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City Editing: Hierarchical Agentic Execution for Dependency-Aware Urban Geospatial Modification
Early stage nonsmall cell lung cancer: Toward a risk-adaptive paradigm in the era of biologic precision
CA Cancer J Clin. 2026 Sep-Oct;76(5):e70100. doi: 10.3322/caac.70100.
ABSTRACT
The clinical landscape of early stage nonsmall cell lung cancer is at transformative crossroads. Driven by the widespread adoption of low-dose computed tomography screening, the frequent detection of ground-glass opacities, and a rising incidence among never-smokers, the diagnostic center of gravity has shifted toward earlier, potentially curable disease. This shift has been accompanied by equally important therapeutic advances, including parenchyma-sparing surgical techniques, minimally invasive platforms enhanced by digital navigation, and the transformative integration of perioperative immunotherapy and targeted agents. Concurrently, noninvasive monitoring approaches, such as liquid biopsy, have emerged as powerful tools to guide precision management. Despite this progress, substantial barriers to achieving a universal cure persist. Clinicians continue to face uncertainty in the management of ground-glass opacities, the anatomy-based TNM staging system fails to capture the biologic heterogeneity of early tumors, and global disparities in access to innovation remain unresolved. To address these challenges, the authors propose a shift toward a risk-adaptive management paradigm that harnesses artificial intelligence-driven analytics and multi-omics profiling to tailor treatment intensity according to each patient's biologic risk. Such an approach would enable appropriate escalation for high-risk individuals while permitting safe de-escalation for those at low risk. This holistic, lifespan-oriented strategy must be embraced to deliver equitable and durable cures for patients with early stage nonsmall cell lung cancer.
PMID:42713910 | PMC:PMC13555834 | DOI:10.3322/caac.70100
Early stage nonsmall cell lung cancer: Toward a risk-adaptive paradigm in the era of biologic precision
CA Cancer J Clin. 2026 Sep-Oct;76(5):e70100. doi: 10.3322/caac.70100.
ABSTRACT
The clinical landscape of early stage nonsmall cell lung cancer is at transformative crossroads. Driven by the widespread adoption of low-dose computed tomography screening, the frequent detection of ground-glass opacities, and a rising incidence among never-smokers, the diagnostic center of gravity has shifted toward earlier, potentially curable disease. This shift has been accompanied by equally important therapeutic advances, including parenchyma-sparing surgical techniques, minimally invasive platforms enhanced by digital navigation, and the transformative integration of perioperative immunotherapy and targeted agents. Concurrently, noninvasive monitoring approaches, such as liquid biopsy, have emerged as powerful tools to guide precision management. Despite this progress, substantial barriers to achieving a universal cure persist. Clinicians continue to face uncertainty in the management of ground-glass opacities, the anatomy-based TNM staging system fails to capture the biologic heterogeneity of early tumors, and global disparities in access to innovation remain unresolved. To address these challenges, the authors propose a shift toward a risk-adaptive management paradigm that harnesses artificial intelligence-driven analytics and multi-omics profiling to tailor treatment intensity according to each patient's biologic risk. Such an approach would enable appropriate escalation for high-risk individuals while permitting safe de-escalation for those at low risk. This holistic, lifespan-oriented strategy must be embraced to deliver equitable and durable cures for patients with early stage nonsmall cell lung cancer.
PMID:42713910 | DOI:10.3322/caac.70100
Multi-omics integration identifies APOE as a metabolic regulator of macrophage-fibroblast crosstalk in idiopathic pulmonary fibrosis
Front Immunol. 2026 Aug 18;17:1904638. doi: 10.3389/fimmu.2026.1904638. eCollection 2026.
ABSTRACT
BACKGROUND: Aberrant tissue repair and relentless fibroblast activation are hallmark features of idiopathic pulmonary fibrosis (IPF). Although IPF and Alzheimer's disease (AD) share underlying aging-related pathologies, including immune and metabolic dysregulation, the putative genetic mechanisms linking AD susceptibility to pathogenic macrophage remodeling in the fibrotic niche are not fully established.
METHODS: We performed a two-sample Mendelian randomization (MR) analysis to assess the genetic association and potential causal relationship between AD and IPF. Shared hub genes were identified via protein interaction networks. To characterize macrophage heterogeneity and intercellular crosstalk within the IPF microenvironment, we interrogated scRNA-seq data (GSE122960) utilizing Monocle 3 and CellChat algorithms. The functional essentiality of APOE was evaluated bridging computational virtual knockout (scTenifoldKnk) with laboratory in vitro assays. Specifically, downstream transcriptomic shifts and fibroblast activation capacities were validated using APOE-silenced THP-1 macrophages and a Transwell co-culture model with MRC-5 cells.
RESULTS: MR estimates indicated that genetic liability to AD is associated with a lower risk of developing IPF. Integrated profiling identified the lipid-metabolism gene APOE as a central hub, specifically enriched in lung macrophages. Pseudotime modeling captured a pathogenic bifurcation in IPF, where macrophages evolve toward a terminal state marked by profound oxidative phosphorylation defects and massive SPP1 secretion. These SPP1+ macrophages primarily activate fibroblasts via CD44 and integrin signaling axes. Furthermore, both virtual simulations and in vitro THP-1 experiments demonstrated that loss of APOE function triggers the hyperactivation of complement (C1QA) and antigen-presentation (HLA-DR) pathways. Co-culture assays ultimately confirmed that APOE ablation in macrophages strongly exacerbates myofibroblast differentiation (elevated α-SMA and collagen I) in adjacent MRC-5 cells.
CONCLUSION: APOE functions as a vital metabolic barrier against pro-fibrotic macrophage polarization in the lung. Disruption of this specific lipid metabolic network is strongly associated with SPP1-driven fibroblast activation and local immune imbalance, providing a theoretical framework that strictly warrants future in vivo investigation to determine its clinical relevance.
PMID:42682427 | PMC:PMC13529525 | DOI:10.3389/fimmu.2026.1904638
Nitrogen dioxide exposure promotes CD8(+)T cell infiltration and contributes to increased susceptibility to ulcerative colitis: An integrative multi-omics, artificial intelligence, and mouse model study
J Hazard Mater. 2026 Sep 15;516:143449. doi: 10.1016/j.jhazmat.2026.143449. Epub 2026 Aug 30.
ABSTRACT
The global incidence of ulcerative colitis (UC) has significantly increased in rapidly industrializing nations, with numerous studies highlighting environmental exposures, particularly nitrogen dioxide (NO2), as potential contributors to disease susceptibility. However, the clinical implications and molecular mechanisms linking NO2 exposure to UC susceptibility remain poorly understood. This study investigated the associations between NO2 and UC by integrating multi-omics data. We identified a CD8+ T cell subpopulation with a distinct phenotype characterized by perforin production, which potentially exacerbated colonic inflammation related to NO2 exposure. To validate this hypothesis, we established mouse models exposed to NO2, confirming increased CD8+ T cell infiltration and elevated perforin secretion through immunofluorescent (IF) staining. Employing artificial intelligence techniques, we identified Cell Division Cycle 25B (CDC25B) as a gene of interest correlated with putative NO2-related UC signatures. Finally, through molecular docking (MD) and molecular dynamics simulations (MDS), we identified ozanimod as one of several computationally nominated compounds associated with the CDC25B‑related network; however, none of these computational predictions were experimentally validated in the present study. Collectively, these findings suggest a correlative link between perforin or CD8+ T cell-associated colonic inflammation and NO2-associated UC susceptibility, and nominate CDC25B as a candidate gene for further investigation.
PMID:42679583 | DOI:10.1016/j.jhazmat.2026.143449
Ibrutinib-triggered matriptase maintains extracellular CD19 and limits antigen escape in B-cell malignancy
Cell Death Discovery, Published online: 31 August 2026; doi:10.1038/s41420-026-03306-5
Ibrutinib-triggered matriptase maintains extracellular CD19 and limits antigen escape in B-cell malignancySkin-innervating glutamatergic neurons modulate aging
Disentangled Double Machine Learning for Accurate Causal Effect Estimation
PageLLM: A Multi-Grained Reward Framework for Whole-Page Optimization with Large Language Models
ChunkLLM: A Lightweight Pluggable Framework for Accelerating LLMs Inference
SSDAU: Structured Semantic Data Augmentation for Joint Entity and Relation Extraction
circPARPBP promotes cancer stemness and chemoresistance in triple-negative breast cancer through recruiting SRCAP complex to activate CCL20 transcription
Oncogene, Published online: 21 May 2026; doi:10.1038/s41388-026-03819-4
circPARPBP promotes cancer stemness and chemoresistance in triple-negative breast cancer through recruiting SRCAP complex to activate CCL20 transcriptionIntegrative multi-omics and experimental validation reveal UBE2C as a central hub gene and prognostic biomarker in hepatocellular carcinoma
Int Immunopharmacol. 2026 May 19;183:116866. doi: 10.1016/j.intimp.2026.116866. Online ahead of print.
ABSTRACT
Hepatocellular carcinoma (HCC) is a lethal malignancy with a high recurrence rate and limited treatment options. Ubiquitin-conjugating enzyme E2 C (UBE2C) is implicated in various cancers, yet its impact on the HCC immune landscape remains incompletely understood. Herein, hub genes in HCC were identified, by integrating co-expression networks and protein-protein interaction analyses, from the TCGA, GEO, and CPTAC databases. Their expression was analysed using a single-cell transcriptomic database and verified in HCC tissues and cell lines via quantitative reverse transcription-PCR and immunoblotting. Functional roles of UBE2C were assessed using in vitro knockdown experiments and an in vivo subcutaneous tumour model. The tumour immune microenvironment was profiled using spatial transcriptomics, RNA-seq data, and ssGSEA. A prognostic nomogram was constructed based on multivariate Cox regression. UBE2C was identified as a significantly upregulated hub gene in HCC. Single-cell RNA-seq revealed predominant expression of UBE2C in hepatocytes, with dynamic upregulation along differentiation trajectories. UBE2C knockdown suppressed proliferation, induced apoptosis, and inhibited tumour growth. Spatial transcriptomics highlighted UBE2C-high regions within proliferative niches exhibiting immunosuppressive traits-including TGFB1 enrichment, impaired CXCL9-CXCR3 signalling, and exclusion of cytotoxic T cells-which were reduced in immunotherapy responders. UBE2C expression correlated with immune checkpoint genes and specific immune cell subsets. A UBE2C-based nomogram integrating T stage and tumour stage robustly predicted patient survival, and miR-300 and miR-381-3p were identified as potential upstream regulators. These findings establish UBE2C as a key driver of HCC progression and a biomarker for prognosis and immunotherapy stratification.
PMID:42155390 | DOI:10.1016/j.intimp.2026.116866
An activated wheat CCG10-NLR immune receptor forms an octameric resistosome
Unraveling RELA as a potential dioctyl terephthalate-related target regulates M2-like macrophages to induce an immunosuppressive microenvironment in colorectal cancer: a multi-omics data study by experimental validation
Mol Divers. 2026 Apr 12. doi: 10.1007/s11030-026-11545-y. Online ahead of print.
NO ABSTRACT
PMID:41966666 | DOI:10.1007/s11030-026-11545-y
Clinical application of base editing for treating β-thalassaemia
Nature, Published online: 08 April 2026; doi:10.1038/s41586-026-10342-9
A clinical phase 1 trial of a single infusion of CS-101, CD34+ cells modified using a transformer base editor to reactivate fetal haemoglobin production, led to early and enduring transfusion independence in patients with β-thalassaemia.Asymmetric selection of a rice immune module and rebuild of disease resistance
Nature, Published online: 08 April 2026; doi:10.1038/s41586-026-10361-6
Stacking XA48-mediated effector-triggered immunity with XA21-mediated pattern-triggered immunity in Oryza sativa japonica reconstitutes the broad-spectrum resistance from wild rice.