Genome analysis of the mpox (formerly monkeypox) virus and characterization of core/variable regions.

Since smallpox was eradicated in 1980, the monkeypox virus (MPXV) has emerged as the most threatening orthopoxvirus in the world. In this study, we conducted a comprehensive analysis of the currently published complete genome sequences of the monkeypox virus. The core/variable regions were identified through core-pan analysis of MPXV. Besides single-nucleotide polymorphisms, our study also revealed that specific genes, multi-copy genes, repeat sequences, and recombination fragments are primarily distributed in the variable region. This result suggests that variable regions are not only more susceptible to single-base mutations, but also to events such as gene loss or gain, as well as recombination. Taken together, our results demonstrate the genomic characteristics of the core/variable regions of MPXV, and contribute to our understanding of the evolution of MPXV.

Evaluation of immunoregulation and immunoprotective efficacy of Glaesserella parasuis histidine kinase QseC.

QseC is a membrane sensor kinase that enables bacteria to perceive autoinducers -3, adrenaline, and norepinephrine to initiate downstream gene transcription. In this study, we found that the QseC protein of Glaesserella parasuis can serve as an effective antigen to activate the host's immune response. Therefore, we investigated the immunogenicity and host protective effect of this protein. ELISA and indirect immunofluorescence results showed that QseC protein can induce high titer levels of humoral immunity in mice and regularly generate specific serum antibodies. We used MTS reagents to detect lymphocyte proliferation levels and found that QseC protein can cause splenic lymphocyte proliferation with memory and specificity. Further immunological analysis of the spleen cell supernatant revealed significant upregulation of levels of IL-1ß, IL-4 and IFN-γ in the QseC + adjuvant group. In the mouse challenge experiment, it was found that QseC + adjuvant can provide effective protection. The results of this study demonstrate that QseC protein provides effective protection in a mouse model and has the potential to serve as a candidate antigen for a novel subunit vaccine for further research.

Responses of keratinocytes to Trichophyton mentagrophyte infection based on whole transcriptome analysis.

BACKGROUND: Dermatophytosis is an intractable superficial mycosis in humans and animals mainly caused by Trichophyton mentagrophytes (T. mentagrophytes), with a global prevalence of about 20%. Keratinocytes are the most abundant participants in skin immunity, and they also play a role in the first-line defence against T. mentagrophytes. However, no studies of keratinocyte responses against T. mentagrophytes infection based on the whole transcriptome have been reported. OBJECTIVES: Here, we systematically analysed changes in keratinocytes infected with T. mentagrophytes using whole transcriptome sequencing technology. METHODS: The phenotypic changes in keratinocytes after infection with 1 × 105 conidia/mL T. mentagrophytes were observed by light microscopy, scanning electron microscopy, transmission electron microscopy and terminal deoxynucleotidyl transferase dUTP nick end labeling. RNA-sequencing (RNA-seq), small RNA-seq technology and related bioinformatics methods were used to systematically analyse the whole transcriptome changes in keratinocytes upon T. mentagrophytes stimulation. RESULTS: We found that T. mentagrophytes infection caused morphological changes, membrane damage, the formation of irregular organelles and keratinocyte apoptosis. A total of 204 differentially expressed (DE) circular RNAs (circRNAs), 868 DE long noncoding RNAs (lncRNAs), 2973 DE mRNAs and 209 DE micro RNAs (miRNAs) were identified between noninfected and T. mentagrophytes-infected keratinocytes. The expression level of selected RNAs was validated by quantitative real-time polymerase chain reaction (qRT-PCR). Functional enrichment analysis revealed that the parental genes of DE circRNAs were related to cell response, cell death and establishment of the skin barrier. Genes targeted by miRNA were involved in regulating the initiation of the immune response. Based on the expression level of circRNAs, lncRNAs, mRNAs and miRNAs, circRNA-miRNA-mRNA competing endogenous (ceRNA) networks comprised of 159 DE miRNAs, 141 DE circRNAs and 2307 DE mRNAs, and lncRNA-miRNA-mRNA ceRNA networks comprised of 790 DE lncRNAs, 190 DE miRNAs and 2663 DE mRNAs were constructed. The reliability of two selected ceRNA networks was verified using qRT-PCR. Further functional enrichment analysis revealed that the DE mRNAs interacting with circRNAs and lncRNAs in the ceRNA network mainly participated in fungal recognition, inflammation, the innate immune response and the death of keratinocytes. CONCLUSIONS: Our findings might provide new evidence on the pathogenesis of T. mentagrophytes-induced dermatophytosis, which is essential for identifying new therapeutic targets for dermatophytosis treatment.

Gut microbiota is involved in male reproductive function: a review.

Globally, ~8%-12% of couples confront infertility issues, male-related issues being accountable for 50%. This review focuses on the influence of gut microbiota and their metabolites on the male reproductive system from five perspectives: sperm quality, testicular structure, sex hormones, sexual behavior, and probiotic supplementation. To improve sperm quality, gut microbiota can secrete metabolites by themselves or regulate host metabolites. Endotoxemia is a key factor in testicular structure damage that causes orchitis and disrupts the blood-testis barrier (BTB). In addition, the gut microbiota can regulate sex hormone levels by participating in the synthesis of sex hormone-related enzymes directly and participating in the enterohepatic circulation of sex hormones, and affect the hypothalamic-pituitary-testis (HPT) axis. They can also activate areas of the brain that control sexual arousal and behavior through metabolites. Probiotic supplementation can improve male reproductive function. Therefore, the gut microbiota may affect male reproductive function and behavior; however, further research is needed to better understand the mechanisms underlying microbiota-mediated male infertility.

Gut microbiota affects obesity susceptibility in mice through gut metabolites.

Introduction: It is well-known that different populations and animals, even experimental animals with the same rearing conditions, differ in their susceptibility to obesity. The disparity in gut microbiota could potentially account for the variation in susceptibility to obesity. However, the precise impact of gut microbiota on gut metabolites and its subsequent influence on susceptibility to obesity remains uncertain. Methods: In this study, we established obesity-prone (OP) and obesity-resistant (OR) mouse models by High Fat Diet (HFD). Fecal contents of cecum were examined using 16S rDNA sequencing and untargeted metabolomics. Correlation analysis and MIMOSA2 analysis were used to explore the association between gut microbiota and intestinal metabolites. Results: After a HFD, gut microbiota and gut metabolic profiles were significantly different between OP and OR mice. Gut microbiota after a HFD may lead to changes in eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), a variety of branched fatty acid esters of hydroxy fatty acids (FAHFAs) and a variety of phospholipids to promote obesity. The bacteria g_Akkermansia (Greengene ID: 175696) may contribute to the difference in obesity susceptibility through the synthesis of glycerophosphoryl diester phosphodiesterase (glpQ) to promote choline production and the synthesis of valyl-tRNA synthetase (VARS) which promotes L-Valine degradation. In addition, gut microbiota may affect obesity and obesity susceptibility through histidine metabolism, linoleic acid metabolism and protein digestion and absorption pathways.