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Received — 27 May 2026 ⏭

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

Kolmogorov-Arnold Fourier Networks

✇cs.AI, q-bio.NC updates on arXiv.org
By: Jusheng Zhang · Yijia Fan · Kaitong Cai · Keze Wang · Wenhao Wang
26 May 2026 at 12:00
arXiv:2502.06018v3 Announce Type: replace-cross Abstract: Although Kolmogorov-Arnold-based interpretable networks (KANs) possess strong theoretical expressiveness, they suffer from severe parameter explosion and limited ability to capture high-frequency features in high-dimensional tasks. To address these issues, we propose the Kolmogorov-Arnold Fourier Network (KAF), which fundamentally redefines the KAN paradigm through spectral reparameterization. Our key contributions include: (1) proposing a fundamental basis transformation from the local, grid-based B-spline representation to a global, adaptive spectral representation. This shift changes the network's inductive bias, reducing parameter complexity from $O(G)$ to $O(1)$ while preserving expressiveness; (2) introducing trainable Random Fourier Features (RFF) initialized via a spectral alignment strategy, which allows the model to break the smoothness limitation of fixed kernels and accurately capture high-frequency components; and (3) implementing an adaptive hybrid GELU-Fourier activation mechanism that progressively enhances frequency representation during training. Comprehensive experiments demonstrate the superiority of KAF across computer vision (CV), natural language processing (NLP), audio, and partial differential equation (PDE) solving tasks, achieving state-of-the-art performance with improved efficiency. The code is available at https://github.com/kolmogorovArnoldFourierNetwork/KAF.

Activation of methionine metabolism mediated by HNF4α confers ferroptosis resistance in hepatocellular carcinoma

✇Cell Death Discovery nature.com science feeds
By: Xiaolei Zhou · Zhenzhen Li · Libo Wang · Yongdeng Xu · Pinsheng Han · TianYu Zhao · Sen Liu · Liuyang Zhu · Miao Zhang · Chenglong Chu · Xiulin Yi · Fengying Yan · Tao Cui · Xiaoliang Wang · Ze Wang
26 May 2026 at 08:00

Cell Death Discovery, Published online: 26 May 2026; doi:10.1038/s41420-026-03165-0

Activation of methionine metabolism mediated by HNF4α confers ferroptosis resistance in hepatocellular carcinoma

CD300ld on pathologically activated neutrophils promotes tumor immune suppression by binding phosphatidylserine on CD8<sup>+</sup> T cells

✇Nature Cancer
By: Chaoxiong Wang · Peixuan Zheng · Anhui Wang · Xinrui Fan · Tianxiang Li · Jingjing Hong · Runze Wang · Chunyan Zhang · Chaogui Luo · Weiwei Yang · Dong Gao · Adili Salai · Min Luo · Zhigang Lu · Dianfan Li · Moubin Lin · Jiayin Peng · Guohui Li · Shuo Han · Yun Zhao
15 May 2026 at 08:00

Nature Cancer, Published online: 15 May 2026; doi:10.1038/s43018-026-01169-4

Zhao and colleagues show that CD300ld, upregulated in pathologically activated neutrophils, mediates contact-dependent suppression of cytotoxic CD8+ T cells by binding to phosphatidylserine, inhibiting antitumor immune responses.
Received — 8 April 2026 ⏭

XModBench: Benchmarking Cross-Modal Capabilities and Consistency in Omni-Language Models

✇cs.AI, q-bio.NC updates on arXiv.org
By: Xingrui Wang · Jiang Liu · Chao Huang · Xiaodong Yu · Ze Wang · Ximeng Sun · Jialian Wu · Alan Yuille · Emad Barsoum · Zicheng Liu
7 April 2026 at 12:00
arXiv:2510.15148v2 Announce Type: replace-cross Abstract: Omni-modal large language models (OLLMs) aim to unify audio, vision, and text understanding within a single framework. While existing benchmarks primarily evaluate general cross-modal question-answering ability, it remains unclear whether OLLMs achieve modality-invariant reasoning or exhibit modality-specific biases. We introduce XModBench, a large-scale tri-modal benchmark explicitly designed to measure cross-modal consistency. XModBench comprises 60,828 multiple-choice questions spanning five task families and systematically covers all six modality compositions in question-answer pairs, enabling fine-grained diagnosis of an OLLM's modality-invariant reasoning, modality disparity, and directional imbalance. Experiments show that even the strongest model, Gemini 2.5 Pro, (i) struggles with spatial and temporal reasoning, achieving less than 60% accuracy, (ii) reveals persistent modality disparities, with performance dropping substantially when the same semantic content is conveyed through audio rather than text, and (iii) shows systematic directional imbalance, exhibiting lower consistency when vision serves as context compared to text. These findings indicate that current OLLMs remain far from truly modality-invariant reasoning and position XModBench as a fundamental diagnostic tool for evaluating and improving cross-modal competence. All data and evaluation tools will be available at https://xingruiwang.github.io/projects/XModBench/.
Received — 17 March 2026 ⏭

FastDSAC: Unlocking the Potential of Maximum Entropy RL in High-Dimensional Humanoid Control

✇cs.AI, q-bio.NC updates on arXiv.org
By: Jun Xue · Junze Wang · Xinming Zhang · Shanze Wang · Yanjun Chen · Wei Zhang
16 March 2026 at 12:00
arXiv:2603.12612v1 Announce Type: cross Abstract: Scaling Maximum Entropy Reinforcement Learning (RL) to high-dimensional humanoid control remains a formidable challenge, as the ``curse of dimensionality'' induces severe exploration inefficiency and training instability in expansive action spaces. Consequently, recent high-throughput paradigms have largely converged on deterministic policy gradients combined with massive parallel simulation. We challenge this compromise with FastDSAC, a framework that effectively unlocks the potential of maximum entropy stochastic policies for complex continuous control. We introduce Dimension-wise Entropy Modulation (DEM) to dynamically redistribute the exploration budget and enforce diversity, alongside a continuous distributional critic tailored to ensure value fidelity and mitigate high-dimensional value overestimation. Extensive evaluations on HumanoidBench and other continuous control tasks demonstrate that rigorously designed stochastic policies can consistently match or outperform deterministic baselines, achieving notable gains of 180\% and 400\% on the challenging \textit{Basketball} and \textit{Balance Hard} tasks.
Received — 11 March 2026 ⏭

DreamSAC: Learning Hamiltonian World Models via Symmetry Exploration

✇cs.AI, q-bio.NC updates on arXiv.org
By: Jinzhou Tang · Fan Feng · Minghao Fu · Wenjun Lin · Biwei Huang · Keze Wang
10 March 2026 at 12:00
arXiv:2603.07545v1 Announce Type: cross Abstract: Learned world models excel at interpolative generalization but fail at extrapolative generalization to novel physical properties. This limitation arises because they learn statistical correlations rather than the environment's underlying generative rules, such as physical invariances and conservation laws. We argue that learning these invariances is key to robust extrapolation. To achieve this, we first introduce \textbf{Symmetry Exploration}, an unsupervised exploration strategy where an agent is intrinsically motivated by a Hamiltonian-based curiosity bonus to actively probe and challenge its understanding of conservation laws, thereby collecting physically informative data. Second, we design a Hamiltonian-based world model that learns from the collected data, using a novel self-supervised contrastive objective to identify the invariant physical state from raw, view-dependent pixel observations. Our framework, \textbf{DreamSAC}, trained on this actively curated data, significantly outperforms state-of-the-art baselines in 3D physics simulations on tasks requiring extrapolation.
Received — 17 February 2026 ⏭

Top-Down Semantic Refinement for Image Captioning

✇cs.AI, q-bio.NC updates on arXiv.org
By: Jusheng Zhang · Kaitong Cai · Jing Yang · Jian Wang · Chengpei Tang · Keze Wang
17 February 2026 at 13:00
arXiv:2510.22391v2 Announce Type: replace-cross Abstract: Large Vision-Language Models (VLMs) face an inherent contradiction in image captioning: their powerful single-step generation capabilities often lead to a myopic decision-making process. This makes it difficult to maintain global narrative coherence while capturing rich details, a limitation that is particularly pronounced in tasks that require multi-step and complex scene description. To overcome this fundamental challenge, we redefine image captioning as a goal-oriented hierarchical refinement planning problem, and further propose a novel framework, named Top-Down Semantic Refinement (TDSR), which models the generation process as a Markov Decision Process (MDP). However, planning within the vast state space of a VLM presents a significant computational hurdle. Our core contribution, therefore, is the design of a highly efficient Monte Carlo Tree Search (MCTS) algorithm tailored for VLMs. By incorporating a visual-guided parallel expansion and a lightweight value network, our TDSR reduces the call frequency to the expensive VLM by an order of magnitude without sacrificing planning quality. Furthermore, an adaptive early stopping mechanism dynamically matches computational overhead to the image's complexity. Extensive experiments on multiple benchmarks, including DetailCaps, COMPOSITIONCAP, and POPE, demonstrate that our TDSR, as a plug-and-play module, can significantly enhance the performance of existing VLMs (e.g., LLaVA-1.5, Qwen2.5-VL) by achieving state-of-the-art or highly competitive results in fine-grained description, compositional generalization, and hallucination suppression.
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