A5040429139- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Chemical Synthesis and Analysis
- RNA Research and Splicing
- Asymmetric Hydrogenation and Catalysis
- Protein Interaction Studies and Fluorescence Analysis
- International Arbitration and Investment Law
- Bacterial Genetics and Biotechnology
- Catalytic C–H Functionalization Methods
- Bacteriophages and microbial interactions
- Impact of Technology on Adolescents
- Synthesis and Catalytic Reactions
- Metal complexes synthesis and properties
- COVID-19 and Mental Health
- Multicomponent Synthesis of Heterocycles
- Diabetes Treatment and Management
- State Capitalism and Financial Governance
- Drug Transport and Resistance Mechanisms
- Aquaculture Nutrition and Growth
- Toxoplasma gondii Research Studies
- Microwave-Assisted Synthesis and Applications
- Chemical Synthesis and Reactions
- Pancreatic function and diabetes
- Metabolism, Diabetes, and Cancer
- Aquaculture disease management and microbiota
Hunan Normal University
2020-2024
Wuhan University
2009-2024
Zhongnan Hospital of Wuhan University
2009-2024
Fujian Medical University
2024
Union Hospital
2024
Hubei University
2017-2022
Sichuan University
2021
West China Hospital of Sichuan University
2021
Shihezi University
2021
Pfizer (United States)
2008-2020
Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in regulating the levels of plasma low-density lipoprotein cholesterol (LDL-C). Here, we demonstrate that compound PF-06446846 inhibits translation PCSK9 by inducing ribosome to stall around codon 34, mediated sequence nascent chain within exit tunnel. We further show reduces and total rats following oral dosing. Using profiling, is highly selective for inhibition translation. The mechanism action employed reveals...
Adenosine monophosphate-activated protein kinase (AMPK) is a involved in maintaining energy homeostasis within cells. On the basis of human genetic association data, AMPK activators were pursued for treatment diabetic nephropathy. Identification an indazole amide high throughput screening (HTS) hit followed by truncation to its minimal pharmacophore provided acid lead compound. Optimization core and aryl appendage improved oral absorption culminated identification indole acid, PF-06409577...
We report a modular three-component dynamic kinetic resolution (DKR) that affords enantiomerically enriched hemiaminal esters derived from azoles and aldehydes. The novel scalable reaction can be used to synthesize valuable substituted in regioselective manner by capping (e.g., acylation) of the equilibrating azole-aldehyde adduct. With use prolinol-derived DMAP catalyst as chiral Lewis base, products obtained high chemical yield with enantiomeric excess. DKR was performed on multikilogram...
The 5′-untranslated region (5′-UTR) of prokaryotic mRNAs plays an essential role in post-transcriptional regulation. Bacillus species, such as subtilis and licheniformis, have gained considerable attention microbial cell factories for the production various valuable chemicals industrial proteins. In this work, we developed a portable 5′-UTR sequence enhanced protein output strain B. licheniformis DW2. This contains only ∼30 nt forms hairpin structure located right before open reading frame....
Numerous studies have suggested that active social media use can promote well-being by enhancing perceived support. However, the relationship between and support remains inconsistent across studies. This study explores possible mechanisms underlying use, support, during after a COVID-19 lockdown. Using online surveys with Chinese participants ( N = 1,131) 407) lockdown period, our findings sequential mediation model. Specifically, was positively associated network responsiveness, which in...
Compounds that contain the 1-heteroaryl-3-azabicyclo[3.1.0]hexane architecture are of particular interest to pharmaceutical industry yet remain a challenge synthesize. We report herein an expedient and modular approach synthesis 1-heteroaryl-3-azabicyclo[3.1.0]hexanes by Suzuki–Miyaura Chan–Evans–Lam coupling reactions tertiary trifluoroborate salts. Our cross-coupling protocol is compatible with broad range aryl heteroaryl bromides chlorides. The unprecedented trifluoroborates allows facile...
Abstract Targeting of the human ribosome is an unprecedented therapeutic modality with a genome‐wide selectivity challenge. A liver‐targeted drug candidate described that inhibits ribosomal synthesis PCSK9, lipid regulator considered undruggable by small molecules. Key to concept was identification pharmacologically active zwitterions designed be retained in liver. Oral delivery poorly permeable achieved prodrugs susceptible cleavage carboxylesterase 1. The select tetrazole crucial....
The first detailed kinetic analysis and mechanistic interpretation of the reactions between serum albumin second-generation gold drug Auranofin [Et(3)PAuSATg = (triethylphosphine)(2,3,4,6-tetra-O-acetyl-1-beta-D-glucopyranosato-S-) gold(I)] its triisopropylphosphine analogue, iPr(3)PAuSATg, in vitro are reported. were investigated using Penefsky spun columns NMR saturation transfer methods. Under chromatography conditions with 0.4-0.6 mM a wide range Et(3)PAuSATg concentrations, reaction is...
In efforts to curb the spread of COVID-19, many countries have implemented a variety lockdown and quarantine measures. With substantially reduced face-to-face interactions, people may relied heavily on social media for connection, information, entertainment. However, little is known about psychological physical health implications use during strict lockdown. The current study investigates associations with well-being among Wuhan residents (N = 1214). Our findings showed that non-COVID...
Abstract Prokaryotic Argonautes (pAgos) play a vital role in host defense by utilizing short nucleic acid guides to recognize and target complementary acids. Despite being the majority of pAgos, pAgos have only recently received attention. Short are often associated with proteins containing an APAZ domain nuclease including DUF4365, SMEK, or HNH domain. In contrast long that specifically cleave DNA, our study demonstrates pAgo from Thermocrispum municipal, along its DUF4365-APAZ protein,...
Pyridine-<i>N</i>-oxides are often used as reactive precursors in the syntheses of substituted pyridines. Isolation and subsequent reduction associated pyridine-<i>N</i>-oxide intermediates can be challenging. We have discovered that tetrahydroxydiboron functions a mild, versatile, remarkably selective reducing agent for pyridine-<i>N</i>-oxides may an situ fashion, thus obviating isolation <i>N</i>-oxide-containing
Gram-positive bacteria are a nascent platform for synthetic biology and metabolic engineering that can provide new opportunities the production of biomolecules. However, lack standardized methods genetic parts is major obstacle towards attaining acceptance widespread use bacterial chassis industrial bioproduction. In this study, we have engineered novel mRNA leader sequence containing more than one ribosomal binding site (RBS) which could initiate translation from multiple sites, vastly...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOxidation of the phosphine from auranofin analog, triisopropylphosphine(2,3,4,6-tetra-O-acetyl-1-thio-.beta.-D-glucopyranosato-S)gold(I), via a protein-bound phosphonium intermediateC. Frank Shaw III, Anvarhusein A. Isab, James D. Hoeschele, Mary Starich, Locke, Pamela Schulteis, and Jun XiaoCite this: J. Am. Chem. Soc. 1994, 116, 6, 2254–2260Publication Date (Print):March 1, 1994Publication History Published online1 May 2002Published inissue 1...
Background: Whether probiotics helped the Helicobacter pylori ( H. ) eradication was still highly controversial. The non-bacterial Saccharomyces boulardii S. has demonstrated its efficacy in treatment of antibiotic-associated and infectious diarrhea. We aimed to evaluate effects combined with quadruple therapy for associated side effects. Methods: Three hundred sixty pylori- infected patients were recruited this multicenter, randomized controlled trial. who underwent a ratio 1:1 into two...
As peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is frequently expressed in colon, its genetic polymorphism may play a role the etiology of inflammatory bowel disease (IBD). The aims present study were to determine distribution PPAR-gamma polymorphisms Pro12Ala and C161T explore association between genotypes phenotypes IBD patients.A total 244 patients [212 ulcerative colitis (UC) 32 Crohn's (CD)] 220 controls Chinese population 603 (302 UC 301 CD) 180 white Dutch enrolled...
Investigation of the slopes in Wenchuan earthquake shows that tension failures appear upper part many landslides. The typical failure mode can be generalized as "tensile-rupture and sheared-sliding" (TRSS). In this paper, distinct element method (DEM) is employed to simulate gradual process Tangjiashan landslide under excitation earthquake. It found first appearance deep cracks on top, then shearing slip along bottom. posterior fracture deep, steep, rough, bottom shear surface has a...
Optimization of the pharmacokinetic (PK) properties a series activators adenosine monophosphate-activated protein kinase (AMPK) is described. Derivatives previously described 5-aryl-indole-3-carboxylic acid clinical candidate (1) were examined with goal reducing glucuronidation rate and minimizing renal excretion. Compounds 10 (PF-06679142) 14 (PF-06685249) exhibited robust activation AMPK in rat kidneys as well desirable oral absorption, low plasma clearance, negligible clearance...
Indole acids 1, 2, and 3 are potent 5′-adenosine monophosphate-activated protein kinase (AMPK) activators for the potential treatment of diabetic nephropathy. Compounds 1–3 were scaled to supply material preclinical studies, indole was selected advancement first-in-human clinical trials kilogram quantities. The progression synthesis strategy these AMPK is described, as routes efficient structure–activity relationship generation then improved larger scales. developed sequences employed...