- Alzheimer's disease research and treatments
- Protein Structure and Dynamics
- Computational Drug Discovery Methods
- Cyclopropane Reaction Mechanisms
- RNA Research and Splicing
- Catalytic Cross-Coupling Reactions
- Cholinesterase and Neurodegenerative Diseases
- RNA modifications and cancer
- Monoclonal and Polyclonal Antibodies Research
- Nanoplatforms for cancer theranostics
- Drug Transport and Resistance Mechanisms
- Biochemical and Structural Characterization
- Vasculitis and related conditions
- Enzyme Structure and Function
- Protein Interaction Studies and Fluorescence Analysis
- Proteins in Food Systems
- Marine Sponges and Natural Products
- Coordination Chemistry and Organometallics
- DNA and Nucleic Acid Chemistry
- Renal Diseases and Glomerulopathies
- Chemical Synthesis and Analysis
- Microbial Metabolic Engineering and Bioproduction
- Bone health and treatments
- RNA and protein synthesis mechanisms
- Peptidase Inhibition and Analysis
University of Chicago
2017-2024
Peking Union Medical College Hospital
2023-2024
Chinese Academy of Medical Sciences & Peking Union Medical College
2023-2024
Zhengzhou People's Hospital
2017-2024
Oregon State University
2016-2023
Soochow University
2018-2023
The First People's Hospital of Changzhou
2018-2023
Bristol-Myers Squibb (Germany)
2023
Nanjing Tech University
2009-2021
Chongqing Medical University
2021
Ca2+ currents in acutely isolated, adult rat neostriatal neurons were studied with whole-cell voltage-clamp techniques. In the vast majority of (approximately 90%, n > 250), exclusively high-voltage-activated (HVA) type. HVA activated near -40 mV and reached their maximum amplitude 0 mV. Quasi-steady-state inactivation curves many well fitted only a sum Boltzmann functions, suggesting that heterogeneous. Although block current by Cd2+ was single isotherm having an IC50 1 microM, experiments...
The reversible modification of cysteine residues by thioester formation with palmitate (S-palmitoylation) is an abundant lipid post-translational (PTM) in mammalian systems. S-palmitoylation has been observed on mitochondrial proteins, providing intriguing potential connection between metabolic lipids and regulation. However, it unknown whether and/or how regulated. Here we report the development mitoDPPs, targeted fluorescent probes that measure activity levels "erasers" S-palmitoylation,...
The contribution of the inflammatory mediator interleukin-17 (IL-17) in nonsmall cell lung cancer (NSCLC) malignancy has been reported literature. MicroRNA-181a-5p (miR-181a-5p) acts as a tumor suppressor which can regulate target gene at posttranscriptional level. Our study aimed to investigate interaction between IL-17 and miR-181a-5p NSCLC.35 patients with NSCLC 24 COPD controls were selected examined our study. In vitro, H226 H460 lines exposed different doses (20, 40, 60, 80 ng/mL)...
Abstract Technologies capable of programmable translation activation offer strategies to develop therapeutics for diseases caused by insufficient gene expression. Here, we present “translation-activating RNAs” (taRNAs), a bifunctional RNA-based molecular technology that binds specific mRNA interest and directly upregulates its translation. taRNAs are constructed from variety viral or mammalian RNA internal ribosome entry sites (IRESs) upregulate suite target mRNAs. We minimize the taRNA...
GSK-3 is a serine/threonine kinase that has numerous substrates. Many of these proteins are involved in the regulation diverse cellular functions, including metabolism, differentiation, proliferation, and apoptosis. Inhibition may be useful treating number diseases Alzheimer's disease (AD), type II diabetes, mood disorders, some cancers, but approach poses significant challenges. Here, we present class isonicotinamides potent, highly kinase-selective inhibitors, members which demonstrated...
Recombinant proteins are traditionally limited to linear configuration. Herein, we report in vivo protein topology engineering using highly efficient, mechanically interlocking SpyX modules named AXB and BXA. domains composed of p53dim (X), SpyTag (A), SpyCatcher (B). The guides the intertwining two nascent chains followed by autocatalytic isopeptide bond formation between fulfill interlocking, leading a variety backbone topologies. Direct expression or BXA produces catenanes with distinct...
To identify the risk factors for developing renal involvement and severe kidney disease in Chinese childhood Henoch-Schönlein purpura (HSP) patients.This was a retrospective study of 2731 children with HSP diagnosed between 2012 2015. We analyzed their demographic data, clinical manifestations, laboratory tests retrospectively. Multivariate logistic regression analysis used to assess factors.Renal occurred 844 patients (35.60%), 104 (4.39%). Age over 6 years old at onset, colder season, more...
Calcium ion therapy has shown promise for cancer treatment, but its efficacy is limited by the cellular calcium buffering mechanism. Herein, an homeostasis disruptor (PCCa) was synthesized using in situ mineralization method. The surface of porphyrin-metal-organic framework PCN coated with carbonate (CaCO3), aimed at causing Ca2+ overload and disrupting self-defense mechanism during imbalance. Upon internalization into tumor cells, PCCa undergoes lysosomal acidification-induced CaCO3...
The amyloid-β (Aβ) peptide, which likely plays a key role in Alzheimer disease, is derived from the precursor protein (APP) through consecutive proteolytic cleavages by β-site APP-cleaving enzyme and γ-secretase. Unexpectedly γ-secretase inhibitors can increase secretion of Aβ peptides under some circumstances. This "Aβ rise" phenomenon, same inhibitor causing an at low concentrations but inhibition higher concentrations, has been widely observed. Here we show that rise depends on...
Early oligomerization during amyloid-β (Aβ) aggregation is essential for Aβ neurotoxicity. Understanding how unstructured Aβs assemble into oligomers, especially those rich in β-sheets, but remains challenging as the assembly process too transient experimental characterization and slow molecular dynamics simulations. So far, atomic simulations are limited only to studies of either oligomer structures or pathways short segments. To overcome computational challenge, we combine this study a...
1-Aryl-1,2-dialkylethenes were generated by a sequence of electrophilic substitution, 1,2-metalate rearrangement, and β-elimination initiated the addition enantioenriched α-(carbamoyloxy)alkylboronates to lithiated carbamates. The carbenoid stereochemical pairing [i.e., "like"=(S)+(S) or "unlike"=(S)+(R)] elimination mechanism (syn anti), not substituent effects, determined configuration trisubstituted alkene target. For example, (Z)-2,5-diphenyl-2-pentene was produced in 70 % yield with...
Extensive mutation creates a supercharged, intrinsically disordered protein, SpyCatcher(−), with stimuli-responsive reactivity toward SpyTag.
Transforming growth factor-beta (TGF-β) signaling pathways contain both tumor suppressor and promoting activities. We have demonstrated that Nodal, another member of the TGF-β superfamily, its receptors are expressed in prostate cancer cells. Nodal exerted similar biological effects on cells; inhibited proliferation WPE, RWPE1 DU145 cells, whereas neither had any effect LNCaP or PC3 Interestingly, induced migration but not predominantly phosphorylation Smad3, only Smad2. also determined...
S-Palmitoylation is an abundant lipid post-translational modification that dynamically installed on and removed from target proteins to regulate their activity cellular localization. A dearth of tools for studying the activities regulation protein S-depalmitoylases, thioesterase "erasers" cysteine S-palmitoylation, has contributed incomplete understanding role dynamic S-palmitoylation in regulating proteome lipidation. Recently, we developed "depalmitoylation probes" (DPPs), small molecule...
Analogues or isosteres of α,γ-diketoacid (DKA) 1a show potent inhibition hepatitis C virus (HCV) NS5B polymerase through chelation the two magnesium ions at active site. The anti-HCV activity flavonoid quercetin (2) could partly be attributed to it being a structural mimic DKAs. In order delineate features required for inhibitory effect and improve potency, novel types analogues, 7-O-arylmethylquercetins quercetin-3-O-benzoic acid esters, were designed, synthesized evaluated their properties...
Abstract 1‐Aryl‐1,2‐dialkylethenes were generated by a sequence of electrophilic substitution, 1,2‐metalate rearrangement, and β‐elimination initiated the addition enantioenriched α‐(carbamoyloxy)alkylboronates to lithiated carbamates. The carbenoid stereochemical pairing [i.e., “ like ”=( S )+( ) or unlike R )] elimination mechanism ( syn anti ), not substituent effects, determined configuration trisubstituted alkene target. For example, Z )‐2,5‐diphenyl‐2‐pentene was produced in 70 % yield...