Reading view

USP4-Dependent CHAF1B Stabilization Regulates Distinct SETDB1 Ubiquitin States Linked to AKT T308 Signaling and Lipogenic Remodeling in HCC

By: Saiyan Bian · Yun Tong · Wenkai Ni · Zhangzhi Tang · Weiting Chen · Kexin Ma · Lihan Jiang · Jiayu Shao · Xuyang He · Wenjie Zheng

30 September 2026 at 18:00

Adv Sci (Weinh). 2026 Sep 29:e78039. doi: 10.1002/advs.78039. Online ahead of print.

ABSTRACT

Durable responses to current therapies remain limited in hepatocellular carcinoma (HCC), highlighting the need to identify regulators of malignant progression. By integrating multi-omics analyses, spatial transcriptomics, clinical specimens, and multiple models, we identified chromatin assembly factor 1B (CHAF1B) as a functional regulator of HCC phenotypes. Gain- and loss-of-function of CHAF1B altered proliferative, migratory, clonogenic, and tumorigenic phenotypes. LC-MS/MS, DIA proteomics, and cell-based assays revealed CHAF1B-associated lipogenic remodeling characterized by SREBP1C nuclear localization, lipogenic gene/protein induction, and lipid-droplet accumulation. Mechanistically, the WD40 repeat-containing region of CHAF1B contributed to its association with UHRF1 and SETDB1, supporting UHRF1-associated K63-linked ubiquitination and CRM1/exportin-1-dependent cytoplasmic redistribution of SETDB1. Conversely, CHAF1B depletion enhanced SETDB1 association with VHL and favored a predominantly K11-associated degradative ubiquitin state linked to proteasomal SETDB1 loss. SETDB1 redistribution and catalytic activity were associated with AKT T308-linked signaling. A focused CRISPR-based screen of deubiquitinases identified USP4 as an upstream regulator of CHAF1B protein homeostasis. USP4 depletion or Akebia saponin D (ASD) increased K48-linked ubiquitination of CHAF1B, reduced CHAF1B protein abundance, attenuated AKT T308-linked signaling, and suppressed malignant and lipogenic phenotypes. These findings reveal distinct ubiquitin-dependent states governing SETDB1 stability and identify USP4-dependent CHAF1B stabilization as an upstream regulatory node in HCC.

PMID:42811544 | PMC:PMC13624420 | DOI:10.1002/advs.78039

D3S2: Diffusion-Guided Dataset Distillation for Semantic Segmentation

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

By: Wenjie Zheng · Haoji Hu · Jiali Lu · Xingze Zou · Jing Wang

26 May 2026 at 12:00

arXiv:2605.25022v1 Announce Type: cross Abstract: Dataset distillation (DD) aims to compress large-scale datasets into compact synthetic sets while preserving training efficacy. However, existing studies mainly focus on image classification, leaving dense prediction tasks such as semantic segmentation largely underexplored. In this work, we identify three key challenges for segmentation DD: (i) long-tailed class imbalance, (ii) the need for strict pixel-wise alignment between images and dense labels, and (iii) the high computational cost of optimizing high-resolution data with complex models. To address these challenges, we propose D3S2, a Diffusion-guided Dataset Distillation framework for Semantic Segmentation. Our method adopts a two-stage design. In Class-Balanced Mask Selection, we construct a representative mask set via a greedy strategy that prioritizes underrepresented classes. In Diffusion-Guided Image Synthesis, we employ a pretrained layout-to-image diffusion model to generate images conditioned on the selected masks, naturally ensuring spatial alignment. To further enhance the training utility of synthesized data, we introduce guided diffusion sampling with two complementary objectives: a segmentation-consistency loss for pixel-level alignment, and a class-wise feature matching loss for aligning per-class feature statistics across layers. Extensive experiments demonstrate the superiority of D3S2. Notably, at an extremely compression rate of 1%, our method achieves 24.99% and 35.49% mIoU on ADE20K and COCO-Stuff with Mask2Former (Swin-S), outperforming random selection by 9.34% and 5.70%, respectively.