Identify the key emission sources for mitigating ozone pollution: A case study of urban area in the Yangtze River Delta region, China.

Ozone (O3) has become the most critical air pollutant in the Yangtze River Delta (YRD) region of China. Research on the O3 formation mechanism and its precursor sources (including nitrogen oxides (NOX) and volatile organic compounds (VOCs)) could provide a theoretical basis for mitigating O3 pollution in this region. In this study, simultaneous field experiments were conducted for air pollutants in a typical urban area (Suzhou) in the YRD region in 2022. The capacity of in-situ O3 formation, O3-NOX-VOCs sensitivities and sources of O3 precursors were analyzed. The results showed that in-situ formation contributed 20.8 % of the O3 concentration in the warm season (April to October) of the Suzhou urban area. Compared with the warm season average, the concentrations of various O3 precursors increased on pollution days. The O3-NOX-VOCs sensitivity was the VOCs-limited regime based on the average concentrations during the warm season. O3 formation was most sensitive to anthropogenic VOCs, of which oxygenated VOCs, alkenes and aromatics were the key species. There was a VOCs-limited regime in spring and autumn, while a transitional regime in summer due to the changes in NOX concentrations. This study considered NOX emission from VOCs sources and calculated the contribution of various sources to O3 formation. The results of VOCs source apportionment showed that diesel engine exhaust and fossil fuel combustion had a dominant proportion, but O3 formation presented significant negative sensitivities to the above two sources because of their high NOX emissions. There were significant sensitivities of O3 formation to gasoline vehicle exhaust and VOCs evaporative emissions (gasoline evaporation and solvent usage). The contribution of VOCs evaporative emissions during the O3 pollution episode was significantly higher than the average; therefore, controlling VOCs evaporative emissions during the O3 pollution episode is critical. These results provide feasible strategies to mitigate O3 pollution.

Developing China's roadmap for air quality improvement: A review on technology development and future prospects.

Air pollution control policies in China have been experiencing profound changes, highlighting a strategic transformation from total pollutant emission control to air quality improvement, along with the shifting targets starting from acid rain and NOx emissions to PM2.5 pollution, and then the emerging O3 challenges. The marvelous achievements have been made with the dramatic decrease of SO2 emission and fundamental improvement of PM2.5 concentration. Despite these achievements, China has proposed Beautiful China target through 2035 and the goal of 2030 carbon peak and 2060 carbon neutrality, which impose stricter requirements on air quality and synergistic mitigation with Greenhouse Gas (GHG) emissions. Against this background, an integrated multi-objective and multi-benefit roadmap is required to provide decision support for China's long-term air quality improvement strategy. This paper systematically reviews the technical system for developing the air quality improvement roadmap, which was integrated from the research output of China's National Key R&D Program for Research on Atmospheric Pollution Factors and Control Technologies (hereafter Special NKP), covering mid- and long-term air quality target setting techniques, quantitative analysis techniques for emission reduction targets corresponding to air quality targets, and pathway optimization techniques for realizing reduction targets. The experience and lessons derived from the reviews have implications for the reformation of China's air quality improvement roadmap in facing challenges of synergistic mitigation of PM2.5 and O3, and the coupling with climate change mitigation.

Progress towards elimination of mother-to-child transmission of hepatitis B virus infection in China: a modelling analysis.

OBJECTIVE: To determine the projected burden of hepatitis B virus (HBV) in China, the intervention strategies that can eliminate mother-to-child transmission (MTCT) by 2030 or earlier and the measurable parameters that can be used to monitor progress towards this target. METHODS: We developed a dynamic, sex- and age-stratified model of the HBV epidemic in China, calibrated using hepatitis B surface antigen (HBsAg) and e antigen (HBeAg) prevalence data from sequential national serosurveys (1979-2014) and the numbers of HBV-related cancer deaths (2012). We determined whether China can achieve elimination of MTCT of HBV by 2030 under current prevention interventions. We modelled various intervention scenarios to represent different coverage levels of birth-dose HBV vaccination, hepatitis B immunoglobulin to newborns of HBsAg-positive mothers and antiviral therapy (tenofovir) to HBeAg-positive pregnant women. FINDINGS: We project that, if current levels of prevention interventions are maintained, China will achieve the elimination target by 2029. By modelling various intervention scenarios, we found that this can be brought forward to 2025 by increasing coverage of birth-dose vaccination, or to 2024 by the administration of tenofovir to HBeAg-positive pregnant women. We found that achievement of the target by 2025 would be predicted by a measurement of less than 2% MTCT in 2020. CONCLUSION: Our results highlight how high-quality national data can be combined with modelling in monitoring the elimination of MTCT of HBV. By demonstrating the impact of increased interventions on target achievement dates, we anticipate that other high-burden countries will be motivated to strengthen HBV prevention policies.

The long-term trend of PM2.5-related mortality in China: The effects of source data selection.

Quantification of PM2.5 exposure and associated mortality is critical to inform policy making. Previous studies estimated varying PM2.5-related mortality in China due to the usage of different source data, but rarely justify the data selection. To quantify the sensitivity of mortality assessment to source data, we first constructed state-of-the-art PM2.5 predictions during 2000-2018 at a 1-km resolution with an ensemble machine learning model that filled missing data explicitly. We also calibrated and fused various gridded population data with a geostatistical method. Then we assessed the PM2.5-related mortality with various PM2.5 predictions, population distributions, exposure-response functions, and baseline mortalities. We found that in addition to the well documented uncertainties in the exposure-response functions, missingness in PM2.5 prediction, PM2.5 prediction error, and prediction error in population distribution resulted to a 40.5%, 25.2% and 15.9% lower mortality assessment compared to the mortality assessed with the best-performed source data, respectively. With the best-performed source data, we estimated a total of approximately 25 million PM2.5-related mortality during 2001-2017 in China. From 2001 to 2017, The PM2.5 variations, growth and aging of population, decrease in baseline mortality led to a 7.8% increase, a 42.0% increase and a 24.6% decrease in PM2.5-related mortality, separately. We showed that with the strict clean air policies implemented in 2013, the population-weighted PM2.5 concentration decreased remarkably at an annual rate of 4.5 µg/m3, leading to a decrease of 179 thousand PM2.5-related deaths nationwide during 2013-2017. The mortality decrease due to PM2.5 reduction was offset by the population growth and aging population.

Long-term seropositivity, safety, and impact of inactivated and live, attenuated hepatitis a vaccines in China - A cross-sectional study.

BACKGROUND: In 2008, China introduced live, attenuated hepatitis A vaccine (L-HepA, licensed in 1992) and inactivated hepatitis A vaccine (I-HepA, licensed in 2002) nationwide, and is currently the only country using L-HepA in routine immunization. We assessed seropositivity and its duration following vaccination, safety, and association with hepatitis A incidence and population seroprevalence for I-HepA and L-HepA. METHODS: We obtained seroprevalence data from two nationwide serosurveys (in 1992 and 2014), vaccination status from the 2014 serosurvey, and vaccine safety and disease incidence data from the national surveillance system. We compared long-term HAV seropositivity among vaccine recipients and described safety profiles of both vaccines. We categorized the 31 provinces into those predominately using I-HepA and achieving high coverage (n = 4), those predominately using L-HepA achieving high coverage (n = 4), and those predominately using L-HepA achieving lower coverage (n = 23). We compared population HAV seropositivity, coverage, and disease incidence among the three groups. RESULTS: One year after vaccination, seropositivity from I-HepA was significantly higher than from L-HepA (97.8% vs 90.7%), and seropositivity declined to 73.5% for L-HepA and 75.4% for I-HepA after 10 years - not significantly different by vaccine. The annual incidence of serious AEFI was <0.5/100 000 for both vaccines. Prior to licensure of either HepA vaccine, provinces that would go on to predominantly use I-HepA had lower incidences of hepatitis A and lower seropositivity levels to HAV than provinces that would go on to use L-HepA. By 2014, these differences were significantly diminished. Regardless of vaccine selection, all three province groups had lower immunity to HAV among individuals born during the 10 years prior to nationwide vaccine introduction - individuals who were 10 to 24 years old in 2014. CONCLUSION: Evidence of good immunogenicity, safety, and impact on incidence supports continued use of both I-HepA and L-HepA in the EPI system. These results may be useful for countries considering integrating HepA vaccines into their routine programs.

Defending blue sky in China: Effectiveness of the "Air Pollution Prevention and Control Action Plan" on air quality improvements from 2013 to 2017.

Air pollution control has become one of the top priorities of China's "Ecological Civilization" development. As a quick response to the 2013 PM2.5 episodes, the Chinese Government issued the "Air Pollution Prevention and Control Action Plan" as the national strategy and roadmap for air quality improvements consisting of phased quantitative targets and concrete measures. Taking this into account, this study explores the spatiotemporal variations of the five conventional pollutants-PM2.5, PM10, SO2, NO2, and O3-as well as the Air Quality Index and primary pollutants in 338 Chinese cities from 2013 to 2017 in order to comprehensively understand China's current air pollution situation and evaluate the effectiveness of the Action Plan. The results indicate that: (1) the overall air quality has been significantly improved, with the concentrations of PM2.5, PM10, and SO2 decreasing noticeably, although the still high PM level, the dramatically increasing O3 concentration, and the stagnant amounts of NO2 present further challenges, along with the intensification of regional compound air pollution problems; (2) in contrast to the three key regions under the Action Plan exhibiting significant decreases in PM and SO2, the Fen-Wei Plain (FWP) is suffering from serious compound pollution, suggesting that there is an urgent need for the development of a regional joint prevention and control mechanism in the FWP and similar areas; (3) with the exception of the common pollution hot spots mainly concentrated in the FWP as well as Beijing-Tianjin-Hebei (BTH) and its surrounding regions, the distribution of each pollutant exhibited remarkable spatial heterogeneity due to their distinctive emission sources, a finding that strongly indicates the need for regionally differentiated management; and (4) the most frequent primary pollutant at the national level was O3, followed by PM2.5 and PM10. In the Wuhan Metropolitan Area (WHM), Changsha-Zhuzhou-Xiangtan Metropolitan Area (CZT), and Sichuan-Chongqing Region (CY), PM2.5 pollution is playing the dominant role, while in the FWP, BTH, Yangtze River Delta region (YRD), and Pearl River Delta region (PRD), the synergistic control of PM2.5 and O3 pollutants is urgently needed as soon as possible, which will require that more attention be paid to emission mitigation in the transportation sector, as well as the synergistic control of NOx and VOC emissions.

A mechanism-based pharmacokinetic/pharmacodynamic model for CYP3A1/2 induction by dexamethasone in rats.

AIM: To develop a pharmacokinetic/pharmacodynamic (PK/PD) model describing the receptor/gene-mediated induction of CYP3A1/2 by dexamethasone (DEX) in rats. METHODS: A group of male Sprague-Dawley rats receiving DEX (100 mg/kg, ip) were sacrificed at various time points up to 60 h post-treatment. Their blood sample and liver were collected. The plasma concentration of DEX was determined with a reverse phase HPLC method. CYP3A1/2 mRNA, protein levels and enzyme activity were measured using RT-PCR, ELISA and the testosterone substrate assay, respectively. Data analyses were performed using a first-order conditional estimate (FOCE) with INTERACTION method in NONMEM version 7.1.2. RESULTS: A two-compartment model with zero-order absorption was applied to describe the pharmacokinetic characteristics of DEX. Systemic clearance, the apparent volume of distribution and the duration of zero-order absorption were calculated to be 172.7 mL·kg(-1)·h(-1), 657.4 mL/kg and 10.47 h, respectively. An indirect response model with a series of transit compartments was developed to describe the induction of CYP3A1/2 via PXR transactivation by DEX. The maximum induction of CYP3A1 and CYP3A2 mRNA levels was achieved, showing nearly 21.29- and 8.67-fold increases relative to the basal levels, respectively. The CYP3A1 and CYP3A2 protein levels were increased by 8.02-fold and 2.49-fold, respectively. The total enzyme activities of CYP3A1/2 were shown to increase by up to 2.79-fold, with a lag time of 40 h from the Tmax of the DEX plasma concentration. The final PK/PD model was able to recapitulate the delayed induction of CYP3A1/2 mRNA, protein and enzyme activity by DEX. CONCLUSION: A mechanism-based PK/PD model was developed to characterize the complex concentration-induction response relationship between DEX and CYP3A1/2 and to resolve the drug- and system-specific PK/PD parameters for the course of induction.

Contribution of the anterior cingulate cortex to laser-pain conditioning in rats.

The emotional component of nociception is seldom distinguished from pain behavioral testing. The aim of the present study was to develop a behavioral test that indicates the emotional pain responses using the classical conditioning paradigm. The role of the anterior cingulate cortex (ACC) in the process of this pain conditioning response was also evaluated. In laser-pain conditioning, free moving rats were trained to associate a tone (conditioned stimulus, CS) and short CO(2) laser pulsation (unconditioned stimulus, US). Monotonous tone (800 Hz, 0.6 s) was delivered through a loud-speaker as CS. CO(2) laser pulses (5 W at 50 or 100 ms in duration) applied to the hind paw was adopted as US. The CS-US interval was 0.5 s. Laser-pain conditioning was developed during 40 CS-US pairings. CS and US pairing with 100-ms laser pulse stimuli was more effective in establishing conditioning responses than that of 50-ms stimuli. The conditioning responses remained, tested by presenting CS alone, immediate to and 24 h subsequent to training. The performance of laser-pain conditioning was significantly reduced after bilateral lesioning of the ACC. Similar results were also obtained by bilateral lesions of the amygdala. The conditioning responses were also diminished following morphine treatment. The association between a neutral stimulus and a noxious stimulus could be demonstrated in a Pavlovian conditioning test in free moving rats. Thus, the conditioned response may be employed as a measure of the emotional component of the nociception. It is also suggested that the ACC may play an important role in mediating this conditioning effect.