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Dynamic chemistry utilizing both covalent and noncovalent bonds provides valid protocols in manipulating properties of self‐assemblies and functions. Here we employ dynamic chemistry to realize multiple‐route control over supramolecular chirality up to five states. N‐protected fluorinated phenylalanine in the carboxylate state self‐assembled into achiral nanoparticles ascribed to the amphiphilicity. Protonation promoted one‐dimensional growth into helices with shrunk hydrophilicity, which in the presence of disulfide pyridine undergo chirality inversion promoted by the hydrogen bonding‐directed coassembly. Further interacting with the water‐soluble reductant cleavages the disulfide bond to initiate the rearrangement of coassemblies with a chirality inversion as well. Finally, by tuning the pH environments, aromatic nucleophilic substitution reaction between reduced products and perfluorinated phenylalanine occurs, giving distinct chiral nanoarchitectures with emerged luminescence and circularly polarized luminescence. We thus realized a particular five‐state control by combining dynamic chemistry at one chiral compound, which greatly enriches the toolbox in fabricating responsive chiroptical materials. [ABSTRACT FROM AUTHOR]

Leptospirosis is a significant worldwide zoonotic infectious disease that infects a wide range of animals and humans. Leptospira will colonize the animal's urinary and reproductive systems and be excreted with urine, potentially causing a wide range of infections. Dogs are an essential host for Leptospira, and epidemiological investigation studies of leptospirosis must be conducted to clarify the prevalence of leptospirosis and to reduce the risk of transmission to humans. This study aimed to investigate the seroepidemiology of leptospiral infection in dogs from Changchun, China, using Microscopic Agglutination Test (MAT). A total of 1053 canine blood samples were collected and tested by MAT. The positive rate of MAT was approximately 19.1%. The main prevalent Leptospira serogroups were L. Icterohaemorrhagiae (8.1%), L. Canicola (7.6%), L. Australis (5.3%), L. Ballum (4.7%) and L. Pyrogenes (4.2%). No statistically significant difference among different varieties, sexes and sampling seasons (p > 0.05), except the age (p < 0.05). The seropositive rate was much higher in adult and aged dogs than in juvenile dogs. Our results showed the seroprevalence and the prevalent serogroup of Canine leptospirosis in Changchun, China. [ABSTRACT FROM AUTHOR]

Leptospirosis is a re-emerging worldwide zoonotic disease. Infected patients and animals often exhibit intestinal symptoms. Mounting evidence suggests that host immune responses to bacterial infection are closely associated with intestinal homeostasis. Our previous research has shown that the gut microbiota can protect the host from acute leptospirosis, while the specific bacterial metabolic mediators participating in the pathogenesis remain to be identified. Short-chain fatty acids (SCFAs) are metabolites produced mainly by the gut microbiota that play a role in immune regulation. However, whether SCFAs are the key to protecting the host against leptospirosis and the underlying regulatory mechanisms are unknown. In this study, our results showed that the SCFA butyrate is involved in ameliorating leptospirosis. The depletion of SCFAs by antibiotic cocktail treatment reduced survival time after Leptospira infection while supplementation with butyrate but not acetate or propionate significantly amelioration of leptospirosis. In vitro experiments showed that butyrate treatment enhanced the intracellular bactericidal activity mediated by reactive oxygen species (ROS) production. Mechanistically, butyrate functions as a histone deacetylase 3 inhibitor (HDAC3i) to promote ROS production via monocarboxylate transporter (MCT). The protection of butyrate against acute leptospirosis mediated by ROS was also proven in vivo . Collectively, our data provide evidence that the butyrate-MCT-HDAC3i-ROS signaling axis is a potential therapeutic target for acute leptospirosis. Our work not only interprets the microbial metabolite signaling involved in transkingdom interactions between the host and gut microbiota but also provides a possible target for developing a prevention strategy for acute leptospirosis., Importance: Leptospirosis is a worldwide zoonotic disease caused by Leptospira . An estimated 1 million people are infected with leptospirosis each year. Studies have shown that healthy gut microbiota can protect the host against leptospirosis but the mechanism is not clear. This work elucidated the mechanism of gut microbiota protecting the host against acute leptospirosis. Here, we find that butyrate, a metabolite of gut microbiota, can improve the survival rate of hamsters with leptospirosis by promoting the bactericidal activity of macrophages. Mechanistically, butyrate upregulates reactive oxygen species (ROS) levels after macrophage infection with Leptospira by inhibiting HDAC3. This work confirms the therapeutic potential of butyrate in preventing acute leptospirosis and provides evidence for the benefits of the macrophage-HDAC3i-ROS axis., Competing Interests: The authors declare no conflict of interest.

Objective: Neuroinflammation is associated with brain injury and poor outcomes after aneurysmal subarachnoid hemorrhage (SAH). In this study, we performed single-cell RNA sequencing (scRNA-seq) to analyze monocytes and explore the mechanisms of neuroinflammation after SAH., Methods: We recruited two male patients with SAH and collected paired cerebrospinal fluid (CSF) and peripheral blood (PB) samples from each patient. Mononuclear cells from the CSF and PB samples were sequenced using 10x Genomics scRNA-seq. Additionally, scRNA-seq data for CSF from eight healthy individuals were obtained from the Gene Expression Omnibus database, serving as healthy controls (HC). We employed various R packages to comprehensively study the heterogeneity of transcriptome and phenotype of monocytes, including monocyte subset identification, function pathways, development and differentiation, and communication interaction., Results: (1) A total of 17,242 cells were obtained in this study, including 7,224 cells from CSF and 10,018 cells from PB, mainly identified as monocytes, T cells, B cells, and NK cells. (2) Monocytes were divided into three subsets based on the expression of CD14 and CD16: classical monocytes (CM), intermediate monocytes (IM), and nonclassical monocytes (NCM). Differentially expressed gene modules regulated the differentiation and biological function in monocyte subsets. (3) Compared with healthy controls, both the toll-like receptor (TLR) and nod-like receptor (NLR) pathways were significantly activated and upregulated in IM from CSF after SAH. The biological processes related to neuroinflammation, such as leukocyte migration and immune response regulation, were also enriched in IM. These findings revealed that IM may play a key role in neuroinflammation by mediating the TLR and NLR pathways after SAH., Interpretation: In conclusion, we establish a single-cell transcriptomic landscape of immune cells and uncover the heterogeneity of monocyte subsets in SAH. These findings offer new insights into the underlying mechanisms of neuroinflammation and therapeutic targets for SAH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Meng, Su, Ye, Xie, Liu and Qin.)

Leptospirosis is an emerging infectious disease caused by pathogenic Leptospira spp. Humans and some mammals can develop severe forms of leptospirosis accompanied by a dysregulated inflammatory response, which often results in death. The gut microbiota has been increasingly recognized as a vital element in systemic health. However, the precise role of the gut microbiota in severe leptospirosis is still unknown. Here, we aimed to explore the function and potential mechanisms of the gut microbiota in a hamster model of severe leptospirosis. Our study showed that leptospires were able to multiply in the intestine, cause pathological injury, and induce intestinal and systemic inflammatory responses. 16S rRNA gene sequencing analysis revealed that Leptospira infection changed the composition of the gut microbiota of hamsters with an expansion of Proteobacteria. In addition, gut barrier permeability was increased after infection, as reflected by a decrease in the expression of tight junctions. Translocated Proteobacteria were found in the intestinal epithelium of moribund hamsters, as determined by fluorescence in situ hybridization, with elevated lipopolysaccharide (LPS) levels in the serum. Moreover, gut microbiota depletion reduced the survival time, increased the leptospiral load, and promoted the expression of proinflammatory cytokines after Leptospira infection. Intriguingly, fecal filtration and serum from moribund hamsters both increased the transcription of TNF-α , IL-1β , IL-10 , and TLR4 in macrophages compared with those from uninfected hamsters. These stimulating activities were inhibited by LPS neutralization using polymyxin B. Based on our findings, we identified an LPS neutralization therapy that significantly improved the survival rates in severe leptospirosis when used in combination with antibiotic therapy or polyclonal antibody therapy. In conclusion, our study not only uncovers the role of the gut microbiota in severe leptospirosis but also provides a therapeutic strategy for severe leptospirosis., Competing Interests: XX, XC, SZ, JL, WZ, YC No competing interests declared, (© 2024, Xie et al.)