Since the outbreak of Corona Virus Disease 2019, the widespread utilization of antiviral drugs with nucleoside and non-nucleoside structures has inevitably posed environmental risks. However, there is a lack of comprehensive research on whether nucleoside structures have an impact on their degradation behavior in aquatic environments. This study established a simulated sunlight-activated periodate (SSL/PI) system to effectively degrade zidovudine (ZDV), used as a model pollutant representative of antiviral drugs. Results showed that 1 O 2 and O 2 ∙− were identified as the main reactive species responsible for ZDV degradation. The primary degradation pathways involved C-N bond cleavage, dehydrogenation, and the disruption of azide group. The SSL/PI system demonstrated selective oxidation capabilities, with nucleoside analogue antiviral drugs (NAADs) faster than non-nucleoside antiviral drugs (NNADs). It was found that NAADs with low octanol/water partition coefficient and polarizability values are more susceptible to oxidation and removal compared to NNADs. This may be attributed to the higher hydrophilicity, reduced molecular aggregation, and resistance to deformation of NAADs compared to NNADs, thereby accelerating the oxidation process. Overall, this study offers new insights into the selective oxidative mechanisms of SSL/PI for antiviral drugs and the crucial role of nucleoside structures in the removal process.
Background Although short-term high-fat diet (S-HFD) and long-term high-fat diet (L-HFD) induce metabolic disorder, the underlying epigenetic mechanism is still unclear. Results Here, we found that both 4 days of S-HFD and 10 weeks of L-HFD increased mRNA m 6 A level in epididymal white adipose tissue (eWAT) and impaired metabolic health. Interestingly, S-HFD activated transposable elements (TEs), especially endogenous retroviruses (ERVs) in eWAT, while L-HFD activated long interspersed elements (LINEs). Subsequently, we demonstrated that both S-HFD and L-HFD increased m 6 A level of Ehmt2 and decreased EHMT2 protein expression and H3K9me2 level, accounting for activation of ERVs and LINEs. Overexpression of EHMT2 in eWAT or inhibition of ERVs and LINEs by antiviral therapy improved metabolic health under HFD feeding. Notably, we found that both short-term and long-term HFD feeding increased Fimicutes/Bacteroidota ratio and decreased the gut microbiome health index. Fecal microbiota transplantation (FMT) experiments demonstrated that gut microbiota from S-HFD and L-HFD was responsible for increased m 6 A level in eWAT, resulting in glucose intolerance and insulin insensitivity. Furthermore, we identified that both S-HFD and L-HFD increased the abundance of the gut microbial metabolite homogentisic acid (HGA), and HGA level was positively correlated with unclassified_f__Lachnospiraceae which was both increased in S-HFD and L-HFD feeding mice. Administration of HGA increased the m 6 A level of Ehmt2 and decreased the EHMT2 protein expression and H3K9me2 level in eWAT, leading to metabolic disorder in mice. Conclusions Together, this study reveals a novel mechanism that S-HFD and L-HFD induce metabolism disorder through gut microbiota-HGA-m 6 A- Ehmt2 -ERV/LINE signaling. These findings may provide a novel insight for prevention and treatment of metabolism disorder upon short-term or long-term dietary fat intake.
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危险品化学品经营许可证（带存储）