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Distinct multi-omics signatures of clinical subgroups of type 2 diabetes define heterogeneous responses to an insulin sensitizer

✇(Multiomics OR Omics) AND (Pancreatic)
By: Zehui Cao · Ruolan Zhang · Haonan Chen · Naixin Zhang · Qiaochu Chen · Yuanbang Mai · Xintong Yao · Qingwang Chen · Jiaqi Li · Desi Pan · Linong Ji · Weiping Jia · Xianping Lu · Antonio Vidal-Puig · Leming Shi · Yan Zheng · Yuanting Zheng

Nat Commun. 2026 Aug 29;17(1):10311. doi: 10.1038/s41467-026-77187-8.

ABSTRACT

Type 2 diabetes (T2D) subgroups defined by clinical variables differ in disease progression and treatment response. To uncover potential molecular drivers of this heterogeneity, we performed a multi-omics analysis of 826 drug-naïve T2D patients from two phase 3 trials of the insulin sensitizer chiglitazar. Here we show that severe insulin-resistant diabetes (SIRD) is characterized by distinct miRNA profiles (e.g., miR-122-5p) correlated with liver injury, and metabolic shifts in amino acids and primary bile acids. Mild obesity-related diabetes (MOD) showed the lowest level of phenylacetylglutamine, a metabolite known to promote cardiovascular disease. Severe insulin-deficient diabetes (SIDD) exhibited high pancreas-specific miR-7-5p, while mild age-related diabetes (MARD) presented the mildest abnormalities. Finally, integrating these multi-omics signatures into machine learning models enhanced prediction of insulin sensitizer efficacy over clinical data alone. Our findings define the distinct molecular signatures of T2D subgroups, facilitating the prediction of heterogeneous treatment responses and supporting personalized clinical management.

PMID:42805981 | PMC:PMC13620142 | DOI:10.1038/s41467-026-77187-8

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Inhalable carrier-free self-assembled leonurine-ursolic acid nanoaggregates ameliorate acute lung injury by suppressing TLR4/MyD88-NET axis

✇(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)
By: Zhen-Zhen Wang · Lihua Cao · Zhenzhu Zhao · Mengke Zhao · Yanyan Lu · Yanhui Zhu · Weijie Xie · Ping Li · Siqi Liu · Xuejiao Li · Kang Yang · Xiaobo Sun

Mater Today Bio. 2026 Aug 18;40:103583. doi: 10.1016/j.mtbio.2026.103583. eCollection 2026 Oct.

ABSTRACT

TLR4 activation and the cascade of neutrophil extracellular trap (NET) formation exacerbate excessive inflammation and organ damage in the pathogenesis of acute lung injury (ALI), yet effective pharmacological interventions remain unavailable. Nanoaggregates derived from natural products offer promising avenue by leveraging synergistic anti-inflammatory effects. In this study, we surprisingly discovered that leonurine and ursolic acid spontaneously self-assemble into nanoparticles (LUNP) through non-covalent interactions, achieving a drug loading capacity of 100%. The LUNP platform exhibits superior biophysical properties, including enhanced mucus penetration, pH-responsive drug release, improved cellular uptake, and prolonged retention within inflamed lung tissue. Mechanistically, LUNP ameliorates ALI by dampening TLR4/MyD88/NF-κB-driven inflammatory activation, thereby remodeling the microenvironment to limit NOX4-PAD4-mediated NET formation. Notably, inhalational LUNP exhibits outstanding biosafety with minimal off-target distribution. Overall, this work introduces a synergistic self-assembled nanoplatform for precise pulmonary intervention in ALI, showcasing its ability to safely and effectively orchestrate the coordinated modulation of multiple pathological pathways. In summary, by inhibiting both TLR4 activation and NET formation, the synergistic LUNP platform offers an efficient, safe, and easily accessible therapeutic strategy for ALI, providing a promising solution for clinical translation.

PMID:42750707 | PMC:PMC13577835 | DOI:10.1016/j.mtbio.2026.103583

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Integrated multi-omic and functional profiling reveals a ZDHHC16-associated palmitoylation-proteostasis state in hepatocellular carcinoma

✇(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)
By: Lihua Zhang · Xiaolei Zhang · Caiqi Liu · Xiaofei Xin · Xinchi Luan · Jialin Song · Wensheng Qiu

Discov Oncol. 2026 Aug 1;17(1):1333. doi: 10.1007/s12672-026-05700-y.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) remains biologically heterogeneous, and molecular states linking tumor-cell intrinsic programs with post-translational regulation, immune contexture and drug-specific vulnerability remain incompletely defined. ZDHHC16 is a DHHC-family palmitoyl acyltransferase, but its clinical relevance and biological context in HCC remain unclear.

METHODS: Public transcriptomic, clinical, single-cell, proteomic, palmitoylome, immune-related and pharmacogenomic datasets were integrated to characterize ZDHHC16 in HCC. ZDHHC16 expression, exploratory survival separation, cellular localization, pathway activity, palmitoylation-associated candidates, immune microenvironment features and predicted drug response were evaluated. siRNA-mediated knockdown, MTT assays and colony formation assays were performed in HepG2 and Huh7 cells.

RESULTS: ZDHHC16 was upregulated in HCC. In exploratory Kaplan-Meier analyses restricted to primary tumors and using endpoint-specific data-derived cutoffs, the curves showed expression-group separation for overall survival, disease-free interval and progression-free interval (unadjusted log-rank P = 0.019, 0.019 and 0.011, respectively). These analyses were not adjusted for clinical covariates and do not establish independent prognostic value. Single-cell analysis localized ZDHHC16 mainly to malignant epithelial-related compartments. ZDHHC16 knockdown reduced MTT-based cell viability and clonogenic growth in HepG2 and Huh7 cells. ZDHHC16-high tumors were enriched for cell-cycle progression, DNA replication, DNA repair, RNA processing, ubiquitin-mediated proteolysis and proteasome-related programs. After deduplication at the gene-symbol level, palmitoylome-guided integration nominated 28 transcriptionally correlated palmitoylation-associated candidates, including EZH2, PI4K2A and ZDHHC6; the screen did not establish direct ZDHHC16 substrates. ZDHHC16-high tumors also showed immune-remodeled features and drug-specific predicted IC50 patterns.

CONCLUSIONS: Integrated data support ZDHHC16 as a marker of a malignant epithelial, growth-associated HCC state accompanied by palmitoylation- and proteostasis-related programs, altered immune contexture and drug-specific predicted IC50 patterns. Direct ZDHHC16-dependent palmitoylation, independent prognostic value and therapeutic utility require biochemical and prospective clinical validation.

PMID:42742876 | PMC:PMC13578202 | DOI:10.1007/s12672-026-05700-y

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BlueLM-GUI Technical Report: A Real-Device-Centric Flywheel for Self-Improving Mobile GUI Agents

✇cs.AI, q-bio.NC updates on arXiv.org
By: Tong Ye · Kunyang Han · Guozhi Wang · Longqiang Luo · Zhifeng Ding · Yongxiang Zhang · Xiaolei Shen · Yuxuan Zhang · Zhuping Zhang · Tao Xu · Yue Pan · Yucheng Zhao · Yupei Hu · Yuanjiang Ouyang · Danfeng Shen · Runqi Lin · Hongda Cai · Zhaoxiong Wang · Mengjia Yan · Yingjie Zhong · Chen Zhou · Zeyu Zhang · Xuwen Zhu · Penggang Shi · Mingcheng Luo · Ziyang Wu · Min Jin · Mingfu Shen · Zairong Xu · Fan Zhang · Hao Wang · Liang Liu · Zhulin Xie · Lijun Yao · Xiao Liang · Liangmin Wen · Liqiang Feng · Feilong Wu · Min Hu · Min Chen · Guanjing Xiong · Xiaohu Ruan · Xiaoxin Chen
arXiv:2609.12394v1 Announce Type: new Abstract: Mobile GUI agents are shifting from multi-module frameworks to native models trained end-to-end, yet industrial deployment faces three persistent gaps. Sandbox training produces a distribution mismatch with production environments; expensive real-device failures remain underutilized; and fixed benchmarks saturate, losing the power to guide iteration. We present BlueLM-GUI, a 35B-A3B mobile GUI agent built as a real-device-centric flywheel that closes these gaps through three principles. Every Sample Matters: a dual-track pipeline with Heterogeneous Triple-System Consensus evaluation and an Error Correction \& Derivation Module salvages every trajectory into usable supervision. Every Rollout Is Real: a three-stage recipe---continual pre-training, supervised fine-tuning, and agentic reinforcement learning on hundreds of real phones---grounds every rollout in real production environments, so the capability the model learns transfers directly to deployment. Every Query Evolves: a quota-driven benchmark methodology with three orthogonal axes enables precise attribution and allows the benchmark to be systematically upgraded as the model improves. BlueLM-GUI achieves 87.4 on MobileGUI-VBench, surpassing the best closed-source model by 5.1 points, and 84.9 on AndroidWorld, the best result among open-source models and competitive with closed-source models. These results demonstrate that grounding model training and iterative improvement in both real devices and the three Every principles yields strong, robust, and transferable mobile GUI capability.
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SimSkill: A Self-Evolving LLM Agent for Skill and Knowledge Accumulation in Traffic Simulation

✇cs.AI, q-bio.NC updates on arXiv.org
By: Qi Liu · Qinzheng Wang · Can Li · Yiming Bie · Wanjing Ma
arXiv:2609.03753v3 Announce Type: replace Abstract: Cumulative culture enables humans to preserve, reuse, and extend knowledge and skills across experiences and generations. Inspired by this principle, we introduce \textit{SimSkill}, a self-evolving agent built around the Simulation of Urban MObility (SUMO) traffic simulator. SimSkill continually identifies capability gaps, generates and solves environment-grounded tasks, verifies solutions through an action--critic loop, and consolidates experience into episodic, procedural, and semantic memory. Through autonomous exploration, it builds a library of reusable skills and knowledge spanning major stages of the traffic-simulation workflow. We evaluate SimSkill on two held-out benchmarks across three backbone LLMs, with each result independently verified. It improves verified success by up to 25 percentage points, and ablations show complementary contributions from procedural and semantic memory. Its benefits remain backbone- and budget-dependent, as memory does not improve every model or uniformly reduce inference cost. More broadly, SimSkill illustrates a natural-language-centered design paradigm for LLM-based agent systems. Its high-level control logic, operating principles, and accumulated knowledge are expressed in natural language, while an LLM integrates them with executable tools and code to realize precise and reproducible execution. All code and experimental data are publicly available at https://github.com/qiliuchn/SimSkill-V1.
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Inhaled nanosilica orchestrates a pulmonary macrophage-NK cell axis for memory-like NK programming toward synergistic cancer immunotherapy

✇Molecular Therapy
By: Feng Yuan · Qi Li · Yingnan Liu · Fangfang Liu · Wenhe Luo · Qingle Song · Yanqiao Zeng · Jiacheng Bi · Guofang Zhang · Yang Li
Yuan and colleagues demonstrate that inhaled biodegradable nanosilica activates an alveolar macrophage–NK axis, triggering an IL-12/15/18 triad that programs memory-like NK cells. This non-fibrotic, cell-free strategy suppresses melanoma growth, prevents postsurgical recurrence, and synergizes with anti-PD-1, establishing a robust framework for in vivo NK cell immunotherapy.
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Structural Process Supervision for Latent Chain-of-Thought Reasoning

✇cs.AI, q-bio.NC updates on arXiv.org
By: Yiqi Li · Xu Chen · Chen Ju · Jiangchao Yao · Zhaoyang Li · Jinsong Lan · Xiaoyong Zhu · Bo Zheng · Yu Wang
arXiv:2609.09928v1 Announce Type: new Abstract: Latent reasoning approaches enhance token-level efficiency and robustness by replacing verbose, explicit chain-of-thought (CoT) tokens with compact continuous-space embeddings. However, existing methods lack direct process supervision over these latent embeddings, which often leads to representation collapse and uneven information distribution. To address this, we propose Prototype-Mediated Process Supervision (PMPS), which introduces learnable reasoning prototypes as semantic anchors to provide structural process-level supervision for latent reasoning. PMPS projects latent embeddings and explicit CoT embeddings into a shared prototype space, achieving many-to-many soft alignment between unequal-length representations through prototype assignment. Meanwhile, we introduce a Progressive Sequential Alignment (PSA) module to further guide training: positional priors initially encourage sequential alignment structure, then gradually relax to permit adaptive matching. Experimental results show that PMPS compresses output token length to under 50% of explicit CoT on GSM8K-Aug. Compared to leading baseline SIM-CoT, our method achieves average accuracy gains of 2.08% across different model families. On GPT-2, PMPS even surpasses CoT-SFT. On larger models and a more challenging task, PMPS consistently attains the highest accuracy among all latent reasoning methods with comparable output length.
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Show-Harness: Just a VLM Agent Can Play Robots

✇cs.AI, q-bio.NC updates on arXiv.org
By: Yanzhe Chen · Zechen Bai · Zhijun Cao · Wenzheng Zeng · Kevin Qinghong Lin · Yiqi Lin · Guoqiang Liang · Kevin Yuchen Ma · Qiming Huang · Mike Zheng Shou
arXiv:2609.10522v1 Announce Type: cross Abstract: Foundation vision-language models (VLMs) exhibit broad intelligence about the world, yet translating this intelligence into robot control remains challenging. We present Show-Harness, an Embodied Harness that enables VLMs to "play" robots through a compact semantic interface linking intent to action. Show-Harness exposes discrete semantic action units that VLMs can naturally reason over, while embodiment-specific interpreters deterministically ground them into local robot actions, keeping the VLM directly responsible for fine-grained physical decisions. Through the same interface, Show-Harness demonstrates the feasibility of (1) directly unlocking closed-source frontier VLMs for zero-shot robot control, and (2) adapting small-scale open-source VLMs for low-cost deployment with just a few GPU-hours of fine-tuning. We further develop GUMI (GUI Manipulation Interface), which extends the same semantic action space to GUI-based demonstration collection, allowing humans and agents to "play" robots across embodiments without specialized teleoperation hardware. Extensive experiments show that Show-Harness-equipped VLM agents generalize robustly across tasks, embodiments, and environments, outperforming representative agentic and VLA paradigms. These results suggest that the right interface can unlock substantial embodied capability from foundation VLMs, without requiring additional model capacity or costly embodiment-specific pretraining.
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Geo-Expert: Towards Expert-Level Geological Reasoning via Parameter-Efficient Fine-Tuning

✇cs.AI, q-bio.NC updates on arXiv.org
By: Chenyou Guo · Zongqi Liu · Yizhou Zhang · Zhaorui Jiang · Ze Liu
arXiv:2605.24844v1 Announce Type: new Abstract: While general-purpose Large Language Models (LLMs) applied to Geology often hallucinate when reasoning about subsurface structures and deep-time evolution, current AI in Earth sciences predominantly targets surface remote sensing and GIS. To bridge this gap, we introduce Geo-Expert, a family of parameter-efficient geological LLMs fine-tuned on a custom-curated, high-quality instruction dataset processed using our custom instruction synthesis pipeline. We investigate the impact of model scaling and architecture by fine-tuning three base models: Qwen3-8B, Qwen3-32B, and Gemma-3-27B, with Low-Rank Adaptation (LoRA) method. Our extensive evaluation on a novel domain-specific benchmark, Geo-Eval, reveals that a domain-aligned 8B model can outperform open-weight 70B generalists and proprietary GPT-4o on specialized geological reasoning, while a 32B variant approaches frontier reasoning models. The optimized 8B model further offers a competitive cost-performance ratio for deployment. This work provides a reproducible recipe for democratizing scientific LLMs and establishes a baseline for geological artificial intelligence.
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Distributionally Robust Transfer Learning with Structurally Missing Covariates, with Application to Cross-National Cardiac Arrest Prediction

✇cs.AI, q-bio.NC updates on arXiv.org
By: Siqi Li · Chuan Hong · Ziye Tian · Benjamin Sieu-Hon Leong · Koshi Nakagawa · Hideharu Tanaka · Sang Do Shin · Khuong Quoc Dai · Do Ngoc Son · Marcus Eng Hock Ong · Nan Liu · Molei Liu
arXiv:2605.24212v1 Announce Type: cross Abstract: Deploying clinical prediction models across healthcare systems often fails when key training covariates are unavailable at deployment and labeled outcomes are limited in the target domain. For example, high-performing models for out-of-hospital cardiac arrest (OHCA) rely on detailed prehospital measurements routinely collected in high-resource settings but unavailable in many international registries. Existing methods either discard missing covariates, sacrificing predictive information, or rely on untestable assumptions about their target distribution. We propose DRUM (\underline{D}istributionally \underline{R}obust \underline{U}nsupervised transfer learning with structurally \underline{M}issing covariates), a framework that transfers prediction models to target populations where certain covariates are structurally absent and outcome labels are unavailable. DRUM partitions covariates into shared components ($X$), observed across all settings, and missing components ($A$), observed only in the source. Rather than imputing missing covariates, DRUM optimizes worst-case predictive performance over the unknown target distribution of $A \mid X$ using a neural network generator, with a robustness parameter controlling allowable deviation from the source conditional. We further develop a bias correction procedure that reduces sensitivity to nuisance estimation error. Simulations show substantial improvements in both mean and worst-case prediction error under distribution shift. Applied to cross-national OHCA prediction, transferring models from a US registry to multiple Asian registries where prehospital variables are unrecorded, DRUM yields better-calibrated predictions and improved clinical classification performance across sites.
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Cross-Domain Energy-Guided Diffusion Generation for Off-Dynamics Reinforcement Learning

✇cs.AI, q-bio.NC updates on arXiv.org
By: Yu Yang · Yihong Guo · Anqi Liu · Pan Xu
arXiv:2605.24810v1 Announce Type: cross Abstract: Off-dynamics offline reinforcement learning seeks to learn a target-domain policy from a large source dataset and a limited target dataset under mismatched transition dynamics. Existing approaches such as reward augmentation and data filtering are constrained to the source dataset and cannot synthesize new target behavior to improve coverage beyond the collected source trajectories. While recent model-based methods attempt to address this by learning target-aware dynamics, the generated experience is constructed only at the transition level, which leads to accumulated errors over long horizons. These limitations necessitate a shift toward trajectory-level generation for off-dynamics offline RL. We propose CEDGE, a Cross-domain Energy-guided Diffusion GEneration framework. CEDGE trains a trajectory diffusion model on source-domain trajectories and adapts the generated samples to the target domain through energy guidance. This guidance is derived by minimizing the distribution mismatch between the source and desired target-domain trajectories and is decomposed into return, domain, and behavior energy components. The resulting energy-guided trajectories are useful both for direct planning and as synthetic data for policy learning. Since target adaptation is achieved via energy guidance rather than retraining the diffusion model, CEDGE can be efficiently adapted to new target dynamics compared to previous methods. Experiments on the ODRL benchmark demonstrate that trajectory-level energy-guided generation improves diffusion planning under dynamics shifts and produces synthetic data that improves downstream target policy learning.
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DRScaffold: Boosting Dense-Scene Reasoning in Lightweight Vision Language Models

✇cs.AI, q-bio.NC updates on arXiv.org
By: Xinrui Shi · Kai Liu · Ziqing Zhang · Jianze Li · Anqi Li · Yulun Zhang
arXiv:2605.26038v1 Announce Type: cross Abstract: Lightweight vision-language models perform competitively on standard benchmarks yet fail systematically in dense-scene reasoning, where multiple objects, attributes, and relations must be jointly grounded and resolved through multi-step inference. Such capability is critical for real-world applications where models must reliably interpret cluttered environments. Yet existing training signals provide no explicit grounding between reasoning steps and the underlying visual entities and relations, leaving lightweight models free to generate fluent but visually unanchored reasoning chains. To address this gap, we first introduce DRBench, a benchmark of 14,573 questions across 2,943 images, organized into five task categories spanning three progressive reasoning layers. Building on DRBench, we propose DRScaffold, a supervised fine-tuning framework that decomposes the supervision target into four causally ordered stages, enforcing grounded reasoning without architectural modification. Experiments on three lightweight VLMs demonstrate substantial gains on DRBench while preserving or improving performance on general-purpose benchmarks. Notably, Qwen2.5-VL-3B trained with DRScaffold surpasses the frozen Qwen2.5-VL-32B on DRBench, demonstrating that structured supervision can substitute for a significant portion of model scale in dense-scene reasoning. Our code and models are available at https://github.com/irene-shi/DRScaffold .
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AutoResearchClaw: Self-Reinforcing Autonomous Research with Human-AI Collaboration

✇cs.AI, q-bio.NC updates on arXiv.org
By: Jiaqi Liu · Shi Qiu · Mairui Li · Bingzhou Li · Haonian Ji · Siwei Han · Xinyu Ye · Peng Xia · Zihan Dong · Meng Chen · Congyu Zhang · Letian Zhang · Guiming Chen · Haoqin Tu · Xinyu Yang · Lu Feng · Xujiang Zhao · Haifeng Chen · Jiawei Zhou · Xiao Wang · Weitong Zhang · Hongtu Zhu · Yun Li · Jieru Mei · Hongliang Fei · Jiaheng Zhang · Linjie Li · Linjun Zhang · Yuyin Zhou · Sheng Wang · Caiming Xiong · James Zou · Zeyu Zheng · Cihang Xie · Mingyu Ding · Huaxiu Yao
arXiv:2605.20025v2 Announce Type: replace Abstract: Automating scientific discovery requires more than generating papers from ideas. Real research is iterative: hypotheses are challenged from multiple perspectives, experiments fail and inform the next attempt, and lessons accumulate across cycles. Existing autonomous research systems often model this process as a linear pipeline: they rely on single-agent reasoning, stop when execution fails, and do not carry experience across runs. We present AutoResearchClaw, a multi-agent autonomous research pipeline built on five mechanisms: structured multi-agent debate for hypothesis generation and result analysis, a self-healing executor with a \textsc{Pivot}/\textsc{Refine} decision loop that transforms failures into information, verifiable result reporting that prevents fabricated numbers and hallucinated citations, human-in-the-loop collaboration with seven intervention modes spanning full autonomy to step-by-step oversight, and cross-run evolution that converts past mistakes into future safeguards. On ARC-Bench, a 25-topic experiment-stage benchmark, AutoResearchClaw outperforms AI Scientist v2 by 54.7%. A human-in-the-loop ablation across seven intervention modes reveals that precise, targeted collaboration at high-leverage decision points consistently outperforms both full autonomy and exhaustive step-by-step oversight. We position AutoResearchClaw as a research amplifier that augments rather than replaces human scientific judgment. Code is available at https://github.com/aiming-lab/AutoResearchClaw.
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SoK: A Comprehensive Security Analysis of Jailbreak Resilience in GPT and DeepSeek Models

✇cs.AI, q-bio.NC updates on arXiv.org
By: Xiaodong Wu · Xiangman Li · Qi Li · Lingshuang Liu · Jianbing Ni
arXiv:2506.18543v2 Announce Type: replace-cross Abstract: The rapid proliferation of Large Language Models (LLMs) has heightened concerns regarding their exposure to jailbreak attacks, which craft adversarial inputs designed to elicit unsafe content. Although proprietary models such as GPT-4 have been extensively evaluated, the robustness of emerging open-source systems like DeepSeek remains insufficiently examined, despite their growing use in LLM applications. In this paper, we conduct the first comprehensive jailbreak analysis of the DeepSeek model family, comparing it with GPT-3.5 and GPT-4 through the HarmBench benchmark. We investigate seven representative attack methods across 510 harmful behaviors, organized along both functional and semantic dimensions. Findings indicate that DeepSeek provides partial resilience against optimization-driven attacks such as TAP-T, but also results in greater susceptibility to prompt-based and manually engineered adversarial inputs. In contrast, GPT-4 Turbo demonstrates more robust and consistent safety alignment across a wide range of behaviors, likely due to stronger safety optimization and reinforcement learning from human feedback. In addition, fine-grained behavioral analysis and case studies reveal that DeepSeek often fails to consistently apply safety constraints to adversarial prompts, leading to uneven refusal behaviors. Overall, our results highlight an inherent trade-off between model efficiency and alignment generalization, underscoring the importance of targeted safety tuning and robust alignment strategies to ensure secure deployment of open-source LLMs.
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STAPO: Stabilizing Reinforcement Learning for LLMs by Silencing Rare Spurious Tokens

✇cs.AI, q-bio.NC updates on arXiv.org
By: Shiqi Liu · Zeyu He · Guojian Zhan · Letian Tao · Zhilong Zheng · Jiang Wu · Yinuo Wang · Yang Guan · Kehua Sheng · Bo Zhang · Keqiang Li · Jingliang Duan · Shengbo Eben Li
arXiv:2602.15620v5 Announce Type: replace-cross Abstract: Reinforcement Learning (RL) has significantly improved large language model reasoning, but existing RL fine-tuning methods rely heavily on heuristic techniques such as entropy regularization and reweighting to maintain stability. In practice, they often suffer from late-stage performance collapse, leading to degraded reasoning quality and unstable training. We identify a key factor behind this instability: a small fraction of tokens, termed spurious tokens (around 0.01%), which contribute little to the reasoning outcome but receive disproportionately amplified gradient updates due to inheriting the full sequence-level reward. We present a unified framework for evaluating token-level optimization impacts across spurious risk, gradient norms, and entropy changes. Building on the analysis of token characteristics that severely disrupt optimization, we propose the Silencing Spurious Tokens (S2T) mechanism to efficiently suppress their gradient perturbations. Incorporating this mechanism into a group-based objective, we propose Spurious-Token-Aware Policy Optimization (STAPO), which promotes stable and effective large-scale model refinement. Across six mathematical reasoning benchmarks using Qwen 1.7B, 8B, and 14B base models, STAPO consistently demonstrates superior entropy stability and achieves an average performance improvement of 11.49% ($\rho_{\mathrm{T}}$=1.0, top-p=1.0) and 3.73% ($\rho_{\mathrm{T}}$=0.7, top-p=0.9) over GRPO, 20-Entropy, and JustRL.
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Proteomic and lipidomic analyses reveal molecular subtypes and potential targets in early-stage lung adenocarcinoma among non-smokers

✇Pulmonary nodule
By: Yaohui Sun · Jian Liu · Xin Xu · Qiqi Liu · Hua Cheng · Wenwen Huo · Ronghao Wang · Qingdong Cao

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

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Establishment and characterization of an immortalized porcine gastric epithelial cell line and identification of NPC1 as a key mediator of aflatoxin B1 toxicity

✇(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)
By: Liqi Liu · JianLin Yuan · Jinyi Bai · Yuhan Ma · Kaitao Kong · Xiaofei He · Shuangshuang Chen · Jin Chai · Keren Long · Long Jin · Mingzhou Li · Juan Deng

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

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Epigenome-wide Mendelian randomization with multi-omics validation identifies epigenetic drivers of idiopathic pulmonary fibrosis

✇Omics In Lung
By: Zhaoqi Li · Luna Hong · Xingyu Lv · Shuangyu Yang · Fengzhan Ye · Linjie Huang · Shanping Jiang · Huiying Zhao

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

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Epigenome-wide Mendelian randomization with multi-omics validation identifies epigenetic drivers of idiopathic pulmonary fibrosis

✇(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)
By: Zhaoqi Li · Luna Hong · Xingyu Lv · Shuangyu Yang · Fengzhan Ye · Linjie Huang · Shanping Jiang · Huiying Zhao

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

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ClawArena: Benchmarking AI Agents in Evolving Information Environments

✇cs.AI, q-bio.NC updates on arXiv.org
By: Haonian Ji · Kaiwen Xiong · Siwei Han · Peng Xia · Shi Qiu · Yiyang Zhou · Jiaqi Liu · Jinlong Li · Bingzhou Li · Zeyu Zheng · Cihang Xie · Huaxiu Yao
arXiv:2604.04202v1 Announce Type: cross Abstract: AI agents deployed as persistent assistants must maintain correct beliefs as their information environment evolves. In practice, evidence is scattered across heterogeneous sources that often contradict one another, new information can invalidate earlier conclusions, and user preferences surface through corrections rather than explicit instructions. Existing benchmarks largely assume static, single-authority settings and do not evaluate whether agents can keep up with this complexity. We introduce ClawArena, a benchmark for evaluating AI agents in evolving information environments. Each scenario maintains a complete hidden ground truth while exposing the agent only to noisy, partial, and sometimes contradictory traces across multi-channel sessions, workspace files, and staged updates. Evaluation is organized around three coupled challenges: multi-source conflict reasoning, dynamic belief revision, and implicit personalization, whose interactions yield a 14-category question taxonomy. Two question formats, multi-choice (set-selection) and shell-based executable checks, test both reasoning and workspace grounding. The current release contains 64 scenarios across 8 professional domains, totaling 1{,}879 evaluation rounds and 365 dynamic updates. Experiments on five agent frameworks and five language models show that both model capability (15.4% range) and framework design (9.2%) substantially affect performance, that self-evolving skill frameworks can partially close model-capability gaps, and that belief revision difficulty is determined by update design strategy rather than the mere presence of updates. Code is available at https://github.com/aiming-lab/ClawArena.
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