Lei Huang

Listeria monocytogenes (Lm) is a major human and animal foodborne pathogen. Here we show that hypervirulent Lm clones, particularly CC1, are strongly associated with dairy products, whereas hypovirulent clones, CC9 and CC121, are associated with meat products. Clone adaptation to distinct ecological niches and/or different food products contamination routes may account for this uneven distribution. Indeed, hypervirulent clones colonize better the intestinal lumen and invade more intestinal tissues than hypovirulent ones, reflecting their adaption to host environment. Conversely, hypovirulent clones are adapted to food processing environments, with a higher prevalence of stress resistance and benzalkonium chloride tolerance genes and a higher survival and biofilm formation capacity in presence of sub-lethal benzalkonium chloride concentrations. Lm virulence heterogeneity therefore reflects the diversity of the ecological niches in which it evolves. These results also have important public health implications and may help in reducing food contamination and improving food consumption recommendations to at-risk populations.

Abstract Structure-based generative chemistry is essential in computer-aided drug discovery by exploring a vast chemical space to design ligands with high binding affinity for targets. However, traditional in silico methods are limited by computational inefficiency, while machine learning approaches face bottlenecks due to auto-regressive sampling. To address these concerns, we have developed a conditional deep generative model, PMDM, for 3D molecule generation fitting specified targets. PMDM consists of a conditional equivariant diffusion model with both local and global molecular dynamics, enabling PMDM to consider the conditioned protein information to generate molecules efficiently. The comprehensive experiments indicate that PMDM outperforms baseline models across multiple evaluation metrics. To evaluate the applications of PMDM under real drug design scenarios, we conduct lead compound optimization for SARS-CoV-2 main protease (M pro ) and Cyclin-dependent Kinase 2 (CDK2), respectively. The selected lead optimization molecules are synthesized and evaluated for their in-vitro activities against CDK2, displaying improved CDK2 activity.

The viable bacterial strains in conventional yogurt are intolerant to bile acid, which consequently cannot survive the conditions and their beneficial bioactivities are thus lost. We have previously shown that Lactobacillus casei Q14 ( Lac-Q14), a probiotic, has the potential to alleviate diabetes in rats. Herein, we used Lac-Q14 as the starter culture to ferment yogurt and explore the mechanisms of the bioactivity in diabetic rats. The results showed that Lac-Q14 yogurt improved blood glucose and insulin level, lowered gene expression of critical enzymes involved in liver gluconeogenesis. Pyrosequencing showed an obvious change in the composition of intestinal microbiota in Lac-Q14 yogurt treated rats. The abundance of 21 genera differed significantly between the Lac-Q14 yogurt group and diabetes group. Quite a few short-chain fatty acid (SCFA)-producing bacteria were selectively enriched, along with increased concentrations of SCFA and downstream Glucagon-like peptide-1 (GLP-1) and Peptide YY (PYY) secretion.