MultiKD-DTA: Enhancing Drug-Target Affinity Prediction Through Multiscale Feature Extraction.

The discovery and development of novel pharmaceutical agents is characterized by high costs, lengthy timelines, and significant safety concerns. Traditional drug discovery involves pharmacologists manually screening drug molecules against protein targets, focusing on binding within protein cavities. However, this manual process is slow and inherently limited.

In silico modeling of targeted protein degradation.

Targeted protein degradation (TPD) techniques, particularly proteolysis-targeting chimeras (PROTAC) and molecular glue degraders (MGD), have offered novel strategies in drug discovery. With rapid advancement of computer-aided drug design (CADD) and artificial intelligence-driven drug discovery (AIDD) in the biomedical field, a major focus has become how to effectively integrate these technologies into the TPD drug discovery pipeline to accelerate development, shorten timelines, and reduce costs. Currently, the main research directions for applying CADD and AIDD in TPD include: 1) ternary complex modeling; 2) linker generation; 3) strategies to predict degrader targets, activities and ADME/T properties; 4) In silico degrader design and discovery.

Stochastic simulation of soil moisture dynamics in farmland in the eastern region of the Songnen Plain.

Soil moisture is the core of the hydrological cycle in agroecosystems, and most of the studies on soil moisture dynamics modeling adopt deterministic research methods, which are not well suited to study the hydrological processes in agricultural fields under changing conditions. Therefore, the present study adopts a stochastic approach to reveal the distribution characteristics of soil moisture in agroecosystems under the effects of soil, climate, vegetation, and other influencing factors. Using soil moisture and precipitation data and based on a stochastic model of soil moisture dynamics, the point-scale soil moisture dynamic characteristics and soil moisture probability density function of farmland systems in the Songnen Plain region were investigated.

Residual Dynamics of Chlorantraniliprole and Fludioxonil in Soil and Their Effects on the Microbiome.

The increased use of chlorantraniliprole and fludioxonil has sparked concerns about their residues and impact on the soil microbiome, highlighting an urgent issue requiring attention. This study investigates the residue dynamics of corn after chlorantraniliprole and fludioxonil treatments, as well as their effects on soil enzyme activity and microbial community structure. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis showed a significant decrease in chlorantraniliprole and fludioxonil residues in the soil after combined application, especially with chlorantraniliprole.

Decreased expression of promotes apoptosis through the Hippo-YAP1 signaling pathway leading to diabetic erectile dysfunction.

Long non-coding RNAs (lncRNAs) primarily engage with mRNA, DNA, proteins, and microRNAs (miRNAs), thereby regulating gene expression; however, its specific role in diabetic erectile dysfunction (DED) has not been studied. This study aims to investigate the effects and mechanisms of in DED. The differential target gene was identified in the penile tissues of rats with DED through bioinformatics analyses.

Comparative effectiveness of glucagon-like peptide-1 agonists, dipeptidyl peptidase-4 inhibitors, and sulfonylureas on the risk of dementia in older individuals with type 2 diabetes in Sweden: an emulated trial study.

Background: The comparative effectiveness of glucagon-like peptide-1 (GLP-1) agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sulfonylureas on the risk of dementia in older individuals with type 2 diabetes mellitus (T2DM) is unknown.

Methods: We conducted a sequential trial emulation from 1st January 2010 to 30th June 2020 using data from Swedish national registers. Swedish residents who were aged 65 or older, had type 2 diabetes (T2DM), and initiated GLP-1 agonists, DPP-4 inhibitors, or sulfonylureas were followed for up to 10 years to assess the risk of dementia.

Preliminary Validation of Measures of Experienced, Perceived, and Internalized Stigma Among Adults Who Are d/Deaf or Hard of Hearing in the United States and Ghana.

Objectives: In this article, we examine the psychometric performance of 3 scales measuring experienced, perceived, and internalized d/Deaf or hard of hearing (d/DHH) stigma among adult (18 and older) populations of individuals who are d/DHH, including those who have been d/DHH since before they developed language (lifelong) and those who became d/DHH after they developed language (acquired) in the United States and Ghana.

Design: The preliminary validation study took place in the Greater Accra and Eastern regions of Ghana and across the United States. In the United States, all data were collected online via self-administered surveys in English.

Comprehensive analysis of molecular, physiological, and functional biomarkers of aging with neurological diseases using Mendelian randomization.

An increasing burden of neurological diseases (NDs) has been a public health challenge in an aging society. Age, especially biological age, is the most important risk factor for NDs. Identification of biomarkers of aging to capture NDs might lead to a better understanding of the underlying mechanisms of pathological brain aging and the implementation of effective intervention.

Associations between epigenetic aging and diabetes mellitus in a Swedish longitudinal study.

Diabetes mellitus type 2 (T2D) is associated with accelerated biological aging and the increased risk of onset of other age-related diseases. Epigenetic changes in DNA methylation levels have been found to serve as reliable biomarkers for biological aging. This study explores the relationship between various epigenetic biomarkers of aging and diabetes risk using longitudinal data.

Effects of Different Cultivation Modes on Morphological Traits and Correlations between Traits and Body Mass of Crayfish ().

In this study, juvenile crayfish hatched from the same population were cultured in different growing environments: pond (), paddy field (), and aquaculture barrel (), and fed for 60 days. Crayfishes were selected randomly, females and males, 50 tails each from six groups (D1-♀, D1-♂, D2-♀, D2-♂, D3-♀, D3-♂) to measure the following morphological traits: full length (), body length (), chelicerae length (), chelicerae weight (), cephalothorax length (), cephalothorax width (), cephalothorax height (), eye spacing (), caudal peduncle length (), and caudal peduncle weight (). We found that the coefficient of variation (CV) of was the largest in each culture mode, and males (28.

Hyperglycemia Inhibits Hepatic SHBG Synthesis Through the NGBR-AMPK-HNF4 Pathway in Rats with Polycystic Ovary Syndrome Induced by Letrozole in Combination with a High-Fat Diet.

Scope: Polycystic ovary syndrome (PCOS) is closely related to non-alcoholic fatty liver disease (NAFLD), and sex hormone-binding globulin (SHBG) is a glycoprotein produced by the liver. Hepatic lipogenesis inhibits hepatic SHBG synthesis, which leads to hyperandrogenemia and ovarian dysfunction in PCOS. Therefore, this study aims to characterize the mechanism whereby liver lipogenesis inhibits SHBG synthesis.

Exploration and structure-activity relationship research of benzenesulfonamide derivatives as potent TRPV4 inhibitors for treating acute lung injury.

RN-9893, a TRPV4 antagonist identified by Renovis Inc., showcased notable inhibition of TRPV4 channels. This research involved synthesizing and evaluating three series of RN-9893 analogues for their TRPV4 inhibitory efficacy.

Automated molecular structure segmentation from documents using ChemSAM.

Chemical structure segmentation constitutes a pivotal task in cheminformatics, involving the extraction and abstraction of structural information of chemical compounds from text-based sources, including patents and scientific articles. This study introduces a deep learning approach to chemical structure segmentation, employing a Vision Transformer (ViT) to discern the structural patterns of chemical compounds from their graphical representations. The Chemistry-Segment Anything Model (ChemSAM) achieves state-of-the-art results on publicly available benchmark datasets and real-world tasks, underscoring its effectiveness in accurately segmenting chemical structures from text-based sources.

Effects from medications on functional biomarkers of aging in three longitudinal studies of aging in Sweden.

Antihypertensive, lipid-lowering, and blood glucose-lowering drugs have slowed down the aging process in animal models. In humans, studies are limited, have short follow-up times, and show mixed results. Therefore, this study aimed to estimate the effects of commonly used medications on functional aging, cognitive function, and frailty.

Knockdown of programmed cell death factor 4 restores erectile function by attenuating apoptosis in rats with bilateral cavernous nerve crush injury.

Background: Apoptosis is an important pathologic mechanism of erectile dysfunction after radical prostatectomy. Studies have shown that programmed cell death factor 4 is connected to the modulation of apoptosis in many cells. However, the programmed cell death factor 4 function in the cavernous nerve injury erectile dysfunction is unclear.

LC-MS/MS methods for direct measurement of sepiapterin and tetrahydrobiopterin in human plasma and clinical applications.

Tetrahydrobiopterin (BH), a natural cofactor of aromatic amino acid hydroxylases, and sepiapterin, a natural precursor of BH, are endogenously present in human plasma. This is the first report on methods for direct quantification of sepiapterin and BH in human plasma by LC-MS/MS for pharmacokinetic assessment The analytes in plasma were harvested from blood that were treated with 10% ascorbic acid (AA) to a final concentration of 1% AA. The quantification methods were validated for calibration ranges of 0.

The Orco gene involved in recognition of host plant volatiles and sex pheromone in the chive maggot Bradysia odoriphaga.

The insect olfactory recognition system plays a crucial role in the feeding and reproductive behaviors of insects. The odorant receptor co-receptor (Orco), as an obligatory chaperone, is critical for odorant recognition by way of forming heteromeric complexes with conventional odorant receptors (ORs). To investigate the biological functions of Orco in perceiving host plant volatiles and sex pheromone, the Orco gene was identified from the chive maggot Bradysia odoriphaga transcriptome data.

Temporal Dynamics of Epigenetic Aging and Frailty From Midlife to Old Age.

Background: DNA methylation-derived epigenetic clocks and frailty are well-established biological age measures capturing different aging processes. However, whether they are dynamically linked to each other across chronological age remains poorly understood.

Methods: This analysis included 1 309 repeated measurements in 524 individuals aged 50-90 years from the Swedish Adoption/Twin Study of Aging.

.

Emvododstat is a potent inhibitor of dihydroorotate dehydrogenase and is now in clinical development for the treatment of COVID-19 and acute myeloid leukemia. Since the metabolism and pharmacokinetics of emvododstat in humans is time‑dependent, a repeat dose study design using a combination of microtracer radioactivity and high radioactivity doses was employed to evaluate the metabolism and excretion of emvododstat near steady state. Seven healthy male subjects each received 16 mg/0.

The binding mechanism of failed, in processing and succeed inhibitors target SARS-CoV-2 main protease.

Since the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several variants have caused a persistent pandemic. Consequently, it is crucial to develop new potential anti-SARS-CoV-2 drugs with specificity. To minimize potential failures and preserve valuable clinical resources for the development of other useful drugs, researchers must enhance their understanding of the interactions between drugs and SARS-CoV-2.

Bacteria pyruvate metabolism modulates AFB toxicity in Caenorhabditis elegans.

Aflatoxin B (AFB), the most potent mycotoxin and Group 1 human carcinogen, continues to pose a significant public health burden, particularly in developing countries. Increasing evidence has shown the gut microbiota as a key mediator of AFB toxicity through multiple interactive host-microbiota activities. In our previous study we observed that disturbances in bacterial pyruvate metabolism might have a significant impact on AFB in the host.

Advanced biological ageing predicts future risk for neurological diagnoses and clinical examination findings.

Age is a dominant risk factor for some of the most common neurological diseases. Biological ageing encompasses interindividual variation in the rate of ageing and can be calculated from clinical biomarkers or DNA methylation data amongst other approaches. Here, we tested the hypothesis that a biological age greater than one's chronological age affects the risk of future neurological diagnosis and the development of abnormal signs on clinical examination.

Recent Advances in Drug Discovery Toxicology.

Major advances in scientific discovery and insights that stem from the development and use of new techniques and models can bring remarkable progress to conventional toxicology. Although animal testing is still considered as the "gold standard" in traditional toxicity testing, there is a necessity for shift from animal testing to alternative methods regarding the drug safety testing owing to the emerging state-of-art techniques and the proposal of 3Rs (replace, reduce, and refine) towards animal welfare. This review describes some recent research methods in drug discovery toxicology, including in vitro cell and organ-on-a-chip, imaging systems, model organisms (, , and ), and toxicogenomics in modern toxicology testing.