Altered Gut Microbiota and Short-chain Fatty Acids in Chinese Children with Constipated Autism Spectrum Disorder.

Gastrointestinal symptoms are more prevalent in children with autism spectrum disorder (ASD) than in typically developing (TD) children. Constipation is a significant gastrointestinal comorbidity of ASD, but the associations among constipated autism spectrum disorder (C-ASD), microbiota and short-chain fatty acids (SCFAs) are still debated. We enrolled 80 children, divided into the C-ASD group (n = 40) and the TD group (n = 40). In this study, an integrated 16S rRNA gene sequencing and gas chromatography-mass spectrometry-based metabolomics approach was applied to explore the association of the gut microbiota and SCFAs in C-ASD children in China. The community diversity estimated by the Observe, Chao1, and ACE indices was significantly lower in the C-ASD group than in the TD group. We observed that Ruminococcaceae_UCG_002, Erysipelotrichaceae_UCG_003, Phascolarctobacterium, Megamonas, Ruminiclostridium_5, Parabacteroides, Prevotella_2, Fusobacterium, and Prevotella_9 were enriched in the C-ASD group, and Anaerostipes, Lactobacillus, Ruminococcus_gnavus_group, Lachnospiraceae_NK4A136_group, Ralstonia, Eubacterium_eligens_group, and Ruminococcus_1 were enriched in the TD group. The propionate levels, which were higher in the C-ASD group, were negatively correlated with the abundance of Lactobacillus taxa, but were positively correlated with the severity of ASD symptoms. The random forest model, based on the 16 representative discriminant genera, achieved a high accuracy (AUC = 0.924). In conclusion, we found that C-ASD is related to altered gut microbiota and SCFAs, especially decreased abundance of Lactobacillus and excessive propionate in faeces, which provide new clues to understand C-ASD and biomarkers for the diagnosis and potential strategies for treatment of the disorder. This study was registered in the Chinese Clinical Trial Registry ( www.chictr.org.cn ; trial registration number ChiCTR2100052106; date of registration: October 17, 2021).

Ubiquitylome analysis reveals the involvement of ubiquitination in the cold responses of banana seedling leaves.

Low temperature is a crucial environmental factor limiting the productivity and distribution of banana. Ubiquitination (Kub) is one of the main posttranslational modifications (PTMs) involved in plant responses to abiotic stresses. However, little information is available on the effects of Kub on banana under cold stress. In this study, we used label-free quantification (LFQ) to identify changes in the protein expression and Kub levels in banana seedling leaves after chilling treatment. In total, 4156 proteins, 1089 ubiquitinated proteins and 2636 Kub sites were quantified. Western blot assays showed that Kub was abundant in leaves after low-temperature treatment. Our results show that the proteome and ubiquitylome were negatively correlated, indicating that Kub could be involved in the degradation of proteins in banana after chilling treatment. Based on bioinformatics analysis, low-temperature stress-related signals and metabolic pathways such as cold acclimation, glutathione metabolism, calcium signaling, and photosynthesis signaling were identified. In addition, we found that transcription factors and chromatin remodeling factors related to low-temperature stress were ubiquitinated. Overall, our work presents the first systematic analysis of the Kub proteome in banana under cold stress and provides support for future studies on the regulatory mechanisms of Kub during the cold stress response in plants. SIGNIFICANCE: Banana is a typical tropical fruit tree with poor low-temperature tolerance,however, the role of PTMs such as Kub in the cold response of banana remains unclear. This study highlights the fact that the effects of low-temperature on proteome and ubiquitylome in the banana seedling leaves, we discussed the correlation between transcriptome and proteome, ubiquitylome and proteome, and we analyzed the expression and the changes of ubiquitination levels of low-temperature related proteins and pathway after chilling treatment, and we found that transcription factors and chromatin remodeling factors related to low-temperature stress were ubiquitinated. This study provides new insights into the ubiquitination pathway of banana under cold stress.

Sevoflurane combined with ATP activates caspase-1 and triggers caspase-1-dependent pyroptosis in murine J774 macrophages.

Sevoflurane is one of the most commonly used volatile anesthetics. Recent studies have shown that sevoflurane plays an important role in modulation of inflammation and immunity. However, little is known about the related molecular mechanisms. This study was designed to investigate the effects and mechanisms of sevoflurane on inflammatory cell death pyroptosis in the murine macrophage cell line J774 cells. Sevoflurane combined with ATP could increase the level of activated caspase-1, pyroptosis, and reactive oxygen species (ROS). Furthermore, treatment of cells with the caspase-1 inhibitor Ac-YVAD-CMK dramatically decreased the percentage of pyroptosis. In addition, inhibition of ROS with N-acetyl-L-cysteine or diphenyleneiodonium significantly reduced the activated levels of caspase-1. These results demonstrated that sevoflurane combined with ATP could activate caspase-1 and trigger caspase-1-dependent pyroptosis through the modulation of ROS production.