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

Nat Commun. 2026 Mar 20;17(1):2655. doi: 10.1038/s41467-026-70193-w.

ABSTRACT

Pulmonary fibrosis represents a progressive interstitial lung disease marked by excessive extracellular matrix deposition and architectural distortion. Vascular endothelial cells critically contribute to fibrogenesis through paracrine secretion of pro-fibrotic mediators, yet their mechanobiological regulation remains elusive. Using integrated single-cell multi-omics profiling of human pulmonary fibrosis specimens and experimental fibrosis models induced by bleomycin or silica, we identify mechanosensitive Piezo1 upregulation in Endothelial cells as a hallmark of fibrotic progression. Endothelial-specific Piezo1 knockout significantly attenuates Bleomycin-induced fibrotic remodeling in male mice, establishing its pathogenic necessity. Mechanistically, PIEZO1 activation promotes pulmonary fibrosis development via CAPN2-mediated STAT3 phosphorylation, which may regulate the secretion of the pro-fibrotic molecule interleukin-33. These findings suggest that the endothelial PIEZO1-CAPN2-STAT3-IL33 axis is a potential therapeutic target for PF intervention.

PMID:41862476 | PMC:PMC13004862 | DOI:10.1038/s41467-026-70193-w

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

arXiv:2603.03485v1 Announce Type: cross Abstract: Recent video diffusion models have achieved impressive capabilities as large-scale generative world models. However, these models often struggle with fine-grained physical consistency, exhibiting physically implausible dynamics over time. In this work, we present \textbf{Phys4D}, a pipeline for learning physics-consistent 4D world representations from video diffusion models. Phys4D adopts \textbf{a three-stage training paradigm} that progressively lifts appearance-driven video diffusion models into physics-consistent 4D world representations. We first bootstrap robust geometry and motion representations through large-scale pseudo-supervised pretraining, establishing a foundation for 4D scene modeling. We then perform physics-grounded supervised fine-tuning using simulation-generated data, enforcing temporally consistent 4D dynamics. Finally, we apply simulation-grounded reinforcement learning to correct residual physical violations that are difficult to capture through explicit supervision. To evaluate fine-grained physical consistency beyond appearance-based metrics, we introduce a set of \textbf{4D world consistency evaluation} that probe geometric coherence, motion stability, and long-horizon physical plausibility. Experimental results demonstrate that Phys4D substantially improves fine-grained spatiotemporal and physical consistency compared to appearance-driven baselines, while maintaining strong generative performance. Our project page is available at https://sensational-brioche-7657e7.netlify.app/

Learning to Generate and Extract: A Multi-Agent Collaboration Framework For Zero-shot Document-level Event Arguments Extraction

arXiv:2603.02909v2 Announce Type: replace-cross Abstract: Document-level event argument extraction (DEAE) is essential for knowledge acquisition, aiming to extract participants of events from documents . In the zero-shot setting, existing methods employ LLMs to generate synthetic data to address the challenge posed by the scarcity of annotated data. However, relying solely on Event-type-only prompts makes it difficult for the generated content to accurately capture the contextual and structural relationships of unseen events. Moreover, ensuring the reliability and usability of synthetic data remains a significant challenge due to the absence of quality evaluation mechanisms. To this end, we introduce a multi-agent collaboration framework for zero-shot document-level event argument extraction (ZS-DEAE), which simulates the human collaborative cognitive process of "Propose-Evaluate-Revise." Specifically, the framework comprises a generation agent and an evaluation agent. The generation agent synthesizes data for unseen events by leveraging knowledge from seen events, while the evaluation agent extracts arguments from the synthetic data and assesses their semantic consistency with the context. The evaluation results are subsequently converted into reward signals, with event structure constraints incorporated into the reward design to enable iterative optimization of both agents via reinforcement learning.In three zero-shot scenarios constructed from the RAMS and WikiEvents datasets, our method achieves improvements both in data generation quality and argument extraction performance, while the generated data also effectively enhances the zero-shot performance of other DEAE models.

Learning to Generate and Extract: A Multi-Agent Collaboration Framework For Zero-shot Document-level Event Arguments Extraction

arXiv:2603.02909v1 Announce Type: cross Abstract: Document-level event argument extraction (DEAE) is essential for knowledge acquisition, aiming to extract participants of events from documents.In the zero-shot setting, existing methods employ LLMs to generate synthetic data to address the challenge posed by the scarcity of annotated data. However, relying solely on Event-type-only prompts makes it difficult for the generated content to accurately capture the contextual and structural relationships of unseen events. Moreover, ensuring the reliability and usability of synthetic data remains a significant challenge due to the absence of quality evaluation mechanisms. To this end, we introduce a multi-agent collaboration framework for zero-shot document-level event argument extraction (ZS-DEAE), which simulates the human collaborative cognitive process of "Propose-Evaluate-Revise." Specifically, the framework comprises a generation agent and an evaluation agent. The generation agent synthesizes data for unseen events by leveraging knowledge from seen events, while the evaluation agent extracts arguments from the synthetic data and assesses their semantic consistency with the context. The evaluation results are subsequently converted into reward signals, with event structure constraints incorporated into the reward design to enable iterative optimization of both agents via reinforcement learning.In three zero-shot scenarios constructed from the RAMS and WikiEvents datasets, our method achieves improvements both in data generation quality and argument extraction performance, while the generated data also effectively enhances the zero-shot performance of other DEAE models.

MedLA: A Logic-Driven Multi-Agent Framework for Complex Medical Reasoning with Large Language Models

arXiv:2509.23725v3 Announce Type: replace Abstract: Answering complex medical questions requires not only domain expertise and patient-specific information, but also structured and multi-perspective reasoning. Existing multi-agent approaches often rely on fixed roles or shallow interaction prompts, limiting their ability to detect and resolve fine-grained logical inconsistencies. To address this, we propose \textsc{MedLA}, a logic-driven multi-agent framework built on large language models. Each agent organizes its reasoning process into an explicit logical tree based on syllogistic triads (major premise, minor premise, and conclusion), enabling transparent inference and premise-level alignment. Agents engage in a multi-round, graph-guided discussion to compare and iteratively refine their logic trees, achieving consensus through error correction and contradiction resolution. We demonstrate that \textsc{MedLA} consistently outperforms both static role-based systems and single-agent baselines on challenging benchmarks such as MedDDx and standard medical QA tasks. Furthermore, \textsc{MedLA} scales effectively across both open-source and commercial LLM backbones, achieving state-of-the-art performance and offering a generalizable paradigm for trustworthy medical reasoning.

EBPO: Empirical Bayes Shrinkage for Stabilizing Group-Relative Policy Optimization

arXiv:2602.05165v3 Announce Type: replace-cross Abstract: Reinforcement Learning with Verifiable Rewards (RLVR) has proven effective for enhancing the reasoning capabilities of Large Language Models (LLMs). However, dominant approaches like Group Relative Policy Optimization (GRPO) face critical stability challenges: they suffer from high estimator variance under computational constraints (small group sizes) and vanishing gradient signals in saturated failure regimes where all responses yield identical zero rewards. To address this, we propose Empirical Bayes Policy Optimization (EBPO), a novel framework that regularizes local group-based baselines by borrowing strength from the policy's accumulated global statistics. Instead of estimating baselines in isolation, EBPO employs a shrinkage estimator that dynamically balances local group statistics with a global prior updated via Welford's online algorithm. Theoretically, we demonstrate that EBPO guarantees strictly lower Mean Squared Error (MSE), bounded entropy decay, and non-vanishing penalty signals in failure scenarios compared to GRPO. Empirically, EBPO consistently outperforms GRPO and other established baselines across diverse benchmarks, including AIME and OlympiadBench. Notably, EBPO exhibits superior training stability, achieving high-performance gains even with small group sizes, and benefits significantly from difficulty-stratified curriculum learning.

WIMLE: Uncertainty-Aware World Models with IMLE for Sample-Efficient Continuous Control

arXiv:2602.14351v1 Announce Type: cross Abstract: Model-based reinforcement learning promises strong sample efficiency but often underperforms in practice due to compounding model error, unimodal world models that average over multi-modal dynamics, and overconfident predictions that bias learning. We introduce WIMLE, a model-based method that extends Implicit Maximum Likelihood Estimation (IMLE) to the model-based RL framework to learn stochastic, multi-modal world models without iterative sampling and to estimate predictive uncertainty via ensembles and latent sampling. During training, WIMLE weights each synthetic transition by its predicted confidence, preserving useful model rollouts while attenuating bias from uncertain predictions and enabling stable learning. Across $40$ continuous-control tasks spanning DeepMind Control, MyoSuite, and HumanoidBench, WIMLE achieves superior sample efficiency and competitive or better asymptotic performance than strong model-free and model-based baselines. Notably, on the challenging Humanoid-run task, WIMLE improves sample efficiency by over $50$\% relative to the strongest competitor, and on HumanoidBench it solves $8$ of $14$ tasks (versus $4$ for BRO and $5$ for SimbaV2). These results highlight the value of IMLE-based multi-modality and uncertainty-aware weighting for stable model-based RL.
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