MolMod: a molecular modification platform for molecular property optimization via fragment-based generation.

Lead optimization is a crucial step in drug design. Generative AI-driven molecular modification has emerged as a powerful strategy to accelerate lead optimization by efficiently exploring chemical space and enhancing key drug-like properties. However, current AI tools primarily focus on de novo scaffold design rather than targeted modifications of validated lead compounds, limiting their practical utility in medicinal chemistry.

LHX2 Rewires the Metabolic and Epigenetic Landscape to Drive Tumor Progression in Prostate Cancer.

Neuroendocrine prostate cancer (NEPC) evolves as an aggressive phenotype during prolonged androgen deprivation therapy, lacking effective clinical management. Here, we elucidated a reciprocal metabolic-epigenetic mechanism involving a positive feedback loop between glycolysis and the transcription factor LHX2 that promotes PCa progression. Mechanistically, enzalutamide-mediated inhibition of the androgen receptor (AR) led to upregulation of key glycolytic enzymes.

Nuclear Symmetric Dimethylarginine Staining is Indicative of Pancreatic Ductal Adenocarcinoma.

Objective: The protein arginine methyltransferase 5 (PRMT5) is a type II PRMT that is responsible for the majority of symmetric dimethylarginine (SDMA) in eukaryotic cells. While PRMT5 is overexpressed in pancreatic ductal adenocarcinoma (PDAC), the SDMA expression patterns in PDAC tissues have not been examined. This study is aimed to characterize the SDMA expression patterns in PDAC cells and patient tissues.

Stroke risk in women with or without hysterectomy and/or bilateral oophorectomy: evidence from the NHANES 1999-2018 and meta-analysis.

Objective: We aimed to assess the relationship between hysterectomy and/or bilateral oophorectomy and the risk of stroke-a topic of ongoing debate in current research.

Methods: We utilized data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 to estimate both crude and multivariable-adjusted hazard ratios (HRs) and 95% CIs, applying survey-weighted Cox proportional hazards regression model. The modeling incorporated sampling weights and design variables to address NHANES's multistage probability sampling framework.

Long-read sequencing identifies ATXN3 repeat expansions, and transcriptomics reveals disease progression biomarkers and druggable targets for spinocerebellar ataxia type 3.

Background: Hereditary ataxias (HAs) are neurodegenerative disorders characterized by progressive cerebellar degeneration, with autosomal dominant spinocerebellar ataxias (SCAs) representing the most prevalent subtype. SCA3, the most common form worldwide, is caused by CAG repeat expansions in ATXN3, resulting in pathogenic ataxin-3 aggregation. However, the underlying molecular mechanisms driving disease progression remain incompletely understood.

Dietary vitamin E intake is associated with lower mortality among individuals with metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a prominent global health issue within the realm of chronic liver diseases. Dietary interventions are of utmost importance in its management. This research, grounded in data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999-2018 and the National Death Index (NDI), was designed to clarify the association between dietary vitamin E intake and mortality among MASLD patients.

BRCA-CN: a blockchain-based framework to support public variant databases sharing in multi-center community for diagnostic reference and China regulatory science.

High-quality, regulatory-grade databases for precise genetic variant interpretation are critically needed for Chinese populations, where existing fragmented databases impede clinical effectiveness evaluations. We developed BRCA-CN, a consortium blockchain-based governance framework specifically designed for BRCA gene variant interpretation in Chinese populations. Our framework compiled 66,485 variants from 6,031 samples across six Chinese laboratories.

Comparison of LC-PUFAs Biosynthetic Characteristics in Male and Female Tilapia at Different Ontogenetic Stages.

Tilapia possess the ability to biosynthesize long-chain polyunsaturated fatty acids (LC-PUFA); however, variations in this capacity across different growth stages and between sexes remain poorly understood. This study evaluated the LC-PUFA biosynthetic capacity in male and female tilapia fed two distinct diets-perilla oil (rich in α-linolenic acid, ALA) and peanut oil (rich in linoleic acid, LA)-over 24 weeks, spanning four growth stages (I-IV, from fry to adult). The results revealed that during stages I to III, both diets produced similar final body weights.

Exploiting the coordination chemistry of high-valent americium for actinide/lanthanide separations.

Efficient americium (Am)/lanthanide (Ln) separation is highly pursued in advanced nuclear fuel cycle for minimizing the long-term radiotoxicity of nuclear waste and maximizing the utilization of nuclear resources. However, such a task is extremely challenging given the chemical similarity between the inherent thermodynamically stable Am(III) and Ln(III) ions. In recent years, interest in Am/Ln separation through oxidizing Am(III) to higher-valent states is reigniting due to theoretically considerable separation efficiency of this approach.

Mechanical Properties of Nano-TiO-Modified Concrete Under Freeze-Thaw Environment.

This study investigated the freeze-thaw resistance of ordinary and nano-TiO-modified concrete (NTC) based on mass loss, ultrasonic velocity, compressive strength, and fracture toughness. The compressive behavior and internal damage evolution were further analyzed using particle flow code in two dimensions (PFC) simulations. The results show that, although neither material exhibited structural collapse after freeze-thaw cycling, visible surface damage was observed, particularly in ordinary concrete.

Counterintuitive Impact of Polar Solubilizing Group Functionalization on Ligand Solubility and f-Block Element Affinity.

The design of multidentate hydrophilic ligands with high binding affinity and selectivity is fundamentally important for efficient metal separation and the development of highly stable radiopharmaceuticals. A widely adopted strategy involves introducing water-solubilizing groups into originally effective lipophilic ligands, aiming to preserve the metal-binding affinity while imparting aqueous solubility. In this work, we demonstrate that such an intuitive solubilization approach can fail if an appropriate hydrogen-bonding network is not established.

Celastrol Suppresses SHH-MB Growth via ROS-Induced Stress: Evidence From In Vitro and In Vivo Studies.

Celastrol, a bioactive compound derived from the traditional Chinese herb Tripterygium wilfordii, has demonstrated various pharmacological properties, including anticancer effects. Medulloblastoma (MB), particularly the Sonic Hedgehog (SHH) subtype, remains a challenge due to its aggressive nature and limited therapeutic options. This study aims to investigate the inhibitory effects of celastrol on Sonic Hedgehog medulloblastoma (SHH-MB) cells in vitro and in vivo, focusing on its underlying mechanisms and signaling pathways.

On the Design of Effective Water-Soluble Actinide-Masking Ligands Through Ligand Structure Modulation.

Water-soluble actinide-masking ligands are fundamentally important for achieving efficient lanthanide/actinide separation and for the development of water-soluble f-block complexes for bioimaging and radiopharmaceutical applications. However, the underlying design principles remain largely elusive, particularly in achieving a fine balance between ligand water solubility and metal affinity/selectivity. In this study, it is demonstrated that for the well-established phenanthroline diimine ligand framework, topological modifications can preserve water solubility but introduce significant rotational energy barriers.

Multifunctional Hydrogel Materials for Advanced Neural Interfaces.

Conventional rigid neural electrodes mismatch the soft, wet nature of neural tissue, hindering long-term stable interfaces. Multifunctional hydrogels, with their tissue-like compliance, ionic conductivity, and biocompatibility, offer a promising solution to bridge bioelectronic systems and neural tissues. This review systematically examines critical hydrogel properties-mechanical compliance, adhesion, biocompatibility, conductivity, and injectability-for neural interfacing.

Model Rectification With Simultaneous Incremental Feature and Partial Label Set.

Traditional classification problems assume that features and labels are fixed. However, this assumption is easily violated in open environments. For example, the exponential growth of web pages leads to an expanding feature space with the accumulation of keywords.

On-Site Growth of a TaON Nanoshell on ZrO Particles for Photocatalytic Water Splitting.

Low-dimensional nanostructuring has emerged as a promising approach to enhance the photocatalytic performance of transition metal oxynitrides, a class of widely investigated visible-light-responsive photocatalysts. Despite their potential, the synthesis of nanostructured oxynitride materials remains a great challenge. In this study, we present a novel NHCl-assisted vacuum nitridation method for growth of an ultrathin TaON layer on particulate ZrO, resulting in the formation of TaON@ZrO core@shell nanostructures.

Tailoring Microstructure via Rolling to Achieve Concurrent High Strength and Thermal Conductivity in Mg-Zn-Nd-Zr Alloys.

This study examined the comprehensive properties of Mg-Zn-Nd-Zr alloys in order to achieve both high strength and thermal conductivity simultaneously. The impact of rolling on the microstructure, mechanical properties, and thermal conductivity was analyzed for Mg-5Zn-xNd-0.4Zr alloys (x = 1, 2).

Enhanced Mechanical and Electromagnetic Shielding Properties of Mg Matrix Layered Composites Reinforced with Hybrid Graphene Nanosheet (GNS)-Carbon Nanotube (CNT) Networks.

The development of lightweight composites with superior mechanical properties and electromagnetic interference (EMI) shielding performance is essential for various structural and functional applications. This study investigates the effect of hybrid nanocarbon (graphene nanosheet (GNS) and carbon nanotube (CNT)) reinforcements on the properties of magnesium (Mg) matrix composites. Specifically, the GNS-CNT hybrid, which forms a three-dimensional interconnected network structure, was analyzed and compared to composites reinforced with only GNSs or CNTs.

Cracking mechanism and acoustic emission characteristics of granite under varying thermal effects.

Understanding the thermo-mechanical behavior of granite under high-temperature conditions is crucial for the safe and efficient development of deep geothermal resources. This study revealed the physico-mechanical properties, cracking mechanism and fracture precursor of granite via compression experiments with acoustic emission (AE) monitoring. Results indicated that 500 °C is the critical temperature for the brittle-ductile transition of granite, characterized by progressive degradation of P-wave velocity, Young's modulus, and uniaxial compressive strength (UCS) with increasing temperature, while peak strain shows an inverse trend.

Unravelling the Web of Life: Incomplete Lineage Sorting and Hybridisation as Primary Mechanisms Over Polyploidisation in the Evolutionary Dynamics of Pear Species.

The traditional Tree of Life (ToL) model is increasingly challenged by the Web of Life (WoL) paradigm, which offers a more accurate depiction of organismal phylogeny, particularly in light of the incongruences often observed between gene and species trees. However, the absence of a standardised method for resolving evolutionary mechanisms - such as Incomplete Lineage Sorting (ILS), hybridisation, introgression, polyploidisation, and whole-genome duplication - remains a significant obstacle in defining the WoL. Characterised by extensive hybridisation events, the pear genus Pyrus provides an ideal model for exploring these complexities.

Array-Based Rapid Identification of Herbal Medicines via a Bifunctional Color-BiLink Strategy.

Ensuring the authenticity and quality of herbal medicines, particularly licorice, a pivotal component in nearly 60% of traditional Chinese medicine formulations, remains a significant global challenge. However, conventional approaches lack the capacity for direct, rapid, and high-throughput differentiation of licorice mixtures and structurally analogous ingredients. Herein, we present a multisite-binding Color-BiLink () strategy for constructing the dual-mode responsive sensor array, formed by a quantifiable-recognized bifunctional -nitrophenylboronic acid-modified PEI () and four dyes through dynamic, reversible covalent, and electrostatic interactions.

Multispectral imaging and channel allocating for synchronous measurement of temperature and deformation over a wide temperature range.

Synchronous measurement of temperature and deformation over a wide temperature range at elevated temperatures is essential for evaluating material performance and guiding the design of high temperature structural material. However, the significant variations in radiation intensities across different temperatures present challenges in obtaining high quality experimental images, often compromising measurement precision or causing measurement failure. To address this issue, we propose a novel multispectral channel selection method, to our knowledge, based on sensitivity calculations, enabling synchronous temperature and deformation measurements using a multispectral camera over a wide temperature range.

Endosialin promotes vascular maturation by inhibiting Cyr61 expression in melanoma metastasis.

Background: Extensive tumor cell metastasis is associated with poor patient prognosis. Tumor endothelial cells demonstrate distinct proangiogenic phenotypes compared to normal endothelial cells, partially mediated by pericyte-derived secreted factors. Endosialin, a pericyte biomarker implicated in vascular maturation and metastatic progression, remains mechanistically undefined in this context.

Cross-cultural adaptation and validation of the Chinese version of the 25-question Geriatric Locomotive Function Scale in patients undergoing total knee arthroplasty.

Background: Knee osteoarthritis (KOA) is prevalent among the elderly, often necessitating total knee arthroplasty (TKA) for severe cases. However, traditional assessment tools primarily focus on pain and physical function, neglecting the psychosocial aspects that influence postoperative satisfaction. The 25-question Geriatric Locomotive Function Scale (GLFS-25) is a comprehensive measure of locomotor function, however, it has limited validation within populations in Mainland China.