A5010033344- Proteoglycans and glycosaminoglycans research
- Glycosylation and Glycoproteins Research
- Carbohydrate Chemistry and Synthesis
- Protease and Inhibitor Mechanisms
- Platelet Disorders and Treatments
- Alzheimer's disease research and treatments
- Fibroblast Growth Factor Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Protein Kinase Regulation and GTPase Signaling
- Molecular Sensors and Ion Detection
- Cell Adhesion Molecules Research
- Advanced Glycation End Products research
- Wnt/β-catenin signaling in development and cancer
- S100 Proteins and Annexins
- Bone Metabolism and Diseases
- Luminescence and Fluorescent Materials
- Sepsis Diagnosis and Treatment
- Chemical Synthesis and Analysis
- Bone health and treatments
- 14-3-3 protein interactions
- Endoplasmic Reticulum Stress and Disease
- Drug-Induced Hepatotoxicity and Protection
- Biochemical and Structural Characterization
- Advancements in Semiconductor Devices and Circuit Design
- Semiconductor materials and devices
University of North Carolina at Chapel Hill
2017-2025
Hangzhou Red Cross Hospital
2025
NewGen Therapeutics (United States)
2023-2024
University of North Carolina Health Care
2020
Communities In Schools of Orange County
2020
Zhejiang University of Technology
2015-2017
Shanghai Institute of Organic Chemistry
2007-2008
Chinese Academy of Sciences
2007
The Ohio State University
2007
SunEdison (United States)
2002
Septic patients frequently develop cognitive impairment that persists beyond hospital discharge. The impact of sepsis on electrophysiological and molecular determinants learning is underexplored. We observed mice survived or endotoxemia experienced loss hippocampal long-term potentiation (LTP), a brain-derived neurotrophic factor-mediated (BDNF-mediated) process responsible for spatial memory formation. Memory occurred despite preserved BDNF content could be reversed by stimulation...
Abstract Prion‐like transcellular spreading of tau in Alzheimer's Disease (AD) is mediated by binding to cell surface heparan sulfate (HS). However, the structural determinants for tau–HS interaction are not well understood. Microarray and SPR assays structurally defined HS oligosaccharides show that a rare 3‐ O ‐sulfation (3‐ ‐S) significantly enhances binding. In Hs3st1 −/− (HS ‐sulfotransferase‐1 knockout) cells, reduced ‐S levels diminished both internalization tau. culture, addition...
Synthetic heparan sulfate protects against drug-induced acute liver failure by inhibiting the proinflammatory activity of HMGB1/RAGE axis.
Abstract Chondroitin sulfate (CS) is a sulfated polysaccharide that plays essential physiological roles. Here, we report an enzyme‐based method for the synthesis of library 15 different CS oligosaccharides. This covers 4‐O‐sulfated and 6‐O‐sulfated oligosaccharides ranging from trisaccharides to nonasaccharides. We also describe unnatural pentasaccharides containing either 6‐O‐sulfo‐2‐azidogalactosamine or 6‐O‐sulfogalactosamine residue. The availability structurally defined offers novel...
HS3ST1 is a genetic risk gene associated with Alzheimer’s disease (AD) and overexpressed in patients, but how it contributes to the progression unknown. We report analysis of brain heparan sulfate (HS) from AD other tauopathies using LC-MS/MS method. A specific 3- O -sulfated HS displayed sevenfold increase group ( n = 14, P < 0.0005). Analysis modified by recombinant sulfotransferases knockout mice revealed that made -sulfotransferase isoform 1 (3-OST-1), which encoded gene. synthetic...
Apolipoprotein E (ApoE)'s ϵ4 alle is the most important genetic risk factor for late onset Alzheimer's Disease (AD). Cell-surface heparan sulfate (HS) a cofactor ApoE/LRP1 interaction and prion-like spread of tau pathology between cells. 3-O-sulfo (3-O-S) modification HS has been linked to AD through its with tau, enhanced levels 3-O-sulfated 3-O-sulfotransferases in brain. In this study, we characterized ApoE/HS interactions wildtype ApoE3, AD-linked ApoE4, AD-protective ApoE2...
Chondroitin sulfate E (CS-E) is a sulfated polysaccharide that contains repeating disaccharides of 4,6-disulfated N-acetylgalactosamine and glucuronic acid residues. Here, we report the enzymatic synthesis three homogeneous CS-E oligosaccharides, including heptasaccharide (CS-E 7-mer), tridecasaccharide (CS-E13-mer), nonadecasaccharide 19-mer). The anti-inflammatory effect 19-mer was investigated in this study. neutralizes cytotoxic histones cell-based assay mice. We also demonstrate...
Heparan sulfate (HS) has multifaceted biological activities. To date, no libraries of HS oligosaccharides bearing systematically varied sulfation structures are available owing to the challenges in synthesizing a large number oligosaccharides. overcome obstacles and expedite synthesis, divergent approach was designed, where 64 tetrasaccharides covering all possible 2-O-, 6-O- N-sulfation with glucosamine-glucuronic acid-glucosamine-iduronic acid backbone were successfully produced from...
Heparan sulfate (HS) is a heterogeneous, extracellular glycan that interacts with proteins and other molecules affecting many biological processes. The specific binding motifs of HS interactions are interest, but have not been extensively characterized. Glycan microarrays valuable tools can be used to probe the between glycans their ligands while relying on relatively small amounts samples. Recently, chemoenzymatic synthesis has employed produce structures otherwise difficult produce. In...
An automated machine-aided solid phase synthesis of heparan sulfate (HS) has been established for the first time. With significantly reduced number synthetic and purification steps, 16 HS disaccharides have readily assembled.
Understanding the different pharmacodynamic responses to narcotics in patients with or without obesity is particularly important for safety of gastroscopy sedation. This study aimed determine median effective dose (ED50) ciprofol combined low-dose sufentanil inhibit response gastroscope insertion obese nonobese patients. A total 27 (BMI 30-40 kg/m2) and 25 18-25 kg/m2), aged between 18 65 years, ASA physical status 1-2, were included this study. All underwent painless received intravenous at...
Heparan sulfate (HS) and chondroitin (CS) are two structurally distinct natural polysaccharides. Here, we report the synthesis of a library seven homogeneous HS CS chimeric dodecasaccharides (12-mers). The was accomplished using six biosynthetic enzymes four enzymes. chimeras contain domain on reducing end nonreducing end. synthesized display anticoagulant activity as measured by both in vitro ex vivo experiments. Furthermore, H/C 12-mer 5 is reversible protamine, U.S. Food Drug...
A Brønsted acid-catalyzed highly efficient construction of substituted arylanthracenes and heteroacenes is described, which assumed to be initiated through the facile formation a benzylic cation intermediate. This method offers several advantages in comparison with known aromatic cyclodehydration reactions such as high selectivities, mild reaction conditions, easily accessible starting materials.
Abstract Heparan sulfate is a sulfated polysaccharide that displays essential physiological functions. Here, we report LC-MS/MS-based method for quantitatively determining the individual disaccharide composition and total amount of heparan sulfate. Using eight 13 C-labeled calibrants one calibrant, complete analysis in one-pot process. The both sensitive has throughput to analyze from mouse tissues plasma.
Considering the high correlation between functional decline in Alzheimer's disease (AD) and propagation of aggregated tau protein, many research efforts are focused on determining underlying molecular mechanisms spreading. Heparan sulfate proteoglycans (HSPGs) were reported to mediate cellular uptake aggregates. Specifically, heparan sulfates (HS) sulfation plays a critical role interaction HSPGs with tau. HS can be N-/2-O/6-O- or 3-O-sulfated, some which have been take part However, 3-O...
Abstract Sulf-2 is an extracellular heparan 6-O-endosulfatase involved in the postsynthetic editing of sulfate (HS), which regulates many important biological processes. The activity and its substrate specificity remain insufficiently characterized spite more than two decades studies this enzyme. This due, part, to difficulties production isolation highly modified protein due lack well-characterized synthetic substrates for probing catalytic activity. We introduce HS oligosaccharides fill...
Cystatin C (Cst-3) is a potent inhibitor of cysteine proteases with diverse biological functions. As secreted protein, the potential interaction between Cst-3 and extracellular matrix components has not been well studied. Here we investigated heparan sulfate (HS), major component matrix. We discovered that HS-binding protein only at acidic pH. By NMR site-directed mutagenesis, identified two HS binding regions in Cst-3: highly dynamic N-terminal segment flexible region located residue 70-94....
Heparan sulfate (HS) 3-O-sulfotransferase isoform 4 (3-OST-4) is a specialized carbohydrate sulfotransferase participating in the biosynthesis of heparan sulfate. Here, we report expression and purification recombinant 3-OST-4 enzyme use it for synthesis library 3-O-sulfated hexasaccharides octasaccharides. The unique structural feature that each oligosaccharide contains disaccharide domain with 2-O-sulfated glucuronic acid (GlcA2S) glucosamine (GlcNS3S). By rearranging order enzymatic...
Literature has well-established the importance of 3- O -sulfation neuronal cell surface glycan heparan sulfate (HS) to its interaction with herpes simplex virus type 1 glycoprotein D (gD). Previous investigations gD viral receptors HVEM and nectin-1 also highlighted conformational dynamics gD’s N- C-termini, necessary for membrane fusion. However, little is known on structural interactions HS. Here, we present our findings this interface from both protein perspective. We used C-terminal...
Heparan sulfates (HSs) are widely expressed glycans in the animal kingdom. HS plays a role regulating cell differentiation/proliferation, embryonic development, blood coagulation, inflammatory response, and viral infection. The amount of its structural information critically important for investigating functions vivo. A sensitive reliable quantitative technique analysis from biological samples is under development. Here, we report new labeling reagent disaccharides analysis,...