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Received today — 7 October 2026 ⏭

GPAT3 protects against lipid stress-induced ferroptosis in hepatocellular carcinoma: From multi-omics analysis to functional validation

✇Omics in Hepatocellular
By: Yongqing Zhao · Jian Yang · Weixiong Zhu · Guoqing Zhang · Shaozhen Rui · Teng Ma · Zhao Guo · Wence Zhou
24 September 2026 at 18:00

Biochim Biophys Acta Mol Basis Dis. 2027 Jan;1873(1):168471. doi: 10.1016/j.bbadis.2026.168471. Epub 2026 Sep 24.

ABSTRACT

BACKGROUND: The global burden of metabolic-associated hepatocellular carcinoma (HCC) is increasing, with obesity emerging as a key causal factor. However, the molecular mechanisms linking lipid metabolic dysregulation to HCC progression and therapeutic vulnerability remain unclear.

METHODS: We analyzed Global Burden of Disease 2021 data to assess liver cancer burden attributable to metabolic risks from 1990 to 2021. Mendelian randomization was used to evaluate causal associations between metabolic traits and liver cancer risk. TCGA, GTEx, and GEO datasets were integrated to identify lipid stress-responsive regulators. Clinical relevance was assessed using public datasets and tissue microarray immunohistochemistry. Functional validation was performed in HCC cells and a high-fat diet-fed syngeneic mouse tumor model.

RESULTS: Liver cancer deaths and DALYs attributable to metabolic risks increased markedly from 1990 to 2021. Mendelian randomization showed that obesity-related traits, including BMI, waist circumference, and body fat percentage, were causally associated with liver cancer risk, whereas glycemic traits were not. Bioinformatics screening identified GPAT3 as a lipid metabolism regulator upregulated in HCC, induced by palmitic acid, associated with poor prognosis, and enriched in patients with higher BMI. Tissue microarray analysis confirmed increased GPAT3 protein expression in HCC and its association with higher BMI and GPX4 expression. GPAT3 depletion sensitized HCC cells to palmitic acid-induced ferroptosis, whereas Fer-1 rescue and GPAT3 overexpression supported its protective role. In vivo, FSG67 enhanced sorafenib-associated antitumor effects and increased tumor lipid peroxidation.

CONCLUSIONS: GPAT3 protects HCC cells from lipid stress-induced ferroptosis and represents a potential metabolic vulnerability in obesity-associated HCC.

PMID:42785105 | DOI:10.1016/j.bbadis.2026.168471

GPAT3 protects against lipid stress-induced ferroptosis in hepatocellular carcinoma: From multi-omics analysis to functional validation

✇(Multiomics OR Omics) AND (Pancreatic)
By: Yongqing Zhao · Jian Yang · Weixiong Zhu · Guoqing Zhang · Shaozhen Rui · Teng Ma · Zhao Guo · Wence Zhou
24 September 2026 at 18:00

Biochim Biophys Acta Mol Basis Dis. 2027 Jan;1873(1):168471. doi: 10.1016/j.bbadis.2026.168471. Epub 2026 Sep 24.

ABSTRACT

BACKGROUND: The global burden of metabolic-associated hepatocellular carcinoma (HCC) is increasing, with obesity emerging as a key causal factor. However, the molecular mechanisms linking lipid metabolic dysregulation to HCC progression and therapeutic vulnerability remain unclear.

METHODS: We analyzed Global Burden of Disease 2021 data to assess liver cancer burden attributable to metabolic risks from 1990 to 2021. Mendelian randomization was used to evaluate causal associations between metabolic traits and liver cancer risk. TCGA, GTEx, and GEO datasets were integrated to identify lipid stress-responsive regulators. Clinical relevance was assessed using public datasets and tissue microarray immunohistochemistry. Functional validation was performed in HCC cells and a high-fat diet-fed syngeneic mouse tumor model.

RESULTS: Liver cancer deaths and DALYs attributable to metabolic risks increased markedly from 1990 to 2021. Mendelian randomization showed that obesity-related traits, including BMI, waist circumference, and body fat percentage, were causally associated with liver cancer risk, whereas glycemic traits were not. Bioinformatics screening identified GPAT3 as a lipid metabolism regulator upregulated in HCC, induced by palmitic acid, associated with poor prognosis, and enriched in patients with higher BMI. Tissue microarray analysis confirmed increased GPAT3 protein expression in HCC and its association with higher BMI and GPX4 expression. GPAT3 depletion sensitized HCC cells to palmitic acid-induced ferroptosis, whereas Fer-1 rescue and GPAT3 overexpression supported its protective role. In vivo, FSG67 enhanced sorafenib-associated antitumor effects and increased tumor lipid peroxidation.

CONCLUSIONS: GPAT3 protects HCC cells from lipid stress-induced ferroptosis and represents a potential metabolic vulnerability in obesity-associated HCC.

PMID:42785105 | DOI:10.1016/j.bbadis.2026.168471

Received — 18 September 2026 ⏭

FOXD3 Is Functionally Linked to NF-κB Signaling in KRAS G12C-Mutant NSCLC Cells

✇(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)
By: Pengzhen Xu · Jie Peng · Chao Guo · Zhu Liu · Yufeng Cao · Qing Sheng · Wenfei Xu · Xuhui Li
15 September 2026 at 18:00

Cells. 2026 Aug 28;15(17):1564. doi: 10.3390/cells15171564.

ABSTRACT

KRAS G12C mutation is a clinically relevant driver in non-small cell lung cancer (NSCLC), yet the signaling networks that modulate malignant behavior in this context remain incompletely defined. In this study, we examined the functional role of FOXD3 and its relationship with NF-κB signaling in KRAS G12C-mutant NSCLC models. Stable FOXD3 overexpression was established in SW1573 and LU65 cells. FOXD3 reduced cell viability, migration, and invasion while increasing caspase 3/7 activity in both cell lines. Transcriptomic profiling in LU65 cells followed by Hallmark enrichment analysis identified TNFα signaling via NF-κB as a prominently altered pathway associated with FOXD3 overexpression. Consistently, NF-κB dual-luciferase assays showed reduced basal NF-κB transcriptional activity in FOXD3-overexpressing cells. TNFα stimulation partially reversed the inhibitory effects of FOXD3 on proliferation, migration, and invasion and attenuated FOXD3-induced apoptosis. In addition, stable FOXD3 overexpression suppressed xenograft growth in vivo. Collectively, these findings support a functional association between FOXD3 overexpression and reduced NF-κB-related transcriptional activity in KRAS G12C-mutant NSCLC models, although the present data do not establish direct causal mediation by NF-κB.

PMID:42738858 | PMC:PMC13564895 | DOI:10.3390/cells15171564

Received — 15 September 2026 ⏭

Mr.LHDR: A Benchmark for Multimodal Real-World Long-Horizon Deep Research Agents

✇cs.AI, q-bio.NC updates on arXiv.org
By: Minghao Guo · Meng Cao · Sui Zhao · Siyu Ning · Xin Wang · Haoze Zhao · Jiaxuan Yang · Haihong Hao · Mingfei Han · Shunlin Rong · Haijun Wu · Xiaodan Liang · Xiaojun Chang
14 September 2026 at 12:00
arXiv:2609.11318v2 Announce Type: replace Abstract: Deep research agents are increasingly capable of web search, tool use, multimodal evidence analysis, and information synthesis. However, existing benchmarks mainly evaluate medium-horizon exploration and rarely test whether agents can sustain long, dependency-heavy research processes. We introduce Mr. LHDR (Multimodal real-world Long-Horizon Deep Research), a benchmark for evaluating real-world deep research over long, irreducible chains of interdependent evidence across eight categories. Each question is constructed from a hidden Node-Relation graph and requires an average of 12.1 necessary intermediate conclusions with a mean dependency depth of 10.4 before reaching a short, unique, and verifiable answer. Questions incorporate multimodal evidence, including images, maps, PDFs, logos, charts, tables, and video frames, with at least one non-text element that changes the reasoning state. Mr. LHDR evaluates both final answers and the correctness of intermediate conclusions under annotated dependencies. We evaluate general models, deep research systems, and agent frameworks using Overall Accuracy (OA), Strict Accuracy (SA), Checklist Score (CS), and Dependency-Aware Checklist Score (DACS). Results show that even the strongest system achieves only 43.1% OA and 34.3% SA, indicating that final-answer accuracy substantially overestimates complete research success. Removing images reduces DACS by 12.6 points, demonstrating the importance of multimodal evidence, while SA consistently declines as reasoning chains become longer. These findings reveal sustained, dependency-consistent evidence integration, rather than isolated fact retrieval, as a key bottleneck for current deep research agents.
Received — 27 May 2026 ⏭

Beyond Inference-Only Deployment: Comparing Weight-Based Consolidation Against Cascading Compaction

✇cs.AI, q-bio.NC updates on arXiv.org
By: Simon Dennis · Kevin Shabahang · Hao Guo · Rivaan Patil
26 May 2026 at 12:00
arXiv:2605.24657v1 Announce Type: new Abstract: Major LLM platforms deploy models in an inference-only configuration: the model serves requests but never updates per-user weights. Users must repeatedly re-teach preferences, corrections, and project context, and context-based workarounds consume context-window space and degrade under cascading compaction. We evaluate an alternative: nightly consolidation of interaction knowledge into model weights via reflection, synthesis, and Low-Rank Adaptation (LoRA) fine-tuning on a single consumer GPU. Across ten realistic software development conversations (n = 10, 1,146 test questions across three memory types), three cycles of cascading compaction retain 36.8 +/- 3.0% of knowledge (between an 11.8% no-context floor and a 90.1% full-context ceiling), while consolidation retains 80.4 +/- 1.3% -- a 43.6 pp gain (paired t(9) = 14.8, p 74.6%) and episodic project facts (31.5% -> 78.2%). As a methodological aside, mean per-token validation cross-entropy is negatively correlated with LLM-judged accuracy (r = -0.51) while median per-token validation cross-entropy tracks accuracy almost exactly (r = +0.99): under evaluators that tolerate surface-form variation, the mean is misleading and a heavy-tail-robust statistic is the faithful signal. Persistent personalization requires moving beyond inference-only deployment toward architectures that consolidate knowledge into weights.

When Mean CE Fails: Median CE Can Better Track Language Model Quality

✇cs.AI, q-bio.NC updates on arXiv.org
By: Hao Guo · Simon Dennis · Rivaan Patil · Kevin Shabahang
26 May 2026 at 12:00
arXiv:2605.24667v1 Announce Type: new Abstract: Mean cross-entropy is the standard validation metric for language models, but it can fail to track model quality during training. We examine this in two common scenarios. First, in Qwen2.5-1.5B SFT on synthetic fact-learning, we find that mean CE rises substantially after the initial learning phase while held-out fact-recall accuracy remains near its peak. Second, we find that in top-K distillation on TinyStories, decreasing K improves median CE while worsening mean CE; the Top-5 student attains the highest LLM-judge score and crosses below its teacher on median CE, despite having the worst mean CE. In both cases, median CE correlates much more closely with task performance than does mean CE. Analyzing how bulk and tail percentile CE move during training reveals that training reshapes the empirical per-token CE distribution. In top-K distillation, smaller K yields a distribution with more mass at both extremes, decreasing the median and increasing the mean. In Qwen SFT, the bulk saturates quickly while the tail extends in the latter half of training. In both, the task-evaluation metric appears more sensitive to the bulk than to the tail. Practically, we recommend reporting a small set of percentile CE summaries alongside the mean, and using concordance among them as a tool to keep track of distribution reshaping, as well as a low-cost diagnostic for when mean and median CE disagree on model selection.
Received — 4 April 2026 ⏭

KARL: Knowledge-Aware Reasoning and Reinforcement Learning for Knowledge-Intensive Visual Grounding

✇cs.AI, q-bio.NC updates on arXiv.org
By: Xinyu Ma · Ziyang Ding · Zhicong Luo · Chi Chen · Zonghao Guo · Derek F. Wong · Zhen Zhao · Xiaoyi Feng · Maosong Sun
3 April 2026 at 12:00
arXiv:2503.12797v3 Announce Type: replace-cross Abstract: Knowledge-Intensive Visual Grounding (KVG) requires models to localize objects using fine-grained, domain-specific entity names rather than generic referring expressions. Although Multimodal Large Language Models (MLLMs) possess rich entity knowledge and strong generic grounding capabilities, they often fail to effectively utilize such knowledge when grounding specialized concepts, revealing a knowledge-grounding gap between internal knowledge and grounding predictions. To address this challenge, we propose a knowledge-aware training paradigm for KVG. Our approach first constructs knowledge-guided reasoning data to encourage models to activate domain-relevant entity knowledge during grounding, and then introduces KARL, a Knowledge-Aware Reinforcement Learning framework that adaptively modulates reward signals according to the model's estimated knowledge mastery of different entities. To facilitate systematic evaluation, we introduce KVG-Bench, a benchmark spanning 10 domains with 1.3K curated test cases covering 531 images and 882 entities. Extensive experiments show that our approach consistently outperforms a wide range of baseline models and achieves substantially stronger cross-domain generalization on unseen categories. The data, codes, and models are released at https://github.com/thunlp/KARL.
Received — 26 March 2026 ⏭

Graph Structure Learning with Privacy Guarantees for Open Graph Data

✇cs.AI, q-bio.NC updates on arXiv.org
By: Muhao Guo · Jiaqi Wu · Yizheng Liao · Wenke Lee · Shengzhe Chen · Yang Weng
25 March 2026 at 12:00
arXiv:2507.19116v3 Announce Type: replace-cross Abstract: Publishing open graph data while preserving individual privacy remains challenging when data publishers and data users are distinct entities. Although differential privacy (DP) provides rigorous guarantees, most existing approaches enforce privacy during model training rather than at the data publishing stage. This limits the applicability to open-data scenarios. We propose a privacy-preserving graph structure learning framework that integrates Gaussian Differential Privacy (GDP) directly into the data release process. Our mechanism injects structured Gaussian noise into raw data prior to publication and provides formal $\mu$-GDP guarantees, leading to tight $(\varepsilon, \delta)$-differential privacy bounds. Despite the distortion introduced by privatization, we prove that the original sparse inverse covariance structure can be recovered through an unbiased penalized likelihood formulation. We further extend the framework to discrete data using discrete Gaussian noise while preserving privacy guarantees. Extensive experiments on synthetic and real-world datasets demonstrate strong privacy-utility trade-offs, maintaining high graph recovery accuracy under rigorous privacy budgets. Our results establish a formal connection between differential privacy theory and privacy-preserving data publishing for graphical models.
Received — 17 March 2026 ⏭

Cheers: Decoupling Patch Details from Semantic Representations Enables Unified Multimodal Comprehension and Generation

✇cs.AI, q-bio.NC updates on arXiv.org
By: Yichen Zhang · Da Peng · Zonghao Guo · Zijian Zhang · Xuesong Yang · Tong Sun · Shichu Sun · Yidan Zhang · Yanghao Li · Haiyan Zhao · Wang Xu · Qi Shi · Yangang Sun · Chi Chen · Shuo Wang · Yukun Yan · Xu Han · Qiang Ma · Wei Ke · Liang Wang · Zhiyuan Liu · Maosong Sun
16 March 2026 at 12:00
arXiv:2603.12793v1 Announce Type: cross Abstract: A recent cutting-edge topic in multimodal modeling is to unify visual comprehension and generation within a single model. However, the two tasks demand mismatched decoding regimes and visual representations, making it non-trivial to jointly optimize within a shared feature space. In this work, we present Cheers, a unified multimodal model that decouples patch-level details from semantic representations, thereby stabilizing semantics for multimodal understanding and improving fidelity for image generation via gated detail residuals. Cheers includes three key components: (i) a unified vision tokenizer that encodes and compresses image latent states into semantic tokens for efficient LLM conditioning, (ii) an LLM-based Transformer that unifies autoregressive decoding for text generation and diffusion decoding for image generation, and (iii) a cascaded flow matching head that decodes visual semantics first and then injects semantically gated detail residuals from the vision tokenizer to refine high-frequency content. Experiments on popular benchmarks demonstrate that Cheers matches or surpasses advanced UMMs in both visual understanding and generation. Cheers also achieves 4x token compression, enabling more efficient high-resolution image encoding and generation. Notably, Cheers outperforms the Tar-1.5B on the popular benchmarks GenEval and MMBench, while requiring only 20% of the training cost, indicating effective and efficient (i.e., 4x token compression) unified multimodal modeling. We will release all code and data for future research.
Received — 11 March 2026 ⏭

Tree-based Dialogue Reinforced Policy Optimization for Red-Teaming Attacks

✇cs.AI, q-bio.NC updates on arXiv.org
By: Ruohao Guo · Afshin Oroojlooy · Roshan Sridhar · Miguel Ballesteros · Alan Ritter · Dan Roth
10 March 2026 at 12:00
arXiv:2510.02286v2 Announce Type: replace-cross Abstract: Despite recent rapid progress in AI safety, current large language models remain vulnerable to adversarial attacks in multi-turn interaction settings, where attackers strategically adapt their prompts across conversation turns and pose a more critical yet realistic challenge. Existing approaches that discover safety vulnerabilities either rely on manual red-teaming with human experts or employ automated methods using pre-defined templates and human-curated attack data, with most focusing on single-turn attacks. However, these methods did not explore the vast space of possible multi-turn attacks, failing to consider novel attack trajectories that emerge from complex dialogue dynamics and strategic conversation planning. This gap is particularly critical given recent findings that LLMs exhibit significantly higher vulnerability to multi-turn attacks compared to single-turn attacks. We propose DialTree, an on-policy reinforcement learning framework integrated with tree search that autonomously discovers diverse multi-turn attack strategies by treating the dialogue as a sequential decision-making problem, enabling systematic exploration without manually curated data. Through extensive experiments, our approach not only achieves more than 44.2% higher ASR across 12 target models compared to previous state-of-the-art approaches, but also effectively uncovers new attack strategies by learning optimal dialogue policies that maximize attack success across multiple turns.

Bee: A High-Quality Corpus and Full-Stack Suite to Unlock Advanced Fully Open MLLMs

✇cs.AI, q-bio.NC updates on arXiv.org
By: Yi Zhang · Bolin Ni · Xin-Sheng Chen · Heng-Rui Zhang · Yongming Rao · Houwen Peng · Qinglin Lu · Han Hu · Meng-Hao Guo · Shi-Min Hu
10 March 2026 at 12:00
arXiv:2510.13795v4 Announce Type: replace-cross Abstract: Fully open multimodal large language models (MLLMs) currently lag behind proprietary counterparts, primarily due to a significant gap in data quality for supervised fine-tuning (SFT). Existing open-source datasets are often plagued by widespread noise and a critical deficit in complex reasoning data, such as Chain-of-Thought (CoT), which hinders the development of advanced model capabilities. Addressing these challenges, our work makes three primary contributions. First, we introduce Honey-Data-15M, a new SFT dataset comprising approximately 15 million QA pairs, processed through multiple cleaning techniques and enhanced with a novel dual-level (short and long) CoT enrichment strategy. Second, we introduce HoneyPipe, the data curation pipeline, and its underlying framework DataStudio, providing the community with a transparent and adaptable methodology for data curation that moves beyond static dataset releases. Finally, to validate our dataset and pipeline, we train Bee-8B, an 8B model on Honey-Data-15M. Experiments show that Bee-8B establishes a new state-of-the-art (SOTA) for fully open MLLMs, achieving performance that is competitive with, and in some cases surpasses, recent semi-open models such as InternVL3.5-8B. Our work delivers to the community a suite of foundational resources, including: the Honey-Data-15M corpus; the full-stack suite comprising HoneyPipe and DataStudio; training recipes; an evaluation harness; and the model weights. This effort demonstrates that a principled focus on data quality is a key pathway to developing fully open MLLMs that are highly competitive with their semi-open counterparts.
Received — 5 March 2026 ⏭

When Relevance Meets Novelty: Dual-Stable Periodic Optimization for Serendipitous Recommendation

✇cs.AI, q-bio.NC updates on arXiv.org
By: Hongxiang Lin · Hao Guo · Zeshun Li · Erpeng Xue · Yongqian He · Zhaoyu Hu · Lei Wang · Sheng Chen · Long Zeng
5 March 2026 at 13:00
arXiv:2508.00450v3 Announce Type: replace-cross Abstract: Traditional recommendation systems tend to trap users in strong feedback loops by excessively pushing content aligned with their historical preferences, thereby limiting exploration opportunities and causing content fatigue. Although large language models (LLMs) demonstrate potential with their diverse content generation capabilities, existing LLM-enhanced dual-model frameworks face two major limitations: first, they overlook long-term preferences driven by group identity, leading to biased interest modeling; second, they suffer from static optimization flaws, as a one-time alignment process fails to leverage incremental user data for closed-loop optimization. To address these challenges, we propose the Co-Evolutionary Alignment (CoEA) method. For interest modeling bias, we introduce Dual-Stable Interest Exploration (DSIE) module, jointly modeling long-term group identity and short-term individual interests through parallel processing of behavioral sequences. For static optimization limitations, we design a Periodic Collaborative Optimization (PCO) mechanism. This mechanism regularly conducts preference verification on incremental data using the Relevance LLM, then guides the Novelty LLM to perform fine-tuning based on the verification results, and subsequently feeds back the output of the continually fine-tuned Novelty LLM to the Relevance LLM for re-evaluation, thereby achieving a dynamic closed-loop optimization. Extensive online and offline experiments verify the effectiveness of the CoEA model in serendipitous recommendation.
Received — 17 February 2026 ⏭

PhyScensis: Physics-Augmented LLM Agents for Complex Physical Scene Arrangement

✇cs.AI, q-bio.NC updates on arXiv.org
By: Yian Wang · Han Yang · Minghao Guo · Xiaowen Qiu · Tsun-Hsuan Wang · Wojciech Matusik · Joshua B. Tenenbaum · Chuang Gan
17 February 2026 at 13:00
arXiv:2602.14968v1 Announce Type: cross Abstract: Automatically generating interactive 3D environments is crucial for scaling up robotic data collection in simulation. While prior work has primarily focused on 3D asset placement, it often overlooks the physical relationships between objects (e.g., contact, support, balance, and containment), which are essential for creating complex and realistic manipulation scenarios such as tabletop arrangements, shelf organization, or box packing. Compared to classical 3D layout generation, producing complex physical scenes introduces additional challenges: (a) higher object density and complexity (e.g., a small shelf may hold dozens of books), (b) richer supporting relationships and compact spatial layouts, and (c) the need to accurately model both spatial placement and physical properties. To address these challenges, we propose PhyScensis, an LLM agent-based framework powered by a physics engine, to produce physically plausible scene configurations with high complexity. Specifically, our framework consists of three main components: an LLM agent iteratively proposes assets with spatial and physical predicates; a solver, equipped with a physics engine, realizes these predicates into a 3D scene; and feedback from the solver informs the agent to refine and enrich the configuration. Moreover, our framework preserves strong controllability over fine-grained textual descriptions and numerical parameters (e.g., relative positions, scene stability), enabled through probabilistic programming for stability and a complementary heuristic that jointly regulates stability and spatial relations. Experimental results show that our method outperforms prior approaches in scene complexity, visual quality, and physical accuracy, offering a unified pipeline for generating complex physical scene layouts for robotic manipulation.
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