目的·分析Fbxo22基因敲除小鼠的表型,为探索FBXO22的生物学功能提供理论依据。方法·利用CRISPR-Cas9(clustered regularly interspaced short palindromic repeats-CRISPR associated protein 9)技术成功构建Fbxo22全身敲除小...目的·分析Fbxo22基因敲除小鼠的表型,为探索FBXO22的生物学功能提供理论依据。方法·利用CRISPR-Cas9(clustered regularly interspaced short palindromic repeats-CRISPR associated protein 9)技术成功构建Fbxo22全身敲除小鼠,观察胚胎和小鼠的外观,测定其数量和质量,并分析小鼠的进食量和存活时间。结果·Fbxo22敲除小鼠胚胎期17.5/18.5 d的胚胎数量符合孟德尔遗传定律,外观未见异常,但是多数Fbxo22敲除小鼠在出生后48 h内死亡。少数存活小鼠体型偏小,进食减少,存活时间缩短。结论·FBXO22对于小鼠出生后早期存活和正常发育有重要作用。展开更多
Cefquinome is the only fourth-generation cephalosporin used solely for veterinary applications.In this study,we established the wild-type cut-off(CO_(WT))and pharmacokinetic/pharmacodynamic cut-off(CO_(PD))of cefquino...Cefquinome is the only fourth-generation cephalosporin used solely for veterinary applications.In this study,we established the wild-type cut-off(CO_(WT))and pharmacokinetic/pharmacodynamic cut-off(CO_(PD))of cefquinome against Escherichia coli and Staphylococcus aureus.A total of 210 E.coli and 160 S.aureus isolates were collected from pigs in Guangdong Province between 2014 and 2018.The minimum inhibitory concentrations(MICs)were determined using a microdilution broth method.MIC_(50)and MIC_(90)were 0.06 and 0.25μg m L^(–1)for E.coli and 0.5 and 1μg m L^(–1)for S.aureus,respectively.Statistical analysis and the ECOFFinder Program showed that the CO_(WT)for cefquinome against E.coli and S.aureus were0.125 and 2μg m L^(–1),respectively.The resistance rates were 11.9%for E.coli and 6.25%for S.aureus.Based on a5000-subject Monte Carlo simulation,the CO_(PD)value for cefquinome against E.coil and S.aureus was 0.25μg m L^(–1)under the recommended dose(2 mg kg^(–1),twice a day for 3 days),confirming that infections caused by strains with MIC≤0.25μg m L^(–1)could be effectively treated.Following adjustment of the dosing regimen to 4.5 mg kg^(–1),effective treatment(>90)was achieved for S.aureus infections with MIC_(90)1μg m L^(–1).This susceptibility breakpoint determination is significant for resistant surveillance and cefquinome dosage guidance against E.coli and S.aureus in pigs.展开更多
基金supported by the National Natural Science Foundation of China(31972733)。
文摘Cefquinome is the only fourth-generation cephalosporin used solely for veterinary applications.In this study,we established the wild-type cut-off(CO_(WT))and pharmacokinetic/pharmacodynamic cut-off(CO_(PD))of cefquinome against Escherichia coli and Staphylococcus aureus.A total of 210 E.coli and 160 S.aureus isolates were collected from pigs in Guangdong Province between 2014 and 2018.The minimum inhibitory concentrations(MICs)were determined using a microdilution broth method.MIC_(50)and MIC_(90)were 0.06 and 0.25μg m L^(–1)for E.coli and 0.5 and 1μg m L^(–1)for S.aureus,respectively.Statistical analysis and the ECOFFinder Program showed that the CO_(WT)for cefquinome against E.coli and S.aureus were0.125 and 2μg m L^(–1),respectively.The resistance rates were 11.9%for E.coli and 6.25%for S.aureus.Based on a5000-subject Monte Carlo simulation,the CO_(PD)value for cefquinome against E.coil and S.aureus was 0.25μg m L^(–1)under the recommended dose(2 mg kg^(–1),twice a day for 3 days),confirming that infections caused by strains with MIC≤0.25μg m L^(–1)could be effectively treated.Following adjustment of the dosing regimen to 4.5 mg kg^(–1),effective treatment(>90)was achieved for S.aureus infections with MIC_(90)1μg m L^(–1).This susceptibility breakpoint determination is significant for resistant surveillance and cefquinome dosage guidance against E.coli and S.aureus in pigs.
