A5082943207- Viral gastroenteritis research and epidemiology
- Antibiotic Resistance in Bacteria
- Animal Virus Infections Studies
- Virus-based gene therapy research
- Viral Infections and Immunology Research
- Respiratory viral infections research
- Bacterial Genetics and Biotechnology
- Enzyme Structure and Function
- Infant Nutrition and Health
- Antibiotics Pharmacokinetics and Efficacy
- Bacteriophages and microbial interactions
- Escherichia coli research studies
- Protein Structure and Dynamics
- Lipid metabolism and biosynthesis
- Biochemical and Molecular Research
- RNA Research and Splicing
- RNA modifications and cancer
- Pneumonia and Respiratory Infections
- Hepatitis Viruses Studies and Epidemiology
- 3D Printing in Biomedical Research
- Drug Transport and Resistance Mechanisms
- Antimicrobial Resistance in Staphylococcus
- Cancer-related molecular mechanisms research
- Cancer Cells and Metastasis
- Trace Elements in Health
Baylor College of Medicine
2015-2024
Eye & ENT Hospital of Fudan University
2024
Zhejiang University of Science and Technology
2023
Huazhong University of Science and Technology
2013-2023
Tongji Hospital
2013-2023
Southern Medical University
2023
Guangdong Provincial People's Hospital
2023
Indiana University Bloomington
2020-2022
Tianjin Third Central Hospital
2021
Tianjin Medical University
2018-2021
Neonatal rotavirus infections are predominantly asymptomatic. While an association with gastrointestinal symptoms has been described in some settings, factors influencing differences clinical presentation not well understood. Using multidisciplinary approaches, we show that a complex interplay between human milk oligosaccharides (HMOs), microbiome, and infant gut microbiome impacts neonatal infections. Validating vitro studies where HMOs decoy receptors for strain G10P[11], population...
Human milk contains a rich set of soluble, reducing glycans whose functions and bioactivities are not well understood. Because human (HMGs) have been implicated as receptors for various pathogens, we explored the functional glycome using shotgun glycomics. The free from pooled samples donors with mixed Lewis Secretor phenotypes were labeled fluorescent tag separated via multidimensional HPLC to generate tagged glycan library containing 247 HMG targets that printed microarray (SGM). To...
Immunocyte infiltration and cytotoxicity play critical roles in both inflammation immunotherapy. However, current cancer immunotherapy screening methods overlook the capacity of T cells to penetrate tumor stroma, thereby significantly limiting development effective treatments for solid tumors. Here, we present an automated high-throughput microfluidic platform simultaneous tracking dynamics cell within 3D cultures with a tunable stromal makeup. By recourse clinical tumor-infiltrating...
Cooperative interactions between amino acids are critical for protein function. A genetic reflection of cooperativity is epistasis, which when a change in the acid at one position changes sequence requirements another position. To assess epistasis within an enzyme active site, we utilized CTX-M β-lactamase as model system. hydrolyzes β-lactam antibiotics to provide antibiotic resistance, allowing simple functional selection rapid sorting modified enzymes. We created all pairwise mutations...
Naturally occurring bovine-human reassortant rotaviruses with a P[11] VP4 genotype exhibit tropism for neonates. Interaction of the VP8* domain spike protein sialic acid was thought to be key mediator rotavirus infectivity. However, recent studies have indicated role nonsialylated glycoconjugates, including histo-blood group antigens (HBGAs), in infectivity human rotaviruses. We sought determine if bovine rotavirus-derived neonatal G10P[11] virus interacts hitherto uncharacterized glycans....
Abstract New Delhi metallo-β-lactamase-1 exhibits a broad substrate profile for hydrolysis of the penicillin, cephalosporin and ‘last resort’ carbapenems, thus confers bacterial resistance to nearly all β-lactam antibiotics. Here we address whether high catalytic efficiency these diverse substrates is reflected by similar sequence structural requirements catalysis, i.e., same machinery used achieve each class. Deep sequencing randomized single codon mutation libraries that were selected...
Abstract Rotaviruses (RVs) cause life-threatening diarrhea in infants and children worldwide. Recent biochemical epidemiological studies underscore the importance of histo-blood group antigens (HBGA) as both cell attachment susceptibility factors for globally dominant P[4], P[6], P[8] genotypes human RVs. How these interact with HBGA is not known. Here, our crystal structures P[4] a neonate-specific P[6] VP8*s alone complex H-type I reveal unique glycan binding site that conserved allows ABH...
Neuroinflammation plays a central role in the progression of many neurodegenerative diseases such as Alzheimer's disease, and challenges remain modeling complex pathological or physiological processes. Here, we report an acoustofluidic method that can rapidly construct 3D neurospheroids inflammatory microenvironments for microglia-mediated neuroinflammation disease. By incorporating unique contactless label-free acoustic assembly, this cell culture platform assemble dissociated embryonic...
Abstract The rational development of norovirus vaccine candidates requires a deep understanding the antigenic diversity and mechanisms neutralization virus. Here, we isolate characterize panel broadly cross-reactive naturally occurring human monoclonal IgMs, IgAs IgGs reactive with (HuNoV) genogroup I or II (GI GII). We note three binding patterns identify antibodies (mAbs) that neutralize at least one GI GII HuNoV strain when using histo-blood group antigen (HBGA) blocking assay. HBGA assay...
Abstract Human noroviruses (HuNoVs) cause sporadic and epidemic viral gastroenteritis worldwide. The GII.4 variants are responsible for most HuNoV infections, virus-like particles (VLPs) being used in vaccine development. atomic structure of the capsid native T = 3 state has not been determined. Here we present VLP with symmetry determined using X-ray crystallography cryo-EM at 3.0 Å 3.8 resolution, respectively, which reveals unanticipated novel features. A aspect crystal without imposing...
Abstract Tumor microenvironment crosstalk, in particular interactions between cancer cells, T and myeloid‐derived suppressor cells (MDSCs), mediates tumor initiation, progression, response to treatment. However, current patient‐derived models such as organoids 2D cultures lack some essential niche cell types (e.g., MDSCs) fail model complex tumor‐immune interactions. Here, the authors present novel acoustically assembled clusters (APCCs) that can preserve original tumor/immune compositions,...
Rationale: Predicting tumor responses to adjuvant therapies can potentially help guide treatment decisions and improve patient survival.Currently, pathology, histology, molecular profiles are being integrated into personalized therapeutic decisions.However, it remains a grand challenge evaluate immunotherapy for medicine.Methods: We present microfluidics-based mini-tumor chip approach predict cancer in preclinical model.By uniformly infusing dissociated cells isolated microfluidic...
Acute gastroenteritis caused by human noroviruses (HuNoVs) is a significant global health and economic burden without licensed vaccines or antiviral drugs. The GII.4 HuNoV causes most epidemics worldwide. This virus undergoes epochal evolution with periodic emergence of variants new antigenic profiles altered specificity for histo-blood group antigens (HBGA), the determinants cell attachment susceptibility, hampering development immunotherapeutics. Here, we show that llama-derived nanobody...
ABSTRACT Rotavirus (RV) replication occurs in cytoplasmic inclusions called viroplasms whose formation requires the interactions of RV proteins NSP2 and NSP5; however, specific role(s) viroplasm assembly remains largely unknown. To study context infection, we characterized two new monoclonal antibodies (MAbs) for NSP2. These MAbs show high-affinity binding to differentially recognize distinct pools RV-infected cells; a previously unrecognized cytoplasmically dispersed (dNSP2) is detected by...
We have shown that recombinant forms of VP8* domains the human rotavirus outer capsid spike protein VP4 from neonatal strains (N155(G10P[11]) and RV3(G3P[6]) a bovine strain (B223) recognize unique glycans within repertoire milk glycans. The accompanying study by Yu et al.(2), describes glycan shotgun microarray led to identification 32 specific in tagged library were recognized these rotaviruses. These analyses also provided variety metadata about structures compiled anti-glycan antibody...
Strain-dependent variation of glycan recognition during initial cell attachment viruses is a critical determinant host specificity, tissue-tropism and zoonosis. Rotaviruses (RVs), which cause life-threatening gastroenteritis in infants children, display significant genotype-dependent variations resulting from sequence alterations the VP8* domain spike protein VP4. The structural basis this particularly human RVs, remains poorly understood. Here, crystallographic studies, we show how...
β-Lactamases are bacterial enzymes that hydrolyze β-lactam antibiotics. TEM-1 is a prevalent plasmid-encoded β-lactamase in Gram-negative bacteria efficiently catalyzes the hydrolysis of penicillins and early cephalosporins but not oxyimino-cephalosporins. A previous random mutagenesis study identified W165Y/E166Y/P167G triple mutant displays greatly altered substrate specificity with increased activity for oxyimino-cephalosporin, ceftazidime, decreased toward all other β-lactams tested....
RNA binding proteins (RBPs) play a key role in genome regulation. Here we report the post-transcript regulation of IGF2BP3, which belongs to insulin-like growth factor 2 mRNA protein family. We used iRIP-seq and RNA-seq analyze transcript alternative splicing on IGF2BP3 treated with overexpression cells control. Overexpressed has broadly increased genes expression involved G-protein coupled receptor signaling pathway, positive cell proliferation, signal transduction. regulated multiple...
Bacterial resistance to β-lactam antibiotics is largely mediated by β-lactamases, which catalyze the hydrolysis of these drugs and continue emerge in response antibiotic use. β-Lactamases that hydrolyze last resort carbapenem class (carbapenemases) are a growing global health threat. Inhibitors have been developed prevent β-lactamase-mediated restore efficacy antibiotics. However, there few inhibitors available for problematic carbapenemases such as oxacillinase-48 (OXA-48). A DNA-encoded...
Abstract Human NANOG expression resets stem cells to ground-state pluripotency. Here we identify the unique features of human that relate its dose-sensitive function as a master transcription factor. is largely disordered, with C-terminal prion-like domain phase-transitions gel-like condensates. Full-length readily forms higher-order oligomers at low nanomolar concentrations, orders magnitude lower than typical amyloids. Using single-molecule Förster resonance energy transfer and...