•PFAS mixture exposure was associated with higher HDL cholesterol and lower waist circumference.•Postnatal PFAS were the main contributors to the identified mixtures.•Prenatal PFOA was positively ...related with the pro-inflammatory biomarker IL-1beta.
Developing children are particularly vulnerable to the effects of exposure to per- and polyfluoroalkyl substances (PFAS), a group of endocrine disrupting chemicals. We hypothesized that early life exposure to PFASs is associated with poor metabolic health in children.
We studied the association between prenatal and postnatal PFASs mixture exposure and cardiometabolic health in children, and the role of inflammatory proteins.
In 1,101 mothers-child pairs from the Human Early Life Exposome project, we measured the concentrations of PFAS in blood collected in pregnancy and at 8 years (range = 6–12 years). We applied Bayesian Kernel Machine regression (BKMR) to estimate the associations between exposure to PFAS mixture and the cardiometabolic factors as age and sex- specific z-scores of waist circumference (WC), systolic and diastolic blood pressures (BP), and concentrations of triglycerides (TG), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) cholesterol. We measured thirty six inflammatory biomarkers in child plasma and examined the underlying role of inflammatory status for the exposure-outcome association by integrating the three panels into a network.
Exposure to the PFAS mixture was positively associated with HDL-C and systolic BP, and negatively associated with WC, LDL-C and TG. When we examined the independent effects of the individual chemicals in the mixture, prenatal PFHxS was negatively associated with HDL-C and prenatal PFNA was positively associated with WC and these were opposing directions from the overall mixture. Further, the network consisted of five distinct communities connected with positive and negative correlations. The selected inflammatory biomarkers were positively, while the postnatal PFAS were negatively related with the included cardiometabolic factors, and only prenatal PFOA was positively related with the pro-inflammatory cytokine IL-1beta and WC.
Our study supports that prenatal, rather than postnatal, PFAS exposure might contribute to an unfavorable lipidemic profile and adiposity in childhood.
Brucellosis is a global zoonotic infection caused by
bacteria, which poses a significant burden on society. While transmission prevention is currently the most effective method, the absence of a ...licenced vaccine for humans necessitates the urgent development of a safe and effective vaccine. Recombinant protein-based subunit vaccines are considered promising options, and in this study, the
BP26 protein is expressed using prokaryotic expression systems. The immune responses are evaluated using the well-established adjuvant CpG-ODN. The results demonstrate that rBP26 supplemented with a CpG adjuvant induces M1 macrophage polarization and stimulates cellular immune responses mediated by Th1 cells and CD8
T cells. Additionally, it generates high levels of rBP26-specific antibodies in immunized mice. Furthermore, rBP26 immunization activates, proliferates, and produces cytokines in T lymphocytes while also maintaining immune memory for an extended period of time. These findings shed light on the potential biological function of rBP26, which is crucial for understanding brucellosis pathogenesis. Moreover, rBP26 holds promise as an effective subunit vaccine candidate for use in endemic areas.
is a common human and animal parasitic disease that seriously endangers human health and animal husbandry. Although studies have been conducted on vaccines for
, to date, there is no human vaccine ...available for use. One of the main reasons for this is the lack of in-depth research on basic immunization with vaccines. Our previous results confirmed that recombinant antigen P29 (rEg.P29) induced more than 90% immune protection in both mice and sheep, but data on its induction of sheep-associated cellular immune responses are lacking. In this study, we investigated the changes in CD4
T cells, CD8
T cells, and antigen-specific cytokines IFN-γ, IL-4, and IL-17A after rEg.P29 immunization using enzyme-linked immunospot assay (ELISPOT), enzyme-linked immunosorbent assay (ELISA), and flow cytometry to investigate the cellular immune response induced by rEg.P29 in sheep. It was found that rEg.P29 immunization did not affect the percentage of CD4
and CD8
T cells in peripheral blood mononuclear cells (PBMCs), and was able to stimulate the proliferation of CD4
and CD8
T cells after immunization
. Importantly, the results of both ELISPOT and ELISA showed that rEg.P29 can induce the production of the specific cytokines IFN-γ and IL-17A, and flow cytometry verified that rEg.P29 can induce the expression of IFN-γ in CD4
and CD8
T cells and IL-17A in CD4
T cells; however, no IL-4 expression was observed. These results indicate that rEg.P29 can induce Th1, Th17, and Tc1 cellular immune responses in sheep against
infection, providing theoretical support for the translation of rEg.P29 vaccine applications.
Echinococcus granulosus causes echinococcosis, an important zoonotic disease worldwide and a major public health issue. Vaccination is an economical and practical approach for controlling E. ...granulosus. We have previously revealed that a recombinant protein P29 (rEg.P29) is a good vaccine candidate against E. granulosus. However, T cell immunogenic epitopes have not been identified. In the present study, we use rEg.P29-immunized mice as models to screen immunogenic epitopes for the construction of a novel multi-epitope vaccine. We search for immunodominant epitopes from an overlapping peptide library to screen the peptides of rEg.P29. Our results confirm that rEg.P29 immunization in mice elicits the activation of T cells and induces cellular immune responses. Further analyses show that a T cell epitope within amino acids 86–100 of rEg.P29 elicits significant antigen-specific IFN-γ production in CD4+ and CD8+ T cells and promotes specific T-cell activation and proliferation. Collectively, these results provide a reference for the construction of a novel vaccine against broad E. granulosus genotypes based on epitopes of rEg.P29.
Several strategies exist to prevent and control echinococcosis, a global parasitic disease. However, most treatments are ineffective and adverse effects are common. Therefore, we aimed to screen ...protoscolex antigen molecules of
Echinococcus granulosus
to identify a diagnostic biomarker for hydatid disease. Published
E. granulosus
transcriptome sequencing data were analyzed to screen for antigen molecules that are highly expressed in protoscoleces but not in oncospheres. The membrane protein EG-06283 (annotated as Frizzled-4) was selected from 16 antigens, and its gene fragment was subjected to codon optimization and synthesis. rEG-06283 expression was induced in the pET-24a/EG-06283/BL21 strain; subsequently, the protein was purified and subcutaneously injected into ICR mice at weeks 0, 2, 4, and 6. Blood sampling occurred periodically to quantify serum immunoglobulin G (IgG) levels via enzyme-linked immunosorbent assays (ELISA). Immunogenicity was determined by western blot assays using sera from normal mice and mice with secondary hydatid infections. The antigen’s immune reactivity and diagnostic value were validated using sera of patients with hydatid disease. ELISA results confirmed that the antigen molecule induced specific IgG production in mice, resulting in significantly higher levels than those in the adjuvant and control groups (
P
< 0.05). The western blot results indicated that the protein was recognized by antibodies in the sera of mice with hydatid infection and the antisera of immunized mice. Quantification of protein levels in the sera of patients with hydatid disease significantly differed from levels in healthy participants (
P
< 0.05). These results indicate that rEG-06283 is a potential diagnostic antigen for
E. granulosus
infections.
Environmental exposure during earlier life stages can govern the assembly and development of gut microbiota, yet it is insufficiently understood. In this study, ex-germ-free mice were cohoused with ...distinct soil-microbiota (from desert, steppe, and forest) beddings within 60 days after birth and subsequently transferred to new soil beddings from 60 to 90th day. Using metagenomic shotgun sequencing, firstly, we found soil microbes from natural environments (birthplace) greatly influenced the gut community assembly in the housing experiment. About 27% microbial species and 12% functional components that associated with birthplaces at Day 60 were still discriminatory of birthplaces after transferring mice to new environments. Moreover, prior soil-exposure types are associated with the magnitude of temporal microbiome change due to environmental shifts. The appropriate soil-exposure (e.g., steppe) might help mice gut microbiome adapt to changing environments or host development. Our study demonstrated the continuous soil-exposure history earlier is associated with the gut microbiome individuality and development later.
Objective
Cystic echinococcosis (CE), a zoonotic parasitic disease caused by Echinococcus granulosus, remains a public health and socioeconomic issue worldwide, making its prevention and treatment of ...vital importance. The aim of this study was to investigate changes in the intestinal microbiota of mice immunized with three peptide vaccines based on the recombinant antigen of E. granulosus, P29 (rEg.P29), with the hope of providing more valuable information for the development of vaccines against CE.
Methods
Three peptide vaccines, rEg.P29T, rEg.P29B, and rEg.P29T + B, were prepared based on rEg.P29, and a subcutaneous immunization model was established. The intestinal floras of mice in the different immunization groups were analyzed by 16 S rRNA gene sequencing.
Results
The intestinal microbiota analysis at both immunization time points revealed that Firmicutes, Bacteroidota, and Verrucomicrobiota were the predominant flora at the phylum level, while at the genus level, Akkermansia, unclassified_Muribaculaceae, Lachnospiraceae_NK4A136_group, and uncultured_rumen bacterium were the dominant genera. Some probiotics in the intestines of mice were significantly increased after immunization with the peptide vaccines, such as Lactobacillus_taiwanensis, Lactobacillus_reuteri, Lachnospiraceae_NK4A136_group, Bacteroides_acidifaciens, and so forth. Meanwhile, some harmful or conditionally pathogenic bacteria were decreased, such as Turicibacter sanguinis, Desulfovibrio_fairfieldensis, Clostridium_sp, and so forth, most of which are associated with inflammatory or infectious diseases. Kyoto Encyclopaedia of Genes and Genomes enrichment analysis revealed that the differential flora were enriched in multiple metabolic pathways, primarily biological systems, human diseases, metabolism, cellular processes, and environmental information processing.
Conclusion
In this study, we comprehensively analyzed and compared changes in the intestinal microbiota of mice immunized with three peptide vaccines as well as their related metabolic pathways, providing a theoretical background for the development of novel vaccines against E. granulosus.
Cystic echinococcosis (CE), a zoonotic parasitic disease caused by Echinococcus granulosus, remains a public health and socioeconomic issue worldwide, making its prevention and treatment of vital importance. The aim of this study was to investigate changes in the intestinal microbiota of mice immunized with three peptide vaccines based on the recombinant antigen of E. granulosus, P29 (rEg.P29), with the hope of providing more valuable information for the development of vaccines against CE.
Urinary metabolic profiling is a promising powerful tool to reflect dietary intake and can help understand metabolic alterations in response to diet quality. Here, we used
H NMR spectroscopy in a ...multicountry study in European children (1147 children from 6 different cohorts) and identified a common panel of 4 urinary metabolites (hippurate,
-methylnicotinic acid, urea, and sucrose) that was predictive of Mediterranean diet adherence (KIDMED) and ultra-processed food consumption and also had higher capacity in discriminating children's diet quality than that of established sociodemographic determinants. Further, we showed that the identified metabolite panel also reflected the associations of these diet quality indicators with C-peptide, a stable and accurate marker of insulin resistance and future risk of metabolic disease. This methodology enables objective assessment of dietary patterns in European child populations, complementary to traditional questionary methods, and can be used in future studies to evaluate diet quality. Moreover, this knowledge can provide mechanistic evidence of common biological pathways that characterize healthy and unhealthy dietary patterns, and diet-related molecular alterations that could associate to metabolic disease.
The purity of hydrogen seriously affects the performance and life of proton exchange membrane fuel cells (PEMFC), indirectly affects the cost and becomes one of the bottlenecks of its commercial ...applications. In order to explore the upper limit and allowable concentration of impurities in hydrogen, researchers have carried out a lot of researches. This article collects relevant literatures in recent years, and then elaborates the impacts, mechanisms and mitigation measures of several major impurities (CO, CO2, NH3, H2S, SO2, etc.) in PEMFC. In addition, some researches on other possible contaminations (N2, C2H2, NO2, Na+, Li+, etc) are also introduced extensively to make the readers fully understand the contaminations in the fuel cells and know the progress of current researches, which may provide some guidances and references for their studies. Finally, the research methodologies( and ideas commonly used in the literature are introduced, involving some differences and advices, to provides guidance and reference for later researches and also contributes to the commercialization process of PEMFC.
There are different impurities in different hydrogen sources, which have great effects on the performance of PEMFC. From three aspects of self recovery, tolerance and mitigation measures, different impurities have different effects on the PEMFC performance. Display omitted
•Na+, Ca2+ et al. will reduce the conductivity and water content of the membrane.•The ternary combination Pt–Ru–Sn of catalysts is more resistant to CO than the binary combination Pt–Ru.•Au and Ir have better tolerance to N-compounds, the combination with Pt may be a better tolerance combination.•The in-situ N2 cycle method can make the performance completely restored from SO2 poisoning.
•Under the tensile test, bolted spherical joints suffered three failure modes.•Factors influencing the stiffness and ultimate strength of bolted spherical joints.•Behaviours of bolted spherical ...joints were predicted by XFEM method.•Formulas were proposed to evaluate the tensile strength of bolted spherical joints.
Aiming at evaluating the reliability of the high-strength bolts’ fake tightened-up phenomena of the bolted spherical joints in a spatial grid structure, this research studied the tensile strength, stiffness, and failure modes of the bolted spherical joints with different bolt types and screwing depths using a combined method of the lab experiments and numerical simulations. A total of 40 axial tension tests of the bolted spherical joints were conducted with five different bolt types and eight different screwing depths. The test results showed that the bolted spherical joints with the different bolt screwing depths of high strength bolts suffered three failure modes, namely, the thread failure, bolt fracture failure, and sphere rupture failure. Validated by its feasibility and accuracy, the proposed numerical simulation method of the bolted spherical joints can estimate the ultimate strengths and failure modes, as well as the detailed stress distribution and failure development process. According to the test and numerical analysis results, a group of calculation formulas was developed for predicting the tensile strength of bolted spherical joints with different bolt screwing depths.
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