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Don't Retrain, Just Reuse: Recovering Dual-Target Molecules from Single-Target Diffusion Models
Self-supervised Hierarchical Visual Reasoning with World Model
Rethinking the Comparison Unit in Sequence-Level Reinforcement Learning: An Equal-Length Paired Training Framework from Loss Correction to Sample Construction
Pulmonary-Intestinal Axis: Shared Genetic Basis and Mediating Factors Identified Through Multi-Omics Analysis
Int J Chron Obstruct Pulmon Dis. 2026 Apr 7;21:561645. doi: 10.2147/COPD.S561645. eCollection 2026.
ABSTRACT
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a systemic condition with comorbidities beyond the lung (eg, cardiovascular and metabolic disorders), and gastrointestinal (GI) disorders are also common. The shared genetic basis of COPD-GI comorbidity and its mediating factors remain unclear. We hypothesized that COPD and GI diseases share pleiotropic genetic architecture implicating lipid-metabolic pathways, with smoking mediating part of the association.
METHODS: We analyzed publicly available European-ancestry GWAS summary statistics for COPD (Global Biobank Meta-analysis Initiative), 15 GI diseases (FinnGen), and smoking phenotypes (UK Biobank). Genetic correlation was estimated using linkage disequilibrium score regression (LDSC) and high-definition likelihood (HDL). Multi-trait analysis of GWAS (MTAG) boosted COPD discovery by leveraging genetically correlated GI traits. We integrated locus-to-gene mapping with multi-tissue expression quantitative trait loci (eQTL) and plasma protein quantitative trait loci (pQTL) evidence to prioritize shared loci, genes, and proteins. Bidirectional two-sample Mendelian randomization (MR) tested causal directions, and two-step mediation MR evaluated smoking.
RESULTS: COPD showed significant genetic correlation with nine GI diseases. We identified six comorbidity-associated loci (three with CADD > 12.37) and 13 unique candidate pleiotropic genes; APOE was supported by proteomic evidence. Enrichment analyses highlighted lipid-metabolism pathways. MR suggested COPD increases risk of gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), acute appendicitis, and gastric ulcer, while diverticular disease showed reverse causality toward COPD. Smoking partially mediated the COPD effect on GERD, acute appendicitis, and gastric ulcer.
CONCLUSION: COPD and multiple GI disorders share a distributed pleiotropic genetic basis within the broader systemic comorbidity spectrum of COPD. Multi-omics evidence supports a genomic pulmonary-intestinal axis in which lipid metabolism and smoking-related mechanisms contribute to COPD and GI comorbidity, providing targets for risk stratification and potential intervention.
PMID:41978582 | PMC:PMC13070119 | DOI:10.2147/COPD.S561645
Large Language ModelβBased Analysis of Statin Therapy Discussions and Sentiment on Social Media: Cross-Sectional Observational Study
Development and multi-center evaluation of domain-adapted speech recognition for human-AI teaming in real-world gastrointestinal endoscopy
Efficient Reasoning with Balanced Thinking
UniMark: Artificial Intelligence Generated Content Identification Toolkit
Predicting Neuromodulation Outcome for Parkinson's Disease with Generative Virtual Brain Model
LatentPilot: Scene-Aware Vision-and-Language Navigation by Dreaming Ahead with Latent Visual Reasoning
Expressive Power of Implicit Models: Rich Equilibria and Test-Time Scaling
Gut-Brain Axis Dysregulation in Inflammatory Bowel Disease: Implications for Coagulation Abnormalities and Extraintestinal Manifestations
Int J Gen Med. 2026 Mar 24;19:590621. doi: 10.2147/IJGM.S590621. eCollection 2026.
ABSTRACT
Inflammatory bowel disease (IBD) involves chronic intestinal inflammation driven by gut-brain axis imbalance, fostering complications through an "inflammation-neuro-coagulation" triad. Current staging systems inadequately capture the dynamics of this multidimensional network. Therefore, integrated multi-omics analyses-including metagenomics, metabolomics, and single-cell transcriptomics-are essential to construct dynamic models that monitor coagulation, microbiome, and metabolism for precise assessment of disease activity and thrombotic or bleeding risks. Interventions targeting gut-brain axis nodes, such as eliminating tissue factor-positive (TFβΊ) T cells or modulating vagal activity, show potential to disrupt the inflammation-coagulation cycle, although rigorous randomized trials are still needed. Artificial intelligence (AI)-assisted systems that integrate real-time biomarker monitoring with multi-omics predictions represent a novel paradigm for managing IBD-related coagulation dysfunction. Key challenges include elucidating gut-brain-liver axis regulation of coagulation and characterizing platelet functional heterogeneity. Future efforts must prioritize ethically compliant multi-omics platforms and racially stratified risk models to advance personalized coagulation management in IBD.
PMID:41913906 | PMC:PMC13033200 | DOI:10.2147/IJGM.S590621
Robot-Assisted Therapy for Upper Limb Rehabilitation After Stroke: Umbrella Review
FAAR: Format-Aware Adaptive Rounding for NVFP4
An Accurate and Interpretable Framework for Trustworthy Process Monitoring
From Context to Intent: Reasoning-Guided Function-Level Code Completion
19-Hydroxybufalin Inhibits Gastric Cancer Cell Proliferation by Modulating Metabolic Reprogramming
J Proteome Res. 2026 Apr 3;25(4):2014-2023. doi: 10.1021/acs.jproteome.5c00983. Epub 2026 Mar 17.
ABSTRACT
OBJECTIVE: 19-Hydroxybufalin (19-H) is a natural bioactive compound with anticancer potential, but its molecular target and mechanism of action remain unclear. This study aimed to systematically evaluate its antigastric cancer activity and identify potential molecular targets.
METHODS: The antitumor effect of 19-H was evaluated in both in vitro and in vivo models. Multiomics analysis, thermal proteome profiling, molecular docking, and molecular dynamics simulations were employed to elucidate the mechanism of action. Functional assays were further conducted to validate the key target.
RESULTS: 19-H exhibited nanomolar-level inhibitory activity against various gastric cancer cell lines, significantly suppressing tumor growth in subcutaneous xenograft and patient-derived xenograft models. Multiomics analysis revealed that 19-H reshaped metabolic pathways in gastric cancer. TPP screening identified PLPP2 as a potential target with significantly increased thermal stability upon 19-H treatment. Molecular simulations further revealed that 19-H binds stably to the Ξ±-helical region of PLPP2.
CONCLUSIONS: 19-H exerts its antigastric cancer effect by targeting PLPP2 and remodeling the metabolic network. PLPP2 may represent a novel therapeutic target for gastric cancer.
PMID:41842934 | DOI:10.1021/acs.jproteome.5c00983