A5100344296- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- Cell Adhesion Molecules Research
- Force Microscopy Techniques and Applications
- Cellular Mechanics and Interactions
- SARS-CoV-2 and COVID-19 Research
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Glycosylation and Glycoproteins Research
- Lipid Membrane Structure and Behavior
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Gene expression and cancer classification
- CRISPR and Genetic Engineering
- COVID-19 Clinical Research Studies
- Chronic Lymphocytic Leukemia Research
- Single-cell and spatial transcriptomics
- Immunodeficiency and Autoimmune Disorders
- Galectins and Cancer Biology
- NF-κB Signaling Pathways
- RNA Interference and Gene Delivery
- RNA Research and Splicing
- Computational Drug Discovery Methods
- Ubiquitin and proteasome pathways
- Protein Structure and Dynamics
Zhejiang University
2015-2025
Nanchang University
2025
Hangzhou First People's Hospital
2009-2025
Zhejiang Lab
2021-2025
Second Affiliated Hospital of Zhejiang University
2018-2024
Hangzhou Normal University
2024
Shandong First Medical University
2023-2024
Zhengzhou Central Hospital
2024
The First Affiliated Hospital, Sun Yat-sen University
2024
Zhongshan Hospital
2024
As adhesion molecules, integrins connect a cell to its environment and transduce signals across the membrane. Their different functional states correspond distinct conformations. Using biomembrane force probe, we observed real-time reversible switches between bent extended conformations of single integrin, αLβ2, on surface living by measuring nanometer-scale headpiece displacements, bending unbending frequencies, molecular stiffness changes. We determined stabilities these conformations,...
Cancer expression of PD-L1 suppresses anti-tumor immunity. has emerged as a remarkable therapeutic target. However, the regulation degradation is not understood. Here, we identify several compounds inducers using high-throughput drug screen. We find EGFR inhibitors promote ubiquitination and proteasomal following GSK3α-mediated phosphorylation Ser279/Ser283. ARIH1 E3 ubiquitin ligase responsible for targeting to degradation. Overexpression tumor growth promotes cytotoxic T cell activation in...
The early diagnosis of hepatocellular carcinoma (HCC) can greatly improve patients' 5-year survival rate, and the efficacy assessment is important for oncologists to harness anti-programmed cell death protein 1 (PD-1) immunotherapy in patients with advanced HCC. lack effective predicting biomarkers not only leads delayed detection disease but also results ineffective limited clinical benefit.We exploited single-cell approach (cytometry by time flight (CyTOF)) analyze peripheral blood...
The TCR integrates forces in its triggering process upon interaction with pMHC. Force elicits catch-slip bonds strong pMHCs but slip-only weak pMHCs. We develop two models and apply them to analyze 55 datasets, demonstrating the models' ability quantitatively integrate classify a broad range of bond behaviors biological activities. Comparing generic two-state model, our can distinguish class I from II MHCs correlate their structural parameters TCR/pMHC's potency trigger T cell activation....
L-selectin requires a threshold shear to enable leukocytes tether and roll on vascular surfaces. Transport mechanisms govern flow-enhanced tethering, whereas force governs rolling by prolonging the lifetimes of L-selectin–ligand complexes (catch bonds). Using selectin crystal structures, molecular dynamics simulations, site-directed mutagenesis, single-molecule kinetics experiments, Monte Carlo modeling, flow chamber adhesion studies, we show that eliminating hydrogen bond increase...
Abstract Targeted inhibition of Rho-associated kinase (ROCK)2 downregulates the proinflammatory T cell response while increasing regulatory arm immune in animals models autoimmunity and Th17-skewing human culture vitro. In this study, we report that oral administration a selective ROCK2 inhibitor, KD025, reduces psoriasis area severity index scores by 50% from baseline 46% patients with vulgaris, it decreases epidermal thickness as well infiltration skin. We observed significant reductions...
Abstract The combinatorial action of co-localizing chromatin modifications and regulators determines structure function. However, identifying features in a high-throughput manner remains technical challenge. Here we describe novel reChIP-seq approach tailored bioinformatic analysis tool, normR that allows for the sequential enrichment detection DNA-associated proteins an unbiased genome-wide manner. We illustrate utility method by H3K4me3 or H3K27me3 bivalently modified nucleosomes primary...
The outbreak of SARS-CoV-2 (SARS2) has caused a global COVID-19 pandemic. spike protein SARS2 (SARS2-S) recognizes host receptors, including ACE2, to initiate viral entry in complex biomechanical environment. Here, we reveal that tensile force, generated by bending the cell membrane, strengthens recognition ACE2 and accelerates detachment spike's S1 subunit from S2 rapidly prime fusion machinery. Mechanistically, such mechano-activation is fulfilled force-induced opening rotation...
Abstract Atherosclerosis (AS), a leading cause of cardio-cerebrovascular disease worldwide, is driven by the accumulation lipid contents and chronic inflammation. Traditional strategies primarily focus on reduction to control AS progression, leaving residual inflammatory risks for major adverse cardiovascular events (MACEs). While anti-inflammatory therapies targeting innate immunity have reduced MACEs, many patients continue face significant risks. Another key component in progression...
Significance Cell-expressed integrins mediate adhesion with other cells and extracellular matrix are essential for embryonic development controlling leukocyte migration in later life. Integrin depends on conformational change leading to activation, although it remains unknown exactly how alter their state response guidance cues. We show that the molecule plexinD1 controls clustering of patches cell membrane activation individual these can be switched off by binding sema3E plexinD1....
The mechanosensing ability of lymphocytes regulates their activation in response to antigen stimulation, but the underlying mechanism remains unexplored. Here, we report that B cell mechanosensing-governed requires BCR signaling molecules. PMA-induced PKCβ can bypass Btk and PLC-γ2 molecules are usually required for cells discriminate substrate stiffness. Instead, PKCβ-dependent FAK is required, leading FAK-mediated potentiation spreading adhesion responses. inactivation or deficiency...
BackgroundOn 20th Jan 2020, a new coronavirus epidemic with "human-to-human" transmission was officially announced, which inevitably caused public panic in China. Perinatal depression (PND) is one of the most common mental health problems. The purpose this study to explore impact COVID-19 outbreak on pregnant women.MethodsA total 4124 women during third trimester from 25 hospitals 10 provinces were recruited cross-sectional study, Jan/01 Feb/09, 2020. Among them, 1285 assessed after Jan/20,...
Stimulatory immune receptor NKG2D binds diverse ligands to elicit differential anti-tumor and anti-virus responses. Two conflicting degeneracy recognition models based on static crystal structures in-solution binding affinities have been considered for almost two decades. Whether how recognizes discriminates still remain unclear. Using live-cell-based single-molecule biomechanical assay, we characterized the in situ kinetics of interacting with different absence or presence mechanical force....
ABSTRACT As SARS-CoV-2 continues to evolve, increasing in its potential for greater transmissibility and immune escape, updated vaccines are needed boost adaptive immunity protect against COVID-19 caused by circulating strains. Here, we report features of the monovalent Omicron XBB.1.5-adapted BNT162b2 vaccine, which contains same mRNA backbone as original modified incorporation XBB.1.5-specific sequence changes encoded prefusion-stabilized spike protein (S(P2)). Biophysical characterization...
A common event upon receptor–ligand engagement is the formation of receptor clusters on cell surface, in which signaling molecules are specifically recruited or excluded to form hubs regulate cellular events. These often transient and can be disassembled terminate signaling. Despite general relevance dynamic clustering signaling, regulatory mechanism underlying dynamics still poorly understood. As a major antigen immune system, T receptors (TCR) spatiotemporally mediate robust yet temporal...
Cyclin Dependent Kinase 8 (CDK8) is a valuable drug target for cancer suppression. Through an effective reaction‐based virtual screening method consisting of pharmacophore modeling, Scifinder database searches, and energy evaluations, number new type II CDK8 ligands were discovered with comparable or better binding free energies than the ones reported in literature. In this method, model, derived from seven crystal structures ligands, was able to catch key interactions at ATP site CDK8. This...