Short-chain fatty acids in diseases.

Short-chain fatty acids (SCFAs) are the main metabolites produced by bacterial fermentation of dietary fibre in the gastrointestinal tract. The absorption of SCFAs is mediated by substrate transporters, such as monocarboxylate transporter 1 and sodium-coupled monocarboxylate transporter 1, which promote cellular metabolism. An increasing number of studies have implicated metabolites produced by microorganisms as crucial executors of diet-based microbial influence on the host. SCFAs are important fuels for intestinal epithelial cells (IECs) and represent a major carbon flux from the diet, that is decomposed by the gut microbiota. SCFAs play a vital role in multiple molecular biological processes, such as promoting the secretion of glucagon-like peptide-1 by IECs to inhibit the elevation of blood glucose, increasing the expression of G protein-coupled receptors such as GPR41 and GPR43, and inhibiting histone deacetylases, which participate in the regulation of the proliferation, differentiation, and function of IECs. SCFAs affect intestinal motility, barrier function, and host metabolism. Furthermore, SCFAs play important regulatory roles in local, intermediate, and peripheral metabolisms. Acetate, propionate, and butyrate are the major SCFAs, they are involved in the regulation of immunity, apoptosis, inflammation, and lipid metabolism. Herein, we review the diverse functional roles of this major class of bacterial metabolites and reflect on their ability to affect intestine, metabolic, and other diseases. Video Abstract.

Spatiotemporal absorption fluctuation imaging based on U-Net.

SIGNIFICANCE: Full-field optical angiography is critical for vascular disease research and clinical diagnosis. Existing methods struggle to improve the temporal and spatial resolutions simultaneously. AIM: Spatiotemporal absorption fluctuation imaging (ST-AFI) is proposed to achieve dynamic blood flow imaging with high spatial and temporal resolutions. APPROACH: ST-AFI is a dynamic optical angiography based on a low-coherence imaging system and U-Net. The system was used to acquire a series of dynamic red blood cell (RBC) signals and static background tissue signals, and U-Net is used to predict optical absorption properties and spatiotemporal fluctuation information. U-Net was generally used in two-dimensional blood flow segmentation as an image processing algorithm for biomedical imaging. In the proposed approach, the network simultaneously analyzes the spatial absorption coefficient differences and the temporal dynamic absorption fluctuation. RESULTS: The spatial resolution of ST-AFI is up to 4.33 µm, and the temporal resolution is up to 0.032 s. In vivo experiments on 2.5-day-old chicken embryos were conducted. The results demonstrate that intermittent RBCs flow in capillaries can be resolved, and the blood vessels without blood flow can be suppressed. CONCLUSIONS: Using ST-AFI to achieve convolutional neural network (CNN)-based dynamic angiography is a novel approach that may be useful for several clinical applications. Owing to their strong feature extraction ability, CNNs exhibit the potential to be expanded to other blood flow imaging methods for the prediction of the spatiotemporal optical properties with improved temporal and spatial resolutions.

Enhanced O-linked Glcnacylation in Crohn's disease promotes intestinal inflammation.

BACKGROUND: Treatment of Crohn's disease (CD) remains to be a challenge due to limited insights for its pathogenesis. We aimed to determine the role of O-Linked ß-N-acetylglucosamine (O-GlcNAc) in the development of CD and evaluate therapeutic effects of O-GlcNAc inhibitors on CD. METHODS: O-GlcNAc in intestinal epithelial tissues of CD, adherent-invasive Escherichia coli (AIEC) LF82-infected cells and mice was determined by immunoblot and immunohistochemistry. AIEC LF82 and dextran sulfate sodium were administrated into C57BL/6 mice for estabolishing inflammatory bowel disease model and for therapeutic study. FINDINGS: O-GlcNAc was increased in intestinal epithelial tissues of CD patients and AIEC LF82-infected mice. Infection of AIEC LF82 up-regulated the level of UDP-GlcNAc and increased O-GlcNAc in human colon epithelial HCT116 and HT-29 cells. We identified that IKKß and NF-κB were O-Glycosylated in AIEC LF82-treated cells. Mutations of IKKß (S733A) and p65 (T352A) abrogated the O-GlcNAc in IKKß and NF-κB and inhibited AIEC LF82-induced activation of NF-κB. Application of 6-diazO-5-oxO-L-norleucine, an agent that blocks the production of UDP-GlcNAc and inhibits O-GlcNAc, inactivated NF-κB in AIEC LF82-infected cells, enhanced the formation of autophagy, promoted the removal of cell-associated AIEC LF82, alleviated intestinal epithelial inflammation, and improved the survival of the colitis mice. INTERPRETATION: Intestinal inflammation in CD is associated with increased O-GlcNAc modification, which is required for NF-κB activation and suppression of autophagy. Targeting O-GlcNAc could be an effective therapy for inflammatory bowel disease. FUNDING: National Natural Science Foundation of China (Nos. 81573087 and 81772924) and International Cooperation Foundation of Jilin Province (20190701006GH).