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Mechanism of Action of Hedyotis diffusa Extract in a Rat Model of Acute Lung Injury Based on Transcriptomic Analysis

✇(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)
By: Chenyi Lu · Xinyi Yang · Xin Yang

Biology (Basel). 2026 Sep 4;15(17):1549. doi: 10.3390/biology15171549.

ABSTRACT

OBJECTIVE: This study established a rat model of lipopolysaccharide (LPS)-induced acute lung injury (ALI) to evaluate pathological damage, collagen deposition, inflammatory cytokine levels, and key gene/protein expression following Hedyotis diffusa water extract (HDWE) intervention. Combined with ultra-high-performance liquid chromatography-quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS), transcriptomic analysis, and molecular simulation, this study identified the bioactive components of HDWE, evaluated their potential interactions with ALI-related targets, and explored the multi-omics-based protective mechanisms of HDWE.

METHODS: Thirty-six Sprague-Dawley (SD) rats were randomly divided into six groups: Control group, ALI group, DXMS group, HDWE-L group (100 mg/kg), HDWE-M group (200 mg/kg), and HDWE-H group (300 mg/kg). Hematoxylin and eosin (H&E) and Masson's trichrome staining were used to evaluate lung pathological changes and collagen deposition. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum tumor necrosis factor-α TNF-α interleukin-1β IL-1β, erleukin-6 (IL-6), and interleukin-10 (IL-10) levels. Transcriptomic analysis identified differentially expressed genes (DEGs), followed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), receiver operating characteristic (ROC), and immune infiltration analyses. Quantitative real-time polymerase chain reaction (qRT-PCR) detected the mRNA expression levels of SPHK1, RELA, and NFKBIA. Immunohistochemistry evaluated the expression of eight hub targets, including endothelin-1 (EDN1), sphingosine kinase 1 (SPHK1), intercellular adhesion molecule 1 (ICAM1), interleukin-17 (IL-17), prostaglandin-endoperoxide synthase 2 (PTGS2/COX-2), NF-κB p65 (encoded by RELA), WT1-associated protein (WTAP), and myeloperoxidase (MPO). UHPLC-Q-Orbitrap HRMS characterized HDWE constituents. Molecular docking analysis was performed between 22 compounds and eight hub targets, followed by 100 ns molecular dynamics simulations and molecular mechanics-Poisson-Boltzmann surface area (MM/PBSA) binding free energy calculations for five core targets. Compared with the control group, the ALI group showed increased levels of TNF-α (86%), IL-1β (107%), and IL-6 (66%), accompanied by a 43% reduction in IL-10 and a 300% increase in lung collagen deposition. All HDWE doses alleviated inflammatory responses, with medium-dose HDWE showing the most pronounced effects. Specifically, medium-dose HDWE increased IL-10 levels by 52% and reduced IL-6, TNF-α, and IL-1β levels by 18%, 22%, and 11%, respectively. Transcriptomic analysis identified 2512 DEGs between the control group and ALI groups, 832 exclusive DEGs between the ALI group and HDWE-M groups, and 876 overlapping DEGs enriched in TNF, IL-17, and NF-κB signaling pathways. The eight-hub-gene diagnostic model achieved an area under the curve (AUC) of 0.969. RELA, SPHK1, and four other hub genes showed positive correlations with Th1, Th17, and neutrophil infiltration. In the ALI group, SPHK1, RELA, and NFKBIA mRNA expression levels were 1.30-, 0.96-, and 0.71-fold of those in the control group, respectively. Compared with the ALI group, high-dose HDWE treatment and low-dose HDWE treatment reduced SPHK1 expression to 0.62- and 0.57-fold, respectively, and increased NFKBIA expression to 1.68- and 1.58-fold, respectively. High-dose HDWE treatment reduced RELA expression to 0.43-fold. The expression levels of inflammation-related proteins were increased in the ALI group and were reduced after HDWE treatment. Twenty-two HDWE components were identified, 16 of which met the docking criteria. Asperulosidic acid exhibited favorable predicted binding affinities with all eight targets, with calculated binding free energies of -14.74, -14.92, -17.58, -23.04, and -16.10 kcal/mol for MPO, IL-17, NF-κB p65, PTGS2/COX-2, and SPHK1, respectively.

CONCLUSIONS: This study provides systematic in vivo pharmacodynamic and in silico component-target evidence regarding the protective effects of HDWE against LPS-induced ALI. HDWE treatment increased NFKBIA expression and reduced SPHK1, RELA, and multiple inflammatory protein levels, suggesting that HDWE may regulate the IL-17/NF-κB-associated inflammatory network, although direct causal relationships require further validation. Asperulosidic acid may represent a key bioactive component with broad target-binding potential. This study was limited by the use of an LPS-induced rat ALI model without gene knockout or target inhibitor validation; therefore, further functional experiments are required to confirm the proposed regulatory mechanisms.

PMID:42737981 | PMC:PMC13564518 | DOI:10.3390/biology15171549

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OpenFinGym: A Verifiable Multi-Task Gym Environment for Evaluating Quant Agents

✇cs.AI, q-bio.NC updates on arXiv.org
By: Kaicheng Zhang · Wen Ge · Lei Jiang · Weixin Yang · Jordan Langham-Lopez · Jialin Yu · Lukasz Szpruch · Hao Ni
arXiv:2606.26350v2 Announce Type: replace Abstract: Although large language model agents are increasingly applied to quantitative-finance workflows, their evaluation remains fragmented across isolated tasks, while the financial relevance of benchmark tasks is often overlooked. Yet financial workflows are inherently multi-stage, spanning interdependent tasks such as forecasting, strategy construction, risk management, and trading. Existing platforms typically focus on a single task, and can therefore overstate agent competence and fail to reveal weaknesses in generalization, real-market interaction, and financially meaningful decision-making. We introduce OpenFinGym, a unified gym environment for quantitative-finance agent development that covers forecasting, market generation, real-time trading, and fraud detection under a single execution and verification interface. OpenFinGym additionally provides an automated task-construction pipeline that turns quantitative finance publications into executable task packages; a containerised runtime with a host-side verifier service that supports scalable agent rollouts and prevents runtime train-test leakage; a paper trading engine with a low-latency data-stream design; deferred-resolution support for long-horizon and event-market forecasts; and integration for SFT and RL post-training
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AgentHijack: Visual Patch Attacks on Multimodal Computer-Use Agents

✇cs.AI, q-bio.NC updates on arXiv.org
By: Zhihao Liu · Hongyu Sun · Zhiyuan Fu · Xiaonan Duan · Jice Wang · Shangru Zhao · Weizhi Meng · Wuxin Yang · Yangfan Zhou · Yuqing Zhang
arXiv:2609.09212v1 Announce Type: cross Abstract: This paper presents an end-to-end evaluation framework for image-triggered command injection against computer-use agents (CUAs). The goal is to test whether a local visual patch can induce verifiable environmental consequences along the full chain of screenshot input, VLM generation, action parsing, and environment execution. We train and deploy patches on author-controlled GitHub Pages pages and a locally deployed CSDN clone, and evaluate them in real environments across five open-source or publicly available GUI-agent or vision-language-model (VLM) backends. Our experiment aggregates 600 instance-level online cases, with T-ASR, TAPR, and E2E-ASR reaching 84.5%, 47.0%, and 20.3%, respectively. Trajectory analysis further shows that in some successful cases the agent first executes a malicious terminal command and then continues the original benign task. These results indicate that optimized local visual signals can affect not only VLM outputs but also propagate through the execution pipeline of open CUAs and create real environmental risk.
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A GPX1-OSBPL8 axis mediates noncanonical in vivo ferroptosis and cancer growth suppression

✇Cell
By: Zhangchuan Xia · Xin Yang · Sviatlana N. Samovich · Yulia Y. Tyurina · Vladimir A. Tyurin · Ning Kon · Jiankang Zhang · Xuejun Jiang · Brent R. Stockwell · Jian Jin · Hülya Bayir · Valerian E. Kagan · Wei Gu
An in vivo, noncanonical ferroptosis pathway, critical for tumor supression, is driven by reactive oxygen species-induced phosphatidic acid peroxidation at the ER under the control of the GPX1-OSBPL8 signaling axis.
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Associations Between Short-Video Platform Use and Health Across Health Distribution and Usage Behaviors in China: Cross-Sectional Questionnaire Study

✇Journal of Medical Internet Research
By: Yangyang Pan · Kangkang Zhang · Yilin Wei · Yangzhen Huang · Chengxu Long · Chenxin Yang · Shangfeng Tang
Background: Short-video platforms, characterized by algorithmic curation and passive consumption, have emerged as dominant components of digital life. However, the associations between short-video platform use and health across different groups and usage behaviors remain understudied. Objective: This study investigates associations between short-video platform use and health, examining whether these relationships vary across health status, usage behaviors, and socioeconomic status. Methods: A cross-sectional study was conducted using multistage stratified sampling across eastern, central, and western China from July to September 2024. The inclusion criteria were age 18 years or older, ability to communicate effectively, and no cognitive disorders or mental disturbance. Of 7725 participants enrolled, 46.96% (n=3628) were male, and the average age was 65.49 (SD 8.39) years. The data were collected via face-to-face interviews using a structured questionnaire. Self-rated health and relative health deprivation (Kakwani index) were used to measure health. Quantile regression explored associations between whether using short-video platform and health varies across the health distribution, while linear regression examined associations of years, frequency, daily duration, and purpose diversity of short-video platform use with health. Moderating effect analysis explored the role of socioeconomic status in the relationship between the daily duration of use and health. Results: Coefficients were tested using 2-tailed tests, and statistical significance was defined as a 2-sided value less than .05. Quantile regression revealed heterogeneous associations. Compared to nonusers, short-video platform users had better self-rated health at the 70th to 90th quantiles and lower relative health deprivation at the 10th to 30th quantiles. However, the users at the 10th quantile of self-rated health had worse self-rated health (=−2.224, 95% CI −3.835 to −0.613). Longer engagement (≥3 y) correlated with lower relative health deprivation (=1.970, 95% CI 0.308-3.632), while daily use of 1‐4 hours was associated with poorer self-rated health (=−3.385, 95% CI −4.872 to −1.898; =−3.038, 95% CI −5.054 to −1.022) and higher relative health deprivation (=0.035, 95% CI 0.021-0.050;
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Towards Self-Robust LLMs: Intrinsic Prompt Noise Resistance via CoIPO

✇cs.AI, q-bio.NC updates on arXiv.org
By: Xin Yang · Letian Li · Abudukelimu Wuerkaixi · Xuxin Cheng · Cao Liu · Ke Zeng · Xunliang Cai · Wenyuan Jiang
arXiv:2603.03314v1 Announce Type: cross Abstract: Large language models (LLMs) have demonstrated remarkable and steadily improving performance across a wide range of tasks. However, LLM performance may be highly sensitive to prompt variations especially in scenarios with limited openness or strict output formatting requirements, indicating insufficient robustness. In real-world applications, user prompts provided to LLMs often contain imperfections, which may undermine the quality of the model's responses. To address this issue, previous work has primarily focused on preprocessing prompts, employing external tools or even LLMs to refine prompt formulations in advance. However, these approaches overlook the intrinsic robustness of LLMs, and their reliance on external components introduces additional computational overhead and uncertainty. In this work, we propose a Contrastive Learning-based Inverse Direct Preference Optimization (CoIPO) method that minimizes the discrepancy between the label-aligned logits produced by the model under a clean prompt and its noisy counterpart, and conduct a detailed analysis using mutual information theory. We augment the FLAN dataset by constructing paired prompts, each consisting of a clean prompt and its corresponding noisy version for training. Additionally, to evaluate the effectiveness, we develop NoisyPromptBench, a benchmark enhanced and derived from the existing PromptBench. Experimental results conducted on NoisyPromptBench demonstrate that our proposed method achieves a significant improvement in average accuracy over the current state-of-the-art approaches. The source code of CoIPO, pair-wise FLAN datasets, and NoisyPromptBench have already been released on https://github.com/vegetable-yx/CoIPO.
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Anatomy of Agentic Memory: Taxonomy and Empirical Analysis of Evaluation and System Limitations

✇cs.AI, q-bio.NC updates on arXiv.org
By: Dongming Jiang · Yi Li · Songtao Wei · Jinxin Yang · Ayushi Kishore · Alysa Zhao · Dingyi Kang · Xu Hu · Feng Chen · Qiannan Li · Bingzhe Li
arXiv:2602.19320v1 Announce Type: cross Abstract: Agentic memory systems enable large language model (LLM) agents to maintain state across long interactions, supporting long-horizon reasoning and personalization beyond fixed context windows. Despite rapid architectural development, the empirical foundations of these systems remain fragile: existing benchmarks are often underscaled, evaluation metrics are misaligned with semantic utility, performance varies significantly across backbone models, and system-level costs are frequently overlooked. This survey presents a structured analysis of agentic memory from both architectural and system perspectives. We first introduce a concise taxonomy of MAG systems based on four memory structures. Then, we analyze key pain points limiting current systems, including benchmark saturation effects, metric validity and judge sensitivity, backbone-dependent accuracy, and the latency and throughput overhead introduced by memory maintenance. By connecting the memory structure to empirical limitations, this survey clarifies why current agentic memory systems often underperform their theoretical promise and outlines directions for more reliable evaluation and scalable system design.
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