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EvoRS: On-Policy Self-Evolution of Reward Systems for Open-Ended Reinforcement Learning

✇cs.AI, q-bio.NC updates on arXiv.org
By: Weiyuan Li · Aili Chen · Xintao Wang · Yikai Zhang · Qingqing Dong · Jinghan Xu · Hongru Hou · Wenxuan Zhao · Chengkun Lang · Jun Gao · Yuanli Guo · Hongcheng Guo · Yanghua Xiao · Deqing Yang
arXiv:2609.12459v1 Announce Type: new Abstract: Open-ended reinforcement learning often relies on rubric-based rewards for tasks without directly verifiable answers. Yet the policy and reward system form a dynamic feedback loop: as the policy optimizes the current reward, an initially useful reward system may become unreliable due to reward hacking or reduced response discriminability. The reward system should therefore evolve rather than remain fixed during training. Existing dynamic-rubric methods adapt evaluation criteria, but reward failures can also arise from scoring mechanisms or signal composition. We introduce EvoRS, a self-evolving RL framework that evolves the reward system from on-policy experience, representing it as an executable Reward-DAG. Specifically, an agentic designer updates this system from on-policy rollouts and reward traces to maintain train-time reliability. Across writing and roleplay, EvoRS achieves the best quality under all three judges, outperforming the policy by \(2.107\) and \(4.767\) points, respectively, while reducing reward hacking and coverage failures and preserving reward informativeness. Ablations confirm that a comprehensive fixed reward system cannot remain reliable in open-ended tasks and must evolve throughout training.
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From the invasive front to organotropic pre-metastatic niches: spatial immune regulatory networks governing cholangiocarcinoma dissemination and metastasis-intercepting immunotherapy

✇Omics In Lung
By: Longhao Zhang · Kai Zhang · Zhihong Chen · Xin Lu

Front Immunol. 2026 Aug 20;17:1919864. doi: 10.3389/fimmu.2026.1919864. eCollection 2026.

ABSTRACT

Cholangiocarcinoma is an aggressive biliary tract malignancy in which metastatic relapse and primary or acquired resistance to immunotherapy remain major causes of mortality. Although immune checkpoint inhibitors have improved first-line treatment for advanced biliary tract cancer, most patients do not achieve durable benefit, indicating that immune failure is not explained by a single checkpoint pathway. In this Review, we propose a spatial immune-regulatory continuum for cholangiocarcinoma dissemination. Most direct single-cell and spatial evidence currently derives from intrahepatic cholangiocarcinoma, and its applicability to perihilar and distal disease remains to be established. This continuum begins in the tumor core and invasive front, where malignant cells, cancer-associated fibroblasts, tumor-associated macrophages, endothelial and lymphatic cells, regulatory T cells, immature neutrophils and excluded or dysfunctional cytotoxic T cells form a pro-invasive ecosystem. It then extends through extracellular vesicles, soluble mediators and lymphovascular routes that may educate organotropic pre-metastatic niches. Finally, lymph node, lung, liver, peritoneal and bone microenvironments provide organ-specific extracellular matrix, myeloid and stromal programs that enable immune evasion and metastatic colonization. By integrating clinical evidence, multi-omics studies, single-cell and spatial transcriptomics, extracellular vesicle biology, pre-metastatic niche concepts and emerging therapeutic strategies, we argue that cholangiocarcinoma metastasis should be targeted before overt dissemination whenever possible. In this Review, "metastasis-intercepting immunotherapy" is used as an author-defined conceptual framework for strategies intended to prevent or disrupt the immune-stromal conditions that enable dissemination and colonization, rather than merely shrink established metastatic lesions. Metastasis-intercepting immunotherapy will likely require rational combinations that reprogram the invasive front, restore dendritic-cell-mediated antigen presentation, block tumor-stroma-myeloid circuits, disrupt EV-mediated communication that may contribute to niche formation and select patients using spatial biomarkers rather than bulk immune markers alone.

PMID:42694469 | PMC:PMC13539491 | DOI:10.3389/fimmu.2026.1919864

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Gastrointestinal motility in microgravity: a critical review of multi-level mechanisms and model-dependent effects

✇Omics in Gastric
By: Qian Niu · Tong Mu · Junhai Zhang · Yue Chen · Zhikun Guo · Yuanmin Zhu · Lin Li

Front Physiol. 2026 Aug 20;17:1930628. doi: 10.3389/fphys.2026.1930628. eCollection 2026.

ABSTRACT

BACKGROUND: Gastrointestinal motility disturbances rank among the most frequently reported medical complications of spaceflight. Astronauts experience delayed gastric emptying, erratic small intestinal transit and reduced colonic propulsion. The underlying mechanisms are multifactorial. Microgravity alters intra-abdominal physical mechanics, disrupts autonomic and enteric neural circuits, shifts gastrointestinal hormone secretion profiles, inflicts oxidative stress upon effector cells, and perturbs gut microbial communities. Cross-model comparisons reveal substantial disagreement, suggesting that no single ground-based analog fully captures the pathophysiology of orbital flight.

AIM: To critically review how weightlessness affects gastric emptying, small intestinal transit and colonic motility; to critically evaluate contradictory findings across simulation platforms; and to delineate the neural, humoral, cellular and microbiological mechanisms involved.

METHODS: We searched PubMed, Web of Science and the NASA Technical Reports Server for articles published between January 1990 and June 2026 (last search 30 June 2026). Search terms included: "microgravity", "weightlessness", "spaceflight", "gastrointestinal motility", "gastric emptying", "intestinal transit", "gut microbiome", "interstitial cells of Cajal" and "oxidative stress". Studies using head-down bed rest, hindlimb unloading, clinorotation, parabolic flight and actual spaceflight were included. The review follows a critical narrative design; the full search strategy and the framework used to appraise the evidence are described in Section 1.1.

RESULTS: Altered-gravity studies suggest that gastrointestinal dysmotility may involve neurohumoral dysregulation, oxidative injury to interstitial cells of Cajal and smooth muscle, barrier dysfunction and altered enteric signaling; however, most mechanistic evidence derives from simulated models and has not been directly validated during human spaceflight. Direct human motility measurements remain sparse, and the evidence comprises a mixture of direct observations, model-dependent inferences and testable hypotheses. Cross-study agreement is poor: some head-down bed rest trials report accelerated small-bowel transit, whereas tail-suspension models and limited flight observations suggest motor suppression. These divergences may reflect model-specific confounding rather than a uniform effect of microgravity.

CONCLUSION: Current ground-based models each capture only partial aspects of orbital GI pathophysiology. Future work should combine multi-omics profiling with next-generation simulation platforms to develop evidence-based countermeasures for long-duration missions.

PMID:42694486 | PMC:PMC13539599 | DOI:10.3389/fphys.2026.1930628

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FrontierOR: Benchmarking LLMs' Capacity for Efficient Algorithm Design in Large-Scale Optimization

✇cs.AI, q-bio.NC updates on arXiv.org
By: Minwei Kong · Chonghe Jiang · Ao Qu · Wenbin Ouyang · Zhaoming Zeng · Xiaotong Guo · Zhekai Li · Junyi Li · Yi Fan · Xinshou Zheng · Xi Jing · Yikai Zhang · Zhiwei Liang · Seonghoo Kim · Runqing Yang · Zijian Zhou · Sirui Li · Han Zheng · Wangyang Ying · Ou Zheng · Chonghuan Wang · Jinglong Zhao · Hanzhang Qin · Cathy Wu · Paul Pu Liang · Jinhua Zhao · Hai Wang
arXiv:2605.25246v2 Announce Type: new Abstract: Large language models (LLMs) are increasingly used for optimization modeling and solver-code generation, yet practical operations research and optimization problems often require a harder capability: designing scalable algorithms that exploit problem structure and outperform direct formulation-and-solve baselines. Existing benchmarks are limited to small or simplified examples far below real-world scale and complexity. We introduce FrontierOR, among the first benchmarks to systematically evaluate LLM-based efficient algorithm design for realistic large-scale optimization problems. FrontierOR includes 180 tasks derived from methodologically diverse papers published in top-tier operations research venues, each with standardized instances and a hidden, expert-verified evaluation suite. We evaluate seven LLMs spanning frontier, cost-effective, and open-source models both in one-shot and test-time evolution settings. The results reveal that frontier models still struggle to move from executable formulations to efficient optimization algorithms: the strongest one-shot model outperforms Gurobi in only 31% of cases in both solution quality and computational efficiency, and even strong coding agents with test-time evolution achieve only 50% on selected hard tasks. FrontierOR establishes a practical evaluation platform for LLM-based optimization algorithm design, which enables future LLMs and agents to be systematically tested on whether they can move beyond correct formulation toward a feasible, high-quality, and efficient algorithm.
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IVR-R1: Refining Trajectories through Iterative Visual-Grounded Reasoning in Reinforcement Learning

✇cs.AI, q-bio.NC updates on arXiv.org
By: Chenghao Li · Fusheng Hao · Xikai Zhang · Likang Xiao · Yanwei Ren · Fuxiang Wu · Quan Chen · Liu Liu
arXiv:2605.23997v1 Announce Type: cross Abstract: Multimodal large language models via reinforcement learning (RL) have demonstrated remarkable capabilities in complex visual reasoning tasks, yet they remain limited in long-horizon multimodal scenarios, often suffering from visual hallucination and logical error. Current methods typically pre-encode high-dimensional visual scenes into discrete textual proxies to facilitate downstream reasoning. As the reasoning chain unfolds, however, the inherent information asymmetry between text and visual scenes tends to erode visual grounding, resulting in misguided reasoning and erroneous outputs. To address this issue, we introduce IVR-R1 (Iterative Visual-grounded Reasoning), a novel RL training framework that facilitates dynamic visual re-alignment that actively rectifies reasoning trajectories to guide policy optimization. Specifically, by leveraging a reward-driven screening mechanism to identify flawed rollouts, IVR-R1 executes a fine-grained, step-level error attribution within the multimodal context. By iteratively cross-referencing intermediate reasoning states against pristine visual priors, a Re-Reasoning Loop enables automated trajectory rectification, effectively synthesizing expert-level demonstrations that serve as high-fidelity reasoning templates for the policy model. Our experiments across diverse multimodal benchmarks demonstrate that IVR-R1 consistently outperforms existing reinforcement learning methods, establishing a superior paradigm for maintaining logical and visual consistency in complex multimodal reasoning.
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Agent Learning via Early Experience

✇cs.AI, q-bio.NC updates on arXiv.org
By: Kai Zhang · Xiangchao Chen · Bo Liu · Tianci Xue · Zeyi Liao · Zhihan Liu · Xiyao Wang · Yuting Ning · Zhaorun Chen · Xiaohan Fu · Jian Xie · Yuxuan Sun · Boyu Gou · Qi Qi · Zihang Meng · Jianwei Yang · Ning Zhang · Xian Li · Ashish Shah · Dat Huynh · Hengduo Li · Zi Yang · Sara Cao · Lawrence Jang · Shuyan Zhou · Jiacheng Zhu · Huan Sun · Jason Weston · Yu Su · Yifan Wu
arXiv:2510.08558v3 Announce Type: replace Abstract: A long-term goal of language agents is to learn and improve through their own experience, ultimately outperforming humans in complex, real-world tasks. However, training agents from experience data with reinforcement learning remains difficult in many environments, which either lack verifiable rewards (e.g., websites) or require inefficient long-horizon rollouts (e.g., multi-turn tool use). As a result, most current agents rely on supervised fine-tuning on expert data, which is challenging to scale and generalizes poorly. This limitation stems from the nature of expert demonstrations: they capture only a narrow range of scenarios, and expose the agent to limited environment diversity. We address this limitation with a middle-ground paradigm we call early experience: interaction data generated by the agent's own actions, where the resulting future states serve as supervision without reward signals. Within this paradigm, we study two strategies of using such data: (1) implicit world modeling, which uses collected states to ground the policy in environment dynamics; and (2) self-reflection, where the agent learns from its suboptimal actions to improve reasoning and decision-making. Evaluation across eight diverse environments and multiple model families shows that our approaches consistently improve effectiveness and out-of-domain generalization, highlighting the value of early experience. Moreover, in environments with verifiable rewards, our results provide promising signals that early experience offers a strong foundation for subsequent reinforcement learning, making it a practical bridge between imitation learning and fully experience-driven agents.
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A framework for building a synthetic cell from the SynCell Asia Initiative

✇Nature Biotechnology - Issue - nature.com science feeds
By: Zhuojun Dai · Wataru Aoki · Pimchai Chaiyen · Matthew Wook Chang · Xixian Chen · Zibo Chen · Byung-Kwan Cho · Nan-Nan Deng · Shishen Du · Jee Loon Foo · Julius Fredens · Meifang Fu · Xiaojun Han · Tomohisa Hasunuma · Norikazu Ichihashi · Nurulfiza Mat Isa · Daisuke Kiga · Dong-Myung Kim · Jongmin Kim · Akihiko Kondo · Yuishin Kosaka · Kobkul Laoteng · Joongoo Lee · Jian Li · Junbai Li · Ming Li · Sierin Lim · Jianbo Liu · Xingguo Liu · Yuan Lu · Nan Luo · Tomoaki Matsuura · Wataru Mizunashi · Yan Qiao · Ahmad Bazli Ramzi · Sang Woo Seo · Yoshihiro Shimizu · Kwanwoo Shin · Liangfei Tian · Wanwipa Vongsangnak · Baojun Wang · Cheng-Cai Zhang · Xian-En Zhang · Guoping Zhao · Bo Zheng · Yaoqi Zhou · Chenli Liu

Nature Biotechnology, Published online: 26 May 2026; doi:10.1038/s41587-026-03153-w

Building a living cell from scratch requires overcoming a bottleneck that has remained unresolved despite decades of progress: orchestrating the spatiotemporal integration of core functional modules. To tackle this barrier, the SynCell Asia Initiative outlines a strategy for developing core functional modules followed by their systems-level integration through the establishment of a centralized, artificial intelligence (AI)-driven biofoundry.
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Beyond Retrieval: Modeling Confidence Decay and Deterministic Agentic Platforms in Generative Engine Optimization

✇cs.AI, q-bio.NC updates on arXiv.org
By: XinYu Zhao · ChengYou Li · XiangBao Meng · Kai Zhang · XiaoDong Liu
arXiv:2604.03656v1 Announce Type: new Abstract: Generative Engine Optimization (GEO) is rapidly reshaping digital marketing paradigms in the era of Large Language Models (LLMs). However, current GEO strategies predominantly rely on Retrieval-Augmented Generation (RAG), which inherently suffers from probabilistic hallucinations and the "zero-click" paradox, failing to establish sustainable commercial trust. In this paper, we systematically deconstruct the probabilistic flaws of existing RAG-based GEO and propose a paradigm shift towards deterministic multi-agent intent routing. First, we mathematically formulate Semantic Entropy Drift (SED) to model the dynamic decay of confidence curves in LLMs over continuous temporal and contextual perturbations. To rigorously quantify optimization value in black-box commercial engines, we introduce the Isomorphic Attribution Regression (IAR) model, leveraging a Multi-Agent System (MAS) probe with strict human-in-the-loop physical isolation to enforce hallucination penalties. Furthermore, we architect the Deterministic Agent Handoff (DAH) protocol, conceptualizing an Agentic Trust Brokerage (ATB) ecosystem where LLMs function solely as intent routers rather than final answer generators. We empirically validate this architecture using EasyNote, an industrial AI meeting minutes product by Yishu Technology. By routing the intent of "knowledge graph mapping on an infinite canvas" directly to its specialized proprietary agent via DAH, we demonstrate the reduction of vertical task hallucination rates to near zero. This work establishes a foundational theoretical framework for next-generation GEO and paves the way for a well-ordered, deterministic human-AI collaboration ecosystem.
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BAAI Cardiac Agent: An intelligent multimodal agent for automated reasoning and diagnosis of cardiovascular diseases from cardiac magnetic resonance imaging

✇cs.AI, q-bio.NC updates on arXiv.org
By: Taiping Qu · Hongkai Zhang · Lantian Zhang · Can Zhao · Nan Zhang · Hui Wang · Zhen Zhou · Mingye Zou · Kairui Bo · Pengfei Zhao · Xingxing Jin · Zixian Su · Kun Jiang · Huan Liu · Yu Du · Maozhou Wang · Ruifang Yan · Zhongyuan Wang · Tiejun Huang · Lei Xu · Henggui Zhang
arXiv:2604.04078v1 Announce Type: cross Abstract: Cardiac magnetic resonance (CMR) is a cornerstone for diagnosing cardiovascular disease. However, it remains underutilized due to complex, time-consuming interpretation across multi-sequences, phases, quantitative measures that heavily reliant on specialized expertise. Here, we present BAAI Cardiac Agent, a multimodal intelligent system designed for end-to-end CMR interpretation. The agent integrates specialized cardiac expert models to perform automated segmentation of cardiac structures, functional quantification, tissue characterization and disease diagnosis, and generates structured clinical reports within a unified workflow. Evaluated on CMR datasets from two hospitals (2413 patients) spanning 7-types of major cardiovascular diseases, the agent achieved an area under the receiver-operating-characteristic curve exceeding 0.93 internally and 0.81 externally. In the task of estimating left ventricular function indices, the results generated by this system for core parameters such as ejection fraction, stroke volume, and left ventricular mass are highly consistent with clinical reports, with Pearson correlation coefficients all exceeding 0.90. The agent outperformed state-of-the-art models in segmentation and diagnostic tasks, and generated clinical reports showing high concordance with expert radiologists (six readers across three experience levels). By dynamically orchestrating expert models for coordinated multimodal analysis, this agent framework enables accurate, efficient CMR interpretation and highlights its potentials for complex clinical imaging workflows. Code is available at https://github.com/plantain-herb/Cardiac-Agent.
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Autonomous Agents for Scientific Discovery: Orchestrating Scientists, Language, Code, and Physics

✇cs.AI, q-bio.NC updates on arXiv.org
By: Lianhao Zhou · Hongyi Ling · Cong Fu · Yepeng Huang · Michael Sun · Wendi Yu · Xiaoxuan Wang · Xiner Li · Xingyu Su · Junkai Zhang · Xiusi Chen · Chenxing Liang · Xiaofeng Qian · Heng Ji · Wei Wang · Marinka Zitnik · Shuiwang Ji
arXiv:2510.09901v2 Announce Type: replace Abstract: Computing has long served as a cornerstone of scientific discovery. Recently, a paradigm shift has emerged with the rise of large language models (LLMs), introducing autonomous systems, referred to as agents, that accelerate discovery across varying levels of autonomy. These language agents provide a flexible and versatile framework that orchestrates interactions with human scientists, natural language, computer language and code, and physics. This paper presents our view and vision of LLM-based scientific agents and their growing role in transforming the scientific discovery lifecycle, from hypothesis discovery, experimental design and execution, to result analysis and refinement. We critically examine current methodologies, emphasizing key innovations, practical achievements, and outstanding limitations. Additionally, we identify open research challenges and outline promising directions for building more robust, generalizable, and adaptive scientific agents. Our analysis highlights the transformative potential of autonomous agents to accelerate scientific discovery across diverse domains.
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SelfGrader: Stable Jailbreak Detection for Large Language Models using Token-Level Logits

✇cs.AI, q-bio.NC updates on arXiv.org
By: Zikai Zhang · Rui Hu · Olivera Kotevska · Jiahao Xu
arXiv:2604.01473v1 Announce Type: cross Abstract: Large Language Models (LLMs) are powerful tools for answering user queries, yet they remain highly vulnerable to jailbreak attacks. Existing guardrail methods typically rely on internal features or textual responses to detect malicious queries, which either introduce substantial latency or suffer from the randomness in text generation. To overcome these limitations, we propose SelfGrader, a lightweight guardrail method that formulates jailbreak detection as a numerical grading problem using token-level logits. Specifically, SelfGrader evaluates the safety of a user query within a compact set of numerical tokens (NTs) (e.g., 0-9) and interprets their logit distribution as an internal safety signal. To align these signals with human intuition of maliciousness, SelfGrader introduces a dual-perspective scoring rule that considers both the maliciousness and benignness of the query, yielding a stable and interpretable score that reflects harmfulness and reduces the false positive rate simultaneously. Extensive experiments across diverse jailbreak benchmarks, multiple LLMs, and state-of-the-art guardrail baselines demonstrate that SelfGrader achieves up to a 22.66% reduction in ASR on LLaMA-3-8B, while maintaining significantly lower memory overhead (up to 173x) and latency (up to 26x).
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Editing strigolactone hormone receptor for robust antiviral silencing in rice

✇Cell
By: Guoyi Yang · Ming Wu · Shuai Zhang · Yucen Huang · Yixiao Liu · Xiyuan Yu · Jiayang Hu · Le Mi · Peng Gan · Yuansheng Wu · Jing Zou · Baogang Zhang · Qun Hu · Jie Hu · Ruifeng Yao · Bojian Zhong · Xianbo Huang · Huiting Xie · Yinghua Ji · Yi Li · Jie Zhang · Liming Yan · Shou-wei Ding · Shanshan Zhao · Jianguo Wu
Precise genome editing of the rice strigolactone receptor DWARF14 confers robust, transgene-free antiviral resistance by blocking viral suppression of endogenous RNA silencing, offering a promising strategy for durable disease protection without a yield penalty.
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Learning to Generate Formally Verifiable Step-by-Step Logic Reasoning via Structured Formal Intermediaries

✇cs.AI, q-bio.NC updates on arXiv.org
By: Luoxin Chen · Yichi Zhou · Huishuai Zhang
arXiv:2603.29500v1 Announce Type: new Abstract: Large language models (LLMs) have recently demonstrated impressive performance on complex, multi-step reasoning tasks, especially when post-trained with outcome-rewarded reinforcement learning Guo et al. 2025. However, it has been observed that outcome rewards often overlook flawed intermediate steps, leading to unreliable reasoning steps even when final answers are correct. To address this unreliable reasoning, we propose PRoSFI (Process Reward over Structured Formal Intermediates), a novel reward method that enhances reasoning reliability without compromising accuracy. Instead of generating formal proofs directly, which is rarely accomplishable for a modest-sized (7B) model, the model outputs structured intermediate steps aligned with its natural language reasoning. Each step is then verified by a formal prover. Only fully validated reasoning chains receive high rewards. The integration of formal verification guides the model towards generating step-by-step machine-checkable proofs, thereby yielding more credible final answers. PRoSFI offers a simple and effective approach to training trustworthy reasoning models.
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$V_0$: A Generalist Value Model for Any Policy at State Zero

✇cs.AI, q-bio.NC updates on arXiv.org
By: Yi-Kai Zhang · Zhiyuan Yao · Hongyan Hao · Yueqing Sun · Qi Gu · Hui Su · Xunliang Cai · De-Chuan Zhan · Han-Jia Ye
arXiv:2602.03584v2 Announce Type: replace-cross Abstract: Policy gradient methods rely on a baseline to measure the relative advantage of an action, ensuring the model reinforces behaviors that outperform its current average capability. In the training of Large Language Models (LLMs) using Actor-Critic methods (e.g., PPO), this baseline is typically estimated by a Value Model (Critic) often as large as the policy model itself. However, as the policy continuously evolves, the value model requires expensive, synchronous incremental training to accurately track the shifting capabilities of the policy. To avoid this overhead, Group Relative Policy Optimization (GRPO) eliminates the coupled value model by using the average reward of a group of rollouts as the baseline; yet, this approach necessitates extensive sampling to maintain estimation stability. In this paper, we propose $V_0$, a Generalist Value Model capable of estimating the expected performance of any model on unseen prompts without requiring parameter updates. We reframe value estimation by treating the policy's dynamic capability as an explicit context input; specifically, we leverage a history of instruction-performance pairs to dynamically profile the model, departing from the traditional paradigm that relies on parameter fitting to perceive capability shifts. Focusing on value estimation at State Zero (i.e., the initial prompt, hence $V_0$), our model serves as a critical resource scheduler. During GRPO training, $V_0$ predicts success rates prior to rollout, allowing for efficient sampling budget allocation; during deployment, it functions as a router, dispatching instructions to the most cost-effective and suitable model. Empirical results demonstrate that $V_0$ significantly outperforms heuristic budget allocation and achieves a Pareto-optimal trade-off between performance and cost in LLM routing tasks.
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In vivo generation of anti-BCMA CAR-T cells in relapsed or refractory multiple myeloma: a phase 1 study

✇Nature Medicine
By: Ning An · Di Wang · Peiling Zhang · Jishuai Zhang · Philippe Parone · Jianlin Hu · Yuhan Bao · Li Xu · Haitao Ruan · Ying Wan · Xinyu Wen · Yang Gao · Chunrui Li

Nature Medicine, Published online: 25 March 2026; doi:10.1038/s41591-026-04244-6

In a phase 1 trial, the in vivo generation of anti-BCMA CAR-T cells by lentiviral delivery was feasible and did not lead to dose-limiting toxicities in five patients with relapsed or refractory multiple myeloma.
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Research on the compatibility mechanism of the Tingli Dazao Xiefei Decoction by multi-organ metabolomics strategy

✇(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)
By: Rui-Feng Wang · Pei-Pei Yuan · Long Chen · Zhen-Kai Zhang · Bing-Xian Zhang · Lin Chen · Shu-Miao Yuan · Yan-Fang Zhao · Ning Zhou · Xiao-Ke Zheng · Wei-Sheng Feng

J Ethnopharmacol. 2026 Mar 21:121548. doi: 10.1016/j.jep.2026.121548. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: The Tingli Dazao Xiefei Decoction (TD) is a traditional phlegm-eliminating prescription composed of Descurainia sophia (L.) Webb. ex Prantl (TLZ) and Ziziphus jujuba Mill. (DZ), which can relieve lung, heart and kidney injury in asthma. TLZ acts as the monarch drug in the TD. Based on the research mode of "material basis of traditional Chinese medicinal properties can be divided and combined", we have confirmed that the flavonoid glycosides components /the oligosaccharide components/the fatty oil component (FG/Oli/FO) are effective components of TLZ. However, the compatibility mechanism of the TD, and the contribution of the effective components of TLZ to the efficacy were still unclear.

AIM OF THE STUDY: To clarify the compatibility mechanism of TD, and the contribution of the effective components of TLZ to the efficacy from a comprehensive perspective of lung, heart, and kidney.

METHODS: First, we chose the asthma model corresponding to the efficacy of TD in purging the lungs and relieving asthma, and the rats were divided into the normal (NC) group, model (M) group, dexamethasone (DEX) group, and treatment groups of TD/TLZ/DZ/FO+DZ/Oli+DZ/FG+DZ. Second, metabolomics and network pharmacology were applied to elucidate the comprehensive protective effect of TD/FG+DZ/Oli+DZ/FO+DZ. Third, the multi-omics results were validated using Western blotting, RT-qPCR, flow cytometry, and immunofluorescence.

RESULTS: FO+DZ/Oli+DZ/FG+DZ had different degrees of protective effects against lung/heart/kidney injury in asthma. In metabolomics research, the principal component analysis (PCA) and cluster analysis results showed that the TLZ group was closer to TD group than DZ group, the FO+DZ and Oli+DZ group clustered with TD/NC groups in the lung and kidney, and the FO+DZ and FG+DZ group clustered with TD/NC groups in the heart. Pathway enrichment analysis suggested that the comprehensive protective effect of TLZ and its effective components combined with DZ on lung/heart/kidney may be achieved by regulating the arginine and proline metabolism, alanine, aspartate and glutamate metabolism, and unsaturated fatty acid biosynthesis. Multi-organ metabolomics and network pharmacology revealed consistent biological functions in KEGG pathways. Validation experiment showed that TLZ and its effective components combined with DZ could reverse the abnormal expression of proteins and RNA related to inflammation, airway remodeling, excitotoxicity, and energy-supply, apoptosis at different levels. Furthermore, FO+DZ may reduce asthma damage by inhibiting the FABP4/PPAR-γ/NF-κB signaling pathway.

CONCLUSION: TLZ played the key role in TD, and FO had the best therapeutic effect on each organ; the efficacy of Oli was mainly reflected in reducing lung and kidney damage, and FG was mainly involved in enhancing energy metabolism in the heart. These findings proved that traditional Chinese medicine could exert comprehensive efficacy in a 'multi-components trigger multi-channel' way.

PMID:41871629 | DOI:10.1016/j.jep.2026.121548

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Research on the compatibility mechanism of the Tingli Dazao Xiefei Decoction by multi-organ metabolomics strategy

✇Omics In Lung
By: Rui-Feng Wang · Pei-Pei Yuan · Long Chen · Zhen-Kai Zhang · Bing-Xian Zhang · Lin Chen · Shu-Miao Yuan · Yan-Fang Zhao · Ning Zhou · Xiao-Ke Zheng · Wei-Sheng Feng

J Ethnopharmacol. 2026 Mar 21:121548. doi: 10.1016/j.jep.2026.121548. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: The Tingli Dazao Xiefei Decoction (TD) is a traditional phlegm-eliminating prescription composed of Descurainia sophia (L.) Webb. ex Prantl (TLZ) and Ziziphus jujuba Mill. (DZ), which can relieve lung, heart and kidney injury in asthma. TLZ acts as the monarch drug in the TD. Based on the research mode of "material basis of traditional Chinese medicinal properties can be divided and combined", we have confirmed that the flavonoid glycosides components /the oligosaccharide components/the fatty oil component (FG/Oli/FO) are effective components of TLZ. However, the compatibility mechanism of the TD, and the contribution of the effective components of TLZ to the efficacy were still unclear.

AIM OF THE STUDY: To clarify the compatibility mechanism of TD, and the contribution of the effective components of TLZ to the efficacy from a comprehensive perspective of lung, heart, and kidney.

METHODS: First, we chose the asthma model corresponding to the efficacy of TD in purging the lungs and relieving asthma, and the rats were divided into the normal (NC) group, model (M) group, dexamethasone (DEX) group, and treatment groups of TD/TLZ/DZ/FO+DZ/Oli+DZ/FG+DZ. Second, metabolomics and network pharmacology were applied to elucidate the comprehensive protective effect of TD/FG+DZ/Oli+DZ/FO+DZ. Third, the multi-omics results were validated using Western blotting, RT-qPCR, flow cytometry, and immunofluorescence.

RESULTS: FO+DZ/Oli+DZ/FG+DZ had different degrees of protective effects against lung/heart/kidney injury in asthma. In metabolomics research, the principal component analysis (PCA) and cluster analysis results showed that the TLZ group was closer to TD group than DZ group, the FO+DZ and Oli+DZ group clustered with TD/NC groups in the lung and kidney, and the FO+DZ and FG+DZ group clustered with TD/NC groups in the heart. Pathway enrichment analysis suggested that the comprehensive protective effect of TLZ and its effective components combined with DZ on lung/heart/kidney may be achieved by regulating the arginine and proline metabolism, alanine, aspartate and glutamate metabolism, and unsaturated fatty acid biosynthesis. Multi-organ metabolomics and network pharmacology revealed consistent biological functions in KEGG pathways. Validation experiment showed that TLZ and its effective components combined with DZ could reverse the abnormal expression of proteins and RNA related to inflammation, airway remodeling, excitotoxicity, and energy-supply, apoptosis at different levels. Furthermore, FO+DZ may reduce asthma damage by inhibiting the FABP4/PPAR-γ/NF-κB signaling pathway.

CONCLUSION: TLZ played the key role in TD, and FO had the best therapeutic effect on each organ; the efficacy of Oli was mainly reflected in reducing lung and kidney damage, and FG was mainly involved in enhancing energy metabolism in the heart. These findings proved that traditional Chinese medicine could exert comprehensive efficacy in a 'multi-components trigger multi-channel' way.

PMID:41871629 | DOI:10.1016/j.jep.2026.121548

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Tiny but Mighty: A Software-Hardware Co-Design Approach for Efficient Multimodal Inference on Battery-Powered Small Devices

✇cs.AI, q-bio.NC updates on arXiv.org
By: Yilong Li · Shuai Zhang · Yijing Zeng · Hao Zhang · Xinmiao Xiong · Jingyu Liu · Pan Hu · Suman Banerjee
arXiv:2510.05109v5 Announce Type: replace-cross Abstract: Large Multimodal Models (LMMs) are inherently modular, consisting of vision and audio encoders, projectors, and large language models. Yet, they are almost always executed monolithically, which underutilizes the heterogeneous accelerators (NPUs, GPUs, DSPs) in modern SoCs and leads to high end-to-end latency. In this paper, we present NANOMIND, a hardware--software co-design inference framework for Large Multimodal Models (LMMs) that breaks large models into modular ``bricks'' (vision, language, audio, etc.) and maps each to its ideal accelerator. The key insight is that large models can be broken into modular components and scheduled to run on the most appropriate compute units. It performs module-level dynamic offloading across accelerators on unified-memory SoCs. By combining customized hardware design, system-level scheduling, and optimized low-bit computation kernels, we demonstrate our framework with a compact, battery-powered device capable of running LMMs entirely on device. This prototype functions as a self-contained intelligent assistant that requires no network connectivity, while achieving higher throughput and superior power efficiency under strict resource constraints. The design further bypasses CPU bottlenecks and reduces redundant memory usage through token-aware buffer management and module-level coordination. Our system outperforms existing implementations in resource efficiency, cutting energy consumption by 42.3\% and GPU memory usage by 11.2\%. This enables a battery-powered device to run LLaVA-OneVision with a camera for nearly 20.8 hours.
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Towards Efficient Federated Learning of Networked Mixture-of-Experts for Mobile Edge Computing

✇cs.AI, q-bio.NC updates on arXiv.org
By: Song Gao · Songyang Zhang · Shusen Jing · Shuai Zhang · Xiangwei Zhou · Yue Wang · Zhipeng Cai
arXiv:2511.01743v2 Announce Type: replace-cross Abstract: Recent advancements in large artificial intelligence models (LAMs) are driving significant innovations in mobile edge computing within next-generation wireless networks. However, the substantial demands for computational resources and larges-cale training data required to train LAMs conflict with the limited storage and computational capacity of edge devices, posing significant challenges to training and deploying LAMs at the edge. In this work, we introduce the Networked Mixture-of-Experts (NMoE) system, in which clients perform inference collaboratively by distributing tasks to suitable neighbors based on their expertise and aggregate the returned results. For training the NMoE, we propose a federated learning framework that integrates both supervised and self-supervised learning to balance personalization and generalization, while preserving communication efficiency and data privacy. We conduct extensive experiments to demonstrate the efficacy of the proposed NMoE system, providing insights for the NMoE training algorithms.
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Zero-Permission Manipulation: Can We Trust Large Multimodal Model Powered GUI Agents?

✇cs.AI, q-bio.NC updates on arXiv.org
By: Yi Qian · Kunwei Qian · Xingbang He · Ligeng Chen · Jikang Zhang · Tiantai Zhang · Haiyang Wei · Linzhang Wang · Hao Wu · Bing Mao
arXiv:2601.12349v2 Announce Type: replace-cross Abstract: Large multimodal model powered GUI agents are emerging as high-privilege operators on mobile platforms, entrusted with perceiving screen content and injecting inputs. However, their design operates under the implicit assumption of Visual Atomicity: that the UI state remains invariant between observation and action. We demonstrate that this assumption is fundamentally invalid in Android, creating a critical attack surface. We present Action Rebinding, a novel attack that allows a seemingly-benign app with zero dangerous permissions to rebind an agent's execution. By exploiting the inevitable observation-to-action gap inherent in the agent's reasoning pipeline, the attacker triggers foreground transitions to rebind the agent's planned action toward the target app. We weaponize the agent's task-recovery logic and Android's UI state preservation to orchestrate programmable, multi-step attack chains. Furthermore, we introduce an Intent Alignment Strategy (IAS) that manipulates the agent's reasoning process to rationalize UI states, enabling it to bypass verification gates (e.g., confirmation dialogs) that would otherwise be rejected. We evaluate Action Rebinding Attacks on six widely-used Android GUI agents across 15 tasks. Our results demonstrate a 100% success rate for atomic action rebinding and the ability to reliably orchestrate multi-step attack chains. With IAS, the success rate in bypassing verification gates increases (from 0% to up to 100%). Notably, the attacker application requires no sensitive permissions and contains no privileged API calls, achieving a 0% detection rate across malware scanners (e.g., VirusTotal). Our findings reveal a fundamental architectural flaw in current agent-OS integration and provide critical insights for the secure design of future agent systems. To access experimental logs and demonstration videos, please contact yi_qian@smail.nju.edu.cn.
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