- SARS-CoV-2 and COVID-19 Research
- RNA Research and Splicing
- RNA modifications and cancer
- Bacteriophages and microbial interactions
- Monoclonal and Polyclonal Antibodies Research
- RNA and protein synthesis mechanisms
- Immunotherapy and Immune Responses
- Viral gastroenteritis research and epidemiology
- Phagocytosis and Immune Regulation
- Erythrocyte Function and Pathophysiology
- Cancer-related molecular mechanisms research
- Genomics and Chromatin Dynamics
- CAR-T cell therapy research
- Glycosylation and Glycoproteins Research
- Cancer Immunotherapy and Biomarkers
- Streptococcal Infections and Treatments
- Poxvirus research and outbreaks
- Bacillus and Francisella bacterial research
- Viral Infections and Immunology Research
- Toxin Mechanisms and Immunotoxins
- Antimicrobial Resistance in Staphylococcus
- DNA Repair Mechanisms
- Botulinum Toxin and Related Neurological Disorders
- Natural product bioactivities and synthesis
- Galectins and Cancer Biology
Chinese Academy of Sciences
2020-2025
Institute of Biophysics
2020-2025
Academy of Military Medical Sciences
2025
Institute of Pharmacology
2021-2025
University of Chinese Academy of Sciences
2021-2025
Henan University
2022
Dali University
2022
Chinese PLA General Hospital
2021-2022
Hunan Normal University
2022
Shenyang Pharmaceutical University
2021
Abstract SARS-CoV-2 carries the largest single-stranded RNA genome and is causal pathogen of ongoing COVID-19 pandemic. How folded in virion remains unknown. To fill knowledge gap facilitate structure-based drug development, we develop a situ conformation sequencing technology, named vRIC-seq, for probing viral structure unbiasedly. Using vRIC-seq data, reconstruct tertiary reveal surprisingly “unentangled globule” conformation. We uncover many long-range duplexes higher-order junctions,...
A series of novel linear aliphatic amine-linked triaryl derivatives as inhibitors PD-1/PD-L1 were designed, synthesized, and evaluated in vitro vivo. In this chemical series, compound 58 showed the most potent inhibitory activity binding affinity with hPD-L1, an IC50 value 12 nM a KD 16.2 pM, showing potency approximately 2000-fold that hPD-1. Compound could bind hPD-L1 on cellular surface competitively block interaction hPD-1 hPD-L1. T cell function assay, restored function, leading to...
Botulinum neurotoxin (BoNT) is a highly lethal toxin produced by the anaerobic bacterium Clostridium botulinum, which leads to nerve paralysis following poisoning. At present, there no specific drug officially approved. Antibodies, particularly single-domain antibodies, represent safe and effective candidates for drugs against BoNT. In this study, receptor-binding domain of botulinum (BoNT/AHCC) was utilized immunize Bactrian camels, resulting in generation nanobody phage library. From...
Nuclear RNA decay has emerged as a mechanism for post-transcriptional gene regulation in cultured cells. However, whether this process occurs animals and holds biological relevance remains largely unexplored. Here, we demonstrate that MTR4, the central cofactor of nuclear exosome, is essential embryogenesis spermatogenesis. Embryonic development Mtr4 knockout mice arrests at 6.5 day. Germ cell-specific results male infertility with specific severe defect meiotic initiation. During...
The continuous mutation of SARS-CoV-2 has presented enormous challenges to global pandemic prevention and control. Recent studies have shown evidence that the genome sequence nucleocapsid proteins is relatively conserved, their biological functions are being confirmed. There increasing N protein will not only provide a specific diagnostic marker but also become an effective treatment target. In this study, 2G4, which specifically recognizes protein, was identified by screening human phage...
Abstract SARS-CoV-2 carries the largest single-stranded RNA genome and is causal pathogen of ongoing COVID-19 pandemic. How folded in virion remains unknown. To fill knowledge gap facilitate structure-based drug development, we developed a situ conformation sequencing technology, named vRIC-seq, for probing viral structure unbiasedly. Using vRIC-seq data, reconstructed tertiary revealed surprisingly "unentangled globule" conformation. We uncovered many long-range duplexes higher-order...
Phagocytic resistance plays a key role in tumor-mediated immune escape, so phagocytosis checkpoints are potential target for cancer immunotherapy. CD47 is one of the important checkpoints; thus, blocking interaction between and signal regulatory protein <i>α</i> (SIRP<i>α</i>) may provide new options treatment. Using computer-aided targeted epitope mammalian cell-displayed antibody library, we screened obtained an engineered SIRP<i>α</i> variant fragment crystallizable fusion protein, FD164,...
Abstract SARS-CoV-2 carries the largest single-stranded RNA genome and is causal pathogen of ongoing COVID-19 pandemic. How folded in virion remains unknown. To fill knowledge gap facilitate structure-based drug development, we developed a situ conformation sequencing technology, named vRIC-seq, for probing viral structure unbiasedly. Using vRIC-seq data, reconstructed tertiary revealed surprisingly "unentangled globule" conformation. We uncovered many long-range duplexes higher-order...
Sialic acid-binding Ig-like lectin-15 is an important immunosuppressive molecule considered to be a key target in next-generation tumor immunotherapy. In this study, we screened 22 high-affinity antibodies that specifically recognize human Siglec-15 by using large phage antibody library, and five representative sequences were selected for further study. The results showed the binding activity of (EC<sub>50</sub> ranged from 0.02368 μg/mL 0.07949 μg/mL), two Siglec-15-overexpressed cell...
CD47, as an innate immune checkpoint molecule, is important target of cancer immunotherapy. We previously reported that a high-affinity SIRPα variant FD164 fused with IgG1 subtype Fc showed better antitumor effect than wild-type in immunodeficient tumor-bearing model. However, CD47 widely expressed blood cells, and the drugs targeting may cause potential hematological toxicity. Herein, we modified molecule by mutation (N297A) to inactivate Fc-related effector function named it nFD164....
SUMMARY RNA-binding proteins bind at different positions of pre-mRNA molecules to promote or reduce the usage a particular exon. Seeking understand working principle these positional effects, we develop CRIC-seq method enrich single RBP-mediated in situ RNA-RNA spatial interacting fragments for deep sequencing. We determine hnRNPA1- and PTBP1-mediated interactions regulatory mechanisms HeLa cells. Unexpectedly, 3D RNA map analysis shows that loops introns preferably cassette exon splicing by...
Immunotherapy with anti-programmed cell death protein-1 (PD-1)/programmed ligand-1 (PD-L1) monoclonal antibodies has become routine in the treatment of many kinds human cancers, such as lung cancer, intestinal and melanoma. The PD-1/PD-L1 pathway inhibits T activation micro-environment, making it an attractive target against cancer. Wild-type (WT) PD-1 ectodomain been shown to have difficulty blocking mixture formation due its low affinity. present work uses three-dimensional (3D) crystal...
SARS-CoV-2 RNA interacts with host factors to suppress interferon responses and simultaneously induces cytokine release drive the development of severe coronavirus disease 2019 (COVID-19). However, how hijacks RNAs elicit such imbalanced immune remains elusive. Here, we analyzed in situ structures interactions infected cells patient lung samples using RIC-seq. We discovered that forms 973 potential duplexes 3'UTRs 142 mRNAs increase their stability by recruiting RNA-binding protein YBX3....
RNA-binding proteins (RBPs) can bind and mediate RNA-RNA contacts. However, identifying specific RBP-organized contacts remains challenging. Here, we present a capture RIC-seq (CRIC-seq) technique to map RBP-associated globally. We describe steps for formaldehyde cross-linking fix RNA in situ conformation, pCp-biotin labeling mark juncture, proximity ligation join proximal RNAs. then detail immunoprecipitation isolate contacts, biotin-streptavidin selection enrich chimeric RNAs, library...
Siglec-15, as an important immunosuppressive molecule, is considered target in the next generation of tumor immunotherapy. In this study, we screened multiple high affinity antibodies that specifically recognized human siglec-15 by using phage antibody library with large capacity, and verified their binding, blocking biological activities vitro vivo. The results showed selected could effectively bind to overexpressed cell lines. As reported ligands siglec-15, binding activity sialyl-Tn,...