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Lost in Translation: Policymakers are not really listening to Citizen Concerns about AI
MolBridge: Atom-Level Joint Graph Refinement for Robust Drug-Drug Interaction Event Prediction
User Perceptions of Privacy and Helpfulness in LLM Responses to Privacy-Sensitive Scenarios
Automated Extraction of Fluoropyrimidine Treatment and Treatment-Related Toxicities from Clinical Notes Using Natural Language Processing
FieldGen: From Teleoperated Pre-Manipulation Trajectories to Field-Guided Data Generation
Position: The Current AI Conference Model is Unsustainable! Diagnosing the Crisis of Centralized AI Conference
VaultGemma: A Differentially Private Gemma Model
Elucidating lipid nanoparticle properties and structure through biophysical analyses
Nature Biotechnology, Published online: 23 October 2025; doi:10.1038/s41587-025-02855-x
Guidance for optimizing lipid nanoparticle formulations is derived using sophisticated biophysical techniques.A Multi-faceted Analysis of Cognitive Abilities: Evaluating Prompt Methods with Large Language Models on the CONSORT Checklist
MSC-Bench: A Rigorous Benchmark for Multi-Server Tool Orchestration
KnowMol: Advancing Molecular Large Language Models with Multi-Level Chemical Knowledge
RoboGPT-R1: Enhancing Robot Planning with Reinforcement Learning
ScholaWrite: A Dataset of End-to-End Scholarly Writing Process
Landscape of T-cell exhaustion heterogeneity and HBV integration in virus-related HCC revealed by whole-exome, transcriptome, and single-cell sequencing
JHEP Rep. 2025 Jul 10;7(11):101518. doi: 10.1016/j.jhepr.2025.101518. eCollection 2025 Nov.
ABSTRACT
BACKGROUND & AIMS: To enhance our understanding of the tumor immune microenvironment (TIME) in hepatocellular carcinoma (HCC), we investigated the heterogeneity of T-cell exhaustion and its association with HBV integrations and direct oncogenic potential in HCC.
METHODS: We conducted a multi-omics analysis, including single-cell RNA sequencing, whole-exome sequencing, whole-transcriptome sequencing, and next-generation sequencing (NGS)-based HBV integration analysis, in eight patients with virus-related HCC. For validation, bulk RNA sequencing and NGS-based HBV integration analysis were performed in an independent cohort (n = 106).
RESULTS: Based on the expression scores of exhaustion markers in effector CD8+ T cells, patients were classified into high (n = 2) and low (n = 6) exhaustion groups (p <0.001). The high-exhaustion group exhibited higher clonal expansion (Gini index: 0.83 vs. 0.48, p = 0.006) and sharing of CD8+ T effector memory and cycling T cells with elevated exhaustion markers. This group also showed increased clonal expansion of CD4+ regulatory T cells and follicular helper T cells (p <0.001) with higher PDCD1 expression. In addition, the high-exhaustion group had higher TP53 mutation rates and signature scores for proliferation subtypes compared with the low-exhaustion group, who predominantly harbored TERT mutations. Moreover, the high-exhaustion group demonstrated more pronounced HBV integrations with elevated intrahepatic covalently closed circular DNA (cccDNA) and pregenomic (pg)RNA levels. Similarly, in the validation cohort, the high-exhaustion group (n = 28) demonstrated stronger proliferation subtype signatures (p <0.001), along with higher HBV integrations, S-fusion transcripts, and an increased intrahepatic viral reservoir (cccDNA/pgRNA) (p <0.05) compared with the low-exhaustion group (n = 78).
CONCLUSIONS: Our study revealed the heterogeneity in T-cell exhaustion in the TIME of HCC, along with differences in HBV integrations and molecular subtypes. These findings provide insight into the intricate relationship between high exhaustion, proliferation subtype, increased HBV integrations, and enhanced HBV-induced oncogenic potential in virus-related HCC.
IMPACT AND IMPLICATIONS: This study provides a comprehensive immune landscape of T-cell exhaustion using multi-omics analysis, offering critical insights into T cell heterogeneity in virus-related HCC. It establishes a strong association between higher HBV integration, enhanced oncogenic potential, T-cell exhaustion, and proliferation subtypes in HCC. Our results also establish a basis for personalized therapies tailored to the immune-exhaustion status within the TIME of each patient with HCC.
PMID:41113120 | PMC:PMC12529496 | DOI:10.1016/j.jhepr.2025.101518
Single-cell multi-omics analysis reveals cancer regulatory elements of transcriptional programs and clinical implications
Cell Death Dis. 2025 Oct 21;16(1):746. doi: 10.1038/s41419-025-08060-7.
ABSTRACT
The regulatory mechanisms governing transcriptional programs in the cancer genome remain elusive, particularly those concerning cell-type specificity. We carefully curated single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) and single-cell RNA sequencing (scRNA-seq) data from eight distinct carcinoma tissues, including breast, skin, colon, endometrium, lung, ovary, liver, and kidney. Using single-cell multi-omics analysis, we identified extensive open chromatin regions and constructed peak-gene link networks, which can reveal distinct cancer gene regulation and genetic risks. We further explored conserved epigenetic regulation across cell types within cancer and elucidated their functional implications. Moreover, we identified cell-type-associated transcription factors (TFs) that regulate key cellular functions, such as the TEAD family of TFs, which widely control cancer-related signaling pathways in tumor cells. In colon cancer, we further identified tumor-specific TFs that are more highly activated in tumor cells than in normal epithelial cells, including CEBPG, LEF1, SOX4, TCF7, and TEAD4, which are pivotal in driving malignant transcriptional programs and represent potential therapeutic targets, as corroborated by single-cell sequencing data from multiple sources and in vitro experiments. Our findings provide a comprehensive understanding of the regulatory dynamics underlying carcinomas and offer valuable insights into potential therapeutic interventions.
PMID:41120274 | PMC:PMC12541060 | DOI:10.1038/s41419-025-08060-7
Exploring Patient Perspectives, Engagement, and Output Quality in Doctor-Supervised Use of Artificial Intelligence During Informed Consent Consultation With ChatGPT and Retrieval Augmented Generation (RAG): Quantitative Exploratory Study
Assessing Large Language Models in Building a Structured Dataset From AskDocs Subreddit Data: Methodological Study
Meflin is a druggable target using antibody-drug conjugates in progressive osteosarcoma
Oncogene, Published online: 21 October 2025; doi:10.1038/s41388-025-03605-8
Meflin is a druggable target using antibody-drug conjugates in progressive osteosarcomaIntegrated epigenetic and genetic programming of primary human T cells
Nature Biotechnology, Published online: 21 October 2025; doi:10.1038/s41587-025-02856-w
Multiplexed editing in primary human T cells generates enhanced immune cell therapies.