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Agrimol B induces autophagic death in TP53-mutant pancreatic cancer by targeting the S100A6-HDAC2-mutant p53 acetylation axis

Phytomedicine. 2026 Aug 26;161:158760. doi: 10.1016/j.phymed.2026.158760. Online ahead of print.

ABSTRACT

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) harbors TP53 mutations at high frequency, yet therapeutic strategies that specifically target mutant p53 remain limited.

PURPOSE: This study aimed to identify S100A6, a calcium-binding protein frequently upregulated in TP53-mutant PDAC, as a critical regulator of mutant p53 stability and tumor progression, and to explore potential S100A6-targeting agents for therapeutic intervention.

METHODS: We integrated computer-assisted drug screening with transcriptomics, acetylation omics, and molecular biology techniques to identify Agrimol B (AgrB), a bioactive compound derived from the traditional Chinese herb Agrimonia pilosa Ledeb., as a potential S100A6-targeting agent.

RESULTS: High S100A6 expression was closely associated with poor prognosis in patients with TP53-mutant PDAC, whereas S100A6 depletion markedly suppressed PDAC cell growth and metastatic potential. Mechanistically, AgrB enhanced the interaction between S100A6 and the deacetylase HDAC2, leading to reduced acetylation of mutant p53 at lysine 382. This disruption activated autophagy-dependent cell death and thereby inhibited PDAC progression.

CONCLUSION: Our findings reveal an S100A6-HDAC2-mutant p53 acetylation axis that regulates TP53-mutant pancreatic tumorigenesis, providing mechanistic evidence supporting S100A6 as a therapeutic vulnerability and highlighting AgrB as a promising natural-product-derived candidate for further development against this aggressive malignancy.

PMID:42700714 | DOI:10.1016/j.phymed.2026.158760

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Molmo2: Open Weights and Data for Vision-Language Models with Video Understanding and Grounding

arXiv:2601.10611v4 Announce Type: replace-cross Abstract: Today's strongest video-language models (VLMs) remain proprietary. The strongest open-weight models either rely on synthetic data from proprietary VLMs, effectively distilling from them, or do not disclose their training data or recipe. As a result, the open-source community lacks the foundations needed to improve on the state-of-the-art video (and image) language models. Crucially, many downstream applications require more than just high-level video understanding; they require grounding -- either by pointing or by tracking in pixels. Even proprietary models lack this capability. We present Molmo2, a new family of VLMs that are state-of-the-art among open-source models and demonstrate exceptional new capabilities in point-driven grounding in single image, multi-image, and video tasks. Our key contribution is a collection of 7 new video datasets and 2 multi-image datasets, including a dataset of highly detailed video captions for pre-training, a free-form video Q&A dataset for fine-tuning, a new object tracking dataset with complex queries, and an innovative new video pointing dataset, all collected without the use of closed VLMs. We also present a training recipe for this data utilizing an efficient packing and message-tree encoding scheme, and show bi-directional attention on vision tokens and a novel token-weight strategy improves performance. Our best-in-class 8B model outperforms others in the class of open weight and data models on short videos, counting, and captioning, and is competitive on long-videos. On video-grounding Molmo2 significantly outperforms existing open-weight models like Qwen3-VL (35.5 vs 29.6 accuracy on video counting) and surpasses proprietary models like Gemini 3 Pro on some tasks (38.4 vs 20.0 F1 on video pointing and 56.2 vs 41.1 J&F on video tracking).
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3D Wavelet-Based Structural Priors for Controlled Diffusion in Whole-Body Low-Dose PET Denoising

arXiv:2601.07093v4 Announce Type: replace-cross Abstract: Low-dose Positron Emission Tomography (PET) imaging reduces patient radiation exposure but suffers from increased noise that degrades image quality and diagnostic reliability. Although diffusion models have demonstrated strong denoising capability, their stochastic nature makes it challenging to enforce anatomically consistent structures, particularly in low signal-to-noise regimes and volumetric whole-body imaging. We propose Wavelet-Conditioned ControlNet (WCC-Net), a fully 3D diffusion-based framework that introduces explicit frequency-domain structural priors via wavelet representations to guide volumetric PET denoising. By injecting wavelet-based structural guidance into a frozen pretrained diffusion backbone through a lightweight control branch, WCC-Net decouples anatomical structure from noise while preserving generative expressiveness and 3D structural continuity. Extensive experiments demonstrate that WCC-Net consistently outperforms CNN-, GAN-, and diffusion-based baselines. On the internal 1/20-dose test set, WCC-Net improves PSNR by +1.21 dB and SSIM by +0.008 over a strong diffusion baseline, while reducing structural distortion (GMSD) and intensity error (NMAE). Moreover, WCC-Net generalizes robustly to unseen dose levels (1/50 and 1/4), achieving superior quantitative performance and improved volumetric anatomical consistency.
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A Very Big Video Reasoning Suite

arXiv:2602.20159v1 Announce Type: cross Abstract: Rapid progress in video models has largely focused on visual quality, leaving their reasoning capabilities underexplored. Video reasoning grounds intelligence in spatiotemporally consistent visual environments that go beyond what text can naturally capture, enabling intuitive reasoning over spatiotemporal structure such as continuity, interaction, and causality. However, systematically studying video reasoning and its scaling behavior is hindered by the lack of large-scale training data. To address this gap, we introduce the Very Big Video Reasoning (VBVR) Dataset, an unprecedentedly large-scale resource spanning 200 curated reasoning tasks following a principled taxonomy and over one million video clips, approximately three orders of magnitude larger than existing datasets. We further present VBVR-Bench, a verifiable evaluation framework that moves beyond model-based judging by incorporating rule-based, human-aligned scorers, enabling reproducible and interpretable diagnosis of video reasoning capabilities. Leveraging the VBVR suite, we conduct one of the first large-scale scaling studies of video reasoning and observe early signs of emergent generalization to unseen reasoning tasks. Together, VBVR lays a foundation for the next stage of research in generalizable video reasoning. The data, benchmark toolkit, and models are publicly available at https://video-reason.com/ .
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