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The global outbreak of the 2022 monkeypox virus infection of human raised the public health concerns of the threat of human-to-human transmission of zoonotic diseases. Given the evidence that other orthopoxviruses including cowpox and camelpox were also reported infectious to human, and that the reemerging risk of smallpox as a bioterrorist or accidental laboratory escape exists, there is an urgent need to develop a poxvirus vaccine with a broad protection of orthopoxviruses to stockpile for future emergency. Extensive studies of vaccinia virus (VACV) suggested that multiple VACV antigens, such as A27, L1, A33 and B5, showed high level similarity in terms of immunogenicity to their respective homologous antigens of other orthopoxviruses. These findings paved the ground for VACV antigens to be used as potential vaccine targets for development of a universal poxvirus vaccine. In this study, we construct a novel poxvirus vaccine candidate, mRNA-ALAB-LNP, encoding four vaccinia viral antigens A27, L1, A33 and B5. Strong anti-L1-specific antibody and moderate anti-A33-, anti-A27- and anti-B5-specific antibody responses were induced in mice after a single immunization. The antibody responses to all four antigens were significantly boosted after the second shot with all IgG titers >5 logs and highest being anti-A33 IgG. The high level of binding antibodies showed potent neutralizing capability against vaccinia virus. Specific IFN-γ responses were detected to all four antigens with the highest cellular response being that induced by the same antigen, A33. When evaluating the cross reactivity, equivalent or better serum IgG responses were seen in responses to corresponding monkeypox antigens A35, M1, A29 and B6, in comparison to vaccinia antigens. Apparently, the mRNA vaccine encoding four vaccinia antigens induced immunity not only to vaccinia virus but also to monkeypox, suggesting that the mRNA-ALAB may be a candidate for potential vaccine development against infection of monkeypox, smallpox and possibly other orthopoxviruses.

Cardiovascular disease has always been the most serious public health problem in China. Although many studies have found that the risk of death caused by cardiovascular disease is related to air pollutants, the existing results are still inconsistent. The aim of this study was to investigate the effects of air pollutants on the risk of daily cardiovascular deaths in Hefei, China. Daily data on cardiovascular deaths, daily air pollutants, and meteorological factors from 2007 to 2016 were collected in this study. A time-series study design using a distributed lag nonlinear model was employed to evaluate the association between air pollutants and cardiovascular deaths. First, a single air pollutant model was established based on the minimum value of Akaike information criterion (AIC), and the single day lag effects and multi-day lag effects were discussed separately. Then, two-pollutant models were fitted. Subgroup analyses were conducted by gender (male and female), age (< 65 age and ≥ 65 age), and disease type (ischemic heart disease and cerebral vascular disease). There were 34,500 cases of cardiovascular deaths during the period 2007-2016, and the average concentrations of air pollutants (PM10, SO2, NO2, PM2.5, CO, O3) were 106.11, 20.34, 30.49, 72.59, 958.7, and 67.88 μg/m3, respectively. An increase of interquartile range (IQR) in PM10, SO2, NO2, PM2.5, CO, and O3 were associated with an increase of 4.34% (95%CI 1.54~7.23%) at lag 0-6, 5.79% (95%CI 2.43~9.27%) at lag 0-5, 4.47% (95%CI 1.64~7.37%) at lag 0-5, 3.14% (95%CI 0.03~6.36%) at lag 0-4, 3.11% (95%CI 0.21~6.10%) at lag 0-3, and 8.17% (95%CI 1.89~14.84%) at lag 0-5 in cardiovascular deaths, respectively. Females, older group (≥ 65 years) and deaths from cerebral vascular disease were more vulnerable to air pollution than males, younger individuals (< 65 years) and deaths from ischemic heart disease. Our results suggest that air pollution increased the risk of cardiovascular deaths in Hefei. These findings can provide evidence for effective air quality interventions in Hefei.

Many studies have quantified the hospitalization risk for cardiovascular disease (CVD) caused by temperature, but the results of most studies are not consistent. In this study, we evaluate the effect of temperature on CVD hospitalizations. We use a quasi-Poisson regression with a distributed-lag nonlinear model (DLNM) to evaluate the effect of temperature on CVD hospitalizations between July 1, 2015, and October 31, 2017, in Hefei City, China. We found that the cold effect and heat effect of temperature can impact CVD hospital admissions. Compared with the 25th percentile of temperature (10.3 °C), the cumulative relative risk (RR) of extremely low temperature (first percentile of temperature, 0.075 °C) over lags 0–27 days was 0.616 (95% CI 0.423–0.891), and the cumulative RR of moderate low temperature (10th percentile of temperature, 5.16 °C) was 1.081 (95% CI 1.019–1.147) over lags 0–7 days. Compared with the 75th percentile of temperature (25.6 °C), the cumulative RR of extremely high temperature (99th percentile of temperature, 33.7 °C) was 1.078 (95% CI 0.752–1.547) over lags 0–27 days, and the cumulative RR of moderate-high temperature (90th percentile of temperature, 29.0 °C) was 1.015 (95% CI 0.988–1.043) over lag 0 day. In the subgroup, the

Deca-bromodiphenyl ether (BDE-209) regulates various aspects of spermatogenesis and male fertility through its effect on estrogen receptor α (ERα), but the underlying mechanism remains unclear. Because molecular mechanisms such as remodeling of the blood-testis barrier (BTB) play crucial roles in spermatogenesis, we investigated the disruptive effects of ERα agonists on the BTB in spermatogenesis. In this study, 0, 300, and 500 mg/kg/day of BDE-209 were administered to pregnant adult mice by oral gavage from gestation day 7 to postnatal day 21. SerW3 cells were treated with methylpiperidino pyrazole (MPP) for 30 min before being treated with 50 μg/mL of BDE-209. BDE-209 increases ERα in time- and dose-dependent manners and decreases formin 1 and BTB-associated protein in F1 male mice. Furthermore, BDE-209 impairs the structure and function of the BTB. Activation of ERα signaling could disrupt the BTB, leading to spermatogenesis dysfunction. The results identified the role of ERα in BTB disruption during spermatogenesis and suggested that BTB disruption occurs because of exposure to BDE-209, which could potentially affect spermatogenesis. In conclusion, Sertoli cells seem to be the primary target of BDE-209 in the perinatal period, and this period constitutes a critical window of susceptibility to BDE-209. Also, the SerW3 cell model may not be a particularly useful cell model for studying the function of the cytoskeleton.

Although several studies indicated an association between diurnal temperature range (DTR) and mortality, the results about modifiers are inconsistent, and few studies were conducted in developing inland country. This study aims to evaluate the effects of DTR on cause-specific mortality and whether season, gender, or age might modify any association in Hefei city, China, during 2007–2016. Quasi-Poisson generalized linear regression models combined with a distributed lag non-linear model (DLNM) were applied to evaluate the relationships between DTR and non-accidental, cardiovascular, and respiratory mortality. We observed a J-shaped relationship between DTR and cause-specific mortality. With a DTR of 8.3 °C as the reference, the cumulative effects of extremely high DTR were significantly higher for all types of mortality than effects of lower or moderate DTR in full year. When stratified by season, extremely high DTR in spring had a greater impact on all cause-specific mortality than other three seasons. Male and the elderly (≥ 65 years) were consistently more susceptible to extremely high DTR effect than female and the youth (

Objective To investigate the association between air pollution and upper respiratory tract infection (URTI) in children aged 0–14 years in Hefei, China in 2014–2015. Study design An ecological method (i.e. generalised additive model [GAM]) was used to explore the effects of air pollutants on paediatric hospital outpatients with URTI. Methods GAM was used to evaluate the lag effects (including lag0 to lag6, lag01 and lag06) between daily changes in particulate matter (PM10), fine particulate matter (PM2.5), sulphur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3) and carbon monoxide (CO) and the number of hospital outpatients with URTI in 2014–2015, after controlling for the confounding effects of long-term trends, seasonality, day of the week, public holidays and meteorological factors. Results PM10, PM2.5, SO2, NO2 and CO in the single-pollutant models had significant positive effects on the number of paediatric hospital outpatients with URTI. It was found that per 10 μg/m3 increasing in concentrations of PM10 at lag3, PM2.5, SO2, NO2 and CO at lag06 were associated with an increase of Excess risk (ER) with 0.15% (95% CI: 0.07%∼0.23%), 0.38% (95% CI: 0.17%∼0.60%), 2.92% (95% CI: 1.88%∼3.97%), 4.47% (95% CI: 3.69%∼5.25%) and 0.05% (95% CI: 0.02%∼0.08%), respectively. Only NO2 remained significantly positively associated with the number of hospital outpatients with URTI in the full-pollutant models, and ERs were 4.72% (95% CI = 3.76%–5.69%) and 4.70% (95% CI = 3.76%–5.65%) per 10 μg/m3 increase in NO2 in Model 1 (including PM10, SO2, NO2, O3 and CO) and Model 2 (including PM2.5, SO2, NO2, O3 and CO), respectively. Conclusion This study showed that short-term exposure to air pollution was associated with increased risk of URTI among paediatric hospital outpatients aged 0–14 years in Hefei. NO2 was the major air pollutant affecting the daily number of paediatric hospital outpatients with URTI.