Cellular immunity in children with successful immunoprophylactic treatment for mother-to-child transmission of hepatitis B virus

Background: The administration of hepatitis B immunoglobulin followed by hepatitis B vaccine can result in a protective efficacy of almost 90% in mother-to-child transmission of hepatitis B virus (HBV). However, little is known about immunity against HBV infection in children after immunoprophylactic treatment. We tried to assess the association between T-cell responses and viremia in children after successful prophylactic treatment. Methods: Thirteen children and their 8 HBV carrier mothers (8 families), who were positive for human leukocyte antigen (HLA)-A24, were enrolled in this study. All of the 13 children received immunoprophylactic treatment and became negative for hepatitis B surface antigen (HBsAg) after birth. HBV-specific cytotoxic T lymphocyte (CTL) responses were evaluated using IFNγ - enzyme-linked immunosorbent spot (ELISPOT) and major histocompatibility complex class I peptide pentamer assays. Serum HBV DNA was measured by real-time PCR. Results: Significant HBV-specific T-cell responses were detected in 2 (15%) of the 13 children by ELISPOT. However, the frequency of HLA-A24-HBV-specific CTLs was very low in both HBV carrier mothers and children using pentamers. Of the 13 children, 4 (31%) were positive for serum HBV DNA. However, the levels of serum HBV DNA were 100 copies/ml or less. One of the 2 children in whom significant HBV-specific CTL responses were detectable was positive for serum HBV DNA. Conclusions: HBV core and polymerase-specific T-cell responses were detected and a low-dose viremia was observed in children after successful immunoprophylaxis treatment. Although the presence of viremia was not related to HBV-specific T-cell responses, CTLs might play a role in the control of HBV infection in children born to HBsAg-positive mothers after immunoprophylactic treatment. </p

Gene expression profiling of monkeypox virus-infected cells reveals novel interfaces for host-virus interactions

Monkeypox virus (MPV) is a zoonotic Orthopoxvirus and a potential biothreat agent that causes human disease with varying morbidity and mortality. Members of the Orthopoxvirus genus have been shown to suppress antiviral cell defenses, exploit host cell machinery, and delay infection-induced cell death. However, a comprehensive study of all host genes and virus-targeted host networks during infection is lacking. To better understand viral strategies adopted in manipulating routine host biology on global scale, we investigated the effect of MPV infection on Macaca mulatta kidney epithelial cells (MK2) using GeneChip rhesus macaque genome microarrays. Functional analysis of genes differentially expressed at 3 and 7 hours post infection showed distinctive regulation of canonical pathways and networks. While the majority of modulated histone-encoding genes exhibited sharp copy number increases, many of its transcription regulators were substantially suppressed; suggesting involvement of unknown viral factors in host histone expression. In agreement with known viral dependence on actin in motility, egress, and infection of adjacent cells, our results showed extensive regulation of genes usually involved in controlling actin expression dynamics. Similarly, a substantial ratio of genes contributing to cell cycle checkpoints exhibited concerted regulation that favors cell cycle progression in G1, S, G2 phases, but arrest cells in G2 phase and inhibits entry into mitosis. Moreover, the data showed that large number of infection-regulated genes is involved in molecular mechanisms characteristic of cancer canonical pathways. Interestingly, ten ion channels and transporters showed progressive suppression during the course of infection. Although the outcome of this unusual channel expression on cell osmotic homeostasis remains unknown, instability of cell osmotic balance and membrane potential has been implicated in intracellular pathogens egress. Our results highlight the role of histones, actin, cell cycle regulators, and ion channels in MPV infection, and propose these host functions as attractive research focal points in identifying novel drug intervention sites

Spatiotemporal DNA methylome dynamics of the developing mouse fetus

Cytosine DNA methylation is essential for mammalian development but understanding of its spatiotemporal distribution in the developing embryo remains limited. Here, as part of the mouse Encyclopedia of DNA Elements (ENCODE) project, we profiled 168 methylomes from 12 mouse tissues or organs at 9 developmental stages from embryogenesis to adulthood. We identified 1,808,810 genomic regions that showed variations in CG methylation by comparing the methylomes of different tissues or organs from different developmental stages. These DNA elements predominantly lose CG methylation during fetal development, whereas the trend is reversed after birth. During late stages of fetal development, non-CG methylation accumulated within the bodies of key developmental transcription factor genes, coinciding with their transcriptional repression. Integration of genome-wide DNA methylation, histone modification and chromatin accessibility data enabled us to predict 461,141 putative developmental tissue-specific enhancers, the human orthologues of which were enriched for disease-associated genetic variants. These spatiotemporal epigenome maps provide a resource for studies of gene regulation during tissue or organ progression, and a starting point for investigating regulatory elements that are involved in human developmental disorders

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.

BACKGROUND: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. RESULTS: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. CONCLUSIONS: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk

Iron-organic frameworks as effective fenton-like catalysts for peroxymonosulfate decomposition in advanced oxidation processes

Abstract Although Fenton-like reactions have been extensively used to treat various organic contaminants in wastewaters (oily wastewaters, landfill leachate, denitrification with Fenton oxidized non-degradable large molecular organic pollutants, and removal of phosphorus, etc.), the difficulty in catalyst recovery and the instability of catalytic activity limit their practical application. Herein, iron atoms were inserted in a metal-organic framework (FeNC) with dual reaction sites as highly reactive and stable electro-Fenton-like catalysts for the catalytic oxidation of organic pollutants via the electro-Fenton-like activation reaction of peroxymonosulfate (PMS) with fractional leaching of metal ions. Experiments and density functional theory (DFT) calculations indicate that FeNC with FeN4 and Fe–Fe active sites can rapidly deliver electrons for PMS dissociation. Further, an electrolysis reactor was constructed for the on-site generation of reactive oxygen species, which can stably and continuously purify various organic wastewaters. The combined use of an electrolysis reactor and magnetic catalyst in the current study provides a direction for the long-term remediation of organic pollutants on an industrial scale

Synergistic Antimicrobial Effectiveness of Plant Essential Oil and Its Application in Seafood Preservation: A Review

The synergistic potential of plant essential oils (EOs) with other conventional and non-conventional antimicrobial agents is a promising strategy for increasing antimicrobial efficacy and controlling foodborne pathogens. Spoilage microorganisms are one of main concerns of seafood products, while the prevention of seafood spoilage principally requires exclusion or inactivation of microbial activity. This review provides a comprehensive overview of recent studies on the synergistic antimicrobial effect of EOs combined with other available chemicals (such as antibiotics, organic acids, and plant extracts) or physical methods (such as high hydrostatic pressure, irradiation, and vacuum-packaging) utilized to reduce the growth of foodborne pathogens and/or to extend the shelf-life of seafood products. This review highlights the synergistic ability of EOs when used as a seafood preservative, discovering the possible routes of the combined techniques for the development of a novel seafood preservation strategy

Synergistic Antimicrobial Effectiveness of Plant Essential Oil and Its Application in Seafood Preservation: A Review

The synergistic potential of plant essential oils (EOs) with other conventional and non-conventional antimicrobial agents is a promising strategy for increasing antimicrobial efficacy and controlling foodborne pathogens. Spoilage microorganisms are one of main concerns of seafood products, while the prevention of seafood spoilage principally requires exclusion or inactivation of microbial activity. This review provides a comprehensive overview of recent studies on the synergistic antimicrobial effect of EOs combined with other available chemicals (such as antibiotics, organic acids, and plant extracts) or physical methods (such as high hydrostatic pressure, irradiation, and vacuum-packaging) utilized to reduce the growth of foodborne pathogens and/or to extend the shelf-life of seafood products. This review highlights the synergistic ability of EOs when used as a seafood preservative, discovering the possible routes of the combined techniques for the development of a novel seafood preservation strategy

Evaluation of car air filters' efficiency as active samplers for polycyclic aromatic hydrocarbons and heavy metals

In this study, an innovative and inexpensive approach, based on car engine air filters (CAFs) was used to monitor polycyclic aromatic hydrocarbons (PAHs) and heavy metals (HMs). CAFs were collected from two Taxi garages in Guangzhou and analyzed for PAHs and heavy metals. The total concentrations of eight high molecular weight PAHs (ΣPAHs) ranged from 923 to 11378 µg/CAF. The average ΣPAHs concentration in winter was slightly higher than in summer, a seasonal signal that is observed in most studies. The most abundant individual PAH was chrysene, followed by benzo[a]anthracene, benzo[b]fluoranthene and benzo[k]fluoranthene. Concentrations of benzo[a]pyrene (BaP) varied between 8.22 and 632 µg/CAF. Based on estimated air volumes that pass through each CAF, atmospheric PAHs and heavy metals were estimated. ΣPAHs ranged from ~20 to ~200 ng/m3 for the average air volume estimate, being comparable to those reported previously using a high volume air sampler. BaP-equivalent carcinogenic potency were between 1 and 15.0 ng/m3 (again, for the average scenario). The average concentrations of heavy metals in CAFs decreased in order of Zn > Cu > Pb > Cd

Mechanism and Implication of the Sorption of Perfluorooctanoic Acid by Varying Soil Size Fractions

Sorption of perfluorooctanoic acid (PFOA), a toxic and persistent organic pollutant, by various size fractions of an agricultural soil at environmentally relevant concentrations was evaluated. PFOA sorption to all fractions involved both film diffusion and intraparticle diffusion with the rate-limiting step by the latter. PFOA isotherm data fitted a linear model. Organic matter (OM), cation exchange capacity, pore volume, and the Brunauer-Emmett-Teller area played key roles in PFOA sorption. The sorption capacity followed the order of humic acid > clay (0.15-4.4 mm) > fine silt (1.9-39.8 mm) > coarse silt (17.3-79.4 mm) > fine sand (45.7-316.2 mm) > coarse sand (120-724.4 mm), opposite to their contributions to overall PFOA sorption due to the influence of their percentage weight in the original soil. Percentage OM content was the dominant factor controlling the fraction contributions to overall PFOA sorption, demonstrating influence of the hydrophobic force on sorption. PFOA should be highly mobile and bioavailable in soil-crop systems due to the low log K-oc values