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FEAT: A Linear-Complexity Foundation Model for Extremely Large Structured Data
An engineered nanopore identifies saccharides, amino acids, peptides and ribonucleotides
Nature Biotechnology, Published online: 14 September 2026; doi:10.1038/s41587-026-03308-9
Modified nanopore simultaneously identifies diverse biomolecules and their modifications.A clinically derived lipid-endothelial signature links serum multi-omics to immune exclusion and clinical stratification in hepatocellular carcinoma
Ther Adv Med Oncol. 2026 Aug 31;18:17588359261481797. doi: 10.1177/17588359261481797. eCollection 2026.
ABSTRACT
BACKGROUND: Hepatocellular carcinoma (HCC) is driven by extensive metabolic reprogramming, vascular remodeling, and immune microenvironmental dysfunction. Although numerous stratification signatures have been proposed, few are grounded in clinically derived serum multi-omics and biologically linked to endothelial remodeling, endothelial regulation, and immune exclusion.
OBJECTIVES: This study aimed to identify a serum-derived lipid-endothelial program associated with immune exclusion and clinical stratification in HCC.
DESIGN: A translational multi-omics study integrating clinically collected serum samples, public transcriptomic cohorts, single-cell RNA sequencing, and experimental validation.
METHODS: Proteomic and metabolomic sequencing was performed on serum samples from patients with HCC and normal controls. Dysregulated pathways were integrated with transcriptomic data from TCGA-LIHC and ICGC-LIRI-JP cohorts to identify genes jointly associated with lipid metabolism and leukocyte transendothelial migration. A risk score was calculated using the expression of PON1, TXNRD1, CLDN4, CLDN6, CYP2C9, and CTSA. Higher expression of TXNRD1, CLDN4, CLDN6, and CTSA contributed to a higher risk score, whereas PON1 and CYP2C9 contributed protective coefficients. Immune contexture, tumor mutation burden, and exploratory therapeutic sensitivity patterns were further evaluated using transcriptome-based drug sensitivity prediction, followed by single-cell RNA sequencing and experimental expression validation.
RESULTS: Serum multi-omics analysis revealed prominent dysregulation of lipid metabolic pathways and leukocyte transendothelial migration-related processes in HCC. Integrative analysis identified a six-gene lipid-endothelial signature (PON1, TXNRD1, CLDN4, CLDN6, CYP2C9, and CTSA) that stratified patients into high- and low-risk groups. In the TCGA-LIHC cohort, high-risk patients had significantly poorer overall survival than low-risk patients (log-rank P < 0.0001), and this survival-stratifying association was externally supported in the ICGC-LIRI-JP cohort (log-rank P = 0.016). The high-risk phenotype was associated with immune-excluded features, distinct somatic mutation patterns, and altered predicted sensitivity to several selected anticancer agents. Single-cell analysis and experimental assays further supported the association between the six-gene program, malignant epithelial states, endothelial-related remodeling, and immune microenvironmental heterogeneity.
CONCLUSION: This study defines a clinically derived lipid-endothelial program associated with immune exclusion, adverse prognosis, and potential differences in therapeutic vulnerability in HCC. The proposed signature provides a biologically informed framework for prognostic assessment and may support future evaluation of targeted interventions in HCC.
PMID:42682961 | PMC:PMC13530516 | DOI:10.1177/17588359261481797
Emotional intelligence in large language models is fragmented across perception, cognition, and interaction
Adaptive Stopping for Multi-Turn LLM Reasoning
Adaptive Stopping for Multi-Turn LLM Reasoning
GUIDE: Resolving Domain Bias in GUI Agents through Real-Time Web Video Retrieval and Plug-and-Play Annotation
Unraveling the role of cuproptosis in pulmonary fibrosis pathogenesis and prognosis: an integrative single-cell transcriptomics and microarray analysis
Mol Cell Biochem. 2026 Mar 13. doi: 10.1007/s11010-026-05510-4. Online ahead of print.
ABSTRACT
Pulmonary fibrosis (PF), a progressive interstitial lung disease with elusive pathogenesis, remains a therapeutic challenge. Emerging evidence suggests cuproptosis-a copper-dependent cell death pathway-may play a regulatory role in disease progression. This study aims to elucidate cuproptosis's biological function and establish a prognostic model for PF. Through integrative analysis of single-cell RNA-seq data from bleomycin (BLM)-induced mouse models and bulk RNA-seq data from idiopathic pulmonary fibrosis (IPF) patients, we identified cuproptosis-related genes (CRGs) using LASSO regression and Cox regression. A novel 4-CRG signature (LIAS, LIPT1, ATP7A, PDHB) was constructed to stratify patients into distinct risk groups in the GSE70866 cohort, where high-risk individuals exhibited poorer survival and enhanced extracellular matrix/lipid metabolism activity via GO/KEGG analysis. Experimental validation in BLM-induced mouse models, TGF-Ξ²1-stimulated fibroblast-to-myofibroblast transition assays, and human IPF specimens demonstrated significant downregulation of CRGs through qRT-PCR and immunohistochemical analyses. Functional assays revealed impaired cell viability and elevated cuproptosis markers in fibrotic microenvironments. Our findings establish an inverse correlation between cuproptosis and PF progression, and propose a robust risk-score model for clinical prognosis prediction. This multi-omics approach provides new insights into copper-mediated regulatory mechanisms in fibrogenesis.
PMID:41824199 | DOI:10.1007/s11010-026-05510-4