Communication-Efficient and Privacy-Preserving Verifiable Aggregation for Federated Learning.

Federated learning is a distributed machine learning framework, which allows users to save data locally for training without sharing data. Users send the trained local model to the server for aggregation. However, untrusted servers may infer users' private information from the provided data and mistakenly execute aggregation protocols to forge aggregation results. In order to ensure the reliability of the federated learning scheme, we must protect the privacy of users' information and ensure the integrity of the aggregation results. This paper proposes an effective secure aggregation verifiable federated learning scheme, which has both high communication efficiency and privacy protection function. The scheme encrypts the gradients with a single mask technology to securely aggregate gradients, thus ensuring that malicious servers cannot deduce users' private information from the provided data. Then the masked gradients are hashed to verify the aggregation results. The experimental results show that our protocol is more suited for bandwidth-constraint and offline-users scenarios.

Short-chain fatty acids affect the development of inflammatory bowel disease through intestinal barrier, immunology, and microbiota: A promising therapy?

Intestinal metabolites are attracting increasing interest, especially more and more studies have found they are closely related to diseases. Microbial fermentation of indigestible dietary fibers in the gut produces short chain fatty acids (SCFAs) as the main product. SCFAs can exert influences on the integrity of the intestinal epithelial and mucosal barrier, immune reactions, and the diversity of microbiota in humans. Thus, alteration in SCFAs may affect inflammatory bowel disease (IBD). In IBD, SCFAs are involved in the main pathogenic process and play an important role in the development of intestinal inflammation. Although many studies have proved that pretreatment with SCFAs can effectively ameliorate inflammation in the gut, the mechanisms are not fully understood. In this review, we describe the relationship between SCFAs and IBD from the aspects of defense barrier, immune effects, and microbial alterations. We also summarize the effects of SCFAs on comorbidities in IBD via the gut-brain, gut-liver, and gut-lung axis, and we give an overview of the prospects of their clinical application. A better understanding of the relevance of SCFAs in IBD may reveal novel targets for future study.

Kuijie decoction ameliorates ulcerative colitis by affecting intestinal barrier functions, gut microbiota, metabolic pathways and Treg/Th17 balance in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Currently, the clinical treatment is limited and difficult to achieve satisfactory results for ulcerative colitis (UC). The role of traditional Chinese medicine (TCM) in the treatment of UC is very complex. Kuijie decoction (KJD) as a classic TCM, is widely used in the clinical treatment of UC, but the mechanism of its action is still unclear. AIM OF THE STUDY: This study is to investigate the protective effects of KJD on UC and the underlying mechanisms. MATERIALS AND METHODS: The experimental model of UC was induced by DSS, and KJD was introduced into the model at the same time. Clinical symptoms, including the body weight, colon length and colon histopathological, were used to measure the severity of colitis. The expression of inflammatory cytokines and tight junction proteins was quantified. The effect of KJD on intestinal flora and intestinal metabolism was determined by 16S rRNA and untargeted metabolomics analysis, respectively. The proportion of Th17 cells and Tregs in the spleen was examined by flow cytometry. RESULTS: Mice treated with KJD showed significantly alleviated clinical symptoms and histological damage, such as more body weight gain, lower disease activity index (DAI) score, and longer colon length. The administration of KJD also led to the down-regulation of inflammatory mediators, upregulation of the expression of ZO-1, occludin and decreased claudin-2, as well as altered microbiota composition against DSS challenges (especially an increase of Lachnospiraceae). KJD enhanced the percentage of Treg cells but decreased the proportion of Th17 cells to maintain intestinal homeostasis by improving gut microbiota metabolism. CONCLUSIONS: In summary, KJD maintained intestinal epithelial homeostasis by regulating epithelial barrier function, intestinal flora, and restoring Th17/Treg balance. KJD has the potential to be a Chinese medicine treatment for UC.

The role of sphingosine-1-phosphate in autophagy and related disorders.

S1P, also referred to as sphingosine-1-phosphate, is a lipid molecule with bioactive properties involved in numerous cellular processes such as cell growth, movement, programmed cell death, self-degradation, cell specialization, aging, and immune system reactions. Autophagy is a meticulously controlled mechanism in which cells repurpose their elements to maintain cellular balance. There are five stages in autophagy: initiation, nucleation, elongation and maturation, fusion, and degradation. New research has provided insight into the complex connection between S1P and autophagy, uncovering their interaction in both normal and abnormal circumstances. Gaining knowledge about the regulatory mechanism of S1P signaling on autophagy can offer a valuable understanding of its function in well-being and illness, potentially leading to innovative therapeutic concepts for diverse ailments. Hence, this review analyzes the essential stages in mammalian autophagy, with a specific emphasis on recent research exploring the control of each stage by S1P. Additionally, it sheds light on the roles of S1P-induced autophagy in various disorders.

The role of Lactobacillus in inflammatory bowel disease: from actualities to prospects.

Inflammatory Bowel Disease (IBD), a chronic nonspecific intestinal inflammatory disease, is comprised of Ulcerative Colitis (UC) and Crohn's Disease (CD). IBD is closely related to a systemic inflammatory reaction and affects the progression of many intestinal and extraintestinal diseases. As one of the representative bacteria for probiotic-assisted therapy in IBD, multiple strains of Lactobacillus have been proven to alleviate intestinal damage and strengthen the intestinal immunological barrier, epithelial cell barrier, and mucus barrier. Lactobacillus also spares no effort in the alleviation of IBD-related diseases such as Colitis-associated Colorectal cancer (CAC), Alzheimer's Disease (AD), Depression, Anxiety, Autoimmune Hepatitis (AIH), and so on via gut-brain axis and gut-liver axis. This article aims to discuss the role of Lactobacillus in IBD and IBD-related diseases, including its underlying mechanisms and related curative strategies from the present to the future.

Autotaxin (ATX) inhibits autophagy leading to exaggerated disruption of intestinal epithelial barrier in colitis.

Inflammatory bowel disease (IBD) is an immune-mediated disease. Autotaxin (ATX) is associated with increased inflammatory molecules, however, its effect on IBD is not well understood. Autophagy plays an important role in IBD, whether ATX and autophagy act in concert in IBD remains unknown. This study is to explore the possible mechanisms of ATX affecting autophagy leading to the disruption of intestinal epithelial barrier, thereby exacerbating colitis. The expression of ATX was upregulated in UC patients and dextran sulfate sodium (DSS)-induced colitis mice. Here, we described that providing an ATX inhibitor during DSS colitis increased autophagy and ameliorated colonic inflammation. Conversely, intrarectal administration with recombinant (r)ATX increased colitis and decreased autophagy. This pro-colitic effect was attenuated in mice treated with rapamycin, resulting in increased autophagy activity and mild colitis. Moreover, the inhibitory effect of rATX on autophagy was confirmed in vitro and was reversed by the addition of rapamycin. The damaging effects of ATX on epithelial barrier function were reversed by ATX inhibitor or rapamycin treatment. In sum, our results show that ATX can inhibit autophagy through the mTOR pathway, resulting in exaggerated damage to the intestinal epithelial barrier during colitis. These findings suggest that ATX may be a key pro-colitic factor, and represent a potential therapeutic target for treating IBD in the future.

Hepatic HRC induces hepatocyte pyroptosis and HSCs activation via NLRP3/caspase-1 pathway.

The histidine-rich calcium-binding protein (HRC) is a regulator of Ca2 + homeostasis and it plays a significant role in liver fibrosis. Pyroptosis, a specific inflammatory cell death, can lead to hepatic stellate cells (HSCs) activation and liver fibrosis. However, the role of HRC in pyroptosis has not been explored. In this study, we demonstrated that HRC, mainly located in the hepatocyte, was over expressed in fibrotic liver tissues. We further found that enforced expression of HRC in hepatocytes induced pyroptosis and HMGB1 release, and subsequently led to HSCs activation by NLRP3/caspase-1 pathway. In addition, the proliferation and migration of HSCs were also enhanced by HRC overexpression in hepatocytes. Furthermore, NLRP3 inhibitor MCC950 and caspase-1 inhibitor VX-765 alleviated hepatic HRC-mediated hepatocytes pyroptosis and HSCs activation. This study demonstrated that hepatic HRC promoted HSCs activation by inducing hepatocyte pyroptosis, which suggests that HRC may be a promising therapeutic target to prevent liver fibrosis.