Reading view
Uncertainty as a Planning Signal: Multi-Turn Decision Making for Goal-Oriented Conversation
How AI Aggregation Affects Knowledge
Autonomous Agents for Scientific Discovery: Orchestrating Scientists, Language, Code, and Physics
From Seeing to Doing: Bridging Reasoning and Decision for Robotic Manipulation
Embodied-R1: Reinforced Embodied Reasoning for General Robotic Manipulation
Unmasking FCGR2B as a high-grade serous ovarian cancer specific marker of immune suppression and tumor progression through multi-omics mining
Transl Oncol. 2026 Apr 3;67:102748. doi: 10.1016/j.tranon.2026.102748. Online ahead of print.
ABSTRACT
BACKGROUND: Epithelial ovarian cancer (EOC) encompasses five major histological subtypes with marked genetic, immunological, and clinical heterogeneity. While genome-wide association studies (GWAS) have identified subtype-specific risk loci, a critical gap remains in understanding how plasma proteins influence immune-cell traits and contribute to EOC pathogenesis.
METHODS: We integrated subtype-stratified GWAS data from two EOC cohorts with plasma proteomics and immune-cell traits to construct protein-immune-EOC regulatory landscapes using a three-stage Mendelian randomization framework. Single-cell RNA-seq and multiplex immunofluorescence were employed to delineate the cellular distribution and spatial context of causal proteins. Subsequent analyses characterized immune infiltration, macrophage polarization, and clinicopathological associations. Drug-gene correlations were used to identify potential therapeutic targets, and transcriptomic analyses were applied to delineate the underlying transcriptional landscape.
RESULTS: We identified 20 subtype-specific protein-immune-EOC regulatory axes, with FCGR2B emerging as a causal plasma protein in immune regulation and high-grade serous ovarian cancer (HGSOC) progression. FCGR2B was highly expressed in tumor-associated macrophages and was associated with an M2-like polarization phenotype. Functional characterization revealed that FCGR2B was associated with shorter progression-free survival and an immunosuppressive tumor microenvironment. Transcriptomic analyses revealed altered NF-κB signaling upon FCGR2B knockdown, and drug-response data suggested a potential association between high FCGR2B expression and sensitivity to NF-κB inhibitors.
CONCLUSIONS: These findings delineate subtype-specific genetically informed protein-immune regulatory landscapes in EOC and identify FCGR2B as a key immunoregulatory and prognostic biomarker in HGSOC, suggesting FCGR2B as a potential therapeutic vulnerability that warrants further investigation.
PMID:41934917 | DOI:10.1016/j.tranon.2026.102748
Do Phone-Use Agents Respect Your Privacy?
PRET is a few-shot system for pan-cancer recognition without example training
Nature Cancer, Published online: 03 April 2026; doi:10.1038/s43018-026-01141-2
Li et al. present PRET, a few-shot system for pan-cancer detection not requiring model fine-tuning, validated it in multicenter datasets and found that it outperformed existing approaches across tasks and pathologists in lymph node metastasis detection.Metabolite-gated vascular contractility switch: OXGR1 activation mechanism enables agonist therapy for rosacea erythema
Editing strigolactone hormone receptor for robust antiviral silencing in rice
GISTBench: Evaluating LLM User Understanding via Evidence-Based Interest Verification
Predicting Neuromodulation Outcome for Parkinson's Disease with Generative Virtual Brain Model
C-TRAIL: A Commonsense World Framework for Trajectory Planning in Autonomous Driving
Time is Not Compute: Scaling Laws for Wall-Clock Constrained Training on Consumer GPUs
Efficient and Scalable Granular-ball Graph Coarsening Method for Large-scale Graph Node Classification
Electric dipole moment drives the dynamics of the TNFR1 complex I signalosome
Nature, Published online: 01 April 2026; doi:10.1038/s41586-026-10304-1
Long-range interactions mediated by protein electric dipole moments have a role in driving the assembly and disassembly of super-signalling complex I for promoting NF-κB signalling.SynLeaF: A Dual-Stage Multimodal Fusion Framework for Synthetic Lethality Prediction Across Pan- and Single-Cancer Contexts
p63 in skin homeostasis and disease: molecular mechanisms and therapeutic potentials
Cell Death Discovery, Published online: 24 March 2026; doi:10.1038/s41420-026-03060-8
p63 in skin homeostasis and disease: molecular mechanisms and therapeutic potentialsHypoxia-related and immune phenotype-related fusion model for non-invasive prognostication of hepatocellular carcinoma treated by TACE: a multicentre study
Gut. 2026 Mar 30:gutjnl-2025-337938. doi: 10.1136/gutjnl-2025-337938. Online ahead of print.
ABSTRACT
BACKGROUND: Survival outcomes after transarterial chemoembolisation (TACE) vary in hepatocellular carcinoma (HCC) patients, and existing prognostic scores and imaging models often lack generalisability and biological interpretability.
OBJECTIVE: To develop and validate a multimodal prognostication model for HCC that allows for a precise assessment of survival outcomes of HCC patients receiving TACE therapy.
DESIGN: This study enrolled 1448 HCC patients, including a TACE cohort (n=1349), a biomarker subset from a randomised trial (n=41), a single-cell RNA sequencing cohort and The Cancer Genome Atlas (TCGA) HCC cohort (n=50). Pre-treatment contrast-enhanced CT images were used to construct deep learning and conventional radiomic models. The early-fusion and late-fusion models (LFMs) were compared, and a clinical-radiologic model (CRM) was formed by integrating the better-performing LFM with clinical variables. Using TCGA data and single-cell transcriptomic profiles, the differences between high-score and low-score groups in tumour immune microenvironment, cellular functional states and key signalling pathways were investigated.
RESULTS: The CRM effectively stratified patients' survival across multiple independent cohorts and achieved more granular risk stratification than the existing clinical models. Multi-omic analyses revealed that in the LFM high-score group, myelocytomatosis oncogene was activated, epithelial-mesenchymal transition enhanced, glycolysis upregulated and hypoxia pathway activated. Single-cell transcriptomic data confirmed that virtually all cell types in high-risk patients scored high in hypoxia, and cytotoxic T cells had a reduced cytotoxic activity.
CONCLUSION: The CRM model can non-invasively predict the prognosis of HCC patients treated by TACE therapy.
PMID:41856522 | DOI:10.1136/gutjnl-2025-337938