Hemophilia

Multi-cohort integration and machine learning identify CPVL as a novel oncogenic driver in gastric cancer.

BACKGROUND: Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide, and the prognosis of advanced GC remains poor. Systematic identification of robust biomarkers through multi-cohort integration and computational prioritization may facilitate the discovery of novel therapeutic targets. AIM: To identify key genes associated with gastric cancer progression through integrat...

The natural isoflavone puerarin mitigates cerebral ischemia-reperfusion injury by directly targeting CaMKⅡδ to block DLG4-Ser654 phosphorylation.

BACKGROUND: Synaptic collapse drives severe neurological deficits following cerebral ischemia-reperfusion (I/R) injury. Puerarin, a bioactive isoflavone from Pueraria lobata, exhibits neuroprotective properties, yet the precise kinase-substrate networks orchestrating its targeted efficacy remain elusive. PURPOSE: To systematically identify the pathogenic kinase networks in I/R injury and elucidate...

Machine learning-driven prioritization and experimental validation of traditional Chinese medicine-derived STING-inhibitory candidates.

The stimulator of interferon genes (STING) is a key signalling adaptor in the cGAS-STING pathway of the innate immune system and plays a significant r...

Quinazolinone and Phthalazinone Inhibitors of the HDAC6/Ubiquitin Protein-Protein Interaction.

Histone deacetylase 6 (HDAC6) is a class IIb histone deacetylase that regulates diverse cytosolic acetylation through its two catalytic deacetylase do...

Metabolic determinants of cancer immunotherapy outcomes identified by plasma profiling.

Immune-checkpoint inhibitors benefit a subset of patients with advanced cancer, and the metabolic determinants of response remain unclear. Here, using...

Integrative multi-omics and single-cell analysis identifies EGFR pathway activation and metabolic reprogramming as potential synthetic lethal vulnerabilities in resistance to the FGFR inhibitor AZD4547.

BACKGROUND: Although fibroblast growth factor receptor (FGFR) inhibitors (FGFRi) have demonstrated clinical promise, the inevitable emergence of acqui...

AI-enabled structural bioinformatics identifies repositioned kinase inhibitor against Poxviridae kinases.

BACKGROUND: Emerging zoonotic poxviruses such as lumpy skin disease virus (LSDV) and monkeypox pose significant threats to animal and human health, ye...

Identification of small-molecule TNF-α inhibitor candidates using machine learning-guided screening and multiscale molecular modelling.

Lumbar disc herniation (LDH) is a major cause of chronic low back pain, in which tumor necrosis factor-alpha (TNF-α) plays a central role in inflammat...

Identifying Patients at Elevated Risk of Stroke After.

BACKGROUND: Transcarotid artery revascularization (TCAR) has assumed a significant role in the surgical treatment of extracranial carotid occlusive di...

2-Hydroxyisobutyrylation and Phosphorylation Crosstalk Guides Metastasis Prediction and Immunotherapy in Esophageal Squamous Cell Carcinoma.

Posttranslational modification (PTM) is pivotal in cancer progression. However, the mechanisms, biological function, and clinical significance underly...

Identification and validation of exosome-related biomarkers in pediatric glioblastoma.

Pediatric glioblastoma (pGBM) is an aggressive central nervous system (CNS) tumor whose pathological progression is significantly influenced by exosom...

Discovery of TYR inhibitors from de novo molecular generation to dual-track lead optimization: "Competition" between AI and chemists.

This study introduces a unified framework combining artificial intelligence (AI)-directed de novo molecular generation with dual-track lead optimizati...

Machine learning algorithms develop a tumor-educated platelets-related gene signature to predict colorectal cancer prognosis and therapy response.

Tumor-educated platelets (TEPs) have recently emerged as an important component of liquid biopsy, yet the clinical relevance in colorectal cancer (CRC...

Heterogeneity of Clazosentan Benefit after Aneurysmal Subarachnoid Hemorrhage Demonstrated in an Externally Validated Causal Policy Tree.

BACKGROUND: Clazosentan reduces angiographic vasospasm after aneurysmal subarachnoid hemorrhage (aSAH), but functional benefit may vary across patient...

Single-cell multi-omics dissection of RevitalAge Markers uncovers age-dependent immunotherapy resistance and druggable targets in melanoma.

Aging-related molecular reprogramming profoundly influences melanoma progression and therapeutic sensitivity, yet underlying mechanisms remain poorly ...

Integrating Machine Learning and Structure-Guided Discovery of a Novel Type II SYK Inhibitor for Treating Triple-Negative Breast Cancer.

Spleen tyrosine kinase (SYK) is a cytoplasmic nonreceptor kinase involved in immune signaling and homologous recombination (HR) repair of DNA double-s...

[Construction and validation of a prognostic prediction model for children-onset initial steroid-resistant nephrotic syndrome].

Objective: To analyze the risk factors for poor prognosis in children with steroid-resistant nephrotic syndrome (SRNS) and to construct and validate a...

Enhancing the Efficacy of Ulcerative Colitis Treatment by Inhibiting LCN2-Mediated Pyroptosis Through Traditional Processing Techniques: With the rhizome of Atractylodes macrocephala Koidz. as an Example.

ETHNOPHARMACOLOGICAL RELEVANCE: Atractylodes Macrocephala Rhizome (AMR), the dried rhizome of Atractylodes macrocephala Koidz (family Asteraceae), is ...

Identification of compounds that repress DUX4 expression in facioscapulohumeral muscular dystrophy.

Facioscapulohumeral muscular dystrophy (FSHD) is caused by epigenetic dysregulation of the disease locus, leading to pathogenic misexpression of DUX4 ...

Amplifier or inhibitor? A moderated mediation analysis of generative AI's impact on creative self-efficacy through dual-process thinking.

This study examined the impact of generative AI use on university students' creative self-efficacy-a key motivational construct within the broader dom...