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Summary Heat acclimation (HA) is the best strategy to improve heat stress tolerance by inducing positive physiological adaptations. Evidence indicates that the gut microbiome plays a fundamental role in the development of HA, and modulation of gut microbiota can improve tolerance to heat exposure and decrease the risks of heat illness. In this study, for the first time, we applied 16S rRNA gene sequencing and untargeted liquid chromatography–mass spectrometry (LC‐MS) metabolomics to explore variations in the gut microbiome and faecal metabolic profiles in rats after HA. The gut microbiota of HA subjects exhibited higher diversity and richer microbes. HA altered the gut microbiota composition with significant increases in the genera Lactobacillus (a major probiotic) and Oscillospira alongside significant decreases in the genera Blautia and Allobaculum. The faecal metabolome was also significantly changed after HA, and among the 13 perturbed metabolites, (S)‐AL 8810 and celastrol were increased. Moreover, the two increased genera were positively correlated with the two upregulated metabolites and negatively correlated with the other 11 downregulated metabolites, while the correlations between the two decreased genera and the upregulated/downregulated metabolites were completely contrary. In summary, both the structure of the gut microbiome community and the faecal metabolome were improved after 28 days of HA. These findings provide novel insights regarding the improvement of the gut microbiome and its functions as a potential mechanism by which HA confers protection against heat stress., Evidence indicates that the gut microbiome plays a fundamental role in the development of HA. In this study, we applied 16S rRNA gene sequencing and untargeted liquid chromatography‐mass spectrometry (LC‐MS) metabolomics to explore variations in the gut microbiome and fecal metabolic profiles in rats after HA. Our study demonstrates for the first time that HA has a significant effect on the gut microbiome and fecal metabolome, and this may be a potential mechanism by which HA confers protection against heat stress.

Summary Characterizing biomarkers based on microbiome profiles has great potential for translational medicine and precision medicine. Here, we present microbiomeMarker, an R/Bioconductor package implementing commonly used normalization and differential analysis (DA) methods, and three supervised learning models to identify microbiome markers. microbiomeMarker also allows comparison of different methods of DA and confounder analysis. It uses standardized input and output formats, which renders it highly scalable and extensible, and allows it to seamlessly interface with other microbiome packages and tools. In addition, the package provides a set of functions to visualize and interpret the identified microbiome markers. Availability and implementation microbiomeMarker is freely available from Bioconductor (https://www.bioconductor.org/packages/microbiomeMarker). Source code is available and maintained at GitHub (https://github.com/yiluheihei/microbiomeMarker). Supplementary information Supplementary data are available at Bioinformatics online.

Trained immunity is a newly emerging concept that defines the ability of the innate immune system to form immune memory and provide long-lasting protection against previously encountered antigens. Accumulating evidence reveals that trained immunity not only has broad benefits to host defense but is also harmful to the host in chronic inflammatory diseases. However, all trained immunity-related information is scattered in the literature and thus is difficult to access. Here, we describe Trained Immunity DataBase (TIDB), a comprehensive database that provides well-studied trained immunity-related genes from human, rat and mouse as well as the related literature evidence. Moreover, TIDB also provides three modules to analyze the function of the trained-immunity-related genes of interest, including Reactome pathway over-representation analysis, Gene Ontology enrichment analysis and protein–protein interaction subnetwork reconstruction. We believe TIDB will help developing valuable strategies for vaccine design and immune-mediated disease therapy. Database URL: http://www.ieom-tm.com/tidb

Nickel oxide metal-semiconductor-metal structure was fabricated on 4H-SiC substrate by radio frequency magnetron sputtering from nickel oxide target and following electrode process. X-ray diffraction and scanning electron microscopy results indicate that the sputtered non-stoichiometric nickel oxide on silicon carbide is nanocrystalline. The current and voltage characteristic of the fabricated device was measured. When triggered by 365 nm incoming light, the current at 1 V and -1 V are 2.28 mA and -2.26 mA, respectively. Meanwhile, the dark current was as small as 26 $\mu$ A at both 1 V and -1 V. Furthermore, the secondary turn on behavior of the NiO x MSM structure was investigated. The results indicate that there are 3.35 eV barriers for electrons flowing from nickel electrodes to nickel oxide. Based on the investigated results, the equivalent circuit for secondary turn on behavior of the fabricated device was set up and simulated. The simulated curve matches the experimental curve well.

Background & Aims Production of neutralizing antibodies against hepatitis B surface antigen (HBsAg) is dysregulated in patients with persistent hepatitis B virus (HBV) infection. We investigated mechanisms by which this immune response to the virus is disrupted and whether it can be restored to promote clearance of HBV. Methods Immune-competent C57BL/6N and C57BL/6J, as well as mice deficient in follicular helper T cells (Tfh-cell-deficient), B cells, or Foxp3+ T-regulatory cells (Treg cell deficient), were given hydrodynamic injections of pAAV/HBV1.2 plasmids. Some mice were given injections of sorted Tfh cells, pan-B cells, Treg cells, or a blocking antibody against CTLA4. Production of antibodies against HBsAg and clearance of HBV were assessed by flow cytometry, enzyme-linked immunosorbent assay, polymerase chain reaction, and immunohistochemical analyses. We obtained blood samples from patients with HBV infection and isolated Treg cells. We measured the ability of Treg cells to suppress production of interleukin 21 (IL21) in CD4+ T cells. Results Immune-competent C57BL/6N and C57BL/6J mice transfected with the plasmid encoding HBV had features of viral clearance and viral persistence observed in humans. A Tfh-cell response to HBsAg was required for clearance of HBV and was suppressed by Treg cells in mice with persistent HBV infection. Depletion of Treg cells or inhibition of Treg-cell function (with blocking antibody against CTLA4) restored the Tfh-cell response against HBsAg and clearance of HBV in mice. Impaired Tfh-cell response to HBsAg was observed in blood from patients with chronic HBV infection, responsiveness was restored by depletion of Treg cells or blocking antibody against CTLA4. Conclusions In studies of HBV-infected mice and blood from patients with chronic HBV infection, we found a Tfh-cell response to HBsAg of to be required for HBV clearance, and that this response was blocked by Treg cells. Inhibiting Treg-cell activity using neutralizing antibody against CTLA4 restored the ability of Tfh cells to clear HBV infection; this approach might be developed for treatment of patients with chronic HBV infection.

Food safety has become an important public health issue worldwide. However, conventional methods for detection of food-borne pathogens are complicated, and labor-intensive. Moreover, the sensitivity is often low, and it is difficult to achieve high-throughput detection. This study developed a TaqMan real-time polymerase chain reaction (PCR) assay for the simultaneous detection and quantification of 12 common pathogens in a single reaction, including Escherichia coli O157:H7, Listeria monocytogenes/ivanovii, Salmonella enterica, Vibrio parahaemolyticus, β-streptococcus hemolyticus, Yersinia enterocolitica, Enterococcus faecalis, Shigella spp., Proteus mirabilis, Vibrio fluvialis, Staphylococcus aureus, and Campylobacter jejuni in food and drinking water. Based on published sequence data, specific primers, and fluorescently-labeled hybridization probes were designed targeting based on the virulence genes of the 12 pathogens, and these primers and probes were optimized to achieve consistent reaction conditions. The assay was evaluated using 106 pure bacterial culture strains. There was no cross-reaction among the different pathogens. The analytical sensitivity was 1 copy/μL for E. coli O157:H7, L. monocytogenes/ivanovii, β-streptococcus hemolyticus, Shigella spp., P. mirabilis, and V. fluvialis, 10 copies/μL for S. enterica, V. parahaemolyticus, Y. enterocolitica, E. faecalis, S. aureus, and C. jejuni, respectively. The limit of detection (LOD) was 296, 500, 177, 56, 960, 830, 625, 520, 573, 161, 875, and 495 CFU/mL for E. coli O157:H7, L. monocytogenes/ivanovii, S. enterica, V. parahaemolyticus, β-streptococcus hemolyticus, Y. enterocolitica, E. faecalis, Shigella spp., P. mirabilis, V. fluvialis, S. aureus, and C. jejuni, respectively. The limit of detection for the assay in meat samples was 103 CFU/g for V. parahaemolyticus and 104 CFU/g for other 11 strains. Together, these results indicate that the optimized TaqMan real-time PCR assay will be useful for routine detection of pathogenic bacteria due to its rapid analysis, low cost, high-throughput, high specificity, and sensitivity.

Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-α and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-α and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response., Author Summary Ebola virus (EBOV), a highly virulent pathogen, causes a severe hemorrhagic fever syndrome. The fatal infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is thought to contribute to disease pathogenesis, as high amounts of shed GP from virus-infected cells are detected in patients, and activate macrophages and dendritic cells (DCs) to produce proinflammatory cytokines. Here, we show that LSECtin plays an important role in GP-mediated inflammatory responses in human DCs. LSECtin is a DAP12-coupled receptor able to initiate specific signaling events in human DCs. LSECtin interacts with Ebola GP and results in DAP12 phosphorylation. LSECtin knockdown impairs the production of proinflammatory cytokines induced by Ebola GP. Thus, this study suggests that LSECtin may contribute to Ebola GP-mediated pathogenicity.