A5069515960- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Genetic Neurodegenerative Diseases
- Organometallic Complex Synthesis and Catalysis
- RNA Research and Splicing
- Metal-Catalyzed Oxygenation Mechanisms
- Magnetism in coordination complexes
- Carbon dioxide utilization in catalysis
- Cardiomyopathy and Myosin Studies
- Meat and Animal Product Quality
- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Enzyme Structure and Function
- Metal complexes synthesis and properties
- Animal Nutrition and Physiology
- Synthesis and Biological Evaluation
- Cell death mechanisms and regulation
- Fluorine in Organic Chemistry
- Fungal and yeast genetics research
- Bee Products Chemical Analysis
- N-Heterocyclic Carbenes in Organic and Inorganic Chemistry
- Metabolism, Diabetes, and Cancer
- RNA Interference and Gene Delivery
- Cancer Research and Treatments
Tianjin Medical University Cancer Institute and Hospital
2022-2023
Tianjin Medical University
2021-2023
National Clinical Research
2022
Tsinghua University
2006-2022
State Key Joint Laboratory of Environment Simulation and Pollution Control
2022
Minhang District Central Hospital
2022
Fudan University
2022
Cornell University
2013-2018
Hefei University of Technology
2016-2017
Affiliated Hospital of Jining Medical University
2015
Abstract Metabolic enzymes and metabolites display non-metabolic functions in immune cell signalling that modulate attack ability. However, whether how a tumour’s metabolic remodelling contributes to its resistance remain be clarified. Here we perform functional screen of genes rescue tumour cells from effector T cytotoxicity, identify the embryo- tumour-specific folate cycle enzyme methylenetetrahydrofolate dehydrogenase 2 (MTHFD2). Mechanistically, MTHFD2 promotes basal IFN-γ-stimulated...
We have developed a general and highly efficient copper-catalyzed method for synthesis of quinazoline quinazolinone derivatives, the target products were obtained in good to excellent yields via cascade reactions amidine hydrochlorides with substituted 2-halobenzaldehydes, 2-halophenylketones, or methyl 2-halobenzoates, is simple, economical practical advantages.
Lipid-derived electrophiles (LDEs) that can directly modify proteins have emerged as important small-molecule cues in cellular decision-making. However, because these diffusible LDEs many targets [e.g., >700 cysteines are modified by the well-known LDE 4-hydroxynonenal (HNE)], establishing functional consequences of modification on individual remains devilishly difficult. Whether modifications a single protein biologically sufficient to activate discrete redox signaling response downstream...
Abstract Amyloid‐β peptide (Aβ) is the principal constituent of plaques associated with Alzheimer's disease (AD) and thought to be responsible for neurotoxicity disease. Copper binding Aβ has been hypothesized play an important role in neruotoxicity free radical damage, Cu 2+ chelators represent a possible therapy AD. However, many properties copper have not elucidated clearly, location sites on also controversy. Here we used range spectroscopic techniques characterize coordination Aβ(1–16)...
In-depth chemical understanding of complex biological processes hinges upon the ability to systematically perturb individual systems. However, current approaches study impacts biologically relevant reactive small molecules involve bathing entire cell or isolated organelle with excess amounts, leading off-target effects. The resultant lack biochemical specificity has plagued our how electrophiles mediate signal transduction regulate responses that confer defense mechanisms cellular...
Myotonic dystrophy type 1 (DM1) is caused by an expanded CUG repeat (CUG(exp)) that sequesters muscleblind-like protein (MBNL1), a regulates alternative splicing. CUG(exp) RNA validated drug target for this currently untreatable disease. Herein, we develop bioactive small molecule (1) targets and able to inhibit the CUG(exp)·MBNL1 interaction in cells model DM1. The core of based on ligand 2, which was previously reported be active vitro assay. A polyamine-derivative side chain conjugated...
An expanded CUG repeat transcript (CUG(exp)) is the causative agent of myotonic dystrophy type 1 (DM1) by sequestering muscleblind-like protein (MBNL1), a regulator alternative splicing. On basis ligand (1) that was previously reported to be active in an vitro assay, we present synthesis small library containing 10 dimeric ligands (4-13) differ length, composition, and attachment point linking chain. The oligoamino linkers gave greater gain affinity for RNA were more effective when compared...
This paper investigated the effects of l-lysine (Lys) and l-arginine (Arg) on water-holding capacity (WHC) hardness myosin gel as well mechanism these effects. The results showed that Lys, Arg, KOH increased WHC but decreased in all cases. At pH 6.32, order control < Lys ≈ while > Arg. shortened low field nuclear magnetic resonance spin-spin relaxation times (T2), Arg slightly affected T2. had different influences molecular forces gels distribution size. formed a with porous clusters,...
Myotonic dystrophy type 2 (DM2) is an incurable neuromuscular disease caused by expanded CCUG repeats that may exhibit toxicity sequestering the splicing regulator MBNL1. A series of triaminotriazine- and triaminopyrimidine-based small molecules (ligands 1-3) were designed, synthesized tested as inhibitors MBNL1-CCUG interaction. Despite structural similarities triaminotriazine triaminopyrimidine units, ligands bind with low micromolar affinity to (K(d) ∼ 0.1-3.6 µM) whereas do not repeats....
Muscleblind-like proteins (MBNL) are RNA-binding that bind to the poly(CUG) and poly(CCUG) sequences causative agents of myotonic dystrophy. It has been suggested as a result binding repeating RNA sequences, MBNL1 is abnormally expressed translocated, which leads many misregulated events in In this work, steady-state fluorescence quenching experiments suggest alters structure helical targets upon binding, may explain selectivity for less structured sites. The removal one pair zinc fingers...
Atmospheric aerosols have significant effects on the climate and human health. New particle formation (NPF) is globally an important source of but its relevance especially towards aerosol mass loadings in highly polluted regions still controversial. In addition, uncertainties remain regarding processes leading to severe pollution episodes, concerning e.g. role atmospheric transport. this study, we utilize air history analysis combination with different fields related intensity anthropogenic...
Abstract Metabolites are important for cell fate determination. Fructose‐1,6‐bisphosphate (F1,6P) is the rate‐limiting product in glycolysis and substrate gluconeogenesis. Here, it discovered that nuclear‐accumulated F1,6P impairs cancer viability by directly binding to high mobility group box 1 (HMGB1), most abundant non‐histone chromosome structural protein with paradoxical roles tumor development. disrupts association between HMGB1 A‐box C‐tail targeting K43/K44 residues, inhibits...
Discoidin domain receptor 1 (DDR1) has been demonstrated to be able promote tumor invasion and metastasis being closely related immune infiltration. However, DDR1 rarely studied in gastric cancer. Here, we primarily evaluated expression cancer its cell lines using multiple databases. Subsequently, the prognosis was investigated relation expression. After analysis, discovered that highly expressed significantly connected with poor To comprehensively understand molecular mechanism of DDR1,...
The aim of the present study was to investigate correlations between toll-like receptor 6 (TLR6) expression in peripheral blood mononuclear cells (PBMCs) and auxiliary T children with purpura. A total 42 acute Henoch-Schönlein purpura (HSP) were selected for study, a further 30 healthy as control group. Enzyme-linked immunosorbent assays performed detect levels plasma interferon (IFN)-γ, interleukin (IL)-4 IL-17, flow cytometry TLR6 protein PBMCs. IL-4, IFN-γ IL-17 HSP group significantly...
An N-terminal-domain (NTD) and adjacent catalytic body (CB) make up subunit-α of ribonucleotide reductase (RNR), the rate-limiting enzyme for de novo dNTP biosynthesis. A strong linkage exists between ligand binding at NTD oligomerization-coupled RNR inhibition, inducible by both dATP nucleotide chemotherapeutics. These observations have distinguished as an oligomeric regulation domain dictating assembly inactive oligomers. Inactive states differ eukaryotes prokaryotes (α6 in human versus...
Abstract Human ribonucleotide reductase (hRNR) is a target of nucleotide chemotherapeutics in clinical use. The nucleotide‐induced oligomeric regulation hRNR subunit α increasingly being recognized as an innate and drug‐relevant mechanism for enzyme activity modulation. In the presence negative feedback inhibitor dATP leukemia drug clofarabine nucleotides, hRNR‐α assembles into catalytically inert hexameric complexes, whereas effectors that govern substrate specificity typically trigger...
[(C 7 H 13 N 2 )I]BF 4 cristallise dans P2 1 3 avec affinement jusqu'a 0,029. Le cation organique est lineaire, les anions mineraux etant situes sur axes C
Delivery of functional proteins into cells may help us understand how specific protein influences cell behavior as well treat diseases caused by deficiency or loss-of-function mutations. However, cannot enter diffusion. In this work, a novel biology tool for delivering recombinant mammalian was developed. We hijacked the intracellular transport routes used cholera toxin and took advantage recent development on split intein that is compatible with denatured conditions shows an exceptional...