A Non-Canonical Role of SMAD4 in Regulating 3D Genome Architecture to Inhibit Lung Squamous Cell Carcinoma Development

(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)

By: Qian Tang · Chen Lian · Xinyan Han · Xuhan Zhang · Zihan Wang · Boyu Wang · Taoyu Zhu · Xinrui Lin · Xiaolei Wang · Yaping Xu · Manyu Xiao · Zijin Wang · Junming Li · Silin Chen · Yunze Wang · Yufei Liu · Songsong Li · Zuolin Shen · Xi Lu · Xueqi Han · Yilu Zhou · Mingyang Xiao · Jiayi Ran · Xiaoran Cao · Xinyi Xu · Hugo Sámano-Sánchez · Alfredo Rodríguez · Lian Wang · Shuifang Chen · Zhanyu Xu · Shirong Zhang · Nuo Yang · Yong Tang · Jian Liu

26 May 2026 at 18:00

Adv Sci (Weinh). 2026 May 26:e75839. doi: 10.1002/advs.75839. Online ahead of print.

ABSTRACT

Lung squamous cell carcinoma (LUSC) lacks clearly defined key drivers and effective targeted therapies, reflecting an incomplete understanding of its molecular pathogenesis. Here, we identify SMAD4 as a critical regulator of three-dimensional (3D) genome organization in LUSC and uncover a mechanistic link between tumor suppressor loss and oncogenic transcriptional activation. By integrating clinical datasets, genetically engineered mouse models, human and murine LUSC cell lines, and multi-omics analyses, we demonstrate that SMAD4 deficiency promotes LUSC progression by unleashing EP300-mediated enhancer-promoter looping at the SOX2 locus. Mechanistically, SMAD4 does not directly bind SOX2 regulatory elements but instead constrains chromatin looping by sequestering EP300 away from loop anchor regions. Loss of SMAD4 leads to enhanced H3K27ac deposition, aberrant SOX2 activation, and increased LUSC tumor cell proliferation. Together, these findings reveal a non-canonical role for a transcription factor (e.g., SMAD4) in regulating dysregulated 3D genome architecture to inhibit tumor development.

PMID:42189071 | DOI:10.1002/advs.75839

A Non-Canonical Role of SMAD4 in Regulating 3D Genome Architecture to Inhibit Lung Squamous Cell Carcinoma Development

Omics In Lung

By: Qian Tang · Chen Lian · Xinyan Han · Xuhan Zhang · Zihan Wang · Boyu Wang · Taoyu Zhu · Xinrui Lin · Xiaolei Wang · Yaping Xu · Manyu Xiao · Zijin Wang · Junming Li · Silin Chen · Yunze Wang · Yufei Liu · Songsong Li · Zuolin Shen · Xi Lu · Xueqi Han · Yilu Zhou · Mingyang Xiao · Jiayi Ran · Xiaoran Cao · Xinyi Xu · Hugo Sámano-Sánchez · Alfredo Rodríguez · Lian Wang · Shuifang Chen · Zhanyu Xu · Shirong Zhang · Nuo Yang · Yong Tang · Jian Liu

26 May 2026 at 18:00

Adv Sci (Weinh). 2026 May 26:e75839. doi: 10.1002/advs.75839. Online ahead of print.

ABSTRACT

Lung squamous cell carcinoma (LUSC) lacks clearly defined key drivers and effective targeted therapies, reflecting an incomplete understanding of its molecular pathogenesis. Here, we identify SMAD4 as a critical regulator of three-dimensional (3D) genome organization in LUSC and uncover a mechanistic link between tumor suppressor loss and oncogenic transcriptional activation. By integrating clinical datasets, genetically engineered mouse models, human and murine LUSC cell lines, and multi-omics analyses, we demonstrate that SMAD4 deficiency promotes LUSC progression by unleashing EP300-mediated enhancer-promoter looping at the SOX2 locus. Mechanistically, SMAD4 does not directly bind SOX2 regulatory elements but instead constrains chromatin looping by sequestering EP300 away from loop anchor regions. Loss of SMAD4 leads to enhanced H3K27ac deposition, aberrant SOX2 activation, and increased LUSC tumor cell proliferation. Together, these findings reveal a non-canonical role for a transcription factor (e.g., SMAD4) in regulating dysregulated 3D genome architecture to inhibit tumor development.

PMID:42189071 | DOI:10.1002/advs.75839

Equip Pre-ranking with Target Attention by Residual Quantization

cs.AI, q-bio.NC updates on arXiv.org

By: Yutong Li · Yu Zhu · Yichen Qiao · Ziyu Guan · Lv Shao · Tong Liu · Bo Zheng

26 May 2026 at 12:00

arXiv:2509.16931v3 Announce Type: replace-cross Abstract: The pre-ranking stage in industrial recommendation systems faces a fundamental conflict between efficiency and effectiveness. While powerful models like Target Attention (TA) excel at capturing complex feature interactions in the ranking stage, their high computational cost makes them infeasible for pre-ranking, which often relies on simplistic vector-product models. This disparity creates a significant performance bottleneck for the entire system. To bridge this gap, we propose TARQ, a novel pre-ranking framework. Inspired by generative models, TARQ's key innovation is to equip pre-ranking with an architecture approximate to TA by Residual Quantization. This allows us to bring the modeling power of TA into the latency-critical pre-ranking stage for the first time, establishing a new state-of-the-art trade-off between accuracy and efficiency. Extensive offline experiments and large-scale online A/B tests at Taobao demonstrate TARQ's significant improvements in ranking performance. Consequently, our model has been fully deployed in production, serving tens of millions of daily active users and yielding substantial business improvements. The code and data are available at https://github.com/zyody/tarq_sigir2026.

Nonlinear atomic tunnelling boosted by bright squeezed vacuum

Nature - Issue - nature.com science feeds

By: Zhejun Jiang · Shengzhe Pan · Jianqi Chen · Mingyu Zhu · Chenhao Zhao · Yiwen Wang · Ru Zhang · Jianshi Lu · Lulu Han · Suwen Xiong · Dian Wu · Wenxue Li · Shicheng Jiang · Hongcheng Ni · Jian Wu

20 May 2026 at 08:00

Nature, Published online: 20 May 2026; doi:10.1038/s41586-026-10485-9

Bright squeezed vacuum light boosts nonlinear atomic tunnelling ionization more than 20-fold compared with coherent light, enabling quantum control of strong-field processes without increasing classical intensity.

An activated wheat CCG10-NLR immune receptor forms an octameric resistosome

Cell

By: Guanghao Guo · He Zhao · Kaihong Bai · Jian Lu · Qiuhong Wu · Lei Lu · Yue Zhang · Lingli Dong · Guangwei Li · Yongxing Chen · Yikun Hou · Ping Lu · Miaomiao Li · Huaizhi Zhang · Gaojie Wang · Keyu Zhu · Baoge Huang · Xuejia Cui · Hongkui Fu · Chenchen Hu · Zhiying Chu · Xue Lyu · Sophien Kamoun · Chao Wang · Zhiyong Liu · Muniyandi Selvaraj · Jonathan D.G. Jones

20 March 2026 at 08:00

An activated CCG10-NLR WAI3 plant immune receptor forms an octameric resistosome, which induces calcium influx and immune responses through a unique channel architecture.

RaPA: Enhancing Transferable Targeted Attacks via Random Parameter Pruning

cs.AI, q-bio.NC updates on arXiv.org

By: Tongrui Su · Qingbin Li · Shengyu Zhu · Wei Chen · Xueqi Cheng

7 April 2026 at 12:00

arXiv:2504.18594v3 Announce Type: replace-cross Abstract: Compared to untargeted attacks, targeted transfer-based attack is still suffering from much lower Attack Success Rates (ASRs), although significant improvements have been achieved by kinds of methods, such as diversifying input, stabilizing the gradient, and re-training surrogate models. In this paper, we find that adversarial examples generated by existing methods rely heavily on a small subset of surrogate model parameters, which in turn limits their transferability to unseen target models. Inspired by this, we propose the Random Parameter Pruning Attack (RaPA), which introduces parameter-level randomization during the attack process. At each optimization step, RaPA randomly prunes model parameters to generate diverse yet semantically consistent surrogate variants.We show this parameter-level randomization is equivalent to adding an importance-equalization regularizer, thereby alleviating the over-reliance issue. Extensive experiments across both CNN and Transformer architectures demonstrate that RaPA substantially enhances transferability. In the challenging case of transferring from CNN-based to Transformer-based models, RaPA achieves up to 11.7% higher average ASRs than state-of-the-art baselines(with 33.3% ASRs), while being training-free, cross-architecture efficient, and easily integrated into existing attack frameworks. Code is available in https://github.com/molarsu/RaPA.

Low-dose intestinal irradiation enhances the efficacy and prognosis of PD-1 blockade in metastatic non-small cell lung cancer

Omics In Lung

By: Baiyang Huang · Jiarui Zhao · Jingyu Zhu · Xingpeng Wang · Min Li · Jing Xu · Kaiyue Wang · Xiaohan Wang · Weiqing Wang · Cong Bo · Jinquan Yao · Menglin Bai · Bo Cheng · Jinming Yu · Guoxin Cai · Xue Meng

18 March 2026 at 18:00

Clin Cancer Res. 2026 Mar 18. doi: 10.1158/1078-0432.CCR-25-4153. Online ahead of print.

ABSTRACT

PURPOSE: Intestinal low-dose irradiation (ILDR) may enhance immunotherapy efficacy by modulating the gut microbiota and metabolism; however, its role in metastatic non-small cell lung cancer (mNSCLC), particularly in the first-line setting, remains unclear.

EXPERIMENTAL DESIGN: This multicenter retrospective and prospective study included mNSCLC patients receiving first- and second-line programmed cell death protein 1 (PD-1) inhibitors along with abdominopelvic radiotherapy between 2018 and 2025. Patients were stratified by the mean intestinal radiation dose into <1 Gy, 1-3 Gy, and >3 Gy groups and treatment outcomes were compared. The blood and fecal samples were subjected to multi-omics profiling.

RESULTS: g>309 patients were included in the retrospective analysis. Optimal efficacy was observed with a small intestinal mean radiation dose (SIMRD) of 1-3 Gy, showing longer progression-free survival (PFS, 10.2 months) and overall survival (OS, 22.8 months) (P < 0.01), which was consistent across subgroups. Compared with 1-3 Gy, SIMRD >3 Gy (Hazard ratio [HR] = 4.87, P < 0.001) and <1 Gy (HR = 1.85, P < 0.001) independently predicted worse OS. Prospective results confirmed the best disease control rate (P = 0.041) and PFS (P = 0.046) with SIMRD of 1-3 Gy. Responders were enriched in Bacillota, Clostridia, and indole derivatives, particularly indole-3-carboxylic acid. Moreover, the 1-3 Gy group exhibited increased circulating macrophage inflammatory protein-3α and reduced circulating α4β7+ regulatory T cells.

CONCLUSIONS: ILDR influences the efficacy of PD-1 blockade in patients with mNSCLC, particularly when SIMRD is maintained within the 1-3 Gy range, likely through modulation of the gut microbiota-metabolite-immune axis.

PMID:41849236 | DOI:10.1158/1078-0432.CCR-25-4153

Contextual Drag: How Errors in the Context Affect LLM Reasoning

cs.AI, q-bio.NC updates on arXiv.org

By: Yun Cheng · Xingyu Zhu · Haoyu Zhao · Sanjeev Arora

4 March 2026 at 13:00

arXiv:2602.04288v2 Announce Type: replace-cross Abstract: Central to many self-improvement pipelines for large language models (LLMs) is the assumption that models can improve by reflecting on past mistakes. We study a phenomenon termed contextual drag: the presence of failed attempts in the context biases subsequent generations toward structurally similar errors. Across evaluations of 11 proprietary and open-weight models on 8 reasoning tasks, contextual drag induces 10-20% performance drops, and iterative self-refinement in models with severe contextual drag can collapse into self-deterioration. Structural analysis using tree edit distance reveals that subsequent reasoning trajectories inherit structurally similar error patterns from the context. We demonstrate that neither external feedback nor successful self-verification suffices to eliminate this effect. While mitigation strategies such as fallback-behavior fine-tuning and context denoising yield partial improvements, they fail to fully restore baseline performance, positioning contextual drag as a persistent failure mode in current reasoning architectures.

MolReasoner: Toward Effective and Interpretable Reasoning for Molecular LLMs

cs.AI, q-bio.NC updates on arXiv.org

By: Guojiang Zhao · Zixiang Lu · Yutang Ge · Sihang Li · Zheng Cheng · Haitao Lin · Lirong Wu · Hanchen Xia · Hengxing Cai · Wentao Guo · Hongshuai Wang · Mingjun Xu · Siyu Zhu · Guolin Ke · Linfeng Zhang · Zhifeng Gao

24 February 2026 at 13:00

arXiv:2508.02066v2 Announce Type: replace-cross Abstract: Large Language Models (LLMs) have shown impressive performance across various domains, but their ability to perform molecular reasoning remains underexplored. Existing methods mostly rely on general-purpose prompting, which lacks domain-specific molecular semantics, or fine-tuning, which faces challenges in interpretability and reasoning depth, often leading to structural and textual hallucinations. To address these issues, we introduce MolReasoner, a two-stage framework that transitions LLMs from memorization to high-fidelity chemical reasoning. In the Mol-SFT stage, knowledge-enhanced Chain-of-Thought (CoT) data provides a strong foundation, while the Mol-RL stage refines reasoning using a novel, task-adaptive reward system to mitigate hallucinations. Extensive evaluations demonstrate that MolReasoner significantly outperforms a wide range of strong baselines in both molecule generation and captioning tasks. Further analyses highlight the framework's synergistic design and its ability to produce more interpretable outputs. Our work presents a principled and effective new approach for advancing high-fidelity molecular reasoning.

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