Results 101 to 110 of about 255,773 (233)

Testicular mRNA‐LNP Delivery: A Novel Therapy for Genetic Spermatogenic Disorders

Advanced Science, EarlyView.
In the current study, we developed a novel therapy for genetic spermatogenic disorders. It was revealed that in vivo delivery of mRNA LNP3 could restore spermatogenesis in Msh5D486Y/D486Y and Maps KO mouse models with meiotic arrest. Notably, the offspring without genomic integration was born using ICSI derived from the rescue of Msh5D486Y/D486Y mouse ...
Chenwang Zhang, Nan Liang, Wenbo Li, Shuai Xu, Peng Li, Wanze Ni, Na Li, Sha Han, Ningjing Ou, Haowei Bai, Yuxiang Zhang, Furong Bai, Yifan Sun, Dewei Qian, Xinjie Bu, Erlei Zhi, Ruhui Tian, Yuhua Huang, Jingpeng Zhao, Fujun Zhao, Hao Chen, Zheng Li, Chencheng Yao   +22 more
wiley   +1 more source

TBK1 Induces the Formation of Optineurin Filaments That Condensate with Polyubiquitin and LC3 for Cargo Sequestration

Advanced Science, EarlyView.
Phosphorylation of Optineurin by TBK1 induces the formation of filaments that condensate upon binding to linear polyubiquitin. Membrane‐anchored LC3 partitions into these condensates, suggesting that phase separation of filamentous Optineurin with ubiquitylated cargo promotes the sequestration of cargo and its subsequent alignment with LC3‐positive ...
Maria G. Herrera, Lena Kühn, Lisa Jungbluth, Verian Bader, Laura J. Krause, David Kartte, Elias Adriaenssens, Sascha Martens, Jörg Tatzelt, Carsten Sachse, Konstanze F. Winklhofer   +10 more
wiley   +1 more source

Comprehensive Profiling of N6‐methyladnosine (m6A) Readouts Reveals Novel m6A Readers That Regulate Human Embryonic Stem Cell Differentiation

Advanced Science, EarlyView.
This research deciphers the m6A transcriptome by profiling its sites and functional readout effects: from mRNA stability, translation to alternative splicing, across five different cell types. Machine learning model identifies novel m6A‐binding proteins DDX6 and FXR2 and novel m6A reader proteins FUBP3 and L1TD1.
Zhou Huang, Rucong Liu, Zibaguli Wubulikasimu, Wanqing Zhao, Jiaqi Huang, Jiaxuan Wang, Tianyuan Zhang, Rui Fan, Wei Kong, Qinghua Cui, Yang Li, Yuan Zhou   +11 more
wiley   +1 more source

Temporal and Cell‐Specific Regulation of Synaptic Homeostasis by the Chromatin Remodeler Chd1

Advanced Science, EarlyView.
Chd1, the Drosophila homologue of mammalian CHD2 ‐ a gene linked to autism, epilepsy, and intellectual disability, is required for synaptic homeostatic plasticity. Chd1 in glia is necessary for the rapid induction of synaptic homeostasis, whereas Chd1 in motoneurons, muscle, and glia is critical for long‐term maintenance.
Danielle T. Morency, Tao Cui, Yimei Cai, Chloe Lok, Rachel E. Nokku, Ruoxian Huang, Grace L. Chu, Yumeng Xie, Saleem W. Abu‐Tayeh, Kaikai He, Chengjie Qiu, Junyi Wang, Paxton M. Paganelli, Ting Wang, Gabrielle Williams, Sreejith Nair, Huadong Pei, Dion K. Dickman, Stefano Vicini, Tingting Wang   +19 more
wiley   +1 more source

p16Ink4a‐Positive Hepatocytes Drive Liver Fibrosis Through Activation of LIFR Family Pathway

Advanced Science, EarlyView.
This study found that, following the long‐term CCl4 treatment, p16high hepatocytes appeared in zone 3, spatially co‐localizing with fibrotic areas. A specific cluster of p16high hepatocytes upregulated CTF1/LIF expression which induced HSC activation and further liver fibrosis, as revealed by single cell transcriptomic analysis.
Koji Nishikawa, Teh‐Wei Wang, Satoshi Kawakami, Shota Tanimoto, Kiyoshi Yamaguchi, Taketomo Kido, Masamichi Kimura, Tsunekazu Hishima, Yuki T. Okamura, Satotaka Omori, Takumi Iritani, Toshikaze Chiba, Takehiro Jimbo, Michio Katano, Kansuporn Kamataki, Ryoichi Yokoyama, Eigo Shimizu, Kiminori Kimura, Satoshi Yamzaki, Seiya Imoto, Yoichi Furukawa, Atsushi Miyajima, Yoshikazu Johmura, Makoto Nakanishi   +23 more
wiley   +1 more source

Gαi1/3 Is a Novel Regulatory Target for RANKL Signal Transduction and Osteoporosis

Advanced Science, EarlyView.
ABSTRACT Osteoporosis, characterized by progressive bone loss and increased fracture risk, is a growing concern as the population ages. Current treatments, though advanced, remain limited, underscoring the necessity for novel therapeutic targets. Recent studies have shown that the immune system plays a key role in osteoporosis, with osteoclasts driving
Chaowen Bai, Mingchao Zhang, Le Liu, Lide Tao, Chenyang Xu, Hao Chai, Xin Shi, Yin Wang, Xiaopei Zhang, Qiong Chen, Dong Liu, Jinyu Bai, Chang She, Xiaozhong Zhou, Cong Cao, Huajian Shan   +15 more
wiley   +1 more source

B4GALNT4‐Mediated Glycosylation of PDK1 Activates the PI3K‐AKT Signaling Pathway to Promote Prostate Cancer Progression

Advanced Science, EarlyView.
This study identifies B4GALNT4 as a key driver of prostate cancer (PCa). It shows that B4GALNT4 glycosylates PDK1 protein at the N531 site, which stabilizes the PDK1 and constitutively activates the PI3K‐AKT pathway. This mechanism promotes tumor cell proliferation, migration, and invasion. The findings establish the B4GALNT4‐PDK1 glycosylation axis as
Shaoqin Jiang, Mengqiang Li, Qingfu Su, Ruiling Dou, Shaoshan Lin, Jili Zhang, Xiaochen Sun, Haolan Yu, Wei Bao, Min Qu, Yan Wang, Chenghua Yang, Xu Gao   +12 more
wiley   +1 more source

CDK4/6 Inhibition Induces CD8+ T Cell Antitumor Immunity via MIF‐Induced Functional Orchestration of Tumor‐Associated Macrophages

Advanced Science, EarlyView.
CDK4/6 inhibition promotes CD8+ T cell expansion through tumor‐macrophage crosstalk by activating HIF‐1α and enhancing MIF‐CD44/CD74 signaling. This reprograms TAMs to boost MHC‐I antigen presentation, and CDK4/6 inhibitor‐trained M1 TAM supernatant therapy synergizes with low‐dose PD‐1 blockade to restore antitumor immunity.
Lin He, Yuzhong Peng, Lat‐lun Leong, Jingbo Zhou, Dongyang Tang, Weilu Wang, Xiaoran Wu, Josh haipeng Lei, Yongqin Ye, Yangyang Feng, Yunfeng Qiao, Xiangpeng Chu, Di Mu, Qi Zhao, Tzuming Liu, Yan Chen, Paul Kwonghang Tam, Chu‐Xia Deng   +17 more
wiley   +1 more source

Pathogenic Role of FGFR3 Autoantibodies in Small Fiber Neuropathy

Advanced Science, EarlyView.
Autoantibodies against fibroblast growth factor receptor 3 (FGFR3) are identified as pathogenic drivers of pain in small fiber neuropathy. By binding to sensory neurons in dorsal root ganglia, FGFR3 autoantibodies activate MAPK signaling and induce hyperexcitability and mechanical hypersensitivity, establishing FGFR3 autoantibodies as a therapeutic ...
Lyuba Y. Salih, Nicolas L.A. Dumaire, Clémence Gieré, Erin Vest, Haya Alkhateeb, Christian P. Moritz, Yannick Tholance, Jean‐Philippe Camdessanché, Jean‐Christophe Antoine, Jérôme Honnorat, Jafar Kafaie, Liberty François‐Moutal, Aubin Moutal   +12 more
wiley   +1 more source

Aberrant SUMOylation Restricts the Targetable Cancer Immunopeptidome

Advanced Science, EarlyView.
Pharmacological SUMOylation inhibition (SUMOi) counteracts tumor immune evasion by unmasking an immunogenic HLA‐I peptide and neoepitope repertoire. By restoring HLA‐I ligand availability through increased antigen processing and presentation, enhanced proteasomal cleavage, and modulated TAP1 peptide affinity, SUMOi boosts tumor immunogenicity ...
Uta M. Demel, Anna Meurer, Badeel Kh. Q. Zaghla, Bilge Atay, Daniel Steiert, Luca V. Hummel, Konstandina Isaakidis, Chuanbing Zang, Michael Korenkov, Marlon Schielin, Schayan Yousefian, Shima Mecklenbräuker, Marieluise Kirchner, Simon Haas, Antonia Busse, Philipp Mertins, Stefan Müller, Matthias Wirth, Martin G. Klatt, Ulrich Keller   +19 more
wiley   +1 more source