Results 151 to 160 of about 730,800 (305)

A Bifunctional T3SS‐Effector Simultaneously Cleaves Host MAP Kinase and Inhibits PPM1A Phosphatase

Advanced Science, EarlyView.
Pathogenic bacteria exploit the metalloprotease effector NleD to subvert host defenses. Structural, biochemical, and infection analyses reveal a bifunctional mechanism by which NleD binds and inhibits the host phosphatase PPM1A while preserving its proteolytic activity against MAPKs.
Yaakov Socol, Lihi Gur‐Arie, Netanel Tzarum, Tamara Wellins, Naama Katsowich, Miriam Ravins, Michal Bejerano‐Sagie, Klil Cohen, Oded Livnah, Joshua N. Adkins, Ernesto Nakayasu, Alexei Savchenko, Yeu Khai Choong, Nikhil Kumar Tulsian, Saturo Machida, Sigal Ben‐Yehuda, Yael Litvak, J. Sivaraman, Ilan Rosenshine   +18 more
wiley   +1 more source

GATA4‐Driven Transcription of HtrA1 Promotes Cellular Senescence in Ménière's Disease and Age‐Related Audio‐Vestibular Dysfunction

Advanced Science, EarlyView.
This study identifies the HDAC6/GATA4/HtrA1 axis as a critical driver of cellular senescence in the inner ear. GATA4 nuclear translocation, facilitated by HDAC6 downregulation, transcriptionally activates HtrA1, promoting hair cell senescence, SASP, and audio‐vestibular dysfunction in models of Ménière's disease and age‐related audio‐vestibular ...
Na Zhang, Na Li, Yan Wang, Jing Zhang, Jiahui Liu, Lei Chen, Yongdong Song, Yurong Mu, Yuechen Han, Yafeng Lyu, Xiaofei Li, Hanyue Wang, Jing Wang, Yao Lu, Zhaomin Fan, Daogong Zhang, Haibo Wang   +16 more
wiley   +1 more source

Fibrates Inhibit PLTP‐induced M2 Macrophage Infiltration and Increase the Sensitivity of Hepatocellular Carcinoma to ICIs

Advanced Science, EarlyView.
Phospholipid transfer protein(PLTP) plays a critical role in forming a complex with kinase A (AURKA) and P65. This interaction facilitates phosphorylation of P65 at Ser536, leading to the activation of the NF‐κB signaling pathway. Ultimately, this leads to the upregulation of downstream cytokines, including IL‐6, IL‐8, and CSF‐1, which promotes M2 ...
Xinyue Liang, Yaning Li, Jianxun Cai, Lisi Luo, Pengfei Yang, Yutong Chen, Jiancong Zhou, Yan Zeng, Jiaping Yu, Weiyu Zhang, Wenzheng Pang, Yufang Li, Chunhua Wen, Jian Li, Linjuan Zeng   +14 more
wiley   +1 more source

Endocytic Control of Cell‐Autonomous and Non‐Cell‐Autonomous Functions of p53

Advanced Science, EarlyView.
NUMB Ex3‐containing isoforms localize to the plasma membrane, where they recruit p53 through SNX9 and direct it to multivesicular bodies and exosomes. Exported p53 is taken up by neighboring cells and activates nuclear programs, revealing an intercellular, exosome‐based pathway that might help establish a tumor‐suppressive microenvironment.
Roberta Cacciatore, Andrea Basile, Stefano Freddi, Irene Schiano Lomoriello, Carlo Ribelle Zucca, Giuseppe Ciossani, Luigi Scietti, Alessandro Cuomo, Simona Ronzoni, Simone Pelicci, Mario Faretta, Elena Zaccheroni, Giuliana Pelicci, Vittoria Matafora, Angela Bachi, Rosalind Helen Gunby, Salvatore Pece, Sara Sigismund, Letizia Lanzetti, Ivan Nicola Colaluca, Pier Paolo Di Fiore   +20 more
wiley   +1 more source

Zinc Exposure Causes Disulfidptosis to Induce Miscarriage by Up‐Regulating GATA1/METTL1/SLC7A11 Axis

Advanced Science, EarlyView.
Zn exposure up‐regulates GATA1, promoting GATA1‐mediated METTL1 and SLC7A11 transcription. It also enhances METTL1‐mediated m7G modification on SLC7A11 mRNA, increasing SLC7A11 mRNA stability. Ultimately, Zn exposure up‐regulates SLC7A11 at both transcriptional and post‐transcriptional levels, causing disulfidptosis. Knockdown of murine Slc7a11, Gata1,
Wenxin Huang, Yi Sun, Yanxin Wang, Haijun Yan, Xiaoping Yue, Weidong Wu, Xueyu Chen, Jinfang Zhang, Yanbing Lin, Qiong Lei, Nan Ji, Shuaishuai Xing, Liqin Zeng, Qingzheng Kang, Depeng Zhao, Geng Guo, Huidong Zhang   +16 more
wiley   +1 more source

NPM1 Mediates mRNA Sorting into Extracellular Vesicles via Specific RNA Motif Binding and Phase Separation

Advanced Science, EarlyView.
NPM1 selectively sorts specific mRNAs into extracellular vesicles (EVs) by recognizing RNA motifs and forming phase‐separated condensates. These mRNA cargos—including EGFR—are then loaded via multivesicular bodies. This active sorting pathway, validated in EVs derived from both lung cancer cells and patient serum, reveals a specific mechanism for ...
Kaixiang Zhang, Gaoge Sun, Xiangzheng Liu, Shuai Zuo, Pengyuan Wang, Boxiao Zhan, Zhi John Lu, Hang Yin, Ying Zhang   +8 more
wiley   +1 more source

Restriction of Individual Branched‐Chain Amino Acids has Distinct Effects on the Development and Progression of Alzheimer's Disease in 3xTg Mice

Advanced Science, EarlyView.
Protein restriction (PR) slows Alzheimer's disease (AD) in mice, and other benefits of PR are due to decreased branched‐chain amino acids (BCAAs). We show that restricting any BCAA has benefits, with sex‐ and BCAA‐specific impacts on pathology, molecular signaling, and cognition.
Reji Babygirija, Cara L. Green, Michelle M. Sonsalla, Izabelle Marie F. Le, Fan Xiao, Sarah Yandell, Mariah F. Calubag, Michaela E. Trautman, Anna Tobon, Ryan Matoska, Chung‐Yang Yeh, Charles I. Opara, Isaac Grunow, Diana Vertein, Sophia Schlorf, Bailey A. Knopf, Michael J. Rigby, David A. Harris, Mark P. Keller, Alan D. Attie, Luigi Puglielli, Cholsoon Jang, Dudley W. Lamming   +22 more
wiley   +1 more source

De Novo Design and Directed Evolution Refinement of Mirror‐Image Protein Binders Targeting Interleukin‐4

Advanced Science, EarlyView.
This study presents the de novo design and directed evolution of a mirror‐image D‐protein inhibitor targeting human interleukin‐4 (IL‐4). The engineered molecule exhibits nanomolar binding affinity for IL‐4 and effectively inhibits IL‐4–mediated signaling.
Liqing Xu, Yuxiang Ren, Tongyue Wang, Hongyong Li, Yue Yao, Lei Liu, Ke Sun, Peilong Lu   +7 more
wiley   +1 more source

Functional Analysis of Ligand‐Gated Chloride Channels in a Cnidarian Sheds Light on the Evolution of Inhibitory Signaling

Advanced Science, EarlyView.
We uncover a large variety of putative inhibitory ligand‐gated ion channels (LGICs) in the phylum Cnidaria, the sister group to all bilaterian animals. Phylogenetic analysis suggests a complex evolutionary history of inhibitory LGICs with diverse neurotransmitter ligands.
Abhilasha Ojha, Linda Kloss, Juan D. Montenegro, Simone Albani, Audrey Ortega‐Ramírez, Mihaela Raycheva, Sylvia Joussen, Sabrina Kaul, Michèle Bachmann, Lisa Huf, Günther Schmalzing, Alison G. Cole, Ulrich Technau, Stefan Gründer   +13 more
wiley   +1 more source

De Novo Multi‐Mechanism Antimicrobial Peptide Design via Multimodal Deep Learning

Advanced Science, EarlyView.
Current AI‐driven peptide discovery often overlooks complex structural data. This study presents M3‐CAD, a generative pipeline that leverages 3D voxel coloring and a massive database of over 12 000 peptides to capture nuanced physicochemical contexts.
Xiaojuan Li, Haifan Gong, Yue Wang, Yinuo Zhao, Lixiang Li, Peijing Bao, Qingzhou Kong, Jialu Fu, Boyao Wan, Yumeng Zhang, Jinghui Zhang, Jiekun Ni, Zhongxue Han, Xueping Nan, Kunping Ju, Longfei Sun, Yuerui Ma, Huijun Chang, Mengqi Zheng, Yanbo Yu, Xiaoyun Yang, Xiuli Zuo, Haina Wang, Yanqing Li   +23 more
wiley   +1 more source