Apis mellifera, especially weak ones, are highly vulnerable to Carpoglyphus lactis mites, which can rapidly infest and consume stored pollen, leading to weakened colonies and potentially colony collapse. This study aimed to ascertain and investigate the prevalence of this mite in honeybee colonies across 9 provinces in the Republic of Korea (ROK). A total of 615 honeybee colonies were collected, from 66 apiaries during the spring and 58 apiaries during the summer of 2023. A 1,242 bp segment of the the Cytochrome c oxidase subunit 1 (COI) gene was amplified using the polymerase chain reaction method. The detection levels of C. lactis in the honeybees were compared between winter and summer. Based on the COI sequence analysis, the nucleotide sequence similarity of C. lactis mites isolated in the ROK with those from China (NC048990.1) was found to be 99.5%, and with those from the United Kingdom (KY922482.1) was 99.3%. This study is the first report of C. lactis in Korean apiaries. The findings in this study demonstrate a significantly higher detection rate in winter, which is 4.1 times greater than that in summer (p < 0.001). Furthermore, the results underscore the usefulness of molecular diagnostic techniques for detecting C. lactis mites.

Candidiasis is considered an emerging public health concern because of the occurrence of drug-resistant Candida strains and the lack of available structurally diverse antifungal drug armamentariums. The indole alkaloid globospiramine from the anticandidal Philippine medicinal plant Voacanga globosa exhibits a variety of biological activities; however, its antifungal properties remain to be explored. In this study, we report the in vitro antifungal activities of globospiramine against Candida albicans and Candida tropicalis and explore its possible target proteins using in silico methods. The colony-forming unit (CFU) viability assay revealed time- and concentration-dependent anticandidal effects of the alkaloid by decreasing almost 50% of the viable CFUs 60 min after treatment. Results of the MIC and MFC assays indicated inhibitory and fungicidal effects of globospiramine against C. albicans (MIC = 8 µg/mL; MFC = 4 µg/mL) and potential fungistatic effects against C. tropicalis at lower concentrations (MIC = 4 µg/mL; MFC > 64 µg/mL). The FAM-FLICA poly-caspase assay showed metacaspase activation in C. albicans cells at concentrations of 16 and 8 µg/mL, which agreed with the MIC and MFC values. Molecular docking and molecular dynamics simulation experiments indicated stable, strong binding of globospiramine with the target proteins 1,3-β-glucan synthase and Als3 adhesin enzymes, which are indirectly involved in apoptotic-driven candidal inhibition.

The olive tree (Olea europaea L.) is an evergreen tree that occupies 19% of the woody crop area and is cultivated in 67 countries on five continents. The largest olive production is concentrated in the Mediterranean basin, where the olive tree has had an enormous economic, cultural and environmental impact since the 7th century BC. In the Mediterranean region, salinity stands out as one of the main abiotic stress factors significantly affecting agricultural production. Moreover, climate change is expected to lead to increased salinisation in this region, threatening olive productivity. Salt stress causes combined damage by osmotic stress and ionic toxicity, restricting olive growth and interfering with multiple metabolic processes. A large variability in salinity tolerance among olive cultivars has been described. This paper aims to synthesize information from the published literature on olive adaptations to salt stress and its importance in salinity tolerance. The morphological, physiological, biochemical, and molecular mechanisms of olive tolerance to salt stress are reviewed.

Despite available global efforts and funding, Tuberculosis (TB) continues to affect a considerable number of patients worldwide. Policy makers and stakeholders set clear goals to reduce TB incidence and mortality, but the emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) complicate the reach of these goals. Drug-resistance TB needs to be diagnosed rapidly and accurately to effectively treat patients, prevent the transmission of MDR-TB, minimise mortality, reduce treatment costs and avoid unnecessary hospitalisations. In this narrative review, we provide a comprehensive overview of laboratory methods for detecting drug resistance in MTB, focusing on phenotypic, molecular and other drug susceptibility testing (DST) techniques. We found a large variety of methods used, with the BACTEC MGIT 960 being the most common phenotypic DST and the Xpert MTB/RIF being the most common molecular DST. We emphasise the importance of integrating phenotypic and molecular DST to address issues like resistance to new drugs, heteroresistance, mixed infections and low-level resistance mutations. Notably, most of the analysed studies adhered to the outdated definition of XDR-TB and did not consider the pre-XDR definition, thus posing challenges in aligning diagnostic methods with the current landscape of TB resistance.

Obesity has increasingly become a worldwide epidemic, as demonstrated by epidemiological and clinical studies. Obesity may lead to development of a broad spectrum of cardiovascular diseases (CVDs), such as coronary heart disease (CHD), hypertension, heart failure (HF), cerebrovascular disease, atrial fibrillation (AF), ventricular arrhythmias, and sudden cardiac death (SCD). In addition to hypertension, there are other cardiometabolic risk factors (CRFs) such as visceral adiposity, dyslipidemia, insulin resistance, diabetes, elevated levels of fibrinogen, and C-reactive protein and others, all of which increase the risk of CVD events. Mechanisms involved between obesity and CVD mainly include insulin resistance, oxidative stress, inflammation, and adipokines dysregulation, which cause maladaptive structural and functional alterations of the heart, particularly left ventricular (LV) remodeling and diastolic dysfunction. Natural products of plants, provide a diversity of nutrients and different bioactive compounds, including phenolics, flavonoids, terpenoids, carotenoids, anthocyanins, vitamins, minerals, fibers, and others, which possess a wide range of biological activities including antihypertensive, antilipidemic, antidiabetic, and other activities, thus conferring cardiometabolic benefits. In this review, we discussed the main therapeutic interventions using extracts from herbs and plants in preclinical and clinical trials with protective properties targeting CRFs. Molecular mechanisms and therapeutic targets of herbs and plants extracts for the prevention and treatment of CRFs are also reviewed.

CO2 geological sequestration in coal seams can achieve the dual objectives of CO2 emission reduction and enhanced coalbed methane production, making it a highly promising carbon capture and storage technology. However, the injection of CO2 into coal reservoirs in the form of supercritical fluid (ScCO2) leads to complex physicochemical reactions with the coal seam, altering the properties of the coal reservoir and impacting the effectiveness of CO2 sequestration and methane production enhancement.In this paper, theoretical calculations based on ReaxFF-MD were conducted to study the interaction mechanism between ScCO2 and the macromolecular structure of both low-rank and high-rank coal, to address the limitations of experimental methods. The reaction of ScCO2 with low-rank coal and high-rank coal exhibits significant differences. At swelling stage, the low-rank coal experiences a decrease in aromatic structure and aliphatic structure, high-rank coal shows an increase in aromatic structure and a decrease in aliphatic structure, while swelling phenomenon is more pronounced in high-rank coal. At dissolution stage, low-rank coal is initially decomposed into two secondary molecular fragments, and then recombine to form new molecular structure, the aromatic structure increased and the aliphatic structure decreased. In contrast, high-rank coal occurs stretches-breakage-movement-reconnection, a reduction in aromatic structure and an increase in aliphatic structure.The primary reasons for these variations lie in distinct molecular structure compositions and the properties of ScCO2, leading to different reaction pathways of functional group and aromatic structure. The reaction pathways of functional groups and aromatic structures in coal can be summarized as follows: the breakage of the O-H bond in hydroxyl groups, the breakage of the C-OH bond in carboxyl groups, transformation of aliphatic structures into smaller hydrocarbon compounds or formation of long-chain alkenes, and various pathways involving broken, rearrangement, recombination of aromatic structures. In low-rank coal, there is a higher abundance of oxygen-containing functional groups and aliphatic structures. The breakage of O-H and C-OH chemical bonds results in the formation of free radical ions, while some aliphatic structures detach to produce hydrocarbons. Additionally, some of these aliphatic structures combine with carbonyl groups and free radical ions to generate new aromatic structures. Conversely, in high-rank coal, the lower content of oxygen-containing functional groups and aliphatic structures, along with stronger intramolecular forces, results in fewer chemical bond breakages and makes it less conducive to the formation of new aromatic structures.These results elucidate the specific deformations of different chemical groups, offering a molecular-level understanding of the interaction between CO2 and coal.

Kidneys of mice, rats and humans possess progenitors that maintain daily homeostasis and take part in endogenous regenerative processes following injury, owing to their capacity to proliferate and differentiate. In the glomerular and tubular compartments of the nephron, consistent studies demonstrated that well-characterized, distinct populations of progenitor cells, localized in the parietal epithelium of Bowman capsule and scattered in the proximal and distal tubules, could generate segment-specific cells in physiological conditions and following tissue injury. However, defective or abnormal regenerative responses of these progenitors can contribute to pathologic conditions. The molecular characteristics of renal progenitors have been extensively studied, revealing that numerous classical and evolutionarily conserved pathways, such as Notch or Wnt/β-catenin, play a major role in cell regulation. Others, such as retinoic acid, renin-angiotensin-aldosterone system, TLR2 (Toll-Like Receptor 2) and leptin, are also important in this process. In this review, we summarize the plethora of molecular mechanisms directing renal progenitor responses during homeostasis and following kidney injury. Finally, we will explore how single cell RNA sequencing could bring the characterization of renal progenitors to the next level, while knowing their molecular signature is gaining relevance in the clinic.

Infectious diseases are a global health problem affecting billions of people. Developing rapid and sensitive diagnostic tools is key for successful patient management and curbing disease spread. Currently available diagnostics are very specific and sensitive but time-consuming and require expensive laboratory settings and well-trained personnel; thus, they are not available in resource-limited areas, for the purposes of large-scale screenings and in case of outbreaks and epidemics. Developing new, rapid, and affordable point-of-care diagnostic assays is urgently needed. This review focuses on CRISPR-based technologies and their perspectives to become platforms for point-of-care nucleic acid detection methods and as deployable diagnostic platforms that could help to identify and curb outbreaks and emerging epidemics. We describe the mechanisms and function of different classes and types of CRISPR-Cas systems, including pros and cons for developing molecular diagnostic tests and applications of each type to detect a wide range of infectious agents. Many Cas proteins (Cas9, Cas12, Cas13, Cas14) have been leveraged to create highly accurate and sensitive diagnostic tools combined with technologies of signal amplification and fluorescent, potentiometric, colorimetric, or lateral flow assay detection. In particular, the most advanced platforms -- SHERLOCK/v2, DETECTR, or CRISPR-Chip -- enable detection of attomolar amounts of pathogenic nucleic acids with specificity comparable to that of PCR but with minimal technical settings. Further developing CRISPR-based diagnostic tools promises to dramatically transform molecular diagnostics, making them easily affordable and accessible virtually anywhere in the world. The burden of socially significant diseases, frequent outbreaks, recent epidemics (MERS, SARS and the ongoing coronoviral nCov-2019 infection) urgently need the developing of express-diagnostic tools. Recently devised CRISPR-technologies represent the unprecedented opportunity to reshape epidemiological surveillance and molecular diagnostics.

Background: The bacterium Capnocytophaga spp. is a part of the oral microbiome of dogs, which has zoonotic potential. This study aimed to assess factors that influence the prevalence of Capnocytophaga cynodegmi and Capnocytophaga canimorsus in Wrocaw’s dog population. Methods: Molecular detection (PCR) involved 105 swabs, examining parameters such as oral cavity condition, underlying health issues, recent antibiotics, age, medications, material collection, and dog chews. Results: The study highlighted significant associations between the presence of Capnocytophaga cynodegmi and oral cavity condition, material collection method, and use of dog’s chews. Conclusions: Correlations obtained in this study between the oral health of Wroclaw's dog population and the presence of Capnocytophaga cynodegmi suggest its significance in the oral microbiome of dogs. Limitations, including the small sample size, highlight the need for more research to comprehensively understand additional factors that affect the prevalence of Capnocytophaga spp. in dogs

Trichoderma has been widely studied for its potential as a biocontrol agent against plant pathogenic organisms. Trichoderma's biological control mechanisms include competition, modification of environmental conditions, antibiosis, induction of plant defensive mechanisms, and mycoparasitism. Trichoderma species are known to produce a variety of secondary metabolites that have antifungal activity. These metabolites include peptaibols, gliotoxin, and trichokonins. Trichoderma also produces chitinases and β-1,3-glucanases that can degrade the cell walls of fungal pathogens. In addition to direct antagonism against fungal pathogens, Trichoderma can also induce systemic or localised resistance in plants, which is achieved through the production of elicitors such as chitin oligosaccharides and β-glucans that activate plant defence responses. Trichoderma can also form mutualistic associations with plants. In these associations, Trichoderma colonises the roots of plants and promotes plant growth by increasing nutrient uptake and inducing systemic resistance. Using Trichoderma as a biocontrol agent has several advantages over conventional crop protection techniques based on applying synthetic pesticides.

It’s been reported that Mori Folium (MF) and Eucommiae Cortex (EC) exhibit pharmacological effects on the treatment of immunosuppression. However, the mechanism of MF and EC against immunosuppression remains unclear. This study aims to explore the mechanism of action of MF and EC for the treatment of immunosuppression through network pharmacology, molecular docking, molecular dynamics simulations and animal experiments. As a result, 11 critical components, 9 hub targets, and related-signaling pathways of treatment of immunosuppression were obtained based on network pharmacology. The molecular docking suggested that 11 critical components exhibited great binding affinity to 9 hub targets of immunosuppression. The molecular dynamics simulations results showed that (-)-Tabernemontanine-AR, beta-sitosterol-AR and Dehydrodieugenol-HSP90AA1 complexes are stably bound. Additionally, in the animal experiments, the treated group results compared to the control group suggest that MF and EC have a significant effect on the treatment of immunosuppression. Therefore, the MF and EC treatment for immunosuppression may take effects in a multi-component, multi-target, and multi-pathway manner. The results would provide novel insights into the treatment of immunosuppression in humans.

Muscle is one of the most critical organs for mammals, which governs multiple movement and physiological functions. Circular RNA (circRNA) is a kind of novel endogenous RNA without 5'-Caps and 3'-poly(A) structures formed by pre-mRNA's back-splicing. RNA binding proteins (RBPs) control the production and degradation of circRNA, help nucleus-cytoplasm transport and locate circRNA, and regulate circRNA translation. Therefore, circRNAs and the chaperoned RBPs play critical roles in muscle growth, development, and disease progression. In this review, we systematically characterize the possible molecular mechanism of circRNA-protein interactions. Also, we summarize the latest researches on circRNA-protein interactions in muscle development and diseases. Besides, we provide several valid prediction methods and experimental verification approaches. Our review reveals the importance of circRNAs and their protein chaperones and provides a reference for further study in this field.

A sedentary lifestyle associated with unregulated diets rich in high-calorie foods have contributed to the great prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) latterly, with up to 60% in high-risk population and 25% in the general population. The absence of specific pharmacological strategies for this syndrome represents one of the major problems in the management of MASLD patients. Lifestyle interventions and adherence to a healthy diet are the main cornerstones of current therapies. The identification of nutraceuticals useful in the treatment of MASLD appears to be one of the most promising strategies for the development of new effective and safe treatments for this disease. The onion, one of the most widely studied foods in the field of nutraceuticals, serves as an inexhaustible reservoir of potent compounds with various beneficial effects. The following preliminary study analyses, mediating in silico studies, the iteration of a library of typical onion compounds with 3-hydroxy-3-methylglutaryl-coenzyme A reductase, Liver receptors X α and β as well as Peroxisome proliferator-activated receptors α and γ. In this study fort the first time promising smart molecules from the onion that could have a beneficial action in MASLD patients were identified.

Cancer cells utilize a number of mechanisms to increase their survival and progression as well as their resistance to anticancer therapy: deregulation of growth regulatory pathways by acquiring grow factor independence, immune system suppression, reducing the expression of antigens activating T lymphocyte cells (mimicry), induction of anti-apoptotic signals to counter the action of drugs, activation of several DNA repair mechanisms and driving the active efflux of drugs from the cell cytoplasm and epigenetic regulation by microRNAs (miRNAs). Due to the fact that it is commonly diagnosed late, lung cancer remains a major malignancy with a low five-year survival rate; when diagnosed, the cancer is often highly advanced and the cancer cells may have acquired drug resistance. This review summarizes the main mechanisms involved in cisplatin resistance and in interactions between cisplatin-resistant cancer cells and the tumor microenvironment. It also analyses changes in the gene expression profile of cisplatin sensitive vs. cisplatin resistant non–small cell lung cancer (NSCLC) cellular model using the GSE108214 Gene Expression Omnibus database. It describes a protein-protein interaction network that indicates highly-dysregulated TP53, MDM2 and CDKN1A genes as they encodes the top networking proteins that may be involved in cisplatin tolerance, these all being upregulated in cisplatin-resistant cells. Furthermore, it illustrates the multifactorial nature of cisplatin resistance by examining the diversity of dysregulated pathways present in cisplatin-resistant NSCLC cells based on KEGG pathway analysis.

Rice, a globally important food crop, faces significant challenges due to salt and drought stress. These abiotic stresses severely impact rice growth and yield, manifesting as reduced plant height, decreased tillering, reduced biomass, and poor leaf development. Recent advances in molecular biology and genomics have uncovered key physiological and molecular mechanisms that rice employs to cope with these stresses, including osmotic regulation, ion balance, antioxidant re-sponses, signal transduction, and gene expression regulation. Transcription factors such as DREB, NAC, and bZIP, as well as plant hormones like ABA and GA, have been identified as crucial reg-ulators. Utilizing CRISPR/Cas9 technology for gene editing holds promise for significantly en-hancing rice stress tolerance. Future research should integrate multi-omics approaches and smart agriculture technologies to develop rice varieties with enhanced stress resistance, ensuring food security and sustainable agriculture in the face of global environmental changes.

The tsscds method, recently developed in our group, discovers chemical reaction mechanisms with minimal human intervention. It employs accelerated molecular dynamics, spectral graph theory, statistical rate theory and stochastic simulations to uncover chemical reaction paths and to solve the kinetics at the experimental conditions. In the present review, its application to solve mechanistic/kinetics problems in different research areas will be presented. Examples will be given of reactions involved in photodissociation dynamics, mass spectrometry, combustion chemistry and organometallic catalysis. Some planned improvements will also be described.

The subject of this article is the dynamics of water in a soil pedostructure sample whose internal environment is subjected to a potential gradient created by the departure of water through surface evaporation. This work refers entirely to the results and conclusions of a fundamental theoretical study focused on the molecular thermodynamic equilibrium of the two aqueous phases of the soil pedostructure. The new concepts and descriptive variables of the hydro-thermodynamic equilibrium state of the soil medium, which have been established at the molecular level of the fluid phases of the pedostructure (water and air) in a previous article, are recalled here in the systemic paradigm of hydrostructural pedology. They allow access to the molecular description of water migration in the soil and go beyond the classical mono-scale description of soil water dynamics. We obtain a hydro-thermodynamic description of the soil's pedostructure at different hydro-functional scale levels including those relating to the water molecule and its atoms. The experimental results show a perfect agreement with the theory, validating at the same time the systemic approach which was the framework.

Peyronie's disease (PD) is a benign condition caused by plaque formation on the tunica albuginea of the penis. It is associated with penile pain, curvature, and shortening, and contributes to erectile dysfunction, which worsens patient quality of life. In recent years, understanding of the detailed mechanisms and risk factors involved in development of PD has been increasing. In this review, the pathological mechanisms and several closely related signaling pathways, including TGF-β, WNT/β-catenin, Hedgehog, YAP/TAZ, MAPK, ROCK, and PI3K/AKT, are described. Findings regarding cross-talk among these pathways are then discussed to elucidate the complicated cascade behind tunica albuginea fibrosis. Finally, various risk factors including genetic involved in the development of PD are presented and their association with the disease summarized. The purpose of this review is to provide better understanding regarding involvement of risk factors in the molecular mechanisms associated with PD pathogenesis, as well as provide insight into disease prevention and novel therapeutic interventions.

In humans, coronaviruses can cause infections of the respiratory system, with damage of varying severity depending on the virus examined: ranging from mild or moderate upper respiratory tract diseases, such as the common cold, to pneumonia, severe acute respiratory syndrome, kidney failure and even death. Human coronaviruses known to date, common throughout the world, are seven. The most common - and least harmful - ones were discovered in the 1960s and cause a common cold. Others, more dangerous, were identified in the early 2000s and cause more severe respiratory tract infections. Among these the SARS-CoV, isolated in 2003 and responsible for the Severe Acute Respiratory Syndrome (the so-called SARS), which appeared in China in November 2002, the Coronavirus 2012 (2012-nCoV) cause of the Middle Eastern Respiratory Syndrome from Coronavirus (MERS), which exploded in June 2012 in Saudi Arabia, and actually SARS-CoV-2. On December 31, 2019, a new Coronavirus strain was reported in Wuhan, China, identified as a new Coronavirus beta strain ß-CoV from Group 2B, with a genetic similarity of approximately 70% to SARS-CoV, the virus responsible. of SARS. In the first half of February, the International Committee on Taxonomy of Viruses (ICTV), in charge of the designation and naming of the viruses (i.e., species, genus, family, etc.), thus definitively named the new coronavirus as SARS-CoV-2. This article highlights the main knowledge we have about the biomolecular and pathophysiologic mechanisms of SARS-CoV-2.

Crossostephium chinense is a wild species with strong salt tolerance, which has great potential to improve the salt tolerance of cultivated chrysanthemums. Conversely, the unique salt-tolerant molecular mechanisms of Cr. chinense are still unclear. This study performed a comparative physiological and transcriptome analysis of Cr. chinense, Chrysanthemum lavandulifolium and their hybrids. The physiological results showed that Cr. chinense maintained a higher superoxide dismutase (SOD) activity, to alleviate the oxidative damage to membrane. KEGG enrichment analysis showed that the plant hormone signaling transduction and the MAPK signaling pathway were mostly enriched in Cr. chinense and hybrids under salt stress. Further weighted gene co-expression network analysis (WGCNA) of DEGs suggested that the abscisic acid (ABA) signaling transduction may play a significant role in the salt-tolerant mechanisms of Cr. chinense and hybrids. The tissue-specific expression patterns of the candidate genes related to ABA signaling transduction and MAPK signaling pathway indicated that genes related to ABA signaling transduction performed significant expression levels under salt stress. This study provides a theoretical foundation for future research into the molecular mechanism of salt tolerance in chrysanthemums under salt stress.

Adipose tissue has acquired considerable importance due to its role in maintaining body homeostasis. Beyond storing energy, adipose tissue is essential in numerous processes of energy metabolism, food intake, endocrine and immunological functions as well as neromodulatory functions by secreting hormones that participate in the regulation of homeostasis and being responsive to soluble proteins secreted by other tissues. An imbalance of these functions will generate structural and functional changes in the adipose tissue, favouring the secretion of deleterious adipocytokines that benefit a pro-inflammatory state, allowing the development of metabolic and cardiovascular diseases. Obesity is a disease that has increased rapidly in recent decades and is caused by environmental, hormonal, and genetic factors, which probably work in combination. Environmental factors that contribute to the increase in obesity include decreased physical activity, associated with increased screen time, increased accessibility and consumption of foods rich in fats and sugars. Weight loss should be recommended for all obese patients and overweight patients with comorbidities. For many patients who need to lose weight for medical reasons, the initial goal is to lose 5-10% of their body weight in the first 6 months. A common theme worldwide has been the development of professional guidelines for the control and treatment of obesity and in Chile, the Chilean Society of Metabolic and Bariatric Surgery led the process of adopting the adult obesity clinical practice guideline, which establishes changes in the approach to managing obesity as a chronic disease, with an emphasis on multifactorial lifestyle interventions that include dietary changes, increased physical activity, and behavioural modifications. Pharmacotherapy, medical devices, and bariatric surgery are other options for patients who need additional interventions, so the objective of this review is to know the pathophysiological mechanisms of obesity from its origin to the current treatments available for treatment.

Anthracnose stands as the primary obstacle to lupin cultivation, impeding development despite the considerable agronomic, ecological, and economic potential of such legume crops. This review explores recent efforts to unravel the complexities of anthracnose in domesticated lupins, focusing on both the plant perspective and the causative pathogenic agent, Colletotrichum lupini. Leveraging cutting-edge technologies has yielded crucial insights into various facets of this devastating disease, encompassing plant and pathogen biology, genetic and molecular regulations of the interaction, fungal diversity and population dynamics, and screening of plant genetic resources for anthracnose resistance. The lack of effective disease control measures, relying primarily on the use of disease-free seeds, highlights the need to develop anthracnose-resistant varieties. However, challenges arise from the intricacy of lupin's response to the disease, influenced by polygenic inheritance, in spite of loci with major effects, and environmental factors. The slow pace of genetic improvement underscores the need for more efficient breeding processes, including biotechnological approaches. This review offers a comprehensive overview of current progress and knowledge gaps, stressing the urgent need to further enhance understanding of C. lupini pathogenic mechanisms and lupin‘s resistance. Integrating advanced technologies and accelerated research efforts is paramount for achieving efficient disease management and sustainable lupin cultivation in the face of anthracnose challenges.

Hyperlipidemia (HLP) is a metabolic disease caused by abnormal lipid metabolism. Recently, the prevalence of HLP caused by poor dietary habits in the population has been increasing yearly. In addition, the current clinical use of lipid-lowering drugs has significant ameliorating effects on lipid levels but these actions are accompanied by certain side effects. However, bioactive marine substances have been verified to have various physiological activities such as hypoglycemic, antioxidant, antithrombotic, and effects on blood pressure. Therefore, marine biological sources of hypolipidemic active substances have attracted much attention. Moreover, some of the identified active substances have been found to induce hypolipidemia by inhibiting cholesterol synthesis and absorption, or by improving the composition of intestinal microorganisms. This article introduces the sources and classification of marine-derived hypolipidemic active substances, and describes current progress in research on the main mechanism of the hypolipidemic activity of these substances.

Viral infections are a natural part of our existence. They can affect us in many ways that are the result of the interaction between the viral pathogen and our immune system. Most times the resulting immune response is beneficial for the host. The pathogen gets cleared thus protecting our vital organs with no other consequences. Conversely, the reaction of our immune system against the pathogen can cause organ damage (immunopathology) or lead to autoimmune disease. To date, there are several mechanisms for virus-induced autoimmune disease, including molecular mimicry and bystander activation, in support of the “fertile field” hypothesis, terms defined in our review. On the flip side, viral infections have been associated with protection from autoimmunity through mechanisms that include Treg invigoration and immune deviation, in support of the “hygiene hypothesis”, also defined here. Infection with lymphocytic choriomeningitis virus (LCMV) is one of the prototypes showing that the interaction of our immune system with viruses can either accelerate or prevent autoimmunity. Studies using mouse models of LCMV have helped conceive and establish several concepts that we today know and explain how viruses can lead to autoimmune activation or induce tolerance. Some of the most important mechanisms established during the course LCMV are described in this short review.

G protein-coupled receptors (GPCRs) play a key role in many cellular signaling mechanisms, and must select among multiple coupling possibilities in a ligand-specific manner in order to carry out a myriad of functions in diverse cellular contexts. Much has been learned about the molecular mechanisms of ligand-GPCR complexes from Molecular Dynamics (MD) simulations. However, to explore ligand-specific differences in the response of a GPCR to diverse ligands, as is required to understand ligand bias and functional selectivity, necessitates creating very large amounts of data from the needed large-scale simulations. This becomes a Big Data problem for the high dimensionality analysis of the accumulated trajectories. Here we describe a new machine learning (ML) approach to the problem that is based on transforming the analysis of GPCR function-related, ligand-specific differences encoded in the MD simulation trajectories into a representation recognizable by state-of-the-art deep learning object recognition technology. We illustrate this method by applying it to recognize the pharmacological classification of ligands bound to the 5-HT2A and D2 subtypes of class A GPCRs from the serotonin and dopamine families. The ML-based approach is shown to perform the classification task with high accuracy, and we identify the molecular determinants of the classifications in the context of GPCR structure and function. This study builds a framework for the efficient computational analysis of MD Big Data collected for the purpose of understanding ligand-specific GPCR activity.

The complement system is part of the innate immune response, where it provides immediate protection from infectious agents and plays a fundamental role in homeostasis. Complement dysregulation occurs in several diseases, where the tightly regulated proteolytic cascade turns offensive. Prominent examples are atypical hemolytic uremic syndrome, paroxysmal nocturnal hemoglobinuria and Alzheimer’s disease. Therapeutic intervention targeting complement activation may allow treatment of such debilitating diseases. In this review, we describe a panel of complement targeting nanobodies that allow modulation at different steps of the proteolytic cascade, from the activation of the C1 complex in the classical pathway to formation of the C5 convertase in the terminal pathway. Thorough structural and functional characterization has provided a deep mechanistic understanding of the mode of inhibition for each of the nanobodies. These complement specific nanobodies are novel powerful probes for basic research and offer new opportunities for in vivo complement modulation.

Cellular aging is considered as one of the main factors leading to female infertility. The process called “inflammaging”, which was proposed by C. Franceschi in 2014 is characterized by chronic asymptomatic inflammation state resulting to whole body aging and age-associated diseases. In this work the inflammaging model was developed; markers expression associated with SASP (senescence associated secretory phenotype) and cell aging were verified in endometrial cells; the correlation analysis with the known inflammaging markers was done; as well as the age dynamic of markers expression in the groups of young reproductive age and late reproductive age was evaluated. For the first time, the comparative study of the expression of the key signalling molecules involved in the mechanisms of the aging was carried out: IL-6, IL-8, IL-1a, MMP3, SIRT1,6, TERF-1, CALR in endometrial cells in the age aspect and under the influence of the genotoxic stress. The SASP phenotype characterizing the phenomenon of inflammaging can be significantly expanded by the including of the studied molecules - SIRT-1, SIRT-6, TERF, CALR, that we demonstrated for the first time. These signalling molecules may be new therapeutic targets for the age-associated female reproductive system diseases treatment.

Molecular mechanisms for N2 fixation (solar NH3) and CO2 conversion to C2+ products in enzymatic conversion (Nitrogenase), electrocatalysis, metal-complexes and plasma-catalysis are analysed and compared. It is evidenced that differently from what present in thermal and plasma-catalysis, the electrocatalysis path requires not only the direct coordination and hydrogenation of undissociated N2 molecule, but to realize a series of features present in the Nitrogenase mechanism. There is the need of i) a multi-electron and -proton simultaneous transfer, not as sequential steps, ii) forming bridging metal hydride species, iii) generate intermediates stabilized by bridging multiple metal atoms, iv) have the capability of the same sites to be effective both in N2 fixation and in COx reduction to C2+ products. Only iron oxide/hydroxide stabilized at defective sites of nanocarbons was found to have these features. This comparison of the molecular mechanisms in solar NH3 production and relations with CO2 reduction is proposed to be a source of inspiration to develop the next generation electrocatalysts to address the challenging transition to a future sustainable energy and chemistry beyond fossil fuels.

The selectivity in the simultaneous detection of ascorbic acid (AA), dopamine (DA), and uric acid (UA) has been an open problem in the biosensing field. Many surface modification methods were carried out for glassy carbon electrodes (GCE), including the use of graphene oxide and amino acids as a selective layer. In this work, molecular dynamics (MD) simulations were performed to investigate the role of serine oligomers on the selectivity of the AA, DA, UA analytes. Our models consisted of a graphene oxide (GO) sheet under a solvent environment. Serine tetramers were added into the simulation box and were adsorbed on the GO surface. Then, the adsorption of each analyte on the mixed surface was monitored from MD trajectories. It was found that the adsorption of AA was preferred by serine oligomers due to the largest number of hydrogen-bond forming functional groups of AA, while UA was the least preferred due to its highest aromaticity. Finally, the role of hydrogen bonds on the electron transfer selectivity of biosensors was discussed with some previous studies.

The Neurodegenerative Diseases are, according to recent studies, one of the main causes of disability and death worldwide. Interest in molecular genetics has started to have an exponential growth thanks to numerous advancements in tech, shifts in the understanding of the disease as a phenomenon, and the change of perspective regarding gene editing and the upsides of this action. The aim of this paper is to analyse the newest approaches in genetics and molecular sciences regarding four of the most important neurodegenerative disorders: Alzheimer’s Disease, Parkinson’s Disease, Huntington’s Disease and Amyotrophic Lateral Sclerosis. We intend through this review to focus on the newest treatment, diagnosis and predictions plans regarding this large group of diseases, in order to obtain a better accuracy analysing and spotting the emerging signs that could lead to a better outcome in order to increase both the quality and the life span of the patient. Moreover, this review could provide future evidence of possible novelty therapies that target the specific genes and could be useful to be taken into consideration when the classical approaches fail to shed light.

Worldwide, hypoxia-related conditions, including cancer, COVID-19, and neuro-degenerative diseases, often lead to multi-organ failure and significant mortality. Oxygen, crucial for cellular function, becomes scarce as levels drop below 10 mmHg (<2% O2), triggering mitochondrial dysregulation and activating hypoxia-induced factors (HiFs). Herein, Oxygen nanoBubbles (OnB), an emerging versatile oxygen de-livery platform, implies to offer a novel approach to address hypoxia-related pathologies. This review explores OnB oxygen delivery strategies and systems, including diffusion, ultrasound, photodynamic, and pH-responsive nanobubbles. It delves into the nanoscale mechanisms of OnB, elucidating their role in mitochondrial metabolism (TFAM, PGC1alpha), hypoxic responses (HiF-1alpha), and their interplay in chronic pathologies including cancer and neurodegenerative disorders, amongst others. By understanding these dynamics and underlying mechanisms, this article aims to contribute to our accruing knowledge of OnB and the developing potential in ameliorating hypoxia- and metabolic stress-related conditions and fostering innovative therapies.

The growing interest in Kv7.2/7.3 agonists originates from the involvement of these channels in several brain hyperexcitability disorders. In particular, Kv7.2/7.3 mutants have been clearly associated with epileptic encephalopathies (DEE) as well as with a spectrum of focal epilepsy disorders, often associated with developmental plateauing or regression. Nevertheless, there is a lack of available therapeutic options, considering that retigabine, the only molecule used in clinic as broad-spectrum Kv7 agonist, has been withdrawn from the market in the late 2016. This is why several efforts have been made both by both academia and industry in the search for suitable chemotypes acting as Kv7.2/7.3 agonists. In this context, in silico methods have played a major role, since the precise structures of different Kv7 homotetramers have been only recently disclosed. In the present review the computational methods used for the design of Kv.7.2/7.3 small molecule agonists and the underlying medicinal chemistry are discussed in the context of their biological and structure-function properties.

Bibliometric studies on inherited metabolic diseases(IMDs) didn't exist in the literature.Our research aims to conduct a bibliometric study to determine the current status,trending topics,and missing points of publications on IMDs.Between 1968-2023, we conducted a literature search with keyword "inherited metabolic disease" in the SCOPUS-database.We included research articles in medicine written in English,published in the final section.We created our data pool using VoSviewer, SciMAT, and Rstudio software programs for bibliometric parameters of the articles that met the inclusion criteria.We performed bibliometric analysis of the data with R-package "bibliometrix" and BibExcel programs.We included 2702 research articles published on IMDs.Top three countries that have written the most articles in this field are; USA(n= 501), United Kingdom(n=182), and China(n= 172).The most preferred keywords by the authors were;newborn screening(n=54), mutation(n=43), phenylketonuria(n=42), children(n=35), genetics(n= 34) and maple syrup urine disease(n=32).Trending topics were osteoporosis, computed tomography, bone marrow transplantation in the early years of the study, chronic kidney disease, urea cycle disorders, next-generation sequencing, newborn screening, and familial hypercholesterolemia in the final years of the study. This study provides clinicians with a new perspective showing that molecular and genetic studies in inherited metabolic diseases will play an essential role in diagnosis and treatment in the future.

The bipartite entanglement is comprehensively investigated in the mononuclear molecular complex (Et3NH)[Ni(hfac)2L], where HL denotes 2-(2-hydroxy-3-methoxy-5-nitrophenyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-3-oxide-1-oxyl and hfacH stands for hexafluoroacetylacetone. From the magnetic point of view, the molecular compound (Et3NH)[Ni(hfac)2L] consists of an exchange-coupled spin-1 Ni2+ magnetic ion and a spin-12 nitronyl-nitroxide radical substituted nitrophenol. The nickel-radical molecular complex affords an experimental realization of a mixed spin-(12, 1) Heisenberg dimer with a strong antiferromagnetic exchange coupling J/kB= 505 K and two distinct g-factors gRad=2.005 and gNi=2.275. By adopting this set of magnetic parameters we demonstrate that the Zeeman splitting of a quantum ferrimagnetic ground-state doublet due to a weak magnetic field may substantially reinforce the strength of bipartite entanglement at low temperatures. The molecular compound (Et3NH)[Ni(hfac)2L] maintains sufficiently strong thermal entanglement even at room temperature, vanishing only above 546 K. Specifically, the thermal entanglement in the nickel-radical molecular complex retains approximately 40% of the maximum value corresponding to perfectly entangled Bell states at room temperature, which implies that this magnetic compound provides suitable platform of a molecular qubit with potential implications for room-temperature quantum computation and quantum information processing.

Cancer is a devastating disease, causing tremendous morbidity and mortality each year. Cancer can be considered as a genetic disease in the sense that instabilities in protooncogenes and tumor suppressor genes are among the hallmarks of cancer progression and metastasis. However, a particular cancer can express different proteins in different patients, making cancer a heterogeneous disease. This heterogeneity in part influences treatment resistance and failure. Therefore, it is crucial to understand the mechanism by which cancer cells develop and enhance resistance to different agents. This review aims to present the general paradigm and recent updates on cancer cell resistance to different antitumor agents. It demonstrates that tumor resistance results from a myriad of factors, including tumor microenvironment, supporting immune cells, and cancer stem cells. This interaction contributes to cancer cells overcoming the therapeutic effects of different classes of antitumor agents, such as cytotoxic chemotherapeutics, targeted agents, and immunotherapies. With the development of advanced molecular analysis, specialized genomic assessment has assisted clinicians and researchers in choosing selected agents combating cancer cells. Together, this approach can potentially reduce treatment toxicity, health system burden, and financial costs while improving patient quality of life. Understanding the exact mechanism of drug resistance in cancer cells can open the way to new effective and less toxic therapeutics.

Caveolin-1 (Cav-1) is 22 kDa caveolae protein, acts as a scaffold within caveolar membranes. It interacts with alpha subunits of G-protein and thereby regulates their activity. Earlier studies reported elevated or up-regulated levels of caveolin-1 in the serum of prostate cancer patients. Secreted Cav-1 promotes angiogenesis, cell proliferation and anti-apoptotic activities in prostate cancer patients. Cav-1 upregulation is mainly related to prostate cancer metastasis. Keeping above facts in view, the present study was designed to explore Cav-1 as a target for prostate cancer therapy using computational approach. Molecular docking, structural base molecular modelling and molecular dynamics simulations were performed to investigate Cav-1 inhibitors. A predictive model was generated and validated to establish a stable structure. ZINC database of biogenic compounds was used for induced fit docking (IFD) and high throughput virtual screening. The H-bond interactions of the compounds with active site residues of Cav-1 were estimated by IFD and 100 ns long molecular dynamic simulations. The reported compounds showed significant binding and thus can be considered as potent therapeutic inhibitors of Cav-1. This study provides a valuable insight into biochemical interactions of Cav-1 for therapeutic applications and warrants for experimental validation of the predicted ‘active(s)’.

The formation of atroposelective biaryl compounds in plants and fungi is well understood; however, the polyketide aglycone synthesis and dimerization in bacteria remain unclear. Thus, the biosynthetic gene cluster (BGC) responsible for antibacterial setomimycin production from Streptomyces nojiriensis JCM3382 was examined in comparison with the BGCs of spectomycin, julichromes, lincolnenins, and huanglongmycin. Setomimycin BGC includes post-PKS assembly/cycling enzymes StmD (C-9 ketoreductase), StmE (aromatase), and StmF (thioesterase) as key components. The heterodimeric TcmI-like cyclases StmH and StmK are proposed to aid in forming the setomimycin monomer. In addition, StmI (P-450) is predicted to catalyze biaryl coupling of two monomeric setomimycin units, with StmM (ferredoxin) specific to setomimycin BGC. The roles of StmL and StmN, part of the nuclear transport factor 2 (NTF-2)-like protein family and unique to setomimycin BGCs, could particularly interest biochemists and combinatorial biologists. α-Glucosidase, a key enzyme in type 2 diabetes, hydrolyzes carbohydrates into glucose, thereby elevating blood glucose levels. This study aimed to assess the α-glucosidase inhibitory activity of EtOAc extracts of JCM 3382 and setomimycin. The JCM 3382 EtOAc extract and setomimycin exhibited greater potency than the standard inhibitor, acarbose, with IC50 values of 285.14 ± 2.04 μg/mL and 231.26 ± 0.41 μM, respectively. Kinetic analysis revealed that setomimycin acts as a competitive inhibitor of α-glucosidase. Molecular docking demonstrated two hydrogen bonds with maltase-glucoamylase chain A residues Thr205 and Lys480 (binding energy = −6.8 kcal·mol⁻¹), two π-π interactions with Trp406 and Phe450, and one π-cation interaction with Asp542. Residue-energy analysis highlighted Trp406 and Phe450 as key in setomimycin's binding to maltase-glucoamylase. These findings suggest that setomimycin is a promising candidate for further enzymological research and potential antidiabetic therapy.

In this paper, the nanoscale dissipative mechanisms of a Cu pad in a Ball Grid Array (BGA) packaging structure during isothermal ageing and uniaxial tension were investigated by the molecular dynamics (MD) method and experiments. From the result of the isothermal ageing test, a nonuniform consumption of Cu and large amount of Kirkendall voids were observed at the interface of Cu and Cu₃Sn. To study the effect of pressure and orientation on this phenomenon, MD simulations were conducted on four types of Cu-Cu₃Sn interface structures with different orientations of Cu. By comparing the diffusion coefficients of atoms in those cases, it was found that the tensile stress would inhibit the diffusion of atoms, whereas compressive stress would accelerate it, and this would be more significant under a larger magnitude of stress and temperature. Note that, in the model with the (101) surface Cu at the interface, both Cu and Cu₃Sn have a higher diffusion coefficient compared with the model with (001) surface Cu. Thus, the orientation of Cu will also contribute to the uniform consumption of the pad. Uniaxial tension simulation combined with DXA and CSP analyses on those models also shows the model with (001) surface Cu has a greater mechanical reliability in our simulations and related experiments.

Precise classification of sarcomas is crucial to drive optimal clinical management. In this prospective, multicenter, observational study within the Hellenic Group of Sarcoma and Rare Cancers (HGSRC) we assessed the effect of expert pathology review, coupled with the application of molecular diagnostics, on diagnosis and management of sarcoma patients. Newly diagnosed sarcoma patients were addressed by their physicians to one of the two sarcoma pathologists of HGSRC for histopathological diagnostic assessment. RNA next-generation sequencing was per-formed to all samples, using a platform targeting 86 sarcoma gene fusions. Additional molecular methods were performed on the opinion of the expert pathologist. Therefore, the expert pathologist provided a final diagnosis based on the histopathological findings and, when necessary on molecular tests. In total, 128 specimens from 122 patients were assessed. Among the 119 cases in which there was a preliminary diagnosis by a non-sarcoma pathologist, there were 37 modifications in diagnosis (31.1%) by the sarcoma pathologist, resulting in 17 (14.2%) modifications in management. Among the 110 cases in which molecular tests were performed, there were 29 modifications in diagnosis (26.4%) through the genomic results, resulting in 12 (10.9%) modifications in management. Our study confirms that expert pathology review is of utmost importance for the optimal sarcoma diagnosis and management and should be assisted by molecular methods in selected cases.

Many neurodegenerative diseases are directly related to the formation of toxic protein aggregates, such as Parkinson’s and Alzheimer’s diseases, which are associated with the aggregation of alpha-synuclein (α-syn) and beta-amyloid (Aβ ), respectively. In this context, protein fibrils are the hallmark of these neurodegenerative diseases. In this sense, planning or designing compounds that are capable of preventing or reducing the formation of protein aggregation in the brain can be of fundamental importance for the curative treatment of these diseases. This work presents an in silico and experimental study to investigate the inhibitory potential of the ligands Octovespin (bioinspired by the wasp venom Polybia Occidentalis) and Fraternine-10 (bioinspired by the wasp venom Parachartergus fraternus wasp) against the aggregation of fibrils of the peptides Aβ(17-42) and α-syn, respectively. Using molecular docking and molecular dynamics simulations with 100 ns, the disaggregation capacity of these ligands was studied. The results obtained indicate that Octovespin and Fraternine-10 interact with the Aβ and α-syn protein fibrils throughout the simulation time. The RMSD values and the interactions with amino acids responsible for fibril aggregation demonstrate that both Octovespin and Fraternine-10 have a significant disaggregation potential, which corroborates the observations in vitro and in vivo. Furthermore, experimental results of Fraternine-10 demonstrate an anti-aggregation effect, indicating that it can promote the disaggregation of fibrils and prevent them from aggregating again to form oligomers. These discoveries qualify these molecules as potential candidates to become medicines against Parkinson’s and Alzheimer’s diseases.

Coxsackievirus A6 (CV-A6) has emerged as the predominant causative agent of hand, foot, and mouth disease (HFMD) in young children. Since the declaration of coronavirus disease 2019 (COVID-19) as a global pandemic, the incidence of infectious diseases, including HFMD, has decreased markedly. When social mitigation was relaxed during the COVID-19 pandemic in 2022, re-emergence of HFMD was observed in Gwangju, South Korea, and seasonal characteristics of the disease appeared to have changed. To investigate the molecular characteristics of enterovirus (EV) associated with HFMD during 2022, 277 specimens were collected. Children aged under 5 years accounted for the majority of affected individuals. EV detection and genotyping were performed using real-time RT-PCR and nested RT-PCR followed by sequence analysis. EV detection rate was found to be 82.3%, and the main genotype identified was CV-A6. Sixteen CV-A6 samples were selected for whole genome sequencing. According to phylogenetic analysis, all CV-A6 strains from this study belonged to the sub-genotype D3 clade based on VP1 sequences. Analysis of 3D polymerase phylogeny showed that only the recombinant RF-A group was identified. In conclusion, circulating EV types should be continuously monitored to understand pathogen emergence and evolution during the post-pandemic era.

Mutations affecting codon 172 of the isocitrate dehydrogenase 2 (IDH2) gene define a subgroup of sinonasal undifferentiated carcinomas (SNUCs) with a relatively favorable prognosis and a globally hypermethylated phenotype. They are also recurrent (along with IDH1 mutations) in gliomas, acute myeloid leukemia, and intrahepatic cholangiocarcinoma. Commonly reported mutations, all associated with aberrant IDH2 enzymatic activity, include R172S, R172T, R172G, and R172M. We present a case of SNUC with a never-before-described IDH2 mutation, R172A. Our report compares the methylation pattern of our sample to other cases from the GEO database. Hierarchical clustering suggests a strong association between our sample and other IDH-mutant SNUCs and a clear distinction between sino-nasal normal tissues and tumors. Principal component analysis (PCA), using 100 principal components explaining 94.5% of the variance, shows the position of our sample within 1.02 standard deviation of the other IDH-mutant SNUCs. Molecular modeling analysis of the IDH2 R172A versus other R172 variants provides a structural explanation to how they affect the protein active site. Our findings thus suggest that the R172A mutation in IDH2 confers a gain of function similar to other R172 mutations in IDH2, resulting in a similar hypermethylated profile.

Introduction: Rotavirus-induced acute diarrhoea continues to pose a significant health threat to children under 5 years old worldwide, despite the availability of effective vaccines. This study aimed to assess the prevalence, associated risk factors, and circulating genotypes of rotavirus among children under 5 admitted to Ikom Medical Centre due to diarrhea. Methodology: Stool samples were collected from 294 children under 5 with diarrhoea at Ikom Medical Centre. Rotavirus antigen detection was performed using rapid chromatographic immunoassay. Molecular techniques such as polyacrylamide gel electrophoresis (PAGE), RT-PCR, and semi-nested multiplex RT-PCR were used to analyze rotavirus strains. Data were obtained through questionnaires, and statistical significance was assessed using the chi-square test (P < 0.05). Results: Among the 294 samples, 20.4% (60/294) tested positive for rotavirus. Significant risk factors influencing rotavirus prevalence included feeding status, toilet system, and duration of diarrhoea. The most prevalent genotype for VP7 was G4 (26.7%), and for VP4, it was genotype P[4] (23.3%). Predominant genotype combinations were G4P [4] (11.6%) and G12P[4] (6.7%), while non-typeable P[NT] was observed in 41.7% of cases. Conclusion: This study highlights the circulation of rotavirus in Ikom, Cross River State, emphasizing its neglected status despite its significant global impact on child mortality. Urgent attention is needed to address rotavirus as a serious public health concern, particularly in low-resource settings.

Indole derivatives are key components of natural products and possesses a wide range of biological and pharmaceutical applications. Here we present the synthesis of a new indole derivative namely 2-(1-ethyl-5-nitro-1H-indole-7-carbonyl) butyl 4-methylbenzenesulfonate (5). The structural elucidation of 5 was accomplished through comprehensive spectroscopic analysis, including Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and high-resolution mass spectrometry (HRMS). Our molecular docking study revealed that compound 5 exhibits strong affinity towards Tyrosinase, making it a promising candidate as an antioxidant agent. Keywords: Indole derivative; Tosyl group; Molecular docking; Antioxidant agent.

This study aims to characterize the molecular profile of hepatitis B virus (HBV) among socially vulnerable immigrants residing in Brazil to investigate the introduction of uncommon HBV strains into the country. Serum samples from 102 immigrants with positive serology for HBV core antibody (anti-HBc) were tested for the presence of HBV DNA by PCR assays. Among these, 24 were also positive for the HBV surface antigen (HBsAg). The full or partial genome was sequenced to determine genotype by phylogenetic analysis. Participants were from Haiti (79.4%), Guinea Bissau (11.8%), Venezuela (7.8%), and Colombia (1%). Of the 21 HBV DNA-positive samples, subgenotypes A1 (52.4%), A5 (28.6%), E (9.5%), F2 (4.8%), and F3 (4.8%) were identified. Among the 78 HBsAg-negative participants, four were positive for HBV DNA, resulting in an occult HBV infection rate of 5.1%. Phylogenetic analysis suggested that most strains were likely introduced to Brazil by migration. Importantly, 80% of A5 sequences had the A1762T/G1764A double mutation, linked to an increased risk of hepatocellular carcinoma development. In conclusion, this study is the first report of HBV subgenotype A5 in Brazil, shedding new light on the diversity of HBV strains circulating in the country. Understanding the genetic diversity of HBV in immigrant communities can lead to better prevention and control strategies, benefiting both immigrants and the broader society.

Intrahepatic cholangiocarcinoma (ICCA) is a malignant epithelial neoplasm characterized by biliary differentiation within the liver. ICCA is molecularly heterogeneous and exhibits a broad spectrum of histopathological features. It is a highly aggressive carcinoma with high mortality and poor survival rates. ICCAs are classified into two main subtypes: small duct type and large duct types. These two tumor types have different cell origins and clinicopathological features. ICCAs are characterized by numerous molecular alterations, including mutations in KRAS, TP53, IDH1/2, ARID1A, BAP1, BRAF, SAMD4, and EGFR, and FGFR2 fusion. Two main molecular subtypes–inflammation and proliferation–have been proposed. Recent advances in high-throughput assays using next-generation sequencing have improved our understanding of ICCA pathogenesis and molecular genetics. The diagnosis of ICCA poses a significant challenge for pathologists because of its varied morphologies and phenotypes. Accurate diagnosis of ICCA is essential for effective patient management and prognostic determination. This article provides an updated overview of ICCA pathology, focusing particularly on molecular features, histological subtypes, and diagnostic approaches.

During COVID-19 pandemic, drug repurposing represented an effective strategy to obtain quick answers to medical emergencies. Basing on previous data on Methotrexate (MTX), we evaluated the anti-viral activity of several DHFR inhibitors in two cell lines. We observed that this class of compounds showed a significant influence on the virus-induced cytopathic effect (CPE) partly associated to the intrinsic antimetabolic activity of these drugs, but also to a specific antiviral function. To elucidate the molecular mechanisms, we took advantage of our EXSCALATE platform for in-silico molecular modelling and further validated the influence of these inhibitors on nsp13 and viral entry. Interestingly, Pralatrexate and Trimetrexate showed superior effects in counteracting the viral infection compared to other DHFR inhibitors. Our results indicate that their higher activity is due to their polypharmacological and pleiotropic profile. These compounds can thus potentially give a clinical advantage in the management of SARS-CoV-2 infection in patients already treated with this class of drugs.

Calicioids form a research field that has encompassed ascomycetous fungi with stalked ascomata similar to those of the lichen genus Calicium. Early generic circumscriptions in calicioid lichens and fungi were mainly based on morphological and secondary chemistry information. After the introduction of molecular data, taxonomy in the group has been reconsidered. Here, based on a broad geographical sampling, Coniocybe Ach. was revised using molecular and morphological features. Three loci (ITS, LSU and rpb1) were compared to infer its phylogenetic position, and a total of 52 new sequences (14 ITS, 24 LSU and 14 rpb1) were produced. Coniocybe was revised and emended to include, apart for its type C. furfuracea, also C. brachypoda and C. confusa. In addition, a new species Coniocybe eufuracea, was described, and a key to the species of Coniocybe provided.

Our primary objectives were a) to determine the need for, and the availability of point-of-care testing (POCT) for infectious diseases and b) to recommend point-of-care testing strategies and spatial care paths (SCPs) that enhance public health preparedness in regional districts of Thua Thien Hue Province (TTHP), Central Vietnam, where we conducted field surveys. Medical professionals in 7 community health centers (CHCs), 7 district hospitals (DHs) and 1 provincial hospital (PH) participated. Survey questions (English and Vietnamese) determined the status of diagnostic testing capabilities for infectious diseases and other acute medical challenges in TTHP. Infectious disease testing was limited: 6 of 7 CHCs (86%) lacked infectious disease tests. One CHC (14%, 1/7) had two forms of diagnostic tests available for the detection of Malaria. All CHCs lacked adequate microbiology laboratories. District hospitals had few diagnostic tests for infectious diseases (Tuberculosis, Syphilis), blood culture (29%, 2/7), and pathogen culture (57%, 4/7) available. The PH had broader diagnostic testing capabilities but lacked preparedness for highly infectious disease threats (e.g., Ebola, MERS-CoV, SARS, Zika, and Monkeypox). All sites reported having COVID-19 rapid antigen tests; COVID-19 RT-PCR tests were limited to higher tier hospitals. We conclude that infectious disease diagnostic testing should be improved and POC tests must be supplied near patients’ homes and in primary care settings for the early detection of infected individuals and mitigation of the spread of new COVID-19 variants and other highly infectious diseases.

Rice production, owing to its high-water requirement for cultivation, is very vulnerable to the threat of changing climate, particularly prolonged drought and high temperature. Such threats heighten the need for abiotic stress-resilient rice varieties with better yield potential. This review examines the physiological and molecular mechanisms of rice varieties to cope with stress conditions of drought (DS), high temperature (HTS) and their combination (DS-HTS). It appraises research studies in rice about its various phenotypic traits, genetic loci and response mechanisms to stress conditions to help craft new breeding strategies for rice varieties with improved resilience to abiotic stresses. This review consolidates available information on promising rice cultivars with desirable traits as well as advocates synergistic and complementary approaches in molecular and systems biology to develop new rice breeds that favorably respond to climate-induced abiotic stresses. The development of new breeding and cultivation strategies for climate-resilient rice varieties is a challenging task. It requires a comprehensive understanding of the various morphological, biochemical, physiological, and molecular components governing yield under drought and high temperature, but possible by implementing cohesive approaches involving molecular and systems biology approaches in genomics and molecular breeding, including genetic engineering.

Histones are keys to many epigenetic events and their complexes have therapeutic and diagnostic importance. The determination of the structures of histone complexes is fundamental in the design of new drugs. Computational molecular docking is widely used for the prediction of target-ligand complexes. Large, linear peptides like the tail regions of histones are challenging ligands for docking due to their large conformational flexibility, extensive hydration, and weak interactions with the shallow binding pockets of their reader proteins. Thus, fast docking methods often fail to produce complex structures of such peptide ligands at a level appropriate for drug design. To answer this challenge, and improve the structural quality of the docked complexes, post-docking refinement has been applied using various molecular dynamics (MD) approaches. However, a final consensus has not been reached on the desired MD refinement protocol. In the present study, MD refinement strategies were systematically explored on a set of problematic complexes of histone peptide ligands with relatively large errors in their docked geometries. Six protocols were compared that differ in their MD simulation parameters. In all cases, pre-MD hydration of the complex interface regions was applied to avoid the unwanted presence of empty cavities. The best-performing protocol achieved a median of 32 % improvement over the docked structures in terms of the change of root mean squared deviations from the experimental references. The influence of structural factors and explicit hydration on the performance of post-docking MD refinements was also discussed to help their implementation in future methods and applications.

The shikimate pathway is crucial for the biosynthesis of aromatic amino acids in plants and represents a promising target for developing new herbicides. This work aimed to identify inhibitors of shikimate dehydrogenase (SDH), a key enzyme of the shikimate pathway that catalyzes the conversion of 3-dehydroshikimate to shikimate. Virtual screening and molecular docking were performed on the SDH active site of Arabidopsis thaliana (AtSDH), and 6-nitroquinazoline-2,4-diol (NQD) was identified as a potential inhibitor. In vitro assays showed that NQD decreased the activity of AtSDH by reducing Vmax while keeping KM unchanged, indicating noncompetitive inhibition. In vivo, hydroponic experiments revealed that NQD reduced the root length of soybean and maize. Additionally, NQD increased the total protein content and certain amino acids. Soybean roots uptake NQD more efficiently than maize roots. Furthermore, NQD reduced shikimate accumulation in glyphosate-treated soybean roots, suggesting its potential to restrict the flow of metabolites along the shikimate pathway in soybean. Simultaneous treatment of maize seedlings with glyphosate and NQD accumulated gallic acid in the roots, indicating that NQD inhibits SDH in vivo. Overall, the data indicate that NQD inhibits SDH both in vitro and in vivo, providing valuable insights into the potential development of herbicides targeting SDH.

Abstract: The Willows, belonging to the genus Salix, encompass a vast array of species and hybrids, totaling between 330 to 500 species along with approximately 200 hybrids. These plants are found across continents such as Africa, North America, Europe, and Asia, exhibiting diverse forms ranging from trees to shrubs and prostrate plants. Traditionally, Willows have been utilized in folk medicine due to their rich reservoir of biologically active compounds, with salicin being a notable example, serving as a prodrug for salicylic acid.The chemical composition of Willows is highly diverse, with 322 secondary metabolites identified thus far. These include various classes such as flavonoids (94 types encompassing flavonols, flavones, flavanones, isoflavones, flavan-3-ols like catechins and procyanidins, chalcones, dihydrochalcone, anthocyanins, and dihydroflavonols), phenolic glycosides (76), organic acids (28), non-phenolic glycosides (17), sterols, and terpenes (17), simple phenolics (13), lignans (7), as well as volatiles and fatty acids (69). This rich chemical di-versity underpins the various pharmacological activities exhibited by Willows. The pharmacological properties attributed to Willows are extensive and include analgesic, an-ti-inflammatory, antioxidant, anticancer, cytotoxic, antidiabetic, antimicrobial, antiobesity, neuroprotective, and hepatoprotective effects. These properties make Willows a subject of con-siderable interest in the fields of medicine and pharmacology. In summary, Willows represent a valuable natural resource with a diverse chemical composition and a wide range of pharmacological activities. This study aimed to enhance our comprehension of the medicinal characteristics of willow bark extract, focusing on its antimicrobial properties. This investigation holds significance in validating the traditional usage of willow bark and investi-gating its potential utility in contemporary medicine.

Powdery mildew is a severe disease causing substantial yield losses in wheat production worldwide. The Chinese wheat landrace Changanhongmai (CAHM) exhibits high resistance to the physiological race E09 of powdery mildew. This study aims to characterize the powdery mildew resistance gene in CAHM, and develop molecular markers for marker-assisted selection of wheat. To investigate the genetic characteristics of this resistant gene, we developed F1 plants, F2 generation population, and F2:3 families from a cross between CAHM and SY225. Genetic analysis demonstrated that all F1 plants were resistant to the disease, while the ratio of resistant to susceptible plants was 3: 1 in both the F2 population and F2:3 families, indicating that CAHM is inherited in a manner of single dominant powdery mildew resistance gene, which was tentatively designated as PmCAHM. By using bulk segregation analysis, we constructed a genetic map encompassing Xgwm273, Xwmc626, Xgwm11, Xgwm18, Xgdm28, Xgpw7812, Xgpw5195, Xwmc694 and PmCAHM. Among these markers, Xgpw7812 and Xgpw5195 were flanking markers tightly linked to PmCAHM at a genetic distance of 2.5 cM and 8.4 cM, respectively. Furthermore, nullisomic-tetrasomic analysis revealed that PmCAHM is located on chromosome 1B. These results indicate that PmCAHM differs from the internationally recognized powdery mildew resistance genes in both location and source. In addition, a new germplasm/line NW1748 with large seeds and powdery mildew resistance was developed from the cross and back cross populations of Fengyou 1718 (FY1718)/CAHM//FY 1718. Therefore, PmCAHM can serve as a novel powdery mildew resistance source for breeding of wheat by using NW1748 as the donor in the future.

Background and Objectives Neurofibromatosis 1 (NF1 MIM # 162200), also known as von Recklinghausen disease, is among the most common autosomal dominantly transmitted disorders characterized mainly by neurocutaneous manifestations such as café au lait spots, intertriginous freckling, various types of neurofibromas (cutaneous neurofibromas or plexiform tumors), neurological manifestations, and bone abnormalities. It occurs with an incidence of 1:3000–1:4000 cases. Cone-rod dystrophies belong to the large group of retinal dystrophies, a highly heterogeneous group of disorders clinically manifested mainly by damage to cone and rod cells and have a broad spectrum of clinical manifestations. Many genes are involved in their etiology, with more than 100 currently identified, including the CRX gene responsible for the autosomal dominant form of cone-rod dystrophy (ad CORD). Materials and Methods: The authors present an intriguing case of a patient diagnosed with Neurofibromatosis type 1 (NF1) as an infant and ocular involvement (myopia and astigmatism onset at age 15), which yielded a surprising molecular testing result. Results: Molecular DNA analysis identified a rare occurrence of two mutational variants, including a pathogenic variant in the NF1 gene, c.3871-2A, and a likely pathogenic variant in the CRX gene c.119G>A. Conclusions: The authors present this case to highlight the surprises offered by molecular testing in a condition where the diagnosis is usually based on clinical criteria, thus providing patients with competent genetic advice.

The de-oxygenation process in water used in well injection operations is an important matter to eliminate corrosion in petroleum industry. This study used molecular dynamics simulations to understand the behavior of siloxane surface through studding the surface properties with two functional groups attached to the end of siloxane and their effect on de-oxygenation process. The simulations were performed using LAMMPS to characterize of surface properties. Jmol software was used to generate siloxane chains with (8, 20, and 35) repeat units. Firstly, we evaluated properties such as total energy, surface tension and viscosity. Then, we used siloxane as a membrane to compare the efficiency of de-oxygenation for the both types of functional groups. The results indicated that longer chains length increased total energy, viscosity while decreased surface tension. Replacing methyl groups with trifluoromethyl (CF3) groups increased all the above mentioned properties in varying proportions. Trifluoromethyl (CF3) groups showed better removal efficiency than methyl (CH3) groups but allowed more water to pass. Furthermore, the simulations were run using the class II potential developed by Sun, Rigby, and others within an explicit-atom (EA) model.

Exploring therapeutic options is crucial in the ongoing COVID-19 pandemic caused by SARS-CoV-2. Nirmatrelvir, a potent inhibitor targeting the SARS-CoV-2 Mpro, shows promise as an antiviral treatment. Additionally, Ivermectin, a broad-spectrum antiparasitic drug, has demonstrated effectiveness against the virus in laboratory settings. However, its clinical implications are still debated. Using computational methods such as molecular docking and 100 ns molecular dynamics simulations, we investigated how Nirmatrelvir and Ivermectin interact with SARS-CoV-2 Mpro(A). Calculations using density functional theory have been instrumental in elucidating the behavior of isolated molecules, primarily by analyzing the frontier molecular orbitals. Our analysis revealed distinct binding patterns: Nirmatrelvir formed strong interactions with amino acids like MET49, MET165, HIS41, HIS163, HIS164, PHE140, CYS145, GLU166, and ASN142, showing stable binding with a root mean square deviation (RMSD) of around 2.0 Å. On the other hand, Ivermectin interacted with THR237, THR239, LEU271, LEU272, and LEU287, displaying an RMSD of 1.87 Å, indicating enduring interactions. Both ligands stabilized Mpro(A), with Ivermectin showing stability and persistent interactions despite forming fewer hydrogen bonds. These findings offer detailed insights into how Nirmatrelvir and Ivermectin bind to the SARS-CoV-2 main protease, providing valuable information for potential therapeutic strategies against COVID-19.

Any homeostatic protometabolism would have required orchestration of disparate biochemical pathways into integrated circuits. Extraordinarily specific moieties were also required. Assembly Theory conflated with its cousins—Complexity Theory, Chaos theory, Quantum Mechanics, Irreversible Nonequilibrium Thermodynamics and Molecular Evolution theory— collectively have great naturalistic appeal in hopes of their providing the needed exquisite steering and controls. They collectively offer the best hope of circumventing the need for active selection required to formally orchestrate bona fide formal organization (as opposed to the mere self-ordering of chaos theory) [1]. This paper focuses specifically on Assembly Theory’s contribution to life-origin models.

This study aims the preparation of QCM sensor for the detection of bilirubin in human plasma. Bilirubin imprinted poly-(2-hydroxyethyl methacrylate-N-methacryloyl-L-tryptophan methyl ester) (PHEMATrp) nanofilm (MIP) on the gold surface of QCM chip was synthesized by molecular imprinting technique. Meanwhile, the non-imprinted PHEMATrp (NIP) nanofilm was synthesized by the same experimental technique to examine the imprinting effect. Characterization of MIP and NIP nanofilms on the QCM chip surface was achieved by atomic force microscopy (AFM), ellipsometry, fourier transform infrared spectrophotometry-attenuated total reflectance (FTIR-ATR) and contact angle measurements (CA). The observations indicated that the nanofilm was almost monolayer. Thereinafter, the imprinted and the non-imprinted QCM chipss were connected to QCM system to investigate kinetic and affinity properties. In order to examine the selectivity of the MIP-PHEMATrp nanofilm, competitive adsorption of bilirubin, cholesterol and estradiol was performed. Limit of detection (LOD) and limit of quantitation (LOQ) values were calculated as 0.45 μg/mL and 0.9 μg/mL, respectively.

In this paper, the boiling flow inside a nanochannel with 700000 argon particle has been simulated by molecular dynamics (MD) simulation. This approach has been employed to analysis the superheated flow and its heat transfer pattern as well. For all simulations an external thrust force varying from 1 PN to 12 PN is exerted on inlet nanoparticles along the channel to have the forced annular boiling flow. Computations reveal that saturation condition and superheat degree have significant impacts on the liquid-vapor interface. Furthermore, because of the major influence of surface tension throughout a nanochannel, the x-velocity of liquid film and vapor core has not considerable fluctuations and stay smooth. All provided results show the behaviors completely similar to the available outcomes in the literature.

Cancers, a large and heterogeneous group of malignancies, are becoming an increasingly important cause of premature mortality worldwide. 2% of these are primary CNS tumors, of which 24% are gliomas. These tumors are diverse, but what they have in common is one of the most unfavorable prognoses among all cancers. A patient's future varies depending on the grade of the diagnosed glioma. To date, however, no standard treatment for grade IV has been established. All glioblastomas eventually undergo progression or recurrence. The current standard of treatment, which includes surgical intervention, radiation therapy and chemotherapy, is therefore far from sufficient. Work is constantly underway to discover a new, effective form of glioma therapy. Photodynamic therapy (PDT) may be one of them. It involves the local or systemic application of a photosensitive compound - a photosensitizer (PS), which accumulates in the affected tissues. Photosensitizer molecules absorb light of the appropriate wavelength, initiating activation processes leading to the formation of reactive oxygen species and selective destruction of inappropriate cells. Currently, this method has been approved for the treatment of several cancers. Research focusing on the effective use of PDT in glioma therapy is already underway, with promising results. In our work, we present molecular insights into PDT of glioma. Based on the available literature, we analyze and systematize the impact of various molecules, proteins, transporters and transmitters on the efficacy of PDT and the effect of PDT on their expression. In addition, we highlight gaps in current knowledge and point out directions for future research that may contribute to the efficacy of PDT glioma.

Several pathotypes of enteric E. coli have been identified. The group represented by Shiga toxin-producing E. coli (STEC) is of particular interest. Raw milk and raw milk products are significant sources of STEC infection in humans; therefore, identifying pathogens at the herd level is crucial for public health. Most national surveillance programs focus solely on raw milk and raw milk cheeses that are ready for retail sale, neglecting the possibility of evaluating the source of contamination directly at the beginning of the dairy chain. In order to assess the viability of new molecular methodologies applied to raw milk filters enabling the identification of the presence of STEC serotypes in milk production and apply the same methods to identify the presence of these pathogens in calf feces we analyzed, through a commercial real-time PCR assay, a total of 290 samples coming from 18 different dairy herds; 88 bulk tank milk (BTM), 104 raw milk filters (RMF) and 98 calves’ feces samples. In total 3.4% of BTM, 41.4% of RMF and 73.4% of calves’ feces tested positive for stx presence, supporting our hypothesis that BTM is not a suitable matrix to assess the STEC presence at herd level, underestimating it. Our conclusion is that the surveillance program needs critical and extensive improvements such as RMF and calves’ feces analysis implementation in order to be more efficient in detecting and preventing STEC infections. The epidemiology of these infections and the characteristics of the pathogen clearly show how a One Health approach will be pivotal to improve our capabilities to control the spread of these infections.

A basic problem in all postulated pathways of prebiotic chemistry is the low concentration which generally is expected for interesting reactants in fluid environments. Even though compounds like nucleobases, sugars or peptides principally may form spontaneously under environmental conditions, they will always be rapidly diluted in an aqueous environment. In addition, any such reaction leads to side products which often exceed the desired compound and generally hamper the first steps of a subsequent molecular evolution. Therefore, a mechanism of selection and accumulation of relevant prebiotic compounds seems to be crucial for molecular evolution. A very efficient environment for selection and accumulation can be found in the fluid continuum circulating in tectonic fault zones. Vesicles which form spontaneously at a depth of approximately 1 km present a selective trap for amphiphilic molecules, especially for peptides composed of hydrophilic and hydrophobic amino acids in a suitable sequence. The accumulation effect is shown in a numeric simulation on a simplified model. Further, possible mechanisms of a molecular evolution in vesicle membranes are discussed. Altogether, the proposed scenario can be seen as an ideal environment for constant, undisturbed molecular evolution in and on cell-like compartments, the latter offering preferential starting conditions for a subsequent RNA world.

Low efficiency of in vivo transfection of a few fibers revealed a novel tissue network which temporally amplified growth stimulation in the entire regenerating rat soleus muscle. This acupuncture-like effect was demonstrated when the fibers began to grow after complete fiber degradation, synchronous inflammation, myoblast and myotube formation. The first detection of neonatal sarcoplasmic/endoplasmic reticulum ATPase (SERCA1b) has been made in this system. The neonatal, fast and slow SERCA isoforms displayed consequent change with innervation and differentiation, recapitulating events in muscle development. In vivo transfection of myotubes with plasmids expressing dominant negative Ras or a calcineurin inhibitor peptide (Cain/cabin) proved that the expression of the slow myosin heavy chain and the slow muscle type SERCA2a are dif-ferently regulated. In vivo transfection of a few nuclei of myotubes with dnRas or SER-CA1b shRNA stimulated fiber size growth in the whole regenerating muscle but only until the full size had been reached. Growth stimulation by Ras and SERCA1b antisense was abolished in co-transfection with Cain or in case of perimuscular injection with IL4 antibody. This revealed a novel signalling network resembling to scale-free networks which, starting from transfected fiber myonuclei as “hubs”, can amplify growth stimula-tion uniformly in the entire regenerating muscle.

Type 2 diabetes mellitus (T2DM), a multifactorial and complicated metabolic disorder, is a growing public health problems. Numerous studies indicated that bioactive compounds from herbal medicine have beneficial effects on T2DM prevention and treatment, owing to their numerous biological properties. Curcumin, the major curcuminoid of turmeric, is one of the most studied bioactive components of herbal supplements, which has a variety of biological activities. Clinical trials and preclinical research have recently produced compelling data to demonstrate the crucial functions of curcumin against T2DM via several routes. Accordingly, this review systematically summarizes the antidiabetic activity of curcumin, along with various mechanisms. Results showed that effectiveness of curcumin on T2DM is due to it being anti-inflammatory, anti-oxidant, anti-hyperglycemic, anti-apoptotic, anti-hyperlipidemia and other activities. In light of these results, curcumin may be a promising prevention/treatment choice for T2DM.

Motivated by experimental success in designing linear amphiphilic copolymers with selective demicellization capabilities through head-to-tail depolymerization triggered by specific stimuli, we advanced the design paradigm by increasing the number of triggering groups on the copolymer chain through architectural modifications. Utilizing molecular dynamics simulations, we explored the demicellization and cargo release dynamics of linear and miktoarm copolymers, featuring one, two and three hydrophobic block or branches, each capable for head-to-tail depolymerization. Our findings revealed that, under stoichiometric trigger molecule concentrations, miktoarms with three branches exhibited consistently faster depolymerization rates than those with two branches and linear copolymers. Conversely, at constant trigger molecule concentrations, the depolymerization rates of copolymers exhibited more complex behavior influenced by two opposing factors: the excess of trigger molecules, which increased with a decrease in the number of hydrophobic branches or blocks, and simultaneous head-to-tail depolymerization, which intensified with an increasing number of branches. Our study elucidates the intricate interplay between copolymer architecture, trigger molecule concentrations, and depolymerization dynamics, providing valuable insights for the rational design of amphiphilic copolymers with tunable demicellization and cargo release properties.

Hyperuricemia is mainly caused by the overproduction of uric acid (UA) catalyzed from xanthine by xanthine oxidase (XO) in abnormal purine metabolism in human body. There is an increasing demand for developing novel XO inhibitors of plant origins. The inhibition kinetics and type as well as actions of hesperetin against XO were investigated in vitro using multi-spectroscopic methods including UV-Vis absorption, Fourier transform infrared spectroscopy (FT-IR), fluorescence spectroscopy and molecular docking simulation. Results indicated that hesperetin reversibly inhibited XO in a competitive manner with an inhibition constant (Ki) value of (2.15 ± 0.05) × 10-6 mol/L. Hesperetin had a higher scavenging rate against O2- radical generated by the XO reaction system. The binding of hesperetin to the active site of XO altered the protein’s secondary structure as demonstrated by FT-IR and fluorescence spectra. Molecular docking study revealed that hesperetin had highly affinity to XO and the bonding of hesperetin to the molybdopterin (Mo-pt) active center inhibited not only substrate entry, but also prevented oxygen binding to flavin adenine dinucleotide (another active center in XO). Additionally, hydrophobic interactions and hydrogen bonds contributed to the stabilization of the hesperetin-XO complex. The results suggested that hesperetin be a promising natural XO inhibitor to alleviate hyperuricemia and gout.

Fibroin-chitosan composites, especially those containing nanohydroxyapatite, show potential for bone tissue regeneration. The physicochemical properties of these biocomposites depend on the compatibility between their components. In this study, the intermolecular interactions of fibroin and chitosan were analyzed using a molecular dynamics approach. Two types of systems were investigated: one containing acetic acid and the other containing calcium (Ca²⁺) and hydrogen phosphate (HPO₄²⁻) ions mimicking hydroxyapatite conditions. After obtaining the optimal equilibrium structures, the distributions of several types of interactions including hydrogen bonds, ionic contacts, and hydrophobic contacts along with the structural and energetical features were examined. The calculated binding energy values for the fibroin-chitosan complexes confirm their remarkable stability. The high affinity of fibroin for chitosan can be explained by the formation of a dense network of interactions between considered biopolymers. These interactions were found to be primarily hydrogen bonds and ionic contacts involving ALA, ARG, ASN, ASP, GLN, GLU, GLY, LEU, PRO, SER, THR, TYR, and VAL residues. As it was established, the complexation of fibroin with chitosan maintains the β-sheet conformation of the peptide. β-Sheet fragments in fibroin are involved in the formation of significant amount of hydrogen bonds and ionic contacts with chitosan.

A better understanding of high temperature processes in slags contributes to facilitate knowledge based design of the solidified product. Here, a slag analogue with a nominal composition of 17 wt% LiMnO2 and 83 wt% Ca2SiO4 was synthesized encountering fairly high cooling rates. The Mn species from 1223 K to 1773 K was simulated using a thermodynamic model assuming a homogeneous melt. The micro-composition including the Mn species of the solidified slag was determined experimentally and was used as basis for molecular dynamics (MD) simulation. The MD simulation provides information on structure and viscosity at high temperatures, otherwise difficult to access. These parameters significantly influence oxidation state of redox-active elements and the solidified product. The micro-composition analyzed by electron probe micro analysis (EPMA) and synchrotron based micro-X-ray fluorescence (micro-XRF) showed that Mn-rich and Ca-Si-rich phases are separated. While the Mn-O phases did not contain noticeable Ca, the Ca2SiO4 phase had incorporated 0.6 wt% of Mn. The slag solidified into round shaped and droplet shaped grains of a Li-Mn-oxide, some Mn3O4 and Ca2SiO4. The powder X-ray diffraction (PXRD) confirmed the formation of larnite, the identity of the Li-Mn-oxide however remained inconclusive. The Mn oxidation state (OS) was identified using synchrotron based micro-X-ray absorption near edge spectroscopy (micro-XANES). The Mn-O grains, matched well with Li-Mn-oxides and a Mn OS: +3 e.g. LiMn3+O2. Small areas matching Hausmannite (Mn2+Mn23+O4) were also identified. The OS of Mn in the silicate phase could not be identified. For comparison a slowly cooled slag analogue with similar composition however higher Si content, was also subjected to micro-XANES. The slowly cooled slag formed long Mn-rich needles in a matrix of large calcium silicate crystals. The Mn-rich crystals matched well with the XANES spectrum of a Mn3+ Li-oxide like LiMn3+O2. At the rim of the needles the Mn-spectra matched well the Hausmannite (Mn2+Mn23+O4) reference. In the silicate phases Mn had a OS: +2, unambiguously. The melt structure at different temperatures of two compositions i.e. LiMn3+O2 and Ca2SiO4 was simulated using molecular dynamics (MD). They serve as model compositions assuming a heterogeneous melt. The results show significant different degrees of polymerization and viscosity. Information from MD simulations can support the identification of potentially different oxygen permeability and with that prediction of oxidation states. The bulk composition was identified by inductively coupled plasma optical emission spectrometry (ICP-OES), bulk structure by PXRD and bulk species by lab-XANES. The synchrotron micro analysis including micro-XRD were performed at the microfocus beamline I18 at the Diamond Light Source. Pure reference compounds were prepared and characterized with the same multi-modal approach.

Gliomas are common primary central nervous system (CNS) tumours which are often very difficult to diagnose, stage and manage because of their heterogeneity and molecular aberrations. The notable hallmark of gliomas is integrated genome mutations and methylome that correlates with distinctive patterns of transcription that potentiates glioma heterogeneity, angiogenesis and ultimately poor prognosis. The World Health Organization (WHO) has decided to reclassify gliomas based on molecular markers rather than the traditional anatomical basis; use of Nuclear Medicine techniques e.g. SPECT/PET and Magnetic Resonance Imaging (MRI) techniques based on molecular markers is set to become the future gold standards. This has led to the investigations on potential for the use of non-invasive imaging techniques such as [68Ga]68Ga-RGD positron emission tomography (PET) to be utilised routinely in clinical practice based on angiogenic markers and also the potential to add information that may assist in drug-design and therapeutic decision making. This review aims to provide an overview of the basis of recent advances in glioma imaging using molecular targeting with positron emission tomography and SPECT imaging, as well as the role in patient management i.e. diagnosis, staging, recurrence detection etc.

Morphological and phylogenetic (45S nrDNA+RPB1 gene) analyses of three glomoid spore-producing arbuscular mycorrhizal fungi revealed the presence of two new species be-longing to the genus Glomus in the family Glomeraceae. In the field, Glomus highlandensis sp. nov. was found in a saltmarsh of the Scottish Highlands and in maritime sand dunes of the Baltic Sea in Poland, both saline environments, while G. mongioie sp. nov. originates from the Italian Alps. Phylogenetic placement analysis using environmental sequences indicated that G. highlandensis could have likely worldwide distribution while G. mongioie seems to be a rare species in the world. The molecular and phylogenetic analysis provided important insights about the presence of ribosomal variants in Glomus, with potential negative implication in phylogeny and species recognition.

The kinase pathway plays a crucial role in blood vessel function. Particular attention is paid to VEGFR-type 2 angiogenesis and vascular morphogenesis as the tyrosin kinase pathway is preferentially activated. In silico studies were performed on several peptides that affect VEGFR2 in both stimulating and inhibitory ways. This investigation aims to examine the molecular properties of VEGFR2, a molecule primarily involved in the processes of vasculogenesis and angiogenesis. These relationships were defined by the interactions between vascular endothelial growth factor receptor 2 (VEGFR2) and the structural features of the systems. The chemical space of the inhibitory peptides and stimulators was described using topological and energetic properties. Furthermore, chimeric models of stimulating and inhibitory proteins (for VEGFR2) were computed using the protein system structures. The interaction between the chimeric proteins and VEGFR was computed. The chemical space was further characterized using complex manifolds and high-dimensional data visualization. The results show that a slightly similar chemical area is shared by VEGFR2 and is shared by stimulating and inhibitory proteins. On the other hand, the stimulator peptides and the inhibitors have distinct chemical spaces.

The mesoporous heteroatom molecular sieve MCM-41 bulk crystals with the crystalline phase were synthesized via a one-step hydrothermal method using an ionic complex as template. The ionic complex template was formed by interaction between cetyltrimethylammonium ions and metal complex ion [M (EDTA)]2- (M=Co or Ni ). The materials were characterized by X-ray diffraction, scanning electron microscopy, high-resolution transmission electron microscopy, N2 adsorption–desorption isotherms, and X-ray absorption fine structure spectroscopy. The results showed that the materials possess a highly ordered mesoporous structure with the crystalline phase and possess high uniform ordered arrangement channels. The structure is in the vertical cross directions with a crystalline size of about 12 µm and high specific surface areas. The metal atoms were incorporated into the zeolite frameworks in the form of octahedral coordinate and have a uniform distribution in the materials. The amount of metal complexes formed by metal ion and EDTA is an essential factor for the formation of the vertical cross structure. Comparing to Si-MCM-41, the samples exhibited better conversion, higher selectivity for cumene cracking.

Rotavirus (RV) replicates within viroplasms, membrane-less electron-dense globular cytosolic inclusions with liquid-liquid phase properties. In these structures occur the virus transcription, replication, and packaging of the virus genome in newly assembled double-layered particles. The viroplasms are composed of virus proteins (NSP2, NSP5, NSP4, VP1, VP2, VP3, and VP6), single and double-stranded virus RNAs, and host components such as microtubules, perilipin-1 and chaperonins. The formation, coalescence, maintenance, and perinuclear localization of viroplasms rely on their association with the cytoskeleton. A stabilized microtubule network involving microtubules and kinesin Eg5 and dynein molecular motors is associated with NSP5, NSP2, and VP2, facilitating dynamic processes such as viroplasm coalescence and perinuclear localization. Key post-translation modifications, particularly phosphorylation events of RV proteins NSP5 and NSP2, play pivotal roles in orchestrating these interactions. Actin filaments also contribute, triggering the formation of the viroplasms through the association of soluble cytosolic VP4 with actin and the molecular motor myosin. This review explores the evolving understanding of RV replication, emphasizing the host requirements essential for viroplasm formation and highlighting their dynamic interplay within the host cell.

Mosquitoes genus Aedes are the most important arthropod disease vector. Dengue Virus (DENV) and Chikungunya Virus (CHIKV) are the main arboviruses distributed in the world. Based on entomo-virological surveillance, appropriating public health strategies can be addressed to contain cases and control outbreaks. This study aims to show the potential performance of two new molecular methods for detecting DENV serotypes and CHIKV in mosquitoes. Mosquitoes were collected in urban areas and sylvatic areas between July to August 2023, DENV and CHIKV were screened using new multiplex RT-PCR and RT-q PCR. A total of 2150 mosquitoes were trapped including 976 Aedes (959 Ae. egypti, 6 Ae. furcifer and 11 Ae. Vittatus) and 1174 Culex from 39 pools of a maximum of 30 mosquitoes each, tested by molecular screening, 7.7% (3/39) were positive for DENV, DENV-1 was detected in one pool (1/3), and DENV-3 in two pools (2/3). All the pools were negative for CHIKV. The overall minimum infection rate (MIR) of DENV in this study was 3.07 (95% CI: 2.24 —19.86). This study shows the usefulness of our new molecular tools in DENV serotypes and CHIKV surveillance.

Coarse-grained molecular dynamics simulations are employed to investigate the spatiotemporal evolution of vesicles (polymersomes) by the self-assembly of randomly distributed amphiphilic BAB triblock copolymers with hydrophilic A and hydrophobic B blocks in an aqueous solution. The vesiculation pathway consists of several intermediate structures, such as an interconnected network of copolymer aggregates, a cage of cylindrical micelles and a lamellar cage. The cage-to-vesicle transition occurs at a constant aggregation number and practically eliminates the hydrophobic interfacial area between the B block and solvent. Molecular reorganization under-lying the sequence of morphology transitions from a cage-like aggregate to a vesicle is nearly isentropic. The end-to-end distances of isolated copolymer chains in solution and those within a vesicular assembly follow log normal probability distributions. This is attributed to the pre-ponderance of folded chain configurations in which the two hydrophobic end groups of a given chain stay close to each other. However, the probability distribution of end-to-end distances is broader for chains within the vesicle as compared to that of a single chain. This is due to the swelling of the folded configurations within the hydrophobic bilayer. Increasing the hydropho-bicity of the B block reduces the vesiculation time without qualitatively altering the self-assembly pathway.

Improper disposal of waste plastic has caused serious ecological and environmental pollution problems. Transforming plastics into high value-added chemicals can not only achieve efficient recycling of waste plastics, but also an effective way to control white pollution. The catalyst selectively breaks the C-C bond of polyolefin plastic under heat treatment and converts it into liquid fuel, thus realizing sustainable recycling of plastics and has a good development prospect. This review provides a detailed overview of the current development of catalytic pyrolysis, catalytic hydrolysis, solvent decomposition and supercritical hydrothermal liquefaction for cracking plastics to make fuel oil. The reaction mechanism, influencing factors and promoting effects of catalysts in various degradation technologies are analyzed and summarized and the latest proposed tandem reaction for degrading plastics is briefly introduced. Finally, some optimization paths of waste plastic pyrolysis to fuel oil technology are proposed: synergies between mixed raw materials, in-depth exploration of catalysts, design and manufacture of reactors that match the pyrolysis technology. All these are important research directions for promoting the industrialization of plastic pyrolysis to fuel oil.

Based on screening in computational biology and biological in vitro assays, five natural products isolated from extracts of the herbal medicine toad skin, such as cinobufagin (CBFi), bufalin (BFi), arenobufagin (ABFi), telocinobufagin (TBFi), bufotalin (BFTi), were subjected to molecular docking calculations with the use of SARS-CoV-2 main protease (PDB 6LU7 and 7BTF) and top-scoring ligand-receptor complexes were obtained. The results showed that the binding energy of ABFi to the 3CL protein was -17.044kcal/mol, which was higher than CBFi and TBFi. However, the binding energy of ABFi to the RdRp protease was -23.250 kcal/mol, which was much lower than that of CBFi and TBFi, EVEN lower than that of ABFi to the 3CL protein. ABFi also has polar interactions with amino acids such as Glu811, Ser814, Ser681 and Thr680 of RdRp enzyme. The results revealed that ABFi had a moderate inhibitory effect on the cell proliferation of SARS-CoV-2 in vitro, with an inhibition rate of 61.12%, even weaker than Remdesivir. This new discovery provides us with new ideas for in-depth studies on the development of natural products with this class of structural generalizations as inhibitors of SARS-CoV-2, and provides an experimental basis for the next step of mechanistic studies.

A novel investigation into the structure-function relationship was undertaken to enhance understanding of the mechanism of action of the vasoactive peptide angiotensin II (AngII) using unconventional substitutions such as AIB (α-aminobutyric acid), CHA (cyclohexylalanine acid), IAP (isonipecotic acid), TOAC (2,2,6,6-tetramethylpiperidine-1-oxyl-4-amine-4-carboxylic acid) at position 3, and DMT (2,6-dimethyl-Tyrosine) at position 4. Biological potency assays were conducted on guinea pig ileum, and structural features were analyzed using circular dichroism (CD) and molecular dynamics (MD). CHA3-AngII and AIB3-AngII analogs retained some agonistic activity, whereas IAP3-AngII and TOAC3-AngII derivatives were inactive. CD results indicated low conformational flexibility for AIB3-AngII and CHA3-AngII, and greater conformational restrictions for IAP3-AngII and TOAC3-AngII, consistent with computational modeling analyses. DMT4-AngII exhibited significant agonistic activity compared to the inactive Phe4AngII. Molecular modeling suggested a potential interaction between the hydroxyl group of Tyr4 and the amide bond between positions 7 and 8. AngII showed greater conformational restriction compared to DMT4-AngII and Phe4-AngII, underscoring the importance of tyrosine at position 4.

Oncolytic virotherapy is a promising immunotherapy approach for cancer treatment, utilizing viruses to preferentially infect and eliminate cancer cells while stimulating immune responses. In this review we synthesize current literature on the molecular circuits of immune sensing and response to oncolytic virotherapy; focusing on viral DNA or RNA sensing by infected cells, cytokine and danger-associated signal sensing by neighboring cells, and subsequent downstream activation of immune pathways. The sequential sense-and-response mechanisms involve the triggering of molecular sensors by viruses or infected cells to activate transcription factors and related genes for a breadth of immune responses. We describe how molecular signals induced in the tumor upon virotherapy can trigger diverse immune signaling pathways, activating both antigen-presenting cell-based innate and T cell-based adaptive immune responses. Insights into these complex mechanisms provide valuable knowledge for enhancing oncolytic virotherapy strategies.

Understanding the interplay among organophosphorus flame-retardants (OPFRs), microplastics, and freshwater organisms is crucial for unravelling the dynamics within freshwater environments and foreseeing the potential impacts of organic pollutants and plastic contamination. For that purpose, the present research assessed the exposure impact of 10 mg L–1 flame-retardant alumin-ium diethylphosphinate (ALPI), 10 μg mg–1liver microplastics polyurethane (PU), and the combina-tion of ALPI and PU on the freshwater planarian Girardia tigrina. The exposure of G. tigrina to both ALPI and PU revealed a sequential effect, i.e., a decrease in locomotor activity, while other molecular biomarkers (oxidative stress biomarkers and metabolic response) remained unaffected. Despite this fact, it was possible to observe that the range (min-max) of responses of exposed or-ganisms were altered, in the particular case of electron transport system, cholinesterase activity, glutathione S-transferase, catalase and levels of total glutathione and proteins, showing that the energetic costs for detoxification and antioxidant capacity might be causing less energy allocated for the planarian activity. By examining the physiological, behavioural, and ecological responses of planarians to these pollutants, insights can be gained into broader ecosystem-level effects and inform strategies for mitigating environmental risks associated with OPFRs and microplastic pol-lution in freshwater environments.

This study presents a detailed computational investigation aimed at identifying and evaluating potential small organic molecular scaffolds as inhibitors targeting the Pks13 protein, a critical enzyme in tuberculosis (TB) drug discovery. Our approach integrates multiple computational techniques, including quantitative structure-activity relationship (QSAR) modelling, compound library generation, molecular docking, biological activity prediction, re-evaluation of screened compounds, molecular dynamics (MD) analysis, and binding free energy estimation using the MM-GBSA approach. We developed a robust QSAR model using multiple linear regression (MLR) techniques, specifically tailored to predict the minimum inhibitory concentration (MIC) values of potential anti-TB agents. This model demonstrated excellent predictive performance, validated through rigorous internal and external validation procedures. Through molecular docking simulations, we identified five promising inhibitors Ethyl (R,Z)-2-(2-((2-chlorobenzyl) oxy)benzylidene)-5-(4-chlorophenyl)-7-methyl-3-oxo-2,3-dihydro-5H-thiazolo [3,2-a] pyrimidine-6-carboxylate (PKD1), (7R,9aR)-7-(2-hydroxyphenyl)-4-(2-methoxyphenyl)-3-methyl-7,8,9,9a-tetrahydroisoxazolo[5,4-b]quinolin-5(6H)-one (PKD2), (7-(4-methoxy phenyl)-2-methyl-3-phenylpyrazolo[1,5-a]pyrimidin-5-yl)(4-(3-(trifluoromethyl)phenyl) piperazin-1-yl)methanone (PKD3), (8S,10S)-10-(((2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyl tetrahydro-2H-pyran-2-yl)oxy)-6,8,11-trihydroxy-8-(2-hydroxyacetyl)-1-methoxy-7,8,9,10-tetra-hydrotetracene-5,12-dione (PKD4), 3-(3,4-dimethylphenyl)-5-((2-(4-fluorophenyl)-2-oxoethyl) thio)-6-phenyl-2-thioxo-2,3,5,7a-tetrahydrothiazolo[4,5-d]pyrimidin-7(6H)-one (PKD5)with high binding affinities, prioritizing them based on their binding energies. These selected compounds were further assessed for their biological activity predictions, guiding the selection of candidates for experimental validation. Subsequent re-evaluation using absolute binding free energy estimation and MD simulations provided insights into the stability and dynamics of the protein-ligand complexes over time. Our findings highlighted the potential of identified compounds as stable binders within the Pks13-TE domain binding pocket, underscoring their viability as drug candidates. Additionally, binding free energy analysis using MM-GBSA reaffirmed the strong affinity of the proposed compounds towards Pks13. Our integrated computational approach offers a systematic and detailed framework for the identification and characterization of potential Pks13 inhibitors with specific relevance to TB drug discovery.

The causal networks are important for understanding the signaling alterations in diseases. To reveal the network pathways affected in epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs), which are related to poor prognosis of cancer, the molecular networks and gene expression in diffuse- and intestinal-type gastric cancer (GC) have been analyzed. The network pathways in GC were analyzed in Ingenuity Pathway Analysis (IPA). The analysis of the probe sets of which gene expression has significant differences between diffuse- and intestinal-type GC in RNA Sequencing publicly available data identified 1099 causal networks in diffuse- and intestinal-type GC. Master regulators of the causal networks included lenvatinib, pyrotinib, histone deacetylase 1 (HDAC1), mir-196, and erb-b2 receptor tyrosine kinase 2 (ERBB2). The analysis of the HDAC1-interacting network identified the involvement of regulation of EMT by growth factors pathway, coronavirus pathogenesis pathway, and vorinostat. The network had RNA-RNA interactions with microRNAs such as mir-10, mir-15, mir-17, mir-19, mir-21, mir-217, mir-223, mir-25, mir-27, and mir-34. These molecular networks revealed in the study may lead to the identification of drug targets for GC.

The study is based on information as the property of matter and its evolution from chemical to digital information. Consequences of these forms of information include molecular, modular, cel-lular, non-human, and human individual interactions, as well as human-machine interaction, and the formation of corresponding modules through self-organizing selective processes. The function of modular structures is decision-making and is analogous to the behavior of an intelligent agent. The evolutionary modular model is proposed based on the interaction of evolutionary factors (matter, energy, information, self-organization, natural selection, and heritability) among themselves and with the arrow of time. In conclusion, we realize that the essence of the evolution of living organ-isms is modular evolution. Modules through which the survival and reproduction of living organ-isms is ensured, are formed by two basic molecular processes, which are molecular recognition or information and modular self-organization.

The novel coronavirus disease (COVID-19) pandemic has resulted in over 720 million confirmed cases and 7 million deaths worldwide, with insufficient treatment options. Innumerable efforts are being made around the world for faster identification of therapeutic agents to treat the deadly disease. Postacute sequelae of SARS-CoV-2 infection or COVID-19 (PASC), also called Long COVID, is still being understood and lacks treatment options as well. A growing list of drugs are being suggested by various in silico, in vitro and ex vivo models, however currently only two treatment options are widely used: the RNA-dependent RNA polymerase (RdRp) inhibitor remdesivir, and the main protease inhibitor nirmatrelvir in combination with ritonavir. Computational drug development tools and in silico studies involving molecular docking, molecular dynamics, entropy calculations and pharmacokinetics can be useful to identify new targets to treat COVID-19 and PASC, as shown in this work and our recent paper that identified alendronate as a promising candidate. We have now investigated all bisphosphonates which can bind competitively to nidovirus RdRp-associated nucleotidyl (NiRAN) transferase domain, and systematically down selected seven candidates (CHEMBL608526, CHEMBL196676, CHEMBL164344, CHEMBL4291724, CHEMBL4569308, CHEMBL387132, CHEMBL98211), two of which closely resemble the approved drugs minodronate and zoledronate. This work and our recent paper together provide an in silico mechanistic explanation for alendronate and zoledronate users having dramatically reduced odds of SARS-CoV-2 testing, COVID-19 diagnosis, and COVID-19-related hospitalizations, and indicate that similar observational studies with minodronate could be valuable.

Fish is a very healthy food that is a great source of proteins, vitamins, minerals, and essential fatty acids. For many people in developing nations, like Nigeria, smoked and dried fish serves as a significant source of protein and is an integral part of the traditional diet. However, smoked and dried fish are susceptible to fungal growth, especially when the storage conditions are not right, and it has been discovered that many products contain fungi that are easily visible on the surface. This study investigated the diversity and occurrence frequency of contaminated fungi species in dried fishes sold in local markets of Awka in Anambra state, Nigeria. Twenty-four fungal isolates with varying colony morphology were isolated from the various dried fish products. The contaminating species were further subjected to lactophenol cotton blue (LPCB) staining and Ten (10) Unique fungal morphology was detected. Carbohydrate utilization test was used to select unique isolates and further molecular identification showed successful PCR amplification of the isolates. The current study identified various fungal groups contaminating dried fish products sold in Awka Markets. The three dominant genera were the fungal genera' Aspergillus, Penicillium and Fusarium. These results suggest that most dried fish being sold in the Markets are contaminated with multiple fungi, posing a critical health risk to individuals. Thus, there is a need for attention to be paid to the packaging and storage of dried fish to lessen the likelihood of air exposure, lower water activity, and prevent microbiological growth on the dried fish.

Lumpy skin disease (LSD), caused by a virus within the Poxviridae family and Capripoxvirus genus, induces nodular skin lesions in cattle, spreading through direct contact and insect vectors, significantly affecting global cattle farming. Despite available vaccines, their effectiveness is limited by poor bioavailability and adverse effects. Our study aimed to identify potential inhibitors targeting LSD-associated DNA polymerase protein, selecting LSDV039 for further investigation through comprehensive analysis and computational methods. Virtual screening revealed rhein and taxifolin as potent binders among 380 phytocompounds, with respective affinities of -8.965 and -7.195 kcal/mol. Canagliflozin and tepotinib exhibited strong affinities (-9.858 and -8.856 kcal/mol) among 718 FDA-approved antiviral drugs. Molecular dynamics simulations of canagliflozin, tepotinib, rhein, and taxifolin highlighted taxifolin's superior stability and binding energy. Rhein displayed compactness in RMSD and RMSF but fluctuations in Rg and SASA, while canagliflozin demonstrated stability compared to tepotinib. The study highlights the promising potential of repurposed drugs and phytocompounds as LSD therapeutics. However, extensive validation through in-vitro, in-vivo, and clinical trials is crucial for their practical application.

Alkaloid-based urea derivatives were produced with high yield through the reaction of anabasine and cytisine with isoxazolylphenylcarbamates in boiling benzene. Their antitumor ac-tivity in combination with the commonly used six anticancer drugs namely cyclophosphane, fluorouracil, etoposide, cysplatine, ribomustine with different mechanisms of action was investi-gated. Based on the quantum chemical calculations data and molecular docking, hypotheses have been put forward to explain their mutual influence when affecting on the С6 rat glioma model cells.

Asymmetric lithium salts, such as Lithium (difluoromethanesulfonyl)(trifluoromethanesulfonyl)imide (LiDFTFSI), have been demonstrated to surpass traditional symmetric lithium salts with improved Li+ conductivity and the capacity to generate stable solid electrolyte interphase (SEI) while maintaining compatibility with aluminum (Al0) current collector. However, the intrinsic reductive mechanism through which LiDFTFSI influences battery performance remains unclear and under debate. Herein, the detailed SEI reactions of LiDFTFSI-based electrolytes were investigated by combining density functional theory and molecular dynamics, aiming to clarify the formation process and atomic structure of SEI. Our results show that asymmetric DFTFSI– weakens the interaction between carbonate solvents and Li+, and substantially alter the solvation structure, exhibiting a well-balanced coordination capacity to bis(trifluoromethanesulfonyl)imide (TFSI–). Nanoseconds hybrid molecular dynamics simulation further reveals that the preferential decomposition of LiDFTFSI produces sufficient LiF and Li2O to facilitate a robust SEI. Moreover, the abundant F– generated from LiDFTFSI decomposition accumulates on the Al surface and subsequently combines with Al3+ from the current collector to form AlF3, potentially inhibiting corrosion of the current collector. Overall, these findings elucidate how LiDFTFSI regulates the solvation sheath and SEI structure, advancing the development of high-performance electrolytes compatible with current collector.

In genetic conflicts, driver and killer elements achieve biased survival, replication, or transmission over sensitive and targeted elements through a wide range of molecular mechanisms, including mimicry. Driving mechanisms manifest at all organismal levels, from the biased propagation of individual genes, as demonstrated by transposable elements, to the biased transmission of genomes, as illustrated by viruses, to the biased transmission of cell lineages, as in cancer. Targeted genomes are vulnerable to molecular mimicry through the conserved motifs they use for their own signaling and regulation. Mimicking these motifs enables a selfish element to control core target processes, and can occur at the sequence, structure, or functional level. Molecular mimicry was first appreciated as an important phenomenon more than twenty years ago. Modern genomics technologies, databases, and machine learning approaches offer tremendous potential to study the distribution of molecular mimicry across genetic conflicts in nature. Here, we explore the theoretical expectations for molecular mimicry between conflicting genomes, the trends in molecular mimicry mechanisms across known genetic conflicts, and outline how new examples can be gleaned from population genomic datasets. We discuss how mimics involving short sequence-based motifs or gene duplications can evolve convergently from new mutations. Whereas, processes that involve divergent domains or fully-folded structures occur among genomes by horizontal gene transfer. These trends are largely based on a small number of organisms and should be reevaluated in a general, phylogenetically independent framework. Currently, publicly available databases can be mined for genotypes driving non-mendelian inheritance patterns, epistatic interactions, and convergent protein structures. A subset of these conflicting elements may be molecular mimics. We propose approaches for detecting genetic conflict and molecular mimicry from these datasets.

The present article describes the synthesis of an isonicotinate-derived meso-arylporphyrin, that has been fully characterized by spectroscopic methods (including fluorescence spectroscopy), as well as by elemental analysis and by HR-MS. The structure of a n-hexane monosolvate has been determined by single crystal X-ray diffraction analysis. The radical scavenging activity of this new porphyrin against the 2,2-diphenyl-1-picrylhydrazyl (DDPH) radical has been measured. Its antifungal activity against three yeast strains (C. albicans ATCC 90028, C. glabrata ATCC 64677 and C. tropicalis ATCC 64677) has been tested, using the disk diffusion and the microdilution methods. Whereas the measured antioxidant activity was low, the porphyrin showed moderate but encouraging antifungal activity. Finally, a study of its effect on the germination of lentil seeds revealed interesting allelopathic properties.

In recent decades, there has been a rising demand for anti-aging interventions aimed at postponing or potentially reversing indicators of skin aging. The use of collagen-based nutraceutical supplements has gained popularity as they have shown promise in enhancing skin health and reducing signs of aging. The aim of this randomized, placebo-controlled, blinded study was to investigate the effects of 2.5 g COLLinstant® LMW, a novel cosmeceutical containing low molecular weight (≤ 1000 Da) collagen peptides, on skin aging and health. The trial was conducted in 80 healthy women aged 30 years and older. They received a daily oral dose of either the food supplement (n = 40) or placebo (n = 40) for six weeks. Skin assessment was performed based on validated objective methods, such as Visioface 1000D (skin wrinkling), cutometry (elasticity and fatigue) and corneometry (skin hydration) at baseline (T0), and at week 6 (T6). After 6 weeks, participants that received collagen had significant improvements in biometric skin wrinkle parameters from baseline, with a reduction in volume by 46%, in area by 44%, and in depth by 9%, along with a greater increase in skin moisturization (by 34%) than those in the placebo group (p &lt; 0.001). The food supplement did not significantly modify skin firmness or fatigue and had only slight beneficial effects on skin elasticity. The investigational product was well tolerated. The observed effects aligned closely with the subjective assessments reported by study participants. The study provides substantiated evidence supporting the efficacy of low molecular weight collagen peptides in restoring altered skin biometric parameters, as objectively assessed. Thus, regular supplementation with this nutraceutical may contribute to achieving smoother and more radiant skin.

Structural and biochemical studies have recently revealed a range of rationally engineered nanobodies with efficient neutralizing capacity against SARS-CoV-2 virus and resilience against mutational escape. In this work, we combined atomistic simulations and conformational dynamics analysis with the ensemble-based mutational profiling of binding interactions for a diverse panel of SARS-CoV-2 spike complexes with nanobodies. Using this computational toolkit, we identified dynamic signatures and binding affinity fingerprints for the SARS-CoV-2 spike protein complexes with nanobodies Nb6 and Nb20, VHH E, a pair combination VHH E+U, a biparatopic nanobody VHH VE, and a combination of CC12.3 antibody and VHH V/W nanobodies. Through ensemble-based deep mutational profiling of stability and binding affinities, we identify critical hotspots and characterize molecular mechanisms of SARS-CoV-2 spike protein binding with single ultra-potent nanobodies, nanobody cocktails and biparatopic nanobodies. By quantifying dynamic and energetic determinants of the SARS-CoV-2 S binding with nanobodies, we also examine the effects of circulating variants and escaping mutations. We found that mutational escape mechanisms may be controlled through structurally and energetically adaptable binding hotspots located in the host receptor-accessible binding epitope that are dynamically coupled to the stability centers in the distant epitope targeted by VHH U/V/W nanobodies. The results of this study suggested a mechanism in which through cooperative dynamic changes, nanobody combinations and biparatopic nanobody can modulate the global protein response and induce the increased resilience to common escape mutants.

An H-bond involves the sharing of a hydrogen atom between an electronegative atom to which it is covalently bound (the donor) and another electronegative atom serving as an electron acceptor. Such bonds represent a critically important geometrical force in biological macromolecules and, as such, have been characterized extensively. H-bond formation invariably leads to a weakening within the acceptor moiety due to the pulling exerted by the donor hydrogen. This phenomenon can be compared to a spring connecting two masses; pulling one mass stretches the spring, similarly affecting the bond between the two masses. Herein, we describe the opposite phenomenon when investigating the energetics of the C-H...O=C bond. This bond underpins the most prevalent protein transmembrane dimerization motif (GxxxG) in which a glycine C-H on one helix forms a hydrogen bond with a carbonyl in a nearby helix. We use isotope-edited FT-IR spectroscopy and corroborating computational approaches to demonstrate a surprising strengthening of the acceptor C=O bond upon binding with the glycine C-H. We show that electronic factors associated with the C-H bond strengthen the C=O oscillator by increasing the s-character of the -bond, lowering the hyperconjugative disruption of the -bond. In addition, a reduction of the acceptor C=O bond’s polarity is observed upon the formation of the C-H...O=C bond. Our findings challenge the conventional understanding of H-bond dynamics and provide new insights into the structural stability of inter-helical protein interactions.

The application of deep learning algorithms to predict the molecular profiles of various cancers from digital images of hematoxylin and eosin (H&E)-stained slides has been reported in recent years, mainly in gastric and colon cancers. In this study, we investigated the potential use of H&E-stained endometrial cancer slide images to predict the associated mismatch repair (MMR) status. H&E-stained slide images were collected from 127 cases of the primary lesion of endometrial cancer. After digitization using a Nanozoomer virtual slide scanner (Hamamatsu Photonics), we segmented the scanned images into 5,397 tiles of 512 × 512 pixels. The MMR proteins (PMS2, MSH6) were immunohistochemically stained, classified into MMR proficient/deficient, and annotated for each case and tile. We trained several neural networks, including convolutional and attention-based networks, using tiles annotated with the MMR status. Among the tested networks, ResNet50 exhibited the highest area under the receiver operating characteristic curve (AUROC) of 0.91 for predicting the MMR status. The constructed prediction algorithm may be applicable to other molecular profiles and useful for pre-screening before implementing other, more costly genetic profiling tests.

Mink astrovirus infection remains a poorly understood disease entity, and the aetiological agent itself causes disease with a heterogeneous course, including gastrointestinal and neurological symptoms. This paper presents cases of astrovirus infection in mink from continental Europe. RNA was isolated from the brains and intestines of animals showing symptoms typical of shaking mink syndrome (n = 6). RT-PCR was used to detect astrovirus genetic material, and the reaction products were separated on a 1% agarose gel. The specificity of the reaction was confirmed by sequencing all samples. The presence of astrovirus RNA was detected in each of the samples tested. Sequencing and bioinformatic analysis indicated the presence of the same variant of the virus in all samples. Comparison of the variant with the sequences available in bioinformatics databases confirmed that the Polish isolates form a separate clade, closely related to Danish isolates. The similarity of the Polish variant to those isolated in other countries ranged from 2.4% (in relation to Danish isolates) to 7.1% (in relation to Canadian isolates). Phylogenetic relationships between variants appear to be associated with the geographic distances between them. To our knowledge, this work describes the first results on the molecular epidemiology of MAstV in continental Europe. The detection of MAstV in Central Europe indicates the need for further research to broaden our understanding of the molecular epidemiology of MAstV in Europe.

Cholinesterase (ChE) and secretase (BACE) inhibitors, and fibril- and β-amyloid-suppressing medicines are used to treat Alzheimer's disease (AD) symptomatically. The prevalence and complex nature of AD have increased the urgent need for multi-targeted directed ligands (MTDLs). This is because MTDLs can prevent potential drug-drug interactions during poly-therapy and have a better therapeutic profile than single targeted agents. Using piperazine linker or spacer and two primary scaffolds, benzofuran and 8-hydroxyquinoline, a unique class of multi-targeted medicines was recently reported by our group. These compounds showed re-markable effectiveness in inhibiting Aβ1-42 aggregation and acting as iron chelators.The results prompted us to synthesize an additional series of compounds as multimodal anti-AD agents and investigate its inhibitor activities to ChE (AChE/BChE) and BACE1 enzymes. The resulting in-hibitory effects suggested that the compounds under study might be used to improve cognitive function. The docking analysis' findings revealed that the compounds bind to AChE and BChE by forming H-bond interactions with amino acid residues at binding sites and µ-stacking inter-actions with aromatic residues, whereas the binding to BACE1 only revealed H-bond interac-tions with amino acid residues at binding sites.

Helical (frontier) molecular orbitals [Chem. Sci. 2013, 4, 4278] have been reported almost a decade ago. Yet, helical molecular spin densities [Mol. Phys. 2022, e2157774] have been observed by us only very recently. In this work, we have observed that some chiral boron clusters (B–16, B–20, B–24, and B–28) can simultaneously have helical molecular orbitals and helical spin densities. To our best knowledge, it is the first time we have discovered that inorganic boron clusters assume such an unprecedented property. We have unambiguously unraveled that it is chiral Jahn-Teller distortion of quasi-planar boron clusters that drives the formation of helical molecular spin densities. More interestingly, we have shown that elongation/enhancement of helical molecular orbitals can be achieved by simply adding more building blocks via a linker. Aromaticity properties of these boron clusters are also discussed. Implication of this work is straightforward that boron clusters may find potential applications in spintronics, such as molecular magnets.

Molecular classifications of colorectal cancer (CRC) are benefitting cancer research by providing insights into subtype-specific disease prognosis and better therapeutic intervention. So far different conventional DNA markers such as microsatellite instability (MSI), CpG island methylator phenotype (CIMP), chromosomal instability (CIN), and BRAF and KRAS mutations have been used to classify CRC patients but have not shown promising prognostic values. Here, for the first time, we show classification of CRC tumors from Saudi Arabian patients based on gene expression profile (GEP). An existing method of CRC subtyping has been applied to the GEP of tumors from Saudi CRC patients. Survival analysis was carried out on predicted CRC subtypes. In-silico functional analyses were conducted on the gene signature used for subtype prediction. The predicted subtypes showed distinct but statistically insignificant overall survival distribution (log-rank test, p = 0.069). Comparison of predicted subtypes in Saudi CRC patients with that of the French one showed significant dissimilarity in the two populations (Chi-square test, p = 0.0091). Functional analyses of the gene signature used for subtyping suggest their association with “cancer” and “gastrointestinal diseases”. Most of the signature genes were found differentially expressed in CRC tumors compared to adjacent normal tissues. Such a classification framework might help improve the treatment of colorectal cancer patients.

Brucellosis is a zoonoses caused by bacteria of the genus Brucella, which causes economic losses in livestock and threatens public health. A cross-sectional study was conducted to determine the prevalence of Brucella species and risk factors in smallholder dairy cattle in six regions of Tanzania from July 2019 to October 2020. Dairy cattle (n=2048) were sampled from 1371 farms. DNA ex-tracted from blood and vaginal swabs was tested for Brucella using qPCR targeting the IS711 gene and positives were tested for the alkB marker for B. abortus and BMEI1172 marker for B. melitensis. The molecular prevalence was 3.5% (95% CI: 2.8-4.4) with the highest prevalence 8.1% (95%CI: 4.6-13.0) in Njombe region. B. melitensis was the predominant species detected (66.2%). Logistic regression revealed PCR positivity in dairy cattle was higher in the animals with a history of abortion (OR: 3.17, 95%CI: 1.05-9.62) and farms without dogs around (OR: 2.68, 95%CI: 1.12-5.90). Further studies are recommended to understand the source of B. melitensis and the implications to veterinary public health. Livestock keepers should be informed of the risks and biosecurity practices to reduce introduction and control Brucella. Cattle and small ruminant vaccination pro-grams could be implemented to control brucellosis in high-risk populations in the country.