicotiana glauca (Solanaceae) plant, are known for its major cause of health concern. This study investigated the antioxidant activity and polyphenols composition of aerial parts of N.glauca collected from its wild habitat in Jordan, using Methanol-Conventional (MC) and deep eutectic solvents (DESs) extraction methods in addition to nicotine content determination using UHPLC. The results have shown that the MC extract contains fewer total phenols and flavonoid content than the DES extract at ratio of 90% (0.1194 ±0.009 and 0.311± 0.020 mg/mL equivalent to gallic acid) and (0.01084±0.005 and 0.928 ± 0.09 mg/mL equivalent to rutin), respectively. Moreover, the study showed that the MC extract contains 635.07 ppm nicotine compared to the DES extraction method, which contains 1194.91 ppm. Both the MC and the DES extracts exhibited weak antioxidant activities with the highest was 33%inhibition equivalent to ascorbic acid was found for DES at (90%) ratio. The UHPLC-MS/MS analysis revealed the presence of variations in the detected compounds between the two extraction methods used. This study found that en-vironmentally friendly DES extraction of N. glauca produced higher phenol and flavonoid content than MC method, highlighting green chemistry methods' superior efficiency and environmental benefits for extracting valuable phytoconstituents.

In this study, by employing the think-aloud model, schema theory and the perceptual cycle model (PCM) from the perspective of vulnerable road traffic participants, the current traffic imperfections of a target section in Wudaokou were analyzed to explore potential improvement measures to enhance safety. Specifically, the present study recruited 30 local volunteers, which were equally divided into a pedestrian group, bicyclist group and E-cyclist group. The research procedure was mainly divided into three steps. By using the think-aloud method, we analyzed and recorded the contents of oral reports of the experimental road section. Then, through translation, segmentation, coding, analysis and other techniques, we sorted and studied the report data and drew a conclusion that was universal in improving the current road traffic conditions. It is hoped that through this study, on the one hand, the applicability of the oral report method, schema theory and perceptual cycle model in road traffic safety can be verified, and, on the other hand, some better improvement measures can be extracted for the road traffic state of the Wudaokou section.

Early and accurate mapping of winter canola planting areas provides critical support for sustainable cropland management. Although some methods have been proposed to map the winter canola at the flowering or later stage, mapping winter canola planting areas at the early stage is still challenging, due to the insufficient understanding of the multi-source remote sensing features sensitive for winter canola mapping. This study proposed an early-stage winter canola area mapping method by using the combination of optical and synthetic aperture radar (SAR) data. We analyzed the spectral features, backscatter coefficients, and textural features of winter canola based on Sentinel-2 and Sentinel-1 images. Random forest (RF) and Support Vector Machine (SVM) classification models were built to map winter canola based on early-stage images and field samples in 2017 and then apply the best model to corresponding satellite data in 2018-2022. Results showed that: (1) The red edge and near-infrared-related spectral features were most important for the mapping of early-stage winter canola, followed by VV, DVI and GOSAVI, which also showed greater differences than the other features; (2) Based on Sentinel-1 and Sentinel-2 data, winter canola could be earliest mapped around 130 days prior to ripening (i.e., early overwinter stage) with the F-score over 0.85 and the OA over 81%; (3) Adding Sentinel-1 could improve the OA by about 2%-4% and the F-score by about 1% -2% in winter canola mapping. (4) The F-score of winter canola mapping based on the classifier transfer approach in 2018-2022 varied between 0.75 and 0.97, and the OA ranged from 79% to 86%. This study demonstrates the potential of early-stage winter canola mapping using the combination of Sentinel-2 and Sentinel-1 images, which could provide valuable and timely information for stakeholders and decision makers.

Laser powder bed fusion (LPBF) is an additive manufacturing technique that is gaining popularity for producing metallic parts in various industries. However, parts produced by LPBF are prone to residual stress, deformation, cracks and other quality defects due to uneven temperature distribution during the LPBF process. To address this issue, in prior work, the authors have proposed SmartScan, a method for determining laser scan sequence in LPBF using an intelligent (i.e., model-based and optimization-driven) approach, rather than using heuristics, and applied it to simple 2D geometries. This paper presents a generalized SmartScan methodology that is applicable to arbitrary 3D geometries. This is achieved by: (1) expanding the thermal model and optimization approach used in SmartScan to multiple layers; (2) enabling SmartScan to process shapes with arbitrary contours and infill patterns within each layer; (3) providing the optimization in SmartScan with a balance of exploration and exploitation to make it less myopic; and (4) improving SmartScan's computational efficiency via model order reduction using singular value decomposition. Sample 3D test artifacts are simulated and printed using SmartScan in comparison with common heuristic scan sequences. Reductions of up to 92% in temperature inhomogeneity, 86% in residual stress, 24% in maximum deformation and 50% in geometric inaccuracy were observed using SmartScan, without significantly sacrificing print speed. An approach for using SmartScan for printing complex 3D parts in practice, by integrating it as a plug-in to a commercial slicing software, was also demonstrated experimentally, along with its benefits in significantly improving printed part quality.

Focal adhesions (FAs) play a crucial role in cell spreading and adhesion, and their autophagic degradation is an emerging area of interest. Our study investigates the role of Thrombospondin Type 1 Domain-Containing Protein 1 (THSD1) in regulating autophagy and FA stability in brain endothelial cells, shedding light on its potential implications for cerebrovascular diseases. Our research reveals a physical interaction between THSD1 and FAs. Depletion of THSD1 significantly reduces FA numbers, impairing cell spreading and adhesion, in an autophagy-dependent manner. Intriguingly, THSD1-mediated autophagy activation operates independently of changes in mTOR and AMPK activation, implying that THSD1 primarily governs FA dynamics rather than serving as a global regulator of nutrient and energy status. Interestingly, THSD1 negatively regulates Beclin 1, a central autophagy regulator, at FAs through interactions with focal adhesion kinase (FAK). The loss of THSD1 diminishes FAK activity, consequently relieving its inhibitory phosphorylation on Beclin 1. This, in turn, promotes the complex formation between Beclin 1 and ATG14, a critical event for the activation of the autophagy cascade. In summary, our findings identify THSD1 as a novel regulator of autophagy that degrades FAs in brain endothelial cells. This underscores the distinctive nature of THSD1-mediated, cargo-directed autophagy and its potential relevance to vascular diseases due to the loss of endothelial FAs. Investigating the underlying mechanisms of THSD1-mediated pathways holds promise for discovering novel therapeutic targets in vascular diseases.

Wastewater-based surveillance has emerged as an important method for monitoring SARS-CoV-2. This study investigated the presence of SARS-CoV-2 in wastewater in Zambia. We conducted a longitudinal study in the Copperbelt and Eastern provinces of Zambia from October 2023 to December 2023 during which 155 wastewater samples were collected. The samples were subjected to three different concentration methods, namely bag-mediated filtration, skimmed milk flocculation, and polythene glycol-based concentration assays. Molecular detection of SARS-CoV-2 nucleic acid was conducted using real-time PCR. Whole genome sequencing was conducted using Illumina COVIDSEQ assay. Of the 155 wastewater samples, 62 (40%) tested positive for SARS-CoV-2. Of these, 13 sequences of sufficient length to determine SARS-CoV-2 lineages were obtained and two sequences were phylogenetically analyzed. Various Omicron subvariants were detected in wastewater including BA.5, XBB.1.45, BA.2.86, and JN.1. Some of these subvariants have been detected in clinical cases in Zambia. Interestingly, phylogenetic analysis positioned a sequence from the Copperbelt Province in the B.1.1.529 clade, suggesting that earlier Omicron variants detected in late 2021 could still be circulating and may not have been wholly replaced by newer subvariants. This study stresses the need for integrating wastewater surveillance of SARS-CoV-2 into mainstream strategies for monitoring SARS-CoV-2 circulation in Zambia.

Abstract: Antimicrobial peptides (AMPs) are short peptides, usually made up of less than 100 amino acid residues. They are found in many living organisms and are an important factor in their innate immune systems. AMPs can be extracted from various living sources including bacteria, plants, animals and even humans. They are usually cationic peptides with an amphiphilic structure, which allows them to easily bind and interact with the cellular membranes of viruses, bacteria, fungi and other pathogens. They can act against both Gram-negative and Gram-positive pathogens and have various modes of action against them. Some attack the pathogens membrane, while others target their intracellular organelles as well as their nucleic acids, proteins and metabolic pathways. A crucial area of use of AMPs is in their ability to help with emerging antibiotic resistance: some AMPs are active against resistant strains and are susceptible to peptide engineering. This review considers AMPs from three key sources: plants, animals and humans, as well as their modes of action and some AMPs sequences.

The use of plant-based and microorganism-based biological inputs is a sustainable agricultural practice, promoting a suitable and better utilization of non-renewable resources in the environment. The benefits of using microorganisms are associated with both direct and indirect mechanisms, primarily related to improvements in nutrient absorption and availability, as well as plant growth. The main benefits of using biochemical pesticides are the promotion of sustainability and the management of resistance. Although the use of microorganisms and botanical metabolites is a promising agricultural alternative, it is still primarily concentrated in grain crops. However, due to the wide range of mechanisms of action of plant-based and microorganism-based biological inputs, there is an opportunity to expand their use in agriculture. In the Brazilian biological inputs market, various terminologies have been used to characterize biological-based products, with many of these terms being employed incorrectly and sometimes conflicting with the country’s legislation. Therefore, this review presents the classes of biological inputs and the application and evolution of the plant-based and microbiological-based product market in different crops in Brazil.

It remains poorly understood how the life history strategies and transmission ecologies of viruses of plants, arthropods, and vertebrates are interrelated. The present analysis hinges on the virus transmission success. Virus transmission reflects where in the host-body viruses are retained or replicating. Plants, arthropods, and vertebrates share a protective outer-layer, a circulatory system, and reproductive organs. The latter enables vertical virus transmission and associates with virus-host mutualism. Two broadly opposing virus life history strategies are considered. Acute viruses tend to be replicative and are swiftly transmitted to the next host. Instead, persistent viruses keep virus replicating costs and host damage to a minimum. The intertwined life histories and transmission ecologies are accordingly pieced together, based on the virus mono- or instead dual-host tropism, the location of virus retention or replication on or in the host-body, the presence of cyclical or mechanical transmission by arthropods, and of horizontal and vertical host-to-host transmission modes. It is shown that in the arthropod and in the vertebrate animal host, virus circulation in the hemocoel or blood circulation goes hand-in-hand with vertical transmission. Instead, plant phloem viruses do not transmit via seed. The latter is the rule for the plant-only viruses. The risk management implications are discussed in brief.

Fossils constitute the principal repository of data that allow for independent tests of hypotheses of biological evolution derived from observations of the extant biota. Traditionally, transformational series of structure, consisting of sequences of fossils of the same lineage through time, have been employed to reconstruct and interpret morphological evolution. More recently, a move toward an updated paradigm was fueled by the deliberate integration of developmental thinking in the inclusion of fossils in reconstruction of morphological evolution. The vehicle for this is provided by structural fingerprints – recognizable morphological and anatomical structures generated by (and reflective of) the deployment of specific genes and regulatory pathways during development. Furthermore, because the regulation of plant development is both modular and hierarchical in nature, combining structural fingerprints recognized in the fossil record with our understanding of the developmental regulation of those structures produces a powerful tool for understanding plant evolution. This is particularly true when the systematic distribution of specific developmental regulatory mechanisms and modules is viewed within an evolutionary (paleo-evo-devo) framework. Here, we discuss several advances in understanding the processes and patterns of evolution, achieved by tracking structural fingerprints with their underlying regulatory modules across lineages, living and fossil: the role of polar auxin regulation in the cellular patterning of secondary xylem and the parallel evolution of arborescence in lycophytes and seed plants; the morphology and life history of early polysporangiophytes and tracheophytes; the role of modularity in the parallel evolution of leaves in euphyllophytes; leaf meristematic activity and the parallel evolution of venation patterns among euphyllophytes; mosaic deployment of regulatory modules and the diverse modes of secondary growth of euphyllophytes; modularity and hierarchy in developmental regulation and the evolution of equisetophyte reproductive morphology. More generally, inclusion of plant fossils in the evo-devo paradigm has informed discussions on the evolution of growth patterns and growth responses, sporophyte body plans and their homology, sequences of character evolution, and the evolution of reproductive systems.

Total-body PET/CT scanners provide increased sensitivity, enabling the adjustment of imaging parameters by reducing injected activity or shortening acquisition time. This study aimed to evaluate the limitations of reduced [18F]FDG activity doses on image quality, lesion detectabil-ity, and quantification of lesion uptake in the Biograph Vision Quadra, as well as to assess the benefits of the recently introduced ultra-high sensitivity mode in a clinical setting. A number of 26 patients who underwent [18F]FDG-PET/CT (3.0 MBq/kg, 5 min. scan time) were included in this analysis. PET raw data was rebinned for shorter frame durations to simulate 5 min. scans with lower activities in high sensitivity (HS) and ultra-high sensitivity (UHS) modes. Image quality, noise, and lesion detectability (n=82) were assessed using a 5-point Likert scale. The co-efficient of variation (CoV), signal-to-noise ratio (SNR), tumor-to-background ratio (TBR), and standardized uptake values (SUV) including SUVmean, SUVmax, and SUVpeak were evaluated. Sub-jective image ratings were generally superior in UHS compared to HS mode. At 0.5 MBq/kg, le-sion detectability decreased to 95% (HS) and 98% (UHS). SNR was comparable at 1.0 MBq/kg in HS (5.7±0.6) and 0.5 MBq/kg in UHS (5.5±0.5). With lower doses, there were negligible reductions in SUVmean and SUVpeak, whereas SUVmax increased steadily. Reducing [18F]FDG activity to 1.0 MBq/kg (HS/UHS) in a total-body PET/CT provides diagnostic image quality without statistical-ly significant changes in uptake parameters. UHS mode improves image quality, noise, and le-sion detectability compared to HS mode.

The relentless challenges posed by the COVID-19 pandemic have placed immense pressure on densely populated regions, such as Hong Kong, particularly in the context of an aging population. The burgeoning demand for healthcare services has necessitated the optimization of resource al-location within healthcare systems. This research presents an innovative analytical queueing model specifically tailored to address the intricate gridlock dynamics prevalent in healthcare systems, with a focused application in the challenging landscape of COVID-19 management. Hong Kong, like numerous other regions, has experienced a demo-graphic transition leading to heightened healthcare demands. Traditional methodologies for scrutinizing gridlock issues in healthcare settings, including simulation models, often prove suboptimal within the context of sophisticated optimization frameworks. This study, however, delves into analytical queueing models, offering a more efficient and effective approach. These models have been underexplored, primarily due to the intricacies involved in modeling gridlock propagation within restricted capacity, a critical concern magnified by the COVID-19 pandemic. The novel Queueing Model introduced in this research incorporates the maintenance of queue capacities and topological aspects as exogenous parameters, rendering it exceptionally adaptable for diverse gridlock-related applications. This adaptability is especially pertinent to healthcare management during the COVID-19 crisis. The model meticulously integrates the concept of gridlock, furnishing a comprehensive comprehension of its origins and repercussions. Validation of this model involves rigorous comparison with established methodologies, exact results, and simulation data, consistently high-lighting its versatility and precision. By applying the model to healthcare management, we scrutinize the dynamics of patient flow within a Hong Kong hospital, placing specific emphasis on the critical issue of bed blockage, further exacerbated by the COVID-19 pandemic. The model's gridlock decomposition unearths the nuanced impact of bed blockage on distinct hospital units, addressing the imperative requirement for quantifying in-patient bed blockage within healthcare systems during a pandemic.

Parental refusal of childhood vaccines is a growing public health concern. Numerous reasons exist for this refusal, including religious, personal, and philosophical beliefs, and safety concerns. However, parental refusal of childhood vaccines is not simply an individualized problem for the family; this impacts herd immunity and affects the entire community. To improve vaccination rates among the pediatric population, understanding the thought process and decision-making behind parental opposition and refusal of vaccinations is essential. Using a survey developed to assess attitudes towards recommended childhood vaccines and the COVID-19 vaccine, this study examined the correlation between vaccine literacy and hesitancy among parents and legal guardians of elementary school-aged children in the Midwest. Responses were analyzed using Chi-squared tests on “R” software. Significant negative correlations were found between COVID-19 hesitancy and vaccine literacy, and resistance towards all vaccines and vaccine literacy. No significant negative correlations were found between hesitancy towards all vaccines and vaccine literacy, or hesitancy and literacy among different income and education brackets. Our results suggest that vaccine education may lessen vaccine hesitancy among parents and may be an essential factor in improving vaccination rates among the pediatric population.

Background: This study delves into the examination of racial and ethnic disparities in the distribution of the Monkeypox (MPOX) virus vaccine within the United States, offering a critical healthcare perspective on an emerging public health concern. It particularly focuses on the demographic patterns associated with MPOX transmission and the allocation of vaccines. Methods: A comprehensive analysis was conducted, drawing on a wide array of data sources to understand the vaccine distribution and demographic trends in the United States. The study scrutinized three main aspects: MPOX cases by race and ethnicity, vaccine administration across different racial and gender categories, and the potential disparities therein. Results: The findings reveal significant disparities in the distribution of vaccine doses, with males, particularly gay, bisexual, and other Men who have sex with men (MSM), receiving the majority of doses. Moreover, substantial variations in MPOX cases are observed among different racial and ethnic groups, emphasizing the need for culturally sensitive public health strategies. Conclusions: The study underscores the urgent need for targeted public health interventions to address disparities and safeguard the well-being of those at higher risk, particularly MSM. It highlights the importance of equity in vaccine distribution and culturally sensitive approaches, and serves as a foundation for shaping effective public health policies and strategies to mitigate the spread of MPOX. This research advances our understanding of healthcare disparities in the context of an emerging viral infection, providing valuable insights for future public health initiatives.

Due to their distinct physical, chemical, and biological characteristics, biopolymers, in particular Poly Ethylene Glycol (PEG) and Cellulose, are frequently used in biomedical medicine as drug or vaccine delivery systems. In this study, we have done a systematic review and a meta-analysis to compare current developments in many PEG and cellulose-based hydrogels, including double network hydrogels, injectable hydrogels, sliding hydrogels, conductive hydrogels, responsive hydrogels, and nanocomposite hydrogels. The pharmacokinetic properties, including physicochemical properties, biocompatibility, biodegradability, temperature, and pH, have been studied as these critical factors are to be considered for deciding the suitability of the drug for delivery. Moreover, the study has evaluated the controlled-release parameters such as half-life, circulation time, maximum release percentage of loaded drug released, burst release, maximum release, and drug-release kinetics. Finally, the efficacy and immune response of hydrogel was studied for future choice, including the cellulose hydrogel system in COVID-related long-term vaccine delivery. The finding revealed that cellulose-based hydrogel is effective for vaccine delivery.

2-(Morpholin-4-yl)-4,5-bis(2’’,2’’,2’’-trinitroethoxy)-1,3,5-triazine having QSAR-predicted anti-tumor activity was tested for the cytotoxicity using MTT and LDH cell viability tests. The experiments were conducted using human fibroblasts, peripheral blood mononuclear cells and breast cancer cells and allowed to identify effective cytotoxic concentration ant therapeutic range of this compound. The data obtained suggest the feasibility of the further studies of the test compound as a potential anti-cancer agent.

Natural killer (NK) cell therapy is one of the most promising treatments for Glioblastoma Multiforme (GBM). However, this emerging technology is limited by the availability of sufficient numbers of fully functional cells. Here, we investigated the efficacy of NK cells that were expanded and treated by interleukin-2 (IL-2) and heat shock protein70 (HSP70), both in vitro and in vivo. Proliferation and cytotoxicity assays were used to assess the functionality of NK cells in vitro, after which treated and naïve NK cells were administrated intra-cranially and systemically to compare the potential antitumor activities in our in vivo rat GBM models. In vitro assays provided strong evidence of NK cell efficacy against C6 tumor cells. In vivo tracking of NK cells showed efficient homing around and within the tumor site. Furthermore, significant amelioration of the tumor in rats treated with HSP70/Il-2 treated NK cells as compared to those subjected to non-treated NK cells, as confirmed by MRI, proved the efficacy of adoptive NK cell therapy. Moreover, results obtained with systemic injection confirmed migration of activated NK cells over the blood brain barrier and subsequent targeting of GBM tumor cells. Our data suggest that administration of HSP70/Il-2 treated NK cells may be a promising therapeutic approach to be considered in the treatment of GBM.

In this work, optimal consumption and investment strategies are derived for risk-averse investors under the 4/2 stochastic volatility class of models. We work under an expected utility (EUT) framework and consider a Constant Relative Risk Aversion (CRRA) investor, who might also be ambiguity-averse. The corresponding Hamilton-Jacobi-Bellman (HJB) and HJB-Isaacs (HJBI) equations are solved in closed-form for a subset of the parametric space and under some restrictions on the portfolio setting, for complete markets. Conditions for proper changes of measure and well defined solutions are provided. These are the first analytical solutions for the 4/2 stochastic volatility model and the embedded 3/2 model for the type of excess returns established in .

Determining the maturity of compost and other organic fertilizers is very important because of possible phytotoxic or phytostimulative effects. The maturity of the compost can be assessed on the basis of chemical analyses, and the germination test with different test plants is most often used to determine phytotoxicity. In this research, using the results of chemical analyses, the maturity of compost produced from plant residues after maintenance of green public areas was assessed. At the same time, a germination test was carried out with 4 test plant species (cucumber, garden cress, triticale, barley) to determine the phytotoxicity of compost (i.e. compost extract in a ratio of 1:2.5 and 1:10) and 3 ammonium N solutions (in concentrations of 200, 400 and 600 mg/L NH4-N). According to the chemical properties of compost, primarily the C/N and NH4-N/NO3-N ratios, as well as the NH4-N concentration, and the germination test with cu-cumber and garden cress, we can conclude that the tested compost was mature and that we do not expect a phytotoxic effect. The choice of the plant is very significant because the germination test with compost extract shows an undoubted phytostimulative effect on garden cress and cu-cumber with more pronounced phytostimulative effect of compost 1:10 than 1:2.5 extract. No such effect was found on the monocotyledonous test plants triticale and barley since the 1:10 ex-tract had no significant effect, and the 1:2.5 extract had a phytotoxic effect, moderate on triticale and high on barley. The conclusion is that garden cress and cucumber are suitable test plants for determining phytostimulative effect of compost, but they are not suitable for determining phytotoxicity for monocotyledonous plants, especially if the cause of phytotoxicity is some non-ammonium component. Barley is the most suitable species for determining non-ammonium phytotoxicity of compost and phytostimulative or phytotoxic effect of ammonium form of nitrogen. It would be very useful to conduct a comparative germination test with compost extracts in the ratio 1:2.5 and 1:10, whereby the 1:2.5 extract is used as a test for phytotoxicity, and the 1:10 extract for testing phytostimulative effect.

Background: The validation of laser usage during laparoscopic procedures, notably by Camran Nezhat in the late 1980s, has been significant. Lasers offer precision and depth control in tissue vaporization without bleeding. Surgical intervention remains central in managing endometrio-sis-associated pain and infertility, especially for patients unresponsive to hormonal therapy. Methods: This retrospective cohort study included 200 patients with SPE who underwent laparo-scopic laser vaporization. Surgery was performed using a CO2 laser, and histological confirma-tion of endometriosis was obtained for all cases. Pain scores and SF-36 questionnaire domains were assessed preoperatively and postoperatively. Fertility outcomes were evaluated among pa-tients desiring pregnancy. Results: Significant improvements in pain score and SF-36 questionnaire domains were ob-served postoperatively (p-value

Although WHO declared the end of the pandemic based on the report by International Health Regulations Emergency Committee on May 4th 2023 the health authorities stresses that COVID-19 is still an ongoing health issue and especially the populations in the high-priority risk need booster doses to sustain the gains. However the vaccination rates decrease all around the world according to WHO’s Strategic Advisory Group of Expert’s on Immunization (SAGE). One of the main reasons of this dramatic decrease can be vaccine hesitancy or refusal. Vaccine hesitancy is defined as refusal or delay in vaccination, although there is a sufficient supply available (SAGE working group, 2014). MacDonald (2015) stated that vaccine hesitancy is higher among the people who has lack of confidence or trust both to the vaccines themselves and health authorities within the country. However hesitancy can be towards specific vaccines or selective. One of the most salient selective vaccine hesitancy is the childhood vaccine hesitancy. In the current study we examined the predictors of vaccine hesitancy for children and their parents. A total of 199 parents (age range: 26-58; Mean Age: 35) have been recruited by using an online survey. Seventy six percent of the parents who responded were mothers. Education level of the sample was relatively high; 48% of the participants had bachelor degree while %32 had postgraduate degrees. Results indicated that ruminative thinking about Covid-19 was the strongest predictor and decreased the risk for childhood vaccine hesitancy. Surprisingly, lower poor supervision predicted higher vaccine hesitancy/refusal for children. On the other hand conspiracy thoughts about the pandemic increased the refusal of COVID-19 vaccines three times. For parents conspiracy thoughts and ruminative thinking predicted vaccine hesitancy/refusal similar to the previous model. Positive parenting was found to be negatively related with vaccine hesitancy/refusal for the parents themselves. One unit increase in this variable decreased the vaccine hesitancy/refusal for almost five-folds.

In this study, we investigated the role of Giardia EVs in cellular communication and their potential as vaccine candidates. Our findings revealed that Giardia EVs activate pro-inflammatory signalling cascades, including SAPK/JNK and ERK1/ERK2, as well as the NF-kB pathway, resulting in IκB-α degradation and p65 translocation to the nucleus, in mouse macrophages. Moreover, Giardia EVs increased the expression of genes encoding pro-inflammatory molecules, such as Il1β, Il6, Il4, Ptgs2, Nos2, and Tnf. Interestingly, Giardia EVs enhanced the maturation status of human Mo-DCs and significantly increased T-cell proliferation with a Th1 profile. Immunization studies demonstrated that Giardia EVs elicited antigen-specific antibodies, with IgG subclasses indicating a balance Th1/ Th2 response. Mass spectrometry analysis identified EV proteins (22 KDa and 50 KDa) that bind to serum antibodies of immunized mice including elongation factor 1-alpha, Alpha-7.3 giardin, tubulin, and Variant Surface Proteins (VSP), known antigenic proteins in Giardia infections. Overall, our results indicated that Giardia EVs modulate innate immune cells in vitro, induce antibody-based immune response in vivo, and contain conserved immunogenic proteins. Consequently, Giardia EVs hold promise as a cell-free vaccine candidate for giardiasis.

Despite numerous studies on cancer treatment, cancer remains a challenging disease to cure, even after decades of research. In recent years, cancer vaccine has emerged as a promising approach for cancer treatment, offering few unexpected side effects compared to existing therapies. How-ever, cancer vaccine faces obstacles to commercialization due to its low efficacy. Particularly, the Toll-like receptor (TLR) adjuvant system, specifically the TLR 7/8 agonist, has shown potential for activating Th1 immunity, which stimulates both innate and adaptive immune responses through T cells. In this study, we developed ProLNG-S, a cholesterol-conjugated form of resiquimod (R848), to enhance immune efficacy by stimulating the immune system and reducing toxicity. ProLNG-S was formulated as ProLNG-001, a positively charged liposome, and co-administered with oval-bumin (OVA) protein in the B16-OVA model. ProLNG-001 effectively targeted secondary lym-phoid organs, resulting in a robust systemic anti-tumor immune response and tumor-specific T cell activation. Consequently, ProLNG-001 demonstrated potential for preventing tumor progression and improving survival compared to AS01 by enhancing anti-tumor immunity.

During the COVID-19 pandemic, online media were the most widely used source of scientific information. Often, they are also the only ones on science-related topics. Research has shown that much of the information available on the Internet about the health crisis lacked scientific rigor and that misinformation about health issues can pose a threat to public health. In turn, millions of Catholics were found to be demonstrating against vaccination against COVID-19 based on "false" and misleading religious arguments. This research analyses publications about the vaccine in Catholic online media with the aim of understanding the presence of information (and misinformation) in this community. An algorithm designed for each media outlet collected COVID-19 vaccine-related publications from 109 Catholic media outlets in five languages. In total, 970 publications were analysed for journalistic genres, types of headlines and sources of information. The results show that most publications are informative and most of their headlines are neutral. However, opinion articles have mostly negative headlines. Also, a higher percentage of the opinion authors come from the religious sphere and most of the sources cited are religious. Finally, 35% of the publications relate the vaccine to the framing issue of abortion.

Healthcare workers (HCWs) are regarded as role models regarding health-related issues including vaccination. Therefore, it is essential to identify the predictors for COVID-19 vaccine acceptance among them. A cross-sectional study to assess the risk perception, attitudes and knowledge of HCWs toward COVID-19 vaccination was carried out. A total of 710 responses were received between September 2021 to March 2022, from HCWs in the Northern, Western and Eastern regions of Nigeria. Cross tabulations were performed to determine statistical relations between sociodemographic variables, knowledge, attitudes and risk perceptions concerning COVID-19 vaccine acceptance. Multinomial Logistic Regression analysis was performed to determine the predictive variables for COVID-19 vaccine acceptance. Statistical analyses were performed and P-values less than 0.05 were considered statistically significant at a CI of 95%. Results showed that 59.3% of the participants were amenable to COVID-19 vaccines. Multinomial regression analysis identified 14 variables at α <0.05 as predictors for vaccine acceptance. Male HCWs were 2.8 times more likely to accept the vaccine than their female counterparts. HCWs that were knowledgeable of the different kinds of vaccines, willing to recommend the vaccines to their patients, believe that the timing of COVID-19 vaccination was appropriate and had recent vaccination history within three years were 1.6, 24.9, 4.4 and 3.1 times more likely to take COVID-19 vaccine than those not sure. The study found a relatively high trust (51.3%) in the Nigerian Center for Disease Control (NCDC) for information regarding COVID-19 vaccines. Therefore, the NDCD should disseminate more robust insights regarding the safety profiles of various COVID-19 vaccines.

This study focuses on cardiovascular effects, particularly myocarditis and pericarditis events, after BNT162b2 mRNA COVID-19 vaccine injection in Thai adolescents. This prospective cohort study enrolled students from two schools aged 13–18 years who received the second dose of the BNT162b2 mRNA COVID-19 vaccine. Data including demographics, symptoms, vital signs, ECG, echocardiography and cardiac enzymes were collected at baseline, Day 3, Day 7, and Day 14 (optional) using case record forms.We enrolled 314 participants; of these, 13 participants were lost to follow up, leaving 301 participants for analysis. The most common cardiovascular effects were tachycardia (7.64%), shortness of breath (6.64%), palpitation (4.32%), chest pain (4.32%), and hypertension (3.99%). Seven participants (2.33%) exhibited at least one elevated cardiac biomarker or positive lab assessments. Cardiovascular effects were found in 29.24% of patients, ranging from tachycardia, palpitation, and myopericarditis. Myopericarditis was confirmed in one patient after vaccination. Two patients had suspected pericarditis and four patients had suspected subclinical myocarditis. Conclusion: Cardiovascular effects in adolescents after BNT162b2 mRNA COVID-19 vaccination included tachycardia, palpitation, and myocarditis. The clinical presentation of myopericarditis after vaccination was usually mild, with all cases fully recovering within 14 days. Hence, adolescents receiving mRNA vaccines should be monitored for side effects. Clinical Trial Registration: NCT05288231

Middle East Respiratory Syndrome coronavirus (MERS-CoV) infects dromedary camels and zoonotically infects humans, causing a respiratory disease with severe pneumonia and death. With no approved antiviral or vaccine interventions for MERS, vaccines are being developed for camels to prevent virus transmission into humans. We have previously developed a chimpanzee adenoviral vector-based vaccine for MERS-CoV (ChAdOx1 MERS) and reported its strong humoral immunogenicity in dromedary camels. Here, we looked back at total RNA isolated from three immunised dromedaries pre and post-vaccination during the first day; and performed RNA sequencing and bioinformatic analysis in order to shed light on the molecular immune responses following a ChAdOx1 MERS vaccination. Our finding shows that a number of transcripts were differentially regulated as an effect of the vaccination, including genes that are involved in innate and adaptive immunity, such as type I and II interferon responses. The camel Bcl-3 and Bcl-6 transcripts were significantly upregulated, indicating a strong activation of Tfh cells, B cell, and NF-kB pathways. In conclusion, this study gives an overall view of the first changes in the immune transcriptome of dromedaries after vaccination; it supports the potency of ChAdOx1 MERS as a potential camel vaccine to block transmission and prevent new human cases and outbreaks.

After a long limbo, RNA has gained its credibility as a druggable target, fully earning its de-served role in the next-generation area of pharmaceutical R&D. We have recently probed the Trans-Activation Response element (TAR), a RNA stem–bulge–loop domain of the HIV-1 genome with bis-3-chloropiperidines (B-CePs), and revealed the compounds unique behavior in stabiliz-ing TAR structure, thus impairing in vitro the chaperone activity of the HIV-1 nucleocapsid (NC) protein. Seeking to elucidate the determinants of B-CePs inhibition, we have further characterized here their effects on the target TAR and its NC recognition, while developing quantitative analyti-cal approaches for the study of multicomponent RNA-based interactions.

Visfatin, a member of the adipokine family, plays an important role in many metabolic and stress responses. The mechanisms underlying the direct therapeutic effects of visfatin on wound healing have not been reported yet. In this study, we examined the effects of visfatin on wound healing in vitro and in vivo. Visfatin enhanced the proliferation and migration of human dermal fibroblasts (HDFs) and keratinocytes, and significantly increased the expression of wound healing-related vascular endothelial growth factor (VEGF) in vitro and in vivo. Treatment of HDFs with visfatin induced activation of both extracellular signal-regulated kinases 1 and 2 (ERK1/2) and c-Jun N-terminal kinases 1 and 2 (JNK1/2) in a time-dependent manner. Inhibition of ERK1/2 and JNK1/2 led to a significant decrease in visfatin-induced proliferation and migration of HDFs. Importantly, blocking VEGF with its neutralizing antibodies suppressed the visfatin-induced proliferation and migration of HDFs and human keratinocytes, indicating that visfatin induces the proliferation and migration of HDFs and human keratinocytes via increased VEGF expression. Moreover, visfatin effectively improved wound repair in vivo, which was comparable to the wound healing activity of epidermal growth factor (EGF). Taken together, we demonstrate that visfatin promotes the proliferation and migration of HDFs and human keratinocytes by inducing VEGF expression and can be used as a potential novel therapeutic agent for wound healing.

Humans are exposed to the environmental pollutants 2, 4-dichlorophenol (2, 4-DCP) and 2, 5-dichlorophenol (2, 5-DCP) through air, use of water and consuming products. In this study, we evaluated the urinary concentrations of these compounds in Korean people from the age of 18 to 69 years by making use of the data from the Korean National Human Biomonitoring Survey that was completed in 2009. Of 1,865 representative Koreans, 63.4% and 97.9% were found to have concentrations of 2, 4-DCP and 2, 5-DCP > 0.05 μg/L (limit of detection) in their urine. The geometric mean urinary concentrations were 0.14 μg/L (confidence interval of 95% = 0.13–0.16) and 0.44 μg/L (confidence interval = 0.41–0.48), respectively. It was fond that the adjusted proportional changes in 2, 4-DCP concentrations were significantly associated with body mass index, whereas those of 2, 5-DCP concentrations were influenced by place of residence. From these findings, it is evident that most adults in Korea have levels of 2, 4-DCP and 2, 5-DCP that are detectable in their urine and burden of these compounds on their bodies varies depending on numerous demographic factors.

Natural Gas (NG) processing is a prominent industrial separation process. Among the available techniques, the innovative membrane process shows potential for efficient removal of impurities, including carbon dioxide (CO₂). This study focuses on utilizing breakthroughs in membrane separation to drive sustainable CO₂ extraction from natural gas. Through comprehensive research and analysis, we explore the effectiveness and feasibility of membrane-based systems in removing CO₂ impurities from NG, thus promoting greener and more sustainable industrial practices. Our findings underscore the transformative nature of membrane separation technology, presenting new possibilities for a more environmentally-friendly and sustainable approach to CO₂ extraction from natural gas.Natural Gas (NG) processing utilizes various techniques for impurity removal, with the membrane process emerging as a promising option for efficient carbon dioxide (CO₂) extraction. This research proposes the integration of a simple mathematical model into ASPEN HYSYS to design a membrane system for CO₂/CH₄ separation. The study also investigates parameter sensitivities by altering operating conditions, such as feed composition and pressure, as well as membrane properties, including selectivity. By analyzing these variables, we aim to optimize the performance and efficiency of the membrane system, facilitating the sustainable extraction of CO₂ from NG. The findings contribute to advancing the design and operation of membrane-based processes for CO₂ separation, paving the way for greener and more sustainable industrial practices. In addition, this study explores various configurations for optimizing the design of the membrane system, including single-stage with and without recycling as well as double-stage configurations. The investigation demonstrates that methane recovery can be enhanced through the recycling of the permeate stream and by implementing a double stage membrane system. These findings highlight the potential for improving the efficiency and performance of the membrane system, enabling higher methane recovery rates. By considering different configurations, this research contributes to the development of more effective and sustainable CO₂ extraction processes from natural gas.

Airborne wind energy (AWE) systems use tethered flying devices to harvest higher-altitude winds to produce electricity. For a successful deployment of these systems, it is crucial to understand how the public perceives them. If public concerns about the technology are not taken seriously, implementation could be delayed or, in some cases, prevented, resulting in increased costs for project developers and a lower contribution of the sector to renewable energy targets. This literature review assessed the current state of knowledge on public responses to AWE. An exhaustive literature search led to the identification of 40 relevant publications that were reviewed. The literature assumed that the safety, visibility, acoustic emissions, ecological impacts, and the siting of AWE systems shape public responses to the technology. The reviewed literature views people’s responses to AWE very optimistically but lacks scientific evidence to back up its claims. It seems to overlook that the influence of AWE’s characteristics (e.g., visibility) on public responses will also depend on a range of situational and psychological factors (e.g., people’s general attitude towards AWE, the public’s trust in project developers). Therefore, empirical social scientific research is needed to increase the field’s understanding of public responses to AWE and thereby facilitate deployment.

Driving simulators are widely used for understanding human-machine interaction, driver behavior and in driver training. The effectiveness of simulators in these process depends largely on their ability to generate realistic motion cues. Though the conventional filter-based motion cueing strategies have provided reasonable results, these methods suffer from poor workspace management. To address this issue, linear MPC-based strategies have been applied in the past. However, since the kinematics of the motion platform itself is non-linear and the required motion varies with the driving conditions, this approach tends to produce sub-optimal results. This paper presents a nonlinear MPC-based algorithm which incorporates the nonlinear kinematics of the Stewart platform within the MPC algorithm in order to increase the cueing fidelity and utilize maximum workspace. Further, adaptive weights-based tuning is used to smoothen the movement of the platform towards its physical limits. Full-track simulations were carried out and performance indicators were defined to objectively compare the response of the proposed algorithm with classical washout filter and linear MPC-based algorithms. The results indicate a better reference tracking with lower root mean square error and higher shape correlation for the proposed algorithm. Lastly, the effect of the adaptive weights-based tuning was also observed in the form of smoother actuator movements and better workspace utilization.

Phytophthora cinnamomi is a devastating soil-borne plant pathogen. The primary source of P. cinnamomi infection is the soil, where the pathogen can persist for long periods. Effective prevention and management of this pathogen in tree crops require an early and reliable detection method. In this study, we develop a simple, fast, reliable, and sensitive method based on real-time quantitative PCR (qPCR) for P. cinnamomi detection and quantification directly in plant or soil samples. Primers were developed targeting the nuclear single-copy ras-related protein gene Ypt1, suitable for Phytophthora-specific PCR. The specificity of the assay was confirmed by testing it against genomic DNA from 50 isolates across 8 different Phytophthora clades, including very similar P. parvispora. The efficiency and reliability of the qPCR protocol were evaluated on challenging environmental samples, such as plant tissue of different host trees (walnut, chestnut, oak) and naturally infected soils in walnut orchards. The main outcome was the development of a qPCR method for the specific identification and quantification of P. cinnamomi in natural soil samples. Additionally, this study established a systematic and repeatable soil sampling method and developed an efficient soil DNA extraction technique to apply the developed qPCR in naturally infested soils of walnut orchards.

The Golden Syrian hamster (Mesocricetus auratus) is now commonly used in preclinical research for the study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the assessment of vaccines, drugs and therapeutics. Here we show that hamsters inoculated via the intranasal route with the same infectious virus dose of prototypical SARS-CoV-2 administered in a different volume present with different clinical signs, weight loss and viral shedding, with a reduced volume resulting in reduced severity of disease similar to that obtained by a 500-fold reduction in challenge dose. The tissue burden of virus and the severity of pulmonary pathology were also significantly affected by different challenge inoculum volumes. These findings suggest that direct comparison between the severity of SARS-CoV-2 variants or studies assessing the efficacy of treatments determined by hamster studies cannot be made unless both the challenge dose and inoculation volume are matched when using the intranasal route. Additionally, analysis of sub-genomic and total genomic RNA PCR data demonstrated no link between sub-genomic and live viral titres and that sub-genomic analyses do not provide any information beyond that provided by more sensitive total genomic PCR.

Chronic obstructive pulmonary disease (COPD) patients are particularly susceptible to respiratory infections like influenza, which exacerbate symptoms and increase healthcare utilization. While smoking cessation and influenza vaccination are recommended preventive measures, their combined impact on healthcare resource utilization is underexplored. The Charlson Comorbidity Index (CCI) assesses comorbidity burden in COPD patients and may influence healthcare outcomes. We conducted a retrospective analysis of 357 COPD patients, evaluating smoking cessation success over one year and influenza vaccination receipt, stratifying patients by CCI scores. Healthcare utilization outcomes included emergency room visits, hospitalizations, and medical expenses. Results showed that 51.82% of patients quit smoking and 59.66% received influenza vaccination, with higher comorbidity prevalence in advanced COPD stages (p=0.002). Both smoking cessation and influenza vaccination independently correlated with decreased emergency room visits, hospital admissions, days, and costs. Patients who both quit smoking and received influenza vaccination exhibited the lowest healthcare utilization rates. In conclusion, smoking cessation and influenza vaccination significantly reduce healthcare resource utilization in COPD patients, with the combination yielding synergistic benefits, particularly in those with lower CCI scores. Integrating these interventions and comorbidity management in COPD strategies is essential for optimizing patient outcomes and healthcare efficiency.

Xanthone derivatives, a class of natural compounds abundantly found in plants such as mangosteen (Garcinia mangostana) and certain herbs, have garnered substantial interest due to their diverse pharmacological properties, including antioxidant, anti-inflammatory, and anti-cancer activities. Recent investigations have unveiled their potential as modulators of enzymatic activity, prompting exploration into their effects on hyaluronidase-mediated HA degradation, and their effects in topical treatment of telangiectasia and rosacea. Telangiectasia and rosacea are common dermatological conditions characterized by chronic skin inflammation, vascular abnormalities, and visible blood vessels, resulting in significant cosmetic concerns and impaired quality of life for affected individuals. This review aims to provide a comprehensive overview of the current understanding regarding the interplay between mechanisms of action by which xanthone derivatives exert their therapeutic effects, including the inhibition of pro-inflammatory cytokines, modulation of oxidative stress pathways, and regulation of vascular endothelial growth factors. Furthermore, we will discuss the implications of harnessing xanthone derivatives as therapeutic agents for mitigating vascular dysfunction and its associated pathologies, thereby offering insights into future research directions and therapeutic strategies in the field of vascular biology.

The rationalization of single molecule magnets’ (SMMs) magnetic properties by quantum mechanical approaches represents a major task in the field of the Molecular Magnetism. The fundamental interpretative key of molecular magnetism is the phenomenological Spin Hamiltonian and the understanding of the role of its different terms by electronic structure calculations is expected to steer the rational design of new and more performing SMMs. This paper deals with the ab initio calculation of isotropic and anisotropic exchange contributions in the Fe(III) dimer [Fe₂(OCH₃)₂(dbm)₄]. This system represents the building block of one of the most studied Single Molecule Magnets ([Fe₄RC(CH₂O)₃)₂(dpm)₆] where R can be an aliphatic chain or a phenyl group just to name the most common functionalization groups) and its relatively reduced size allows the use of a high computational level of theory. Calculations were performed using CASSCF and NEVPT2 approaches on the X-ray geometry as assessment of the computational protocol, which has then be used to evinced the importance of the outer coordination shell nature through organic ligand modelization. Magneto-structural correlations as function of internal degrees of freedom for isotropic and anisotropic exchange contributions are also presented, outlining for the first time the extremely rapidly changing nature of the anisotropic exchange coupling.

Neurofibromatosis type 2 (NF2) is a genetic syndrome characterized by the growth of benign tumors in the nervous system, particularly bilateral vestibular schwannomas, meningiomas, and ependymomas. This review consolidates the current knowledge on NF2 syndrome, emphasizing the molecular pathology associated with the mutations in the gene of the same name, the NF2 gene, and the subsequent dysfunction of its product, the Merlin protein. Merlin, a tumor suppressor, integrates multiple signaling pathways that regulate cell contact, proliferation, and motility, thereby influencing tumor growth. The loss of Merlin disrupts these pathways, leading to tumorigenesis. We discuss the roles of another two proteins potentially associated with NF2-deficiency as well as Merlin: Yes-associated protein 1 (YAP), which may promote tumor growth, and Raf kinase inhibitory protein (RKIP), which appears to suppress tumor development. Additionally, this review discusses the efficacy of various treatments, such as molecular therapies that target specific pathways or inhibit neomorphic protein-protein interaction caused by NF2-deficiency. This overview not only expands on the fundamental understanding of NF2 pathophysiology but also explores the potential of novel therapeutic targets that affect the clinical approach to NF2 syndrome.

Expectation maximization (EM) algorithm is a powerful mathematical tool for estimating statistical parameter when data sample contains hidden part and observed part. EM is applied to learn finite mixture model in which the whole distribution of observed variable is average sum of partial distributions. Coverage ratio of every partial distribution is specified by the probability of hidden variable. An application of mixture model is soft clustering in which cluster is modeled by hidden variable whereas each data point can be assigned to more than one cluster and degree of such assignment is represented by the probability of hidden variable. However, such probability in traditional mixture model is simplified as a parameter, which can cause loss of valuable information. Therefore, in this research I propose a so-called conditional mixture model (CMM) in which the probability of hidden variable is modeled as a full probabilistic density function (PDF) that owns individual parameter. CMM aims to extend mixture model. I also propose an application of CMM which is called adaptive regressive model (ARM). Traditional regression model is effective when data sample is scattered equally. If data points are grouped into clusters, regression model tries to learn a unified regression function which goes through all data points. Obviously, such unified function is not effective to evaluate response variable based on grouped data points. The concept “adaptive” of ARM means that ARM solves the ineffectiveness problem by selecting the best cluster of data points firstly and then evaluating response variable within such best cluster. In order words, ARM reduces estimation space of regression model so as to gain high accuracy in calculation.

The first diastereoselective synthesis of (–)-1-epi-lentiginosine stars from a common chiral trans-epoxyamide derived from 2-pyridincarbaldehyde is reported. This methodology involves a sequential oxirane ring opening and intramolecular 5-exo-tet cyclization of tosylate tras-epoxyalcohol to afford a diastereomeric mixture of indolizinium salts in a one-pot fashion, followed by regio- and diastereospecific pyridinium ring reduction.

The role of foods is shifting from focusing on the provision of energy and basic nutrients to also include bioactive compounds that prevent the development of chronic age-related diseases. Mi-croalgae offer a source of nutritional compounds with important health effects, and have the po-tential for production of health-promoting products, without increasing agricultural land use and negatively impacting the environment. Here we investigate the health effects of microalgal ex-tracts with high levels of the colourless carotenoid phytoene. Phytoene is widely available from dietary sources and can be detected across different tissues in the human body. However, it is usually regarded as a precursor for the synthesis of other carotenoids, rather than a bioactive molecule. We utilised the model organism C. elegans to show that phytoene-rich extracts from Chlorella sorokiniana and Dunaliella bardawil have anti-ageing properties. The extracts protect against oxidative damage and amyloid-β42 proteotoxicity (a major pathology of Alzheimer's disease), and extends lifespan. We show that pure phytoene also has these anti-ageing effects, suggesting that phytoene is a bioactive molecule with positive effects on ageing and longevity.

Background: Increase of collagen I (COL I)/COL III ratio enhances vessel wall stiffness and renders vessels less resistant to blood flow and pressure changes. We hypothesized that COL I/COL III ratio is increased in the brain arteriovenous malformations (bAVMs), which is associated with bAVM hemorrhage. Method: Surgically resected human bAVM samples and mouse bAVMs induced in three transgenic mouse lines with activin receptor-like kinase 1 or endoglin deletion in the endothelial cells or in the brain focally. Colony-stimulating factor receptor inhibitor was used to transiently deplete microglia. COL I and COL III levels, hemorrhage, and gene expression in bAVMs were analyzed. Results: The COL I and COL III levels and the COL I/COL III ratio were higher on human and mouse bAVMs than controls, which was associated with bAVM hemorrhage. Col I and Col III mRNAs were also increased in mouse bAVMs. The degree of microhemorrhage in mouse bAVMs was positively correlated with Col I/Col III ratios. Transient depletion of microglia reduced Col I/Col III ratio and microhemorrhage in mouse bAVMs. Conclusion: COL I/COL III ratio are increased in bAVM vessels, which is associated with bAVM hemorrhage. Depletion of microglia reduces Col I/Col III ratio and hemorrhage in mice bAVMs.

Neuronal cell fate is predominantly controlled by the effects of growth factors, such as neurotrophins, and the activation of a variety of signaling pathways acting through neurotrophin receptors, namely Trk and p75 (p75NTR). Despite their beneficial effects on brain function, their therapeutic use is compromised, due to their polypeptidic nature and blood–brain-barrier impermeability. To overcome these limitations, our previous studies have proven that DHEA-derived synthetic analogs can act like neurotrophins, lacking endocrine side effects. The present study focuses on the biological characterization of a newly synthesized analog, ENT-A044, and its role on inducing cell specific functions of p75NTR. We show that ENT-A044 can induce cell death and phosphorylation of JNK protein by activating p75NTR. Additionally, ENT-A044 can induce the phosphorylation of TrkB receptor, indicating that our molecule can activate both neurotrophin receptors, leading towards the protection of neuronal populations that express both receptors. Furthermore, the present study demonstrates for the first time the expression of p75NTR in human induced Pluripotent Stem Cells - derived Neural Progenitor Cells (hiPSCs - derived NPCs) and receptor-dependent cell death induced by ENT-A044 treatment. In conclusion, ENT-A044 could be proven a lead molecule for the development of novel pharmacological agents, aiming on new therapeutic approaches and research tools, by controlling p75NTR actions.

The lipid composition of biomembranes influence the properties of the lipid bilayer as well as that of the proteins. In this study, the lipidome and the lipid/protein ratio of membranes from High FiveTM insect cells overexpressing mouse P-glycoprotein was characterized. This provides a better understanding of the lipid environment in which P-glycoprotein is embedded, and thus of its functional and structural properties. The relative abundance of the distinct phospholipid classes and their acyl chain composition was characterized. A mass ratio of 0.57 +/- 0.11 phospholipids to protein was obtained. Phosphatidylethanolamines are the most abundant phospholipids, followed by phosphatidylcholines. Membranes are also enriched in negatively charged lipids (phosphatidylserines, phosphatidylinositols and phosphatidylglycerols), and contain small amounts of sphingomyelins, ceramides and monoglycosilatedceramides. The most abundant acyl chains are monounsaturated, with significant amounts of saturated chains. The characterization of the phospholipids by HPLC-MS allowed identification of the combination of acyl chains, with palmitoyl-oleoyl being the most representative for all major phospholipid classes except for phosphatidylserines, which are mostly saturated. A mixture of POPE:POPC:POPS in the ratio 45:35:20 is proposed for the preparation of simple representative model membranes. The adequacy of the model membranes was further evaluated by characterizing their surface potential and fluidity.

Astragalus membranaceus (AM) and Panax ginseng (PG) are two herbal products with a long history of clinical usage in traditional Chinese medicine (TCM), used in treating a variety of diseases especially in stimulating or inhibiting the immune system. To elucidate the immunity effect of these two traditional Chinese medicine on animal model, four pharmacodynamic indexes (spleen index, thymus index, splenic lymphocyte proliferation and cytotoxic activity of natural killer (NK) cells) were observed on mice. Furthermore, metabolic profiles of plasma were also analyzed by ultra-performance liquid chromatography quadrupole-time-of-flight mass spectrometry (UPLC-Q/TOF-MS, LC-MS) method. All mice were intragastric administrated at three doses (low dose, moderate dose and high dose) once daily for 30 days. Principal components analysis (PCA) and orthogonal projection to latent structure discriminant analysis (OPLS-DA) were performed on LC-MS spectra of plasma, showing that all administration groups developed the disturbance of internal milieu, compared to the blank control (BC) group. Besides, correlation analysis was conducted between pharmacodynamic index and metabolic index. It indicated that uracil, lysoPC(18:3(6Z,9Z,12Z)), sphinganine, LPA(0:0/16:0), UDP-glucuronate, PC(14:0/18:0) were five main endogenous substances, much closely related to four immunological indexes. Glycerophospholipid metabolism was found in both AM and PG groups. Pyrimidine metabolism and sphingolipid metabolism were closely regulated in AM groups. Energy metabolism (starch and sucrose metabolism, Pentose and glucuronate interconversions, together with glycerolipid metabolism) and glycerolipid metabolism were found in PG groups. These findings could contribute to the understanding of mice plasmatic metabolic profiling after long-term administration. Comparative immune-related metabolomic analysis of AM and PG was obtained on the base of pathway analysis of immune-related biomarkers. PG groups trended to have effect on cytotoxic activity of NK cells. AM groups trended to effect thymus index. Our work provides a detailed interpretation of immunological characteristics in different traditional Chinese medicine on metabonomic level.

We monitored the water quality and hydrological conditions of a horizontal subsurface constructed wetland (HSSF-CW) in Beijing, China, for 2 years. We simulated the area rate constant and the temperature coefficient with the first-order kinetic model. We examined the relationships between the nitrogen (N) removal rate, N load, seasonal variations in the N removal rate, and environmental factors, such as the area rate constant, temperature, and dissolved oxygen (DO). The effluent ammonia (NH₄⁺-N) and nitrate (NO₃⁻-N) concentrations were significantly lower than the influent concentrations (p<0.01, n=38). The NO₃⁻-N load was significantly correlated with the removal rate (R²=0.9566, p<0.01), but the NH^₄+-N load was not correlated with the removal rate (R²=0.0187, p>0.01). The area rate constants of NO₃⁻-N and NH₄⁺-N at 20 °C were 27.01±26.49 and 16.63±10.58 m∙yr⁻¹, respectively. The temperature coefficients for NO₃⁻-N and NH₄⁺-N were estimated at 1.0042 and 0.9604, respectively. The area rate constants for NO₃⁻-N and NH₄⁺-N were not correlated with temperature (p>0.01). The NO₃⁻-N area rate constant was correlated with the corresponding load (R²=0.9625, p<0.01). The NH₄⁺-N area rate was correlated with DO (R²=0.6922, p<0.01), suggesting that the factors that influenced the N removal rate in this wetland met Liebig's law of the minimum.

Clematis Florida (CF) is a folk medicinal herb in the southeast of China, which is traditionally used for treating osteoarticular diseases. However, the mechanism of action remains unclear. The present study used network pharmacology and experimental validation to explore the mechanism of CF in the treatment of rheumatoid arthritis (RA). Liquid chromatography-mass spectrometry (LC-MS/MS) identified 50 main compounds of CF, then the targets of them were obtained from TCMSP, ETCM, ITCM and Swiss TargetPrediction databases. RA disease related targets were obtained from DisGenet, OMIM and GeneCards databases. 99 overlapped targets were obtained using Venn diagram. The protein-protein interaction network (PPI)、the compound-target network (CT) and the compound-potential target genes-signaling pathways network (CPS) were built and analyzed. The results showed that the core compounds were screened as oleanolic acid, oleic acid, ferulic acid, caffeic acid, and syringic acid. And the core therapeutic targets were identified as PTGS2 (COX-2), MAPK1, NF-κB1, TNF, RELA by network pharmacology analysis, which belong to the MAPK signaling pathway and NF-κB signaling pathway. The animal experiments indicated that topical application of CF showed significant anti-inflammatory activity in mice model of xylene-induced ear edema and strong analgesic effect on acetic acid-induced withing. Furthermore, in the rat model of adjuvant arthritis (AA), topical administration of CF could alleviate toe swelling and ameliorate joint damage. The elevation of serum content of IL-6, COX-2, TNF-α, IL-1β, and RF caused by adjuvant arthritis were reduced by CF treatment. Western blotting tests showed that CF may exert regulation on the ERK and NF-κB pathway. The results provided a new perspective for the topical application of CF on RA.

Aquaculture is expected to play a vital role in solving the challenge of sustainably providing the growing world population with healthy and nutritious food. Pathogen outbreaks are a major risk for the sector, so early detection and a timely response are crucial. This can be enabled by monitoring of pathogen levels in aquaculture facilities. This paper describes a photonic biosensing platform based on silicon nitride waveguide technology with integrated active components, which could be used for such applications. Compared to the state of the art, the current system presents improvements in terms of miniaturization of the Photonic Integrated Circuit (PIC), and the development of wafer level processes for hybrid integration of active components and for material-selective chemical and biological surface modification. Furthermore, scalable processes for integrating the PIC in a microfluidic cartridge have been developed, as well as a prototype desktop readout instrument. Three bacterial aquaculture pathogens (Aeromonas salmonicida, Vagococcus salmoninarum, and Yersinia ruckeri) were selected for assay development. DNA biomarkers were identified, corresponding primer-probe sets designed, and qPCR assays developed. The biomarker for Aeromonas was also detected using the hybrid PIC platform. This is the first successful demonstration of biosensing on the hybrid PIC platform.

Alterations in the expression of glutamate/aspartate transporter (GLAST) have been associated with several neuropathological conditions including Alzheimer’s disease and epilepsy. However, the mechanisms by which GLAST expression is altered are poorly understood. Here we used a combination of pharmacological and genetic approaches coupled with quantitative PCR and Western blot to investigate the mechanism of the regulation of GLAST expression by a Ca2+/calmodulin-activated phosphatase calcineurin (CaN). We show that treatment of cultured hippocampal mouse and fetal human astrocytes with a CaN inhibitor FK506 resulted in a dynamic modulation of GLAST protein expression, being downregulated after 24-48 h, but upregulated after 7 days of continuous FK506 (200 nM) treatment. Protein synthesis, as assessed by puromycin incorporation in neo-synthesized polypeptides, was inhibited already after 1 h of FK506 treatment, while the use of a proteasome inhibitor MG132 (1 μM) shows that GLAST protein degradation was only suppressed after 7 days of FK506 treatment. In astrocytes with constitutive genetic ablation of CaN both protein synthesis and degradation were significantly inhibited. Taken together, our data suggest that, in cultured astrocytes, CaN controls GLAST expression at a posttranscriptional level through regulation of GLAST protein synthesis and degradation.

Human milk (HM) feedings are associated with reduced risks of neurodevelopmental and neurocognitive delays and systemic inflammatory diseases in infants born prematurely and/or at a low birth weight. Utilizing a neonatal piglet model, HM feedings were compared to bovine milk-derived infant formula (IF)-feedings with the aim of understanding the underlying mechanisms involved in reducing these risks. Six male piglets at postnatal-day (PD)2 were randomized into two feeding groups: HM-fed (n = 3) or IF-fed (n = 3) for 28 days. At 3- and 4-weeks-old, piglet memory and learning performance were assessed using novel object recognition (NOR). At PD30 piglets were euthanized, and whole brains were excised, weighed, and preserved for further analyses, and brain microglial morphology, and systemic inflammatory cytokines were quantified. During NOR, HM-fed piglets had significantly more non-novel revisits at both 3- and 4-weeks-old compared to IF-fed piglets. Microglia of HM-fed piglets had longer processes, more branch points, more endpoints, and a larger territorial volume compared to IF-fed piglets at PD30. In a neonatal piglet model, HM-feedings may improve cognition and reduce brain inflammatory response compared to IF-feedings.

Natural products contribute substantially to anticancer therapy; the plant kingdom provides an important source of molecules. Conofolidine is a novel Aspidosperma-Aspidosperma bisindole alkaloid isolated from the Malayan plant Tabernaemontana corymbosa. Herein, we report conofolidine’s anticancer activity together with that of three other bisindoles - conophylline, leucophyllidine and bipleiophylline against human-derived carcinoma cell lines. Remarkably, conofolidine was able to induce apoptosis (as observed in MDA-MB-468 breast cancer cells) or senescence (as detected in HT-29 colorectal carcinoma cells). Annexin V-FITC/PI, caspase activation and PARP cleavage confirmed the former while positive β-gal staining corroborated the latter. Evident cell cycle perturbations were observed comprising S-phase depletion, accompanied by downregulated CDK2, and cyclins (A2, D1) with p21 upregulation. Confocal imaging of HCT-116 cells revealed induction of aberrant mitotic phenotypes - multi-nucleation, membrane blebbing and DNA-fragmentation. The DNA integrity assessment of HCT-116 and MDA-MB-468 showed irreparable damage identified by increased fluorescent γ-H2AX during the G1 cell cycle phase. Furthermore, γ-H2AX foci were visually validated in HCT-116 and MDA-MB-468 cells using confocal microscopy. Conofolidine increased oxidative stress, preceding apoptosis- and senescence-induction in most carcinoma cell lines as seen by enhanced ROS levels accompanied by NQO1 expression. Collectively, we present conofolidine as a potential anticancer candidate capable of inducing heterogeneous modes of cancer cell death in vitro, encouraging further preclinical evaluation of this natural product.