There are several well-known methods for determining enzyme catalytic activity, including spectral techniques and electrochemical approaches. However, at present, there is no definitive solution to the challenges associated with the fluorescent approach in, for instance, systems of reverse micelles, non-aqueous media, and model biomembranes. We propose the use of the fluorescent resonant energy transfer (FRET) technique, which can enhance the selectivity of fluorescent detection of enzyme activity by shifting the maximum emission wavelength to the longer-wavelength range and reducion the influence of medium components. As fluorescence donors, we have used derivatives of 4-methylumbelliferone (MUmb) and 7-amino-4-methylcoumarin (AMC), which also serve as substrates for hydrolases such as chymotrypsin, phosphatase, and asparaginase. During the catalytic depletion of substrates, an accumulation of a highly fluorescent product is observed. This product can be specifically detected using the fluorescent marker rhodamine 6G (R6G), which emits light in the red region of the spectrum (550–600 nm) with high quantum yield. A significant FRET effect is observed when forming AOT reverse micelles. This is due to the proximity of fluorophores within the hydrophobic core of the micelle, which is shorter than in a buffer solution. This approach have practical implications for visualizing intracellular processes. The FRET technique can be used to determine intracellular enzymatic activity by detection with confocal laser scanning microcopy (CLSM), as demonstrated with L-asparaginase, a clinically important anti-leukemia medication. The approach suggested will allow researchers to study enzyme activity within cells. This has the potential to revolutionize medicine by improving drug development and shedding light on previously unknown aspects of cellular metabolism.

As a precious natural resource, forests are being destroyed. In previous studies, there is a lack of interactive assessment of its distribution that comprehensively considers multiple external disturbances. This paper takes the Barcelona Metropolitan Region as an example. Based on remote sensing, it analyzes the development process of the forest from 2006 to 2018 through multiple landscape indicators, and OLS models were established to analyze variables that have direct and indirect effects on forest distribution. In addition, the ecological structure of the forest was analyzed based on NDVI. It was found that the forest area is the largest but has been decreasing, becoming more complex in distribution structure. Much of the forest was converted to agricultural land and grassland. The green quality of forests was increasing, and the broad-leaved forest, the second largest area, contributes the most. NDVI is the most important positively correlated variable, and daytime surface temperature is an important inverse factor related to NDVI. In addition, NDBI is also a negative condition that inhibits forest development. In conclusion: The BMR forest area is decreasing and becoming more fragmented. NDVI and daytime LST are the two most significant factors. Climate warming may lead to worse forest development.

Filamentous manganese (Mn) oxide particles, which occur in the suboxic zone of stratified waterbodies, are important drivers of diverse elemental cycles. Although these particles are considered to be bacteriogenic, the environmental factor responsible for their formation has not been identified. Based on this study of laboratory cultures of a model Mn(II)-oxidizing bacterium, the supply of algal extracellular polymeric substances (EPS) was shown to stimulate Mn(II) oxidation and thus the production of filamentous Mn oxide particles. This observation was consistent with results obtained for naturally occurring particles collected from a near-bottom layer (depth of ~90 m) in the northern basin of Lake Biwa, Japan, that is, most Mn particles resembling delta-MnO2 were associated with an EPS-like gelatinous matrix, which contained dead algal cells and was lectin-stainable. In the lake water column, EPS produced by photosynthesis sank to the bottom layer. The analysis of the quality of water samples, which have been collected from the study site for 18 years, reveals that the annual average total phytoplankton biovolume in the surface layer correlates with the density of filamentous Mn particles in the near-bottom layer. Among different phytoplankton species, green algae appeared to be the key species. The results of this study suggest that algal EPS production induces the formation of filamentous Mn oxide particles in the near-bottom layer of the northern basin of Lake Biwa.

Hu7691 represents a novel Pan-Akt kinase inhibitor, demonstrating excellent selectivity towards non-AGC kinase families and pronounced inhibitory effects on the proliferation of multiple tumor cell lines. However, there is currently a notable absence of in vivo toxicological research evidence concerning Hu7691. This study represents the first investigation into the 14-day repeated dose toxicity of Hu7691 in male and female Sprague-Dawley (SD) rats. Male rats were administered daily doses of 12.5, 50, 100, and 150 mg/kg, while female rats received doses of 12.5, 25, 50, and 75 mg/kg for 14 consecutive days. Hematological assessments, organ weights, and histopathological examinations revealed corresponding alterations, suggesting potential target organs for toxicity including the spleen, thymus, and gastrointestinal tract. It is worth noting that the test substance may also impact the liver, kidneys, heart, and ovaries. The No Observed Effect Level (NOAEL) was determined to be no greater than 12.5 mg/kg. Based on the observed gender-related toxicity differences in preliminary trials, it is recommended that the high dose reference dose for male animals in formal experiments should not be less than 100 mg/kg, while for female animals, it should be less than 50 mg/kg.

The principal aim of this descriptive-survey investigation is to ascertain the factors influencing individuals' choice to purchase organic commodities in Tehran. The statistical populace for this examination comprised all patrons of food retail establishments in Tehran, with the sample size determined using the Cochran formula for an unknown community size, involving the distribution of 30 questionnaires to customers (n=439). Data collection was carried out through a random sampling technique. The survey instrument consisted of a questionnaire with two sections consisting of general queries (7 questions) and specific inquiries (23 items) categorized into four dimensions (product, price, place, and promotion) for the clientele. The questionnaire's validity was confirmed through face and content validation, while its reliability was assessed utilizing Cronbach’s alpha. Data analysis was conducted using SPSS25 software, encompassing both descriptive and inferential statistical analyses. The results revealed a positive and significant correlation between customers' inclination to consume organic goods and the characteristics of the product, price, and promotion. However, no association was found between the propensity to consume organic products and location characteristics. Concerning contextual variables, a solely positive and significant correlation was identified between the willingness to purchase organic items and consumer income levels. No significant relationships were detected between other contextual variables and organic product consumption. A notable contrast was observed between respondents' gender and their readiness to buy organic products, while no significant variances were noted regarding age, income, occupation, and education in relation to the propensity to purchase organic commodities.

The authors undertook pilot studies to assess the accuracy of the reverse engineering process of worn nonstandard spur gears (non-standardized modulus value, unusual profile/pressure angle, high or low teeth), using conventional techniques and measuring instruments. Eight gears were tested, the module of which ranges from 1.020 to 4.98 mm and the number of teeth from 13 to 42. The key parameter, the basic pitch, was selected to estimate the accuracy of the process. The goal is to determine the value of the profile angle. Eleven models were proposed to estimate the nominal tolerance field, using various types of random data distribution. The tested gears were made in IT grade: 6, 7, 8 and 9 according to DIN 3961. Vernier disc micrometers with various measurement ranges were used for research. It has been shown that the nominal module does not have to be treated as a random variable in the population. EIG (Equation of Identity) was developed, allowing conversion of any gear with specific values of geometric parameters into an identical gear with alternative values of these parameters. The directions and degrees of shifts of the estimated tolerance fields relative to the nominal field were determined. The most effective estimating model was selected in the context of the percentage filling of the nominal tolerance field, taking into account the symmetric Student-Fisher distribution with a confidence level of 60%. Further directions of the research activities were described.

With the fintech industry growing at an unprecedented rate, it is critical to protect cybersecurity and ensure data privacy. The research presented here offers a thorough examination of the challenges faced by financial technology companies, highlighting the growing risks posed by malware, phishing, and network vulnerabilities. As essential components of a proactive defense plan, the report promotes strong cybersecurity measures like frequent security assessments, encryption, and stringent access controls. The findings highlight how important it is for fintech companies to give cybersecurity equal importance with open and honest data privacy policies in order to win over customers. In order to protect the industry from cybersecurity risks regulatory compliance, intrusion detection systems, and collaborative information sharing are considered essential components. The article advises businesses to include cybersecurity and data privacy into their core business operations and customer relations, highlighting the critical role these factors play in sustaining success in the rapidly evolving fintech industry.

(1) Introduction: The COVID-19 pandemic presented unique challenges for patients and healthcare providers, especially for those working with obesity and related health problems. E-health has emerged as a crucial tool for the follow-up of users undergoing bariatric surgery during this period, allowing remote monitoring of users' health status and providing access to virtual consultation with health professionals. This study aims to analyze the impact of the use of telemedicine during the COVID-19 pandemic on the results of bariatric surgery and user satisfac-tion with this follow-up. (2) Method: Observational study with retrospective data collection. The variables were divided into several groups: health data, associated comorbidities, quality of life, quality of sleep and satisfaction with telemedicine monitoring. (3) Results: Surgery significantly affected weight loss, in general more than 75% loss of excess weight. Comorbidities, like the qual-ity of life, were reversed over time, with 50% of subjects maintaining excellent levels. Although most users were satisfied with the monitoring, the variables had no relationship. (4) Conclusions: The follow-up assured by telemedicine did not alter the results of bariatric surgery, which may allow us to infer that it may be an option to consider for regular monitoring of the post-bariatric surgery process.

Urban and agricultural runoffs can transport contaminants and pesticides into freshwater ecosystems, particularly in the developing tropics. For instance, organophosphate and pyrethroids pesticides like glyphosate, malathion, and permethrin have been found in tropical streams. The uncontrolled application of these pesticides has become a growing concern due to their adverse effects on various non-targeted organisms. Unfortunately, most studies have focused on a few selected model species, ignoring the effects on other nontarget organisms, which may play an important role in tropical lotic ecosystems. In addition, the biological characteristics of aquatic crustaceans, including their morphology, physiology, and behavior, make them susceptible to toxic chemicals. For this reason, this study used the widely distributed freshwater shrimp Xiphocaris elongata as a model organism to determine the acute toxicity of permethrin, malathion, and glyphosate. Our results show that the proportion of mortality of X. elongata in each concentration group became progressively higher as the concentration of exposure increased. We also found that the synthetic pyrethroid permethrin is the most toxic pesticide tested, followed by organophosphate malathion and glyphosate. Experiments with this freshwater shrimp showed a good control performance and reproducibility for the tested pesticides. This study demonstrated that X. elongata is a suitable test organism that can be a representative bioindicator of pesticide toxicity in tropical streams.

Heme is located in the active site of proteins and has diverse and important biological functions, such as electron transfer and oxygen transport and/or storage. The distortion of heme porphyrin is considered an important factor for the diverse functions of heme because it correlates with the physical properties of heme, such as oxygen affinity and redox potential. Therefore, clarification of the relationship between heme distortion and the protein environment is crucial in protein science. Here, we analyzed the fluctuation in heme distortion in the protein environment for hemoglobin and myoglobin using molecular dynamics (MD) simulations and quantum mechanical (QM) calculations. We also investigated the protein structures of hemoglobin and myoglobin stored in Protein Data Bank and found that heme is distorted along the doming mode, which correlates with its oxygen affinity, more prominently in the protein environment than in the isolated state, and the magnitude of distortion is different between hemoglobin and myoglobin. This tendency was also observed in the results of MD simulations and QM calculations. These results suggest that heme distortion is affected by its protein environment and fluctuates around its fitted conformation, leading to physical properties that are appropriate for protein functions.

(1) Background: The diagnosis of lumbosacral radiculopathy involves anamnesis, assessment of sensitivity and strength, diagnostic imaging—usually magnetic resonance imaging (MRI)—and electrodiagnostic testing (EDX), typically electromyography (EMG) and electroneurography (ENG). MRI evaluates the structures supporting the spinal cord, while EDX evaluates root functionality. The present study aimed to analyze the concordance of MRI and EDX findings in patients with clinically suspected radiculopathy. Additionally, we investigated the comparison between these two reference tests and various clinical variables and questionnaires. (2) Methods: We designed a prospective epidemiological study of consecutive cases with an observational, descriptive, cross-sectional, and double-blind nature following the STROBE guidelines, encompassing 142 patients with clinical suspicion of lumbosacral radiculopathy. (3) Results: Of the sample, 58.5% tested positive for radiculopathy using EDX as the reference test, while 45.8% tested positive using MRI. The comparison between MRI and EDX in the diagnosis of radiculopathy in patients with clinical suspicion was not significant; the overall agreement was 40.8%. Only the years with symptoms were comparatively significant between the positive and negative radiculopathy groups as determined by EDX. (4) Conclusion: The comparison between lumbar radiculopathy diagnoses in patients with clinically suspected pathology using MRI and EDX as diagnostic modalities did not yield statistically significant findings. MRI and EDX are complementary tests assessing different aspects in patients with suspected radiculopathy; degeneration of the structures supporting the spinal cord does not necessarily imply root dysfunction.

The use of omega-3 fatty acids (omega-3 FA) in the treatment of atopic dermatitis (AD) is an area of ongoing research. Some studies suggest that dietary supplementation with omega-3 FA can help manage symptoms of AD by reducing lesion severity, skin inflammation, dryness and itching, while other show no significant beneficial effect. The aim of this study was to evaluate the effect of omega-3 FA form fish oil in combination with GLA form blackcurrant seed oil in children with AD. This is a longitudinal, prospective, randomized, triple blind, placebo-controlled parallel clinical trial. The study was conducted during the 2-year period from autumn, winter, and spring avoiding the summer when AD usually improves. Children were randomized to receive the active study product (Mega Kid®) containing specific blend of omega-3 and omega-6 fatty acids or placebo. Primary outcomes were change in severity of AD measured using SCORing Atopic Dermatitis (SCORAD) patient oriented SCORAD (PO-SCORAD) and the difference in TCS use. Secondary outcomes were change in itch intensity, sleep quality and Family Dermatology Life Quality Index (FDLQI). Data were analyzed for 52 children (26 in the intervention group and 26 in the placebo group). In children receiving active product intention-to-treat analysis showed that after 4 months of treatment, there was a significant decrease in the SCORAD index (from median 42 to 25, p < 0.001) and use of topical corticosteroids (from median 30 to 10 mg/day, p < 0.001) but also significant improvement in itch, sleep quality and overall quality of life. Omega-3 fatty acids in combination with GLA and vitamin D has a great beneficial effect in treatment of atopic dermatitis in children. Therefore, we can conclude that supplementation with this specific combination could be considered a safe and effective intervention that can significantly reduce the severity of AD in pediatric patients.

Eotaxin-3 is a key chemokine with a relevant role in eosinophilic esophagitis, a rare chronic immune/antigen-mediated inflammatory disorder. Eotaxin-3 is a potent activator of eosinophil emergence and migration, which may lead to allergic airway inflammation. We investigated by bioinformatics tools the protein structure and the possible effects of the known variations reported in public databases. Following a procedure already established, we created a 3D model of the whole protein and modelled the structure of 105 protein variants due to known point mutations. The effects of the amino acid substitution at the level of impact on protein structure, stability, and possibly function, were detected by the bioinformatics procedure and described in detail. A web application was implemented to browse the results of the analysis and visualize the 3D models, with the opportunity of downloading the models and analyze by the own software. Among 105 amino acid substitutions investigated, the study evidenced in 44 cases at least one change in any of the investigated structural parameters. Other 6 variations are also relevant, although a structural effect is not detected by our analysis, because they substituted amino acids highly conserved, which suggests a possible function role. All these variations should be the object of particular attention, as they may induce loss of functionality in the protein.

Spatial and temporal variation of the free electron concentration in the ionosphere affects SAR interferograms, in particular at low radar frequencies. In this work the identification, estimation and compensation of ionospheric path delay phases in PALSAR-3 and NISAR-L interferograms is discussed. Both these L-band sensors acquire simultaneously SAR data in a main spectral band and in an additional, spectrally separated, narrower second band to support the mitigation of ionospheric path delays. The methods presented permit separating the dispersive and the non-dispersive phase terms based on the double-difference interferogram between the two available spectral bands and the differential interferogram of the main band. The applicability of the proposed methods is demonstrated using PALSAR-3-like data that was simulated based on PALSAR-2 SM1 mode data.

Objectives (Purpose) This study aims to evaluate the outcomes of the Subcrestally Placed Implant (SPI) technique in single molar cases, focusing on biological stability and aesthetics. It proposes a schematic model to elucidate the interplay between the biological stability of soft tissues and bone around the SPI and the morphological requisites that Implant Abutment Prostheses (IAP) must fulfill to effectively replace natural teeth. Materials and methods I examined 20 cases using the SPI technique with Internal Platform Switching (IPS) design implants for single molar replacements to assess their stability. Routine check-ups utilized plain panoramic X-rays to measure changes in crestal bone on the mesial and distal sides. Additionally, 10 cases with CBCT X-rays taken more than one year after the initial surgery underwent a novel 3-dimensional soft tissue analysis (3DSTA). Measurements included placement depths (PD), soft tissue thickness (STT) at central (cPD, cSTT) and peripheral areas (pPD, pSTT), the length of the Transitional Zone (TZ) on mesial, distal, facial, and lingual aspects, and crestal bone thickness (CBT) at buccal and lingual sites. Results Panoramic analyses showed minimal changes in crestal bone (mean changes of pPD were less than 0.1 mm) over an average period of 3.3 years. Average measurements were as follows: cPD was 1.7 mm, pPD was 2.7 mm, cSTT was 0.2 mm, pSTT was 0.6 mm, TZ length was 3.8 mm, buccal CBT was 3.0 mm, and lingual CBT was 3.7 mm. Conclusions CBCT analyses of the topographical relationships between soft tissue and crestal bone with IAP for SPIs demonstrated stable results over an average 3-year period. The consistency in the relationship between crestal bone and surrounding soft tissue can be ascribed to biological structural integrity. The study classified peri-implant soft tissues into subcrestal and supracrestal (transitional zone – TZ) segments, exploring their characteristics through dimensional measurements and assessing mechanical resistance. Further histological study is needed to identify specific features of each segment.

Spinocerebellar ataxia type 3 is a neurodegenerative disease caused by an abnormal expansion of CAG repeats in the disease gene ATXN3, leading to prolonged polyglutamine (polyQ) tracts in the respective protein ataxin-3. The polyQ-expanded protein forms polyQ-containing aggregates in several brain regions which leads to neuronal cell loss. Autophagy is thought to play a significant role in clearing these polyQ-containing protein aggregates. Therefore, the autophagy mechanism was investigated in SCA3 with focus on the autophagic protein p62/sequestosome-1. Human and mouse RNA sequencing data were analyzed to determine RNA expression level of autophagic genes. Additionally, autophagy was studied in the SCA3 304Q knock-in mouse model and through several cell culture experiments using HEK-293T cells transfected with ATXN3 of differ-ent polyQ lengths. For cell culture experiments, autophagy was induced with rapamycin treat-ment, proteasomal degradation was blocked with MG132 and degradation of autophagic pro-teins was investigated using cycloheximide treatment. Here, we report an increased autophagy impairment with SCA3 disease progression seen in HEK-293T cells transfected with ATXN3 plasmid with expanded polyQ tracts, higher aged 304Q-knock-in mice, or human post-mortem brain material. Furthermore, co-localized aggregation of the autophagic protein p62 and the dis-ease protein ATXN3 was observed in the course of SCA3 disease. Therefore, we suggest a signifi-cant role for p62 in aggregate formation seen in the neurodegenerative disease SCA3.

Ovarian cysts are linked to hormone imbalances and altered gene expressions, but the connection between cysts and ion channel expression is understudied. This study explored the role of TWIK-related acid-sensitive K+ (TASK) channels in bovine ovarian cyst formation. The ovarian follicles were split into small (5 to 10 mm in diameter) and large (> 25 mm in diameter) groups. Among the measured K+, Na+, and Cl- concentrations in follicular fluid (FF) obtained from small-sized follicles (SF) and large-sized follicles (LF), the K+ concentration was significantly lower in LFFF. Quantitative PCR, western blot, and immunocytochemistry data revealed that TASK-3 expression levels significantly decreased by approximately 50% in both LF and granulosa cells obtained from LF (LFGCs) compared to the corresponding controls. The TASK-3 protein was localized to the plasma membrane of GCs. The diameter of LFGCs was larger than that of SFGC. The cell swelling response to exposure to a hypotonic solution (200 mOsm/L) was highly reduced in TASK-3-overexpressing cells compared to vector-transfected cells. TASK-3-knockdown cells showed arrested growth. Senescence markers were detected in LFGCs and TASK-3-knockdown cells. These findings suggest that reduced TASK-3 expression in LF is associated with the inhibition of GC growth, leading to senescence and cyst formation.

Background: We aimed to determine the splenic stiffness (SS) values in healthy individuals as measured by 3 Tesla magnetic resonance elastography (3T MRE) and to investigate the possible effects of parameters such as age, sex, spleen volume, diameter, and parenchyma thickness on SS.Methods: A total of 54 healthy volunteers were included in this cross-sectional study. Participants' age and sex information were recorded, in addition to spleen craniocaudal and anteroposterior diameter, cortical thickness, spleen volume, and SS, which were measured using 3T magnetic resonance imaging and MRE. Results: Twenty-nine male and 25 female subjects with a mean age of 54.78±15.40 years were included in the study. Mean cradiocaudal diameter was 10.46±1.16 cm, anteroposterior diameter was 9.88±1.29 cm, parenchyma thickness was 4.08±0.67 cm, SS was 3721.94±709.69 Pascal (Pa), and median spleen volume was 292.54 (239.40-311.00) cm³. A significant positive correlation was observed between age and SS (r=0.779, p<0.001). The SS values were not associated with sex, craniocaudal diameter, anteroposterior diameter, parenchymal thickness, or volume.Conclusion:Age should be considered when using SS in the diagnosis and staging of relevant diseases such as portal hypertension and esophageal varices. Our results should be confirmed by future studies using 3T MRE in larger populations.

Background: We aimed to determine the splenic stiffness (SS) values in healthy individuals as measured by 3 Tesla magnetic resonance elastography (3T MRE) and to investigate the possible effects of parameters such as age, sex, spleen volume, diameter, and parenchyma thickness on SS. Methods: A total of 54 healthy volunteers were included in this cross-sectional study. Participants' age and sex information were recorded, in addition to spleen craniocaudal and anteroposterior diameter, cortical thickness, spleen volume, and SS, which were measured using 3T magnetic resonance imaging and MRE. Results: Twenty-nine male and 25 female subjects with a mean age of 54.78±15.40 years were included in the study. Mean cradiocaudal diameter was 10.46±1.16 cm, anteroposterior diameter was 9.88±1.29 cm, parenchyma thickness was 4.08±0.67 cm, SS was 3721.94±709.69 Pascal (Pa), and median spleen volume was 292.54 (239.40-311.00) cm3. A significant positive correlation was observed between age and SS (r=0.779, p<0.001). The SS values were not associated with sex, craniocaudal diameter, anteroposterior diameter, parenchymal thickness, or volume Conclusion:Age should be considered when using SS in the diagnosis and staging of relevant diseases such as portal hypertension and esophageal varices. Our results should be confirmed by future studies using 3T MRE in larger populations.

The aim of the study is to develop a population pharmacokinetic (PopPK) model and to investigate the influence of CYP3A5/CYP3A4 and ABCB1 single nucleotide polymorphisms (SNPs) on the Tacrolimus PK parameters after LCP-Tac formulation in stable adult renal transplant patients. The model was developed using NONMEM v7.5, from full PK profiles from a clinical study (n=30) and trough concentrations (C0) from patient follow-up (n=68). The PK profile of the LCP-Tac formulation was best described by a two-compartment model with linear elimination, parameterised in elimination (CL/F) and distributional (CLD/F) clearances and central compartment (Vc/F) and peripheral compartment (Vp/F) distribution volumes. A time lagged first order absorption process was characterized using transit compartment models. According to the structural part of the base model, the LCP-Tac showed an absorption profile characterized by 2 transit compartments and a mean transit time of 3.02 hours. Inter-individual variability was associated with CL/F, Vc/F and Vp/F. Adding inter-occasion variability (IOV) on CL/F caused a statistically significant reduction in the model minimum objective function MOFV (p<0.001). Genetic polymorphism of CYP3A5 and cluster of CYP3A4/A5 SNPs statistically significantly influenced Tac CL/F. In conclusion a PopPK model was successfully developed for LCP-Tac formulation in stable renal transplant patients. CYP3A4/A5 SNPs as a combined cluster including three different phenotypes (high, intermediate, and poor metabolizers) was the most powerful covariate to describe part of inter-individual variability associated with apparent elimination clearance. Incorporating this covariate in the initial dose calculation and during the therapeutic drug monitoring (TDM) would probably optimize Tac exposure attainments.

Cardiovascular diseases (CVD) remain the leading cause of death across the globe, hence, establishing strategies to counteract CVD are imperative to reduce mortality and the burden on health systems. Dietary modification is an effective primary prevention strategy against CVD. Research regarding dietary supplementation has become increasingly popular. This review focuses on the current in vivo, in vitro, and epidemiological studies associated with that of omega-3 polyunsaturated fatty acids (n-3 PUFA) and polar lipids (PLs) and how they play a role against CVD. Furthermore, this review focuses on the results of several major clinical trials examining n-3 PUFA regarding both primary and secondary prevention of CVD. Notably, we place a lens on the REDUCE-IT and STRENGTH trials. Finally, supplementation of PLs has recently been suggested as a potential alternative avenue for the reduction of CVD incidence versus neutral forms of n-3 PUFA. However, the clinical evidence for this argument is currently rather limited. Therefore, we draw on the current literature to suggest future clinical trials for PL supplementation. We conclude that despite conflicting evidence, future human trials must be completed to confirm whether PL supplementation may be more effective than n-3 PUFA supplementation to reduce cardiovascular risk.

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 .

The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with a high rate of mortality in kidney transplant recipients (KTRs). The current vaccine strategy for KTRs seems to be unable to provide effective protection against coronavirus disease 2019 (COVID-19) [2] and the occurrence of severe COVID-19 in some vaccinated KTRs suggested a lack of immunity. We analized here the antibody response in a group of 32 kidney transplant recipients (KTR) followed at the Nephrology and Dialysis unit of the Hospital Pio XI of Desio, Italy, compared with a group of 23 healthy workers classified as Late responders (HCW-LR) (10 males age 27-62) and 13 females (age 46-64). We observed that the patients need additional vaccine boosters due to their immunocompromised status and therapy to protect them from infections related to viral variants, in accordance with the literature.

Open-source 3-D printing has played a pivotal role in revolutionizing the additive manufacturing (AM) landscape, by making distributed manufacturing economic, democratizing access, and fostering far more rapid innovation than antiquated proprietary systems. Unfortunately, some 3-D printing manufacturing companies began deviating from open-source principles and violating licenses for the detriment of the community. To determine if a pattern has emerged of companies patenting clearly open-source innovations, this study presents three case studies from the three primary regions of open-source 3-D printing development (EU, U.S. and China) as well as three aspects of 3-D printing technology (AM materials, an open-source 3-D printer, and core open-source 3-D printing concepts used in most 3-D printers). The results of this review have shown that non-inventing entities called patent parasites are patenting open-source inventions already well-established in the open source community and in the most egregious cases commercialized by one (or several) firms at the time of the patent filing. Patent parasites are able to patent open-source innovations by using a different language, vague patent titles and broad claims that encompass enormous swaths of widely diffused open-source innovation space. This practice poses a severe threat to innovation and several approaches to irradicate the threat are discussed.

Neuroblastoma is the most common tumour in children under 1 year old, accounting for approximately 50% of infant cancer cases. Although current treatments are relatively efficacious against this cancer, associated adverse effects could be detrimental to growth and development. In contrast, glioblastoma accounts for 52% of brain tumours and has an extremely poor prognosis. Current chemotherapeutics include temozolomide, which has numerous negative side-effects and a low-effective rate. Previous studies have shown the manipulation of autophagy to be a promising method for targeting cancers, including glioblastoma. We sought to determine the effects of autophagic alterations in combination with current chemotherapies in both neuroblastoma and glioblastoma. Supplementing cisplatin or temozolomide with autophagy activator rapamycin stabilized cancer cell mitochondria, despite having little effect on apoptosis or oxidative stress. Autophagy inhibition via 3-methyladenine or hydroxychloroquine alongside standard chemotherapies enhanced apoptosis and oxidative stress, with 3-methyladenine also disrupting mitochondrial health. Importantly, combining hydroxychloroquine with 0.5 µM cisplatin or 50 µg/mL temozolomide was as or more effective than 2 µM cisplatin or 100 µg/mL temozolomide alone. Analyzing these interesting results, a combined treatment of autophagy inhibitor with a standard chemotherapeutic agent could help to improve patient prognosis and reduce chemotherapy doses and their associated side-effects.

The co-occurrence of depression and obesity has become a significant public health concern worldwide. Recent studies have shown that metabolic dysfunction, which is commonly observed in obese individuals and characterized by inflammation, insulin resistance, leptin resistance, and hypertension, is a critical risk factor for depression. This dysfunction may induce structural and functional changes in the brain, ultimately contributing to depression's development. Given that obesity and depression mutually increase each other's risk of development by 50-60%, there is a need for effective interventions that address both conditions. The comorbidity of depression with obesity and metabolic dysregulation is thought to be related to chronic low-grade inflammation, characterized by increased circulating levels of pro-inflammatory cytokines, and C-reactive protein (CRP). As pharmacotherapy fails in at least 30-40% of cases to adequately treat major depressive disorder, a nutritional approach is emerging as a promising alternative. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are a promising dietary intervention that can reduce inflammatory biomarkers, particularly in patients with high levels of inflammation, including pregnant women with gestational diabetes, patients with type 2 diabetes mellitus, and overweight individuals with major depressive disorder. Further effort directed to implement these strategies in clinical practice could contribute to improved outcomes in patients with depression and comorbid obesity and/or metabolic dysregulation.

A new treatment option for cluster headache (CH) prevention is needed. Monoclonal antibodies (mABs) against calcitonin gene-related peptide (CGRP) ligands are used as a preventative treatment for migraine. Considering the CGRP’s role in the CH attack’s ignition and upkeep, fremanezumab and galcanezumab have been evaluated for CH preventative treatment. However, only high-dose (300 mg) galcanezumab was proven for episodic CH prevention. We herein report 3 cases of migraine and comorbid CH with previous failures of preventive treatments. The 2 cases were treated with fremanezumab and the one with non-high-dose galcanezumab. All 3 cases showed good results not only on migraine but also on CH attacks. Our report suggested the efficacy of CGRP-mABs for CH prevention. Our cases differed from the cases in the phase 3 trials of CGRP-mABs for CH prevention in the following 2 points. First, the patients had both migraine and comorbid CH. Second, the combined use of CGRP-mABs with preventative drugs for CH, such as verapamil and/or prednisolone, was performed. Future accumulation of real-world data may prove the efficacy of CGRP-mABs for CH prevention.

The addition of active seed for increasing the precipitation rate leads to the formation of fine Al(OH)3 particles that complicates separation of solid from the mother liquor. In this study, the enhanced precipitation of coarse Al(OH)3 from sodium aluminate solution using active agglomerated seed was investigated. Aluminum salt (Al2(SO4)3) were used for active agglomerated seed precipitation at the initial of the process. About 50% of precipitation rate was obtained when these agglomerates were used as a seed in the amount of 20 g L–1 at 25 °C within 10 h. The agglomerated active seed and precipitate samples were characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR). SEM images showed that agglomerates consist of flake-like particles that can be stick together by bayerite (β-Al(OH)3) acting as a binder. The precipitation temperature above 35 °C and the high concentration of free alkali (αk &gt; 3) lead to the agglomerates refinement that can be associated with the bayerite dissolution.

Enterococcus faecalis is a bacterium that can develop a multidrug resistance profile associated with the community as well as nosocomial-acquired infections. Among the treatment options for these infections are aminoglycosides combined with bacterial cell wall inhibitors such as beta-lactams, since E. faecalis is intrinsically resistant to aminoglycosides. One of its most representative resistance mechanisms is the expression of aminoglycoside-modifying enzymes, such as the aminoglycoside phosphotransferase type IIIa of E. faecalis (EfAPH(3')-IIIa). This enzyme acts by phosphorylating aminoglycosides in an ATP-dependent reaction, modifying the 3' position of hydroxyl groups of these antibiotics. Considering this scenario, 3,092 natural products obtained from the ZINC22 database were analyzed to select molecules with the highest affinity for the nucleotide-binding pocket of EfAPH(3')-IIIa, which could be potential aminoglycoside adjuvants. The molecules that showed the best-score results obtained from ensemble docking-based virtual screening were ZINC000000952700 (BS-1), ZINC000014793040 (BS-2) and ZINC000015498603 (BS-3). The most promising results were for BS-2, a flavone derivative, due to its improved stability profile in molecular dynamics simulation (average values of RMSD of 0.23 nm, and Rg of 1.94 nm), binding free energy calculations (average ΔG total of -35.3 nm), as well as better toxicological profile (lower probability of hepatotoxicity, carcinogenic, immunotoxicity, mutagenicity, and cytotoxicity effects), compared to BS-1 and BS-3. These results allow us to propose that a flavone derivative may act as an adjuvant to aminoglycosides in the treatment of E. faecalis infections, acting as an inhibitor in the nucleotide-binding pocket of EfAPH(3')-IIIa.

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.

Background: Brain oxidative lipid damage and inflammation are common in neurodegenerative diseases such as Alzheimer’s disease (AD). Paraoxonase-1 and 3 (PON1 and PON3) protein expression have been described in tissues with no PON1 and PON3 gene expression. In the present study, we aimed to examine differences in PON1 and PON3 protein expression in the brain of a mouse model of AD. Methods: We used peroxidase-based and fluorescence-based immunohistochemistry in 5 brain regions (olfactory bulb, forebrain, posterior midbrain, hindbrain and cerebellum) of transgenic (Tg2576) mice with the Swedish mutation (KM670/671NL) responsible for a familial form of AD and corresponding wild-type mice. Results: We found intense PON1 and PON3 positive staining in star-shaped cells surrounding Aβ plaques in all Tg2576 mouse brain regions studied. Although we could not co-localize PON1 and PON3 with astrocytes, brain star-shaped cells, we found some co-localization of PON3 with microglia. Conclusions: These results suggest that 1) PON1 and PON3 cross the blood-brain barrier in discoidal HDLs and are transferred to specific brain cell types, and 2) PON1 and PON3 play an important role in preventing oxidative stress and lipid peroxidation in particular cell types, likely astrocytes and microglia, in AD pathology, and potentially in other neurodegenerative diseases

Atlantic salmon (Salmo Salar) is one of the fish species that rich in omega-3 fatty acids. Consumption of omega-3 fatty acids can lower down the risk of cardiovascular disease and coronary heart disease. The extraction of omega-3 fish oil from Atlantic salmon by using hexane and isopropanol was conducted in this research. Response Surface Methodology (RSM) was used to study the impact of parameters which were temperature (50-90°C), centrifuge speed (1000-3000rpm) and solvent ratio of hexane to isopropanol (0.5-1.5) to the percentage of oil yield. The results obtained shows that 15.23%± 0.61 of oil yield from Atlantic salmon under an optimum condition of 70°C, 3000 rpm and solvent ratio of hexane to isopropanol of 1.5. The acid value, peroxide value and p-anisidine value of the fish oil obtained were 7.48 mg KOH/g, 1.94 meq/kg and 5.56 respectively which were all within the acceptable limit which stipulated by Global Organization for EPA and DHA (GOED) and Food and Agricultural Organization of the United Nations (FAO). The FTIR analysis proved the presence of alkane and carboxylic acid in the fish oil. Furthermore, GC-MS analysis showed that the fish oil contains higher monounsaturated fatty acids (MUFA) contents followed by polyunsaturated fatty acids (PUFA) and 4.5525% of total omega-3 fatty acids.

Interaction of an electromagnetic field with matter in a laser cavity without the assumption of a fixed direction of the transverse electric field, described by the two-level Maxwell-Bloch equations, is studied. By using a perturbative nonlinear analysis, performed near the laser threshold, we report on the derivation of the laser (3+1)D vectorial complex cubic-quintic complex Ginzburg-Landau equation. Furthermore, we study the modulational instability of the plane waves both theoretically using the linear stability analysis, and numerically, using direct simulations via the split-step Fourier method. The linear theory predicts instability for any amplitude of the primary waves. Our numerical simulations confirm the theoretical predictions of the linear theory as well as the threshold of the amplitude of perturbations. The system understudy shows a deep dependence on the laser cavity parameters, for which there appear wave patterns in accordance with the predictions from the gain spectrum.

Synthesis and characterization of anhydrous LiZn(IO₃)₃ powders prepared from an aqueous solution are reported. Morphological and compositional analyses were carried out by scanning electron microscopy and energy dispersive X-ray measurements. The synthesized powders exhibit a needle-like morphology after annealing at 400°C. A crystal structure for the synthesized compound has been proposed from powder X-ray diffraction and density-functional theory calculations. Rietveld refinements led to a monoclinic structure, which can be described with space group P21, number 4, and unit-cell parameters a = 21.874(9) Å, b = 5.171(2) Å, c = 5.433(2) Å, and beta = 120.93(4)º. Density-functional theory calculations supported the same crystal structure. Infrared spectra were also collected and the vibrations associated to the different modes discussed. The non-centrosymmetric space group determined for this new polymorph of LiZn(IO₃)₃, the characteristics of its infrared absorption spectrum, and the observed second harmonic generation suggest a promising infrared non-linear optical material.

Satellite altimeters have been used to monitor river and reservoir water levels, from which water storage estimates can be derived. Inland water altimetry can therefore play an important role in continental water resource management. Traditionally, satellite altimeters were designed to monitor homogeneous surfaces such as oceans or ice sheets, resulting in a poor performance over small inland water bodies due to the contribution from land contamination in the returned waveforms. The advent of synthetic aperture radar (SAR) altimetry (with its improved along-track spatial resolution) has enabled the measurement of inland water levels with a better accuracy and an increased spatial resolution. This paper presents three specialized algorithms or retrackers to retrieve water levels from SAR altimeter data over inland water bodies dedicated to minimizing land contamination from the waveforms. The performances of the proposed waveform portion selection method with three retrackers, namely, the threshold retracker, Offset Centre of Gravity (OCOG) retracker and 2-step physical-based retracker, are compared. Time series of water levels are retrieved for water bodies in the Ebro River basin (Spain). The results show good agreement with in situ measurements from the Ebro Reservoir (width is approximately 1.8 km) and Ribarroja Reservoir (width is approximately 400 m) with un-biased root-mean-square errors (RMSEs) of approximately 0.28 m and 0.16 m, respectively. The performances of all three retrackers are also compared with the European Space Agency’s ocean retracker in the Sentinel-3 Level-2 product.

The transforming growth factor-β (TGF-β), in which overexpression have been associated with various diseases, has become an attractive molecular target for the treatment of cancers. Three series of 3-substituted-4-(quinoxalin-6-yl) pyrazoles 14a–h, 15a–h, 16a–h, 22a, 22b, 22d, 23a, 23b, 23d, 24b, and 24d were synthesized and evaluated for their activin receptor-like kinase 5 (ALK5) and p38α mitogen activated protein (MAP) kinase inhibitory activity in an enzymatic assays. Among these compounds, the most active compound 16f inhibited ALK5 phosphorylation with an IC₅₀ value of 0.28 µM, with 98% inhibition at 10 µM. Compound 16f also had good selectivity index of >35 against p38α MAP kinase, with 9.0-fold more selective than clinical candidate, compound 3 (LY-2157299). Molecular docking study was performed to identify the mechanism of action of the synthesized compounds and their good binding interactions were observed. ADMET prediction of good active compounds showed that these ones possess good pharmacokinetics and drug-likeness behavior.

Rotavirus species H (RVH) has been detected in pigs, humans and bats. Moreover, porcine RVHs have been recently identified in several swine-producing countries. Despite their zoonotic impact, genome information of RVHs is still limited. This study aimed to establish a tentative complete genome-based genotyping system for RVHs, by appending genomic sequences from 12 porcine RVHs identified in Japan between 2013 and 2015 to those from human and other porcine RVHs reported in previous studies. Phylogenetic analysis of 11 RNA segments indicated that porcine RVHs could be classified into multiple genotypes. Consequently, the genotype classification for RVHs revealed the existence of genotypes 10G, 6P, 6I, 3R, 4C, 7M, 6A, 2N, 4T, 6E, 3H for the genes VP7, VP4, VP6, VP1, VP2, VP3, NSP1, NSP2, NSP3, NSP4 and NSP5, respectively. Surprisingly, two distinctive types in NSP1 and NSP3 genes were identified from among the twelve porcine RVHs. Our data suggest a potentially novel gene rearrangement event between porcine RVH and rotavirus species C in the NSP3 gene. These findings would provide a new insight in understanding for evolution of RV.

Leaf variegation pale yellowing is observed in the Calcineurin B-Like-Interacting Protein Kinase14 (CIPK14) overexpression line (oeCIPK14) and double knockout WHIRLY1/WHIRLY3 (why1/3) lines of Arabidopsis, the distribution of WHIRLY1 (WHY1) protein between plastids and the nucleus are affected by the phosphorylation of WHY1 by CIPK14. To elucidate the coregulation of CIPK14 and WHIRLY1/WHIRLY3 mediated leaf pale yellowing, a differential proteomic analysis is conducted between the oeCIPK14 variegated (oeCIPK14-var) line, why1/3 variegated (why1/3-var) line and wild type (WT). More than 800 protein spots are distinguished on each gel, 67 differential abundance proteins (DAPs) are identified by matrix-assisted laser desorption ionization-time of flight/time of flight mass spectrometry (MALDI-TOF/TOF-MS), of which, 34 DAPs are in the oeCIPK14-var, 33 DAPs are in the why1/3-var compared to WT. Five overlapping proteins differentially change both in the oeCIPK14-var and in the why1/3-var. They are ATP-dependent Clp protease proteolytic subunit-related protein 3 (ClpR3), Ribulose bisphosphate carboxylase large chain (RBL), Beta-amylase 3 (BAM3), Ribosome-recycling factor (RRF), Ribulose bisphosphate carboxylase small chain (RBS). Bioinformatics analysis show that most of DAPs are involved in photosynthesis, defense and antioxidation pathway, protein metabolism, amino acid metabolism, energy metabolism, malate biosynthesis, lipid metabolism and transcription. Thus, the photosystem parameters are measured that the content of chlorophyll, the photochemical efficiency of PSⅡ (Fv/Fm), and electron transport rates (ETR) decrease in the why1/3-var and oeCIPK14-var, but the non-photochemical quenching (NPQ) increases. Both mutants show high sensitivity to strong light. Based on the annotation of DAPs from both why1/3-var and oeCIPK14-var lines, we conclude that CIPK14 phosphorylation mediated WHY1 deficiency in plastids is related to impairment of protein metabolism leading to chloroplast dysfunction.

Background. Escalating global plastic production, expected to reach 34,000 million tons by 2050, poses a significant threat to human and environmental well-being, particularly in aquatic ecosystems. Microplastics (MP) and nanoplastics (NP), which originate from the degradation of plastics, are of concern due to their potential bioaccumulation and uptake of pollutants. This study addresses identification methods and focuses on insect meal, a raw material for aquaculture feed. Methods. By using different techniques, the study was able to detect MP and NP in insect meal samples. Chemical digestion with KOH at 60°C efficiently removed organic matter without affecting the synthetic polymer polyethylene (PE). Filtration, confocal Raman microscopy, SEM and TEM were used for comprehensive analysis and integrity tests on PE films were performed using Raman and FTIR spectroscopy. The results showed the presence of PE microplastic particles in the insect meal, which was confirmed by correlative Raman and SEM mapping on a positively charged surface. In addition, the increased resolution of the Raman microscope identified submicrometric PE NP (800 nm). Transmission electron microscopy (TEM) with energy dispersive X-ray spectroscopy (EDX) confirmed plastic-like structures in the insect meal, highlighting the presence of PE plastics characterized by irregular shapes and some agglomeration. The higher carbon concentration in the EDX analysis supported the plastic nature, which was also confirmed by Raman spectroscopy. Conclusions. The study provides a robust method for the detection of MP and NP in insect meal and provides valuable insight into the possible presence of plastics in insect-based aquafeeds. The combination of different analytical methods increases the reliability of the results and sets the stage for future investigations that could focus on the quantification of NP and the assessment of their potential environmental impact.

The purpose of this study was to identify subgroups of quality of life (QOL) changes in breast cancer survivors (BCS) and to determine factors associated with subgroups of consistently low or deteriorated QOL. We enrolled 101 women recently diagnosed with breast cancer in South Korea and asked them to complete a questionnaire at baseline (within 1 month of diagnosis), 1 year later (Year 1), 2 years later (Year 2), and 3 years later (Year 3). We assessed QOL using the global QOL subscale from the EORTC QLQ-C30. We defined low QOL as a global QOL score 10 points below the mean score of the general population. Based on low QOL as defined in this study, we identified subgroups of QOL changes over 3 years. We identified four subgroups of QOL changes: improved (47.4%), stable (30%), continuously low (8.8%), and deteriorated (13.8%) and considered the last two categories (22.6%) as poor QOL. Logistic regression analyses demonstrated that significant determinants of poor QOL were insomnia at Year 1, fatigue and anxiety at Year 2, and fatigue, depression, and comorbidity at Year 3. In conclusion, persistent symptoms of insomnia, fatigue, anxiety, depression, and comorbidity are potential risk factors for poor QOL in BCS.

The main focus of this paper is to propose a comprehensive framework for the cognitive meas-urement and modelling of the built environment. This will involve exploring and measuring neural mechanisms. The aim is to create a foundation for further studies in this field that are consistent and rigorous. Additionally, this framework will facilitate collaboration with cognitive neuroscientists by establishing a shared conceptual basis. The goal of this research is to develop a human-centric approach for urban design that is scientific and measurable, producing a set of urban design guidelines that incorporate cognitive measurement and modelling. By doing so, the broader intention is to design urban spaces that prioritize human needs and well-being, mak-ing them more liveable.

Background: Prostate cancer remains a significant global health concern, and understanding the molecular drivers of this disease is crucial for developing effective diagnostic and therapeutic strategies. Steroid Receptor Coactivator-3 (SRC-3), a member of the SRC family, has emerged as a key player in prostate cancer pathogenesis. This review comprehensively examine the role of SRC-3 in prostate cancer, encompassing molecular mechanisms, clinical implications, and therapeutic opportunities. Methods: A systematic literature search following PRISMA guidelines was conducted in PubMed, PMC, and other relevant databases to identify studies that investigate SRC-3 in prostate cancer. A total of 67 articles were selected based on predetermined inclusion criteria. Results: 785 articles were retrieved from databases using specific keywords and MeSH terms related to SRC-3 and Prostate Cancer. After removing 461 duplicates, 260 articles were excluded based on title and abstract review. Subsequently, a comprehensive screening by three researchers resulted in 47 relevant articles for this systematic review. We summarize its contributions to AR-mediated transcriptional regulation, tumor growth, and metastasis. Evidence suggests that SRC-3 expression correlates with prostate cancer aggressiveness, disease recurrence, and poor patient outcomes. Its potential as a diagnostic biomarker and therapeutic target is explored, offering insights into personalized medicine approaches. Conclusions: SRC-3 plays a pivotal role in prostate cancer, influencing disease progression and clinical outcomes. Understanding the molecular intricacies of SRC-3 in prostate cancer offers new opportunities for precision medicine and innovative therapeutic approaches. This review provides a comprehensive overview of SRC-3's involvement in prostate cancer, emphasizing its clinical relevance and potential as a therapeutic target, ultimately contributing to improved patient care in the era of personalized oncology.

The p53 tumor suppressor protein is an activator of transcription. Diverse stress factors lead to various sets of posttranslational modifications of p53 what results in different sets of upregulat-ed genes. We noticed that actinomycin D and nutlin-3a (A+N) synergize in inducing activating phosphorylations of p53 and upregulation of selected p53-target genes. Here we found that one of these genes is DUSP13, which codes for poorly-studied, dual-specificity phosphatase having at least two isoforms, one expressed in testis and the other in skeletal muscles. In cancer cells ex-posed to A+N, DUSP13 is expressed from an alternative promoter in intron, what results in ex-pression of isoform named TMDP-L1. The luciferase reporter tests demonstrated that this pro-moter is activated by both endogenous and ectopically expressed p53. We showed for the first time that mRNA expressed from this promoter actually produces the protein, which can be de-tected by Western blotting in all examined cancer cell lines with wild-type p53 exposed to A+N. In some cell lines it is also induced by clinically relevant camptothecin or by nutlin-3a acting alone. This isoform, fused with green fluorescent protein localizes in perinuclear region of cells. Thus, TMDP-L1 isoform may be an important element of p53-regulated stress response system.

One of the most critical aspects in introral impression is the detection of the finish line, in particular in case of subgingival preparations. The aim of these in vitro study was to evaluate the accuracy among four different IntraOral Scanners (IOSs) in scanning a subgingival vertical margins preparation (VP). A reference maxillary typodont (MT) was fabricated with a VP for full crown on #16 and #21. The MT was scanned with a laboratory scanner (Aadva lab scanner, GC, Tokyo, Japan) to obtain a digital MT (dMT) in .stl format file. A group of 40 digital casts (dIOC) were obtained by scanning the MT 10 times with four different IOSs (Trios 3, 3Shape A/S), ( I700, Medit), (Vivascan, Ivoclar), (Experimental IOS, GC). All the obtained dIOCs were imported into an inspection software program (Geomagic Control X; 3D SYSTEMS) to be superimposed to the dMT, to calculate trueness. Therefore, in order to calculate precision all the scans of the same scanner group were superimposed onto the cast that obtained the best result of trueness. Results were collected as root mean square value (RMS) on #16 and #21 abutment surfaces and on a marginal area positioned 1 mm above and below the gingival margin. A nonparametric analysis Kruskal-Wallis test was performed to compare the RMS values obtained in the different iOS groups for trueness and precision. Statistically significance was set at 0.05. The trueness on #16 abutment, did not statistically differ in between the IOS, while on #21 abutment, Vivascan (56.0 ±12.1) and Experimental IOS, GC (59.2±2.7) performed statistically better than the others. Regarding precision Experimental IOS, GC and Trios 3 were significantly better than I700 and Vivascan both in the #16 (10.7±2,1; 15.8 ± 2,7) and in the #21 area (16.9±13.8 ; 18.0±2.7). At marginal level for both #16 and #21 all the IOS reported reduced accuracy compared to clinical acceptance.

Growth hormone (GH) is a peptide hormone that plays a crucial role in controlling growth, development, and lifespan. Molecular regulation of GH is accomplished via the GH receptor (GHR) gene, which is the main factor influencing human development and is essential to optimal functioning of the GH/IGF-I axis. Two GHR isoforms have been studied, according to the presence (flGHR) or absence (d3GHR) of exon 3. The d3GHR variant, which has recently been related to longevity, is associated with enhanced signal transduction and higher receptor function. Many of these studies indicated that the growth response to GH treatment may be affected. Individuals carrying the d3GHR isoform have higher receptor activity, improved signal transduction, and alterations in the treatment response and efficacy compared with those carrying the WT isoform. Further, studies performed in patients with acromegaly, Prader-Willi syndrome, Turner syndrome, small for gestational age (SGA), and growth hormone deficiency (GHD) suggested that the d3GHR variant may have an impact on the relationship between GH and IGF-I levels, height, weight, BMI, and other variables. Other research, however, revealed inconsistent results, which might have been caused by confounding factors, including limited sample sizes and different experimental methods. In this review, we lay out the complexity of the GHR isoforms and provide an overview of the major pharmacogenetic research conducted on this ongoing and unresolved subject.

This work aims to follow the corrosion behavior of copper in 3 wt% NaCl solution in the presence of a bio-oily extract. Spent coffee grounds (SCG), a highly recyclable and usable biomass - often thrown away and becoming a serious threat to the environment - , has a fraction of oils (12%) that we have opted to use as a corrosion inhibitor for copper. The extraction was carried out using n-hexane as the solvent for the decoction. The oily fraction was analyzed by Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA). Potentiodynamic polarization measurements have revealed SCG extract acts as a cathode-type inhibitor for copper in saline media, mainly preventing the diffusion of oxygen molecules toward the substrate. As the extract concentration increased, the inhibition efficiency has improved as well, reaching 95.78 % with 0.6 g/L of SCG extract. The obtained results by electrochemical impedance spectroscopy (EIS) are in accordance with the order of inhibitory efficiency obtained by potentiodynamic polarization. We have found that the SCG extract adsorption process on copper surface is spontaneous and complies with Langmuir isotherm.

Background: Public engagement is needed to make sure urban forestry management efforts align with the values of the public being served. Noting this, we determined current and desired urban forest access of Florida (United States) residents using the criteria from the 3-30-300 rule (i.e., 3 trees visible from home, 30% canopy in neighborhood, and a green space within 300 meters of home). Methods: A survey of 1,716 Florida residents was conducted to assess canopy coverage and green space access. Respondents were then asked if this level of urban forest access was sufficient for their needs. We also asked their perceptions of the benefits and drawbacks of urban trees and whether they had any negative interactions with trees in the past. Results: We found that 37.3% of Florida residents met all three criteria of the 3-30-300 rule. Despite this, half the respondents would prefer more trees in their neighborhoods. When asked to name the top benefits provided by trees, the most common responses were shade, beauty, and attracting wildlife. The most common drawbacks to urban trees included risk to property, leaves/debris, and fears regarding storms and hurricanes. Conclusions: Florida residents largely value their urban forest and would like to see it maintained or enhanced. Improving access to greenspaces for recreation is the most pressing concern for urban forest managers in Florida looking to meet the requirements of the 3-30-300 rule. Results from this study can inform and test urban forest management at national and global scales.

Damping-off caused by Pythium aphanidermatum (Pa) is one of the most destructive diseases for watemelon seedlings. Application of biological control agents against Pa has attracted attention of many researchers for a long time. In this study, an actinomycete isolate JKTJ-3 with strong and broad-spectrum antifungal effect was screened from 23 bacterial isolates. Based on the morphological, cultural, physiological, and biochemical characteristics as well as the feature of 16S rDNA sequence, isolate JKTJ-3 was identified as Streptomyces murinus. We compared the biocontrol efficacy of isolate JKTJ-3 and its metabolites. The results revealed that seed and substrate treatments with the JKTJ-3 cultures showed a significant inhibitory effect on watermelon damping-off disease. Seed treatment with the JKTJ-3 cultural filtrates (CF) had higher control efficacy that of the fermentation cultures (FC). Treatment of the seeding substrate with the wheat grain cultures (WGC) of JKTJ-3 exhibited better control efficacy than that of the seeding substrate with the JKTJ-3 CF. Moreover, the JKTJ-3 WGC showed the preventive effect on suppression of the disease, and the efficacy increased with increase in the inoculation interval between the WGC and Pa. Production of the antifungal metabolite actinomycin D by isolate JKTJ-3 and cell wall-degrading enzymmes such as β-1,3-glucanase and chitosanase was probably the mechanisms for effective control of watermelon damping-off. It was showed for the first time that S. murinus can produce anti-oomycete substances including chitinase and actinomycin D. This is the first report about S. murinus used as biocontrol agent against watermelon Pa-induced damping-off.

Image encryption is increasingly becoming an important area of research in information security and network communications, as digital images are widely used in various applications and are vulnerable to various types of attacks. In this research work, a color image cryptosystem that is based on a 3-layer permutation-substitution network (PSN) is proposed. For every layer, an encryption key and an S-box are generated and utilized. Those are based on a four-dimensional (4D) dynamical Chen system of a fractional-order, the Mersenne Twister, OpenSLL, Rule 30 Cellular Automata and Intel’s MKL. The sequential application of Shannon’s ideas of diffusion and confusion for 3 times guarantees a total distortion of any input plain image, resulting in a totally encrypted one. Apart from the excellent and comparable performance to counterpart algorithms from the literature, showcasing resistance to visual, statistical, entropy, differential, known plaintext and brute-force attacks, the proposed image cryptosystem provides an exceptionally superior performance in 2 aspects: a vast key space of 2^1658 and an average encryption rate of 3.34 Mbps. Furthermore, the proposed image cryptosystem is shown to successfully pass all the tests of the NIST SP 800 suite.

Artificial Intelligence (AI) has the power to generate scenarios and make predictions through the use of advanced algorithms and machine learning techniques. OpenAI’s GPT-3 AI is a state-of-the-art language model that has been trained on a large dataset of text, which allows it to generate hu-man-like text, and it can generate scenarios for different fields. However, GPT-3 was trained on data available up until June 2021, had no access to more recent data nor was connected to the internet. In this study, we investigated the capability of OpenAI’s GPT-3 AI to predict the Ukrainian war es-calation, which started in 2022 and had massive geopolitical effects. We used GPT-3´s capability to generate future scenarios, to check those scenarios for internal consistency, and to create a proba-bility estimate. The results showed that although GPT-3 described an open war as one of the low probability scenarios, its capability on predicting the future was limited. Furthermore, it became evident that checking internal consistency of the generated scenarios could be improved. We ap-preciated GPT-3 as very useful and powerful for generating future scenarios, but also concluded that its prediction capabilities of real-world events are limited, should be used with caution, and require further development.

In previous works we have developed the concept of a relativistic engine taking into account the phenomena of retardation of electromagnetic fields. We have shown that Newton’n third law cannot strictly hold in a distributed system, where the different parts are at a finite distance from each other and thus force imbalance is created at the system’s center of mass. As the system is affected by a total force for a finite period, mechanical momentum and energy are acquired by the system. In previous works we relied on the fact that the bodies were macroscopically natural. Lately we relaxed this assumption and studied charged bodies, thus analyzing the consequences on a possible electric relativistic engine. On the first paper on this subject we investigated this phenomena in general but gave an example of a system only at the stage of reaching a stationary state, a second paper was devoted to the same but on the atomic scale, here we shall analyze the charge relativistic engine in a general time dependent setting.

This research intended to report amine-functionalized multiwall carbon nanotubes (MWCNTs) prepared by a simple method for efficient and rapid removal of Reactive Yellow 2 (RY2) from water. EDS analysis showed that the N content increased from 0 to 2.42% and from 2.42 to 8.66% after modification by APTES and PEI, respectively. BET analysis displayed that the specific surface area, average pore size, and total pore volume were reduced from 405.22 to 176.16 m2/g, 39.67 to 6.30 nm, and 4.02 to 0.28 cm3/g, respectively. These results proved that the PEI/APTES-MWCNTs were successfully prepared. pH edge experiment indicated that pH 2 was optimal for RY2 removal. At pH 2 and 25 °C, the time required for adsorption equilibrium was 10, 15, and 180 min at initial concentrations of 50, 100, and 200 mg/L, respectively; and the maximum RY2 uptake calculated by the Langmuir model was 714.29 mg/g. Thermodynamic studies revealed that the adsorption process was spontaneous and endothermic. 0-0.1 mol/L of NaCl showed negligible effect on RY2 removal by PEI/APTES-MWCNTs. Five adsorption/desorption cycles confirmed the good reusability of PEI/APTES-MWCNTs in RY2 removal. Overall, the PEI/APTES-MWCNTs are a potential and efficient adsorbent for reactive dye wastewater treatment.

In spite of its incidence on pistachio trees, the chemical ecology of Labidostomis lusitanica (Germar) (Coleoptera: Chrysomelidae) has been neglected so far. In this work we provide the first evidence of a biologically active male-specific compound that may be promoting field aggregation. Headspace collections by solid-phase microextraction from feral males and females reported the presence of 2-isobutyl-3-methoxypyrazine exclusively on males. Electroantennographic recordings revealed that males and females responded in a dose-dependent manner to increasing stimuli of 2-isobutyl-3-methoxypyrazine, with females overall displaying a higher response than males. In dual-choice tests, both males and females showed a significant preference for the compound in comparison to a pure air stimulus. In the light of these results, the possible role of 2-isobutyl-3-methoxypyrazine as an aggregation cue in L. lusitanica is discussed.

Mild traumatic brain injury (mTBI) or concussion accounts for the bulk of all head injuries and represents a major health concern. Although an mTBI event may not manifest in neurobehavioral impairment, repeated injuries, known as repeated mTBI (rmTBI), can result in a cumulative effect that may progress to long-term cognitive and functional deficits. To date, there is no FDA-approved drug for TBI in general and rmTBI in particular. In previous studies, we have demonstrated the neuroprotective role of mitoquinone (MitoQ), a mitochondrial antioxidant, in an open head injury model and a model of repeated mild TBI (rmTBI) at a chronic time point (30 days). In this work, we set out to assess the neuroprotective potential of MitoQ at acute (3 days) and subacute time points (7 days) post-injury in a controlled cortical impact model of rmTBI. C57BL/6 male mice were injected intraperitoneally with MitoQ (5 mg/kg) one hour after the first mTBI, and three days after the first injury in both the 3-day and 7-day MitoQ + rmTBI subgroups, with an additional injection four days after the second injection in the 7-day group. Cognitive function was evaluated using the Morris water maze (MWM) while gross and fine motor functions were evaluated by the pole climbing, grip strength, and ladder rung tests. Dihydroethidium (DHE) staining was performed to evaluate oxidative stress while qRT-PCR was used to measure the gene expression of different antioxidant enzymes. Also, immunofluorescence staining was performed on brain tissue to assess the degree of microgliosis and astrocytosis. Our results showed that MitoQ conferred significant protection on days 3 and 7 post-injury against fine motor function impairment induced by rmTBI. Moreover, MitoQ enhanced cognitive function and reduced astrogliosis, microgliosis, and levels of oxidative stress on day 7 post-injury. However, antioxidant gene expression generally remained unaffected. In light of our results, MitoQ administration may be considered a preventive approach that helps to alleviate the neurological manifestations associated with rmTBI early before symptoms progress to long-term deficits.

We previously found increases in uncoupling protein (Ucp)-1 transcription in brown adipose tissue (BAT) of mice following a single oral dose of flavan 3-ols (FL), a fraction of catechins and procyanidins. It was confirmed that these changes were totally reduced by co-treatment of adrenaline blockers. According to these previous results, FL possibly activates sympathetic nervous system (SNS). In this study, we confirmed the marked increase in urinary catecholamine (CA) s projecting SNS activity following a single dose of 50 mg/kg FL. In addition, we examined the impact of the repeated administration of 50 mg/kg FL for 14 days on adipose tissues in mice. In BAT, FL tended to increase the level of Ucp-1 along with thermogenic transcriptome factors, such as peroxisome proliferator-activated receptor γ coactivator (PGC)-1α and PR domain-containing (PRDM)1. Transcription of browning markers, such as CD137 and transmembrane protein (TMEM) 26 in addition to PGC-1α were increased in epididymal adipose (eWAT) by FL. A multilocular morphology with cell size reduction was shown in the inguinal adipose (iWAT), together with increasing the level of Ucp-1 following administration of FL. These results suggest that FL produces browning in adipose through activation of the SNS.

Hydrogenated amorphous silicon (a-Si:H) can be produced by plasma-enhanced chemical vapour deposition (PECVD) of SiH4 (Silane) mixed with Hydrogen. The resulting material shows outstanding radiation resistance properties and can be deposited on a wide variety of different substrates. These devices have been used to detect many different kinds of radiation namely: MIPs, x-rays, neutrons and ions as well as low energy protons and alphas. However, MIP detection using planar diodes has always been difficult due to the unsatisfactory S/N ratio arising from a combination of high leakage current, high capacitance and a limited charge collection efficiency (50% at best for a 30 µm planar diode). To overcome these limitations the 3D-SiAm collaboration proposes to use a 3D detector geometry. The use of vertical electrodes allows for a small collection distance to be maintained while conserving a large detector thickness for charge generation. The depletion voltage in this configuration can be kept below 400 V with consequent reduction in the leakage current. In this paper, following a detailed description of the fabrication process, the results of the tests performed on the planar p-i-n structures made with ion implantation of the dopants and with carrier selective contacts will be illustrated.

With the introduction of HTTP/3, whose transport is no longer the traditional TCP protocol but the novel QUIC protocol, research for solutions to the unfairness of Adaptive Streaming over HTTP (HAS) has become more challenging. That is, because of different transport layers, the HTTP/3 may not be available for some networks and the clients have to use HTTP/2 for their HAS applications instead. Therefore, the scenario that HAS over HTTP/3 (HAS/3) compete against HTTP/2 (HAS/2) must be considered seriously. However, there have been a shortage of investigations on the performance and the origin of the unfairness in such a cross-protocol scenario in order to produce proper solutions. Therefore, this paper provides a performance evaluation and root-cause analysis of the cross-protocol unfairness between HAS/3 and HAS/2. It is concluded that, due to differences in the congestion control mechanisms of QUIC and TCP, HAS/3 clients obtain larger congestion windows, thus requesting higher video bitrates than HAS/2. As the problem lies in the transport layer, existing client-side ABR-based solutions for the unfairness from the application layer may perform suboptimally for the cross-protocol case.

The 32CA reactions of a series of pairs of bent three-atom-components (B-TACs) and linear TACs (L-TACs) towards electrophilic dicyanoethylene (DCE) have been studied within the Molecular Electron Density Theory in order to understand their different reactivity. ELF analysis indicates that while pseudodiradical B-TACs change their electronic structure to pseudoradical or carbenoid L-TACs upon dehydrogenation, zwitterionic B-TACs experience no remarkable change. Analysis of the CDFT indices indicates that five of the nine studied TACs have a strong nucleophilic character, thus participating in polar reactions towards electrophilic ethylenes. The activation energies of the 32CA reactions of the nine TACs towards electrophilic DCE range from 0.6 to 22.0 kcal·mol-1, which are by between 2.0 and 10.1 kcal·mol-1 lower than those involved in the non-polar 32CA reactions with ethylene. In general, B-TACs are more reactive than their L-TAC counterparts. A change of the regioselectivity is found in these polar 32CA reactions; in general, while B-TACs are meta regioselective, L-TACs are ortho regioselective. Analysis of the geometrical parameters indicates that at all TSs, the formation of the single bond involving the most electrophilic C4 carbon of DCE is more advanced than that involving the C5 one. A change of the asynchronicity in the reactions involving B-TACs and L-TACs is also found.

The [3+2] cycloaddition (32CA) reactions of strongly nucleophilic norbornadiene (NBD) with simplest diazoalkane (DAA) and three DAAs of increased electrophilicity have been studied within the Molecular Electron Density Theory (MEDT) at the MPWB1K/6-311G(d,p) computational level. These pmr-type 32CA reactions follow an asynchronous one-step mechanism with activation enthalpies ranging from 17.7 to 27.9 kcal·mol-1 in acetonitrile. The high exergonic character of these reactions makes them irreversible. The presence of electron-withdrawing (EW) substituents in the DAA increases the activation enthalpies, in complete agreement with the experimental slowing-down of the reactions, but contrary to the Conceptual DFT prediction. Despite the nucleophilic and electrophilic character of the reagents, the global electron density transfer at the TSs indicates rather non-polar 32CA reactions. The present MEDT study allows establishing that the depopulation of the NNC core in this series of DAAs with the increase of the EW character of the substituents present at the carbon center is responsible for the experimentally found deceleration.

Cholest-4-en-3-one Δ1-dehydrogenase (AcmB) from Sterolibacterium denitrificans is successfully immobilized on 3-aminopropyltrimethoysilane functionalized MCF and SBA-15 silica supports using adsorption or covalently with glutaraldehyde or divinyl sulfone linkers. The best catalyst, AcmB on MCF linked covalently with glutaraldehyde, retains the specific activity of the homogenous enzyme while exhibiting a substantial increase of the operational stability. The immobilized enzyme was used continuously in the fed-batch reactor for 27 days, catalyzing 1,2-dehydrogenation of androst-4-en-3-one to androst-1,4-dien-3-one with a final yield of 29.9 mM (8.56 g/L) and 99% conversion. The possibility of reuse of the immobilized catalyst was also demonstrated and resulted with a doubling of the product amount compared to that in the reference homogenous reactor. Finally, it was shown that molecular oxygen from the air can efficiently be used as an electron acceptor either reoxidizing directly the enzyme or the reduced DCPIPH2. Keywords: 3-ketosteroid D1-dehydrogenase; KSTD; KSDH; AcmB; 1,2-dehydrogenation; cholest-4-en-3-one Δ1-dehydrogenase; enzyme immobilization, FAD-dependent enzymes; enzyme immobilization;

We study the hadron-quark hybrid equation of state (EOS) of compact-star matter. The Nambu—Jona-Lasinio (NJL) local SU(3) model with vector-type interaction is used to describe the quark matter phase, while the relativistic mean field (RMF) theory with scalar-isovector $\delta$-meson effective field adopted to describe the hadronic matter phase. It is shown that the larger the vector coupling constant, the lower the threshold density for the appearance of strange quarks. For a sufficiently small value of the vector coupling constant, the functions of the mass dependence on the baryonic chemical potential have regions of ambiguity which leads to a phase transition in non-strange quark matter with an abrupt change in the baryon number density. We show that within the framework of the NJL model, the hypothesis on the absolute stability of strange quark matter is not realized. In order to describe the phase transition from hadronic matter to quark matter, the Maxwell's construction is applied. It is shown that the greater the vector coupling, the greater the stiffness of the EOS for quark matter and the phase transition pressure. Our results indicate that the infinitesimal core of the quark phase, formed in the center of the neutron star, is stable.

Information and communication technologies play an increasingly important role in the process of acquiring knowledge from a territory and managing it at different scales. ICTs allow a rapid diffusion of data not only through institutional channels but also through social networks where the smart community share experiences and perceptions. In this sense, ICTs become strategic to support the promotion of sustainable tourism development of territories. An important tool to implement it, can be a circular smart dashboard, a decision support system in which the digital data are organized and processed to produce an information output, to be used, after the evaluation by the decision makers, as a new input for the system. The present paper deals with a wider research the authors are involved in, related to the reconversion and valorization of a former mining area towards slow tourism, as the Santa Barbara Walk (SBW), an ancient mining route in the Sulcis Iglesiente area (Sardinia, Italy) . In particular, we here focus on the design proposal of a dashboard, capable of organizing information concerning the main features of the walk, in order to facilitate a shared governance for an effective tourism promotion. The paper is based on a thorough recognition of the main characteristics of the Walk, both the material ones and the digital, immaterial ones. The SBW represents in fact a network connecting the main points of interest along the Walk. On the contrary, its digital network – consisting of intangible infrastructure and flows - is however fragmented in terms of policies and contents Also a state of disorganization in slow tourism promotion activities can be observed. The goal of this paper is to present and analysis of the area, and to propose an evaluation and planning tool as the design of a circular dashboard of the SBW.

Invasion ecology has a long tradition of searching for traits distinguishing alien invasive and non-invasive plants. Surprisingly, this approach has been so far poorly used to understand why some arable weeds are abundant and widespread while others are rare and narrowly distributed. In the present study, we focused on the characteristics of successful weeds occurring in maize fields, one of the most import crop worldwide. Two national weed surveys conducted in France were used to identify increasing and decreasing species based on 175 and 484 surveyed fields in the 1970s and the 2000s, respectively. Weed trait values related to regional frequency, local abundance and specialization to maize were identified with Phylogenetic Generalized Least-Squares (PGLS). We found a positive relationship between regional frequency and local abundance, i.e. the most widespread weeds were also locally more abundant. We highlighted that weeds with the C4 photosynthetic pathway and summer emergence were more abundant, more frequent and more specialized to maize crops. More generally, we highlighted two successful strategies: on the one hand, traits related to a general weediness syndrome with rapid resource acquisition (high SLA and Ellenberg-N) and high colonization capacity (seed longevity, fecundity and wind dispersal), on the other hand, traits related to specific adaptation to spring cultivation (thermophilous species with summer emergence, late flowering and C4 photosynthetic pathway). Deviations from the abundancy-frequency relationships also indicated that species of the Panicoideae sub-family, species with Triazine-resistant populations and neophyte species were more abundant than expected by their regional frequency. To some extent, it is therefore possible to predict which species can be troublesome in maize crops and use this information in weed risk assessment tools to prevent new introductions or favor early detection and eradication. This study showed how tools developed in functional and macro-ecology can be used to improve our understanding of weed ecology and to develop more preventive management strategies.

Aquaporin-3 (AQP3) is one of the aquaglyceroporins, which is expressed in the basolateral layer of the skin membrane. Studies have reported that human skin squamous cell carcinoma overexpresses AQP3 and inhibition of its function may alleviate skin tumorigenesis. In the present study, we have applied a virtual screening method that encompasses filters for physicochemical properties and molecular docking to select potential hit compounds that bind to the Aquaporin-3 protein. Based on molecular docking results, the top 20 hit compounds were analyzed for stability in the binding pocket using unconstrained molecular dynamics simulations and further evaluated for binding free energy. Furthermore, examined the ligand-unbinding pathway of the inhibitor from its bound form to explore possible routes for inhibitor approach to the ligand-binding site. With a good docking score, stability in the binding pocket, and free energy of binding, these hit compounds can be developed as Aquaporin-3 inhibitors in the near future.

Opioids are highly addictive substances with a relapse rate of over 90%. While preclinical models of chronic opioid exposure exist for studying opioid dependence, none recapitulate the relapses observed in human opioid addiction. The mechanisms associated with opioid dependence, the accompanying withdrawal symptoms and the relapses that are often observed months or years after opioid dependence are poorly understood. Therefore, we developed a novel model of chronic opioid exposure whereby the level of administration is self-directed with periods of behavior acquisition, maintenance and then extinction alternating with reinstatement. This profile arguably mirrors that seen in humans, with initial opioid use followed by alternating periods of abstinence and relapse. Recent evidence suggests that dietary interventions that reduce inflammation, including omega-3 fatty acids such as docosahexaenoic acid (DHA), may reduce substance misuse liability. Using the self-directed intake model, we characterize the observed profile of opioid use and demonstrate that a diet enriched in polyunsaturated fat acids (PUFAs) ameliorates oxycodone-seeking behaviors in the absence of drug availability and reduces anxiety. Guided by the major role gut microbiota have on brain function, neuropathology, and anxiety, we profile the microbiome composition and the effects of chronic opioid exposure and DHA supplementation. We demonstrate that withdrawal of opioids led to a significant depletion in specific microbiota genera whereas DHA supplementation increased microbial richness, phylogenetic diversity, and evenness. Lastly, we examined the activation state of microglia in the striatum and found that DHA supplementation reduced the basal activation state of microglia. These preclinical data suggest that a diet enriched in PUFAs could be used as a treatment to alleviate anxiety induced opioid-seeking behavior and relapse in human opioid addiction.

Untranslated regions (UTRs) of flaviviruses contain a large number of RNA structural elements involved in mediating the viral life cycle, including cyclisation, replication, and encapsidation. Here we report on a comparative genomics approach to characterize evolutionarily conserved RNAs in the 3'UTR of tick-borne, insect-specific and no-known-vector flaviviruses in silico. Our data support the wide distribution of previously experimentally characterized exoribonuclease resistant RNAs xrRNAs within tick-borne and no-known-vector flaviviruses and provide evidence for the existence of a cascade of duplicated RNA structures within insect-specific flaviviruses. On a broader scale, our findings indicate that viral 3'UTRs represent a flexible scaffold for evolution to come up with novel xrRNAs

The proper hydrogenation of Hyper-coal (HPC) using 1, 2, 3, 4-tetrahydroquinoline (THQ) was able to decrease the oxygen content and adjust the molecular structure of HPC for preparing the spinnable pitch with high softening point (SP). The spinnable pitch prepared from the THQ-soluble (QS) fraction of HPC as a precursor consisted more naphthenic carbon groups than that prepared from the 1-methylnaphthalene (1-MN) soluble (MNS) fraction of HPC. The HPC-QS derived pitch showed excellent spinnability even the SP of 260°C, and the tensile strength of the resultant carbon fiber was up to 1350 MPa with a diameter around 8 µm by only heat treatment at 800°C for 5 min.

The efficacy of chemotherapy depends on sensitivity and intrinsic or acquired drug resistance of cancer cells. The n-3 long chain polyunsaturated fatty acids (n-3 LCPUFAs) are considered chemosensitizing agents and revertants of multidrug resistance by pleiotropic mechanisms. The specific mechanisms are not fully understood, but nowadays, it is widely accepted that there are a complex network of mechanisms, including alteration in gene expression, modulation of cellular proliferation and differentiation, induction of apoptosis, generation of reactive oxygen species and lipid peroxidation. A crucial mechanism in the control of cell drug uptake and efflux is related to n-3 LCPUFA influence on membrane lipid composition. The incorporation of docosahexaenoic acid in the lipid rafts produces significant changes in their physical-chemical properties affecting content and functions of transmembrane proteins, such as growth factors, receptors and ATP-binding cassette transporters. Of note, n-3 LCPUFAs often impact on the lipid compositions more in chemoresistant cells than in chemosensitive cells, suggesting their adjuvant role in cancer treatment.

The electronic structure and the participation of the simplest azomethine imine (AI) in [3+2] cycloaddition (32CA) reactions have been analysed within the Molecular Electron Density Theory (MEDT) using DFT calculations at the MPWB1K/6-311G(d) level. Electron localisation function (ELF) topological analysis reveals that AI has a pseudoradical structure, while the conceptual DFT reactivity indices characterise this TAC as a moderate electrophile and a good nucleophile. The non-polar 32CA reaction of AI with ethylene takes place through a one-step mechanism with low activation energy, 5.3 kcal/mol-1. A bonding evolution theory (BET) study indicates that this reaction takes place through a non-concerted [2n+2τ] mechanism in which the C–C bond formation is clearly anticipated prior to the C–N one. On the other hand, the polar 32CA reaction of AI with dicyanoethylene takes place through a two-stage one-step mechanism. Now, the more favourable regioisomeric transition state structure (TS) is located 8.5 kcal•mol⁻¹ below the reagents, in complete agreement with the high polar character of the TS. The current MEDT study makes it possible to extend Domingo’s classification of 32CA reactions to a new pra-type of reactivity.

In this paper, the methods and their analysis for estimating the location of three dimension (3-D) single source buried in lossy medium are presented with uniform circular array (UCA). The mathematical model of the signal in the lossy medium is proposed. Using location information in the covariance matrix obtained by sensors’ output, the equations of the source location (azimuth angle, elevation angle and range) are obtained. The phase and amplitude of the covariance matrix function are used to process these equations respectively. Then, the phase and amplitude of the covariance matrix function are used to process the source localization in the conductive medium together. By analyzing the characteristics of the proposed methods and MUSIC method, the computational complexity and the valid range of these methods are given. From the results, whether the loss is known, we can choose the appropriate method to process the issues (localization in lossless medium or lossy medium).

Exact solutions to conformable time fractional (3+1)- dimensional equations are derived by using the modified form of the Kudryashov method. The compatible wave transformation reduces the equations to an ODE with integer orders. The predicted solution of the finite series of a rational exponential function is substituted into this ODE. The resultant polynomial equation is solved by using algebraic operations. The method works for the Jimbo-Miwa, the Zakharov-Kuznetsov and the modified Zakharov-Kuznetsov equations in conformable time fractional forms. All the solutions are expressed in explicit forms.

The reconstruction of standard at-grade intersection into roundabout is very often motivated by the need to improve the safety of a part of the road network. To assure the effect of the reconstruction before-after analyses based on traffic accidents or some other indirect traffic safety parameter is needed. This paper presents a detailed analysis of four roundabouts reconstructed from the at-grade intersection according to the Croatian Guidelines for Roundabout Design. The analysis included a comparison of speeds at the location - a standard intersection- before and a roundabout – after reconstruction, time distribution of operational speed and applied design elements as well as their correlations. Experimentally gathered data on operational speed showed that the expected effect of speed reduction was not achieved in most of the analyzed cases. The conclusion is that given that the Croatian Guidelines set a very wide range for roundabout elements, the designer has a great influence on the selection and, consequently, on the effects of the roundabout implementation. The revision of the Guidelines is suggested.

(1) Background: This paper illustrates an innovative methodological approach chosen to study and map the colors of the Medieval wall painting of Santa Maria Antiqua in the Roman forum, one of the pilot sites of the EHEM project (Enhancement of Heritage Experiences: The Middle Ages. Digital Layered Models of Architecture and Mural Paintings over Time); (2) Methods: We chose to use two methods for gathering information about colors and mapping, specifically colorimetry by spot measurements and hypercolorimetric multispectral imaging (HMI) to map those same colors sampled through colorimetry; (3) Results: Chromatic data of all colors in the wall paintings were obtained in the CIELAB color space. In those same points, chromatic similarity maps were performed by the innovative HMI system, a multispectral imaging technique able to obtain also color data information by means of the advanced calibration software named SpectraPick®: this allowed to have a complete knowledge of the color characteristics and distribution; (4) Conclusion: The color measurements and mapping was an important result to improve the reading of Medieval wall paintings, fragmentary and stratigraphically complex, giving a new light in the knowledge of the colors and allowing to better understand the original appearance of the iconographic patterns, reconstructed with colors as faithfully as possible similar to the originals.

In a densely populated country like Bangladesh, universities grapple with the challenge of efficiently addressing myriad queries from a large student body, leading to a heightened workload for university stakeholders. To tackle these challenges, we introduce PixieGPT, a tailor-made Generative Pre-Trained Transformer for Bangladeshi universities. PixieGPT significantly mitigates workload by adeptly handling common university-related queries, thereby enhancing user experience. The hierarchical structure plays a crucial role in managing diverse queries from thousands of students about the university system. The solution introduces a modular hierarchical knowledge base (KB) with simpler complexities, addressing the intricacies of efficiently managing large volumes of queries. PixieGPT is designed in a modular way so that the solution is also adaptable for the implementation of other universities worldwide based on the requirements of a particular administrative system. The modular nature facilitates easy adaptation with minor changes based on specific university requirements, ensuring a seamless integration process. This paper delves into the intricacies of PixieGPT's design, emphasizing its pivotal role in mitigating workload challenges for university stakeholders in Bangladesh. The incorporation of BERT for Natural Language Understanding(NLU) and GPT models for Natural Language Generation(NLG) enhances PixieGPT's capabilities, contributing to the scalability and efficiency of the system. The presented use case underscores the practical benefits of PixieGPT, positioning it as a promising solution for universities globally with similar operational frameworks.

A growing body of literature suggests a causative relationship between severe adverse neurological outcomes and early life exposure to paracetamol (acetaminophen) in the presence of oxidative stress. Review of the literature revealed that, although its use is not regularly monitored, paracetamol has achieved near universal acceptance, with exposure in some pediatric populations exceeding 90%. In addition, use of the drug as well as associated adverse outcomes may have risen as a result of pharmaceutical advertising rather than need, and inappropriate use of the drug, both in terms of dose and indication, is widespread. These findings indicate that many clinicians and patients do not, at the present time, evenly weigh the potential risks with the potential benefits of paracetamol exposure early in life. Although retrospective studies might be envisioned to further address the neurodevelopmental risks of paracetamol use during early development, in silico simulations demonstrated that such studies can be thwarted by very high rates of use of the drug combined with associations between paracetamol use and oxidative stressors that act as cofactors in the induction of neurodevelopmental injury. These findings suggest that, despite persistent uncertainty, clinicians and patients should be more aware of available information pointing toward the potential dangers for neurodevelopment of early life exposure to paracetamol. Most importantly, health care workers need to provide a more balanced view, weighing both risks and benefits, when providing advice for patients regarding paracetamol use during periods of brain development.

In the present work, the interactions between hydrocortisone and cyclodextrins were investigated. The cyclodextrins selected for this study were hydroxypropyl-α-cyclodextrin, hydroxypropyl-β-cyclodextrin and hydroxypropyl-γ-cyclodextrin. The study was carried out using density measurements, 1H-NMR and FT-IR spectroscopy. Preliminary studies show that hydroxypropyl-α-cyclodextrin has a low affinity for hydrocortisone, while hydroxypropyl-β-cyclodextrin and hydroxypropyl-γ-cyclodextrin have a good affinity for hydrocortisone in both solid state and solution. The study was carried out at two temperatures: 298.15 K and 310.15 K. The results suggest that at both temperatures, the system 2-HP-β-CD + HC induces an increase in the solvent structure, with increasing the solute concentration in the solution, while on the contrary the system 2-HP-γ-CD + HC induces a decrease in the solvent structure when the concentration of the solute in the system increases.

The objective of the present contribution was to design and characterize resveratrol (RSV) and tocopherol (TOC) loaded 11S quinoa seed protein nanocomplexes. Firstly, molecular docking was performed to describe the probable binding sites between protein and ligands. Isothermal titration calorimetry allowed to obtain the thermodynamic parameters that described the molecular interactions between RSV or TOC with the protein. 11S globulin intrinsic fluorescence spectra showed a quenching effect exerted by RSV and TOC, demonstrating protein-bioactive compounds interactions. Stern-Volmer, Scatchard and Förster resonance energy transfer models application confirmed static quenching and allowed to obtain parameters that described the 11S-RSV or 11S-TOC complexation process. Secondly, protein aggregation induced by bioactive compounds interactions was confirmed by dynamic light scattering and atomic force microscopy with diameters <150 nm, detected by both techniques. Finally, it was found that antioxidant capacity of single 11S globulin did not decrease, meanwhile was additive for 11S-RSV. These nanocomplexes could constitute a real platform for the design of nutraceutical products.

Objective: The effect of long-term performance of one-bottle or two-bottle bonding agents on the shear bond strength to lithium disilicate ceramics (LDS) were to investigate, and the long-term performance of the bond strength of two-bottle bonding agent (Tokuyama Universal Bond II) was investigated under conditions without hydrofluoric acid solution (abbreviated as HF)-pretreatment of LDS. Methods: Nine resin cements (both self-adhesive and adhesive types) were used. It was investigated 1) the adhesion strength of various resin cements to LDS from the presence or absence of HF-treatment, 2) to determine the effect of the deterioration in three times [after one-day storage (abbreviated as Base), and after 5,000 &amp; 20,000 thermocycles (abbreviated as TC 5k and TC 20k)] of one- and two-component bonding agents. And the difference in degradation between one- and two-component bonding gents consist of the silane coupling agent was performed by chemical analysis (High Performance Liquid Chromatography). Results: The trends of resin cements were statistically not very different for each cement 3 times with HF-conditions. Also ESTECEM II and Super-Bond Universal showed the significant greatest values in two conditions (TC 5k and TC 20k) without HF-condition. In TC 20k, ESTECEM II &amp; Super-Bond Universal showed significantly better results than others when treated with the recommended bonding agents without HF-condition. In TC 20k, there was not much statistically significant difference if pretreated with Tokuyama Universal Bond II without HF-condition. Significance: When using LDS, it was found that long-term durability could be maintained by pretreating with Tokuyama Universal Bond II without pretreating with various hazardous HFs.

Background. Epithelial ovarian cancer (EOC) is the deadliest gynecological malignancy worldwide. Brain metastasis (BM) is quite an uncommon presentation. However, the likelihood of central nervous system (CNS) metastasization should be considered in the context of disseminated disease. The therapeutic management of BMs is an unmet clinical need, to date. Case presentation. We identified across different Cancer Centers six cases of both BRCA wild-type and BRCA-mutated EOC spreading to the CNS. They presented either with a single brain lesion or with multiple lesions and most of them had intracranial-only disease. All cases received Poly-ADP ribose polymerase inhibitor (PARPi) maintenance, as by clinical practice, for a long time within a multimodal treatment approach. We also provide an insight into the available body of work regarding the management of this intriguing disease setting, with a glimpse of future therapeutic challenges. Conclusion. Despite the lack of unanimous guidelines, multimodal care pathways should be encouraged for optimal disease control of this unfortunate patient’s subset. Albeit not being directly investigated in BM patients, the PARPi maintenance is deemed to have a valuable role in this setting. Prospective research, aimed to implement worthwhile strategies in the multimodal patient journey of BMs from EOC, is eagerly awaited.

Background/Objectives: The aim of the project is a longitudinal assessment of body image and mental health in scoliosis females pre-, postoperatively and in a follow-up, and implementation (one group-CBT scoliosis sample, CBTSS) or not (second group-control scoliosis sample, CSS) of CBT interventions. A healthy female sample (HFS) was also selected for comparative purposes. Methods. 36 in total AIS patients participated in the 1st and 2nd study phases, whereas 23 were eligible in the follow-up. Regarding HFS, 18 participants were included in the study. The CBT intervention took place pre- and postoperatively, during the patients' stay in hospital. Participants completed the Spinal Appearance Questionnaire (SAQ), Body Esteem Scale (BES) and Strengths and Difficulties Questionnaire-25 (SDQ-25). Body image was also assessed using a virtual reality-based application “Avatar Scoliosis 3D”. Results: The difference between the desired and objective, actual body shape is significant preoperatively both in the CBTSS and CSS at p

The importance of personalized medicine is growing, since there is an urged need to avoid unnecessary and expensive treatments. In nuclear medicine, the theranostic approach is an established tool for a specific molecular targeting in means of diagnostics and therapy. The visualisation of potential targets can help to predict if a patient would benefit from a particular treatment or not. Thanks to the quick development of radiopharmaceuticals and diagnostic techniques, the use of theranostic agents is constantly rising. In this article important milestones of nuclear therapies and diagnostics in the context of theranostics are highlighted. It begins with the well-known radioiodine therapy in patients with thyroid cancer and then guides through different approaches for the treatment of advanced cancer with targeted therapies. The aim of this review is to provide a summary of background knowledge, current applications and advantages of targeted therapies and imaging in nuclear medicine practice.

Omega-3 polyunsaturated fatty acids (PUFAs) play a critical yet underappreciated role in muscle health, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Through a review of current literature, we analyze the effects of these nutrients on muscle protein synthesis, mass, strength, and recovery. Studies demonstrate that omega-3 PUFAs enhance muscle protein synthesis via the mTOR pathway and possess anti-inflammatory properties that may reduce muscle damage and atrophy, particularly in older adults. Their potential to improve muscle function and mitigate exercise-induced damage is also reviewed, highlighting relevance for athletes and active individuals. Further research on optimal dosages and long-term effects of omega-3 supplementation is needed, providing a basis for future studies and practical recommendations for leveraging these nutrients to support muscle health.

Herein we present the biocatalysed preparation of mono-N-carbamate-protected precursor of antitumoral Nutlin-3a, through enantioselective alkoxycarbonylation of meso-1,2-disubstituted-1,2-diaminoethane, using enzyme lipases and dialkyl carbonates as acylating agents. A series of supported or free lipase enzymes were screened in combination with commercially available diallyl-, diethyl and dimethyl- carbonate. The reactions were conducted at different temperatures, reaction times and with variable co-solvent systems to evaluate the effect on the enzyme catalytic activity. The best results in terms of conversion, enantiomeric excess and yield were obtained when lipase from Candida antarctica B (CAL-B) was used with diallyl carbonate (DAC) conducting the reaction solventless at 75 °C.

Conjugated polymers (CPs) offer potentials for sustainable semiconductor devices due to their low cost, and inherent molecular self-assembly. Enhanced crystallinity and molecular orientation in thin films of solution-processable CPs have significantly improved organic electronic device per-formance. In this work, three methods namely spin-coating, dip-coating, and unidirectional float-ing-film transfer method (UFTM) were utilized with their parametric optimization for fabricating RR-P3HT films. These films were then utilized for their characterization via optical and micro-structural analysis to elucidate dominant roles of molecular orientation, and crystallinity in con-trolling charge transport in organic field-effect transistors (OFETs). OFETs fabricated by RR-P3HT thin films using spin-coating and dip-coating displayed field-effect mobility (μ) of 8.0 × 10-4 cm2V-1s-1 and 1.3 × 10-3 cm2V-1s-1, respectively. This two-time enhancement in (µ for dip-coated films was attributed to its enhanced crystallinity. Interestingly, UFTM films based OFETs demon-strated μ of 7.0 × 10-2 cm2V-1s-1, >100 times increment as compared to its spin-coated counterpart This superior device performance is attributed to synergistic influence of higher crystallinity and molecular orientation. Since the crystallinity of dip-coated and UFTM-thin films are similar ~50 times improved µ of UFTM thin films suggest a dominant role of molecular orientation as com-pared to crystallinity in controlling the charge transport.

How hands-on gardening impacts behaviors including healthy eating and physical activity during early childhood can be of critical importance for preventing early onsets of obesity. This research investigates how participating in hands-on gardening impacts preschoolers’ (3-5 years old) physical activity (measured by accelerometers) in childcare centers in the Semi-Arid Climate Zone. The research was conducted in eight licensed childcare centers located in West Texas with 149 children (n=149). Four childcare centers in the experimental group received hands-on garden interventions; the other four in the control group did not. In both experimental (intervention) and control (non-intervention) centers, children wore Actigraph GT3X+ accelerometers continuously for 5 days before and for 5 days after intervention (a total of 10 days). Results show that the duration of sedentary behavior of children in the experimental (intervention) group significantly decreased compared to children in the control (non-intervention) group. The finding suggests that the positive effects of childcare hands-on gardening on physical activity extend to semi-arid climate zones where gardening is challenging due to high temperatures and lack of annual rainfall. The research emphasizes the critical need to incorporate hands-on gardening in childcare centers as an obesity prevention strategy nationally in the U.S. and beyond.

LC-SPIK is a liver cancer-specific isoform of Serine Protease Inhibitor Kazal and has been proposed as a new biomarker for the detection of HCC given its unique 3-D structure which differs from normal pancreatic SPIK. An ELISA technology based on its unique structure was developed to use LC-SPIK as an effective biomarker for the clinical diagnosis of HCC. AFP, the most widely used biomarker for HCC surveillance currently, suffers from poor clinical performance, especially in the detection of early-stage HCC. In one case-control study, which included 164 HCC patients and 324 controls, LC-SPIK had an AUC of 0.87 compared to only 0.70 for AFP in distinguishing HCC from liver disease controls (cirrhosis, HBV/HCV). LC-SPIK also performed significantly better than AFP for the 81 patients with early-stage HCC (BCLC stage 0 and A), with an AUC of 0.85 compared to only 0.61 for AFP. Cirrhosis is the major risk factor for HCC, about 80% of patients with newly diagnosed HCC have preexisting cirrhosis. LC-SPIK’s clinical performance was also studied in HCC patients with viral and non-viral cirrhosis including cirrhosis caused by nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). In a total of 163 viral cirrhosis patients with 93 HCC patients (50 early-stage), LC-SPIK had an AUC of 0.85, while AFP had an AUC of 0.70. For patients with early-stage HCC, LC-SPIK had a similar AUC of 0.83, while AFP had an AUC of only 0.60. For 120 patients with nonviral cirrhosis, including 62 HCC (23 early-stage) patients, LC-SPIK had an AUC of 0.84 while AFP had an AUC of only 0.72. For the 23 patients with early-stage HCC, LC-SPIK had a similar AUC of 0.83, while the AUC for AFP decreased to 0.65. All these results suggest that LC-SPIK has significantly better performance in the detection of HCC than AFP in all etiologies of liver diseases. In addition, LC-SPIK accurately detected the presence of HCC in 71%-91% of HCC patients with false-negative AFP test results in viral associated HCC and non-viral associated HCC.

A new approach is presented for dynamic modeling of chemical and isotopic evolution of C1-3 during the hydrocarbon generation process. Based on systematic data obtained from published papers for pyrolysis of various hydrocarbon sources(type I kerogen/source rock, type II kerogen/source rock, type III kerogen/source rock, crude oil, asphalt, etc), the empirical evolution framework of chemical and isotopic composition of C1-3 during the hydrocarbon generation process was built. Although the empirical framework was built only by fitting large amount of pyrolysis data, the chemical and isotopic composition of C1-3 derived from the pyrolysis experiments all follow the evolution laws, convincing us that it is applicable to the thermal evolution process of various hydrocarbon sources. Based on the simplified formula of the isotopic composition of mixed natural gas at different maturities (δ13Cmixed) δ13Cmixed=(X〖*n〗_iA 〖*δ〗^13 C_iA+Y〖*n〗_iB 〖*δ〗^13 C_iB)/(X〖*n〗_iA+Y〖*n〗_iB ), it can be derived that the cumulative isotopic composition of alkane generated in certain maturity interval can be expressed by the integral of the product of instantaneous isotopic composition and instantaneous yield at certain maturity point, and then divided by the cumulative yield of alkane generated in corresponding maturity interval. Thus, the cumulative isotopic composition(A(X)), cumulative yield(B(X)), instantaneous isotope(C(X)),and instantaneous yield(D(x)) in the dynamic model comply with the following formula during the maturity interval of (X0-X) A(X)=(∫_(X_0)^X▒〖C(X)*D(X)dx〗)/(B(X)), where A(X) and B(X) can be obtained by fitting of pyrolysis data, and D(x) can also be obtained from the derivation of B(X). The dynamic model was applied on the pyrolysis data of Pingliang Shale to illustrate the quantitative evolution of cumulative yield ,instantaneous yield, cumulative isotope and instantaneous isotope of C1-3 with increasing maturity.The dynamic model can quantify the yield of methane, ethane and propane as well as δ13C1, δ13C2 and δ13C3 respectively during the hydrocarbon generation process, which is of great significance to evaluate the natural gas resources of hydrocarbon source rock with different maturity and to identify the origin and evolutionary process of hydrocarbons by chemical and isotopic data. Moreover, this model provides an approach to study the dynamic evolution of isotope series of C1-3 (including reversed isotopic series), which is hopeful to reveal the mechanism responsible for isotopic reversal when combined with post-generation studies.

The current work is dedicated to the search for new high-energy materials (HEMs) with improved characteristics which are gained through agglomeration with salts. The research was performed by Becke’s three-parameter hybrid functional approach with non-local correlation provided by Lee, Yang, and Parr and cc-pVTZ basis set. The geometry, total energy, and heat of formation of the most stable compounds forming due to 3-amino-5-[(2, 4, 6-trinitrophenyl) amino]-1H-1, 2, 4-triazole (APATO) within salts selected were obtained to foresee its influence on resistance to shock stimuli, detonation pressure, and velocity of the materials under study. Results obtained allow us to foresee that only agglomeration with precise salts could lead to significant improvement in the stability of the specific high-energy materials and the resistance to shock stimuli. We also show that the agglomeration leads to better energetic properties of the above compound, although the improvement could be insignificant in some cases.

This article presents the results of studies of the structure and conductive properties of Na3Fe2(PO4)3 polycrystals synthesized by solid-phase and melt (using concentrated optical radiation) methods. It has been established that with the melt method, the synthesis of the material occurs under significantly nonequilibrium temperature-gradient conditions, which leads to the creation of deformations in the sample that contribute to an increase in ionic conductivity. The ability of the Na3Fe2(PO4)3 structure to adapt to anomalous deformations that occur under temperature-gradient conditions indicates the elasticity of the crystalline framework {[Fe2(PO4)]3-}3∞. Through a comparative assessment of the structural parameters and conductive properties of these materials, it is shown that polycrystals obtained by the melt method have a better texture and greater ionic conductivity. The advantage of this method is that the duration of the synthesis of α-Na3Fe2(PO4)3 is halved. It is concluded that this method is applicable to obtain effective polycrystals of other compositions.

Objectives: To evaluate the relationship between the type of conization, the volume and dimensions of the cone, with the persistence/recurrence of CIN 2-3, presence of affected margins and post-cone HR-HPV positivity. Methods: 227 women treated with LLETZ and histologically confirmed CIN2-3 were evaluated between 1996 and 2006 and followed up until June 2016. Age, type of resection according to IFCPC 2011, volume, cone dimensions, margins were studied. of resection, post-cone high-risk human papillomavirus (HR-HPV) status and viral load. Determinants of HR-HPV positivity were estimated using unconditional logistic regression and time to recurrence was assessed using Kaplan-Meier curves. Results: Persistent/recurrent CIN2-3 was found in 12 cases (5.2%), type 1 conization was performed in 81 patients, with 5 recurrences (6.1%), type 2 in 101 patients, with 6 recurrences (5 .9%) and type 3 resection in 45 women, with 1 recurrence (2.2%). Volume and dimensions were not associated with recurrence. The Log-Rank Test did not show a significant difference between the 3 treatments (p= 0.18). The free margins in type 1 were 37%, in type 2 resection 61% and in type 3 71% (p=0.001). Resection type 1 had 15% HR-HPV post positive cone, type 2 reached 16% and type 3 had 9%, this difference being non-significant (p=0.58). The incidence of recurrence at 36 months in type 1 resection was 0.08%, in type 2 treatment it was 0.04% and in type 3 resection it was 0.0%. Conclusions : Type 3 resection had a higher proportion of free margins and lower post-cone HR-HPV positivity, with a lower incidence of persistence/recurrence.

Breast cancer (BCa) is the most frequently diagnosed malignant tumor in women and is also one of the leading causes of cancer-related death. Most breast tumors are hormone-dependent and estrogen signaling plays a critical role in promoting the survival and malignant behaviors of these cells. Estrogen signaling involves ligand-activated cytoplasmic estrogen receptors that translocate to the nucleus with various co-regulators such as steroid receptor co-activator (SRC) family members, and bind to the promoters of target genes and regulate their expression. SRC-3 is a member of this family that interacts with, and enhances the transcriptional activity of the ligand activated estrogen receptor. Although SRC-3 has important roles in normal homeostasis and developmental processes, it has been shown to be amplified and overexpressed in breast cancer and to promote malignancy. The malignancy-promoting potential of SRC-3 is diverse and involves both promoting malignant behavior of tumor cells and creating a tumor microenvironment that has an immunosuppressive phenotype. SRC-3 also inhibits the recruitment of tumor-infiltrating lymphocytes with effector function and promotes stemness. Furthermore, SRC-3 is also involved in the development of resistance to hormone therapy and immunotherapy during breast cancer treatment. The versatility of SRC-3 in promoting breast cancer malignancy in this way makes it a good target, and methodical targeting of SRC-3 probably will be important for the success of breast cancer treatment.

Ribotoxin-like proteins (RL-Ps) are specific ribonucleases found in mushrooms that are able to cleave a single phosphodiester bond located in the Sarcin-Ricin Loop (SRL) of the large rRNA. The cleaved SRL interacts differently with some ribosomal proteins (P-stalk). This action blocks protein synthesis because the damaged ribosomes are unable to interact with elongation factors. Here, the amino acid sequence of eryngitin 3 and 4, RL-Ps isolated from Pleurotus eryngii fruiting bodies, was determined to: i) obtain structural information on this specific ribonuclease family from edible mushrooms; and ii) explore the structural determinants which justify their different biological and antipathogenic activities. Indeed, eryngitin 3 (exhibited higher toxicity with respect to eryngitin 4 against tumoral cell lines and model fungi. Structurally, eryngitin 3 and 4 consist of 132 amino acids, most of them identical and exhibit a single free cysteinyl residue. The amino acidic differences between the two toxins are: i) an additional phenylalanyl residue at the N-terminus of eryngitin 3, not retrieved in eryngitin 4; and ii) an additional arginyl residue at C-terminus of eryngitin 4, not retrieved in eryngitin 3. The 3D-models of eryngitins show slight differences at the N- and C-terminal regions. In particular, the positive electrostatic surface at C-terminal of eryngitin 4 is due to the additional arginyl residue not retrieved in eryngitin 3. This additional positive charge could interfere with the binding to the SRL (substrate) or with some ribosomal proteins (P-stalk structure), during substrate recognition.

Ingrown toenails are a commonly occurring foot complaint. The condition occurs when the nail plate pierces the sulcus, giving rise to pain, inflammation and infection. As the skin attempts to heal itself, hypergranulation tissue may form. This is a case report of phenolic nail surgery treatment for a bilateral presentation with sharp resection of hypergranulation tissue performed in only one (the lateral) of the two affected sulci. Sharp resection of the residual medial hypergranulation tissue was performed two months after the index procedure when this had not settled. The case highlights the potential role of sharp resection in the overall improvement of treatment outcomes.

The Surface Urban Heat Island (UHI) is caused by the difference in temperature between the urban and its surrounding areas. However, in the scientific literature, there is no solid methodology defining urban and non-urban areas, which is essential to estimate the SUHI with greater accuracy. This study uses the official national urban areas limit, to obtain the SUHI more accurately on the nine northeastern Brazilian capitals. The land surface temperature was obtained using the Sentinel 3 satellite data for the years 2019 and 2020. Afterward, the maximum and average SUHI, and the complementary indexes were calculated, such as the Urban Thermal Field Variation Index (UTFVI) and the Thermal Discomfort Index (TDI) for the urban areas and their surrounding areas. The Maximum and Average SUHI, obtained values between 1.85 and 8.25 and -4.92 and 2.59 degree difference, respectively, proving the SUHI existence in the study areas. The UTFVI, with values between 0.010 and 0.040, expresses how bad the eco-environmental spaces of urban are. The TDI, with values between 24.61 and 28.89 ºC, expresses the population’s thermal comfort. Therefore, this study provides a better understanding of the surface UHI pioneeringly for the Brazilian Northeast Region.

Breaching and liquefaction are two types of coastal flow slides proposed in the literature. While their final results are similar, liquefaction and breaching failure are two different processes, with breaching failure characterized by a different progression and sand movement mechanisms. In densely packed sand, breaching causes delayed sand grain discharge and negative excess pore pressures. Liquefaction, when a mass of soil suddenly behaves like a liquid, flow out over overly gentle slopes. Flow slides typically go unnoticed until the slope fails above ground because they start below the water. Without modern technology, diving equipment, risk assessment, and probabilistic and sensitivity assessments, flow slides inherently challenging. The authors developed a new sensitivity index to detect the susceptibility of coastal flow slides. It was established a sophisticated hybrid model that accommodates flow slides in sync with unpredictable variables employed in this new sensitivity index. Innovative hybrid model has three distinctive models. The Hybrid Hydrodynamic Model addresses wave, wind, current, climate change, and sediment transfer. The Monte Carlo Simulation analyses sensitivity, and the Bayesian Network calculates joint probability of coastal flow slide parameters of this new index that includes environmental characteristics, including climate change. With the assistance of these three models, researchers aim at a) presenting a methodology for coupling coastal flow slide projections with outcomes; b) distinguishing two flow slides; c) examining variables influencing flow slides. The use of such a hybrid model and risk index offers a robust and computationally efficient approach to evaluating the critical angle slope for breaching failure.

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

Evolutionary, sequence and structural analyses of tRNA variable (V) loops provides a new understanding. Type I tRNA V loops have a primordial length of 5 nt, and type II tRNA V loops have a primordial length of 14 nt. Sequence-based alignments of type I and type II V loops gave deceptive results. Type II V loops are characterized by the trajectory of the V arm, the size and sequence of the loop and the first and last V loop nucleotides and their known contacts. Depending on the V arm trajectory, type II V stems and loops can be interaction sites for aminoacyl-tRNA synthetases. So, type II V arms for tRNALeu, tRNASer and tRNATyr (found in Bacteria) were coevolved and selected to distinguish determinants to support cognate tRNA charging. The alignment of type I and type II V loops was adjusted based on tRNA evolution. Results are consistent with Archaea being an older and simpler life form than Bacteria. TRNAome sequences were derived from radiation of an ordered tRNAPri (Pri for primordial) sequence comprised of known RNA repeats and inverted repeats. V loop and tRNA sequences, therefore, convey a history of the primary successful pathway in the origin of life.

Fusarium culmorum is a major pathogen of grain crops. Infected plants accumulate deoxynivalenol (DON), 3-acetyl-deoxynivalenol (3-ADON), or nivalenol (NIV), which are mycotoxins of the trichothecene B group. These toxins are also produced by F. graminearum species complex. New trichothecenes structurally similar to trichothecenes B but lacking the carbonyl group on C-8, designated NX toxins, were recently discovered in atypical isolates of F. graminearum from North America. Only these isolates and a few strains of a yet to be characterized Fusarium species from South Africa are known to produce NX-2 and other NX toxins. Here we report that among 20 F. culmorum strains isolated from maize, wheat, and oat in Europe and Asia over a period of 70 years, 18 strains produced NX-2 simultaneously with 3-ADON and DON or NIV. Rice cultures of strains producing 3-ADON accumulated NX-2 in amounts corresponding to 2-8% of 3-ADON (1.2 - 36 mg/kg). A strain producing NIV accumulated NX-2 and NIV at comparable amounts (13.6 and 10.3 mg/kg, respectively). In F. graminearum, producers of NX-2 possess a special variant of cytochrome P450 monooxygenase encoded by TRI1 that is unable to oxidize C-8. In F. culmorum, producers and nonproducers of NX-2 possess identical TRI1; the reason for the production of NX-2 is unknown. Our results indicate that production of NX-2 simultaneously with trichothecenes B is a common feature of F. culmorum.

Films prepared from poly(3-hydroxybutyrate-co-4-hydroxybutyrate) copolymers produced by Aneurinibacillus sp. H1 using an automatic film applicator were homogeneous and had a defined thickness, which allowed a detailed study of physicochemical properties. Their properties were compared with a poly (3-hydroxybutyrate) homopolymer film prepared by the same procedure, which proved to be significantly more crystalline by DSC and XRD. Structural differences between samples had a major impact on their properties. With increasing 4-hydroxybutyrate content, the ductility and release rate of the model hydrophilic active ingredient increased significantly. Other observed properties, such as the release of the hydrophobic active substance, the contact angle with water and ethylene glycol, or the surface morphology and roughness, were also affected by the composition. The identified properties predetermine these copolymers for wide use in areas such as biomedicine or smart biodegradable packaging for food or cosmetics. The big advantage is the possibility of fine-tuning properties simply by changing the fermentation conditions.

A reliable and practical renal-lipid quantification and imaging method is needed. Here, the feasibility of an accelerated MRSI method to map renal fat fractions (FF) at 3T and its repeatability were investigated. A 2D density-weighted concentric-ring-trajectory MRSI was used to accelerate acquiring 48×48 voxels (each of 0.25 ml spatial-resolution) without respiratory navigation implementations. The data was collected over 512 complex-FID timepoints with a 1250 Hz spectral bandwidth. The MRSI sequence was designed with a metabolite-cycling technique for lipid-water separation. The in vivo repeatability performance of the sequence was assessed by conducting a test-reposition-retest study within healthy subjects. The coefficient of variation (CV) in the estimated FF from the test-retest measurements showed a high degree of repeatability of the MRSI-FF (CV= 4.3 ±2.5%). Additionally, the matching level of spectral signature within the same anatomical region was also investigated, and their intrasubject repeatability was also high, with a small standard deviation (8.1 ±6.4%). The MRSI acquisition duration was ~3 minutes only. The proposed MRSI technique can be a reliable technique to quantify and map renal metabolites within a clinically acceptable scan time at 3T that supports the future application of this technique for the non-invasive characterization of heterogeneous renal diseases and tumors.