A5021898065- Microbial Natural Products and Biosynthesis
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- Genomics and Phylogenetic Studies
- Acupuncture Treatment Research Studies
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Peptidase Inhibition and Analysis
- Advanced Computational Techniques and Applications
- Cancer Cells and Metastasis
- Cancer-related gene regulation
- PARP inhibition in cancer therapy
- Viral Infectious Diseases and Gene Expression in Insects
- Chemical Synthesis and Analysis
- Entomopathogenic Microorganisms in Pest Control
- Circular RNAs in diseases
- Botulinum Toxin and Related Neurological Disorders
- Neonatal Respiratory Health Research
- Traditional Chinese Medicine Studies
- Cancer Research and Treatments
- Anomaly Detection Techniques and Applications
- CRISPR and Genetic Engineering
- Antifungal resistance and susceptibility
- Microbial Metabolic Engineering and Bioproduction
- Pancreatic function and diabetes
- BRCA gene mutations in cancer
Kadlec Clinic
2018-2024
University of Manchester
2016-2023
Zigong First People's Hospital
2023
Sun Yat-sen University
2013-2022
Prozomix (United Kingdom)
2021
Kadlec Regional Medical Center
2014-2019
Chinese Academy of Sciences
2007-2014
Institute of Microbiology
2007-2014
Medical Research Associates
2014
Tulane University
2001-2013
The high mortality rate of immunocompromised patients with fungal infections and the limited availability highly efficacious safe agents demand development new antifungal therapeutics. To rapidly discover such agents, we developed a high-throughput synergy screening (HTSS) strategy for novel microbial natural products. Specifically, product library was screened hits that synergize effect low dosage ketoconazole (KTC) alone shows little detectable fungicidal activity. Through approximately...
The aberrant expression of transforming growth factor (TGF)-beta1 in the tumor microenvironment and fibrotic lesions plays a critical role progression tissue fibrosis by inducing epithelial-mesenchymal transition (EMT). EMT promotes cell motility invasiveness. How affects invasion is not well understood. Here we report that HDAC6 novel modulator TGF-beta1-induced EMT. microtubule-associated deacetylase predominantly deacetylates nonhistone proteins, including alpha-tubulin, regulates...
Abstract Background The tumor microenvironment is a crucial determinant in progression. Interstitial extracellular matrix (ECM), such as type I collagen (Col-1), aberrantly enriched the and promotes Long intergenic non-coding RNAs (lincRNA) are new family of regulatory that modulate fundamental cellular processes via diverse mechanisms. Findings We investigated whether expression lincRNAs was regulated by promoting Col-1. In three-dimensional organotypic culture model using reconstituted...
The Covid-19 pandemic highlights the urgent need for cost-effective processes to rapidly manufacture antiviral drugs at scale. Here we report a concise biocatalytic process Molnupiravir, nucleoside analogue recently approved as an orally available treatment SARS-CoV-2. Key success of this was development efficient biocatalyst production N-hydroxy-cytidine through evolutionary adaption hydrolytic enzyme cytidine deaminase. This engineered performs >85 000 turnovers in less than 3 h, operates...
Avermectin and its analogues are produced by the actinomycete Streptomyces avermitilis widely used in field of animal health, agriculture, human health. Here we have adopted a practical approach to successfully improve avermectin production an industrial overproducer. Transcriptional levels wild-type strain overproducer cultures were monitored using microarray analysis. The biosynthetic genes, especially pathway-specific regulatory gene, aveR , up-regulated high-producing strain. upstream...
Re-engineering biosynthetic assembly lines, including nonribosomal peptide synthetases (NRPS) and related megasynthase enzymes, is a powerful route to new antibiotics other bioactive natural products that are too complex for chemical synthesis. However, engineering megasynthases very challenging using current methods. Here, we describe how CRISPR-Cas9 gene editing can be exploited rapidly engineer one of the most lines in nature, 2.0 MDa NRPS enzymes deliver lipopeptide antibiotic...
Bioorthogonal chemistry enables a specific moiety in complex biomolecule to be selectively modified the presence of many reactive functional groups and other cellular entities. Such selectivity has become indispensable biology, enabling biomolecules derivatized, conjugated, labeled, or immobilized for imaging, biochemical assays, therapeutic applications. Methyltransferase enzymes (MTase) that accept analogues cofactor S-adenosyl methionine have been widely deployed alkyl-diversification...
In the wake of Covid-19 pandemic, it has become clear that global access to efficacious antiviral drugs will be critical combat future outbreaks SARS-CoV-2 or related viruses. The orally available main protease inhibitor nirmatrelvir proven an effective treatment option for Covid-19, especially in compromised patients. We report a new synthesis featuring highly enantioselective biocatalytic desymmetrization (>99% ee) and diastereoselective multicomponent reaction (>25:1 dr) as key steps. Our...
PDGF isoforms are a family of polypeptides that bind to cell surface receptors and induce fibroblast proliferation chemotaxis. The PDGF-A -B chain have been implicated in fibroproliferative lung injury animal models human disease. Two recently recognized polypeptides, PDGF-C -D, differ from the they require proteolytic cleavage before can activate receptors. Our findings demonstrate administration bleomycin murine lungs leads significant increase mRNA expression decrease PDGF-D expression....
Epigenetic regulation of gene expression is critical to phenotypic maintenance and transition human breast cancer cells. HOX antisense intergenic RNA (HOTAIR) a long non‐coding that epigenetically represses via recruitment enhancer zeste homolog 2 (EZH2), histone methyltransferase. Elevated HOTAIR promotes progression cancer. In the current study we examined function in MCF‐7‐TNR cells, derivative luminal‐like cell line MCF‐7 acquired resistance TNF‐α‐induced death. The HOTAIR, markers...
We studied cerebral effects of complementary acupuncture in Parkinson's disease using single photon emission computed tomography (SPECT) measures 99mTc-ECD and 99mTc-TRODAT-4, before after five weeks treatment. Ten patients were randomly assigned to receive levodopa alone (controls) or scalp electro-acupuncture. Before treatment, no hemispheric regional blood flow (rCBF) differences found, whereas striatal dopamine transporter (DAT) activity was lower the most affected hemisphere. Treatment...
Abstract Background With the emergence of next-generation sequencing, availability prokaryotic genome sequences is expanding rapidly. A total 5,276 genomes have been released since 2008, yet only 1,692 were complete. The final phase microbial particularly gap closing, frequently rate-limiting step either because complex genomic structures that cause sequence bias even with high coverage, or presence repeat may gaps in assembly. Results We developed a Cytoscape plugin to facilitate closing...
Oxygenase and peroxygenase enzymes generate intermediates at their active sites which bring about the controlled functionalization of inert C-H bonds in substrates, such as enzymatic conversion methane to methanol. To be viable catalysts, however, these must also prevent oxidative damage essential site residues, can occur during both coupled uncoupled turnover. Herein, we use a combination stopped-flow spectroscopy, targeted mutagenesis, TD-DFT calculations, high-energy resolution...
The proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) promotes progression through activation of matrix metalloproteinase (MMP) activity. MMP-9 is a gelatinase secreted by both cancer cells and surrounding stromal cells, it contributes to TNF-alpha-stimulated invasion metastasis. Cyclin-dependent kinase 9 (CDK9), the catalytic component positive transcription elongation factor-b, phosphorylates serine 2 residues in C-terminal domain RNA polymerase II for productive...
We used positron emission tomography (PET) and the 18-flourodeoxyglucose tracer to study cerebral effects of complementary acupuncture in Parkinson's disease. Five patients received scalp-acupuncture Madopa, while other five had Madopa only. PET scans before after 5 weeks treatment show increased glucose metabolisms parietal, temporal, occipital lobes, thalamus, cerebellum light-diseased hemisphere, parietal lobes severe-diseased hemisphere. No changes were observed Madopa-only group....