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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

EchoDistill:Alignment Noisy-to-Clean Self-Distillation for Robust Audio LLMs

✇cs.AI, q-bio.NC updates on arXiv.org
By: Liang Lin · Chunxi Luo · Kaiwen Luo · Jie Zhang · Jin Wang · Yuanhe Zhang · Cai Yuchen · Qiankun Li · Gongli Xi · Zhenhong Zhou · Kun Wang · Junhao Dong
26 May 2026 at 12:00
arXiv:2605.23954v1 Announce Type: cross Abstract: Audio Large Language Models (ALLMs) are highly vulnerable to real-world noise, which often induces severe semantic drift and hallucinations. Existing robustness methods primarily rely on waveform-level acoustic enhancement, answer-level supervision, or the internal suppression of noise representations. To address these issues, we propose echodistill, an alignment-based noisy-to-clean self-distillation framework. Echodistill leverages a frozen clean-audio teacher to provide semantic references for an inference-time noisy-audio student. Specifically, the student samples candidate responses under noisy conditions to expose its test-time behavior. These trajectories are then optimized via group-relative policy optimization (GRPO), where the token-level consistency with the teacher acts as a reward bonus. By aligning the noisy student's candidate responses with clean semantic evidence, and applying audio-aware reward shaping, our method encourages reasoning trajectories that are both correct and genuinely acoustically grounded. Echodistill significantly improves the semantic reliability and task performance of Audio LLMs under complex noise, without introducing any additional inference costs. Extensive experiments show that: (I) Compared with the strongest baseline, echodistill achieves average improvements of 4.18\%$\uparrow$ in GSR under strong noise. (II) Ablation results on Qwen-Omni further show that echodistill improves over the GRPO-only variant by 3.02\%$\uparrow$ in Acc, 3.89\%$\uparrow$ in Noisy, and 4.53\%$\uparrow$ in GSR on average. Our codes are available at https://anonymous.4open.science/r/echodistill-10DE.

DBPnet: Damper Characteristics-Based Bayesian Physics-Informed Neural Network for Wheel Load Estimation

✇cs.AI, q-bio.NC updates on arXiv.org
By: Tianyi Wang · Tianyi Zeng · Zimo Zeng · Feiyang Zhang · Yujin Wang · Xiangyu Li · Yiming Xu · Sikai Chen · Junfeng Jiao · Christian Claudel · Xinbo Chen
26 May 2026 at 12:00
arXiv:2605.24860v1 Announce Type: cross Abstract: Advanced driver assistance systems (ADAS) play an important role in modern automotive intelligence, significantly enhancing vehicle safety and stability. The performance of ADAS critically relies on accurate and reliable vehicle state estimation, particularly from vehicle dynamic sensors. Among these signals, wheel load is a key variable for chassis control and safety-critical functions, yet it remains difficult to estimate robustly due to complex suspension geometry, nonlinear dynamics, and measurement noise. To address this issue, we propose DBPnet, a Bayesian physics-informed neural network (PINN) with a physics-aware embedding module inspired by damper characteristics. First, this paper presents a suspension linkage-level modeling (SLLM) approach that constructs a nonlinear instantaneous dynamic model by explicitly considering the complex geometric structure of the suspension. Building upon SLLM, Bayesian inference is integrated into the PINN to effectively cope with noise and uncertainty in the vehicle chassis system, thereby improving the model's robustness. Then, a physics-informed loss function is employed to ensure consistency with fundamental physical principles, while the damper characteristics-inspired embedding module extracts temporal variation features of input signals and incorporates them into each layer of the PINN, ensuring that physical observations guide the neural network without being constrained by fixed physical models. Extensive evaluations on high-fidelity simulations and real-world experiments demonstrate that our DBPnet consistently achieves lower RMSE and MaxError than baseline methods. These results highlight the potential of our DBPnet to advance wheel load estimation and contribute to the development of more reliable ADAS actuator functions.
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