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Th cells (helper T cells) have multiple functions in

(

) infection. Inducible co-stimulator (ICOS) is induced and expressed in activated T lymphocytes, which enhances the development of B cells and antibody production through the ICOS/ICOSL pathway. It remains unclear about the role and possible regulating mechanism of ICOS

Th cells in the spleen of

-infected C57BL/6 mice.

C57BL/6 mice were infected with cercariae of

through the abdomen. The expression of ICOS, activation markers, and the cytokine production on CD4

ICOS

Th cells were detected by flow cytometry (FCM) and quantitative real-time PCR (qRT-PCR). Moreover, the differentially expressed gene data of ICOS

and ICOS

Th cells from the spleen of infected mice were obtained by mRNA sequencing. Besides, Western blot and chromatin immunoprecipitation (ChIP) were used to explore the role of Ikzf2 on ICOS expression.

After

infection, the expression of ICOS molecules gradually increased in splenic lymphocytes, especially in Th cells re found to play an important role in S. japonicum infection to induce immune response in the spleen of C57BL/6 mice. Additionally, Ikzf2 was found to be one important transcription factor that could regulate the expression of ICOS in the spleen of S. japonicum-infected C57BL/6 mice.In spite of impressive success in treating hematologic malignancies, adoptive therapy with chimeric antigen receptor modified T cells (CAR T) has not yet been effective in solid tumors, where identification of suitable tumor-specific antigens remains a major obstacle for CAR T-cell therapy due to the "on target off tumor" toxicity. Protein tyrosine kinase 7 (PTK7) is a member of the Wnt-related pseudokinases and identified as a highly expressed antigen enriched in cancer stem cells (CSCs) from multiple solid tumors, including but not limited to triple-negative breast cancer, non-small-cell lung cancer, and ovarian cancer, suggesting it may serve as a promising tumor-specific target for CAR T-cell therapy. In this study, we constructed three different PTK7-specific CAR (PTK7-CAR1/2/3), each comprising a humanized PTK7-specific single-chain variable fragment (scFv), hinge and transmembrane (TM) regions of the human CD8α molecule, 4-1BB intracellular co-stimulatory domain (BB-ICD), and CD3ζ intracellular domain s and many other solid cancers with PTK7 overexpression.It is intriguing that, unlike adults with HIV-1, children with HIV-1 reach a greater CD4+ T cell recovery following planned treatment cessation. The reasons for the better outcomes in children remain unknown but may be related to increased thymic output and diversity of T cell receptor repertoires. HIV-1 infected children from the PENTA 11 trial tolerated planned treatment interruption without adverse long-term clinical, virological, or immunological consequences, once antiretroviral therapy was re-introduced. This contrasts to treatment interruption trials of HIV-1 infected adults, who had rapid changes in T cells and slow recovery when antiretroviral therapy was restarted. How children can develop such effective immune responses to planned treatment interruption may be critical for future studies. PENTA 11 was a randomized, phase II trial of planned treatment interruptions in HIV-1-infected children (ISRCTN 36694210). In this sub-study, eight patients in long-term follow-up were chosen with CD4+ count>500/m may be sufficient to reconstitute the T cell immune repertoire and reverse the impact of interruption of antiretroviral therapy. Importantly, the effective T cell receptor repertoires following treatment interruption may inform novel therapeutic strategies in children infected with HIV-1.Argentina is the fifth world-wide wine producer, with an area of emerging importance in the Southwest of Buenos Aires Province, where climatic conditions are rather challenging. We studied the variations in soil and wine bacterial diversity through three consecutive vintages, and how climatic conditions affected said diversity. During the years of our study there were two harsh climatic events, a prolonged drought that extended over two vegetative periods, and an unseasonable spring frost in 2017. We found that the bacterial diversity reacted to these climatic events, given that there was a shift in the taxa exclusive to soil and wine, and shared by both, through time. Our results show a core of microorganisms in soil as well as in wine, belonging to different phyla that are conserved across the vintage years. A trend to an enrichment in Actinobacteria was detected in soil samples, whereas a high relative abundance of the Acetobacteraceae family and a scarcity of Lactic Acid Bacteria (LAB) were detected in the wine samples. We believe our results contribute to a better understanding of the impact of climatic conditions on the soil and wine microbiota, and can provide vintners with valuable knowledge for improving their wine production.Petit Manseng is widely used for fermenting sweet wine and is popular among younger consumers because of its sweet taste and attractive flavor. To understand the mechanisms underlying spontaneous fermentation of Petit Manseng sweet wine in Xinjiang, the dynamic changes in the microbial population and volatile compounds were investigated through high-throughput sequencing (HTS) and headspace solid-phase microextraction (HS-SPME) coupled to gas chromatography-mass spectrometry (GC-MS) technology, respectively. Moreover, the relationship between the microbial population and volatile compounds was deduced via multivariate data analysis. Candida and Mortierella were dominant genera in Petit Manseng wine during spontaneous fermentation. Many fermentative aroma compounds, including ethyl octanoate, isoamyl acetate, ethyl butyrate, ethyl decanoate, isoamyl alcohol, ethyl laurate, isopropyl acetate, hexanoic acid, and octanoic acid, were noted and found to be responsible for the strong fruity and fatty aroma of Petit Manseng sweet wine. Multivariate data analysis indicated that the predominant microorganisms contributed to the formation of these fermentative aroma compounds. Hannaella and Neomicrosphaeropsis displayed a significantly positive correlation with the 6-methylhept-5-en-2-one produced. The current results provide a reference for producing Petit Manseng sweet wine with desirable characteristics.A new formulation, nanoprebiotics [e.g., phthalyl pullulan nanoparticles (PPNs)], was demonstrated to enhance the antimicrobial activity of probiotics [e.g., Lactobacillus plantarum (LP)] in vitro through intracellular stimulation better than that by backbone prebiotics, which are commonly used. In this study, we aimed to investigate whether this combination would exert distinct effects as synbiotics in vivo. Synbiotics combinations of LP, pullulan, and PPNs were used as experimental treatments in a dysbiosis-induced murine model, and their restorative effect was assessed using pathogen Escherichia coli K99 challenge. Our results showed that the E. coli infection was suppressed markedly in the experimental group fed with synbiotics containing PPNs. In addition, the decrease in serum endotoxin level after synbiotics treatment suggested the reinforcement of the gut barrier. Comparison of treatment groups, including a normal control group, showed that synbiotics containing PPNs increased microbial diversity, which is a representative parameter of healthy status. Furthermore, distinct from probiotics treatment alone, synbiotics showed additive effects of enrichment of several well-known beneficial bacteria such as Lactobacillus, Bifidobacterium, and other butyrate-producing bacteria including Faecalibacterium. Collectively, our results indicate that synbiotics containing PPNs are effective at restoring gut dysbiosis, suppressing pathogenic infection, and increasing microbial diversity, suggesting that synbiotics with nanoprebiotics have the potential to be a novel strategy for ameliorating gut dysbiosis and infectious diseases.Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in western countries both in children and adults. Metabolic dysregulation associated with gut microbial dysbiosis may influence disease progression from hepatic steatosis to inflammation and subsequent fibrosis. Using a multi-omics approach, we profiled the oral and fecal microbiome and plasma metabolites from 241 predominantly Latino children with non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver (NAFL), and controls. Children with more severe liver pathology were dysbiotic and had increased gene content associated with lipopolysaccharide biosynthesis and lipid, amino acid and carbohydrate metabolism. These changes were driven by increases in Bacteroides and concomitant decreases of Akkermansia, Anaerococcus, Corynebacterium, and Finegoldia. Non-targeted mass spectrometry revealed perturbations in one-carbon metabolism, mitochondrial dysfunction, and increased oxidative stress in children with steatohepatitis and fibrosis. Random forests modeling of plasma metabolites was highly predictive of non-alcoholic steatohepatitis (NASH) (97% accuracy) and hepatic fibrosis, steatosis and lobular inflammation (93.8% accuracy), and can differentiate steatohepatitis from simple steatosis (90.0% accuracy). PGE2 Multi-omics predictive models for disease and histology findings revealed perturbations in one-carbon metabolism, mitochondrial dysfunction, and increased oxidative stress in children with steatohepatitis and fibrosis. These results highlight the promise of non-invasive biomarkers for the growing epidemic of fatty liver disease.Gut microbiota has been demonstrated to be associated with multiple gastrointestinal diseases, but information regarding the gut microbial alternations in diarrheic giraffe remains scarce. Here, 16S rDNA and ITS gene amplicon sequencing were conducted to investigate the gut microbial composition and variability in diarrheic giraffes. Results demonstrated that Firmicutes and Proteobacteria were the most dominant phyla in the gut bacterial community, whereas Ascomycota and Basidiomycota were observed to be predominant in the gut fungal community regardless of health status. However, the species and relative abundance of preponderant bacterial and fungal genera in healthy and diarrheic giraffes were different. In contrast to the relatively stabilized gut fungal community, gut bacterial community displayed a significant decrease in the alpha diversity, accompanied by distinct changes in taxonomic compositions. Bacterial taxonomic analysis revealed that the relative abundances of eight phyla and 12 genera obviously increased, whereas the relative abundances of two phyla and eight genera dramatically decreased during diarrhea. Moreover, the relative richness of five fungal genera significantly increased, whereas the relative richness of seven fungal genera significantly declined in diarrheic giraffes. Taken together, this study demonstrated that diarrhea could cause significant alternations in the gut microbial composition of giraffes, and the changes in the gut bacterial community were more significant than those in the gut fungal community. Additionally, investigating the gut microbial characteristics of giraffes in different health states is beneficial to provide a theoretical basis for establishing a prevention and treatment system for diarrhea from the gut microbial perspective.

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