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Propofol induces the Ser(1177) phosphorylation-dependent eNOS activation through the drug-stimulated translocation of PKC isoforms to distinct intracellular sites in HUVECs, which is independent of PI3K/Akt-independent pathway.

Curcumin can prevent and ameliorate NASH via lipid reduction, improve insulin resistance, improve anti-inflammatory, and have antioxidant effects, possibly related to its activation of Nrf2.

Gut microbiota plays an important role in drug modi cation, transformation and degradation, which are factors that need to be considered in personalized therapy. Acarbose, an inhibitor of α-glucosidase, is used as a rst-line drug for the treatment of type 2 diabetes; however, its clinical effects vary greatly among individuals, and the underlying mechanisms relating to the contribution of gut microbes remain to be elucidated. Herein, we reported the association between acarbose resistance and enteric bacteria by analyzing clinical samples and anaerobic enrichment culture, and isolated a major acarbose-degrading gut strain, Klebsiella grimontii TD1. Metagenomic analysis of the intestinal microbiome found that the abundance of K. grimontii TD1 was higher in patients with weak acarbose response and increased with longer medication time. In addition, in vivo experiments using a diabetic mouse model showed that this strain signi cantly weakened the hypoglycemic effect of acarbose. Further, we identi ed a key acarbosepreferred glucosidase, Apg, in K. grimontiiTD1 using a combined approach of induced transcriptome and protein pro ling. This enzyme is structurally characteristic, could degrade acarbose into small molecules with loss of inhibitor function, and was widely distributed in intestinal microorganisms, especially in Klebsiella. These results indicate that the risk of acarbose resistance caused by metabolic degradation from intestinal bacteria is widespread in humans, and this "induced degradational inactivation" mechanism may be one of the main causes of non-antibiotic drug resistance. Full TextType 2 diabetes mellitus (T2DM) is a common chronic metabolic disease, and its incidence is increasing globally year by year 1 . Acarbose is a rst-line agent for the treatment of T2DM 2,3 ; however, clinical data

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