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OA-NBV: Occlusion-Aware Next-Best-View Planning for Human-Centered Active Perception on Mobile Robots
Deep learning predicts gene rearrangements from histopathology in large B-cell lymphoma
npj Digital Medicine, Published online: 12 September 2026; doi:10.1038/s41746-026-03238-5
Deep learning predicts gene rearrangements from histopathology in large B-cell lymphomaA clinically derived lipid-endothelial signature links serum multi-omics to immune exclusion and clinical stratification in hepatocellular carcinoma
Ther Adv Med Oncol. 2026 Aug 31;18:17588359261481797. doi: 10.1177/17588359261481797. eCollection 2026.
ABSTRACT
BACKGROUND: Hepatocellular carcinoma (HCC) is driven by extensive metabolic reprogramming, vascular remodeling, and immune microenvironmental dysfunction. Although numerous stratification signatures have been proposed, few are grounded in clinically derived serum multi-omics and biologically linked to endothelial remodeling, endothelial regulation, and immune exclusion.
OBJECTIVES: This study aimed to identify a serum-derived lipid-endothelial program associated with immune exclusion and clinical stratification in HCC.
DESIGN: A translational multi-omics study integrating clinically collected serum samples, public transcriptomic cohorts, single-cell RNA sequencing, and experimental validation.
METHODS: Proteomic and metabolomic sequencing was performed on serum samples from patients with HCC and normal controls. Dysregulated pathways were integrated with transcriptomic data from TCGA-LIHC and ICGC-LIRI-JP cohorts to identify genes jointly associated with lipid metabolism and leukocyte transendothelial migration. A risk score was calculated using the expression of PON1, TXNRD1, CLDN4, CLDN6, CYP2C9, and CTSA. Higher expression of TXNRD1, CLDN4, CLDN6, and CTSA contributed to a higher risk score, whereas PON1 and CYP2C9 contributed protective coefficients. Immune contexture, tumor mutation burden, and exploratory therapeutic sensitivity patterns were further evaluated using transcriptome-based drug sensitivity prediction, followed by single-cell RNA sequencing and experimental expression validation.
RESULTS: Serum multi-omics analysis revealed prominent dysregulation of lipid metabolic pathways and leukocyte transendothelial migration-related processes in HCC. Integrative analysis identified a six-gene lipid-endothelial signature (PON1, TXNRD1, CLDN4, CLDN6, CYP2C9, and CTSA) that stratified patients into high- and low-risk groups. In the TCGA-LIHC cohort, high-risk patients had significantly poorer overall survival than low-risk patients (log-rank P < 0.0001), and this survival-stratifying association was externally supported in the ICGC-LIRI-JP cohort (log-rank P = 0.016). The high-risk phenotype was associated with immune-excluded features, distinct somatic mutation patterns, and altered predicted sensitivity to several selected anticancer agents. Single-cell analysis and experimental assays further supported the association between the six-gene program, malignant epithelial states, endothelial-related remodeling, and immune microenvironmental heterogeneity.
CONCLUSION: This study defines a clinically derived lipid-endothelial program associated with immune exclusion, adverse prognosis, and potential differences in therapeutic vulnerability in HCC. The proposed signature provides a biologically informed framework for prognostic assessment and may support future evaluation of targeted interventions in HCC.
PMID:42682961 | PMC:PMC13530516 | DOI:10.1177/17588359261481797
POC1A promotes the proliferation, metastasis and stemness of bladder cancer by stabilizing BMI1 via USP7
Oncogene, Published online: 31 August 2026; doi:10.1038/s41388-026-03973-9
POC1A promotes the proliferation, metastasis and stemness of bladder cancer by stabilizing BMI1 via USP7Agent-as-Peer-Debriefer: A Multi-Agent Framework with Perspective-Based Refinement for Qualitative Analysis
GPX8<sup>+</sup> cancer-associated fibroblast-derived lactate contributes to lenvatinib resistance by facilitating BRPF1 expression through histone H3 lysine 18 lactylation in hepatocellular carcinoma
Oncogene, Published online: 22 May 2026; doi:10.1038/s41388-026-03711-1
GPX8+ cancer-associated fibroblast-derived lactate contributes to lenvatinib resistance by facilitating BRPF1 expression through histone H3 lysine 18 lactylation in hepatocellular carcinomaGranzyme B-based CAR-T cells targeting membrane-bound HSP70 suppress solid tumor growth and metastasis
Oncogene, Published online: 18 April 2026; doi:10.1038/s41388-026-03797-7
Granzyme B-based CAR-T cells targeting membrane-bound HSP70 suppress solid tumor growth and metastasisApplications and challenges of multi-omics approaches in lung cancer research and precision treatment
Front Genet. 2026 Mar 23;16:1722368. doi: 10.3389/fgene.2025.1722368. eCollection 2025.
ABSTRACT
Lung cancer is one of the most common cancers worldwide and one of the leading causes of cancer death, with a heavy disease burden and severe public health challenges. Multi-omics techniques, such as genomics, proteomics, metabolomics, and radiomics, play a crucial role in the early diagnosis and treatment of lung cancer, revealing the molecular characteristics and mechanisms of lung cancer, and have significant clinical application value. However, it also faces numerous challenges, such as data issues, "black box" problems, and ethical and legal concerns. How to leverage strengths while mitigating weaknesses, achieve clinical translation of technology, and serve patients more effectively deserves our deep reflection. This article reviews the specific applications and challenges of multi-omics methods in lung cancer research and personalized treatment.
PMID:41948518 | PMC:PMC13050793 | DOI:10.3389/fgene.2025.1722368
Engineered immunosuppressive dendritic cells protect against cardiac remodelling
Nature, Published online: 08 April 2026; doi:10.1038/s41586-026-10346-5
Lesion-targeted immune modulation is a feasible strategy to control cardiac fibrosis, and engineered dendritic cells are a promising therapeutic platform for treating cardiac remodelling and heart failure.<i>Fusobacterium nucleatum</i> drives colorectal cancer progression through the <i>circPTBP</i>3/<i>miR-760</i>/<i>PUM1</i> axis
Oncogene, Published online: 31 March 2026; doi:10.1038/s41388-026-03746-4
Fusobacterium nucleatum drives colorectal cancer progression through the circPTBP3/miR-760/PUM1 axisRFC4 drives temozolomide resistance in glioblastoma by activating STK38-BECN1-dependent autophagy
Nat Commun. 2026 Mar 23. doi: 10.1038/s41467-026-70798-1. Online ahead of print.
ABSTRACT
Glioblastoma (GBM) remains a lethal brain tumor due to therapy resistance. While autophagy contributes to temozolomide (TMZ) resistance, its regulation is incompletely understood. This study investigates the role of replication factor RFC4, which is associated with poor prognosis and TMZ resistance in GBM. Multi-omics analyses and molecular experiments reveal that TMZ-induced chromatin accessibility enables transcription factor YY1 to bind the RFC4 promoter and upregulate its expression. RFC4, in turn, stabilizes the kinase STK38, which is essential for autophagosome formation. The RFC4-STK38 interaction facilitates BECN1 recruitment, thereby activating autophagy. Phosphorylation of STK38 at T444 stabilizes this complex, whereas a phospho-deficient mutant impairs autophagy. In vivo, RFC4 overexpression confers TMZ resistance, reversible by autophagy inhibition. Thus, our findings identify the RFC4-STK38-BECN1 axis as a mechanism underlying TMZ resistance and a potential target for precision therapy in GBM.
PMID:41872171 | DOI:10.1038/s41467-026-70798-1
Unannotated noncoding transcripts as a source of intratumor heterogeneity in malignant cell states
Sci China Life Sci. 2026 Mar 16. doi: 10.1007/s11427-025-3273-6. Online ahead of print.
ABSTRACT
Phenotypic diversity of malignant cells within a tumor underlies intratumor heterogeneity (ITH), a key determinant of cancer metastasis and treatment failure. However, the molecular mechanisms driving this heterogeneity are poorly understood. Here, we curated and analyzed a cohort of 3' tag-based single-cell RNA-seq covering 12 common cancer types. We identified thousands of poly(A) site (PAS) peaks representing the 3' ends of previously unannotated transcripts, whose expression is widely associated with diverse malignant cellular states. By integrating multi-omics data, we characterized the expression patterns and epigenetic landscape of these unannotated PAS peak-associated transcripts (UPTs). The expression heterogeneity of UPTs was supported by multi-region sampling bulk RNA-seq data and recapitulated within cancer cell lines. As proof of principle validation, functional experiments confirmed that two noncoding UPTs promoted the proliferation and migration of lung cancer cells. Our results suggest that epigenetic activation of unannotated noncoding transcripts might represent a previously unrecognized mechanism contributing to transcriptomic ITH.
PMID:41870780 | DOI:10.1007/s11427-025-3273-6
Unannotated noncoding transcripts as a source of intratumor heterogeneity in malignant cell states
Sci China Life Sci. 2026 Mar 16. doi: 10.1007/s11427-025-3273-6. Online ahead of print.
ABSTRACT
Phenotypic diversity of malignant cells within a tumor underlies intratumor heterogeneity (ITH), a key determinant of cancer metastasis and treatment failure. However, the molecular mechanisms driving this heterogeneity are poorly understood. Here, we curated and analyzed a cohort of 3' tag-based single-cell RNA-seq covering 12 common cancer types. We identified thousands of poly(A) site (PAS) peaks representing the 3' ends of previously unannotated transcripts, whose expression is widely associated with diverse malignant cellular states. By integrating multi-omics data, we characterized the expression patterns and epigenetic landscape of these unannotated PAS peak-associated transcripts (UPTs). The expression heterogeneity of UPTs was supported by multi-region sampling bulk RNA-seq data and recapitulated within cancer cell lines. As proof of principle validation, functional experiments confirmed that two noncoding UPTs promoted the proliferation and migration of lung cancer cells. Our results suggest that epigenetic activation of unannotated noncoding transcripts might represent a previously unrecognized mechanism contributing to transcriptomic ITH.
PMID:41870780 | DOI:10.1007/s11427-025-3273-6
Low-dose intestinal irradiation enhances the efficacy and prognosis of PD-1 blockade in metastatic non-small cell lung cancer
Clin Cancer Res. 2026 Mar 18. doi: 10.1158/1078-0432.CCR-25-4153. Online ahead of print.
ABSTRACT
PURPOSE: Intestinal low-dose irradiation (ILDR) may enhance immunotherapy efficacy by modulating the gut microbiota and metabolism; however, its role in metastatic non-small cell lung cancer (mNSCLC), particularly in the first-line setting, remains unclear.
EXPERIMENTAL DESIGN: This multicenter retrospective and prospective study included mNSCLC patients receiving first- and second-line programmed cell death protein 1 (PD-1) inhibitors along with abdominopelvic radiotherapy between 2018 and 2025. Patients were stratified by the mean intestinal radiation dose into <1 Gy, 1-3 Gy, and >3 Gy groups and treatment outcomes were compared. The blood and fecal samples were subjected to multi-omics profiling.
RESULTS: g>309 patients were included in the retrospective analysis. Optimal efficacy was observed with a small intestinal mean radiation dose (SIMRD) of 1-3 Gy, showing longer progression-free survival (PFS, 10.2 months) and overall survival (OS, 22.8 months) (P < 0.01), which was consistent across subgroups. Compared with 1-3 Gy, SIMRD >3 Gy (Hazard ratio [HR] = 4.87, P < 0.001) and <1 Gy (HR = 1.85, P < 0.001) independently predicted worse OS. Prospective results confirmed the best disease control rate (P = 0.041) and PFS (P = 0.046) with SIMRD of 1-3 Gy. Responders were enriched in Bacillota, Clostridia, and indole derivatives, particularly indole-3-carboxylic acid. Moreover, the 1-3 Gy group exhibited increased circulating macrophage inflammatory protein-3α and reduced circulating α4β7+ regulatory T cells.
CONCLUSIONS: ILDR influences the efficacy of PD-1 blockade in patients with mNSCLC, particularly when SIMRD is maintained within the 1-3 Gy range, likely through modulation of the gut microbiota-metabolite-immune axis.
PMID:41849236 | DOI:10.1158/1078-0432.CCR-25-4153
Continual Learning in Large Language Models: Methods, Challenges, and Opportunities
OffTopicEval: When Large Language Models Enter the Wrong Chat, Almost Always!
SkillsBench: Benchmarking How Well Agent Skills Work Across Diverse Tasks
Author Correction: Gut stem cell necroptosis by genome instability triggers bowel inflammation
Nature, Published online: 11 March 2026; doi:10.1038/s41586-026-10302-3
Author Correction: Gut stem cell necroptosis by genome instability triggers bowel inflammation