Reading view
SimSkill: A Self-Evolving LLM Agent for Skill and Knowledge Accumulation in Traffic Simulation
Inhaled nanosilica orchestrates a pulmonary macrophage-NK cell axis for memory-like NK programming toward synergistic cancer immunotherapy
Structural Process Supervision for Latent Chain-of-Thought Reasoning
Show-Harness: Just a VLM Agent Can Play Robots
Geo-Expert: Towards Expert-Level Geological Reasoning via Parameter-Efficient Fine-Tuning
Distributionally Robust Transfer Learning with Structurally Missing Covariates, with Application to Cross-National Cardiac Arrest Prediction
Cross-Domain Energy-Guided Diffusion Generation for Off-Dynamics Reinforcement Learning
DRScaffold: Boosting Dense-Scene Reasoning in Lightweight Vision Language Models
AutoResearchClaw: Self-Reinforcing Autonomous Research with Human-AI Collaboration
SoK: A Comprehensive Security Analysis of Jailbreak Resilience in GPT and DeepSeek Models
STAPO: Stabilizing Reinforcement Learning for LLMs by Silencing Rare Spurious Tokens
Proteomic and lipidomic analyses reveal molecular subtypes and potential targets in early-stage lung adenocarcinoma among non-smokers
Cell Rep. 2026 May 26;45(5):117215. doi: 10.1016/j.celrep.2026.117215. Epub 2026 Apr 28.
ABSTRACT
Early-stage lung adenocarcinoma (LUAD) in never smokers exhibits distinct biological features, yet the metabolic programs driving early invasion remain unclear. We integrate proteomic and lipidomic profiling of primary LUAD tumors from never smokers, matched normal adjacent tissues (NATs), and benign pulmonary nodules (BPNs). Integrated multi-omics analysis reveals coordinated dysregulation of lipid metabolism and immune signaling in early LUAD. Proteome-based network fusion stratifies invasive LUAD into immune-metabolic synergistic (IMS) and metabolic-stress-driven (MSD) subtypes. IMS tumors retain apolipoprotein-associated lipid modules and favorable immune features, whereas MSD tumors exhibit stress-response programs. Mechanistically, APOA1 and APOC1 emerge as key nodes linking lipid homeostasis to invasion, and their depletion promotes LUAD cell migration and invasion. We establish a two-protein, four-lipid diagnostic panel demonstrating robust performance across tissue and plasma cohorts. These findings provide a molecular basis for early detection and risk stratification in never smokers.
PMID:42054209 | DOI:10.1016/j.celrep.2026.117215
Establishment and characterization of an immortalized porcine gastric epithelial cell line and identification of NPC1 as a key mediator of aflatoxin B1 toxicity
Gene. 2026 Apr 9:150160. doi: 10.1016/j.gene.2026.150160. Online ahead of print.
ABSTRACT
Porcine gastric epithelial cells (PGECs) serve as a valuable model for studying the molecular and pathogenic mechanisms of the stomach. However, PGECs face limitations such as isolation challenges, short lifespan, and restricted proliferation. To address this, we established an immortalized PGECs (i-PGECs) to enable in vitro investigation of pathogen infection mechanisms. Primary PGECs were isolated from the acid-secreting glands using stepwise digestion with multiple enzymes (dispase II/collagenase I/hyaluronidase). Immortalization was achieved via lentiviral vectors expressing simian virus 40 large T antigen (SV40T) and human telomerase reverse transcriptase (hTERT), with successful expression confirmed by qRT-PCR (P < 0.05). Epithelial identity of i-PGECs was confirmed by stable expression of CK18, EpCAM, and E-cadherin, as shown by qRT-PCR and immunofluorescence. i-PGECs retained the morphological and ultrastructural features of PGECs and exhibited enhanced proliferation, as demonstrated by WST-8 assays, apoptosis and cell cycle analysis, karyotyping, and transmission electron microscopy (TEM). Telomere length analysis and scratch wound assays demonstrated stable telomere maintenance and consistent migration capacity unaffected by passaging. RNA-sequencing and differential expressed genes (DEGs) analysis revealed significantly upregulating of genes involved in cell proliferation pathways (P < 0.01). Following aflatoxin B1 (AFB1) exposure, i-PGECs significantly upregulated immune-related factors, such as NPC1 and PLAUR (P < 0.01). CRISPR/Cas9-mediated knockout of NPC1 in i-PGECs conferred increased resistance to AFB1-induced cytotoxicity, as shown by WST-8 assay. The i-PGECs remained stable after more than 50 passages, supporting their use as a reliable for in vitro model investigating the mechanisms of toxicity infection in the porcine gastric epithelium.
PMID:41966285 | DOI:10.1016/j.gene.2026.150160
Epigenome-wide Mendelian randomization with multi-omics validation identifies epigenetic drivers of idiopathic pulmonary fibrosis
Commun Biol. 2026 Apr 11. doi: 10.1038/s42003-026-10033-1. Online ahead of print.
ABSTRACT
Idiopathic pulmonary fibrosis (IPF) is a complex disease without clear etiology or effective therapy. While DNA methylation has been implicated in IPF pathogenesis, the tissue-specific causal effects of the epigenetic factors on IPF remain undetermined. Here, we perform epigenome-wide Mendelian randomization using blood-based methylation quantitative trait loci of 420,509 CpG sites and genome-wide association study for IPF to elucidate the causal effects of the CpG sites on IPF. Totally, 452 CpG sites has shown putative causal effects on IPF risk after Bonferroni correction. Among them, 13 CpG sites have shown strong colocalization evidence with genetic factors associated with IPF. Specifically, DNA methylation at CpG sites within MAN2A2 and TRIM27 shows significant differences between IPF lungs and controls, correlating with altered mRNA expressions of these genes in lung tissues. The CpG site in MAN2A2 is a binding site of ZNF384 according to transcription factor databases. RNA sequencing in the TGFβ1-induced alveolar epithelia confirms significantly reduced expression of MAN2A2 and ZNF384 comparing to the controls. Collectively, our study suggests a putative causal link between DNA methylation within MAN2A2 and IPF risk, wherein lung-specific DNA methylation in MAN2A2 may perturb the interaction between ZNF384 and MAN2A2, revealing novel roles for these genes in IPF pathogenesis.
PMID:41965819 | DOI:10.1038/s42003-026-10033-1
Epigenome-wide Mendelian randomization with multi-omics validation identifies epigenetic drivers of idiopathic pulmonary fibrosis
Commun Biol. 2026 Apr 11. doi: 10.1038/s42003-026-10033-1. Online ahead of print.
ABSTRACT
Idiopathic pulmonary fibrosis (IPF) is a complex disease without clear etiology or effective therapy. While DNA methylation has been implicated in IPF pathogenesis, the tissue-specific causal effects of the epigenetic factors on IPF remain undetermined. Here, we perform epigenome-wide Mendelian randomization using blood-based methylation quantitative trait loci of 420,509 CpG sites and genome-wide association study for IPF to elucidate the causal effects of the CpG sites on IPF. Totally, 452 CpG sites has shown putative causal effects on IPF risk after Bonferroni correction. Among them, 13 CpG sites have shown strong colocalization evidence with genetic factors associated with IPF. Specifically, DNA methylation at CpG sites within MAN2A2 and TRIM27 shows significant differences between IPF lungs and controls, correlating with altered mRNA expressions of these genes in lung tissues. The CpG site in MAN2A2 is a binding site of ZNF384 according to transcription factor databases. RNA sequencing in the TGFβ1-induced alveolar epithelia confirms significantly reduced expression of MAN2A2 and ZNF384 comparing to the controls. Collectively, our study suggests a putative causal link between DNA methylation within MAN2A2 and IPF risk, wherein lung-specific DNA methylation in MAN2A2 may perturb the interaction between ZNF384 and MAN2A2, revealing novel roles for these genes in IPF pathogenesis.
PMID:41965819 | DOI:10.1038/s42003-026-10033-1