Results 111 to 120 of about 144,899 (217)

Tracking CDK1 Dynamics With a Novel Biosensor Mouse and Clinical Cohorts to Predict CDK4/6 Inhibitor Sensitivity in ER+ Breast Cancer

Advanced Science, EarlyView.
Cyclin‐dependent kinase (CDK) 1 activity is a dynamic marker of treatment response in estrogen receptor positive breast cancer. Patient cohorts reveal CDK1 activity increases during progression to invasive disease, where high expression correlates with poor survival. Using a novel Cdk1 biosensor mouse alongside in vitro models, we demonstrate that CDK1
Sarah Alexandrou, Kristine J. Fernandez, Min Li Huang, Ewan K. A. Millar, Claire Vennin, Leila Eshraghi, Tan Dat Timothy Lam, Victoria Lee, Nyah C. Brooks, Janett Stoehr, Cristian Guaman Mendez, Douglas Strathdee, David Stevenson, David Herrmann, Sandra O'Toole, Paul Timpson, Max Nobis, C. Elizabeth Caldon   +17 more
wiley   +1 more source

Cannabinoid CB1 Receptor in Nociceptors Mediates Postoperative Analgesia via ASIC3 Inhibition

Advanced Science, EarlyView.
CB1R and ASIC3 are co‐expressed in CGRP+ nociceptors of mouse DRG. Plantar incision triggers an upregulation of ASIC3 and activation of ASIC3+ neurons, driving mechanical allodynia. CB1R activation suppresses ASIC3 function and downstream ERK1/2 phosphorylation, thereby braking nociceptive signaling and accelerating pain resolution.
Kangtai Xu, Luyao Ji, Haoyi Yang, Xiying Chen, Qiaodan Hu, Haimei He, Jiawei Wu, Leyan Shan, Shihui Feng, Yingzhi Li, Xiongchang Tan, Hao Wang, Zilong Wang, Chaoran Wu   +13 more
wiley   +1 more source

Molecular Signatures of HIV‐Induced Neuroinflammation and Neurodegeneration in Human Cerebral Organoids: Identification of Therapeutic Targets for NeuroHIV

Advanced Science, EarlyView.
HIV preferentially infects microglia, activating IL‐17A‐driven IFN‐γ/STAT1, CEBPB, and NF‐κB signaling that converges with cGAS‐STING and Notch–NEURL1 pathways, promoting neuroinflammation, mitochondrial dysfunction, and synaptic impairment. cART suppresses viral replication, attenuates inflammatory signaling, and at least partially restores ...
Karthick Chennakesavan, Malaroviyam Samikkannu, Shreyan Gupta, Olasunkanmi Israel Tayo, Arpan Acharya, James J. Cai, Siddappa N. Byrareddy, Thangavel Samikkannu   +7 more
wiley   +1 more source

AI‐Designed TREM1‐Targeted LYTAC Nanoparticles Reprogram the Neuroimmune Microenvironment in Traumatic Brain Injury

Advanced Science, EarlyView.
AI‐enabled de novo design of a TREM1 binder, integrated into a BBB‐crossing and macrophage‐targeted nanoplatform, enables TREM1 degradation and attenuates neuroinflammation, thereby promoting neuroprotection and tissue repair after traumatic brain injury. ABSTRACT Secondary neuroinflammation drives progressive damage after traumatic brain injury (TBI),
Yimin Huang, Yuan Liu, Huan Peng, Yu Ni, Zhengqiao Jiang, Chenxuan Yu, Xincheng Zhang, Huayu Kang, Yanchao Liu, Juan Chen, Kai Zhao, Lin Han, Xin Zou, Kai Shu, Xiaochuan Wang, Jian‐Zhi Wang, Ting Lei, Chao Gan, Jianfeng Liu, Huaqiu Zhang   +19 more
wiley   +1 more source

SCTR–Expressing Astrocyte–Serotonergic Neuron Signaling Drives Sexual Dimorphism in Depression Through KAT7/H4ac–Foxc2 Epigenetic Axis in an AMPK‐Dependent Manner

Advanced Science, EarlyView.
Astrocytic SCTR modulates depressive‐related phenotypes via AMPKα1, whereas lowered Mt1 blunts Megalin‐dependent AMPKα2 signaling in serotonergic neurons. Diminished AMPKα2 hinders KAT7 nuclear translocation, curtails KAT7 occupancy and H4K8ac at the Foxc2 promoter, and represses Foxc2 transcription, revealing cell‐type‐specific AMPK‐linked epigenetic ...
Fantao Meng, Jing Liu, Juanjuan Dai, Min Wu, Wentao Wang, Mengdi Zhang, Shujun Jiang, Yifan Cao, Lihong Xu, Lin Du, Dan Wang, Di Zhao, Gaofeng Qin, Dong Wang, Wei Li, Chen Li   +15 more
wiley   +1 more source

Neonatal Sevoflurane Exposure Induces Long‐Term Cognitive Impairment via Epigenetically Mediated MMP9 Activation and Perineuronal Net Disruption in the Hippocampal CA2

Advanced Science, EarlyView.
Hippocampal CA2 perineuronal nets ensheathing excitatory pyramidal neurons are selectively vulnerable to repeated neonatal sevoflurane exposure. Epigenetic upregulation of MMP9 via reduced H3K27me3 disrupts PNN integrity, impairs BDNF–TrkB signaling, and causes synaptic protein loss and dendritic spine deficits, leading to persistent social and spatial
Lirong Liang, Jiachen Wang, Taozhi Wang, Yanling Li, Youyi Zhao, Guanghui Hao, Peiqin Gong, Ruling Chen, Yilin Fang, Shengxi Wu, Haopeng Zhang, Hui Zhang   +11 more
wiley   +1 more source

Developmentally Guided Differentiation of Ventral Midbrain Dopaminergic Cells Validated in Proteopathy‐Based Parkinson's Disease Models

Advanced Science, EarlyView.
A developmentally guided protocol reproducibly specifies EN1‐positive ventral midbrain dopaminergic (vmDA) progenitors from human pluripotent stem cells and yields functional vmDA neurons. Optogenetic induction of α‐synuclein aggregation elicits selective degeneration of TH‐positive neurons in 2D cultures and 3D neurospheroids, while transplanted ...
Heechang Moon, Heejeong Kim, Elliot H. Lee, Hanseul Kim, Ji Hun Kim, Huisu Jeong, Jiwon Cheon, Ga Ram Jeong, Byoung Dae Lee, Jae‐Won Cho, Soo‐Jin Oh, Yunjong Lee, Yohan Oh   +12 more
wiley   +1 more source

A Spatiotemporal Single‐Cell Atlas Uncovers Dysregulated ECM Dynamics and Septal Remodeling Arrest in Human Ventricular Septal Defects

Advanced Science, EarlyView.
Integrating single‐cell and spatial transcriptomics reveals human ventricular septal defect (VSD) as a disease of microenvironmental insufficiency and structural remodeling arrest. Attenuated endothelial‐fibroblast crosstalk, alongside downregulated THBS1/TGF‐β1 and MMP2 signaling networks, impairs the endothelial‐to‐mesenchymal transition (EndoMT) and
Xiaoyuan Zhang, Lun Zhu, Ze Sun, Ruolin Jia, Ziming Wang, Jiayao Zhao, Bohao Liu, Haiqing Xiong, Xiaowei Yu, Yanzhu Yue   +9 more
wiley   +1 more source

Huntingtin Aggregate‐Responsive Autophagy Gene Circuit Mitigates Disease Pathology in R6/2 Mice

Advanced Science, EarlyView.
CD98‐mediated receptor‐mediated transcytosis enables LIP‐CD98 nanocarriers to cross the blood–brain barrier and deliver ARAA to neurons. mHTT aggregates activate the 11G–NarX sensor, initiating Auto‐P and Trans‐P signaling through the VP48–NarL relay.
Jie Zhu, Xi‐xiu Xie, Lei Li, Chen Tian, Hao‐tian Wang, Xiao‐jie Wang, Xiao‐lin Yu, Gui‐feng Zhang, Rui‐tian Liu   +8 more
wiley   +1 more source

Drug Repurposing for Treating NCOR‐Related Intellectual Disability

Advanced Science, EarlyView.
An autism‐associated NCOR1 heterozygous mutation upregulates NRGs and activates NRG backward signaling in hypothalamic GABAergic neurons in mouse models, leading to Gabra2 downregulation and cognitive deficits, which can be therapeutically targeted by repurposing FDA‐approved drugs.
Yan Kong, Wenjun Zhou, Yuxiang Sun, Zihan Huang, Zhiyue Liu, Udhaya Kumar. S, Chenyan Li, Yi Lu, Chengchuang Song, Veronica C. Ciliberto, Makenna Mack, Lana E. Kim, Zhaoyong Hu, Fang Luo, Aihua Cao, Zheng Sun   +15 more
wiley   +1 more source