A5029413559- Neurotransmitter Receptor Influence on Behavior
- Cholinesterase and Neurodegenerative Diseases
- Computational Drug Discovery Methods
- Forensic Toxicology and Drug Analysis
- Psychedelics and Drug Studies
- Enzyme Catalysis and Immobilization
- Microbial Natural Products and Biosynthesis
- Biological and pharmacological studies of plants
- Nicotinic Acetylcholine Receptors Study
- Neuroscience and Neuropharmacology Research
- Epigenetics and DNA Methylation
- Cancer Mechanisms and Therapy
- RNA modifications and cancer
- Natural product bioactivities and synthesis
- Pharmacogenetics and Drug Metabolism
- Plant biochemistry and biosynthesis
- Monoclonal and Polyclonal Antibodies Research
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Protein Structure and Dynamics
- Cancer-related Molecular Pathways
- Enzyme Structure and Function
- Retinoids in leukemia and cellular processes
- Phytochemistry and Biological Activities
- Heat shock proteins research
Hangzhou Normal University
2018-2024
University of Kentucky
2013-2023
Peking University
2019-2020
Chinese Academy of Medical Sciences & Peking Union Medical College
2009-2015
Zero to Three
2009
Cocaine abuse is a world-wide public health and social problem without US Food Drug Administration-approved medication. An ideal anticocaine medication would accelerate cocaine metabolism, producing biologically inactive metabolites by administration of an efficient cocaine-specific exogenous enzyme. Our recent studies have led to the discovery desirable, highly hydrolases (CocHs) that can efficiently detoxify inactivate affecting normal functions CNS. Preclinical clinical data demonstrated...
Rearranged during transfection (RET) rearrangement oncoprotein-mediated Ras/MAPK signaling cascade is constitutively activated in cancers. Here, we demonstrate a unique signal niche. The niche ternary complex based on the chimeric RET liquid–liquid phase separation. comprises rearranged kinase (RET fusion); adaptor (GRB2), and effector (SHC1). Together, they orchestrate cascade, which dependent tyrosine kinase. CCDC6-RET fusion undergoes LLPS requiring its domain partner. promotes...
Abstract Sustainable inland waterways should meet the needs of navigation without compromising health riverine ecosystems. Here we propose a hierarchical model to describe sustainable development Golden Inland Waterways (GIWs) which are characterized by great bearing capacity and transport need. Based on datasets from 66 large rivers (basin area > 100,000 km 2 ) worldwide, identify 34 GIWs, mostly distributed in Asia, Europe, North America, South typically following three-stage path...
Gene transfer of a human cocaine hydrolase (hCocH) derived from butyrylcholinesterase (BChE) by 5 mutations (A199S/F227A/S287G/A328W/Y332G) has shown promise in animal studies for treatment addiction. To predict the physiological fate and immunogenicity this enzyme humans, comparable was created tested conspecific host. Thus, similar (A199S/S227A/S287G/A328W/Y332G) were introduced into mouse BChE to obtain CocH (mCocH). The cDNA incorporated viral vectors based on: a) serotype-5...
Cocaine is a widely abused drug without an FDA (Food and Drug Administration)-approved medication. It has been recognized that ideal anti-cocaine medication would accelerate cocaine metabolism producing biologically inactive metabolites via route similar to the primary cocaine-metabolizing pathway, i.e. human BChE (butyrylcholinesterase)-catalysed hydrolysis. However, native low catalytic activity against cocaine. We recently designed discovered mutant (A199S/F227A/S287G/A328W/Y332G) with...
Cocaine esterase (CocE) is known as the most efficient natural enzyme for cocaine hydrolysis. The major obstacle to clinical application of wild-type CocE thermoinstability with a half-life only ∼12 min at 37 °C. previously designed T172R/G173Q mutant (denoted E172–173) an improved in vitro ∼6 h °C currently trial Phase II overdose treatment. Through molecular modeling and dynamics simulation, we characterized promising new E172–173 extra L196C/I301C mutations E196–301) produce cross-subunit...
Abstract Four cyclopentenone‐containing ansamycin polyketides (mccrearamycins A–D), and six new geldanamycins (Gdms B–G, including linear mycothiol conjugates), were characterized as metabolites of Streptomyces sp. AD‐23‐14 isolated from the Rock Creek underground coal mine acid drainage site. Biomimetic chemical conversion studies using both simple synthetic models Gdm D confirmed that mccrearamycin cyclopentenone derives benzilic rearrangement 19‐hydroxy Gdm, thereby provides a...
Cyclooxygenase-2 (COX-2) plays important roles in the modulation of apoptosis, angiogenesis, immune response, and tumor invasion. Elevated COX-2 expression has been reported to be correlated with reduced survival after radiotherapy. This study examined whether genetic variations gene are associated different inoperable locally advanced non-small cell lung cancer (NSCLC) treated chemoradiotherapy or radiotherapy alone.One hundred thirty-six patients stage IIIA-B NSCLC receiving thoracic...
The structures of 12 new "enantiomeric"-like abyssomicin metabolites (abyssomicins M–X) from Streptomyces sp. LC-6-2 are reported. Of this set, the W (11) contains an unprecedented 8/6/6/6 tetracyclic core, while bicyclic X (12) represents first reported naturally occurring linear spirotetronate. Metabolite were determined based on spectroscopic data and X-ray crystallography, genome sequencing also revealed corresponding putative biosynthetic gene cluster.
Cocaine is one of the most addictive drugs without a U.S. Food and Drug Administration (FDA)-approved medication. Enzyme therapy using an efficient cocaine-metabolizing enzyme recognized as promising approach to cocaine overdose treatment. The actual enzyme, known RBP-8000, under current clinical development for treatment our previously designed T172R/G173Q mutant bacterial esterase (CocE). effective in hydrolyzing but inactive against benzoylecgonine (a major, biologically active metabolite...
Carboxylesterase-1 (CE-1) is a crucial enzyme responsible for metabolism/activation/inactivation of xenobiotics (therapeutic agents, prodrugs, abused drugs, and organophosphorus nerve agents etc.) also involved in many other biological processes. In this study, we performed extensive computational modeling simulations to understand the fundamental reaction mechanism cocaine hydrolysis catalyzed by CE-1, revealing that CE-1-catalyzed follows novel pathway with only two steps: single-step...
Abstract It is a grand challenge to develop truly effective medication for treatment of cocaine overdose. The current available, practical emergence overdose includes administration benzodiazepine anticonvulsant agent ( e.g . diazepam) and/or physical cooling with an aim relieve the symptoms. inherent difficulties antagonizing physiological effects drugs in central nervous system have led exploring protein-based pharmacokinetic approaches using biologics like vaccines, monoclonal antibodies,...
Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease with an elusive etiology. Aberrant activation of c-Jun N-terminal kinase 1 (JNK1) has been implicated in its pathogenesis. Through combination structure-based drug design structure-activity relationship (SAR) optimization, series pyrimidine-2,4-diamine scaffold derivatives have developed as potent JNK1 inhibitors. Compound
A novel 6/6/5/6 tetracyclic polyketide named chartspiroton (1) was isolated from a medicinal plant endophytic Streptomyces in Dendrobium officinale. The complete structure assignment with absolute stereochemistry elucidated through spectroscopic data, computational calculations, and single-crystal X-ray diffraction. Chartspiroton features an unprecedented naphthoquinone derivative spiro-fused benzofuran lactone moiety. plausible biosynthetic pathway for 1 suggested intriguing oxidative...
Twelve guaianolide-type sesquiterpene oligomers with diverse structures were isolated from the whole plants of Ainsliaea fragrans, including a novel trimer (1) and two new dimers (2, 3). The chemical compounds elucidated through spectroscopic data interpretation computational calculations. Ainsfragolide is an unusual guaianolide generated C-C linkage at C2'-C15″, which may be biosynthesized prospectively further Michael addition. Cytotoxicity results showed that ainsfragolide was most potent...
Endophyte has now become a potential source for the discovery of novel natural products, as they participate in biochemical pathways their hosts and produce analogous or bioactive compounds. As an epiphytic plant, Dendrobium officinale is one precious Chinese medicines with various activities. It well known containing diverse endophytes, but so far not much about secondary metabolites.the plant tissues were cut cultured on agar plates to isolate purify endophytic bacteria from officinale....