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Received — 10 September 2026 ⏭

Ammonium tetrathiomolybdate improves auditory and vestibular function after gentamicin exposure via the NRF2–GPX4 axis

✇Molecular Therapy
By: Qiong Wu · Minchao Wu · Mingwei Xu · Tianyu Gong · Yuan Yao · Qianqian Zhang · Linrui Chen · Jianhui Qiu · Yulian Jin · Guisheng Zhong · Yu Zhao · Ce Zheng · Qing Zhang
2 September 2026 at 08:00
Zhang and colleagues reveal that GPX4 serves as a critical regulator of NRF2-mediated otoprotection against aminoglycoside-induced hair cell injury. Their findings identify a GPX4-dependent antioxidant mechanism that enables therapeutic activation of NRF2 and provides new insights into strategies for preventing drug-induced hearing loss.

A Taxonomy of Architecture Options for Foundation Model-based Agents: Analysis and Decision Model

✇cs.AI, q-bio.NC updates on arXiv.org
By: Jingwen Zhou · Qinghua Lu · Jieshan Chen · Liming Zhu · Xiwei Xu · Zhenchang Xing · Stefan Harrer
10 September 2026 at 12:00
arXiv:2408.02920v2 Announce Type: replace-cross Abstract: The rapid advancement of AI technology has led to widespread applications of agent systems across various domains. However, the need for detailed architecture design poses significant challenges in designing and operating these systems. This paper introduces a taxonomy focused on the architectures of foundation-model-based agents, addressing critical aspects such as functional capabilities and non-functional qualities. We also discuss the operations involved in both design-time and run-time phases, providing a comprehensive view of architectural design and operational characteristics. By unifying and detailing these classifications, our taxonomy aims to improve the design of foundation-model-based agents. Additionally, the paper establishes a decision model that guides critical design and runtime decisions, offering a structured approach to enhance the development of foundation-model-based agents. Our contributions include providing a structured architecture design option and guiding the development process of foundation-model-based agents, thereby addressing current fragmentation in the field.

MCAT-mediated mitochondrial fatty acid metabolism regulates Lauren subtype divergence and suppresses gastric cancer progression through ROS/P53-dependent mitophagy and ferroptosis

✇Omics in Gastric
By: Yufei Wang · Meng Zhu · Xin Yin · Tianyi Fang · Lei Zhang · Yujuan Jiao · Hongxin Wang · Zipu Dong · Tengteng Liu · Yingwei Xue
9 September 2026 at 18:00

Cell Death Differ. 2026 Sep 8. doi: 10.1038/s41418-026-01867-7. Online ahead of print.

ABSTRACT

Gastric cancer (GC) displays marked heterogeneity under the Lauren classification, yet the metabolic determinants of subtype divergence remain unclear. Here, we identify Malonyl-CoA:ACP transacylase (MCAT), a Lauren subtype-associated gene encoding a key mitochondrial fatty acid synthesis (mtFAS) enzyme, as a subtype-specific tumor suppressor in GC. Integrative multi-omics profiling revealed that MCAT expression is enriched in intestinal-type GC and correlates with favorable prognosis. Mechanistically, MCAT overexpression drives metabolic reprogramming through mitochondrial free fatty acid overload, suppressing β-oxidation while elevating mitochondrial reactive oxygen species (ROS), which triggers P53 phosphorylation at Ser15. This event concurrently activates PINK1/Parkin-mediated mitophagy and suppresses the SLC7A11/GPX4 axis to induce ferroptosis. Genetic rescue experiments confirmed that P53-Ser15 phosphorylation is essential for both mitophagy and ferroptosis induction. Endogenous MCAT levels are sufficient to determine basal ROS/P53/mitophagy/ferroptosis axis activity, and knockdown in high-expressing cells reverses these phenotypes, supporting a physiological, threshold-dependent role. In vivo, MCAT overexpression suppresses tumor growth and enhances mitophagy and ferroptosis markers. Collectively, these findings establish MCAT as a metabolic switch that links mtFAS to ROS/P53-dependent cell death, providing a potential biomarker and therapeutic target for GC.

PMID:42711380 | DOI:10.1038/s41418-026-01867-7

MCAT-mediated mitochondrial fatty acid metabolism regulates Lauren subtype divergence and suppresses gastric cancer progression through ROS/P53-dependent mitophagy and ferroptosis

✇(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)
By: Yufei Wang · Meng Zhu · Xin Yin · Tianyi Fang · Lei Zhang · Yujuan Jiao · Hongxin Wang · Zipu Dong · Tengteng Liu · Yingwei Xue
9 September 2026 at 18:00

Cell Death Differ. 2026 Sep 8. doi: 10.1038/s41418-026-01867-7. Online ahead of print.

ABSTRACT

Gastric cancer (GC) displays marked heterogeneity under the Lauren classification, yet the metabolic determinants of subtype divergence remain unclear. Here, we identify Malonyl-CoA:ACP transacylase (MCAT), a Lauren subtype-associated gene encoding a key mitochondrial fatty acid synthesis (mtFAS) enzyme, as a subtype-specific tumor suppressor in GC. Integrative multi-omics profiling revealed that MCAT expression is enriched in intestinal-type GC and correlates with favorable prognosis. Mechanistically, MCAT overexpression drives metabolic reprogramming through mitochondrial free fatty acid overload, suppressing β-oxidation while elevating mitochondrial reactive oxygen species (ROS), which triggers P53 phosphorylation at Ser15. This event concurrently activates PINK1/Parkin-mediated mitophagy and suppresses the SLC7A11/GPX4 axis to induce ferroptosis. Genetic rescue experiments confirmed that P53-Ser15 phosphorylation is essential for both mitophagy and ferroptosis induction. Endogenous MCAT levels are sufficient to determine basal ROS/P53/mitophagy/ferroptosis axis activity, and knockdown in high-expressing cells reverses these phenotypes, supporting a physiological, threshold-dependent role. In vivo, MCAT overexpression suppresses tumor growth and enhances mitophagy and ferroptosis markers. Collectively, these findings establish MCAT as a metabolic switch that links mtFAS to ROS/P53-dependent cell death, providing a potential biomarker and therapeutic target for GC.

PMID:42711380 | DOI:10.1038/s41418-026-01867-7

CAFs shape the immunosuppressive microenvironment of pancreatic cancer through the Lin28b-STING Axis

✇(Multiomics OR Omics) AND (Pancreatic)
By: Minghe Fan · Ziyang Zhang · Wei Xu · Yuwei Liu · Ruoxuan Wang · Wenqin Hao · Sihan Huo · Yuyao Guo · Lina Wang · Ang Lv · Xiangyu Liu · Wei Wang · Chuanhui Han · Ying Zhao
3 September 2026 at 18:00

Nat Commun. 2026 Aug 7;17(1):9491. doi: 10.1038/s41467-026-76495-3.

ABSTRACT

Cancer-associated fibroblasts comprise diverse functionally distinct cellular subsets, with certain subpopulations exerting pivotal influence in shaping the pancreatic cancer immune microenvironment. Here we show that Lin28b+ cancer-associated fibroblasts contribute to establishing an immunologically cold tumor microenvironment in pancreatic ductal adenocarcinoma. Mechanistically, Lin28b directly binds to STING mRNA and promotes its degradation, thereby suppressing STING expression and downstream type I interferon signaling. Loss of Lin28b in cancer-associated fibroblasts activates the cGAS-STING-interferon signaling cascade, enhancing dendritic cell antigen presentation and CD8+ T cell cytotoxic function. Importantly, genetic inhibition of Lin28b in cancer-associated fibroblasts enhances sensitivity to anti-PD-L1 immune checkpoint blockade therapy. These findings reveal that targeting the Lin28b-STING axis represents a promising therapeutic strategy for overcoming the intrinsic resistance of pancreatic ductal adenocarcinoma to immunotherapy.

PMID:42693143 | PMC:PMC13542369 | DOI:10.1038/s41467-026-76495-3

Multi-omics screening and functional validation identify SLC5A6 as a candidate disulfidptosis-related gene and prognostic biomarker in hepatocellular carcinoma

✇Omics in Hepatocellular
By: Chong Fu · Zejing Fang · Yanping Zhang · Wei Xu
29 August 2026 at 18:00

Front Oncol. 2026 Aug 14;16:1918635. doi: 10.3389/fonc.2026.1918635. eCollection 2026.

ABSTRACT

OBJECTIVE: Hepatocellular carcinoma (HCC) is characterized by frequent recurrence, therapeutic resistance, and marked metabolic adaptability. Disulfidptosis is a recently described form of regulated cell death associated with glucose deprivation and disulfide stress. This study aimed to identify disulfidptosis-related genes associated with HCC progression and to investigate the potential biological role of SLC5A6.

METHODS: Single-cell RNA sequencing and TCGA-LIHC transcriptomic data were integrated. A literature-derived, non-directional disulfidptosis-related gene-set enrichment score was calculated using ssGSEA, and copy-number alterations were inferred using inferCNV. WGCNA, differential expression analysis, and the SLC-family gene list were integrated to identify candidate genes. Bayesian deconvolution, ESTIMATE, TIDE, and GSVA were used to evaluate tumor-microenvironment-related features and pathway signatures. The biological effects of SLC5A6 silencing were assessed using proliferation, migration, invasion, apoptosis, and xenograft assays. Glucose-deprivation-induced disulfide stress was further evaluated by measuring protein disulfide content, the NADP+/NADPH ratio, and FLNA and FLNB band patterns under non-reducing conditions.

RESULTS: Single-cell analysis showed that malignant hepatocytes with higher inferCNV-derived CNV scores exhibited greater enrichment of the disulfidptosis-related gene signature. Integration of glucose-deprivation-associated DEGs, WGCNA modules, and SLC-family genes identified SLC5A6 as a candidate disulfidptosis-related gene that was upregulated in HCC and associated with poor prognosis. Bayesian deconvolution, ESTIMATE, TIDE, and GSVA analyses linked elevated SLC5A6 expression to advanced disease, stromal and immunosuppressive cell enrichment, higher T-cell exclusion scores, and activation of Wnt/mTOR-related signaling signatures. In SLC7A11-high HCC cells, glucose deprivation increased protein disulfide content and the NADP+/NADPH ratio and altered non-reducing FLNA and FLNB band patterns, whereas these changes were partially attenuated by SLC5A6 silencing. Under conventional culture conditions, SLC5A6 silencing inhibited proliferation, migration, invasion, and xenograft growth and increased apoptosis.

CONCLUSION: SLC5A6 is a candidate disulfidptosis-related gene and prognostic biomarker associated with malignant progression in HCC. The findings suggest that SLC5A6 may participate in glucose-deprivation-induced disulfide stress, while its direct role in regulating disulfidptotic cell death remains to be established. Its associations with immune-exclusion-related features also require further functional validation.

PMID:42666251 | PMC:PMC13521847 | DOI:10.3389/fonc.2026.1918635

Received — 27 May 2026 ⏭

A governance horizon for ethical-use constraints in open-weight AI models

✇cs.AI, q-bio.NC updates on arXiv.org
By: Weiwei Xu · Hengzhi Ye · Haoran Ye · Kai Gao · Vladimir Filkov · Minghui Zhou
26 May 2026 at 12:00
arXiv:2605.24383v1 Announce Type: new Abstract: Ethical constraints on open-weight AI models are both a reflection of societal concerns and a foundation for AI governance policy. They are expected to propagate to downstream derivatives while implemented as voluntary metadata disclosures that must be restated at each generation of reuse. We audit 2,142,823 model repositories on Hugging Face Hub to test whether this disclosure-based governance infrastructure can sustain traceability across deep model lineages. Restriction evidence decays with a half-life of 1.31 derivation steps ($R^2$=0.98), and beyond seven downstream generations at least 80% of descendant models lack sufficient public evidence for a governance determination, a depth boundary we formalize as the governance horizon. Platform-level interventions to restore missing licence metadata reveal that policy design (not enforcement alone) is the binding factor: inheritance-only designs require near-complete enforcement to move the horizon, whereas a mandatory-declaration design that explicitly resolves orphan lineage components shifts the horizon already at moderate enforcement. The structural bottleneck is lineages with no inheritable upstream intent: such orphan components remain undecidable under any inheritance-only policy regardless of enforcement rate, and unresolved upstream nodes additionally create direct downstream undecidability bottlenecks that inheritance rules alone cannot recover. Comparison with PyPI, where governance signals are carried by explicit machine-readable declarations, corroborates that the collapse is topology-specific to open-weight derivation rather than inherent to open ecosystems. These results establish that disclosure-based governance has a shallow, structurally determined reach in open-weight AI, and that achieving deep supply-chain accountability requires provenance mechanisms propagating governance signals through derivation itself.

Knowledge Graph Modulated Deep Learning for Limited-Sample Clinical Data Analysis

✇cs.AI, q-bio.NC updates on arXiv.org
By: Yuwei Xue · Sakib Mostafa · James Zou · Joseph Liao · Maximilian Diehn · Ash A. Alizadeh · Lei Xing · Md. Tauhidul Islam
26 May 2026 at 12:00
arXiv:2605.24162v1 Announce Type: cross Abstract: Biological systems are governed by structured molecular interactions, where pathways, regulatory circuits, and functional gene relationships shape cellular behavior and disease progression. Much of this knowledge is naturally represented as graphs. However, most biomedical AI models cannot directly use graph-encoded biological knowledge and instead require compressed low-dimensional representations, which can lose important structure and reduce performance, especially in limited-sample clinical studies. Here, we introduce Graph-in-Graph (GiG), a knowledge graph-modulated deep learning framework for data-efficient clinical prediction. GiG represents each patient as a standalone modular graph, in which curated biological knowledge graphs define edges and patient-specific measurements, such as gene expression, define node features. This design allows multiple biological knowledge graphs to be integrated while preserving gene-gene interactions and pathway topology during patient-level representation learning. Across cohorts comprising nearly 9,700 patients and five clinical tasks, including liquid biopsy cancer detection, prostate cancer diagnosis, and 32-class pan-cancer classification, GiG consistently outperforms traditional and state-of-the-art methods, with the largest gains in limited-sample settings. On the challenging prostate cancer diagnosis task, GiG improves macro-F1 by up to 49 percentage points relative to competing methods. Control experiments replacing real pathway graphs with random topologies confirm that these gains arise from biologically grounded knowledge graph structure rather than graph modeling alone. These findings show that knowledge graph-modulated deep learning can improve robustness, interpretability, and sample efficiency in clinical data analysis, and provide a principled framework for integrating biological knowledge graphs into predictive modeling.

MOSS: Self-Evolution through Source-Level Rewriting in Autonomous Agent Systems

✇cs.AI, q-bio.NC updates on arXiv.org
By: Qianshu Cai · Yonggang Zhang · Xianzhang Jia · Huajiang Zheng · Wei Xue · Jun Song · Xinmei Tian · Yike Guo
26 May 2026 at 12:00
arXiv:2605.22794v2 Announce Type: replace Abstract: Autonomous agentic systems are largely static after deployment: they do not learn from user interactions, and recurring failures persist until the next human-driven update ships a fix. Self-evolving agents have emerged in response, but all confine evolution to text-mutable artifacts -- skill files, prompt configurations, memory schemas, workflow graphs -- and leave the agent harness untouched. Since routing, hook ordering, state invariants, and dispatch live in code rather than in any text artifact, an entire class of structural failure is physically unreachable from the text layer. We argue that source-level adaptation is a fundamentally more general medium: it is Turing-complete, a strict superset of every text-mutable scope, takes effect deterministically rather than through base-model compliance, and does not erode under long-context drift. We present MOSS, a system that performs self-rewriting at the source level on production agentic substrates. Each evolution is anchored to an automatically curated batch of production-failure evidence and proceeds through a deterministic multi-stage pipeline; code modification is delegated to a pluggable external coding-agent CLI while MOSS retains stage ordering and verdicts. Candidates are verified by replaying the batch against the candidate image in ephemeral trial workers, then promoted via user-consent-gated, in-place container swap with health-probe-gated rollback. On OpenClaw, MOSS lifts a four-task mean grader score from 0.25 to 0.61 in a single cycle without human intervention.
Received — 13 April 2026 ⏭

Evaluating AI in leukocyte classification: performance of the AI system against 15 morphology experts

✇npj Digital Medicine
By: Wei Xu · Haoqin Jiang · Jingxian Zhang · Kun Chen · Yang Fei · Ping Guo · Yongjian He · Yi Ye · Linlin Qu · Mingkang Yang · Lizhi Yan · Di Wang · Huan Qi · Shihong Zhang · Chi Zhang · Jianbiao Wang · Ming Guan
11 April 2026 at 08:00

npj Digital Medicine, Published online: 11 April 2026; doi:10.1038/s41746-026-02601-w

Evaluating AI in leukocyte classification: performance of the AI system against 15 morphology experts
Received — 8 April 2026 ⏭
  • ✇cs.AI, q-bio.NC updates on arXiv.org
  • Symbolic-Vector Attention Fusion for Collective Intelligence Hongwei Xu
    arXiv:2604.03955v1 Announce Type: cross Abstract: When autonomous agents observe different domains of a shared environment, each signal they exchange mixes relevant and irrelevant dimensions. No existing mechanism lets the receiver evaluate which dimensions to absorb. We introduce Symbolic-Vector Attention Fusion (SVAF), the content-evaluation half of a two-level coupling engine for collective intelligence. SVAF decomposes each inter-agent signal into 7 typed semantic fields, evaluates each thr
     
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Symbolic-Vector Attention Fusion for Collective Intelligence

✇cs.AI, q-bio.NC updates on arXiv.org
By: Hongwei Xu
7 April 2026 at 12:00
arXiv:2604.03955v1 Announce Type: cross Abstract: When autonomous agents observe different domains of a shared environment, each signal they exchange mixes relevant and irrelevant dimensions. No existing mechanism lets the receiver evaluate which dimensions to absorb. We introduce Symbolic-Vector Attention Fusion (SVAF), the content-evaluation half of a two-level coupling engine for collective intelligence. SVAF decomposes each inter-agent signal into 7 typed semantic fields, evaluates each through a learned fusion gate, and produces a remix -- new knowledge from the intersection of two domains. A band-pass model yields four outcomes (redundant, aligned, guarded, rejected), solving both selectivity and redundancy. The fusion gate independently discovers a cross-domain relevance hierarchy: mood emerges as the highest-weight field by epoch 1, before accuracy plateaus -- consistent with independent mechanistic evidence that LLM emotion representations are structurally embedded along valence-arousal axes. SVAF forms Layer 4 of the Mesh Memory Protocol (MMP); the other half of the coupling engine is a per-agent Closed-form Continuous-time (CfC) neural network at Layer 6, whose learned per-neuron time constants (tau) create the temporal dynamics from which collective intelligence emerges: fast neurons synchronise affect across agents in seconds, while slow neurons preserve domain expertise indefinitely. SVAF determines what enters each agent's cognitive state; CfC determines how that state evolves. Trained on 237K samples from 273 narrative scenarios, SVAF achieves 78.7% three-class accuracy. We verify the complete mesh cognition loop -- from per-field evaluation through remix, CfC state evolution, tau-modulated peer blending, and autonomous action -- in a live deployment with 7 nodes across macOS, iOS, and web.

ShadowNPU: System and Algorithm Co-design for NPU-Centric On-Device LLM Inference

✇cs.AI, q-bio.NC updates on arXiv.org
By: Wangsong Yin · Daliang Xu · Mengwei Xu · Gang Huang · Xuanzhe Liu
7 April 2026 at 12:00
arXiv:2508.16703v3 Announce Type: replace-cross Abstract: On-device running Large Language Models (LLMs) is nowadays a critical enabler towards preserving user privacy. We observe that the attention operator falls back from the special-purpose NPU to the general-purpose CPU/GPU because of quantization sensitivity in state-of-the-art frameworks. This fallback results in a degraded user experience and increased complexity in system scheduling. To this end, this paper presents shadowAttn, a system-algorithm codesigned sparse attention module with minimal reliance on CPU/GPU by only sparsely calculating the attention on a tiny portion of tokens. The key idea is to hide the overhead of estimating the important tokens with a NPU-based pilot compute. Further, shadowAttn proposes insightful techniques such as NPU compute graph bucketing, head-wise NPU-CPU/GPU pipeline and per-head fine-grained sparsity ratio to achieve high accuracy and efficiency. shadowAttn delivers the best performance with highly limited CPU/GPU resource; it requires much less CPU/GPU resource to deliver on-par performance of SoTA frameworks.
Received — 2 April 2026 ⏭

Semantic Voting: A Self-Evaluation-Free Approach for Efficient LLM Self-Improvement on Unverifiable Open-ended Tasks

✇cs.AI, q-bio.NC updates on arXiv.org
By: Chunyang Jiang · Yonggang Zhang · Yiyang Cai · Chi-Min Chan · Yulong Liu · Mingming Chen · Wei Xue · Yike Guo
1 April 2026 at 12:00
arXiv:2509.23067v2 Announce Type: replace-cross Abstract: The rising cost of acquiring supervised data has driven significant interest in self-improvement for large language models (LLMs). Straightforward unsupervised signals like majority voting have proven effective in generating pseudo-labels for verifiable tasks, while their applicability to unverifiable tasks (e.g., translation) is limited by the open-ended character of responses. As a result, self-evaluation mechanisms (e.g., self-judging and entropy minimization) are predominantly used to derive pseudo-labels. However, self-evaluation relying on LLMs typically incurs high computational overhead and introduces overconfidence issues due to intrinsic biases. To address these challenges, we propose a novel self-evaluation-free approach for unverifiable tasks, designed for lightweight yet effective self-improvement. Inspired by majority voting commonly employed in verifiable tasks, we propose semantic voting as a novel mechanism that relaxes the principle of hard matching (i.e., exact matching) toward soft matching (i.e., semantic similarity). Soft matching is achieved by leveraging a lightweight sentence embedding model to quantify semantic similarity, thereby mitigating excessive computational burden and intrinsic bias-associated limitations of self-evaluation. Comprehensive experiments demonstrate that our method achieves substantial gains in computational efficiency and overall better performance than self-evaluation methods across diverse model architectures and tasks.

Correction: The multifunctional RNA helicase DDX39A drives glioblastoma progression by modulating WISP1 alternative splicing that induces an immunosuppressive macrophage polarization

✇Oncogene - Issue - nature.com science feeds
By: Yan Zhang · Zhiwei Xue · Naibin Zhang · Yuehua Zhu · YanZhao Wu · Meilin Lv · Zhihan Zhang · Feiyu Mu · Wenchen Xing · Ziyi Tang · Chunjie Wang · Zhiyi Xue · Wenjing Zhou · Xiaofei Liu · Xingang Li · Rolf Bjerkvig · Bin Huang · Mingzhi Han · Jian Wang · Donghai Wang
1 April 2026 at 08:00

Oncogene, Published online: 01 April 2026; doi:10.1038/s41388-026-03756-2

Correction: The multifunctional RNA helicase DDX39A drives glioblastoma progression by modulating WISP1 alternative splicing that induces an immunosuppressive macrophage polarization

Nanoscale transfer-printed full-colour ultrahigh-resolution quantum dot LEDs

✇Nature - Issue - nature.com science feeds
By: Lihua Lin · Jie Wang · Hailong Hu · Haolin Luo · Yanbin Liu · Xingjie Yang · Jingnan Su · De’er Li · Zhongwei Xu · Chengyu Luo · Yongshen Yu · Tailiang Guo · Fushan Li
1 April 2026 at 08:00

Nature, Published online: 01 April 2026; doi:10.1038/s41586-026-10333-w

A dual-action force dynamics strategy using a hard silicon template as a nanoimprinting stamp combined with inverted transfer printing is described for the manufacture of high-performance full-colour ultrahigh-resolution quantum dot light-emitting diodes (LEDs) for active-matrix displays, while revealing electric-field reconstruction in nanoscale arrays and introducing dielectric matching to mitigate field concentration and performance degradation.
Received — 26 March 2026 ⏭

Comprehensive multi omics profiling and Mendelian randomization assessment of lipid metabolites in lung cancer prognosis

✇(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)
By: Zhiwei Xu · Jingjing Li
23 March 2026 at 18:00

Discov Oncol. 2026 Mar 23. doi: 10.1007/s12672-026-04893-6. Online ahead of print.

ABSTRACT

BACKGROUND: Lung cancer remains the leading cause of cancer-related mortality worldwide. This study aimed to develop prognostic prediction models for lung squamous cell carcinoma (LUSC) through multi-omics integration using Mendelian randomization analysis.This study addresses a critical gap in lung cancer research through two complementary approaches in major lung cancer subtypes: (1) hypothesis-generating multi-omics analysis in LUSC to identify prognostic biomarkers and characterize the metabolic-immune landscape. This integrated framework provides both predictive tools for personalized medicine and mechanistic insights into metabolic causality.

METHODS: Multi-omics analysis was performed using TCGA data, including RNA-seq, DNA methylation, and whole-exome sequencing. Machine learning models incorporating 15 algorithms were developed and externally validated in two independent GEO cohorts. Mendelian randomization analysis assessed causal relationships between 32 lipid metabolites and SCLC risk. RT-qPCR experiments validated key prognostic genes in lung squamous cell carcinoma (LUSC) cell lines.

RESULTS: The optimal machine learning model (StepCox [forward] + Random Survival Forest) demonstrated superior performance with C-index of 0.73 in internal testing and 0.71 and 0.68 in external validation cohorts. High CD8 + T cell and M1 macrophage infiltration was associated with favorable prognosis. Most lipid metabolites showed no significant causal associations with SCLC risk after multiple testing correction, though two phosphatidylcholine metabolites demonstrated potential protective effects. RT-qPCR validation confirmed significant upregulation of all four key genes in LUSC cell lines.

CONCLUSIONS: This study successfully developed robust machine learning-based prognostic models for LUSC with clinical utility for risk stratification and provided evidence that lipid alterations in lung cancer are likely downstream consequences rather than causal drivers of tumorigenesis.

PMID:41870745 | DOI:10.1007/s12672-026-04893-6

Comprehensive multi omics profiling and Mendelian randomization assessment of lipid metabolites in lung cancer prognosis

✇Omics In Lung
By: Zhiwei Xu · Jingjing Li
23 March 2026 at 18:00

Discov Oncol. 2026 Mar 23. doi: 10.1007/s12672-026-04893-6. Online ahead of print.

ABSTRACT

BACKGROUND: Lung cancer remains the leading cause of cancer-related mortality worldwide. This study aimed to develop prognostic prediction models for lung squamous cell carcinoma (LUSC) through multi-omics integration using Mendelian randomization analysis.This study addresses a critical gap in lung cancer research through two complementary approaches in major lung cancer subtypes: (1) hypothesis-generating multi-omics analysis in LUSC to identify prognostic biomarkers and characterize the metabolic-immune landscape. This integrated framework provides both predictive tools for personalized medicine and mechanistic insights into metabolic causality.

METHODS: Multi-omics analysis was performed using TCGA data, including RNA-seq, DNA methylation, and whole-exome sequencing. Machine learning models incorporating 15 algorithms were developed and externally validated in two independent GEO cohorts. Mendelian randomization analysis assessed causal relationships between 32 lipid metabolites and SCLC risk. RT-qPCR experiments validated key prognostic genes in lung squamous cell carcinoma (LUSC) cell lines.

RESULTS: The optimal machine learning model (StepCox [forward] + Random Survival Forest) demonstrated superior performance with C-index of 0.73 in internal testing and 0.71 and 0.68 in external validation cohorts. High CD8 + T cell and M1 macrophage infiltration was associated with favorable prognosis. Most lipid metabolites showed no significant causal associations with SCLC risk after multiple testing correction, though two phosphatidylcholine metabolites demonstrated potential protective effects. RT-qPCR validation confirmed significant upregulation of all four key genes in LUSC cell lines.

CONCLUSIONS: This study successfully developed robust machine learning-based prognostic models for LUSC with clinical utility for risk stratification and provided evidence that lipid alterations in lung cancer are likely downstream consequences rather than causal drivers of tumorigenesis.

PMID:41870745 | DOI:10.1007/s12672-026-04893-6

Single-cell multiomics uncovers an endothelial mechanosensitive PIEZO1-IL-33 axis driving pulmonary fibrosis

✇Omics In Lung
By: Lanlan Zhang · Xuezhen Gui · Ruijie Hou · Liping Jia · Shu Xia · Xin Zhang · Yingyun Fu · Qian-Fang Meng · Qun Luo · Xing Shi · Bingxin Guo · Ruifang Liang · Ludan Yue · Xue Chen · Haizhao Xu · Pengbo Wang · Xia Tong · Lujie Liu · Lingwei Wang · Baicun Li · Zi Chen · Linfu Zhou · Linshu Zhang · Rongchang Chen · Changbin Sun · Wei Xu · Lang Rao · Haibo Zhou · Bi-Sen Ding · Shanze Chen
21 March 2026 at 18:00

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

Received — 11 March 2026 ⏭

DC-W2S: Dual-Consensus Weak-to-Strong Training for Reliable Process Reward Modeling in Biological Reasoning

✇cs.AI, q-bio.NC updates on arXiv.org
By: Chi-Min Chan · Ehsan Hajiramezanali · Xiner Li · Edward De Brouwer · Carl Edwards · Wei Xue · Sirui Han · Yike Guo · Gabriele Scalia
10 March 2026 at 12:00
arXiv:2603.08095v1 Announce Type: cross Abstract: In scientific reasoning tasks, the veracity of the reasoning process is as critical as the final outcome. While Process Reward Models (PRMs) offer a solution to the coarse-grained supervision problems inherent in Outcome Reward Models (ORMs), their deployment is hindered by the prohibitive cost of obtaining expert-verified step-wise labels. This paper addresses the challenge of training reliable PRMs using abundant but noisy "weak" supervision. We argue that existing Weak-to-Strong Generalization (W2SG) theories lack prescriptive guidelines for selecting high-quality training signals from noisy data. To bridge this gap, we introduce the Dual-Consensus Weak-to-Strong (DC-W2S) framework. By intersecting Self-Consensus (SC) metrics among weak supervisors with Neighborhood-Consensus (NC) metrics in the embedding space, we stratify supervision signals into distinct reliability regimes. We then employ a curriculum of instance-level balanced sampling and label-level reliability-aware masking to guide the training process. We demonstrate that DC-W2S enables the training of robust PRMs for complex reasoning without exhaustive expert annotation, proving that strategic data curation is more effective than indiscriminate training on large-scale noisy datasets.
Received — 5 March 2026 ⏭

Phys4D: Fine-Grained Physics-Consistent 4D Modeling from Video Diffusion

✇cs.AI, q-bio.NC updates on arXiv.org
By: Haoran Lu · Shang Wu · Jianshu Zhang · Maojiang Su · Guo Ye · Chenwei Xu · Lie Lu · Pranav Maneriker · Fan Du · Manling Li · Zhaoran Wang · Han Liu
5 March 2026 at 13:00
arXiv:2603.03485v1 Announce Type: cross Abstract: Recent video diffusion models have achieved impressive capabilities as large-scale generative world models. However, these models often struggle with fine-grained physical consistency, exhibiting physically implausible dynamics over time. In this work, we present \textbf{Phys4D}, a pipeline for learning physics-consistent 4D world representations from video diffusion models. Phys4D adopts \textbf{a three-stage training paradigm} that progressively lifts appearance-driven video diffusion models into physics-consistent 4D world representations. We first bootstrap robust geometry and motion representations through large-scale pseudo-supervised pretraining, establishing a foundation for 4D scene modeling. We then perform physics-grounded supervised fine-tuning using simulation-generated data, enforcing temporally consistent 4D dynamics. Finally, we apply simulation-grounded reinforcement learning to correct residual physical violations that are difficult to capture through explicit supervision. To evaluate fine-grained physical consistency beyond appearance-based metrics, we introduce a set of \textbf{4D world consistency evaluation} that probe geometric coherence, motion stability, and long-horizon physical plausibility. Experimental results demonstrate that Phys4D substantially improves fine-grained spatiotemporal and physical consistency compared to appearance-driven baselines, while maintaining strong generative performance. Our project page is available at https://sensational-brioche-7657e7.netlify.app/
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