Pharmacophore-oriented 3D molecular generation toward efficient feature-customized drug discovery.

Molecular generation is a cutting-edge technology with the potential to revolutionize intelligent drug discovery. However, currently reported ligand-based or structure-based molecular generation methods remain unpractical for real-world drug discovery. Here we propose an explicit pharmacophore-oriented 3D molecular generation method, termed PhoreGen.

Evaluated dietary quality is associated with reduced probability of epilepsy.

Background: The occurrence of epilepsy is significantly associated with the intake of specific nutrients such as calcium. However, the potential association between overall dietary quality and epilepsy remains undetermined.

Methods: Analytical data were retrieved from three consecutive cycles (2013-2018) of the National Health and Nutrition Examination Survey.

Targeting ATF4-DDIT4/TXNIP induced mitochondrial dysfunction and ferroptosis: ISRIB as novel therapy for septic cardiomyopathy.

Introduction: Sepsis-induced cardiomyopathy (SIC) is a reversible lesion in the early clinical stage, but often induces a high mortality rate in the late stage, and its specific mechanism is unknown. Thus, in-depth exploration of the biological progression mechanism of SIC plays a crucial role.

Methods: Through co-immunoprecipitation and molecular biological experiments, the functional interaction relationship between DDIT4 and TXNIP was clarified, and the effect of DDIT4/TXNIP on the progression of SIC was investigated both in vitro/vivo.

Interpretable Rotation-Equivariant Multiary-Valued Network for Attribute Obfuscation.

This paper focuses on the problem of preventing information leakage in neural networks, i.e., assuming that attackers have obtained intermediate-layer features of a neural network, and preventing attackers from inverting these features to the input with private information.

A Novel Peculiarity of TXNIP Reversing the Radioresistance of NPC and Inducing Ferroptosis by xCT-GSH-GPX4-ROS Axis.

Background: Radioresistance is a major problem in clinical treatment of nasopharyngeal carcinoma (NPC), and molecular mechanisms of radioresistance related to the antioxidant system are unknown. TXNIP (thioredoxin-interacting protein) is an endogenous inhibitor of thioredoxin. The system xCT/GSH/GPX4 axis is an important antioxidant system of ferroptosis in drug-resistant solid tumor therapy.

Attributable burden of steatotic liver disease on cardiovascular outcomes in Asia.

Background & Aims: The associations between metabolic dysfunction-associated steatotic liver disease (MASLD) and specific cardiovascular events, as well as their attributable burdens, remain inconsistent and underexplored within a single population. This large-scale prospective cohort evaluated the associations between MASLD and various cardiovascular outcomes. Two additional steatotic liver disease (SLD) subtypes - MASLD with increased alcohol consumption (MetALD) and alcohol-related liver disease (ALD) - were also evaluated.

The intricate interactions between the lungs and gut in patients: unraveling the crosstalk mechanism.

There is a growing body of evidence indicating that the stimulation of one organ can significantly influence the functioning of another. For instance, intestinal complications are frequently observed during respiratory diseases, and conversely, pulmonary complications can arise during intestinal diseases-a phenomenon referred to as lung-gut crosstalk. Patients suffering from mechanical ventilator-induced lung injury, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), and other pulmonary conditions have been shown to experience gastrointestinal dysfunction and related disorders.

Sustainable Substitution of Petroleum-Based Processing Oils with Soybean-Derived Alternatives in Styrene-Butadiene Rubber: Effects on Processing Behavior and Mechanical Properties.

This study evaluates the replacement of petroleum-based naphthenic oil with four types of soybean-derived alternatives-virgin soybean oil (SBO), epoxidized SBO (ESBO), expired SBO, and recycled SBO-in styrene-butadiene rubber (SBR) composites. The materials were tested in both staining rubber (SR) and non-staining rubber (NSR) systems to assess processing characteristics, mechanical performance, and environmental durability. Among the alternatives, SBO demonstrated the best overall performance, improving processability and tensile strength by over 10%, while ESBO enhanced ozone resistance by 35% due to its epoxide functionality.

Metabolic profiling of amniotic fluid by differential C-/C-isotope dansylation labeling LC-MS for application in trisomy 21 fetuses.

Introduction: Down syndrome, caused by the triplication of human chromosome 21 (trisomy 21 [T21]) or its distal segment, is the most prevalent chromosomal anomaly associated with intellectual disability in newborns.

Objectives: To investigate the relationship between T21 and hydrops by analyzing metabolomic alterations, identifying correlations, and exploring pathway regulation mechanisms. This study goes beyond biomarker discovery, aiming to elucidate the pathogenesis of T21 and to explore the underlying mechanism.

HDT2-mediated lysine deacetylation promotes phytochrome A degradation during photomorphogenesis in Arabidopsis.

The shift from skotomorphogenesis to photomorphogenesis, a developmental transition in seed plants, involves dramatic proteomic changes. Lysine acetylation (Lys-Ac) is an evolutionarily conserved and recognized post-translational modification that plays a crucial role in plant development. However, its role in seedling deetiolation remains unclear.

Single Cell Sequencing Reveals Cellular Heterogeneity in Mouse Dorsal Root Ganglion.

The dorsal root ganglion plays a crucial role in sensory transduction and modulation. Nevertheless, the specific physiological functions of the diverse cell types within the dorsal root ganglion remain poorly understood. Here, three physiologic mouse dorsal root ganglion data (GSE155622) were obtained from the NCBI database, yielding data on a total of 14 902 cells.

Ionic liquid modified MOF-808 for efficient adsorption and stable capture of radioactive iodine.

Radioactive iodine (I) is a potential risk to environmental safety and human health. The design of efficient and stable functional materials for I capture remains a challenge. In this work, a simple in-situ impregnation method is used to load Ionic Liquid (IL)-[Cmim][TfN] into the pores of MOF-808, named IL@MOF.

Bacterial co-infection and secondary infection in critically ill patients with acute respiratory failure of coronavirus disease 2019.

Objectives: The objective of the study is to understand the prevalence of bacterial co-infection and secondary infection in severe coronavirus disease 2019 (COVID-19) pneumonia in a tertiary hospital intensive care unit (ICU), the spectrum of pathogens, and the impact of these infections on clinical outcomes.

Materials And Methods: Retrospective analysis of all patients with COVID-19 with acute hypoxemic respiratory failure who were admitted to the ICU requiring invasive mechanical ventilation (IMV) or high-flow nasal cannula (HFNC) from January 2021 to August 2022.

Results: Of the 123 cases, 59.

Response to two Janus kinase inhibitors in a boy with SAVI during 2-year follow-up: case report and literature review.

STING-associated vasculopathy with onset in infancy (SAVI) represents an identified rare type I interferonopathy, triggered by gain-of-function mutations in the gene. It is characterized by early-onset systemic inflammation, cutaneous vasculopathy, pulmonary involvement, and recurrent bacterial infections. When conventional treatments prove ineffective in managing clinical symptoms, a high index of suspicion and prompt genetic testing become pivotal in considering the potential therapeutic role of Janus kinase (JAK) inhibitors, with ruxolitinib and tofacitinib emerging as promising treatment options.

SenExo-cCCT2 Reprograms Senescence Response and Anti-Tumor Immunity Following FOLFIRINOX Chemotherapy in Pancreatic Ductal Adenocarcinoma.

Combination chemotherapy and immunotherapy have failed to achieve breakthroughs in pancreatic ductal adenocarcinoma (PDAC). Chemotherapy-induced senescence is a potential solution for this problem. This study integrates clinical samples with single-cell transcriptomic sequencing, proteomics, and RNA sequencing and reveals that FOLFIRINOX (a combination regimen of 5-fluorouracil, oxaliplatin, irinotecan, and leucovorin) treatment induces a higher proportion of senescent tumor cells (senTCs).

Energy-based segmentation methods for images with non-Gaussian noise.

This paper proposes an energy-based segmentation method facilitated by the change point detection. We apply the Kullback-Leibler (KL) divergence to demonstrate the feasibility of our method for non-Gaussian noisy images. Notably, the algorithm automatically determines whether the model is solvable using a Gaussian approach and, if not, effortlessly switches to a non-Gaussian alternative.

Seasonal water level fluctuations regulate the source, distribution, and risk of antibiotics in the largest floodplain-lake in China.

Seasonal water fluctuations in floodplain-lake occur globally, yet their effect on spatiotemporal distribution of antibiotics in the lakes remains poorly understood. This study explores how seasonal water level fluctuations and resulting shifts in land use and environmental factors influence antibiotic sources, distribution, and ecological risks in the largest floodplain-lake (Poyang Lake) in China. The lake was divided into three areas based on water level dynamics: high-water level (HWL) area, fluctuating water level (FWL) area, and dish-shaped lake (DSL) area.

Self-assembled human arteriole-on-a-chip for arterial functionality testing and disease modeling.

In recent years, various vascularized organ-on-a-chip models have been designed for drug development and screening, and many of them have also advanced to serve as disease models for studying infectious diseases and gene disorders. Currently, most vascular models are capillary-like structures with only a layer of endothelium. Some of them may have pericytes to support the vessel structure.

Involvement of ferroptosis in lipopolysaccharide-induced intestinal inflammation in broilers.

This study aimed to investigate whether lipopolysaccharide (LPS)-induced intestinal inflammation involves ferroptosis and its impact on broiler gut health. Two animal trials were conducted. In the first trial, 192 ROSS 308 broilers were randomly assigned to four groups and intraperitoneally injected with either 0.

Pellitorine protects chronic restraint stress-induced cognitive deficits via inhibiting neural inflammation and ferroptosis.

Background: It has not been known that pellitorine, an active ingredient of Piper sarmentosum Roxb. with therapeutic effects against epilepsy and anxiety disorders, has the neurological effects. Our study aimed to investigate the therapeutic potential of pellitorine in addressing chronic restraint stress (CRS)-associated cognitive deficits.

Adaptive PI nonlinear cooperative control for motor cluster.

To address the effects of nonlinearities and uncertainties in the speed regulation of permanent magnet synchronous motors (PMSMs), an adaptive PI nonlinear control strategy is introduced. First, a nonlinear system model is developed using the PMSM mathematical model, and an adaptive PI nonlinear control approach is designed. Numerical simulations are conducted to demonstrate that this control method effectively tracks the system's desired values.

Awareness and willingness towards Mpox vaccination among men who have sex with men seeking HIV-related services.

We conducted a multicenter, on-line questionnaire interview of 1576 men who have sex with men planning to undergo or having undergone 2-dose MVA-BN vaccination to investigate the risk for acquiring Mpox, Mpox-related knowledge, awareness and willingness of Mpox vaccination, and the vaccination status. Upon the questionnaire interview, 794 (64.3%) people with HIV and 239 (69.

Rewired m6A of promoter antisense RNAs in Alzheimer's disease regulates neuronal genes in 3D nucleome.

N-methyladenosine (m6A) is an abundant internal RNA modification that can impact gene expression at both post-transcriptional and transcriptional levels. However, the landscapes and functions of m6A in human brains and neurodegenerative diseases, including Alzheimer's disease (AD), are under-explored. Here, we examined RNA m6A methylome using total RNA-seq and meRIP-seq in middle frontal cortex of post-mortem brains from individuals with or without AD, which revealed m6A alteration on both mRNAs and various noncoding RNAs.

Effects of RAAS blockade on acute kidney injury in head and neck cancer patients post-chemoradiotherapy.

Background: The incidence of acute kidney injury (AKI) is high among head and neck cancer (HNC) patients following Platinum-based concurrent chemo-radiotherapy (CCRT). However, the effect of renin-angiotensin-aldosterone system (RAAS) blockade on the risk of AKI in HNC patients undergoing CCRT is controversial. This study aimed to investigate the association between RAAS blockade, AKI and survival in HNC patients undergoing CCRT.

Optimized processing and formulation for retaining the sensory and nutritional quality of mustard leaf tea.

The potential of mustard () leaves as a raw material for herbal tea remains unexplored. This study aimed to evaluate the suitability of mustard leaves for tea production and optimize processing and formulation. Four mustard varieties were evaluated using traditional green tea processing techniques, demonstrating that purple-leaf mustard is an excellent raw material for herbal tea, both in terms of sensory properties and bioactive compounds.