A5000349809- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Diabetes Treatment and Management
- Ion Transport and Channel Regulation
- Pancreatic function and diabetes
- RNA regulation and disease
- Retinal Imaging and Analysis
- Chronic Lymphocytic Leukemia Research
- Biochemical and Molecular Research
- Cardiovascular Health and Disease Prevention
- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- RNA Research and Splicing
- Renal and Vascular Pathologies
Guangdong Academy of Medical Sciences
2024
Southern Medical University
2024
Guangdong Provincial People's Hospital
2024
Huazhong University of Science and Technology
2021-2022
Abstract Glucose homeostasis, regulated by glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon (GCG) is critical to human health. Several multi-targeting agonists at GIPR, GLP-1R or GCGR, developed maximize metabolic benefits with reduced side-effects, are in clinical trials treat type 2 diabetes obesity. To elucidate the molecular mechanisms which tirzepatide, a GIPR/GLP-1R dual agonist, peptide 20, GIPR/GLP-1R/GCGR triagonist, manifest their...
Viral infections can alter host transcriptomes by manipulating splicing machinery. Despite intensive transcriptomic studies on SARS-CoV-2, a systematic analysis of alternative (AS) in severe COVID-19 patients remains largely elusive. Here we integrated proteomic and sequencing data to study AS changes patients. We discovered that RNA is among the major down-regulated signatures The transcriptome showed SARS-CoV-2 infection induces widespread dysregulation transcript usage expression,...
Significance Glucagon-like peptide-1 receptor (GLP-1R) agonists are efficacious in the treatment of type 2 diabetes and obesity. While most clinically used agents require subcutaneous injection, Boc5, as first orthosteric nonpeptidic agonist GLP-1R, suffers from poor oral bioavailability that hinders its therapeutic development. The cryoelectron microscopy structures Boc5 closely related analog WB4-24 presented here reveal a binding pocket located deeper transmembrane domain for GLP-1R...
Abstract Class B1 of G protein-coupled receptors (GPCRs) comprises 15 members activated by physiologically important peptide hormones. Among them, vasoactive intestinal polypeptide receptor 2 (VIP2R) is expressed in the central and peripheral nervous systems involved a number pathophysiological conditions, including pulmonary arterial hypertension, autoimmune psychiatric disorders, which it thus valuable drug target. Here, we report cryo-electron microscopy structure human VIP2R bound to its...
Nanobodies and chemical cross-linking were used to gain information on the identity positions of flexible domains PI3Kα. The application mass spectrometry (CXMS) facilitated identification p85 BH, cSH2, SH3 as well their docking PI3Kα catalytic core. Binding individual nanobodies induced activation or inhibition enzyme activity caused conformational changes that could be correlated with function. nanobody Nb3-126 BH domain p85α substantially improved resolution for parts complex, binding...
To address challenges in screening for chronic kidney disease (CKD), we devised a deep learning-based CKD model named UWF-CKDS. It utilizes ultra-wide-field (UWF) fundus images to predict the presence of CKD. We validated with data from 23 tertiary hospitals across China. Retinal vessels and retinal microvascular parameters (RMPs) were extracted enhance interpretability, which revealed significant correlation between renal function RMPs. UWF-CKDS, utilizing UWF images, RMPs, relevant medical...
Summary Glucose homeostasis, regulated by glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon (GCG) is critical to human health. Several multi-targeting agonists at GIPR, GLP-1R or GCGR, developed maximize metabolic benefits with reduced side-effects, are in clinical trials treat type 2 diabetes obesity. To elucidate the molecular mechanisms which tirzepatide, a GIPR/GLP-1R dualagonist, peptide 20, GIPR/GLP-1R/GCGR triagonist, manifest their...
Abstract Glucagon-like peptide-1 receptor (GLP-1R) agonists are effective in treating type 2 diabetes and obesity with proven cardiovascular benefits. However, most of them peptides require subcutaneous injection except for orally available semaglutide. Boc5 was identified as the first orthosteric non-peptidic agonist GLP-1R that mimics a broad spectrum bioactivities GLP-1 vitro vivo . Here, we report cryo-electron microscopy structures its analog WB4-24 complex human G s protein. Bound to...
Abstract Activated by physiologically important peptide hormones, class B1 G protein-coupled receptors (GPCRs) modulate key physiological functions and serve as valuable drug targets for many diseases. Among them, vasoactive intestinal polypeptide receptor 2 (VIP2R) is the last member whose full-length 3-dimensional structure has yet to be determined. VIP2R, expressed in central peripheral nervous systems involved a number of pathophysiological conditions, implicated pulmonary arterial...