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Sepsis progression is significantly associated with the disruption of gut eubiosis. However, the modulatory mechanisms of gut microbiota operating during sepsis are still unclear. Herein, we investigated how gut commensals impact sepsis development in a pre-clinical model. Cecal ligation and puncture (CLP) surgery was used to establish polymicrobial sepsis in mice. Mice depleted of gut microbiota by an antibiotic cocktail (ABX) exhibited a significantly higher level of mortality than controls. As determined by metabolomics analysis, ABX treatment has depleted many metabolites, and subsequent supplementation with l-rhamnose (rhamnose, Rha), a bacterial carbohydrate metabolite, exerted profound immunomodulatory properties with a significant enhancement in macrophage phagocytosis, which in turn improved organ damage and mortality. Mechanistically, rhamnose binds directly to and activates the solute carrier family 12 (potassium-chloride symporter), member 4 (SLC12A4) in macrophages and promotes phagocytosis by activating the small G-proteins, Ras-related C3 botulinum toxin substrate1 (Rac1) and cell division control protein 42 homolog (Cdc42). Interestingly, rhamnose has enhanced the phagocytosis capacity of macrophages from sepsis patients. In conclusion, by identifying SLC12A4 as the host interacting protein, we disclosed that the gut commensal metabolite rhamnose is a functional molecular that could promote the phagocytosis capacity of macrophages and protect the host against sepsis.

Summary: Obesity and type 2 diabetes (T2D) remain major global healthcare challenges, and developing therapeutics necessitates using nonhuman primate models. Here, we present a transcriptomic and proteomic atlas of all the major organs of cynomolgus monkeys with spontaneous obesity or T2D in comparison to healthy controls. Molecular changes occur predominantly in the adipose tissues of individuals with obesity, while extensive expression perturbations among T2D individuals are observed in many tissues such as the liver and kidney. Immune-response-related pathways are upregulated in obesity and T2D, whereas metabolism and mitochondrial pathways are downregulated. Moreover, we highlight some potential therapeutic targets, including SLC2A1 and PCSK1 in obesity as well as SLC30A8 and SLC2A2 in T2D. Our study provides a resource for exploring the complex molecular mechanism of obesity and T2D and developing therapies for these diseases, with limitations including lack of hypothalamus, isolated islets of Langerhans, longitudinal data, and body fat percentage.

Speech recognition (SR) systems based on deep neural networks are increasingly widespread in smart devices. However, they are vulnerable to human-imperceptible adversarial attacks, which cause the SR to generate incorrect or targeted adversarial commands. Meanwhile, audio adversarial attacks are particularly susceptible to various factors, e.g., ambient noise, after applying them to a real-world attack. To circumvent this issue, we develop a universal adversarial perturbation (UAP) generation method to construct robust real-world UAP by integrating ambient noise into the generation process. The proposed UAP can work well in the case of input-agnostic and independent sources. We validate the effectiveness of our method on two different SRs in different real-world scenarios and parameters, the results demonstrate that our method yields state-of-the-art performance, i.e. given any audio waveform, the word error rate can be up to 80%. Extensive experiments investigate the impact of different parameters (e.g, signal-to-noise ratio, distance, and attack angle) on the attack success rate.

Liver health has long been linked to the homeostasis of gut microbiota. Although some studies have shown that alterations in the species and function of gut microbiota contribute to the initiation and development of acute liver injury (ALI), studies investigating the effects of ALI on gut microbial dynamic composition changes are still limited. To observe whether liver damage can alter the composition of gut microbiota dynamically, we established three chemical models (e.g., acetaminophen, carbon tetrachloride, lipopolysaccharide) of ALI. Using these models, multiple time points of liver injury and intestinal microbiome were analyzed through plasma biochemical analysis and 16S rRNA gene sequencing. We assessed α-diversity, Unifrac principal coordinates analysis (PCoA), and linear discriminant analysis effect size (LEfSe) in the injury and control groups. The composition of the gut microbiota underwent dramatic shifts with liver injury and recovery in each model. Additionally, specific microbial abundance was significantly correlated with the level of plasma alanine transaminase and aspartate transaminase. These data provide new evidence that liver dysfunction and restoration is dynamically linked with the changes in the intestinal microbiome.

Tea residue is a by-product of tea processing and contains ∼ 60 % insoluble dietary fiber. We investigated the physicochemical properties and structure of the insoluble dietary fiber of tea (T-IDF), and its defecation function was evaluated. The physical and chemical indexes of the T-IDF, including its water holding, oil holding, swelling, cation exchange, and cholesterol exchange capacities, were measured, while its structure was analyzed by a range of analytical techniques. Furthermore, the related indexes of the animal defecation function were determined, and the in vitro detection of fermented short chain fatty acid was conducted. We found that T-IDF exhibits excellent physical and chemical properties. Moreover, the consumption of T-IDF significantly promoted defecation in slow transit intestinal dyskinesia mice and enhanced the production of short chain fatty acids. Overall, we demonstrated a good correlation between the physicochemical properties and the structure/function of T-IDF.