Childhood exposure to polycyclic aromatic hydrocarbons is associated with emotional and behavioral problems in adolescence: a longitudinal study in China.

PURPOSE: The aim of this study was to investigate the relationship between childhood polycyclic aromatic hydrocarbon (PAH) exposure and emotional and behavioral problems in adolescence. METHODS: Participants included 998 school-age children aged 7-12 years (514 girls and 484 boys). Metabolite concentrations of four PAHs (1-hydroxypyrene [1-OHPyr], 2-hydroxynaphthalene [2-OHNap], 2-hydroxyfluorine [2-OHFlu], and 9-hydroxyphenanthrene [9-OHPhe]) were measured in urine samples at baseline (Dec 2014-Dec 2015). During adolescence, we measured emotional and behavioral problems in study participants. We used logistic regression models to assess the effects of different levels of PAH metabolite concentrations on emotional and behavioral problems for boys and girls, separately. RESULTS: Boys exposed to 1-OHPyr and 2-OHFlu had a significantly higher risk of externalizing problems (OR: 2.62, 95% CI: 1.09 ~ 6.29; OR: 2.92, 95% CI: 1.15 ~ 7.42). 2-OHNap exposure faced a higher risk of internalizing problems (OR: 3.85, 95% CI: 1.28 ~ 11.58; OR: 3.63, 95% CI: 1.13 ~ 11.63) and externalizing problems (OR: 4.27, 95% CI: 1.44 ~ 12.70; OR: 4.68, 95% CI: 1.49 ~ 14.73). Moreover, boys exposed to 9-OHPhe exhibited a significant risk of anxiety (OR: 2.84, 95% CI: 1.01 ~ 7.97; OR: 3.00, 95% CI: 1.04 ~ 8.68). Similarly, girls exposed to 9-OHPhe had a significant risk of anxiety (OR: 2.41, 95% CI: 1.25 ~ 4.64). CONCLUSION: Childhood PAH exposures are associated with emotional and behavioral problems in adolescence, and boys seem more susceptible than girls.

Associations between short-term exposure of PM2.5 constituents and hospital admissions of cardiovascular diseases among 18 major Chinese cities.

Previous studies showed different risk effects on exposure of fine particulate matter (PM2.5) mass for cardiovascular disease (CVD) globally, which is likely due to different constituents of PM2.5. This study aimed to investigate the association between short-term exposure of PM2.5 constituents and hospital admissions of CVD. Daily counts of city-specific hospital admissions for CVD in 18 cities in China between 2014 and 2017 were extracted from the national Urban Employee Basic Medical Insurance database and the Beijing Municipal Commission of Health and Family Planning Information Center database. Directly measured PM2.5 constituents, including ions and polycyclic aromatic hydrocarbons, were collected by the Chinese Environmental Public Health Tracking system. We used the time-stratified case-crossover design to estimate the association between PM2.5 constituents and hospital admissions of CVD. Concentrations of ions accounted for the majority of the detected constituents. Excess risk (ER) of average ions concentrations for CVD was highest as 2.30% (95% CI: 1.62-2.99%) for NH4+, whose major sources are residential and agricultural emissions. This was followed by 1.85% (1.30-2.41%) for NO3- (generally from vehicles), 0.95% (0.28-1.63%) for SO42- (often from fossil fuel burning) respectively. The association for ions were generally consistent with ischemic heart disease (IHD) and ischemic stroke, e.g., NH4+ was associated with IHD (2.50%; 1.52-3.48%) and ischemic stroke (1.77%; 0.65-2.9%). For polycyclic aromatic hydrocarbons (PAHs), mainly from coal and vehicle-related oil combustion, the constituents were all associated with ischemic stroke but not for IHD. The ER for ischemic stroke was highest at 1.69% (0.99-2.39%) for indeno (123-cd) pyrene. Thus, in terms of the subtypes of CVD, the risks of hospital admissions varied with exposure to different PM2.5 constituents. Exposed to NH4+ had the highest risk to IHD and ischemic stroke, whereas PAHs were predominately associated with ischemic stroke only.

Molecular characterization and functional analysis of duck CCCH-type zinc finger antiviral protein (ZAP).

This is the first study to clone duck CCCH-type zinc finger antiviral protein (duZAP) from Jingjiang duck (Anas platyrhynchos). Full-length duZAP cDNA was 2154 bp and encoded a 717-amino acid polypeptide containing four highly conserved CCCH-type finger motifs, a WWE domain and a poly (ADP-ribose) polymerase (PARP) domain. duZAP was expressed in multiple duck tissues, with the highest mRNA expression in the spleen. Overexpression of duZAP in duck embryo fibroblast cells (DEFs) led to activation of the transcription factors IRF1 and NF-κB, and induction of IFN-ß. Analysis of deletion mutants revealed that both the WWE and PARP domains of duZAP were essential for activating the IFN-ß promoter. Knockdown of duZAP in DEFs significantly reduced poly (I:C)- and duck Tembusu virus (DTMUV)-induced IFN-ß activation. Our findings further the understanding of the role of duZAP in the duck innate immune response.

Molecular cloning and functional characterization of duck DEAD (Asp-Glu-Ala-Asp) box RNA helicase 3 (DDX3X).

DEAD (Asp-Glu-Ala-Asp) box RNA helicase 3 (DDX3X) is demonstrated to have crucial functions in the antiviral immune response. To our knowledge, little information focuses on the function of duck DDX3X. In this study, duck DDX3X (duDDX3X) was cloned and its role in the type I interferon (IFN) signaling pathway was investigated using duck embryo fibroblast (DEF) cells. Full-length duDDX3X cDNA encodes 652 amino acid residues and contains a DEADc domain and a HELICc domain. According to tissue distribution analysis, duDDX3X mRNA was widely expressed in different tissues, especially the spleen and the liver. Overexpression of duDDX3X in DEF cells induced IFN-ß by activating transcription factors IRF1 and NF-κB. Knockdown of duDDX3X in DEF cells with siRNA significantly reduced IFN-ß expression induced by poly(I:C), a double-stranded RNA (dsRNA) analog. Our results demonstrated that duck DDX3X was involved in the dsRNA-mediated type I IFN signaling pathway in DEF cells.

Internal exposure levels of polycyclic aromatic hydrocarbons in children and adolescents: a systematic review and meta-analysis.

Polycyclic aromatic hydrocarbons (PAHs) are widely found in the environment, and comparing to adults, children are more vulnerable to PAHs exposure. Urinary metabolites of PAHs are used as preferred biomarkers to estimate the PAHs exposure. Systematic review on the internal exposure level of children and adolescents is rare. We aimed to calculate the internal exposure levels of PAHs in children and adolescents and compare the levels of PAHs internal exposure in various children groups. We searched PubMed, OVID, Web of Science, EBSCO, ACS, and four Chinese databases, and all studies examining the urinary concentrations of PAHs in children and adolescent were identified. The total exposure level of 11 PAHs metabolites were pooled. Standard mean difference (SMD) and 95% confidence intervals (CIs) of PAHs urinary concentration were calculated and pooled by RevMan5.3 to compare the exposure levels of different children groups. We found that 1-OHPyr, 2-OHNap, 2-OHFlu, 3-OHPhe, and 4-OHPhe were five PAHs metabolites most commonly studied in existing studies in children, and their total exposure levels were 0.38 ± 0.98, 2.32 ± 4.83, 0.81 ± 1.54, 0.09 ± 0.14, 0.03 ± 0.10 µmol/mol creatinine, respectively. The meta-analysis showed that the levels of 1-OHPyr were higher in higher environmental exposure group (SMD = 0.21, 95% CI = 0.03~0.40), ETS exposure group (SMD = 0.31, 95% CI = 0.08~0.54), and 6~11 years group (SMD = 0.16, 95% CI = 0.09~0.24); the level of 2-OHNap (SMD = 0.27, 95% CI = 0.01~0.53) was higher in higher environmental exposure group; however, the levels of 3-OHPhe (SMD = - 0.34, 95% CI = - 0.57~- 0.12) and 4-OHPhe (SMD = - 0.48, 95% CI = - 0.69~- 0.28) were higher in lower environmental exposure group. The levels of 1-OHPyr (SMD = - 0.01, 95% CI = - 0.11~0.10) and 2-OHNap (SMD = 0.01, 95% CI = - 0.20~0.22) were not statistically different between boys and girls. In conclusions, we found that the internal diversity of PAHs existed in children and adolescents, and the level of 1-OHPyr in children and adolescents was in higher status compared with non-occupational people who do not smoke.

[Determination of polycyclic aromatic hydrocarbons in girls and association between polycyclic aromatic hydrocarbons exposure and puberty timing].

OBJECTIVE: To develop amethod for simultaneous determination of four metabolites of polycyclic aromatic hydrocarbons( PAHs), and to study the association between puberty timing of girls and PAHs exposure levels in Chongqing. METHODS: Through purposeful sampling, questionnaire survey of the general information, physical examination of growth and development, collection of urine sample were carried out among1-4 grades of four primary school girls in a district of Chongqing. High performance liquid chromatography with mass spectrometry( HPLC-MS) was applied to qualitativelyand quantitatively detect four kinds of PAHs metabolites( 1-hydroxy pyrene( 1-OHP), 2-hydroxy beta( 2-OHNa), 2-hydroxy fluorene( 2-OHFlu) and 9-hydroxyl( 2-OHPh)) in the urine sample. RESULTS: The method had high correlation coefficients and the detection limits of the four metabolites were 0. 1 ng/mL. A total of 737 girls were investigated in this study, of which, 209 girls were classified into early puberty timing group and 528 girls were classified into normal group. Urine determination result showed that four kinds of PAHs metabolites were detected in all the 737 girls, and urinary concentration ranges of the four PAHs metabolites were as follows: 1-OHP( 0. 01-4. 77 ng/mL), 2-OHNa( 0. 15-50. 00 ng/mL), 2-OHFlu( 0. 06-12. 59 ng/mL) and 9-OHPh( 0. 29-23. 17ng/mL). The exposure levels of 2-OHFlu( Z =-1. 996) and 9-OHPh( Z =-3. 161)were statistically different between early puberty timing group and those in normal group( P < 0. 05). After control the variable of obesity, the exposure level of 9-OHPh( Z =-3. 012) in early group were still higher than normal group( P < 0. 05). CONCLUSION: This determination method is suitable to simultaneously determine four PAHs metabolites in urine samples. All the girls in the study area have exposed to PAHs during their early stages of pubertal development, and exposure to PAHs might be one of the factors causing early puberty timing in girls.

[Relevant factors of early puberty timing in urban primary schools in Chongqing].

OBJECTIVE: To investigate the status of puberty timing and relevant factors of early puberty timing in children from grade one to four in urban primary schools of Chongqing. METHODS: According to the purposive sample method, four urban primary schools in Chongqing were selected and of which 1471 children from grade one to four who have obtained informed consent were recruited. Questionnaire survey on social-demographic characteristics and family environment (e.g., age, parents' relationship, diet and lifestyle, etc), and Pubertal Development Scale (PDS) survey and physical examination (measurements of height, weight, pubertal development status, etc) were conducted. P25, P50, P75 ages of each important pubertal event were calculated by probit regression. Univariate and multivariate analysis were used to analyze relevant factors. RESULTS: The detection rate of early puberty timing was 17.7%, and the median ages of the onset of breast and testicular development were 10.77 and 11.48 years old, respectively. Multivariate logistic regression showed that early puberty timing occurred more likely in girls than in boys (OR = 0.561, 95% CI 0.406-0.774), and bad relationship between parents (OR = 1.320, 95% CI 1.007-1.729) and hair-products-use (OR = 1.685, 95%, CI 1.028-2.762) were risk factors of early puberty timing. CONCLUSION: Early onset of puberty in urban Chongqing is still exist. Gender, parents' relationship, and hair-products-use have an essential impact on early puberty timing.

Paracrine factors from adipose-mesenchymal stem cells enhance metastatic capacity through Wnt signaling pathway in a colon cancer cell co-culture model.

BACKGROUND: Mesenchymal stem cells (MSCs) in tumors have emerged as progenitors involved in stroma formation and metastasis of cancers, partially owing to their abilities to differentially express paracrine factors related to the proliferation and invasion of cancer cells. In this regard, increasing evidence has shown that MSCs have impacts on the malignancy of colon cancer, however, the underpinning mechanisms by which MSCs promote cancer metastasis remain elusive. METHODS: To investigate the crosstalk between adipose-derived MSCs (AMSCs) isolated from adipose tissues and colon cancer cells, a co-culture transwell model of AMSCs and colon cancer cells was employed, and the activation of Wnt signaling and paracrine factors in colon cancer cells and AMSCs were measured. RESULTS: The results showed that AMSCs could enhance the metastatic capacity of colon cancer cells with an elevated expression of mesenchymal-epithelial transition (EMT)-associated genes in a contact-dependent manner. Reciprocally, colon cancer cells were able to induce AMSCs to produce metastasis-related factors and cytokines, such as FGF10, VEGFC and matrix metalloproteinases (MMPs) in part through a mechanism of an activation of Wnt signaling, by which these factors in turn activate Wnt signaling of colon cancer cells. Intriguingly, an inhibition of Wnt signaling leads a reduced capacity of invasion and colony formation of colon cancer cells in vitro, and the tumorigenicity of cancer cells in a murine model. CONCLUSIONS: These findings thus suggest that the crosstalk between the Wnt signaling of cancer cells and paracrine factors of AMSCs has an implication in colon cancer malignancy. This study thus uncovers a novel Wnt-paracrine factors mediated-crosstalk between colon cancer cells and AMSCs in cancer malignancy.

Prepubertal exposure to polycyclic aromatic hydrocarbons are associated with early pubertal development onset in boys: A longitudinal study.

OBJECTIVE: To investigate the effects of polycyclic aromatic hydrocarbons(PAHs) on puberty in boys. METHODS: 695 subjects were selected from four primary schools in Chongqing, China. 675 urine samples from these boys were collected four PAH metabolites: 1-hydroxypyrene, 2-hydroxynaphthoic, 2-hydroxyfluorene, and 9-hydroxyphenanthrene. Pubertal development of 695 boys was assessed at follow-up visits starting in December 2015 and occurring every six months thereafter until now, data used in this article ending in June 2021. A total of 12 follow-up visits were performed. Cox proportional hazards regression models were used to analyze the relationship between PAH metabolite concentrations and indicators of pubertal timing. RESULTS: The mean age at puberty onset of testicular volume, facial hair, pubic hair, first ejaculation, and axillary hair in boys was 11.66, 12.43, 12.51, 12.72 and 13.70 years, respectively. Cox proportional hazards regression models showed that boys with moderate level of 1-OHPyr exposure was associated with earlier testicular development (hazard ratio [HR] = 1.276, 95% confidence interval [CI]: 1.006-1.619), with moderate level of 2-OHNap were at higher risk of early testicular development (HR = 1.273, 95% CI: 1.002-1.617) and early axillary hair development (HR = 1.355, 95% CI: 1.040-1.764), with moderate level of 2-OHFlu was associated with earlier pubic hair development (HR = 1.256, 95% CI: 1.001-1.577), with high level of 9-OHPhe were at higher risk of early fisrt ejaculation (HR = 1.333, 95% CI: 1.005-1.767) and early facial hair development (HR = 1.393, 95% CI: 1.059-1.831). CONCLUSION: Prepubertal exposure to PAHs may be associated with earlier pubertal development in boys.

Psychosocial Stress Trajectories are Associated with Puberty Timing: Findings from A 7-year Cohort in Chongqing, China.

OBJECTIVES: To evaluate the association between psychosocial stress (PS) trajectories and pubertal outcomes of girls and boys in a Chinese cohort (2015-2022). METHODS: Pubertal outcomes of 732 girls and 688 boys were physically examined every 6 months. Stressful life events were repeatedly assessed 7 times. Group-Based Trajectory Model was fitted for the optimum trajectories of total PS and PS from 5 sources. Cox model adjusted for age, BMI and socioeconomic factors was used to evaluate the association. RESULTS: Compared to the "low, gradual decline" trajectory, the "moderate, gradual decline" trajectory of total PS was associated with late menarche (HR: 0.816, 95% CI: 0.677-0.983), late pubic hair development (HR: 0.729, 95% CI: 0.609-0.872) and late axillary hair development (HR: 0.803, 95% CI: 0.661 - 0.975) in girls. Girls following the "high, rise then decline" trajectory of PS from family life demonstrated delayed axillary hair development (HR: 0.752, 95% CI: (0.571-0.990). As for boys, the "high, rise then decline" trajectory of PS from academic adaptation (HR: 0.670, 95% CI: 0.476 - 0.945) and life adaptation (HR: 0.642, 95% CI: 0.445 - 0.925) was associated with late axillary hair development. Boys in the "moderate, gradual decline" trajectory of PS from peer relationship was at risk of early testicular development (HR: 1.353, 95% CI: 1.108 - 1.653). CONCLUSIONS: Chronic PS may be associated with delayed onset of several pubertal signs in both girls and boys. It may also accelerate testicular development of boys, indicating its varying impact on pubertal timing during early and later stages.

A nanoparticle vaccine based on the VP121-26 and VP2 structural proteins of Senecavirus A induces robust protective immune responses.

Senecavirus A (SVA) is a causative agent that can cause vesicular disease in swine, which causes a great threat to the swine husbandry in the world. Therefore, it is necessary to develop a vaccine that can effectively prevent the spread of SVA. In this study, we developed a 24-polymeric nano-scaffold using ß-annulus peptide from tomato bushy effect virus (TBSV) by coupling this antigen to SVA B cell epitope VP121-26 and VP2 proteins via linkers, respectively. The SVA-based nanoparticle protein of the VP1(B)-ß-VP2 was expressed and purified by low-cost prokaryotic system to prepare a SVA nanoparticle vaccine. The immunological protective effect of SVA nanoparticle vaccine was evaluated in mouse and swine models, respectively. The results suggested that both mice and swine could induce high levels SVA neutralizing antibodies and IgG antibodies after two doses immunization. In addition, the swine challenge protection experiment showed that the protection rate of immune SVA nanoparticle vaccine and SVA inactivated vaccine both were 80 %, while the negative control had no protection effect. It demonstrated that SVA nanoparticle vaccine effectively prevented SVA infection in swine. In summary, the preparation of SVA vaccine by using ß-annulus peptide is a promising candidate vaccine for prevent SVA transmission, and provides a new idea for the development of novel SVA vaccines.

Pathogenicity Studies of NADC34-like Porcine Reproductive and Respiratory Syndrome Virus LNSY-GY and NADC30-like Porcine Reproductive and Respiratory Syndrome Virus GXGG-8011 in Piglets.

The porcine reproductive and respiratory syndrome virus (PRRSV) has caused significant economic losses to the swine industry. The U.S., China, and Peru have reported NADC30-like or NADC34-like PRRSV-infected piglets, which have been identified as the cause of a significant number of abortions in clinics. Although the pathogenicity of NADC30-like PRRSV and NADC34-like PRRSV in piglets exhibits significant variability globally, studies on their pathogenicity in China are limited. In this study, the animal experiments showed that within 8-14 days post-infection, both piglets infected with NADC30-like PRRSV GXGG-8011 and those infected with NADC34-like PRRSV LNSY-GY exhibited significant weight loss compared to the control piglets. Additionally, the viremia of the LNSY-GY persisted for 28 days, while the viremia of piglets infected with the GXGG-8011 lasted for 17 days. Similarly, the duration of viral shedding through the fecal-oral route after the LNSY-GY infection was longer than that observed after the GXGG-8011 infection. Furthermore, post-infection, both the LNSY-GY and GXGG-8011 led to pronounced histopathological lesions in the lungs of piglets, including interstitial pneumonia and notable viral colonization. However, the antibody production in the LNSY-GY-infected group occurred earlier than that in the GXGG-8011-infected group. Our research findings indicate that LNSY-GY is a mildly pathogenic strain in piglets, whereas we speculate that the GXGG-8011 might be a highly pathogenic strain.

Placental mesenchymal stem cells ameliorate NLRP3 inflammasome-induced ovarian insufficiency by modulating macrophage M2 polarization.

BACKGROUND: Premature ovarian insufficiency (POI) is a common clinical problem, however, there are currently no effective therapies. Pyroptosis induced by the NLRP3 inflammasome is considered a possible mechanism of POI. Placental mesenchymal stem cells (PMSCs) have excellent immunomodulatory potential and offer a promising method for treating POI. METHODS: Female Sprague-Dawley rats were randomly divided into four treatment groups: control (no POI), POI with no PMSCs, POI with PMSCs transplant, and POI with hormones (estrogen + progesterone) as positive control. POI was induced by exposure to 4-vinylcyclohexene diepoxide (VCD) for 15 days. After four weeks, all animals were euthanized and examined for pathology. Hormone levels were measured and ovarian function was evaluated in relation to the estrous cycle. Levels of NLRP3 inflammasome pathway proteins were determined by immunohistochemistry and western blot. RESULTS: VCD significantly damaged rat follicles at different estrous stages. Injection of human PMSCs improved ovarian function and reproductive ability of POI rats compared to the sham and hormone groups. Our data also showed that PMSCs markedly suppress cell pyroptosis via downregulation of the NLRP3 inflammasome, caspase-1, IL-1ß and IL-18 compared to the other two groups. The human PMSCs increased the expression of IL-4 and IL-10 and decreased pro-inflammatory factors by phenotypic changes in macrophages. CONCLUSIONS: Our findings revealed a novel mechanism of follicular dysfunction and ovarian fibrosis via activation of the NLRP3 inflammasome followed by secretion of pro-inflammatory factors. Transplantation of PMSCs into POI rats suppressed pro-inflammatory factor production, NLRP3 inflammasome formation and pyroptosis, and improved ovarian function.

The multidrug-resistant Pseudomonas fluorescens strain: a hidden threat in boar semen preservation.

Although the bacterial composition of boar ejaculate has been extensively studied, the bacterial composition of extended boar semen is often overlooked, despite the potential risks these microorganisms may pose to the long-term preservation of extended boar semen at 15-17°C. In this study, we characterized the bacterial community composition of extended semen and discovered that Pseudomonas spp. was the dominant flora. The dominant strains were further isolated and identified as a potential new species in the Pseudomonas fluorescens group and named GXZC strain, which had adverse effects on sperm quality and was better adapted to growth at 17°C. Antimicrobial susceptibility testing showed that the GXZC strain was resistant to all commonly used veterinary antibiotics. Whole-genome sequencing (WGS) and genome annotation revealed the large genetic structure and function [7,253,751 base pairs and 6,790 coding sequences (CDSs)]. Comparative genomic analysis with the closest type strains showed that the GXZC strain predicted more diversity of intrinsic and acquired resistance genes to multi-antimicrobial agents. Taken together, our study highlights a problem associated with the long-term storage of extended boar semen caused by a P. fluorescens group strain with unique biological characteristics. It is essential to develop a new antibacterial solution for the long-term preservation of boar semen.

Epidemiological and Genetic Characteristics of Porcine Reproductive and Respiratory Syndrome Virus in South China Between 2017 and 2021.

Porcine reproductive and respiratory syndrome virus (PRRSV) remains a major threat to the swine industry in China and has caused enormous losses every year. To monitor the epidemiological and genetic characteristics of PRRSV in South China, 6,795 clinical samples from diseased pigs were collected between 2017 and 2021, and 1,279 (18.82%) of them were positive for PRRSV by RT-PCR detecting the ORF5 gene. Phylogenetic analysis based on 479 ORF5 sequences revealed that a large proportion of them were highly-pathogenic PRRSVs (409, 85.39%) and PRRSV NADC30-like strains (66, 13.78%). Furthermore, 93.15% of these highly-pathogenic strains were found to be MLV-derived. We next recovered 11 PRRSV isolates from the positive samples and generated the whole genome sequences of them. Bioinformatic analysis showed that seven isolates were MLV-derived. Besides, six isolates were found to be recombinant strains. These eleven isolates contained different types of amino acid mutations in their GP5 and Nsp2 proteins compared to those of the PRRSVs with genome sequences publicly available in GenBank. Taken together, our findings contribute to understanding the prevalent status of PRRSV in South China and provide useful information for PRRS control especially the use of PRRSV MLV vaccines.

Long-term exposure to ozone and cardiovascular mortality in a large Chinese cohort.

BACKGROUND: Evidence for the association between long-term exposure to ozone (O3) and cause-specific cardiovascular disease (CVD) mortality is inconclusive, and this association has rarely been evaluated at high O3 concentrations. OBJECTIVES: We aim to evaluate the associations between long-term O3 exposure and cause-specific CVD mortality in a Chinese population. METHODS: From 2009 to 2018, 744,882 subjects (median follow-up of 7.72 years) were included in the CHinese Electronic health Records Research in Yinzhou (CHERRY) study. The annual average concentrations of O3 and fine particulate matter (PM2.5), which were estimated using grids with a resolution up to 1 × 1 km, were assigned to the community address for each subject. The outcomes were deaths from CVD, ischemic heart disease (IHD), myocardial infarction (MI), stroke, and hemorrhagic/ischemic stroke. Time-varying Cox model adjusted for PM2.5 and individual-level covariates was used. RESULTS: The mean of annual average O3 concentrations was 68.05 µg/m3. The adjusted hazard ratio per 10 µg/m3 O3 increase was 1.22 (95% confidence interval [CI]: 1.13-1.33) for overall CVD mortality, 1.08 (0.91-1.29) for IHD, 1.21 (0.90-1.63) for MI, 1.28 (1.15-1.43) for overall stroke, 1.39 (1.16-1.67) for hemorrhagic stroke and 1.22 (1.00-1.49) for ischemic stroke, respectively. The study showed that subjects without hypertension had a higher risk for CVD mortality associated with long-term O3 exposure (1.66 vs. 1.15, p = 0.01). CONCLUSIONS: We observed the association between long-term exposure to high O3 concentrations and cause-specific CVD mortality in China, independent of PM2.5 and other CVD risk factors. This suggested an urgent need to control O3 pollution, especially in developing countries.

Fc-Mediated E2-Dimer Subunit Vaccines of Atypical Porcine Pestivirus Induce Efficient Humoral and Cellular Immune Responses in Piglets.

Congenital tremor (CT) type A-II in piglets is caused by an emerging atypical porcine pestivirus (APPV), which is prevalent in swine herds and a serious threat to the pig production industry. This study aimed to construct APPV E2 subunit vaccines fused with Fc fragments and evaluate their immunogenicity in piglets. Here, APPV E2Fc and E2ΔFc fusion proteins expressed in Drosophila Schneider 2 (S2) cells were demonstrated to form stable dimers in SDS-PAGE and western blotting assays. Functional analysis revealed that aE2Fc and aE2ΔFc fusion proteins could bind to FcγRI on antigen-presenting cells (APCs), with the affinity of aE2Fc to FcγRI being higher than that of aE2ΔFc. Moreover, subunit vaccines based on aE2, aE2Fc, and aE2ΔFc fusion proteins were prepared, and their immunogenicity was evaluated in piglets. The results showed that the Fc fusion proteins emulsified with the ISA 201VG adjuvant elicited stronger humoral and cellular immune responses than the IMS 1313VG adjuvant. These findings suggest that APPV E2 subunit vaccines fused with Fc fragments may be a promising vaccine candidate against APPV.

Porcine deltacoronavirus (PDCoV) infection antagonizes interferon-λ1 production.

Porcine deltacoronavirus (PDCoV) is a novel swine enteropathogenic coronavirus that causes watery diarrhea, vomiting and mortality in nursing piglets. Type III interferons (IFN-λs) are the major antiviral cytokines in intestinal epithelial cells, the target cells in vivo for PDCoV. In this study, we found that PDCoV infection remarkably inhibited Sendai virus-induced IFN-λ1 production by suppressing transcription factors IRF and NF-κB in IPI-2I cells, a line of porcine intestinal mucosal epithelial cells. We also confirmed that PDCoV infection impeded the activation of IFN-λ1 promoter stimulated by RIG-I, MDA5 and MAVS, but not by TBK1 and IRF1. Although the expression levels of IRF1 and MAVS were not changed, PDCoV infection resulted in reduction of the number of peroxisomes, the platform for MAVS to activate IRF1, and subsequent type III IFN production. Taken together, our study demonstrates that PDCoV suppresses type III IFN responses to circumvent the host's antiviral immunity.

Susceptibility of porcine IPI-2I intestinal epithelial cells to infection with swine enteric coronaviruses.

Swine enteric coronavirus (CoV) is an important group of pathogens causing diarrhea in piglets. At least four kinds of swine enteric CoVs have been identified, including transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV), and the emerging HKU2-like porcine enteric alphacoronavirus (PEAV). The small intestines, particularly the jejunum and ileum, are the most common targets of these four CoVs in vivo, and co-infections by these CoVs are frequently observed in clinically infected pigs. This study was conducted to investigate the susceptibility of the porcine ileum epithelial cell line, IPI-2I, to different swine enteric CoVs. We found that IPI-2I cells are highly susceptible to TGEV, PDCoV, and PEAV, as demonstrated by cytopathic effect and virus multiplication. However, only a small number of cells could be infected by PEDV, possibly due to the heterogeneity of IPI-2I cells. A homogeneous cell line, designated IPI-FX, obtained from IPI-2I cells by sub-cloning with limited serial dilutions, was found to be highly susceptible to PEDV. Furthermore, IPI-FX cells were also highly susceptible to TGEV, PDCoV, as well as PEAV. Thus, this sub-cloned IPI-FX cell line is an ideal cell model to study the mechanisms of infection, particularly co-infections of swine enteric CoVs.

The effectiveness and safety of pertussis booster vaccination for adolescents and adults: A systematic review and meta-analysis.

BACKGROUND: Due to the resurgence of pertussis, many countries have revised the pertussis immunization schedules and recommended booster doses of pertussis component vaccine for adolescents and adults. Here we aim to investigate the effectiveness and safety of pertussis component vaccines in adolescents and adults. METHODS: Based on a prospectively registered protocol, we reviewed the literature and selected trials in adolescents and adults using pertussis component vaccine. We followed Cochrane and GRADE (Grading of Recommendations, Assessment, Development and Evaluation) guidance to assess risk of bias, quality of evidence and to perform meta-analyses. RESULTS: A total of 17 clinical trials were included. At post-vaccination with pertussis component vaccine, the vaccine protective rate of pertussis reached 88.89%, the vaccine response rate of pertussis antibodies in most trials were above 85%, and the antibody titers at post-vaccination were higher than at pre-vaccination. Reduced-antigen-content diphtheria-tetanus-acellular pertussis vaccine was associated with significantly higher incidences of nausea [RR = 1.26, 95%CI:1.01, 1.57] and vomiting [RR = 2.08, 95%CI:1.21, 3.58] in acellular pertussis vaccines combined with tetanus and diphtheria (Tdap) group than diphtheria tetanus-toxoid vaccines (Td) group. Higher dose of diphtheria toxoid and adjuvant in dTap might cause higher incidence of fever. CONCLUSIONS: Except for significant difference in gastrointestinal reaction (nausea, vomiting), acellular pertussis component vaccines are quite safe and has short-term effectiveness for the adolescents and adults. The adverse event of acellular pertussis component vaccine is similar to or safer than that of placebo or other vaccines without pertussis component.