Results 141 to 150 of about 215,799 (266)

Salvianolic Acid a Disrupts the HSP90α‐AKT‐PERK Ternary Complex to Alleviate Atherosclerosis by Activating Endoplasmic Reticulum Stress of Senescent Vascular Smooth Muscle Cells

Advanced Science, EarlyView.
Salvianolic acid A (SAA) selectively induces senescent vascular smooth muscle cell apoptosis, alleviating atherosclerosis. Mechanistically, SAA targets heat shock protein 90 alpha (HSP90α) to disrupt the protein inase B (AKT)‐PRKR‐Like Endoplasmic Reticulum Kinase (PERK) scaffold, driving ubiquitin‐proteasome‐dependent AKT degradation.
Xiuya Guan, Mengkai Lu, Xinhai Cui, Dawei Zhang, Lei Zhang, Lin Lin, Yuan Li, Yuanlong Hu, Chao Li   +8 more
wiley   +1 more source

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

Immune Checkpoint Inhibitor as a Fifth Component of Lipid Nanoparticles Enables Lymph Node‐Targeting and Augments mRNA Vaccine Efficacy

Advanced Science, EarlyView.
Here, a PDL1 inhibitor is employed as a fifth component to modify lipid nanoparticles (LNPs). PDL1 inhibitor‐loaded LNPs show enhanced lymph node targeting, resulting in greater lymph node expansion, immune cell infiltration, and improved mRNA vaccine efficacy. This fifth component LNP could be a novel platform for mRNA vaccines.
Minki Ha, Jaehyun Kim, Seyoung Kim, Gonna Somu Naidu, Sungchan Cho, Seok‐Beom Yong   +5 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

Stimulation of OGG1 Enhances Oxidative DNA Damage Repair and Protects Against Acute Liver Failure by Acetaminophen

Advanced Science, EarlyView.
Chemical switching of OGG1 by CMM‐98 accelerates oxidative DNA damage repair and enhances hepatocyte resilience during acetaminophen‐induced acute liver injury. By promoting efficient processing of OGG1‐generated repair intermediates, CMM‐98 reduces oxidative damage, preserves cellular integrity, and protects against acute liver failure, identifying ...
Zhenjun Zhao, Rahul Upadhyay, Alice Eddershaw, Chenchen Wang, Yudong Zhao, Olov Wallner, Jinhye Ryu, Nayere Taebnia, Heather Gildie, Emma Scaletti‐Hutchinson, Jonathan R. Davies, Nicole Ziegler, Andreas Krämer, Samantha C. Robinson, Marek Varga, Karolina Singerova, Zuzanna Szaruga, Elisée Wiita, İrşil Güneş, Sheila S. David, Stefan Knapp, Aimo Kannt, Miguel de Vega, Pål Stenmark, Volker M Lauschke, Maurice Michel   +25 more
wiley   +1 more source

Thermal Shifts Dominate Single‐Gene Responses to Transcription‐Targeting Antibiotics

Advanced Science, EarlyView.
Thermal shifts reshape bacterial responses to transcription‐targeting antibiotics. In E. coli, temperature can dominate antibiotic‐induced genome‐wide expression, particularly outside 30°C–39°C, through changes in adenosine triphosphate (ATP), nucleoid organization, and drug‐target engagement.
Rahul Jagadeesan, Amir M. Arsh, Vatsala Chauhan, Suchintak Dash, Pooja Ravaria, Andre S. Ribeiro   +5 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

qcGEM: A Graph‐Based Molecular Representation With Quantum Chemistry Awareness

Advanced Science, EarlyView.
In this work, we introduce qcGEM, a quantum‐chemistry‐aware graph‐based embedding of molecules that incorporates physical priors into molecular representation learning. Through a specially designed model architecture to adequately process quantum chemistry information as well as three‐dimensional molecular geometry, qcGEM provides a compact, physics ...
Haoyu Wang, Ziyan Zhang, Swee Hong Ng, Haipeng Gong   +3 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

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