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Robot-Assisted Therapy for Upper Limb Rehabilitation After Stroke: Umbrella Review

✇Journal of Medical Internet Research
By: Sijia Liu · Xianghong Zhang · Lijun Zhou · Jiashan Zhang · Jialin Liu · Chengqi He
Background: Stroke is a leading cause of long-term upper limb disability, severely impacting patients’ independence and quality of life. Robot-assisted therapy (RAT) has emerged as a promising, high-intensity rehabilitation alternative. However, conclusions from existing systematic reviews on its efficacy are inconsistent and often lack a holistic framework, limiting their use for guiding personalized clinical decisions. Objective: This study aims to systematically synthesize recent evidence on RAT for upper limb rehabilitation after stroke. Guided by the International Classification of Functioning, Disability and Health framework, it moves beyond singular outcomes to provide a multidimensional evaluation across body function, activity, and participation levels. The review aims to provide stratified guidance for clinical decision-making based on patient- and intervention-specific characteristics, thereby supporting evidence-based practice and informing future research. Methods: This study included systematic reviews and meta-analyses published from January 1, 2019, to December 26, 2025, comparing RAT with conventional therapy for upper limb rehabilitation after stroke. Overall, 6 databases, including PubMed, Web of Science, and Embase, were searched. Two reviewers (XZ and LZ) independently performed study selection, data extraction, and quality assessment using the AMSTAR 2 tool. The synthesis integrated outcome measures and subgroup analyses derived from the included studies. Results: This umbrella review included 21 meta-analyses encompassing 535 randomized controlled trials and 27,598 patients across acute, subacute, and chronic stroke stages. According to AMSTAR 2, 17 reviews were high quality, 3 moderate, and 1 critically low. The synthesis demonstrated that RAT was superior in improving upper limb motor function, but no statistically significant advantages were observed in activities of daily living compared to conventional therapy. Subgroup analyses revealed that treatment effects were influenced by stroke stage, upper limb motor impairment level, and robot type. Conclusions: RAT is an effective intervention for improving upper limb motor function after stroke. However, its benefits are primarily observed at the level of body function, with limited evidence for long-term maintenance. The current evidence is constrained by significant outcome heterogeneity and methodological limitations inherent to umbrella reviews. Future research should validate these findings in broader clinical practice, focus on translating functional gains into sustained improvements in daily activities and participation, and include cost-effectiveness evaluations. Trial Registration: PROSPERO CRD42024497183; https://www.crd.york.ac.uk/PROSPERO/view/CRD42024497183
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Ran Score: a LLM-based Evaluation Score for Radiology Report Generation

✇cs.AI, q-bio.NC updates on arXiv.org
By: Ran Zhang · Yucong Lin · Zhaoli Su · Bowen Liu · Danni Ai · Tianyu Fu · Deqiang Xiao · Jingfan Fan · Yuanyuan Wang · Mingwei Gao · Yuwan Hu · Shuya Gao · Jingtao Li · Jian Yang · Hong Song · Hongliang Sun
arXiv:2603.22935v1 Announce Type: new Abstract: Chest X-ray report generation and automated evaluation are limited by poor recognition of low-prevalence abnormalities and inadequate handling of clinically important language, including negation and ambiguity. We develop a clinician-guided framework combining human expertise and large language models for multi-label finding extraction from free-text chest X-ray reports and use it to define Ran Score, a finding-level metric for report evaluation. Using three non-overlapping MIMIC-CXR-EN cohorts from a public chest X-ray dataset and an independent ChestX-CN validation cohort, we optimize prompts, establish radiologist-derived reference labels and evaluate report generation models. The optimized framework improves the macro-averaged score from 0.753 to 0.956 on the MIMIC-CXR-EN development cohort, exceeds the CheXbert benchmark by 15.7 percentage points on directly comparable labels, and shows robust generalization on the ChestX-CN validation cohort. Here we show that clinician-guided prompt optimization improves agreement with a radiologist-derived reference standard and that Ran Score enables finding-level evaluation of report fidelity, particularly for low-prevalence abnormalities.
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PERMA: Benchmarking Personalized Memory Agents via Event-Driven Preference and Realistic Task Environments

✇cs.AI, q-bio.NC updates on arXiv.org
By: Shuochen Liu · Junyi Zhu · Long Shu · Junda Lin · Yuhao Chen · Haotian Zhang · Chao Zhang · Derong Xu · Jia Li · Bo Tang · Zhiyu Li · Feiyu Xiong · Enhong Chen · Tong Xu
arXiv:2603.23231v1 Announce Type: new Abstract: Empowering large language models with long-term memory is crucial for building agents that adapt to users' evolving needs. However, prior evaluations typically interleave preference-related dialogues with irrelevant conversations, reducing the task to needle-in-a-haystack retrieval while ignoring relationships between events that drive the evolution of user preferences. Such settings overlook a fundamental characteristic of real-world personalization: preferences emerge gradually and accumulate across interactions within noisy contexts. To bridge this gap, we introduce PERMA, a benchmark designed to evaluate persona consistency over time beyond static preference recall. Additionally, we incorporate (1) text variability and (2) linguistic alignment to simulate erratic user inputs and individual idiolects in real-world data. PERMA consists of temporally ordered interaction events spanning multiple sessions and domains, with preference-related queries inserted over time. We design both multiple-choice and interactive tasks to probe the model's understanding of persona along the interaction timeline. Experiments demonstrate that by linking related interactions, advanced memory systems can extract more precise preferences and reduce token consumption, outperforming traditional semantic retrieval of raw dialogues. Nevertheless, they still struggle to maintain a coherent persona across temporal depth and cross-domain interference, highlighting the need for more robust personalized memory management in agents. Our code and data are open-sourced at https://github.com/PolarisLiu1/PERMA.
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Enhancing AI-Based Tropical Cyclone Track and Intensity Forecasting via Systematic Bias Correction

✇cs.AI, q-bio.NC updates on arXiv.org
By: Peisong Niu · Haifan Zhang · Yang Zhao · Tian Zhou · Ziqing Ma · Wenqiang Shen · Junping Zhao · Huiling Yuan · Liang Sun
arXiv:2603.22314v1 Announce Type: cross Abstract: Tropical cyclones (TCs) pose severe threats to life, infrastructure, and economies in tropical and subtropical regions, underscoring the critical need for accurate and timely forecasts of both track and intensity. Recent advances in AI-based weather forecasting have shown promise in improving TC track forecasts. However, these systems are typically trained on coarse-resolution reanalysis data (e.g., ERA5 at 0.25 degree), which constrains predicted TC positions to a fixed grid and introduces significant discretization errors. Moreover, intensity forecasting remains limited especially for strong TCs by the smoothing effect of coarse meteorological fields and the use of regression losses that bias predictions toward conditional means. To address these limitations, we propose BaguanCyclone, a novel, unified framework that integrates two key innovations: (1) a probabilistic center refinement module that models the continuous spatial distribution of TC centers, enabling finer track precision; and (2) a region-aware intensity forecasting module that leverages high-resolution internal representations within dynamically defined sub-grid zones around the TC core to better capture localized extremes. Evaluated on the global IBTrACS dataset across six major TC basins, our system consistently outperforms both operational numerical weather prediction (NWP) models and most AI-based baselines, delivering a substantial enhancement in forecast accuracy. Remarkably, BaguanCyclone excels in navigating meteorological complexities, consistently delivering accurate forecasts for re-intensification, sweeping arcs, twin cyclones, and meandering events. Our code is available at https://github.com/DAMO-DI-ML/Baguan-cyclone.
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Generalizing Dynamics Modeling More Easily from Representation Perspective

✇cs.AI, q-bio.NC updates on arXiv.org
By: Yiming Wang · Zhengnan Zhang · Genghe Zhang · Jiawen Dan · Changchun Li · Chenlong Hu · Chris Nugent · Jun Liu · Ximing Li · Bo Yang
arXiv:2603.22655v1 Announce Type: cross Abstract: Learning system dynamics from observations is a critical problem in many applications over various real-world complex systems, e.g., climate, ecology, and fluid systems. Recently, neural dynamics modeling method have become a prevalent solution that embeds the object's observations into a latent space before learning dynamics using neural methods such as neural Ordinary Differential Equations (ODE). Existing dynamics modeling methods induce a specific model for each observation of different complex systems, resulting in poor generalization across systems. Inspired by the great success of pre-trained models, we conduct a generalized Pre-trained Dynamics EncoDER (PDEDER) which can embed the original state observations into a latent space where the dynamics can be captured more easily. To conduct the generalized PDEDER, we pre-train any Pre-trained Language Model (PLM) by minimizing the Lyapunov exponent objective, which constrains the chaotic behavior of governing dynamics learned in the latent space. By penalizing the divergence of embedded observations, our PDEDER promotes locally stable and well-structured latent dynamics, thereby facilitating more effective dynamics modeling than in the original observation space. In addition, we incorporate reconstruction and forecasting objectives to mitigate the risk of obtaining an over-smoothed latent space. Specifically, we collect 152 sets of real-world and synthetic observations from 23 complex systems as pre-training corpora and employ them to pre-train PDEDER. Given any future dynamic observation, we can fine-tune PDEDER with any specific dynamics modeling method. We evaluate PDEDER on 12 dynamic systems by short/long-term forecasting under both in-domain and cross-domain settings, and the empirical results indicate the effectiveness and generalizability of PDEDER.
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KARMA: Knowledge-Action Regularized Multimodal Alignment for Personalized Search at Taobao

✇cs.AI, q-bio.NC updates on arXiv.org
By: Zhi Sun · Wenming Zhang · Yi Wei · Liren Yu · Zhixuan Zhang · Dan Ou · Haihong Tang
arXiv:2603.22779v1 Announce Type: cross Abstract: Large Language Models (LLMs) are equipped with profound semantic knowledge, making them a natural choice for injecting semantic generalization into personalized search systems. However, in practice we find that directly fine-tuning LLMs on industrial personalized tasks (e.g. next item prediction) often yields suboptimal results. We attribute this bottleneck to a critical Knowledge--Action Gap: the inherent conflict between preserving pre-trained semantic knowledge and aligning with specific personalized actions by discriminative objectives. Empirically, action-only training objectives induce Semantic Collapse, such as attention ``sinks''. This degradation severely cripples the LLM's generalization, failing to bring improvements to personalized search systems. We propose KARMA (Knowledge--Action Regularized Multimodal Alignment), a unified framework that treats semantic reconstruction as a train-only regularizer. KARMA optimizes a next-interest embedding for retrieval (Action) while enforcing semantic decodability (Knowledge) through two complementary objectives: (i) history-conditioned semantic generation, which anchors optimization to the LLM's native next-token distribution, and (ii) embedding-conditioned semantic reconstruction, which constrains the interest embedding to remain semantically recoverable. On Taobao search system, KARMA mitigates semantic collapse (attention-sink analysis) and improves both action metrics and semantic fidelity. In ablations, semantic decodability yields up to +22.5 HR@200. With KARMA, we achieve +0.25 CTR AUC in ranking, +1.86 HR in pre-ranking and +2.51 HR in recalling. Deployed online with low inference overhead at ranking stage, KARMA drives +0.5% increase in Item Click.
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Reasoning over Semantic IDs Enhances Generative Recommendation

✇cs.AI, q-bio.NC updates on arXiv.org
By: Yingzhi He · Yan Sun · Junfei Tan · Yuxin Chen · Xiaoyu Kong · Chunxu Shen · Xiang Wang · An Zhang · Tat-Seng Chua
arXiv:2603.23183v1 Announce Type: cross Abstract: Recent advances in generative recommendation have leveraged pretrained LLMs by formulating sequential recommendation as autoregressive generation over a unified token space comprising language tokens and itemic identifiers, where each item is represented by a compact sequence of discrete tokens, namely Semantic IDs (SIDs). This SID-based formulation enables efficient decoding over large-scale item corpora and provides a natural interface for LLM-based recommenders to leverage rich world knowledge. Meanwhile, breakthroughs in LLM reasoning motivate reasoning-enhanced recommendation, yet effective reasoning over SIDs remains underexplored and challenging. Itemic tokens are not natively meaningful to LLMs; moreover, recommendation-oriented SID reasoning is hard to evaluate, making high-quality supervision scarce. To address these challenges, we propose SIDReasoner, a two-stage framework that elicits reasoning over SIDs by strengthening SID--language alignment to unlock transferable LLM reasoning, rather than relying on large amounts of recommendation-specific reasoning traces. Concretely, SIDReasoner first enhances SID-language alignment via multi-task training on an enriched SID-centered corpus synthesized by a stronger teacher model, grounding itemic tokens in diverse semantic and behavioral contexts. Building on this enhanced alignment, SIDReasoner further improves recommendation reasoning through outcome-driven reinforced optimization, which guides the model toward effective reasoning trajectories without requiring explicit reasoning annotations. Extensive experiments on three real-world datasets demonstrate the effectiveness of our reasoning-augmented SID-based generative recommendation. Beyond accuracy, the results highlight the broader potential of large reasoning models for generative recommendation, including improved interpretability and cross-domain generalization.
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Retrieval-Augmented Generation with Covariate Time Series

✇cs.AI, q-bio.NC updates on arXiv.org
By: Kenny Ye Liang · Zhongyi Pei · Huan Zhang · Yuhui Liu · Shaoxu Song · Jianmin Wang
arXiv:2603.04951v2 Announce Type: replace Abstract: While RAG has greatly enhanced LLMs, extending this paradigm to Time-Series Foundation Models (TSFMs) remains a challenge. This is exemplified in the Predictive Maintenance of the Pressure Regulating and Shut-Off Valve (PRSOV), a high-stakes industrial scenario characterized by (1) data scarcity, (2) short transient sequences, and (3) covariate coupled dynamics. Unfortunately, existing time-series RAG approaches predominantly rely on generated static vector embeddings and learnable context augmenters, which may fail to distinguish similar regimes in such scarce, transient, and covariate coupled scenarios. To address these limitations, we propose RAG4CTS, a regime-aware, training-free RAG framework for Covariate Time-Series. Specifically, we construct a hierarchal time-series native knowledge base to enable lossless storage and physics-informed retrieval of raw historical regimes. We design a two-stage bi-weighted retrieval mechanism that aligns historical trends through point-wise and multivariate similarities. For context augmentation, we introduce an agent-driven strategy to dynamically optimize context in a self-supervised manner. Extensive experiments on PRSOV demonstrate that our framework significantly outperforms state-of-the-art baselines in prediction accuracy. The proposed system is deployed in Apache IoTDB within China Southern Airlines. Since deployment, our method has successfully identified one PRSOV fault in two months with zero false alarm.
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From Context to Intent: Reasoning-Guided Function-Level Code Completion

✇cs.AI, q-bio.NC updates on arXiv.org
By: Yanzhou Li · Tianlin Li · Yiran Zhang · Shangqing Liu · Aishan Liu · Xianglong Liu · Yang Liu
arXiv:2508.09537v2 Announce Type: replace-cross Abstract: The growing capabilities of Large Language Models (LLMs) have led to their widespread adoption for function completion within code repositories. Recent studies on such tasks show promising results when explicit instructions, often in the form of docstrings, are available to guide the completion. However, in real-world scenarios, clear docstrings are frequently absent. Under such conditions, LLMs typically fail to produce accurate completions. To enable more automated and accurate function completion in such settings, we aim to enable LLMs to accurately infer the developer's intent prior to code completion. Our key insight is that the preceding code, namely the code context before the function to be completed, often contains valuable cues that help the model understand the intended functionality. However, inferring intent from such implicit context is non-trivial and constitutes a core challenge in function-level code completion. To tackle this challenge, inspired by how humans interpret context, we propose a reasoning-based prompting framework that guides LLMs to utilize these contextual cues to infer intent step by step. To incentivize LLMs to reason through the preceding code and infer intent, we further curate a dataset of 40k examples, each annotated with intermediate reasoning traces and corresponding docstrings. Extensive experiments on DevEval and ComplexCodeEval demonstrate consistent performance improvements across multiple models, achieving over 25% relative gains in pass@1 for both DeepSeekCoder and CodeLLaMA families. Building upon our framework, we further develop an intent-interactive platform that supports lightweight human feedback. This platform allows developers to select from a set of candidate intentions or edit the intent to better guide the model. Our experiments show that this interactive approach leads to further performance improvements.
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From Noisy Labels to Intrinsic Structure: A Geometric-Structural Dual-Guided Framework for Noise-Robust Medical Image Segmentation

✇cs.AI, q-bio.NC updates on arXiv.org
By: Tao Wang · Zhenxuan Zhang · Yuanbo Zhou · Xinlin Zhang · Yuanbin Chen · Tao Tan · Guang Yang · Tong Tong
arXiv:2509.02419v2 Announce Type: replace-cross Abstract: The effectiveness of convolutional neural networks in medical image segmentation relies on large-scale, high-quality annotations, which are costly and time-consuming to obtain. Even expert-labeled datasets inevitably contain noise arising from subjectivity and coarse delineations, which disrupt feature learning and adversely impact model performance. To address these challenges, this study propose a Geometric-Structural Dual-Guided Network (GSD-Net), which integrates geometric and structural cues to improve robustness against noisy annotations. It incorporates a Geometric Distance-Aware module that dynamically adjusts pixel-level weights using geometric features, thereby strengthening supervision in reliable regions while suppressing noise. A Structure-Guided Label Refinement module further refines labels with structural priors, and a Knowledge Transfer module enriches supervision and improves sensitivity to local details. To comprehensively assess its effectiveness, we evaluated GSD-Net on six publicly available datasets: four containing three types of simulated label noise, and two with multi-expert annotations that reflect real-world subjectivity and labeling inconsistencies. Experimental results demonstrate that GSD-Net achieves state-of-the-art performance under noisy annotations, achieving improvements of 1.58% on Kvasir, 22.76% on Shenzhen, 8.87% on BU-SUC, and 1.77% on BraTS2020 under SR simulated noise. The codes of this study are available at https://github.com/ortonwang/GSD-Net.
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Residual Decoding: Mitigating Hallucinations in Large Vision-Language Models via History-Aware Residual Guidance

✇cs.AI, q-bio.NC updates on arXiv.org
By: Xinrong Chen · Xu Chu · Yingmin Qiu · Hengyuan Zhang · Jing Xiong · Shiyu Tang · Shuai Liu · Shaokang Yang · Cheng Yang · Hayden Kwok-Hay So · Ngai Wong
arXiv:2602.01047v3 Announce Type: replace-cross Abstract: Large Vision-Language Models (LVLMs) can reason from image-text inputs and perform well in various multimodal tasks. Despite this success, they are affected by language priors and often produce hallucinations. Hallucinations denote generated content that is grammatically and syntactically coherent, yet bears no match or direct relevance to visual input. To address this problem, we propose Residual Decoding (ResDec). It is a novel training-free method that uses historical information to aid decoding. The method relies on the internal implicit reasoning mechanism and token logits evolution mechanism of LVLMs to correct biases. Extensive experiments demonstrate that ResDec effectively suppresses hallucinations induced by language priors, significantly improves visual grounding, and reduces object hallucinations. In addition to mitigating hallucinations, ResDec also performs exceptionally well on comprehensive LVLM benchmarks, highlighting its broad applicability.
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Children's Intelligence Tests Pose Challenges for MLLMs? KidGym: A 2D Grid-Based Reasoning Benchmark for MLLMs

✇cs.AI, q-bio.NC updates on arXiv.org
By: Hengwei Ye · Yuanting Guan · Yuxuan Ge · Tianying Zhu · Zhenhan Guan · Yijia Zhong · Yijing Zhang · Han Zhang · Yingna Wu · Zheng Tian
arXiv:2603.20209v2 Announce Type: replace-cross Abstract: Multimodal Large Language Models (MLLMs) combine the linguistic strengths of LLMs with the ability to process multimodal data, enbaling them to address a broader range of visual tasks. Because MLLMs aim at more general, human-like competence than language-only models, we take inspiration from the Wechsler Intelligence Scales - an established battery for evaluating children by decomposing intelligence into interpretable, testable abilities. We introduce KidGym, a comprehensive 2D grid-based benchmark for assessing five essential capabilities of MLLMs: Execution, Perception Reasoning, Learning, Memory and Planning. The benchmark comprises 12 unique tasks, each targeting at least one core capability, specifically designed to guage MLLMs' adaptability and developmental potential, mirroring the stages of children's cognitive growth. Additionally, our tasks encompass diverse scenarios and objects with randomly generated layouts, ensuring a more accurate and robust evluation of MLLM capabilities. KidGym is designed to be fully user-customizable and extensible, allowing researchers to create new evaluation scenarios and adjust difficuly levels to accommodate the rapidly growing MLLM community. Through the evaluation of state-of-the-art MLLMs using KidGym, we identified significant insights into model capabilities and revealed several limitations of current models. We release our benchmark at: https://bobo-ye.github.io/KidGym/.
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When Models Judge Themselves: Unsupervised Self-Evolution for Multimodal Reasoning

✇cs.AI, q-bio.NC updates on arXiv.org
By: Zhengxian Wu · Kai Shi · Chuanrui Zhang · Zirui Liao · Jun Yang · Ni Yang · Qiuying Peng · Luyuan Zhang · Hangrui Xu · Tianhuang Su · Zhenyu Yang · Haonan Lu · Haoqian Wang
arXiv:2603.21289v2 Announce Type: replace-cross Abstract: Recent progress in multimodal large language models has led to strong performance on reasoning tasks, but these improvements largely rely on high-quality annotated data or teacher-model distillation, both of which are costly and difficult to scale. To address this, we propose an unsupervised self-evolution training framework for multimodal reasoning that achieves stable performance improvements without using human-annotated answers or external reward models. For each input, we sample multiple reasoning trajectories and jointly model their within group structure. We use the Actor's self-consistency signal as a training prior, and introduce a bounded Judge based modulation to continuously reweight trajectories of different quality. We further model the modulated scores as a group level distribution and convert absolute scores into relative advantages within each group, enabling more robust policy updates. Trained with Group Relative Policy Optimization (GRPO) on unlabeled data, our method consistently improves reasoning performance and generalization on five mathematical reasoning benchmarks, offering a scalable path toward self-evolving multimodal models. The code are available at https://github.com/OPPO-Mente-Lab/LLM-Self-Judge.
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Effects of multisensory stimulation based on immersive virtual reality in postoperative neuropsychiatric recovery after gynecological laparoscopy

✇npj Digital Medicine
By: Jiang Liu · Yuxiu Liu · Liuna Bi · Li Zhao · Fuchan Hu · Mengyao Huang · Jingyuan Zhang · Xun Zhou · Ting Wang · Shirong Fang · Fengxian Zhang · Yuanjian Song

npj Digital Medicine, Published online: 24 March 2026; doi:10.1038/s41746-026-02515-7

Effects of multisensory stimulation based on immersive virtual reality in postoperative neuropsychiatric recovery after gynecological laparoscopy
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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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Single-cell multiomics uncovers an endothelial mechanosensitive PIEZO1-IL-33 axis driving pulmonary fibrosis

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

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

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Trem1 regulates neutrophil metabolism and recruitment in lung ischemia-reperfusion injury

✇Omics In Lung
By: Fengjing Yang · Song Tong · Junhao Wan · Yixing Li · Jiani Gao · Yan Sun · Xiangfu Sun · Huikang Fu · Wenzhuo Luo · Jiayang Xu · Ting Zhou · Sowe Babou · Junqi Wu · Guangjian Zhang · Chang Chen · Sihua Wang

Redox Biol. 2026 Jan 14;92:104026. doi: 10.1016/j.redox.2026.104026. Online ahead of print.

ABSTRACT

Primary graft dysfunction (PGD) caused by ischemia-reperfusion injury (IRI) is a major complication after lung transplantation, yet its underlying mechanisms remain unclear. Triggering receptor expressed on myeloid cells 1 (Trem1) is an important mediator of inflammation, but its role in neutrophil function and metabolic reprogramming during lung IRI is not well understood. In this study, we used a murine orthotopic lung transplantation model with cold ischemia and reperfusion, and Trem1 knockout (Trem1-/-) and myeloid-specific Trem1 conditional knockout mice (LysmCreTrem1fl) to explore the role of Trem1 in neutrophil recruitment, neutrophil extracellular trap (NET) formation, and metabolism. Our results show that Trem1 expression increases in both mouse and human lungs after reperfusion and correlates with neutrophil infiltration and lung injury. Trem1 deficiency significantly reduced neutrophil and macrophage recruitment, NET formation, and tissue damage. Multi-omics analysis revealed that Trem1 deletion suppressed oxidative phosphorylation (OXPHOS) and induced a metabolic shift in neutrophils toward glycolysis. In clinical samples, the abundance of TREM1+ neutrophils was correlated with PGD severity and OXPHOS activity. These findings identify Trem1 as a key regulator of neutrophil metabolism and recruitment in lung IRI, and suggest that targeting Trem1 may provide a novel therapeutic strategy to mitigate PGD and improve lung transplant outcomes.

PMID:41861599 | DOI:10.1016/j.redox.2026.104026

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Extracellular Vesicles in Osteosarcoma: Mechanisms, Diagnostics and Therapeutic Applications

✇Omics In Lung
By: Chaoyi Yin · Yiqi Wu · Xiliang Qu · Wenren Wu · Binshan Zhang · Jinshui Chen

Drug Des Devel Ther. 2026 Jan 6;20:565059. doi: 10.2147/DDDT.S565059. eCollection 2026.

ABSTRACT

Osteosarcoma is a primary bone malignancy of adolescents and young adults with marked heterogeneity and a high metastatic propensity. Five-year survival exceeds 70% in localized disease but falls to about 20% with pulmonary metastasis or chemoresistance, and overall outcomes have plateaued for decades. Extracellular vesicles (EVs) have emerged as critical mediators of osteosarcoma progression and metastasis. EVs remodel the tumor microenvironment (TME) by promoting immune evasion, extracellular matrix reprogramming, and angiogenesis, while also facilitating invasion, epithelial-mesenchymal transition (EMT)-like plasticity, and formation of lung pre-metastatic niches through organotropic integrins and glycoproteins. Their cargo, including proteins, lipids, and nucleic acids, drives intercellular communication that sustains proliferation, migration, and therapy resistance under metabolic or hypoxic stress. Clinically, the stability of EVs in body fluids and their tumor-specific molecular signatures highlight their promise as liquid-biopsy biomarkers for early diagnosis, prognosis, and treatment monitoring. Therapeutically, EVs are being engineered as delivery vehicles for drugs or RNA therapeutics, and interventions targeting their biogenesis, cargo sorting, or uptake are under exploration. Future research should integrate single-EV multi-omics, longitudinal cohort validation, and causal perturbation models to delineate functional mechanisms. Rational strategies that modulate EV dynamics and incorporate standardized analytic pipelines may transform EVs into actionable biomarkers and therapeutic targets, offering new avenues to overcome resistance and improve clinical outcomes in osteosarcoma.

PMID:41858917 | PMC:PMC12998350 | DOI:10.2147/DDDT.S565059

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