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Obesity is one of the greatest challenges to public health (Aleem et al., 2015). Hyperlipidemia, which mainly manifests as an abnormal increase in serum lipid and/or lipoprotein content (Guo et al., 2018), is a major complication of obesity (Heymsfield & Wadden, 2017). It is usually caused by an unhealthy lifestyle and diet . Recently, due to an increase in the consumption of animal meat, which contains a large amount of energy, saturated fatty acids, and sterols, the risk of obesity and hyperlipidemia has increased (Akiyama et al., 1996).

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Obesity is associated with the gut microbiota and has been shown to cause gut microbiota disturbances. Our previous studies have demonstrated that Miao sour soup (SS) contains abundant short‐chain fatty acids (SCFAs) which can be used as energy substrates of intestinal flora to selectively stimulate their growth and reproduction. Therefore, we explored whether the intestinal microbiota of rats with high‐fat diet‐induced obesity could be restored to normal by SS intervention. Male obese rats were divided into five groups randomly after successful modeling of obese rats: normal diet, high‐fat diet (HDF), HFD + SS, HFD with antibiotic, and HFD with antibiotic + SS. After 12 weeks of intervention, the weight and serum lipid of obese rats decreased. Furthermore, 16S rRNA analysis showed an imbalance and a decrease in the abundance and diversity of intestinal flora in obese rats, which improved after SS intervention. At the phylum level, Firmicutes increased while Proteobacteria decreased. The composition of the intestinal flora recovered at the genus level, inhibiting the reproduction of pathogenic bacteria, while the levels of SCFA‐producing bacteria such as Blautia and Lactococcus and the levels of SCFAs in cecal contents increased. In addition, SS reduced the levels of TNF‐α and IL‐6 in the intestinal mucosa of obese rats, increased the contents of PYY and GLP‐1 in colon tissue, and increased the expression of tight junction protein Occludin and ZO‐1 in the intestinal epithelium. Taken together, SS can regulate the intestinal flora of obese rats and improve the intestinal flora to facilitate weight loss and lipid reduction.

Aim: The p21-activated kinases (PAKs) are involved in many important biological activity regulations. FRAX019, FRAX414, FRAX597, FRAX1036 and G-5555 were identified as PAKs inhibitors. Their detailed inhibitory mechanisms deserve further investigation. Results: Molecular dynamics simulations and further calculations for the PAK1/inhibitor and PAK4/inhibitor complexes indicate that their binding free energies are basically consistent with the trend of experimental activity data. Conclusion: The anchoring of residues Leu347PAK1 and Leu398PAK4 is the structural basis for designing Afraxis PAK inhibitors. This study discloses the inhibitory mechanisms of FRAX019, FRAX414, FRAX597, FRAX1036 and G-5555 toward PAK1 and PAK4 and some clues to enhance kinase activities and selectivities, which will provide valuable information to the development of more potent and selective PAK inhibitors.