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An operational perturbation proteomics-based virtual cell model

✇Nature - Issue - nature.com science feeds
By: Rui Sun · Liujia Qian · Yongge Li · Tong Liu · Honghan Cheng · Xuedong Zhang · Xueya Zhou · Yuecheng Zhan · Guangmei Zhang · Zhengchao Luo · Kunpeng Ma · Chunlong Wu · Dongchen Ji · Zhangzhi Xue · Hongxue Meng · Yuhang Xiang · Dingwei Lei · Qianhe Zhou · Wenbin Hu · Yuhan Deng · Lingling Tan · Qi Xiao · Zhiwei Liu · Lei Zeng · Liqin Qian · Xuan Zheng · Qiong Hu · Nianzi Luo · Weinan E · Peijie Zhou · Han Wen · Yi Zhu · Tiannan Guo

Nature, Published online: 09 September 2026; doi:10.1038/s41586-026-11001-9

Temporal protein-abundance measurements from systematically perturbed breast cancer cell lines were generated to develop ProteinTalks, a virtual cell model that functions as an operational tool for diverse drug discovery tasks.
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Protective Effects of the Ethyl Acetate Fraction from Madeng'ai on Lipopolysaccharide-Induced Acute Lung Injury in Mice: Insights from Integrated Multi-Omics Analysis

✇(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)
By: Ziyang Zhang · Tianyi Zhu · Liang Cao · Yan Wang · Xiao-Liang Xing · Zaiqi Zhang

J Ethnopharmacol. 2026 Apr 4:121650. doi: 10.1016/j.jep.2026.121650. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Madeng'ai (MDA) is a traditional medicinal plant of the Dong ethnic group. Its roots have been widely used in folk medicine for clearing heat and removing toxins, alleviating swelling and relieving pain, dispersing blood stasis and arresting bleeding, as well as promoting wound healing. It is taxonomically classified as a variety of Potentilla freyniana Bornm.

AIM OF THE STUDY: Acute lung injury (ALI) is a life-threatening pulmonary disorder associated with high mortality, underscoring the urgent need to explore novel therapeutic strategies. This study aimed to evaluate the protective effects of the ethyl acetate fraction of MDA (MEA) against LPS-induced ALI in mice and to investigate its underlying mechanisms.

MATERIALS AND METHODS: LC-MS/MS was employed to tentatively identify the bioactive components of MEA. A mouse model of ALI was established by LPS induction. The protective effects of MEA were evaluated through assessments of lung histopathology, inflammatory cytokine levels, and oxidative stress markers. The underlying mechanisms were systematically investigated by integrating transcriptomics, metabolomics, network pharmacology, molecular docking, and Western blotting.

RESULTS: MEA significantly attenuated LPS-induced pulmonary pathological lesions, pulmonary edema, and excessive inflammatory responses in ALI mice. Comprehensive bioinformatics analyses predicted potential mechanisms involving oxidative stress and the regulation of metabolic pathways. Experimental validation via Western blotting confirmed that MEA inhibited TLR4-mediated inflammatory signaling and modulated the PI3K/AKT pathway, thereby exerting multi-pathway protective effects against ALI.

CONCLUSIONS: Collectively, this study confirms that MEA, as a traditional herbal extract, holds potential as an adjuvant therapeutic agent for ALI, providing experimental evidence for the modernization and development of ethnic medicines.

PMID:41941987 | DOI:10.1016/j.jep.2026.121650

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Protective Effects of the Ethyl Acetate Fraction from Madeng'ai on Lipopolysaccharide-Induced Acute Lung Injury in Mice: Insights from Integrated Multi-Omics Analysis

✇Omics In Lung
By: Ziyang Zhang · Tianyi Zhu · Liang Cao · Yan Wang · Xiao-Liang Xing · Zaiqi Zhang

J Ethnopharmacol. 2026 Apr 4:121650. doi: 10.1016/j.jep.2026.121650. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Madeng'ai (MDA) is a traditional medicinal plant of the Dong ethnic group. Its roots have been widely used in folk medicine for clearing heat and removing toxins, alleviating swelling and relieving pain, dispersing blood stasis and arresting bleeding, as well as promoting wound healing. It is taxonomically classified as a variety of Potentilla freyniana Bornm.

AIM OF THE STUDY: Acute lung injury (ALI) is a life-threatening pulmonary disorder associated with high mortality, underscoring the urgent need to explore novel therapeutic strategies. This study aimed to evaluate the protective effects of the ethyl acetate fraction of MDA (MEA) against LPS-induced ALI in mice and to investigate its underlying mechanisms.

MATERIALS AND METHODS: LC-MS/MS was employed to tentatively identify the bioactive components of MEA. A mouse model of ALI was established by LPS induction. The protective effects of MEA were evaluated through assessments of lung histopathology, inflammatory cytokine levels, and oxidative stress markers. The underlying mechanisms were systematically investigated by integrating transcriptomics, metabolomics, network pharmacology, molecular docking, and Western blotting.

RESULTS: MEA significantly attenuated LPS-induced pulmonary pathological lesions, pulmonary edema, and excessive inflammatory responses in ALI mice. Comprehensive bioinformatics analyses predicted potential mechanisms involving oxidative stress and the regulation of metabolic pathways. Experimental validation via Western blotting confirmed that MEA inhibited TLR4-mediated inflammatory signaling and modulated the PI3K/AKT pathway, thereby exerting multi-pathway protective effects against ALI.

CONCLUSIONS: Collectively, this study confirms that MEA, as a traditional herbal extract, holds potential as an adjuvant therapeutic agent for ALI, providing experimental evidence for the modernization and development of ethnic medicines.

PMID:41941987 | DOI:10.1016/j.jep.2026.121650

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LDHA-driven lactate metabolism promotes MDSC activation and immunosuppressive microenvironment in prostate cancer

✇Oncogene - Issue - nature.com science feeds
By: Xiyi Wei · Xiao Li · Yitong Pan · Yuwei Zhang · Da Zhong · Weiyu Kong · Yue Wang · Zijie Yu · Wenchuan Shao · Yuxiang Dong · Silin Jiang · Zige Qiu · Xiang Li · Yize Li · Shouyong Gu · Chenxi Tian · Chao Qin · Qingyi Zhu · Ninghan Feng · Ninghong Song · Bing Yao · Zhou Yang

Oncogene, Published online: 01 April 2026; doi:10.1038/s41388-026-03737-5

LDHA-driven lactate metabolism promotes MDSC activation and immunosuppressive microenvironment in prostate cancer
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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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Think Before You Drive: World Model-Inspired Multimodal Grounding for Autonomous Vehicles

✇cs.AI, q-bio.NC updates on arXiv.org
By: Haicheng Liao · Huanming Shen · Bonan Wang · Yongkang Li · Yihong Tang · Chengyue Wang · Dingyi Zhuang · Kehua Chen · Hai Yang · Chengzhong Xu · Zhenning Li
arXiv:2512.03454v3 Announce Type: replace-cross Abstract: Interpreting natural-language commands to localize target objects is critical for autonomous driving (AD). Existing visual grounding (VG) methods for autonomous vehicles (AVs) typically struggle with ambiguous, context-dependent instructions, as they lack reasoning over 3D spatial relations and anticipated scene evolution. Grounded in the principles of world models, we propose ThinkDeeper, a framework that reasons about future spatial states before making grounding decisions. At its core is a Spatial-Aware World Model (SA-WM) that learns to reason ahead by distilling the current scene into a command-aware latent state and rolling out a sequence of future latent states, providing forward-looking cues for disambiguation. Complementing this, a hypergraph-guided decoder then hierarchically fuses these states with the multimodal input, capturing higher-order spatial dependencies for robust localization. In addition, we present DrivePilot, a multi-source VG dataset in AD, featuring semantic annotations generated by a Retrieval-Augmented Generation (RAG) and Chain-of-Thought (CoT)-prompted LLM pipeline. Extensive evaluations on six benchmarks, ThinkDeeper ranks #1 on the Talk2Car leaderboard and surpasses state-of-the-art baselines on DrivePilot, MoCAD, and RefCOCO/+/g benchmarks. Notably, it shows strong robustness and efficiency in challenging scenes (long-text, multi-agent, ambiguity) and retains superior performance even when trained on 50% of the data.
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UIS-Digger: Towards Comprehensive Research Agent Systems for Real-world Unindexed Information Seeking

✇cs.AI, q-bio.NC updates on arXiv.org
By: Chang Liu · Chuqiao Kuang · Tianyi Zhuang · Yuxin Cheng · Huichi Zhou · Xiaoguang Li · Lifeng Shang
arXiv:2603.08117v1 Announce Type: new Abstract: Recent advancements in LLM-based information-seeking agents have achieved record-breaking performance on established benchmarks. However, these agents remain heavily reliant on search-engine-indexed knowledge, leaving a critical blind spot: Unindexed Information Seeking (UIS). This paper identifies and explores the UIS problem, where vital information is not captured by search engine crawlers, such as overlooked content, dynamic webpages, and embedded files. Despite its significance, UIS remains an underexplored challenge. To address this gap, we introduce UIS-QA, the first dedicated UIS benchmark, comprising 110 expert-annotated QA pairs. Notably, even state-of-the-art agents experience a drastic performance drop on UIS-QA (e.g., from 70.90 on GAIA and 46.70 on BrowseComp-zh to 24.55 on UIS-QA), underscoring the severity of the problem. To mitigate this, we propose UIS-Digger, a novel multi-agent framework that incorporates dual-mode browsing and enables simultaneous webpage searching and file parsing. With a relatively small $\sim$30B-parameter backbone LLM optimized using SFT and RFT training strategies, UIS-Digger sets a strong baseline at 27.27\%, outperforming systems integrating sophisticated LLMs such as O3 and GPT-4.1. This demonstrates the importance of proactive interaction with unindexed sources for effective and comprehensive information-seeking. Our work not only uncovers a fundamental limitation in current agent evaluation paradigms but also provides the first toolkit for advancing UIS research, defining a new and promising direction for robust information-seeking systems.
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The Algorithmic Gaze of Image Quality Assessment: An Audit and Trace Ethnography of the LAION-Aesthetics Predictor

✇cs.AI, q-bio.NC updates on arXiv.org
By: Jordan Taylor · William Agnew · Maarten Sap · Sarah E. Fox · Haiyi Zhu
arXiv:2601.09896v3 Announce Type: replace-cross Abstract: Visual generative AI models are trained using a one-size-fits-all measure of aesthetic appeal. However, what is deemed "aesthetic" is inextricably linked to personal taste and cultural values, raising the question of whose taste is represented in visual generative AI models. In this work, we study an aesthetic evaluation model--LAION-Aesthetics Predictor (LAP)--that is widely used to curate datasets to train visual generative image models, like Stable Diffusion, and evaluate the quality of AI-generated images. To understand what LAP measures, we audited the model across three datasets. First, we examined the impact of aesthetic filtering on the LAION-Aesthetics Dataset (approximately 1.2B images), which was curated from LAION-5B using LAP. We find that the LAP disproportionally filters in images with captions mentioning women, while filtering out images with captions mentioning men or LGBTQ+ people. Then, we used LAP to score approximately 330k images across two art datasets, finding the model rates realistic images of landscapes, cityscapes, and portraits from western and Japanese artists most highly. In doing so, the algorithmic gaze of this aesthetic evaluation model reinforces the imperial and male gazes found within western art history. In order to understand where these biases may have originated, we performed a digital ethnography of public materials related to the creation of LAP. We find that the development of LAP reflects the biases we found in our audits, such as the aesthetic scores used to train LAP primarily coming from English-speaking photographers and western AI-enthusiasts. In response, we discuss how aesthetic evaluation can perpetuate representational harms and call on AI developers to shift away from prescriptive measures of "aesthetics" toward more pluralistic evaluation.
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ShareVerse: Multi-Agent Consistent Video Generation for Shared World Modeling

✇cs.AI, q-bio.NC updates on arXiv.org
By: Jiayi Zhu · Jianing Zhang · Yiying Yang · Wei Cheng · Xiaoyun Yuan
arXiv:2603.02697v1 Announce Type: cross Abstract: This paper presents ShareVerse, a video generation framework enabling multi-agent shared world modeling, addressing the gap in existing works that lack support for unified shared world construction with multi-agent interaction. ShareVerse leverages the generation capability of large video models and integrates three key innovations: 1) A dataset for large-scale multi-agent interactive world modeling is built on the CARLA simulation platform, featuring diverse scenes, weather conditions, and interactive trajectories with paired multi-view videos (front/ rear/ left/ right views per agent) and camera data. 2) We propose a spatial concatenation strategy for four-view videos of independent agents to model a broader environment and to ensure internal multi-view geometric consistency. 3) We integrate cross-agent attention blocks into the pretrained video model, which enable interactive transmission of spatial-temporal information across agents, guaranteeing shared world consistency in overlapping regions and reasonable generation in non-overlapping regions. ShareVerse, which supports 49-frame large-scale video generation, accurately perceives the position of dynamic agents and achieves consistent shared world modeling.
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AlphaOPT: Formulating Optimization Programs with Self-Improving LLM Experience Library

✇cs.AI, q-bio.NC updates on arXiv.org
By: Minwei Kong · Ao Qu · Xiaotong Guo · Wenbin Ouyang · Chonghe Jiang · Han Zheng · Yining Ma · Dingyi Zhuang · Yuhan Tang · Junyi Li · Shenhao Wang · Haris Koutsopoulos · Hai Wang · Cathy Wu · Jinhua Zhao
arXiv:2510.18428v3 Announce Type: replace Abstract: Optimization modeling underlies critical decision-making across industries, yet remains difficult to automate: natural-language problem descriptions must be translated into precise mathematical formulations and executable solver code. Existing LLM-based approaches typically rely on brittle prompting or costly retraining, both of which offer limited generalization. Recent work suggests that large models can improve via experience reuse, but how to systematically acquire, refine, and reuse such experience in structurally constrained settings remains unclear. We present \textbf{AlphaOPT}, a self-improving experience library that enables LLMs to learn optimization modeling knowledge from limited supervision, including answer-only feedback without gold-standard programs, annotated reasoning traces, or parameter updates. AlphaOPT operates in a continual two-phase cycle: a \emph{Library Learning} phase that extracts solver-verified, structured insights from failed attempts, and a \emph{Library Evolution} phase that refines the applicability of stored insights based on aggregate evidence across tasks. This design allows the model to accumulate reusable modeling principles, improve transfer across problem instances, and maintain bounded library growth over time. Evaluated on multiple optimization benchmarks, AlphaOPT steadily improves as more training data become available (65\% $\rightarrow$ 72\% from 100 to 300 training items) and outperforms the strongest baseline by 9.1\% and 8.2\% on two out-of-distribution datasets. These results demonstrate that structured experience learning, grounded in solver feedback, provides a practical alternative to retraining for complex reasoning tasks requiring precise formulation and execution. All code and data are available at: https://github.com/Minw913/AlphaOPT.
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