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GlobalDentBench: A Multinational Benchmark for Evaluating LLM Clinical Reasoning in Dentistry with Expert Calibration
HoloFair: Unified T2I Fairness Evaluation and Fair-GRPO Debiasing
Cuproptosis causes meiotic metaphase I arrest by disrupting mitochondrial functions in oocytes
Cell Death Discovery, Published online: 23 May 2026; doi:10.1038/s41420-026-03168-x
Cuproptosis causes meiotic metaphase I arrest by disrupting mitochondrial functions in oocytesIntegrative multi-omics analysis identifies stromal-immune crosstalk as a determinant of immunotherapy efficacy and establishes a prognostic signature in gastric cancer
Comput Biol Chem. 2026 Apr 23;124(Pt 1):109095. doi: 10.1016/j.compbiolchem.2026.109095. Online ahead of print.
ABSTRACT
Immune checkpoint inhibitors like pembrolizumab exhibit variable efficacy in metastatic gastric cancer (GC). This study aimed to identify molecular drivers of pembrolizumab response, explore mechanisms of immune checkpoint inhibitors (ICIs) efficacy, and develop a prognostic signature. Transcriptomic analysis of pembrolizumab-treated GC (TIGER database) identified 165 response-associated differentially expressed genes (DEGs). Functional annotation and single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) revealed that responder-upregulated genes (R-DEGs) were enriched in immune activation pathways and mainly localized to CD8 + T/NK cells. In contrast, non-responder-upregulated genes (D-DEGs) were linked to extracellular matrix (ECM) remodeling and mainly expressed in fibroblasts/endothelial cells. CellChat analysis demonstrated that key DEGs mediate immune-stromal crosstalk via MHC-I and collagen/laminin signaling. A prognostic signature (Lasso-StepCox[forward] Riskscore; LSR: APOD, APOH, BATF2, GJA1, MAGED1, SLC5A1, SLCO2A1, VWF, VCAN) was derived and validated in four independent GC cohorts from the GEO and Cancer Genome Atlas (TCGA) database. Multi-omics analyses showed that LSR-high tumors exhibited aggressive clinicopathological features, increased stromal components, reduced cytotoxic immune infiltration, diminished tumor mutational burden (TMB), and poorer prognosis. Immunohistochemistry (IHC) and spatial transcriptomics in GC showed that stromal VWF/VCAN expression correlates with reduced CD8⁺ T cell granzyme B expression, suggesting T cell dysfunction. High VWF expression in GC predicted poor survival, and a combined VWF/VCAN score showed enhanced prognostic stratification. This study highlights stromal-immune crosstalk as a driver of pembrolizumab resistance and provides a signature as a clinical tool for prognosis and personalized therapy in metastatic GC.
PMID:42068630 | DOI:10.1016/j.compbiolchem.2026.109095
Integrin β3 deficiency unleashes spontaneous pulmonary inflammation by promoting B cell hyperactivation via the CD40-CD40L axis
Front Immunol. 2026 Mar 24;17:1796926. doi: 10.3389/fimmu.2026.1796926. eCollection 2026.
ABSTRACT
BACKGROUND: Pulmonary immune homeostasis requires tight control of adaptive responses. Integrin β3 is a well-known mediator of cell adhesion and platelet function. However, its role in adaptive immunity, especially in B cell responses, remains unclear.
METHODS: We defined the pulmonary phenotype of constitutive β3-deficient (β3-/-) mice by histopathology. We performed integrated transcriptomic and proteomic profiling of lung tissue to map the molecular signature of spontaneous pulmonary inflammation. We further probed the underlying mechanisms with additional histology and functional assays and tested for biological significance using transcriptomics data from auto-immune disease patients.
RESULTS: β3-/- mice developed spontaneous pulmonary inflammation marked by B cell activation and in situ immune-complex deposition within alveoli. Multi-omics integration implicated the CD40-CD40 Ligand (CD40L) axis as a central driver of this pathology. Mechanistically, loss of β3 enhanced CD40L-CD40 engagement on B cells, resulting in NF-κB pathway hyperactivation. Consistent with our murine data, reduced ITGB3 expression in patients with autoimmune disease correlated with transcriptional signatures of B cell activation and inflammation.
CONCLUSIONS: These results reframe integrin β3 as a threshold regulator of B cell activation. The β3-CD40L-CD40 axis therefore represents a potential therapeutic target for B cell-mediated autoimmune diseases.
PMID:41953039 | PMC:PMC13055533 | DOI:10.3389/fimmu.2026.1796926
Integrin β3 deficiency unleashes spontaneous pulmonary inflammation by promoting B cell hyperactivation via the CD40-CD40L axis
Front Immunol. 2026 Mar 24;17:1796926. doi: 10.3389/fimmu.2026.1796926. eCollection 2026.
ABSTRACT
BACKGROUND: Pulmonary immune homeostasis requires tight control of adaptive responses. Integrin β3 is a well-known mediator of cell adhesion and platelet function. However, its role in adaptive immunity, especially in B cell responses, remains unclear.
METHODS: We defined the pulmonary phenotype of constitutive β3-deficient (β3-/-) mice by histopathology. We performed integrated transcriptomic and proteomic profiling of lung tissue to map the molecular signature of spontaneous pulmonary inflammation. We further probed the underlying mechanisms with additional histology and functional assays and tested for biological significance using transcriptomics data from auto-immune disease patients.
RESULTS: β3-/- mice developed spontaneous pulmonary inflammation marked by B cell activation and in situ immune-complex deposition within alveoli. Multi-omics integration implicated the CD40-CD40 Ligand (CD40L) axis as a central driver of this pathology. Mechanistically, loss of β3 enhanced CD40L-CD40 engagement on B cells, resulting in NF-κB pathway hyperactivation. Consistent with our murine data, reduced ITGB3 expression in patients with autoimmune disease correlated with transcriptional signatures of B cell activation and inflammation.
CONCLUSIONS: These results reframe integrin β3 as a threshold regulator of B cell activation. The β3-CD40L-CD40 axis therefore represents a potential therapeutic target for B cell-mediated autoimmune diseases.
PMID:41953039 | PMC:PMC13055533 | DOI:10.3389/fimmu.2026.1796926
A neural-symbolic AI agent system for biomedical concept mapping
npj Digital Medicine, Published online: 04 April 2026; doi:10.1038/s41746-026-02594-6
A neural-symbolic AI agent system for biomedical concept mappingHoloTrauma 3X Triadic AI Co reasoning for robot assisted emergency maxillofacial reconstruction
npj Digital Medicine, Published online: 04 April 2026; doi:10.1038/s41746-026-02573-x
HoloTrauma 3X Triadic AI Co reasoning for robot assisted emergency maxillofacial reconstructionCountering Catastrophic Forgetting of Large Language Models for Better Instruction Following via Weight-Space Model Merging
Bridging Large-Model Reasoning and Real-Time Control via Agentic Fast-Slow Planning
DIAL: Decoupling Intent and Action via Latent World Modeling for End-to-End VLA
Hepatotoxicity Prediction and Multi-omics Reveal Mitochondrial and Lipid Metabolic Dysregulation in PM<sub>2.5</sub>-Induced Liver Fibrosis
Environ Health (Wash). 2025 Nov 14;4(3):513-521. doi: 10.1021/envhealth.5c00401. eCollection 2026 Mar 20.
ABSTRACT
Prolonged exposure to fine particulate matter (PM2.5) has been linked to chronic liver injury and cancer. However, an alternative risk assessment method to prospective longitudinal studies of exposome-metabolome interactions for liver inflammation-associated hepatocellular carcinoma (HCC) is lacking. This study investigates the risk of long-term real-world PM2.5 exposure in hepatocarcinogenesis through machine learning techniques. Shotgun mass spectrometry (MS) imaging data were acquired from mouse models across a continuum of fibrosis, cirrhosis, and HCC for training a multiclass classification model to identify "No Risk", "Cancer Risk", and "Cancer". Direct infusion-MS data from PM2.5-exposed mouse livers were analyzed to classify risk. By integrating data-driven and knowledge-based approaches, 14 disease progression biomarkers were identified for modeling. Our results suggest that chronic real-world PM2.5 exposure can induce liver fibrosis, presenting cancer risk. Incorporating metabolomics, lipidomics, and transcriptomics, we propose PM2.5 exposure induces mitochondrial dysfunction, activates AMPK signaling, and increases ceramide accumulation, potentially mediating insulin resistance that contributes to nonalcoholic fatty liver disease and HCC progression. This work represents a significant advancement in assessing hepatotoxicity of environmental toxicants by reducing reliance on traditional animal testing methods. It also underscores the potential of emerging technologies in transforming our understanding of PM2.5 exposure, paving the way for targeted interventions.
PMID:41883379 | PMC:PMC13010293 | DOI:10.1021/envhealth.5c00401
Author Correction: 7-Dehydrocholesterol is an endogenous suppressor of ferroptosis
Nature, Published online: 24 March 2026; doi:10.1038/s41586-026-10403-z
Author Correction: 7-Dehydrocholesterol is an endogenous suppressor of ferroptosis