A5103100709- Hepatitis C virus research
- Hepatitis B Virus Studies
- interferon and immune responses
- Bacteriophages and microbial interactions
- Liver Disease Diagnosis and Treatment
- Medical Imaging and Pathology Studies
- Parathyroid Disorders and Treatments
- Medical Imaging Techniques and Applications
- MRI in cancer diagnosis
- Topic Modeling
- Viral Infections and Vectors
- HIV Research and Treatment
- Cancer-related molecular mechanisms research
- Hepatitis Viruses Studies and Epidemiology
- RNA regulation and disease
- HIV/AIDS drug development and treatment
- Alkaloids: synthesis and pharmacology
- Sentiment Analysis and Opinion Mining
- Chemical synthesis and alkaloids
- Sirtuins and Resveratrol in Medicine
- SARS-CoV-2 and COVID-19 Research
- MicroRNA in disease regulation
- Berberine and alkaloids research
- Phagocytosis and Immune Regulation
- Cellular transport and secretion
West China Hospital of Sichuan University
2019-2024
Sichuan University
2018-2024
Baruch S. Blumberg Institute
2016-2023
Jingchu University of Technology
2022
Roche (China)
2021
Chinese Academy of Medical Sciences & Peking Union Medical College
2014-2020
Shanxi Medical University
2020
Hepatitis B Foundation
2017-2020
Henan University
2019
Tsinghua University
2014
ABSTRACT Interferon-induced transmembrane proteins (IFITMs) are restriction factors that inhibit the infectious entry of many enveloped RNA viruses. However, we demonstrated previously human IFITM2 and IFITM3 essential host facilitating coronavirus (HCoV) OC43. In a continuing effort to decipher molecular mechanism underlying IFITM differential modulation HCoV entry, investigated roles structural motifs important for protein posttranslational modifications, intracellular trafficking,...
Hepatitis B virus (HBV) core protein assembles viral pre-genomic (pg) RNA and DNA polymerase into nucleocapsids for reverse transcriptional replication to take place. Several chemotypes of small molecules, including heteroaryldihydropyrimidines (HAPs) sulfamoylbenzamides (SBAs), have been discovered allosterically modulate structure consequentially alter the kinetics pathway assembly, resulting in formation irregularly-shaped aggregates or "empty" capsids devoid polymerase. Interestingly,...
In order to identify host cellular DNA metabolic enzymes that are involved in the biosynthesis of hepatitis B virus (HBV) covalently closed circular (ccc) DNA, we developed a cell-based assay supporting synchronized and rapid cccDNA synthesis from intracellular progeny nucleocapsid DNA. This was achieved by arresting HBV replication HepAD38 cells with phosphonoformic acid (PFA), reversible polymerase inhibitor, at stage single-stranded followed removal PFA allow relaxed (rcDNA) subsequent...
ABSTRACT Hepatitis B virus (HBV) core protein consists of an N-terminal assembly domain and a C-terminal (CTD) with seven conserved serines or threonines that are dynamically phosphorylated/dephosphorylated during the viral replication cycle. Sulfamoylbenzamide derivatives small molecular allosteric modulators (CpAMs) bind to heteroaryldihydropyrimidine (HAP) pocket between dimer-dimer interfaces. CpAM binding alters kinetics pathway capsid can result in formation morphologically “normal”...
ABSTRACT Induction of interferon and proinflammatory cytokines is a hallmark the infection many different viruses. However, hepatitis B virus (HBV) does not elicit detectable cytokine response in infected hepatocytes. In order to investigate molecular mechanism underlying innate immune evasion, functional cyclic GMP-AMP (cGAMP) synthase (cGAS)-stimulator genes (STING) pathway was reconstituted human hepatoma cell line supporting tetracycline-inducible HBV replication. It demonstrated that...
Abstract The cluster of differentiation 36 (CD36) is a membrane protein related to lipid metabolism. We show that HCV infection in vitro increased CD36 expression either surface or soluble form. attachment was facilitated through direct interaction between and E1 protein, causing enhanced entry replication. co-receptor effect independent SR-BI. monoclonal antibodies neutralized the reduced inhibitor sulfo-N-succinimidyl oleate (SSO), which directly bound but not SR-BI, significantly...
Stimulator of interferon genes (STING) is an integral ER-membrane protein that can be activated by 2'3'-cGAMP synthesized cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) upon binding double-stranded DNA. It activates (IFN) and inflammatory cytokine responses to defend against infection microorganisms. Pharmacologic activation STING has been demonstrated induce antiviral state boost antitumor immunity. We previously reported a cell-based high-throughput-screening assay...
Hepatitis B virus (HBV) core protein is a small with 183 amino acid residues and assembles the pregenomic (pg) RNA viral DNA polymerase to form nucleocapsids. During last decades, several groups have reported HBV allosteric modulators (CpAMs) distinct chemical structures. CpAMs bind hydrophobic HAP pocket located at dimer–dimer interface induce conformational changes in subunits. While Type I CpAMs, heteroaryldihydropyrimidine (HAP) derivatives, misdirect dimers assemble noncapsid polymers,...
Abstract Lycorine is reported to be a multifunctional compound. We previously showed that lycorine an HCV inhibitor with strong activity. Further research on the antivirus mechanism indicated does not affect enzymes are indispensable replication but suppresses expression of Hsc70 in host cell limit replication. However, due cytotoxicity and apoptosis induction lycorine, unsafe anti-HCV agent for clinical application. As result increasing interest, its structure was optimized first time novel...
Automatic extraction of new words is an indispensable precursor to many NLP tasks such as Chinese word segmentation, named entity extraction, and sentiment analysis.This paper aims at extracting from large-scale user-generated content.We propose a fully unsupervised, purely data-driven framework for this purpose.We design statistical measures respectively quantify the utility lexical pattern measure possibility being word.The method almost free linguistic resources (except POS tags),...
Abstract A 68 Ga-DOTATATE PET/CT scan was conducted to locate the causative tumor responsible for suspected tumor-induced osteomalacia in a 56-year-old woman. The images showed focus right occipital region. Subsequent MRI an extra-axial nodule region, mimicking meningioma. Although rare, intracranial phosphaturic mesenchymal still because of typical clinical settings. Finally, confirmed by postoperative pathology.
Pegylated IFN-α is the only therapeutic regimen that can induce a functional cure of chronic hepatitis B in small, but significant, fraction treated patients. Understanding mechanisms underlying antiviral functions hepadnaviral infection may reveal molecular targets for development novel agents to improve efficacy IFN-α. By loss-of-function genetic screening individual IFN-stimulated genes (ISGs) on mRNAs transcribed from cccDNA, we found downregulating expression STAT1, SMCHD1, or PML...
Upon infection of hepatocyte, Hepatitis B virus (HBV) genomic DNA in nucleocapsid is transported into the nucleus and converted a covalently closed circular (ccc) to serve as template for transcription viral RNAs. Viral cytoplasmic progeny another resource fuel cccDNA amplification. Apparently, disassembly, or uncoating, an essential step synthesis from both de novo intracellular amplification pathways, has potential activate sensors induce innate immune response infected hepatocytes....
We aimed to construct an artificial intelligence (AI) guided identification of suspicious bone metastatic lesions from the whole-body scintigraphy (WBS) images by convolutional neural networks (CNNs).We retrospectively collected 99mTc-MDP WBS with confirmed 3352 patients malignancy. 14,972 were delineated manually physicians and annotated as benign malignant. The lesion-based differentiating performance proposed network was evaluated fivefold cross validation, compared other three popular...
Background: A new series of potential phenanthridine hepatitis C virus (HCV) inhibitors which work by suppressing Hsc70 expression in the host cell was designed and synthesized from lycorine. Results: Thirty-one HCV were five these compounds exhibited good anti-HCV activity probably inhibit downregulating expression. Structure-activity analysis revealed that double bond between C-11 C-12 substituents at C-8 C-9 are important for their against HCV. Conclusion: Suppression to limit replication...
Bicyclol is a synthetic drug for hepatoprotection in clinic since 2004. Preliminary clinical observations suggest that bicyclol might be active against hepatitis C virus (HCV) with unknown mechanism. Here, we showed significantly inhibited HCV replication vitro and patients. Using as probe, identified glycolipid transfer protein (GLTP) to novel restrictive factor replication. The GLTP preferentially bound host vesicle-associated membrane protein-associated protein-A (VAP-A) competition the...
A previous study reported that ginsenoside-Rd reduced the production of tumor necrosis factor-α by inhibiting nuclear factor-κB in lipopolysaccharide-activated N9 microglia vitro. The aim present was to confirm anti-inflammatory effects and mechanisms animal experiments involving acute inflammation. results indicated at doses ranging from 12.5 50 mg/kg i.m. significantly inhibited swelling hind paws rats for 1–6 h after carrageenan injection. levels proinflammatory cytokines mediators were...
The core protein (Cp) of hepatitis B virus (HBV) assembles pregenomic RNA (pgRNA) and viral DNA polymerase to form nucleocapsids where the reverse transcriptional replication takes place. Core allosteric modulators (CpAMs) inhibit HBV by binding a hydrophobic “HAP” pocket at Cp dimer-dimer interfaces misdirect assembly dimers into aberrant or morphologically “normal” capsids devoid pgRNA. We report herein that panel CpAM-resistant with single amino acid substitution residues interface not...