This study is to investigate the mechanism and action characteristics of 6-chloro-3-methyl-4-(2-methyoxycarbonylthiophene-3-sulfonyl)-3, 4-dihydroquinoxa-lin-2-(1 H)-one (XU07011) against HIV-1 replication. XU07011 anti-HIV activity was tested by using VSVG/HIV pseudotype viral system and confirmed by HIV-1 live viruses' infectious assay. Time of addition was used to test HIV-1 reverse transcription process. RNA-dependent DNA polymerase activity and RNase H activity were tested by using enzyme linked immunoabsorbent assay and fluorescence method. Wild type and nine NNRTIs-resistant reverse transcriptase enzymatic models and cell-based pharmacological models were used to evaluate XU07011 bio-characteristics. The results showed that XU07011 inhibited HIV-1 replication with IC50 of (0.057 +/- 0.01) micromol x L(-1) which was comparable to nevirapine [IC50: (0.046 +/- 0.01) micromol x L(-1)]. Mechanism study data indicated that XU07011 blocked HIV-1 reverse transcription process through acting on reverse transcriptase RNA-dependent DNA polymerase with IC 50 of (1.1 +/- 0.3) micromol x L(-1). The compound showed no effect on RNase H activity. XU07011 exhibited better activities comparing with nevirapine on K103N mutated NNRTIs-resistant HIV-1 strains. This study could provide a theoretical basis for novel anti-HIV reagents development.

Objective:To analyze the relationship between free androgen index and insulin function in obese young men aged from 20 to 35.Methods:A total of 82 young obese men in Obesity Clinic from February to October 2019 were enrolled in the study. The subjects were divided into 3 subgroups according to free androgen index level tertiles. The blood glucose and insulin levels were tested after oral glucose tolerance test. Homeostasis model assessment for insulin resistance (HOMA-IR), homeostasis model assessment for β cell function (HOMA-β), insulin secretion index, and insulin sensitivity index (Matsuda index) were used to evaluate β cell function in oder to analyze the relationship between free androgen index and insulin function.Results:In young obese men, participants with higher free androgen index levels exhibited less waist circumference, lower body mass index, 1 h postprandial insulin, 2 h postprandial insulin, HOMA-IR level but with a higher total testosterone, sex hormone binding globulin, and Matsuda index level (all P<0.05). There was a negative correlation between the free androgen index and the HOMA-IR ( r=-0.386, P=0.016), and the correlation tended to a linear trend after adjustment for age, sex, body mass index, and waist circumference ( Ptrend=0.034). Free testosterone was positively correlated with Matsuda index ( r=0.280, P=0.004), but the correlation disappeared after adjustment ( Ptrend=0.623). The results of further regression analysis showed that the level of free testosterone index decreased by 14.1% ( OR=0.869, 95% CI0.767-0.984, P=0.028) for each increase of HOMA-IR after adjustment. Conclusion:The level of free testosterone index is a predictor of insulin resistance in obese young men, but the association between this parameter and insulin sensitivity may be caused by obesity.