Reading view
OrpQuant: Geometric Orthogonal Residual Projection for Multiplier-Free Power-of-Two Transformer Quantization
Rethinking the Comparison Unit in Sequence-Level Reinforcement Learning: An Equal-Length Paired Training Framework from Loss Correction to Sample Construction
Internalizing Outcome Supervision into Process Supervision: A New Paradigm for Reinforcement Learning for Reasoning
Activation of methionine metabolism mediated by HNF4α confers ferroptosis resistance in hepatocellular carcinoma
Cell Death Discovery, Published online: 26 May 2026; doi:10.1038/s41420-026-03165-0
Activation of methionine metabolism mediated by HNF4α confers ferroptosis resistance in hepatocellular carcinomaIntegrated single-cell and bulk RNA sequencing reveals novel biomarkers of invasive adenocarcinoma subtypes in lung adenocarcinoma
Transl Cancer Res. 2026 Apr 30;15(4):314. doi: 10.21037/tcr-2025-aw-2503. Epub 2026 Mar 20.
ABSTRACT
BACKGROUND: Lung adenocarcinoma (LUAD) is one of the most common lung cancer subtypes worldwide, and its aggressive subtype invasive adenocarcinoma (IAC) has low survival rates. The precise identification of IAC is vital for the clinical diagnosis and treatment. The purpose of this study is to identify novel biomarkers for LUAD using single-cell and bulk RNA sequencing, so as to provide theoretical basis and practical support for the diagnosis, treatment and prognosis evaluation of lung invasive adenocarcinoma.
METHODS: We employed a combination of transcriptomic analysis and single-cell analysis to investigate the molecular characteristics and immune microenvironment of four subtypes of LUAD, including atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and IAC, with the aim of screening for biomarkers to differentiate pre-invasive lesions from invasive lesions.
RESULTS: Transcriptomic and single-cell analyses revealed that IAC subtypes demonstrated the most substantial molecular differences, particularly in immune cell infiltration and immune-related gene expression. Three genes-CD27, TIGIT, and TNFRSF18-that were significantly upregulated in IAC, predominantly expressed in immune cells and closely linked to immune regulatory pathways. We further analyzed T cell subpopulations in the IAC subtype and explored the expression of transcription factors (TFs) corresponding to these three genes, revealing their critical roles in immune cell function. Additionally, communication between T cells and other cells showed significantly enhanced signaling pathways, particularly those related to immune co-stimulatory molecules and inflammation pathways. Immunohistochemical validation of clinical samples showed that these three genes have high diagnostic value in IAC subtypes. These findings establish a crucial biological foundation for diagnosis, classification, and immunotherapy of LUAD, which contributes to the development of individualized treatment strategies.
CONCLUSIONS: This study identifies a three-gene signature (CD27, TIGIT, and TNFRSF18) that not only distinguishes invasive from pre-invasive LUAD with high precision by capturing the immune checkpoint disequilibrium characteristic of IAC, but also provides a clinically actionable biomarker panel for preoperative diagnosis and personalized immunotherapy strategies.
PMID:42180871 | PMC:PMC13190665 | DOI:10.21037/tcr-2025-aw-2503
Carbonyl swapping converts cyclic ketones to saturated heterocycles
Nature, Published online: 15 April 2026; doi:10.1038/s41586-026-10508-5
Carbonyl swapping converts cyclic ketones to saturated heterocyclesCan China’s Great Green Wall shape efforts to keep the world’s deserts at bay?
Nature, Published online: 15 April 2026; doi:10.1038/d41586-026-01102-w
Grand anti-desertification schemes often fail when trees die and funding dries up — yet one project has broken the mould.Can LLMs Learn to Reason Robustly under Noisy Supervision?
VLBiasBench: A Comprehensive Benchmark for Evaluating Bias in Large Vision-Language Model
TRACE-Bot: Detecting Emerging LLM-Driven Social Bots via Implicit Semantic Representations and AIGC-Enhanced Behavioral Patterns
SHOE: Semantic HOI Open-Vocabulary Evaluation Metric
Think, Act, Build: An Agentic Framework with Vision Language Models for Zero-Shot 3D Visual Grounding
Do Phone-Use Agents Respect Your Privacy?
FlowPIE: Test-Time Scientific Idea Evolution with Flow-Guided Literature Exploration
Owl-AuraID 1.0: An Intelligent System for Autonomous Scientific Instrumentation and Scientific Data Analysis
WAter: A Workload-Adaptive Knob Tuning System based on Workload Compression
InCoder-32B: Code Foundation Model for Industrial Scenarios
Androgen activity in the male embryonic hindbrain drives lethal PFA ependymoma
Nature, Published online: 25 March 2026; doi:10.1038/s41586-026-10264-6
Androgen activity in the male embryonic hindbrain prolongs hindbrain differentiation in male individuals and drives sex differences in the incidence and prognosis of posterior fossa type A (PFA) ependymoma, an aggressive childhood brain tumour.Single-cell multiomics uncovers an endothelial mechanosensitive PIEZO1-IL-33 axis driving pulmonary fibrosis
Nat Commun. 2026 Mar 20;17(1):2655. doi: 10.1038/s41467-026-70193-w.
ABSTRACT
Pulmonary fibrosis represents a progressive interstitial lung disease marked by excessive extracellular matrix deposition and architectural distortion. Vascular endothelial cells critically contribute to fibrogenesis through paracrine secretion of pro-fibrotic mediators, yet their mechanobiological regulation remains elusive. Using integrated single-cell multi-omics profiling of human pulmonary fibrosis specimens and experimental fibrosis models induced by bleomycin or silica, we identify mechanosensitive Piezo1 upregulation in Endothelial cells as a hallmark of fibrotic progression. Endothelial-specific Piezo1 knockout significantly attenuates Bleomycin-induced fibrotic remodeling in male mice, establishing its pathogenic necessity. Mechanistically, PIEZO1 activation promotes pulmonary fibrosis development via CAPN2-mediated STAT3 phosphorylation, which may regulate the secretion of the pro-fibrotic molecule interleukin-33. These findings suggest that the endothelial PIEZO1-CAPN2-STAT3-IL33 axis is a potential therapeutic target for PF intervention.
PMID:41862476 | PMC:PMC13004862 | DOI:10.1038/s41467-026-70193-w