Results 71 to 80 of about 37,618 (246)

Dynamic Regulation of Endogenous Transcription Factor Hubs at Single‐Molecule Resolution

Advanced Science, EarlyView.
This study combines single‐molecule microscopy and genome editing to characterize the dynamic behaviors of endogenous oncofusion transcription factor EWS::FLI1 in Ewing sarcoma cells. EWS::FLI1 forms neomorphic hubs that dynamically assemble and dissolve. The hubs are regulated during mitosis, by RNA, and by specific chemicals.
Shawn Yoshida, Yanghao Zhong, Akiko Kumagai, William G. Dunphy, Shasha Chong   +4 more
wiley   +1 more source

A Plug‐and‐Play Platform for Customizing Multivalent Degraders and Degrader‐Drug Conjugates

Advanced Science, EarlyView.
Membrane proteins remain challenging targets for conventional TPD approaches. Here, the authors develop UPTAB, a modular platform leveraging ultrahigh‐affinity orthogonal Im/CL protein pairs for lysosomal degradation of membrane proteins. Mono‐targeted (Type‐I), dual‐targeted (Type‐II), and tri‐targeted (Type‐III) UPTABs enable simultaneous degradation
Mengqing Zhao, Yan Deng, Jianjian Han, Yong Xie, Kai Bao, Lixin Ma, Lilong Liu, Wuxiang Mao   +7 more
wiley   +1 more source

ABHD17C‐Mediated S‐Depalmitoylation of BCL6B Enhances CD24 Transcription to Resist Macrophage Phagocytosis in Pancreatic Cancer

Advanced Science, EarlyView.
ABHD17C‐mediated depalmitoylation of BCL6B at Cys442 blocks its nuclear import and triggers ubiquitin‐dependent degradation, attenuating transcriptional repression of the anti‐phagocytic signal CD24. This mechanism enables pancreatic cancer cells to evade macrophage phagocytosis and fosters an immunosuppressive microenvironment.
Yalu Zhang, Di Cui, Fanzheng Meng, Xu Zhu, Liang Zhu, Liang Wu, Haifeng Hu, Jizhou Wang, Hanhui Yao, Lianxin Liu   +9 more
wiley   +1 more source

Senescent Cell Derived Artificial Vesicle‐Based Senolytic Sonovaccine Platform with Augmented Lymph Node Delivery and Antigen Cross‐Presentation Efficacy

Advanced Science, EarlyView.
A senolytic sonovaccine platform (SenoVac) is developed, in which senescent cell‐derived vesicles serve as broad senescent cell antigen reservior. The “2‐step” click chemistry strategy for effective lymph node delivery, and ultrasound‐triggered endosomal escape to boost cross‐presentation, ensures efficient senescent cell clearance and disease ...
Liang Zhang, Yubo Lai, Jia Wang, Lingling Liu, Jieyuan An, Mi Qu, Yuan Liang, Bijun Tan, Guodong Yang, Xuekang Yang, Lijun Yuan   +10 more
wiley   +1 more source

SIRT6‐Mediated Deacetylation of ATF3 Promotes Silica‐Induced Lung Fibrosis by Enhancing its Nuclear Import via Binding to Importin α

Advanced Science, EarlyView.
SIRT6‐mediated ATF3 acetylation drives MGARP transcription and mitochondrial dysfunction in macrophages, promoting macrophage senescence and pulmonary fibrosis. Mechanistically, HSP70/Importin α competitively binds to ATF3, modulating its nuclear translocation.
Demin Cheng, Wenxia Bu, Fengxu Wang, Yueyuan Jin, Rongzhu Liu, Rui Zhao, Xuehai Wang, Mengna Jiang, Jinping Shen, Xinhang Cheng, Zuming Chen, Li Zhu, Jinlong Li, Zhenzhong Ge, Shichen Miao, Haotian Xu, Xiaoyu Zhou, Dongming Wang, Xinyuan Zhao   +18 more
wiley   +1 more source

Xenogeneic Mitochondrial Transplantation Improves Selected Age‐Associated Phenotypes in Mice

Advanced Science, EarlyView.
Yak‐derived xenogeneic mitochondrial transplantation improves selected age‐associated phenotypes in mice, enhances mitochondrial functional readouts, and engages host mitochondrial quality‐control pathways. Broad tissue biodistribution, increased ATP production and mtDNA copy number, reduced ROS levels and dysfunctional mitochondria, improved motility ...
Wenpeng Li, Xijia Wang, Yaning Hu, Zhen Yang, Tian Niu, Xingbo Zhao   +5 more
wiley   +1 more source

The endoplasmic reticulum, not the pH gradient, drives calcium refilling of lysosomes

eLife, 2016
Impaired homeostasis of lysosomal Ca2+ causes lysosome dysfunction and lysosomal storage diseases (LSDs), but the mechanisms by which lysosomes acquire and refill Ca2+ are not known.
Abigail G Garrity, Wuyang Wang, Crystal MD Collier, Sara A Levey, Qiong Gao, Haoxing Xu   +5 more
doaj   +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

A Dual‐Phase Exosomal Nanotherapy Enhances Continual Efferocytosis by Coordinating Checkpoint Inhibition and Metabolic Reprogramming in Atherosclerosis

Advanced Science, EarlyView.
Here we developed Am@SExo, a dual‐functional engineered exosome that coordinates CD47–SIRPα checkpoint blockade with Arg1 mRNA–mediated metabolic reprogramming. Surface SIRPα promotes recognition of apoptotic cells and plaque targeting, while Arg1 expression enhances arginine–ornithine metabolism, Rac1 activation, and actin remodeling in macrophages ...
Danwen Zheng, Shiteng Cai, Jinfeng Gao, Sheng Zhao, Bohan Wei, Xueyi Weng, Zhengmin Wang, Qiaozi Wang, Qiyu Li, Chengzhi Han, Weiyan Li, Yiwen Tan, Yuyuan Fu, Meng Ji, Zheyong Huang, Yanan Song, Juying Qian, Junbo Ge   +17 more
wiley   +1 more source

Hemoglobin's α‐Helix‐to‐β‐Sheet Transition Enables Targeted mRNA Delivery to the Lung

Advanced Science, EarlyView.
Acidic heating converts hemoglobin into β‐sheet‐rich fibrils with positively charged surfaces. These hemoglobin fibrils electrostatically complex IL‐11 scFv mRNA, selectively bind circulating platelets, and hitchhike to the lung, where they are enriched in fibroblasts.
Xihua Liu, Saiya Li, Guodong Wu, Shuangjian Li, Long Shuang Huang, Xiaoyang Li, Yiguo Zhao, Wei Lu, Cuixia Sun, Qin Cao, Yapeng Fang, Yiping Cao   +11 more
wiley   +1 more source