Results 141 to 150 of about 4,740 (212)

Genome‐Wide CRISPR Screen Identifies a microRNA Orchestrating Pleiotropic Resistance to Targeted Therapy and T Cell Immunity in Melanoma

Advanced Science, EarlyView.
A genome‐wide microRNA CRISPR screen identifies miR‐18a as a master regulator of cross‐resistance in melanoma. Loss of miR‐18a activates the AJUBA–YAP/Hippo axis to confer BRAFi resistance and enhances THBS1–CD47 interaction to impair CD8+ T cell immunity. hnRNP A1 is identified as an upstream regulator of miR‐18a processing.
Zhao Wang, Haotian Liu, Xueqi Wang, Jianjin Teng, Zihan Zheng, Jingya Zhang, Wanyi Xiao, Qian Liang, Jiaxin Li, Xiaomeng Jia, Xin Feng, Hongzhang Cui, Menghan Luo, Tielong Yang, Liuxing Wu, Ke Zhao, Weilong Yang, Mulin Jun Li, Dandan Huang, Jilong Yang   +19 more
wiley   +1 more source

Adipocyte‐Derived Leptolin Enhances Energy Expenditure and Prevents Obesity

Advanced Science, EarlyView.
We identified a novel adipokine, which we named leptolin. In humans, leptolin levels in white adipose tissue were positively correlated with exercise and negatively associated with body mass index. We observed elevated leptolin in serum from athletes and lower leptolin in serum from obese individuals.
Jiarui Liu, Bingwei Wang, Zhijie Su, Xiaoxv Han, Miao He, Yun Zhao, Yujia Hou, Daotong Li, Weiguang Zhang, Lihua Qin, Ke Wang, Yanchun Li, Yi Yan, Siwang Yu, Xiaoshuai Huang, Tairan Yuwen, Jianyuan Luo, Ruimao Zheng   +17 more
wiley   +1 more source

PRMT1‐Mediated LDHA Methylation Drives STAT3 Lactylation to Orchestrate Intestinal Inflammation and Tumorigenesis

Advanced Science, EarlyView.
This study identifies an immunometabolic axis wherein SAM‐driven PRMT1 methylates LDHA, enhancing its activity. The resultant lactate induces STAT3 K709 lactylation, which stabilizes an active conformation to promote STAT3 phosphorylation and IL‐10 expression.
Hui Wang, Mengyu Zhang, Weipeng Gong, Jiaxuan Wu, Junping Zhang, Wenxiu Zhang, Yue Liu, Kui Wang, Canhua Huang, Jun Zhou, Sijin Wu, Yan Li, Tianliang Li   +12 more
wiley   +1 more source

Protein Disulfide Isomerase Disassembles TDP‐43/G3BP1 Condensates and Antagonizes TDP‐43 Pathological Aggregates

Advanced Science, EarlyView.
Cytoplasmic aggregation of TDP‐43 is a common pathological feature in amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and Alzheimer's disease with TDP‐43 pathology. This study reports that wild‐type PDI slows down phase separation of TDP‐43 through direct interaction with TDP‐43.
Jia‐Qi Liu, Hao Liu, Yu‐Xuan Sun, Yuying Li, Xiangyi Liu, Li‐Qiang Wang, Zhaofei Yang, Qi Fu, Xiaojiao Xu, Jie Chen, Yingshuang Zhang, Jun Zhou, Weidong Le, Mengchao Cui, Yi Liang   +14 more
wiley   +1 more source

Enhanced Glycolysis‐Driven Histone H3K18 Lactylation Regulates Epileptogenesis by Modulating the E3 Ubiquitin Ligase COP1

Advanced Science, EarlyView.
Neuronal PKM2‐driven glycolysis generates excess lactate that triggers histone H3K18 lactylation (H3K18la), establishing a pathogenic metabolic‐epigenetic axis in epilepsy. Elevated H3K18la enriches the Cop1 promoter, transcriptionally upregulating the E3 ubiquitin ligase COP1, which subsequently drives proteasomal degradation of GABAARβ2 and impairs ...
Yuan Meng, Yanlin Guo, Liumi Jiang, Jing Luo, Yan Liu, Ziwei Yuan, Pingyang Ke, Ran Duan, Fei Xiao   +8 more
wiley   +1 more source

ZDHHC9‐Mediated Palmitoylation of ACSL4 Drives Ferroptosis in Diabetes Mellitus–Induced Erectile Dysfunction

Advanced Science, EarlyView.
ABSTRACT Diabetes mellitus‐induced erectile dysfunction (DMED) is a highly prevalent complication among diabetic patients; however, its underlying pathogenic mechanisms remain incompletely understood. Metabolic disorder is a hallmark of diabetes, yet its precise contribution to DMED progression is not well defined.
Wanyang Guo, Ming Xiao, Mengjun Huang, Dongzi Peng, Ruijiang Zeng, Ruilin Liu, Yuanqiao Zhao, Zhihan Ouyang, Yulong Hong, Zexian Ding, Zhuo Xing, Hao Su, Jinxiang Wang, Wenjun Mao, Xin Jin   +14 more
wiley   +1 more source

Canagliflozin Alleviates Diabetic Glomerular Endothelial Injury via Melibiose in a Microbiota‐Dependent Manner

Advanced Science, EarlyView.
Canagliflozin treatment reshapes the gut microbiota in DKD and elevates levels of melibiose, a metabolite derived from Roseburia intestinalis. Melibiose directly binds to and enhances the enzymatic activity of glyoxalase 1, leading to decreased methylglyoxal accumulation.
Wei Zhang, Yi Song, Changkun Li, Yuanyuan Luo, Mingwei Shao, Feng Guo, Fangyi Wei, Xunjie Fan, Wenwen Guo, Fengmei Xu, Yanhong Sang, Dongming Zhang, Yanhong Zhou, Lianwei Wang, Zhiqiang Kang, Yingjun Yang, Chunhua Song, Yanxia Liu, Xiaojun Ma, Jiao Wang, Chong Li, Shengnan Ma, Lin Zhao, Zhi Qin, Guolan Xing, Qiubo Zhao, Jun Li, Shumin Song, Dan Zhao, Ting Huang, Qingzhu Wang, Yanyan Zhao, Guijun Qin   +32 more
wiley   +1 more source

CD4+ Tregs Drive Post‐Ischemic Sprouting Angiogenesis via Endothelial YY1/MAML1 Reactivation

Advanced Science, EarlyView.
ABSTRACT Microvascular complications of diabetes are chronic diseases of small vessels. We previously found that CD4+ regulatory T‐cells (Tregs) are markedly reduced in type 2 diabetes (T2D) after ischemic injury in both mice and humans, and that Treg deficiency in immunodeficient mice impairs vascular regeneration.
Hang Qu, Cheng Kiu Ho, Jitao Liu, Lei Cui, Yangfeng Hou, Cai Liang, Wenchu Ye, Randolph H. L. Wong, Shohei Hori, Bin Zhou, Kathy O. Lui   +10 more
wiley   +1 more source

A Toolkit for Targeted Neuromodulation of Striatal Direct Pathway Neurons Rescues Parkinsonian Motor Deficits in Mice

Advanced Science, EarlyView.
An adeno‐associated virus (AAV) toolkit enables selective anatomical and functional targeting of striatal D1‐MSNs through retrograde transduction. Enhanced capsids and engineered enhancers drive robust transgene expression across murine and primate models.
Zexuan Hong, Yujing Zhang, Junjiao Zhang, Hanhe Liu, Qiwei Liu, Yanglei Li, Lixin Yang, Lixia Li, Zhongjie Liu, Zhen Yuan, Zhonghua Lu, Yefei Chen, Yuantao Li, Yuwu Jiang, Taian Liu   +14 more
wiley   +1 more source

Circular RNA circNrip1 Interacts with SYNCRIP to Promote Neuropathic Pain by Stabilizing Tlr2 mRNA in Primary Sensory Neurons

Advanced Science, EarlyView.
Model of circNrip1 (cNrip1) upregulation driving neuropathic pain mechanisms. After peripheral nerve injury, increased FUS triggers the formation and upregulation of cNrip1 in injured DRG neurons. Upregulated cNrip1 recruits SYNCRIP to the 3′‐UTR of Tlr2 mRNA by binding to both, thereby promoting SYNCRIP‐triggered Tlr2 mRNA stability and increasing ...
Xiaozhou Feng, Jifang Xiao, Congcong Huang, Bao‐Chun Jiang, Bing Wang, Xu Li, Shibin Du, Tolga Berkman, Chun‐Hsien Wen, Weihua Cai, Dilip Sharma, Kun Wang, Longfei Ma, Huijuan Hu, Yuan‐Xiang Tao   +14 more
wiley   +1 more source