A5100636216- Single-cell and spatial transcriptomics
- Protein Degradation and Inhibitors
- Pharmacogenetics and Drug Metabolism
- Spectroscopy and Quantum Chemical Studies
- Advanced Chemical Physics Studies
- Drug Transport and Resistance Mechanisms
- Multiple Myeloma Research and Treatments
- Peptidase Inhibition and Analysis
- Quantum, superfluid, helium dynamics
- Cell Image Analysis Techniques
- Peroxisome Proliferator-Activated Receptors
- Metal-Organic Frameworks: Synthesis and Applications
- Cancer-related molecular mechanisms research
- Ubiquitin and proteasome pathways
- Photochemistry and Electron Transfer Studies
- Retinal Diseases and Treatments
- Cancer, Hypoxia, and Metabolism
- Connexins and lens biology
- Spectroscopy and Laser Applications
- Aldose Reductase and Taurine
- Covalent Organic Framework Applications
- Advanced biosensing and bioanalysis techniques
- Free Radicals and Antioxidants
- Gene expression and cancer classification
- Microbial Community Ecology and Physiology
Shandong Jiaotong University
2014-2025
Kunming University of Science and Technology
2025
Zhejiang Shuren University
2021-2024
Chinese Academy of Medical Sciences & Peking Union Medical College
2005-2024
Shandong University
2012-2023
Shenzhen University
2023
Changzhou Third People's Hospital
2023
Dalian Polytechnic University
2023
Chinese Academy of Sciences
2018-2022
Beijing Institute of Genomics
2018-2022
Abstract Global changes such as seawater intrusion and freshwater resource salinization increase environmental stress imposed on the aquatic microbiome. A strong predictive understanding of responses microbiome to will help in coping with “gray rhino” events environment, thereby contributing an ecologically sustainable future. Considering that microbial ecological networks are tied stability ecosystem functioning abundant rare biospheres different biogeographic patterns important drivers...
Apixaban is an oral, direct, and highly selective factor Xa inhibitor in late-stage clinical development for the prevention treatment of thromboembolic diseases. The metabolic drug-drug interaction potential apixaban was evaluated vitro. compound did not show cytochrome P450 inhibition (IC<sub>50</sub> values >20 μM) incubations human liver microsomes with probe substrates CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4/5. any effect at concentrations up to 20 μM on enzyme activities mRNA levels...
The metabolism and disposition of [<sup>14</sup>C]apixaban, a potent, reversible, direct inhibitor coagulation factor Xa, were investigated in mice, rats, rabbits, dogs, humans after single oral administration incubations with hepatocytes. In plasma, the parent compound was major circulating component humans. <i>O</i>-Demethyl apixaban sulfate (M1) represented approximately 25% area under time curve human plasma. This metabolite present, but lower amounts relative to parent, plasma from...
Antihypertensive peptides were screened from thermolysin hydrolysate of Cassia obtusifolia seeds (Jue Ming Zi) using two independent bioassay-guided fractionations, reversed-phase high-performance liquid chromatography (RP-HPLC), and strong cation-exchange (SCX) coupled with angiotensin I-converting enzyme (ACE) inhibitory assay. The identical peptide in the most active RP-HPLC SCX fractions was simultaneously de novo sequenced as FHAPWK high-resolution mass spectrometry. (IC50 = 16.83 ±...
Recent studies have demonstrated that Fischer-344 rats from Japanese Charles River Inc. specifically lack dipeptidyl(amino)peptidase IV (DAP IV-negative; EC 3.4.14.5), whereas sources within the United States IV-positive) possess normal DAP activity. In present study, plasma IV-positive metabolized substance P (SP) (5.37 +/- 0.25 nmol/min/ml) via actions of angiotensin-converting enzyme (EC 3.4.15.1) (1.86 0.50 and (2.56 0.42 nmol/min/ml). sequentially converted SP to SP[3-11] SP[5-11]. The...
Chromosome 17q23 amplification occurs in ~11% of human breast cancers. Enriched HER2+ cancers, the is significantly correlated with poor clinical outcomes. In addition to previously identified oncogene WIP1, we uncover an oncogenic microRNA gene, MIR21, a majority WIP1-containing amplicons. The results aberrant expression WIP1 and miR-21, which not only promotes tumorigenesis, but also leads resistance anti-HER2 therapies. Inhibiting miR-21 selectively inhibits proliferation, survival...
Understanding selectivity-dependent molecular mechanism of inhibitors towards CDK2 over CDK6 is prominent for improving drug design the CDK family. Multiple short dynamics (MD) simulations combined with MM-GBSA approach are adopted to investigate on binding selectivity X64, X3A, and 4 AU CDK6. The RMSF analysis calculations surface areas indicate that local structural global flexibility stronger than CDK2. Based cross-correlation maps (DCCMs), motion modes produce difference due associations...
The geometry of the ladle bottom and position stirring paddles during hot metal significantly influence hydrodynamic characteristics, thereby affecting desulfurization efficiency. Water model experiments simulations were conducted to investigate effects structures stirrer positions on flow field mixing characteristics in desulfurization. results indicate that ladles with a spherical-bottom structure effectively reduced “dead zone” volume flow. In water tests, time for was by 22.5% 20% at...
3D vibrational state-resolved DCS results. (a) DCS1 corresponds to small J (0 ≤ 38) partial waves. (b) DCS2 large (39 58) (c) Total summed over all waves for comparison.
Cyclin-dependent kinase 6 (CDK6) has been identified as a potential drug target in various types of cancers. In our current study, multiple independent molecular dynamics simulations four separate replicates and computations binding free energies are carried out to decipher the mechanisms three inhibitors, LQQ, 6ZV, 0RS, CDK6. The dynamic analyses indicate that presence inhibitors influences conformational alterations, motion modes, internal Binding computed using mechanics generalized Born...
N-(2-Chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazolecarboxamide (dasatinib, Sprycel, BMS-354825; Bristol-Myers Squibb, Princeton, NJ) is a potent protein kinase inhibitor to treat chronic myeloid leukemia. In vivo studies have shown that the primary oxidative metabolites of dasatinib are M4 (N-dealkylation), M5 (N-oxidation), M6 (carboxylic acid formation), M20, and M24 (hydroxylation). To identify enzymes responsible for formation...
Apixaban, a potent and highly selective factor Xa inhibitor, is currently under development for treatment of arterial venous thrombotic diseases. The <i>O</i>-demethyl apixaban sulfate major circulating metabolite in humans but circulates at lower concentrations relative to parent animals. aim this study was identify the sulfotransferases (SULTs) responsible sulfation reaction. Apixaban undergoes <i>O</i>-demethylation catalyzed by cytochrome P450 enzymes apixaban, then conjugated SULTs form...
CDK2 can be used as an attractive target for development of efficient inhibitors curing multiple disease relating with CDK2. In this work, molecular dynamics (MD) simulations and binding free energy calculations were coupled to probe conformational changes due inhibitor associations mechanisms PM1, FMD X64 The results suggest that the strength is stronger than PM1. Principal component (PC) analysis cross-correlation map based on equilibrated MD trajectories demonstrate structural difference...
Fragile X syndrome (FXS) is the leading known inherited intellectual disability and most common genetic cause of autism. The full mutation results in transcriptional silencing Fmr1 gene loss fragile mental retardation protein (FMRP) expression. Defects neuroenergetic capacity are to a variety neurodevelopmental disorders. Thus, we explored integrity forebrain mitochondria knockout mice during peak synaptogenesis. We found inefficient thermogenic respiration due futile proton leak KO caused...
BRD9 and TAF1(2) have been regarded as significant targets of drug design for clinically treating acute myeloid leukemia, malignancies, inflammatory diseases. In this study, multiple short molecular dynamics simulations combined with the mechanics generalized Born surface area method were employed to investigate binding selectivity three ligands, 67B, 67C, 69G, BRD9/TAF1(2) IC50 values 230/59 nM, 1400/46 160/410 respectively. The computed free energies from MM-GBSA displayed good...
Cisplatin (DDP) treatment is one of the most predominant chemotherapeutic strategies for lung cancer patients. Circular RNAs (circRNAs) have been revealed to participate in chemoresistance cancer. Hence, role and mechanism circ_0010235 cisplatin resistance was investigated.Expression levels circ_0010235, microRNA (miR)-379-5p E2F transcription factor 7 (E2F7) were analyzed using quantitative reverse PCR (qRT-PCR) western blot. Cell DDP sensitivity, proliferation, apoptosis, invasion,...
Abstract Background With the development of single-cell technology, many cell traits can be measured. Furthermore, multi-omics profiling technology could jointly measure two or more in a single simultaneously. In order to process various data accumulated rapidly, computational methods for multimodal integration are needed. Results Here, we present inClust+, deep generative framework multi-omics. It’s built on previous inClust that is specific transcriptome data, and augmented with mask...