1.Analysis of Synonymous Codon Usage Bias in 09H1N1
Zhenpeng LI ; Dequan YING ; Peng LI ; Fei LI ; Xiaochen BO ; Shengqi WANG
Virologica Sinica 2010;25(5):329-340
A novel subtype of influenza A virus 09H1N1 has rapidly spread across the world. Evolutionary analyses of this virus have revealed that 09H1N1 is a triple reassortant of segments from swine, avian and human influenza viruses. In this study, we investigated factors shaping the codon usage bias of 09H1N1 and carried out cluster analysis of 60 strains of influenza A virus from different subtypes based on their codon usage bias. We discovered that more preferentially used codons of 09H1N1 are A-ended or U-ended, and the intra-genomic codon usage bias of 09H1N1 is quite low. Base composition constraint, dinucleotide biases and translational selection are the main factors influencing the codon usage bias of 09H1N1. At the genome level, we find that the codon usage bias of 09H1N1 is similar to H1N1 (A/swine/Kansas/77778/2007H1N1), H9N2 from Asia, H1N2 from Asia and North America and H3N2 from North America. Our results provide insight for understanding the processes governing evolution, regulation of gene expression, and revealing the evolution of 09H1N1.
2. A cohort study of abnormal routine blood test results in landfill workers
Mei LI ; Liqiang ZHAO ; Qifu ZHOU ; Yakang YANG ; Dequan FENG ; Nian LIU ; Ying QIN
Chinese Journal of Industrial Hygiene and Occupational Diseases 2017;35(9):676-678
Objective:
To investigate the abnormalities of the blood system in landfill workers.
Methods:
A cohort study was conducted for 224 landfill workers who were followed up for 6 consecutive years with abnormal routine blood test results and a low platelet count as the outcome events. The life-table method was used to analyze the incidence rates of these two outcome events, and the incidence rates were compared between first-and second-line workers.
Results:
A total of 71 workers had abnormal routine blood test results, among whom 29 had abnormal leukocyte count, 14 had abnormal erythrocyte count, 40 had abnormal platelet count, 17 had abnormal hemoglobin, and 29 had a reduction in platelet count. For these landfill workers, the 6-year abnormal rate of routine blood test results was 43.2%, and the incidence rate of low platelet count within 6 years was 13.5%. The first-line workers had a significantly lower abnormal rate of routine blood test results than the second-line workers (
3.Identification of ferroptosis as a novel mechanism for antitumor activity of natural product derivative a2 in gastric cancer.
Ying LIU ; Zan SONG ; Yajie LIU ; Xubin MA ; Wang WANG ; Yu KE ; Yichao XU ; Dequan YU ; Hongmin LIU
Acta Pharmaceutica Sinica B 2021;11(6):1513-1525
Ferroptosis is a type of cell death accompanied by iron-dependent lipid peroxidation, thus stimulating ferroptosis may be a potential strategy for treating gastric cancer, therapeutic agents against which are urgently required. Jiyuan oridonin A (JDA) is a natural compound isolated from Jiyuan
4.Discovery of thiosemicarbazone derivatives as effective New Delhi metallo-β-lactamase-1 (NDM-1) inhibitors against NDM-1 producing clinical isolates
Bing ZHAO ; Xinhui ZHANG ; Tingting YU ; Ying LIU ; Xiaoling ZHANG ; Yongfang YAO ; Xuejian FENG ; Hongmin LIU ; Dequan YU ; Liying MA ; Shangshang QIN
Acta Pharmaceutica Sinica B 2021;11(1):203-221
New Delhi metallo-β-lactamase-1 (NDM-1) is capable of hydrolyzing nearly all β-lactam antibiotics, posing an emerging threat to public health. There are currently less effective treatment options for treating NDM-1 positive “superbug”, and no promising NDM-1 inhibitors were used in clinical practice. In this study, structure–activity relationship based on thiosemicarbazone derivatives was systematically characterized and their potential activities combined with meropenem (MEM) were evaluated. Compounds 19bg and 19bh exhibited excellent activity against 10 NDM-positive isolate clinical isolates in reversing MEM resistance. Further studies demonstrated compounds 19bg and 19bh were uncompetitive NDM-1 inhibitors with Ki = 0.63 and 0.44 μmol/L, respectively. Molecular docking speculated that compounds 19bg and 19bh were most likely to bind in the allosteric pocket which would affect the catalytic effect of NDM-1 on the substrate meropenem. Toxicity evaluation experiment showed that no hemolysis activities even at concentrations of 1000 mg/mL against red blood cells. In vivo experimental results showed combination of MEM and compound 19bh was markedly effective in treating infections caused by NDM-1 positive strain and prolonging the survival time of sepsis mice. Our finding showed that compound 19bh might be a promising lead in developing new inhibitor to treat NDM-1 producing superbug.