Preparation of graphene oxide–stabilized Pickering emulsion adjuvant for Pgp3 recombinant vaccine and enhanced immunoprotection against Chlamydia Trachomatis infection

BackgroundTraditional emulsion adjuvants are limited in clinical application because of their surfactant dependence. Graphene oxide (GO) has unique amphiphilic properties and therefore has potential to be used as a surfactant substitute to stabilize Pickering emulsions.MethodsIn this study, GO–stabilized Pickering emulsion (GPE) was prepared and used as an adjuvant to facilitate an enhanced immune response to the Chlamydia trachomatis (Ct) Pgp3 recombinant vaccine. Firstly, GPE was prepared by optimizing the sonication conditions, pH, salinity, GO concentration, and water/oil ratio. GPE with small-size droplets was characterized and chosen as the candidate. Subsequently, controlled-release antigen delivery by GPE was explored. Cellular uptake behaviors, M1 polarization, and cytokine stimulation by GPE + Pgp3 was considered in terms of the production of macrophages. Finally, GPE’s adjuvant effect was evaluated by vaccination with Pgp3 recombinant in BALB/c mouse models.ResultsGPE with the smallest droplet sizes was prepared by sonication under 163 W for 2 min at 1 mg/mL GO in natural salinity with a pH of 2 when the water/oil ratio was 10:1 (w/w). The optimized average GPE droplet size was 1.8 μm and the zeta potential was –25.0 ± 1.3 mv. GPE delivered antigens by adsorption onto the droplet surface, demonstrating the controlled release of antigens both in vitro and in vivo. In addition, GPE promoted antigen uptake, which stimulated proinflammatory tumor necrosis factor alpha (TNF-α), enhancing the M1 polarization of macrophages in vitro. Macrophage recruitment was also significantly promoted by GPE at the injection site. In the GPE + Pgp3 treatment group, higher levels of immunoglobin (IgG), immunoglobin G1 (IgG1), immunoglobin G2a (IgG2a) sera, and immunoglobin A (IgA) were detected in vaginal fluid, and higher levels of IFN-γ and IL-2 secretion were stimulated, than in the Pgp3 group, showing a significant type 1 T helper (Th1)-type cellular immune response. Chlamydia muridarum challenging showed that GPE enhanced Pgp3’s immunoprotection through its advanced clearance of bacterial burden and alleviation of chronic pathological damage in the genital tract.ConclusionThis study enabled the rational design of small-size GPE, shedding light on antigen adsorption and control release, macrophage uptake, polarization and recruitment, which enhanced augmented humoral and cellular immunity and ameliorated chlamydial-induced tissue damage in the genital tract

Associations between Source-Specific Fine Particulate Matter and Mortality and Hospital Admissions in Beijing, China

The health effects of PM2.5 exposure have become a major public concern in developing countries. Identifying major PM2.5 sources and quantifying the health effects at the population level are essential for controlling PM2.5 pollution and formulating targeted emissions reduction policies. In the current study, we have obtained PM2.5 mass data and used positive matrix factorization to identify the major sources of PM2.5. We evaluated the relationship between short-term exposure to PM2.5 sources and mortality or hospital admissions in Beijing, China, using 441 742 deaths and 9 420 305 hospital admissions from 2013 to 2018. We found positive associations for coal combustion and road dust sources with mortality. Increased hospital admission risks were significantly associated with sources of vehicle exhaust, coal combustion, secondary sulfates, and secondary nitrates. Compared to the cool season, excess mortality risk estimates of coal combustion source were significantly higher in the warm season. Our findings show that reducing more toxic sources of PM2.5, especially coal emissions, and developing clean energy alternatives can have critical implications for improving air quality and protecting public health

Short-term Exposure to Fine Particles and Risk of Cause-Specific Mortality — China, 2013-2018

What is already known about this topic? Short-term exposure to PM2.5 has been associated with population excess death. This issue is of critical concern in China given its high level of exposure to PM2.5 compared to that of the rest of the world. What is added by this report? Existing studies were conducted from 2013-2015 and have failed to capture the full effects of China’s actions towards cleaner air in recent years, such as the first Action Plan for Air Pollution Prevention and Control issued in 2013. This study uses the longest time series data to date from 2013-2018, provides the latest evidence on PM2.5 and cause-specific death nationwide, and identifies regional patterns of PM2.5-related effects as well as PM2.5-related susceptible populations. What are the implications for public health practice? This study suggests that the development of standards and the implementation of actions to clean the air and protect public health should be tailored to PM2.5-related sensitive diseases, susceptible populations, and regional patterns

Estimating mortality burden attributable to short-term PM2.5 exposure: A national observational study in China

Studies worldwide have estimated the number of deaths attributable to long-term exposure to fine airborne particles (PM2.5), but limited information is available on short-term exposure, particularly in China. In addition, most existing studies have assumed that short-term PM2.5-mortality associations were linear. For this reason, the use of linear exposure-response functions for calculating disease burden of short-term exposure to PM2.5 in China may not be appropriate. There is an urgent need for a comprehensive, evidence-based assessment of the disease burden related to short-term PM2.5 exposure in China. Here, we explored the non-linear association between short-term PM2.5 exposure and all-cause mortality in 104 counties in China; estimated county-specific mortality burdens attributable to short-term PM2.5 exposure for all counties in the country and analyzed spatial characteristics of the mortality burden due to short-term PM2.5 exposure in China. The pooled PM2.5-mortality association was non-linear, with a reversed J-shape. We found an approximately linear increased risk of mortality from 0 to 62 μg/m3 and decreased risk from 62 to 250 μg/m3. We estimated a total of 169,862 additional deaths from short-term PM2.5 exposure throughout China in 2015. Models using linear exposure-response functions for the PM2.5-mortality association estimated 32,186 deaths attributable to PM2.5 exposure, which is 5.3 times lower than estimates from the non-linear effect model. Short-term PM2.5 exposure contributed greatly to the death burden in China, approximately one seventh of the estimates from the chronic effect. It is essential and crucial to incorporate short-term PM2.5-related mortality estimations when considering the disease burden attributable to PM2.5 in developing countries such as China. Traditional linear effect models likely underestimated the mortality burden due to short-term exposure to PM2.5. Keywords: mortality burden, non-linear, PM2.5, short-ter

Random forest model based fine scale spatiotemporal O₃ trends in the Beijing-Tianjin-Hebei region in China, 2010 to 2017

Ambient ozone (O₃) concentrations have shown an upward trend in China and its health hazards have also been recognized in recent years. High-resolution exposure data based on statistical models are needed. Our study aimed to build high-performance random forest (RF) models based on training data from 2013 to 2017 in the Beijing-Tianjin-Hebei (BTH) region in China at a 0.01 ° × 0.01 ° resolution, and estimated daily maximum 8h average O₃ (O₃-8hmax) concentration, daily average O₃ (O₃-mean) concentration, and daily maximum 1h O3 (O3-1hmax) concentration from 2010 to 2017. Model features included meteorological variables, chemical transport model output variables, geographic variables, and population data. The test-R² of sample-based O₃-8hmax, O₃-mean and O₃-1hmax models were all greater than 0.80, while the R² of site-based and date-based model were 0.68–0.87. From 2010 to 2017, O₃-8hmax, O₃-mean, and O₃-1hmax concentrations in the BTH region increased by 4.18 μg/m³, 0.11 μg/m³, and 4.71 μg/m³, especially in more developed regions. Due to the influence of weather conditions, which showed high contribution to the model, the long-term spatial distribution of O₃ concentrations indicated a similar pattern as altitude, where high concentration levels were distributed in regions with higher altitude

Heat wave characteristics, mortality and effect modification by temperature zones: a time-series study in 130 counties of China

Background: The substantial disease burden attributed to heat waves, and their increasing frequency and intensity due to climate change, highlight the importance of understanding the health consequences of heat waves. We explore the mortality risk due to heat wave characteristics, including the timing in the seasons, the day of the heat wave, the intensity and the duration, and the modifying effect of temperature zones. Methods: Heat waves were defined as ≥ 2 days with a temperature ≥99th percentile for the county from 1 May through 30 September. Heat waves were characterized by their intensity, duration, timing in the season, and day of the heat wave. Within each county, we estimated the total non-accidental death and cardiovascular disease mortality during each heat wave compared with non-heat wave days by controlling for potential confounders in summer. We combined individual heat wave effect estimates using a random-effects model to calculate overall effects at the temperature zone and national levels. Results: The average daily total number of non-accidental deaths was nine in the warm season (across all the counties). Approximately half of the daily total number of non-accidental deaths were cardiovascular-related deaths (approximately four persons per day). The average and maximum temperatures across the study area were 23.1 °C (range: -1.2–35.9 °C) and 28.3 °C (range: 5.4–42.8 °C), respectively. The average relative humidity during the study was 68.9% (range: 8.0–100.0%). Heat waves increase the risk of total non-accidental death by 15.7% [95% confidence interval (CI): 12.5, 18.9] compared with non-heat wave periods, and the risk of cardiovascular-related death increases by 22.0% (95% CI: 16.9, 27.4). The risk of non-accidental death during the first heat wave of the season increases by 16.3% (95% CI: 12.6, 20.2), the risk during the second heat wave increases by 6.3% (95% CI: 2.8, 9.9) and during subsequent heat waves increases by -2.1% (95% CI: -4.6, 0.4). The first day and the second to third days of heat waves increase the risk of total non-accidental death by 11.7% (95% CI: 7.6, 15.9) and 17.0% (95% CI: 13.1, 21.0), respectively. Effects of heat waves on mortality lasted more than 4 days (6.3%, 95% CI: 2.4, 10.5) and are non-significantly different from the first day of heat waves. We found non-significant differences of the heat wave-associated mortality risks across mid-, warm and subtropical temperature zones. Conclusions: In China, the effect of heat waves on mortality is acute, and varies by certain characteristics of heat waves. Given these results, national heat wave early warning systems should be developed, as well as precautions and protection warranted according to characteristics of heat waves

Hypoglycemia and Death in Mice Following Experimental Exposure to an Extract of Trogia venenata Mushrooms

BACKGROUND: Clusters of sudden unexplained death (SUD) in Yunnan Province, China, have been linked to eating Trogia venenata mushrooms. We evaluated the toxic effect of this mushroom on mice. METHODS: We prepared extracts of fresh T. venenata and Laccaria vinaceoavellanea mushrooms collected from the environs of a village that had SUD. We randomly allocated mice into treatment groups and administered mushroom extracts at doses ranging from 500 to 3500 mg/kg and water (control) via a gavage needle. We observed mice for mortality for 7 days after a 3500 mg/kg dose and for 24 hours after doses from 500 to 3000 mg/kg. We determined biochemical markers from serum two hours after a 2000 mg/kg dose. RESULTS: Ten mice fed T. venenata extract (3500 mg/kg) died by five hours whereas all control mice (L. vinaceoavellanea extract and water) survived the seven-day observation period. All mice died by five hours after exposure to single doses of T. venenata extract ranging from 1500 to 3000 mg/kg, while the four mice exposed to a 500 mg/kg dose all survived. Mice fed 2000 mg/kg of T. venenata extract developed profound hypoglycemia (median= 0.66 mmol/L) two hours after exposure. DISCUSSION: Hypoglycemia and death within hours of exposure, a pattern unique among mushroom toxicity, characterize T. venenata poisoning

Limits of oxygen isotope palaeoaltimetry in Tibet

Measurements of stable water isotopes (oxygen and hydrogen) are commonly used to estimate palaeoelevation and quantify past changes in surface height across Tibet. Isotope palaeoaltimetry is often based on simple Rayleigh fractionation of a “parcel of air”, but must make a considerable number of approximations and assumptions. In this paper, we elaborate on the practicability of oxygen water isotopes in palaeoaltimetry, and evaluate a recent challenge to the palaeoaltimetry community. First, we examine the isotopic composition of oxygen (ẟ18O) versus altitude relationship in a set of five topographic realisations of Tibet using an isotope-enabled palaeoclimate model for the mid-Eocene, a period where a variety of topographic ‘uplift’ models have been proposed, and compare it to modern relationships. Second, we investigate whether isotopic composition is a good predictor of more modest changes in topography, such as the introduction of a valley system or uplift of only part of the Tibetan region. The aim of the paper is not to perform a direct comparison to data, but to use the model to further refine knowledge of the strengths and limitations of using oxygen isotopes in palaeoaltimetry. We find that oxygen isotope palaeoaltimetry works surprisingly well, with the exception that it could not identify low elevation valley systems bounded by high elevations because the isotopic composition of the water in the air becomes depleted at the first high elevation that an air parcel passes over and does not recover when it descends into the valley. Hence, isotope-based elevations are biased towards mountain range peaks. Overall, the application of oxygen isotope palaeoaltimetry does have value, but would be further strengthened when employed together with isotope-enabled models. In conjunction with other techniques such as terrestrial thermal lapse rates and energy conservation approaches, over a wide spatial region, a more accurate and fully three-dimension view of complex palaeo-topography is increasingly possible, which will in turn improve the precision of these palaeoaltimeters