- Receptor Mechanisms and Signaling
- Immune Response and Inflammation
- Drug Transport and Resistance Mechanisms
- Helicobacter pylori-related gastroenterology studies
- Neuropeptides and Animal Physiology
- Cellular transport and secretion
- Biochemical and Structural Characterization
- Mass Spectrometry Techniques and Applications
- Protein Structure and Dynamics
- Diabetes Treatment and Management
- Inflammasome and immune disorders
- Monoclonal and Polyclonal Antibodies Research
- Sphingolipid Metabolism and Signaling
- Thermal properties of materials
- Thermal Radiation and Cooling Technologies
- Machine Learning in Bioinformatics
- Leptospirosis research and findings
- Prostate Cancer Treatment and Research
- Facility Location and Emergency Management
- Fungal and yeast genetics research
- Thermal Regulation in Medicine
- Biotin and Related Studies
- Urban and Freight Transport Logistics
- Metabolism and Genetic Disorders
- Chemical Synthesis and Analysis
University of Chinese Academy of Sciences
2022-2024
National Center for Drug Screening
2016-2024
Shanghai Institute of Materia Medica
2016-2024
Chinese Academy of Sciences
2012-2024
University of Science and Technology of China
2024
Jiangnan University
2020
Chinese University of Hong Kong
2013-2017
Tongji University
2016
Nagoya University
2016
Institute of Hematology & Blood Diseases Hospital
2016
Background: Liver fibrosis affects millions of people worldwide without an effective treatment.Although multiple cell types in the liver contribute to fibrogenic process, hepatocyte death is considered be trigger.Multiple forms death, including necrosis, apoptosis, and necroptosis, have been reported co-exist diseases.Mixed lineage kinase domain-like protein (MLKL) terminal effector necroptosis pathway.Although has play important role a number diseases, function MLKL yet unraveled.Methods...
Abstract GPR84 is an orphan class A G protein-coupled receptor (GPCR) that predominantly expressed in immune cells and plays important roles inflammation, fibrosis, metabolism. Here, we present cryo-electron microscopy (cryo-EM) structures of Gα i human bound to a synthetic lipid-mimetic ligand, LY237, or putative endogenous medium-chain fatty acid (MCFA) 3-hydroxy lauric (3-OH-C12). Analysis these two ligand-bound reveals unique hydrophobic nonane tail -contacting patch, which forms...
Acute lung injury (ALI) is an acute, progressive hypoxic respiratory failure that could develop into acute distress syndrome (ARDS) with very high mortality rate. ALI believed to be caused by uncontrolled inflammation, and multiple types of immune cells, especially neutrophils, are critically involved in the development ALI. The treatment for ALI/ARDS limited, a better understanding pathogenesis new therapies urgently needed. Here we discover GPR84, medium chain fatty acid receptor, plays...
Highly thermally conductive and flexible thermal interface materials (TIMs) are desirable for heat dissipation in modern electronic devices. Here, we fabricated a high-crystalline aligned graphene lamella framework (AGLF) with precisely controlled thickness, pore structure, excellent intergraphene contact by manipulating the expansion behavior of scanning centrifugal casted oxide films. The rational design AGLF balances trade-off between conductivity flexibility TIMs. AGLF-based TIM...
Few molecular events important to platelet biogenesis have been identified. Mice homozygous for the spontaneous, recessive mutation gunmetal ( gm ) prolonged bleeding, thrombocytopenia, and reduced α- δ-granule contents. Here we show by positional cloning that results from a G→A substitution in splice acceptor site within α-subunit of Rab geranylgeranyl transferase Rabggta ), an enzyme attaches groups proteins. Most mRNAs tissues skipped exon 1 lacked start codon. protein (GGTase) activity...
Abstract The putative medium-chain free fatty acid receptor GPR84 is a G protein-coupled primarily expressed in myeloid cells that constitute the innate immune system, including neutrophils, monocytes, and macrophages periphery microglia brain. fact expression leukocytes remarkably increased under acute inflammatory stimuli such as lipopolysaccharide (LPS) TNFα suggests it may play role development of fibrotic diseases. Here we demonstrate highly upregulated inflamed colon tissues active...
Although endogenous ligands for Toll-like receptor (TLR)4–myeloid differentiation factor 2 (MD2) have not been well-understood, we here report that a globo-series glycosphingolipid, globotetraosylceramide (Gb4), attenuates the toxicity of lipopolysaccharides (LPSs) by binding to TLR4–MD-2. Because α1,4-galactosyltransferase (A4galt)-deficient mice lacking glycosphingolipids showed higher sensitivity LPS than wild-type mice, examined mechanisms which attenuate toxicity. Cultured endothelial...
Disulfide bonds are traditionally considered to play only structural roles. In recent years, increasing evidence suggests that the disulfide proteome is made up of disulfides and reversible disulfides. Unlike disulfides, usually important functional roles may serve as redox switches. Interestingly, specific while others not. However, whether can be predicted based on information remains largely unknown. this study, two datasets with both types were compiled using independent approaches. By...
A series of alkylpyrimidine-4,6-diol derivatives were designed and synthesized as novel GRP84 agonists based on a high-throughput screening (HTS) hit 1. 6-Nonylpyridine-2,4-diol was identified the most potent agonist GPR84 reported so far, with an EC50 0.189 nM. These will provide valuable tools for study physiological functions GPR84.
G protein-coupled receptor 84 (GPR84) is a free fatty acid activated by medium-chain acids with 9–14 carbons. It expressed mainly in the immune-related tissues, such as spleen, bone marrow, and peripheral blood leukocytes. GPR84 plays significant roles inflammatory processes may represent novel drug target for treatment of immune-mediated diseases. However, lack potent specific ligands hindered study its functions development potential clinical applications. Here, we report screen 160,000...
GPR84 is a proinflammatory G protein-coupled receptor associated with several inflammatory and fibrotic diseases. antagonists have been evaluated in clinical trials to treat ulcerative colitis, idiopathic pulmonary fibrosis, nonalcoholic steatohepatitis. However, the variety of potent selective still limited. Through high-throughput screening, novel phosphodiester compound hit 1 was identified as antagonist. The subsequent structural optimization led identification 33 improved potency...
ABSTRACT The increasing accumulation of e‐waste containing precious metals calls for the development efficient recycling strategies gold recovery from e‐waste. In this study, we present scalable fabrication (up to 3600 cm 2 ) rGO/cellulose composite papers with a high rGO areal density 7.5 g/m and their use as large‐area adsorbents extraction. resulting rGO@cellulose exhibits excellent extraction capacity, achieving 20 36.3 at 25°C 60°C, respectively, which translates gravimetric capacities...
A new strategy is established for detecting chiral amino acids based on the electron transfer from hemoglobin Fe(II) to Cu(II) in copper complexes of acids. The sensor shows a highly selective recognition arginine enantiomers.
Since the discovery of medium-chain fatty acids as GPR84 ligands, significant advancements have been made in development agonists and antagonists. Most lipid-like structures except for 3,3′-diindolylmethane (DIM), which acts an allosteric agonist. activation macrophages leads to increased cytokine secretion, chemotaxis, phagocytosis, revealing proinflammatory role associated with various inflammatory responses. Three antagonists...
Alzheimer's disease (AD) is the most prevalent form of dementia characterized by extracellular accumulation amyloid β (Aβ) peptides, which are produced proteolytic cleavages precursor protein (APP). Gangliosides involved in AD pathophysiology including Aβ deposition and APP processing, yet detailed mechanisms not fully understood. Here we examined how changes carbohydrate moiety gangliosides alter processing human melanoma cells, neuroectoderm-derived cells. We showed that forced expression...
Type III secretion system (T3SS) plays important roles in bacteria and host cell interactions by specifically translocating type effectors into the cytoplasm of cells. The N-terminal amino acid sequences bacterial determine their specific via conduits. It is still unclear as to how guide this specificity. In work, composition, secondary structure, solvent accessibility N-termini non-type secreted proteins were compared contrasted. A high-efficacy mathematical model based on these joint...
Schwann cells are not only myelinating cells, but also function as immune and express numerous innate pattern recognition receptors, including the Toll-like receptors. Injury to peripheral nerves activates an inflammatory response in cells. However, it is unclear whether specific endogenous damage-associated molecular molecules involved following nerve injury. In present study, we demonstrate that a key molecule, high mobility group box 1 (HMGB1), upregulated rat sciatic axotomy, show...
A general approach is presented for developing small molecule-based fluorogenic probes suitable no-wash imaging of endogenous kinases in live cells.
GPR84 is a proinflammatory G protein-coupled receptor that mediates myeloid immune cell functions. Blocking with antagonists promising approach for treating inflammatory and fibrotic diseases. Previously, antagonist 604c, symmetrical phosphodiester structure, has displayed efficacy in mouse model of ulcerative colitis. However, the low blood exposure resulting from physicochemical properties prevented its uses other In this study, series unsymmetrical phosphodiesters lower lipophilicity were...
Summary. The mutant gunmetal mouse exhibits reduced rates of platelet synthesis, abnormalities alpha and dense granules hypopigmentation. Several these features resemble those human alpha/delta storage pool disease, grey syndrome Hermansky–Pudlak syndrome. Gunmetal mice have levels Rab geranylgeranyltransferase (RabGGTase), which adds lipophilic prenyl groups to the carboxyl terminus proteins. degree prenylation subcellular distribution several proteins were evaluated in platelets,...