Results 181 to 190 of about 13,769 (209)

IKKβ and USP28 Regulate HEY1 Stability to Promote Cancer Stemness and Immune Evasion in Hepatocellular Carcinoma

Advanced Science, EarlyView.
The uncovered IKKβ‐USP28‐HEY1 axis fuels cancer stemness and immune evasion in hepatocellular carcinoma. USP28 deubiquitinates HEY1 upon IKKβ‐mediated phosphorylation, conferring PD‐1/PD‐L1 blockade resistance. Pharmacological inhibition of USP28 sensitizes resistant tumors to anti‐PD‐1 immunotherapy, revealing a promising therapeutic strategy ...
Na Shao, Lin Zhang, Gufang Shen, Yangfan Lv, Tianshu Fang, Ya Cao, Qiongyi Zhang, Feng Xu, Chungang Liu   +8 more
wiley   +1 more source

Targeting KDM3B Elicits Anti‐tumor Immunity by Alleviating SHP1–mediated STING Suppression in Triple–Negative Breast Cancer

Advanced Science, EarlyView.
P3FI–90 treatment targets KDM3B, reshapes the epigenetic landscape, and suppresses SHP1 expression, thereby activating STING–TBK1–IRF3–type I IFN signaling pathway. Consequently, CD8+ T cells are recruited to the tumor site and activated to produce IFN–γ and GZMB, leading to the killing of TNBC cells.
Xiaolong Wang, Wenhao Li, Yifei Wang, Ning Zhang, Bing Chen, Wenjing Zhao, Lijuan Wang, Dan Luo, Qifeng Yang   +8 more
wiley   +1 more source

Leonurine Ameliorates Doxorubicin‐Induced Cardiotoxicity via STING/NF‐κB/NLRP3 Inflammasome Signaling Pathway

Advanced Science, EarlyView.
ABSTRACT Doxorubicin‐induced cardiomyopathy (DIC) remains a dose‐limiting clinical challenge. This study reveals that cardiac vascular endothelial cells (CVECs) act as initial sensors of doxorubicin cardiotoxicity: circulating doxorubicin activates the cGAS‑STING pathway in CVECs, triggering NLRP3 inflammasome‑mediated pyroptosis and release of ...
Wang Jun, Chen Xiaoyang, Xu Jianglin, Yang Zhi, Tao Meijiao, He Jiale, Zhao Jiangfeng, Hei Xuanding, Xu Xuegong, Wang Wei, Li Chun   +10 more
wiley   +1 more source

NMI Regulates Adipose Adaptive Thermogenesis Through TLR4/IRF3 Signaling to Promote Obesity

Advanced Science, EarlyView.
Adipose tissue‐derived NMI is secreted under metabolic stress and suppresses adaptive thermogenesis through TLR4/IRF3 signaling, repressing the PPARα/PGC‐1α/UCP1 thermogenic transcriptional program. Genetic ablation or anti ‐ NMI monoclonal antibody treatment enhances energy expenditure, protects against DIO, and ameliorates adipose tissue inflammation,
Ting‐Ting Li, Xin‐Yuan Zhao, Min Zhang, Zhuang‐Feng Weng, Xiao‐Ran Guo, Ying‐Fang Liu, Qiao‐Ping Wang, Huan‐Huan Liang   +7 more
wiley   +1 more source

PDIA6–SCD1 Axis Rewires Lipid Metabolism to Drive Gastric Cancer Progression

Advanced Science, EarlyView.
Protein disulfide isomerase A6 (PDIA6) is identified as an oncogenic driver in gastric cancer. PDIA6 directly binds and stabilizes SCD1 by limiting its ubiquitin–proteasome‐mediated degradation, thereby sustaining monounsaturated fatty acid (MUFA)‐enriched lipid homeostasis and lipid metabolic reprogramming.
Zhen Tian, Yifan Cheng, Jiajie Zhou, Ruiqi Li, Shuai Zhao, Ben Li, Zijie Xu, Mengli Zi, Yayan Fu, Chenkai Zhang, Qiannan Sun, Shantanu Baral, Sen Wang, Daorong Wang   +13 more
wiley   +1 more source

Stem Cell Differentiation Disperses Transcriptional Clusters via a Conserved Surface‐Condensate Trajectory

Advanced Science, EarlyView.
Stem cell differentiation follows a conserved surface condensate trajectory: H3K27ac super enhancers nucleate large RNA polymerase II clusters that grow and unfold before transcriptional activity disperses them. This work reveals how biophysical forces at enhancer surfaces dynamically build and dismantle stem cell transcription hubs, reshaping cell ...
Tim Klingberg, Irina Wachter, Agnieszka Pancholi, Matthias Akyel, Yomna Gohar, Priya Kumar, Ana Miguel Fernandes, Yuzhi Bao, Alica Schmidt‐Heydt, Marcel Piepers, Alicia Günthel, Marcel Sobucki, Elisa Kämmer, Süheyla Eroğlu‐Kayıkçı, Stephan Allgeier, Sylvia Erhardt, Vasily Zaburdaev, Carmelo Ferrai, Lennart Hilbert   +18 more
wiley   +1 more source

Epidermal METTL1‐Mediated m7G Modification Drives Psoriatic Inflammation by Stabilizing Bdkrb1 and Orchestrating Neutrophil Recruitment

Advanced Science, EarlyView.
This study unveils an unrecognized pro‐inflammatory epitranscriptomic checkpoint in psoriasis. By installing m7G modifications on the 5′ UTR of Bdkrb1 mRNA, METTL1 enhances receptor stability to orchestrate keratinocyte‐driven neutrophil recruitment via p38 MAPK signaling.
Chang Zhang, Jiayi Lu, Sihao Yan, Yirui Wang, Zhuo Li, Weiwei Chen, Yang Han, Ziyan Zhang, Yafen Yu, Qi Zhen, Liangdan Sun   +10 more
wiley   +1 more source

Targeting Lactate‐Driven Stromal Autophagy via MCT1 Disrupts the Immunosuppressive Niche and Sensitizes Pancreatic Cancer to PD‐1 Blockade

Advanced Science, EarlyView.
Tumor‐derived lactate activates PSCs through MCT1‐mediated Vps34 lactylation and autophagy. These activated PSCs secrete CXCL9/10, upregulating PD‐1 on CD8+ T cells via the CXCR3/STAT3 axis to foster immunosuppression. Disrupting this metabolic crosstalk by targeting MCT1 effectively sensitizes pancreatic cancer to PD‐1 blockade, presenting a promising
Wenfeng Zhuo, Rong Hu, Yuhang Hu, Ping Hu, Shengbo Han, Guozheng Lv, Zhu Zeng, Yong Zhao, Yang Li, Yan Huang, Yingsong Zhao, Hongda Wang, Guangyu Zhao, Eryang Zhao, Gang Zhao   +14 more
wiley   +1 more source

Intrinsically Mitochondria‐Targeting Nanozyme via Coordination‐Assembly of Natural Quercetin for Cascade Antioxidant Therapy of Cerebral Ischemia‐Reperfusion Injury

Advanced Science, EarlyView.
This study uncovers that quercetin naturally targets mitochondria. By coordinating quercetin with Fe3+, we engineer an ultrasmall cascade nanozyme (MCN) with superoxide dismutase‐catalase activities. MCN crosses the damaged blood–brain barrier, scavenges mitochondrial ROS, prevents mitochondrial DNA leakage, and blocks the cGAS‐STING pathway, thereby ...
Wenxuan Zheng, Zhicheng Wang, Xin Zhou, Shuya Wang, Xiaojing Shi, Tingli Xiong, Ruishi Li, Yuting Lin, Zhen Chen, Jiawen Wei, Fei Li, Jinwen Ge, Kelong Ai, Chong Liu, Guiming Deng   +14 more
wiley   +1 more source

Pharmacological Inhibition of FKBP51 Mitigates Early Life Adversity‐Induced Social Deficits in Male Mice

Advanced Science, EarlyView.
Early life adversity triggers persistent social subordination and brain‐wide molecular dysregulation. Pharmacological inhibition of the stress‐mediator FKBP51 during the adversity period prevents these long‐term deficits and restores normative social hierarchy.
Joeri Bordes, Xiuqi Ji, Serena Gasperoni, Choham Sudre‐Chinsky, Amirali Kalbasi, Daniela Harbich, Cornelia Flachskamm, Paula Fontanet, Sowmya Narayan, Manfred Uhr, Christian Namendorf, Camilla Bellone, Alon Chen, Felix Hausch, Juan Pablo Lopez, Mathias V. Schmidt   +15 more
wiley   +1 more source