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A Non-Canonical Role of SMAD4 in Regulating 3D Genome Architecture to Inhibit Lung Squamous Cell Carcinoma Development

✇(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)
By: Qian Tang · Chen Lian · Xinyan Han · Xuhan Zhang · Zihan Wang · Boyu Wang · Taoyu Zhu · Xinrui Lin · Xiaolei Wang · Yaping Xu · Manyu Xiao · Zijin Wang · Junming Li · Silin Chen · Yunze Wang · Yufei Liu · Songsong Li · Zuolin Shen · Xi Lu · Xueqi Han · Yilu Zhou · Mingyang Xiao · Jiayi Ran · Xiaoran Cao · Xinyi Xu · Hugo Sámano-Sánchez · Alfredo Rodríguez · Lian Wang · Shuifang Chen · Zhanyu Xu · Shirong Zhang · Nuo Yang · Yong Tang · Jian Liu

Adv Sci (Weinh). 2026 May 26:e75839. doi: 10.1002/advs.75839. Online ahead of print.

ABSTRACT

Lung squamous cell carcinoma (LUSC) lacks clearly defined key drivers and effective targeted therapies, reflecting an incomplete understanding of its molecular pathogenesis. Here, we identify SMAD4 as a critical regulator of three-dimensional (3D) genome organization in LUSC and uncover a mechanistic link between tumor suppressor loss and oncogenic transcriptional activation. By integrating clinical datasets, genetically engineered mouse models, human and murine LUSC cell lines, and multi-omics analyses, we demonstrate that SMAD4 deficiency promotes LUSC progression by unleashing EP300-mediated enhancer-promoter looping at the SOX2 locus. Mechanistically, SMAD4 does not directly bind SOX2 regulatory elements but instead constrains chromatin looping by sequestering EP300 away from loop anchor regions. Loss of SMAD4 leads to enhanced H3K27ac deposition, aberrant SOX2 activation, and increased LUSC tumor cell proliferation. Together, these findings reveal a non-canonical role for a transcription factor (e.g., SMAD4) in regulating dysregulated 3D genome architecture to inhibit tumor development.

PMID:42189071 | DOI:10.1002/advs.75839

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A Non-Canonical Role of SMAD4 in Regulating 3D Genome Architecture to Inhibit Lung Squamous Cell Carcinoma Development

✇Omics In Lung
By: Qian Tang · Chen Lian · Xinyan Han · Xuhan Zhang · Zihan Wang · Boyu Wang · Taoyu Zhu · Xinrui Lin · Xiaolei Wang · Yaping Xu · Manyu Xiao · Zijin Wang · Junming Li · Silin Chen · Yunze Wang · Yufei Liu · Songsong Li · Zuolin Shen · Xi Lu · Xueqi Han · Yilu Zhou · Mingyang Xiao · Jiayi Ran · Xiaoran Cao · Xinyi Xu · Hugo Sámano-Sánchez · Alfredo Rodríguez · Lian Wang · Shuifang Chen · Zhanyu Xu · Shirong Zhang · Nuo Yang · Yong Tang · Jian Liu

Adv Sci (Weinh). 2026 May 26:e75839. doi: 10.1002/advs.75839. Online ahead of print.

ABSTRACT

Lung squamous cell carcinoma (LUSC) lacks clearly defined key drivers and effective targeted therapies, reflecting an incomplete understanding of its molecular pathogenesis. Here, we identify SMAD4 as a critical regulator of three-dimensional (3D) genome organization in LUSC and uncover a mechanistic link between tumor suppressor loss and oncogenic transcriptional activation. By integrating clinical datasets, genetically engineered mouse models, human and murine LUSC cell lines, and multi-omics analyses, we demonstrate that SMAD4 deficiency promotes LUSC progression by unleashing EP300-mediated enhancer-promoter looping at the SOX2 locus. Mechanistically, SMAD4 does not directly bind SOX2 regulatory elements but instead constrains chromatin looping by sequestering EP300 away from loop anchor regions. Loss of SMAD4 leads to enhanced H3K27ac deposition, aberrant SOX2 activation, and increased LUSC tumor cell proliferation. Together, these findings reveal a non-canonical role for a transcription factor (e.g., SMAD4) in regulating dysregulated 3D genome architecture to inhibit tumor development.

PMID:42189071 | DOI:10.1002/advs.75839

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SkillEvolBench: Benchmarking the Evolution from Episodic Experience to Procedural Skills

✇cs.AI, q-bio.NC updates on arXiv.org
By: Yingtie Lei · Zhongwei Wan · Jiankun Zhang · Samiul Alam · Zixuan Zhong · Peizhou Huang · Xin Wang · Jingxuan Zhang · Donghao Zhou · Yunta Hsieh · Zhihao Dou · Hui Shen · Yan Xu · Dimitrios Dimitriadis · Tuo Zhang · Mi Zhang
arXiv:2605.24117v1 Announce Type: new Abstract: Large language model (LLM) agents accumulate rich episodic trajectories while solving real-world tasks, but it remains unclear whether such experience can be distilled into reusable procedural skills. We introduce SkillEvolBench, a diagnostic benchmark for evaluating this step from experience reuse to skill formation. It contains 180 tasks across six real-world agent environments, organized into role-conditioned task families with shared latent procedures. Agents learn from acquisition tasks, update an external skill library using compacted trajectories and verifier feedback, and then face frozen deployment tasks testing context shift, adversarial shortcuts, and composition. By comparing self-generated and curated-start skill evolution against no-skill and raw-trajectory controls, SkillEvolBench separates procedural abstraction from base capability, curated prior knowledge, and direct reuse of episodic traces. Across ten model configurations and three agent harnesses, we find that current agents often adapt locally but rarely form robust reusable skills. Skill-based conditions can improve acquisition or replay, and individual models sometimes gain on specific deployment axes, but these gains are unstable under frozen deployment. Raw-trajectory reuse frequently outperforms distilled skills, suggesting that current abstraction procedures discard contextual and procedural cues that remain useful for future tasks. Capacity and cost analyses further show that writing more skills or larger Tier-3 resource libraries is not sufficient: additional updates can improve coverage while introducing episode-specific drift and procedural clutter. These findings position SkillEvolBench as a testbed for measuring when one-off experience becomes durable procedural knowledge rather than task-local memory.
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GlobalDentBench: A Multinational Benchmark for Evaluating LLM Clinical Reasoning in Dentistry with Expert Calibration

✇cs.AI, q-bio.NC updates on arXiv.org
By: Junjie Zhao · Jingyi Liang · Zhenyang Cai · Jiaming Zhang · Zhenwei Wen · Shuzhi Deng · Wenjing Yi · Chunfeng Luo · Hexian Zhang · Junying Chen · Tianrui Liu · Zhuhui Bai · Zixu Zhang · Pradeep Singh · Xiang Liu · Jianquan Li · Nhan L Tran · Falk Schwendicke · Zuolin Jin · Lijian Jin · Liangyi Chen · Wei-fa Yang · Benyou Wang · Junwen Wang · Shan Jiang
arXiv:2605.24636v2 Announce Type: new Abstract: While large language models (LLMs) hold transformative potential for medicine, their reasoning robustness and safety in real-world clinical scenarios remain critically underexplored, particularly in dentistry. Here we introduce GlobalDentBench, the first multinational dental benchmark, featuring a taxonomy that encompasses 14 dental specialties across 88 countries and regions spanning six continents. The benchmark comprises 8,978 expert-validated questions across three formats (multiple-choice, short-answer, and case-based questions) and assesses three progressive reasoning levels: knowledge recall (L1), routine reasoning (L2), and individualized reasoning (L3). To ensure data quality, the automated construction framework was calibrated by six senior dentists, achieving expert agreement rates of 99.98% for multiple-choice and short-answer questions and 96.78% for the more complex case-based questions. Evaluation of 12 frontier LLMs on GlobalDentBench revealed a sharp, stepwise performance degradation with increasing reasoning complexity. Specifically, accuracy plummeted from 81.34% on multiple-choice to 64.53% on short-answer and 22.34% on case-based questions, while declining markedly from 74.01% at L1 to 55.64% at L2 and 35.71% at L3. More critically, risk analysis of real-world dental cases demonstrated an alarming overall unsafe rate of 31.01% in LLM-generated clinical recommendations, with 4.51% posing risks of irreversible patient harm and risks particularly pronounced in specialties such as orthodontics. These findings expose fundamental limitations in the medical reasoning and safety of current LLMs. Consequently, GlobalDentBench provides a scalable foundation for trustworthy clinical AI evaluation, underscoring the urgent need for rigorous validation before the safe deployment of these models in healthcare.
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LipoAgent: Coordinating Fine-Tuned LLM Agents for Safer Lipid Design

✇cs.AI, q-bio.NC updates on arXiv.org
By: Leshu Li · An Lu · Haiyu Wang · Zhibin Feng · Conghui Duan · Qing Bao · Zongmin Zhao · Sai Qian Zhang
arXiv:2605.25250v1 Announce Type: new Abstract: Lipid nanoparticles (LNPs) are among the most clinically mature platforms for nucleic acid delivery, yet designing lipids that are both effective and biologically safe remains a major bottleneck. In practical screening, toxicity is a decision-level constraint: if a lipid is toxic, its efficiency prediction is clinically irrelevant. We propose LipoAgent, a safety-aware multi-agent LLM framework for lipid discovery. LipoAgent combines domain-specific finetuning with a conditional prediction objective that enforces toxicity as a prerequisite for efficiency prediction, and further improves reliability via multi-agent verification with lightweight human oversight when disagreement persists. Across multiple foundation models, LipoAgent achieves an average 32% relative improvement in mRNA transfection efficiency prediction compared with other reported models for lipid design. Wet-lab validation confirms that virtual screening rankings reliably translate to biological transfection outcomes. The code is publicly available at https://github.com/SAI-Lab-NYU/LipoAgent.git.
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Context-CoT: Enhancing Context Learning via High-Quality Reasoning Synthesis

✇cs.AI, q-bio.NC updates on arXiv.org
By: Hongbo Jin · Mingnan Zhu · Jingqi Tian · Xu Jiang · Zhongjing Du · Haoran Tang · Siyi Xie · Qiaoman Zhang · Jiayu Ding
arXiv:2605.25354v1 Announce Type: new Abstract: While LLMs excel at reasoning over prompts using static pretrained knowledge, they struggle significantly with context learning-the ability to dynamically extract, internalize, and apply new knowledge from complex, task-specific contexts. Recent evaluations on the CL-Bench reveal a critical capability gap: frontier models solve only 17.2% of context-dependent tasks on average.
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CODESKILL: Learning Self-Evolving Skills for Coding Agents

✇cs.AI, q-bio.NC updates on arXiv.org
By: Yanzhou Li · Yiran Zhang · Xiaoyu Zhang · Xiaoxia Liu · Yang Liu
arXiv:2605.25430v1 Announce Type: new Abstract: Coding agents produce rich trajectories while solving software-engineering tasks. To enable agent self-evolution, these trajectories can be distilled into reusable procedural skills that compactly encode experience to guide future behavior. However, existing skill construction and maintenance methods often rely on fixed prompts and heuristic update rules, leaving it unclear how knowledge should be selected, abstracted, and maintained to best serve downstream agents. We propose CODESKILL, an LLM-based framework that reformulates skill extraction and skill-bank maintenance as a learnable management policy. CODESKILL extracts multi-granularity procedural skills from coding-agent trajectories, evolves skills with new experience, and maintains a compact skill bank for future task solving. We train CODESKILL with reinforcement learning, using a hybrid reward that combines dense rubric-based skill-quality feedback with sparse verifiable execution feedback from the frozen downstream agent. Experiments on EnvBench, SWE-Bench Verified, and Terminal-Bench 2 show that CODESKILL improves average pass rate by 9.69 over the no-skill baseline and by 4.01 over the strongest prompt-based or memory baseline, while maintaining the skill bank at a stable size during iterative construction.
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A Signal-Language Foundation Model for Broad-Spectrum Cardiovascular Assessment from Routine Electrocardiography

✇cs.AI, q-bio.NC updates on arXiv.org
By: Ziqing Yu · Yuhui Tao · Jiayu Huo · Lei Pan · Zilong Xiao · Juecheng Chen · Xiao Li · Jianxuan Li · You Zhou · Zhixing Li · Cong Wang · Beijian Zhang · Chen Chen · Hongyang Lu · Konstantinos Patlatzoglou · Daniel B. Kramer · Jonathan W. Waks · Yangang Su · Fu Siong Ng · Shuo Wang · Yixiu Liang · Junbo Ge
arXiv:2605.25446v1 Announce Type: new Abstract: Electrocardiography (ECG) is central to cardiovascular care, but conventional AI models are often restricted to common arrhythmias and may generalize poorly across populations or clinically subtle diseases. We developed ECG Contrastive Language-Image Pre-training (ECGCLIP), a signal-language contrastive learning framework that aligns ECG waveforms with expert diagnostic reports. ECGCLIP was pre-trained on 2,837,962 ECG studies from 1,324,856 patients and evaluated on a held-out internal test set plus nine independent external cohorts comprising about 1.5 million ECGs. Evaluation covered 89 downstream tasks, including 45 ECG diagnoses, 39 echocardiographic targets, and 5 rare cardiac diseases, using PRAUC as the primary metric. ECGCLIP consistently improved performance over random initialization and Merl-R18 baselines. On the internal test set, ECGCLIP-R34 achieved strong performance for atrial fibrillation (PRAUC 0.900) and ST-segment elevation myocardial infarction (PRAUC 0.383), with robust generalization across all external cohorts. It also improved low-prevalence and diagnostically elusive diseases, including Ebstein anomaly, constrictive pericarditis, dextrocardia, and cardiac amyloidosis, with internal PRAUC values of 0.253, 0.175, 0.121, and 0.201, respectively. ECGCLIP was data efficient, matching or exceeding full-dataset baseline performance with only 10% of training data. Feature visualization and saliency analysis suggested clinically meaningful representations aligned with established electrocardiographic criteria. These findings indicate that large-scale ECG-report contrastive pre-training can expand routine ECG interpretation beyond common arrhythmias toward broad cardiovascular assessment and opportunistic screening of echocardiographic and rare conditions.
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CausaLab: A Scalable Environment for Interactive Causal Discovery Toward AI Scientists

✇cs.AI, q-bio.NC updates on arXiv.org
By: Junlin Yang · Dylan Zhang · Xiangchen Song · Qirun Dai · Xiao Liu · Yuen Chen · Aniket Vashishtha · Jing Shi · Chenhao Tan · Hao Peng
arXiv:2605.26029v1 Announce Type: new Abstract: We introduce CausaLab, a scalable environment for evaluating interactive causal discovery by LLM agents. Unlike prior evaluations, CausaLab evaluates both whether an agent can solve a problem using causal evidence and whether its answer is supported by a correct hypothesis about the underlying causal mechanism. Each episode places an agent in a synthetic laboratory: it receives prior measurement records, intervenes on a manipulator crystal, and predicts the resonance frequency of a held-out reactor crystal governed by the same mechanism. The hidden data-generating process is a randomly sampled structural causal model (SCM), so success requires recovering both a causal graph and structural equations rather than recalling prior knowledge. CausaLab also includes a domain-specific language that records the agent's evolving SCM hypothesis, making trajectories inspectable and comparable with ground truth. Experiments show a persistent gap between prediction and mechanism recovery: in the purely observational 6-node setting, GPT-5.2-high reaches 92% task accuracy but only 0.471 all-edge $F_1$. This observation further motivates our exploration of different interaction strategies: Mixed observation--intervention strategies improve structural fidelity: in the mixed 6-node setting, GPT-5.2-high achieves 80% on both task accuracy and all-edge $F_1$. Yet even strong agents struggle to design informative interventions, as pure intervention strategies perform poorly on both task accuracy and all-edge $F_1$. We identify premature stopping as a major weakness of agents, and show that asking the model to verify the consistency between its hypothesis and past data can help mitigate this issue. CausaLab therefore separates predictive success from causal understanding and exposes current LLM agents' limits as experimental causal reasoners.
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Mode-as-Sequence: Translating Multimodal Motion Prediction into Unified Sequential Mode Modeling

✇cs.AI, q-bio.NC updates on arXiv.org
By: Zikang Zhou · Haibo Hu · Xinhong Chen · Yifan Zhang · Nan Guan · Yung-Hui Li · Chun Jason Xue · Jianping Wang
arXiv:2605.24037v1 Announce Type: cross Abstract: Multimodal motion forecasting is inherently under-supervised: each training scene provides only one realized future, yet multiple plausible futures exist. This sparse supervision often leads to mode collapse (redundant hypotheses and insufficient mode coverage) and unreliable confidence ranking when predicting a small set of trajectories. We propose Mode-as-Sequence, a unified decoding framework that translates an unordered mode set into an ordered mode sequence and explicitly models mode-to-mode dependency. Under this framework, we develop two complementary instantiations. ModeSeq performs recurrent mode decoding, where each mode is generated conditioned on the previously generated modes, encouraging diverse, non-redundant hypotheses with calibrated confidence ordering. To remove the mode-by-mode autoregressive bottleneck, we further propose Parallel ModeSeq, which preserves the same causal dependency using masked mode-to-mode self-attention while decoding all modes in a single forward pass, enabling efficient large-$K$ inference and scalable joint-scene prediction. To learn representative modes and calibrated confidence under sparse labels, we introduce Early-Match-Take-All (EMTA) and its joint-scene extension MA-EMTA, together with a lightweight ranking regularizer that reduces confidence inversions. Extensive experiments on large-scale benchmarks demonstrate consistent improvements in both ranking-oriented metrics and best-of-K accuracy across datasets, horizons, and object types. In the Waymo Open Dataset challenges, ModeSeq achieves 1st place in the 2024 LiDAR-free motion prediction track, and Parallel ModeSeq achieves 1st place in the 2025 Interaction Prediction Challenge, validating the effectiveness of Mode-as-Sequence for both accuracy and efficiency.
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Tiny Brains, Giant Impact: Uncovering the Keystone Neurons of LLM with Just a Few Prompts

✇cs.AI, q-bio.NC updates on arXiv.org
By: Xiangtian Ji · Yuxin Chen · Zhengzhou Cai · Xiang Wang · An Zhang · Tat-Seng Chua
arXiv:2605.24846v1 Announce Type: cross Abstract: Large language models (LLMs) display strong comprehensive abilities, yet the internal mechanisms that support these behaviors remain insufficiently understood. In this work, we show that across a wide range of open-weight Transformers, a subset of neurons remains consistently highly activated during inference across tasks of multiple capability dimensions. By probing along the cross-task activation strength, an extremely sparse subset is isolated, whose removal causes a collapse in model behavior, which we term keystone neurons. Our analysis reveals that keystone neurons are a stable and intrinsic neuron subset of the model that is largely established during pretraining. The parameters associated with these neurons are tightly calibrated during the training process, and their precise values are critical for the capabilities of the model. Building on these insights, we propose a supervised fine-tuning approach that updates only keystone neurons, achieving task gains comparable to or even better than full-parameter fine-tuning while better preserving performance in other capability dimensions, despite modifying a much smaller number of parameters.
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Towards a Universal Causal Reasoner

✇cs.AI, q-bio.NC updates on arXiv.org
By: Qirun Dai · Xiao Liu · Jiawei Zhang · Dylan Zhang · Hao Peng · Chenhao Tan
arXiv:2605.24873v1 Announce Type: cross Abstract: Despite the importance of causal reasoning, training LLMs to reason causally remains underexplored. Existing data efforts mostly focus on benchmarking LLMs on specific aspects of causality, making them less suitable for training generalizable causal reasoners. To address this, we propose UniCo, a data generation framework that both (1) addresses 18 causal query types across Pearl's Causal Ladder and (2) translates natively symbolic examples into code and natural language forms to simulate real-world use cases where causal terms are not explicitly specified. To ensure data quality, UniCo grounds answers with exact causal inference and filters cases with reasoning shortcuts. Upon supervised finetuning with 66.6K UniCo-generated instances, Qwen3-4B, Qwen3-8B and Olmo-3-7B-Instruct achieve an average of 22.9% improvements across all 18 in-distribution query types, and 8.1% over state-of-the-art causal data generation frameworks on 7 established causal benchmarks outside the training distribution. More importantly, in real-world medical understanding, legal decision, and tabular reasoning, UniCo-trained models consistently display more faithful reasoning traces, outperforming the base models by an average of 20.2% in faithfulness metrics. These suggest that causality-centered training not only strengthens causal reasoning, but also equips LLMs with a causal mindset in general reasoning tasks.
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Metropolis-Scale Resilient and Trustworthy Traffic Flow Inference Using Multi-Source Data

✇cs.AI, q-bio.NC updates on arXiv.org
By: Qishen Zhou · Yifan Zhang · Michail A. Makridis · Anastasios Kouvelas · Yibing Wang · Simon Hu
arXiv:2605.25004v1 Announce Type: cross Abstract: Inferring network-wide traffic states from sparse observations with high accuracy and trustworthy uncertainty quantification is essential for intelligent transportation systems, yet it remains challenging due to the underdetermined nature of the problem, multifaceted disturbances in sensing networks, and the inherent conflicts among multiple inference sub-tasks when modeled jointly. We propose the Task-Aware Attentive Neural Process (TA-ANP), a unified probabilistic framework for resilient and trustworthy global traffic state inference (GTSI) by fusing floating car data (FCD) with sparse fixed-detector measurements. By casting GTSI as a stochastic process, TA-ANP leverages the meta-learning properties of neural processes to adapt rapidly to changes in sensing configurations without retraining. A task-aware multi-query attention module with distinct spatiotemporal inductive biases is introduced to jointly handle three GTSI sub-tasks, while mitigating cross-task interference. For uncertainty quantification, we combine neural processes with Monte Carlo Dropout to capture both aleatoric and epistemic uncertainty. To support metropolis-scale evaluation, we construct the Metropolitan Multi-Source Traffic Dataset (MMTD), integrating fixed-loop sensor measurements, FCD statistics, and OpenStreetMap road-network data over an urban network of 2,371 road segments. Experiments on MMTD show that TA-ANP achieves state-of-the-art performance across all sub-tasks under deterministic and probabilistic metrics. The resulting well-calibrated uncertainties enable more efficient fixed-sensor placement with fewer sensor deployments. Under a Damage-Repair-Addition sensing lifecycle, TA-ANP demonstrates superior resilience in terms of disturbance absorption, performance recovery, and adaptability to unseen sensing configurations.
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A general tensor-structured compression scheme for efficient large language models

✇cs.AI, q-bio.NC updates on arXiv.org
By: Ying Lu · Peng-Fei Zhou · Qi-Xuan Fang · Pan Zhang · Shi-Ju Ran · Gang Su
arXiv:2605.25344v1 Announce Type: cross Abstract: Large language models (LLMs) are dominated by dense linear transformations, whose storage, memory and computational overheads hinder efficient adaptation and deployment while masking the functional impacts of structural simplification. Here we present Tensor Mixture (MixT), a general tensor-structured compression scheme that replaces targeted dense linear layers with natively executable mixtures of tensor operators. Operating directly on generic linear projections instead of model-specific components, MixT is potentially applicable across Transformer-based LLMs and other dense neural mappings. We evaluate MixT on Qwen3-8B and LLaMA2-7B under a unified recovery protocol, identifying a broad compressible regime in which MMLU accuracy is largely preserved before an abrupt transition at model-specific boundaries. This transition coincides with coordinated shifts in output entropy, prediction entropy and inter-layer geometry. At the LLaMA2-7B transition boundary, MixT reduces full-model parameters by 47.5\%, inference FLOPs by 37.1\%, training FLOPs by 52.1\% and peak inference memory by 60.4\%, demonstrating its practical potential for lower-cost LLM compression.
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Evo-Attacker: Memory-Augmented Reinforcement Learning for Long-Horizon Tool Attacks on LLM-MAS

✇cs.AI, q-bio.NC updates on arXiv.org
By: Bingyu Yan · Xiaoming Zhang · Jinyu Hou · Chaozhuo Li · Ziyi Zhou · Yiming Hei · Litian Zhang
arXiv:2605.25389v1 Announce Type: cross Abstract: While Large Language Model-based Multi-Agent Systems (LLM-MAS) demonstrate remarkable capabilities in solving complex tasks by orchestrating specialized agents and external tools, the implicit trust in tool outputs creates a critical attack surface. Existing tool attacks are limited by domain specificity or fixed and static templates. To address these challenges, we propose Evo-Attacker, which formulates the tool attack as a self-evolving, memory-augmented reinforcement learning process. Evo-Attacker constructs a dynamic attack memory and employs deliberative reasoning to retrieve adversarial patterns and strategize modifying interventions at critical moments. Furthermore, we introduce Attack-Flow GRPO to optimize intermediate reasoning steps via terminal outcomes, addressing the long-horizon credit assignment challenge. Comprehensive experiments demonstrate that Evo-Attacker consistently outperforms baselines, highlighting its generalization and evolutionary capabilities and the urgent need for defensive tool safeguards.
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Autoregression-Free Neural Operators for Time-Dependent PDEs

✇cs.AI, q-bio.NC updates on arXiv.org
By: Jiaquan Zhang · Caiyan Qin · Haoyu Bian · Libin Cai · Yi Lu · Chaoning Zhang · Wei Dong · Yuanfang Guo · Yang Yang · Hen Tao Shen
arXiv:2605.25413v1 Announce Type: cross Abstract: Neural operators learn mappings from function-dependent inputs to solutions, providing an effective framework for solving partial differential equations (PDEs). For time-dependent PDEs, existing methods typically perform long-horizon prediction through autoregressive rollout directly in high-dimensional physical field spaces, where each predicted state is recursively fed back as the input for the next step. Although effective for short-term prediction, this autoregressive rollout and the lack of continuous-time modeling lead to progressive error accumulation over long-horizon rollouts. In this work, we propose Autoregression-Free Neural Operators (AFNO), which map the time evolution of PDEs into a latent space and model continuous-time vector fields within it. AFNO uses flow matching to learn the latent vector field, thereby enabling continuous evolution over extended horizons, avoiding autoregressive rollout and capturing dynamics under varying parameter configurations through explicit conditioning on physical parameters. Theoretical analysis and extensive experiments on six PDEs demonstrate that AFNO improves long-horizon prediction stability and consistently reduces rollout errors compared with the baselines.
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Towards the Connection between Activation Sparsity and Flat Minima

✇cs.AI, q-bio.NC updates on arXiv.org
By: Ze Peng · Jian Zhang · Lei Qi · Yang Gao · Yinghuan Shi
arXiv:2605.25612v1 Announce Type: cross Abstract: The observation that activation sparsity emerges in MLP blocks of standardly trained Transformers offers an opportunity to drastically reduce computation costs without sacrificing performance. To theoretically explain this phenomenon, existing works have shown that activation sparsity does not result from the data properties or data fitting but from the implicit bias of the training process. However, these connections are obtained with strong assumptions, which cannot be applied to deep models standardly trained with a large number of steps. Different from these works, we find that the flatness of loss landscapes is also closely related to the MLP activation sparsity and can serve as a weaker and naturally emerging assumption standard deep networks. Specifically, we find that 1) the MLP activation sparsity equals a ratio between "augmented flatness" (a weighted sum of flatness measures) and the product of the input norm and activation gradient of the MLP. We empirically find that this ratio decreases during training, leading to sparse activations. 2) We also propose the notion of derivative sparsity, which reduces to activation sparsity under ReLU, but further enables pruning in the backward propagation and is more stable than activation sparsity. With the theoretical findings, we can further encourage activation sparsity by decreasing the numerator and increasing the denominator of the ratio using three methods. These plug-and-play modifications can effectively reduce the ratio and produce sparser activations. Experiments on ImageNet-1K and C4 demonstrate relative improvements of at least 36% on inference sparsity and at least 50% on training sparsity over vanilla Transformers, indicating further potential cost reduction in both inference and training
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TIAR: Trajectory-Informed Advantage Reweighting for LLM Abstention Learning

✇cs.AI, q-bio.NC updates on arXiv.org
By: Muyu Pan · Shu Zhao · Nan Zhang · Philip Shin · Varun Parekh · Vijaykrishnan Narayanan · Rui Zhang
arXiv:2605.25850v1 Announce Type: cross Abstract: This paper investigates large language model (LLM) abstention learning, specifically using ternary reward, which incentivize truthfulness in large language models. This paper extends that idea by moving from a ternary reward to a Trajectory-Informed advantage reweighting, dynamically re-weights the abstention reward during Group Relative Policy Optimization (GRPO) training. The objective of this work focuses on abstention learning instead of improving truthfulness, serving as an exploration into hallucination reduction. The novelty of this paper lies in methodological innovation, advantage re-weighting, and benchmark selection. Leveraging GRPO's multiple trajectories as a natural abstention signal, this method uses a reward signal to explore knowledge boundaries and encourage consistency. By demonstrating that trajectories can be used as a confidence indicator of the policy relative to the query, they are then used to dynamically calculate the abstention advantage. AbstentionBench is used as the evaluation benchmark, as this work aims to contribute to the field of abstention learning. All datasets on the benchmark were tested against this method and various baselines. Empirical results demonstrate that TIAR achieves state-of-the-art abstention F1 scores across five of six evaluation categories, outperforming the static ternary baseline on 17 of 31 benchmark datasets while fully preserving baseline accuracy.
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Can LLMs Time Travel? Enhancing Temporal Consistency in Legal Agentic Search through Reinforcement Learning

✇cs.AI, q-bio.NC updates on arXiv.org
By: Wei Fan · Yining Zhou · Mufan Zhang · Yanbing Weng · Yiran HU · Tianshi Zheng · Baixuan Xu · Chunyang Li · Jianhui Yang · Haoran Li · Yangqiu Song
arXiv:2605.25920v1 Announce Type: cross Abstract: While large language models (LLMs) augmented with agentic search capabilities show promise for legal reasoning, they overlook a fundamental constraint that applicable law must match the temporal context of each case, as retroactive application of statutes violates core legal principles and leads to erroneous conclusions. Our observations reveal that current legal LLMs suffer from temporal bias anchored to their training cutoff, while search agents rarely incorporate temporal constraints into queries, and that web search alone cannot provide the precise statute and precedent citations that legal reasoning demands. To address these challenges, we propose LegalSearch-R1, an end-to-end reinforcement learning framework that pairs local statute RAG for precise article matching with online web search for broader legal knowledge, trained on temporally-indexed data spanning multiple amendment periods to enforce temporal consistency. Extensive experiments on our benchmark covering 13 legal tasks demonstrate that our 7B-parameter agent outperforms state-of-the-art deep research frameworks and specialized legal LLMs by 12.9% to 29.8%, surpasses baselines by 57.7% to 80.3% on temporal consistency, and exhibits robust out-of-domain generalization. The code and data are available at https://github.com/AlexFanw/LegalSearch-R1.
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A Multimodal 3D Foundation Model for Light Sheet Fluorescence Microscopy Enables Few-Shot Segmentation, Classification, and Deblurring

✇cs.AI, q-bio.NC updates on arXiv.org
By: Adina Scheinfeld · Haotan Zhang · Shang Mu · Rudolf L. M. van Herten · Lucas Stoffl · Ali Erturk · Zhuhao Wu · Johannes C. Paetzold
arXiv:2605.26026v1 Announce Type: cross Abstract: Light sheet fluorescence microscopy (LSM) enables high-resolution, three-dimensional (3D) imaging of biological specimens, providing rich volumetric data for studying cellular organization, pathology, and vascular networks. However, the size, dimensionality, and annotation burden of LSM data make supervised deep learning approaches costly and difficult to scale. Additionally, despite the abundance of unannotated LSM volumes, foundation models for this modality remain underexplored due to computational challenges and the complexity of volumetric representation learning. In this work, we introduce a 3D foundation model for LSM data, pretrained on a large curated collection of 3D images spanning multiple organisms, stains, and imaging protocols. We learn transferable volumetric representations by jointly optimizing for masked reconstruction and image-text alignment. The pretrained backbone drastically reduces the annotation burden, enabling efficient, few-shot adaptation for varied downstream tasks. We evaluate this approach on downstream segmentation, classification, and deblurring. Our results demonstrate consistent improvements over baselines, (1) when measured using standard evaluation metrics and (2) when rigorously assessed by domain experts. This highlights the potential of foundation model pretraining to reduce annotation requirements while improving performance across diverse LSM analysis tasks. Pretrained model weights and code for pretraining and finetuning are publicly available: https://github.com/AdinaScheinfeld/lsm_fm_public_repo.git.
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