Results 151 to 160 of about 1,697,349 (305)

Discovery of a Novel and Potent Kir4.1 Inhibitor as a Safe and Rapid‐Onset Antidepressant Agent in Mice

Advanced Science, EarlyView.
The preferred derivative JX3212 demonstrates strong inhibitory activity against Kir4.1 with favorable druggability and shows significant antidepressant efficacy in vivo. Abstract Major depressive disorder is a serious psychiatric disorder for which novel and fast‐acting antidepressants are required.
Sisi Wang, Xiaoyu Zhou, Mengdan Li, Chao Zhang, Haiyan Xu, Jingyi He, Li Zhan, Yueling Gu, Hao Gu, Tianyu Tu, Hanfang Liu, Taotao Lu, Yueming Zheng, Jian Li, Zhaobing Gao, Yixiang Xu   +15 more
wiley   +1 more source

CHB‐Induced Immune Zonation Chaos Elicited LXRα‐mediated Lipid Metabolism Disorders in Kupffer Cells to Induce Cancer Stem Cell Formation

Advanced Science, EarlyView.
By profiling the spatiotemporal hepatic landscape of CHB mouse models, the originally peri‐portal localized KCs migrated to the peri‐central in a CXCL9‐CXCR3‐dependent manner, facilitating their interaction with HBV+ hepatocytes. The interaction promoted LMD in KCs through ASGR1‐induced LXRα degradation, which, in turn, induced CSC formation via Stat3 ...
Jingqi Shi, Qingyu Li, Jian Li, Jian Bai, Ji Xi, Qi He, Jianglin Zhou, Xuejun Wang, Xiang Song, Xiaoju Li, Xiangpei Yue, Xiaochang Zhang, Zhen Sun, Jiangbo Li, Wen Yang, Yuke Cui, Wenjie Shu, Liang Guo, Shengqi Wang   +18 more
wiley   +1 more source

The Disordered Region of ASXL1 Acts as an Auto‐Regulator Through Condensation

Advanced Science, EarlyView.
ASXL1's long IDR encodes an electrostatic “basic platform + acidic brake” that autoregulates condensation. Truncation at a clinical hotspot lifts this brake, forming condensates that retarget BRD2, remodel local chromatin accessibility, and impair neutrophil maturation.
Xiao Fang, Qiwei Li, Wenqing Zhang
wiley   +1 more source

Dipiperazine‐Phenyl Derivatives Based on Convergent Molecular Platforms Can Reverse Multidrug Resistance in Gram‐Negative Bacteria by Inhibiting Efflux and Permeabilizing Cell Membranes

Advanced Science, EarlyView.
By integrating a convergent molecular platform strategy, this study designed a novel dual‐target C5 to combat multidrug‐resistant Gram‐negative bacteria. C5 synergistically enhances antibiotic efficacy by inhibiting efflux pumps and increasing bacterial membrane permeability.
Jiale Dong, Ting Guo, Yi Huang, Yangchun Ma, Weijin Chen, Jie Xue, Jun Jiang, Enhui Dong, Yue Kong, Hang Ding, Wenlong Zhang, Shutao Ma   +11 more
wiley   +1 more source

DualPG‐DTA: A Large Language Model‐Powered Graph Neural Network Framework for Enhanced Drug‐Target Affinity Prediction and Discovery of Novel CDK9 Inhibitors Exhibiting in Vivo Anti‐Leukemia Activity

Advanced Science, EarlyView.
This study introduces DualPG‐DTA, a framework integrating two pre‐trained models to generate molecular and protein representations. It constructs dual graphs processed by specialized neural networks with dynamic attention for feature fusion, achieving superior benchmark performance.
Yihao Chen, Jindi Huang, Cong Liu, Shipeng Zhang, Xinze Li, Zhang Zhang, Tie‐Gen Chen, Ling Wang   +7 more
wiley   +1 more source

Learned Conformational Space and Pharmacophore Into Molecular Foundational Model

Advanced Science, EarlyView.
The Ouroboros model introduces two orthogonal modules within a unified framework that independently learn molecular representations and generate chemical structures. This design enables flexible optimization strategies for each module and faithful structure reconstruction without prompts or noise.
Lin Wang, Yifan Wu, Hao Luo, Minglong Liang, Yihang Zhou, Cheng Chen, Chris Liu, Jun Zhang, Yang Zhang   +8 more
wiley   +1 more source

Does Public Service Motivation provide a guide for managers? [PDF]

Public Service Motivation (PSM) has attracted substantial academic interest. Thousands of questionnaires have been administered in many countries to examine and compare the motivation of public servants.
Mark Prebble
core  

HSP70 Interactome‐Mediated Proteolysis Targeting Chimera (HSP70‐PROTAC) for Ferroptosis‐Driven Cancer Treatment

Advanced Science, EarlyView.
This study reports a novel targeted protein degradation strategy termed “HSP70‐PROTAC” that recruits Hsc70 complex to a target protein for inducing degradation. Among them, GDAz‐3 exhibits effective GPX4 degradation activity via UPS/CMA processes, triggering ferroptosis‐driven anticancer activity in vitro and in vivo.
Jinyun Dong, Yulong Li, Hui Liang, Zumei Wu, Shiqun Wang, Yichao Wang, Jieyu Xu, Yanning Lan, Maohua Cai, Guangzhao Pan, Haiyan Yang, Kai Miao, Zhe‐Sheng Chen, Fangfang Tao, Xuelei Ma, Jiang‐Jiang Qin   +15 more
wiley   +1 more source

Assessing changes in academic motivation across medical training stages: a longitudinal study in Malaysia. [PDF]

Ann Med
Aziz CR, Mohd Noor MN, Ibrahim MF, Lin GSS, Azhary JMK, Lye AJ, Vadivelu J, Foong CC.   +7 more
europepmc   +1 more source

Hungry for Knowledge: Octopamine Signaling Regulates Hunger‐Enhanced Olfactory Learning

Advanced Science, EarlyView.
Researchers demonstrate that hunger state facilitates both aversive and appetitive olfactory learning. Two distinct octopamine signaling pathways are involved in aversive or appetitive memory formation in the hunger state. And, hunger state also facilitates the formation of both types of memories via an evolutionarily conserved norepinephrine (the ...
Huijuan Zhao, Guiyuan Shi, Ruixue Qin, Yinghao Sun, Wenbo Guo, Ruixia Shi, Minxian Peng, Jingxuan Yang, Jianjian Zhao, Qiuhan Liu, Jun Xiao, Ke Zhang, Qiang Liu, Wenxing Yang, He Liu   +14 more
wiley   +1 more source