The burden of disease attributable to indoor air pollutants in China from 2000 to 2017.

BACKGROUND: High-level exposure to indoor air pollutants (IAPs) and their corresponding adverse health effects have become a public concern in China in the past 10 years. However, neither national nor provincial level burden of disease attributable to multiple IAPs has been reported for China. This is the first study to estimate and rank the annual burden of disease and the financial costs attributable to targeted residential IAPs at the national and provincial level in China from 2000 to 2017. METHODS: We first did a systematic review and meta-analysis of 117 articles from 37 231 articles identified in major databases, and obtained exposure-response relationships for the candidate IAPs. The exposure levels to these IAPs were then collected by another systematic review of 1864 articles selected from 52 351 articles. After the systematic review, ten IAPs with significant and robust exposure-response relationships and sufficient exposure data were finally targeted: PM2·5, nitrogen dioxide, sulphur dioxide, ozone, carbon monoxide, radon, formaldehyde, benzene, toluene, and p-dichlorobenzene. The annual exposure levels in residences were then evaluated in all 31 provinces in mainland China continuously from 2000 to 2017, using the spatiotemporal Gaussian process regression model to analyse indoor originating IAPs, and the infiltration factor method to analyse outdoor originating IAPs. The disability-adjusted life-years (DALYs) attributable to the targeted IAPs were estimated at both national and provincial levels in China, using the population attributable fraction method. Financial costs were estimated by an adapted human capital approach. FINDINGS: From 2000 to 2017, annual DALYs attributable to the ten IAPs in mainland China decreased from 4620 (95% CI 4070-5040) to 3700 (3210-4090) per 100 000. Nevertheless, in 2017, IAPs still ranked third among all risk factors, and their DALYs and financial costs accounted for 14·1% (95% CI 12·3-15·6) of total DALYs and 3·45% (3·01-3·82) of the gross domestic product. Specifically, the rank of ten targeted IAPs in order of their contribution to DALYs in 2017 was PM2·5, carbon monoxide, radon, benzene, nitrogen dioxide, ozone, sulphur dioxide, formaldehyde, toluene, and p-dichlorobenzene. The DALYs attributable to IAPs were 9·50% higher than those attributable to outdoor air pollution in 2017. For the leading IAP, PM2·5, the DALYs attributable to indoor origins are 18·3% higher than those of outdoor origins. INTERPRETATION: DALYs attributed to IAPs in China have decreased by 20·0% over the past two decades. Even so, they are still much higher than those in the USA and European countries. This study can provide a basis for determining which IAPs to target in various indoor air quality standards and for estimating the health and economic benefits of various indoor air quality control approaches, which will help to reduce the adverse health effects of IAPs in China. FUNDING: The National Key Research and Development Program of China and the National Natural Science Foundation of China.

Lung cancer as adverse health effect by indoor radon exposure in China from 2000 to 2020: A systematic review and meta-analysis.

Indoor radon exposure is thought to be associated with adverse health effect as lung cancer. Lung cancer incidences in China have been the highest worldwide during the past two decades. It is important to quantitively address indoor radon exposure and its health effect, especially in countries like China. In this paper, we have conducted a meta-analysis based on indoor radon and its health effect studies from a systematic review between 2000 and 2020. A total of 8 studies were included for lung cancer. We found that the relative risk (RR) was 1.01 (95% CI: 1.01-1.02) per 10 Bq/m3 increase of indoor radon for lung cancer in China. The subgroup analysis found no significant difference between the conclusions from the studies from China and other regions. The health effect of indoor radon exposure is relatively consistent for the low-exposure and high-exposure groups in the subgroup analysis. With a better understanding of exposure level of indoor radon, the outcomes and conclusions of this study will provide supports for next phase of researches on estimation of environmental burden of disease by indoor radon exposures in countries like China.

Health effects of exposure to sulfur dioxide, nitrogen dioxide, ozone, and carbon monoxide between 1980 and 2019: A systematic review and meta-analysis.

The burden of disease attributed to the indoor exposure to sulfur dioxide (SO2 ), nitrogen dioxide (NO2 ), ozone (O3 ), and carbon monoxide (CO) is not clear, and the quantitative concentration-response relationship is a prerequisite. This is a systematic review to summarize the quantitative concentration-response relationships by screening and analyzing the polled effects of population-based epidemiological studies. After collecting literature published between 1980 and 2019, a total of 19 health outcomes in 101 studies with 182 health risk estimates were recruited. By meta-analysis, the leave-one-out sensitivity analysis and Egger's test for publication bias, the robust and reliable effects were found for SO2 (per 10 µg/m3 ) with chronic obstructive pulmonary diseases (COPD) (pooled relative risks [RRs] 1.016, 95% CI: 1.012-1.021) and cardiovascular diseases (CVD) (RR 1.012, 95%CI: 007-1.018), respectively. NO2 (per 10 µg/m3 ) had the pooled RRs for childhood asthma, preterm birth, lung cancer, diabetes, and COPD by 1.134 (1.084-1.186), 1.079 (1.007-1.157), 1.055 (1.010-1.101), 1.019 (1.009-1.029), and 1.016 (1.012-1.120), respectively. CO (per 1 mg/m3 ) was significantly associated with Parkinson's disease (RR 1.574, 95% CI: 1.069-2.317) and CVD (RR 1.024, 95% CI: 1.011-1.038). No robust effects were observed for O3 . This study provided evidence and basis for further estimation of the health burden attributable to the four gaseous pollutants.

Indoor formaldehyde levels in residences, schools, and offices in China in the past 30 years: A systematic review.

Exposure to formaldehyde causes a variety of adverse health outcomes, while the distributions of indoor formaldehyde in different building types are still not clear in China. In this study, based on the systematic review of previously published data and Monte Carlo simulation, we assessed geographical and temporal distributions of indoor formaldehyde concentrations in residences, schools, and offices across China. A total of 397 studies covered 34 provincial-level regions since 1986 were collected. The results showed that indoor formaldehyde concentrations in residences, schools, and offices in nationwide were decreasing over years due to the publishment of indoor air quality standards since 2002. During 2011 to 2015, the median concentrations of indoor formaldehyde in newly renovated residences, schools, and offices were 153 µg/m3 , 163 µg/m3 , and 94 µg/m3 , with an exceeding rate of 82%, 46%, and 91% considering a standard threshold of 100 µg/m3 at that time, while the exceeding rate was less than 5% for buildings that were renovated beyond one year. Our findings release the temporal trends and geographic distributions of indoor formaldehyde concentrations in residences, schools, and offices in China in the past 30 years, and provide basic data for the comprehensive evaluation of disease burden attributable to indoor formaldehyde exposure.

Indoor exposure levels and risk assessment of volatile organic compounds in residences, schools, and offices in China from 2000 to 2021: A systematic review.

The last two decades have witnessed rapid urbanization and economic growth accompanied by severe indoor air pollution of volatile organic compounds (VOCs) in China. However, indoor VOC pollution across China has not been well characterized and documented. This study is a systematic review of field measurements of eight target VOCs (benzene, toluene, xylenes, acetaldehyde, p-dichlorobenzene, butadiene, trichloroethylene, and tetrachloroethylene) in residences, offices, and schools in China from 2000 to 2021. The results show that indoor pollution of benzene, toluene, and xylenes has been more serious in China than in other countries. Spatiotemporal distribution shows lower indoor VOC levels in east and south-east regions and a declining trend from 2000 to 2021. Moving into a dwelling more than 1 year after decoration and improving ventilation could significantly reduce exposure to indoor VOCs. Reducing benzene exposure is urgently needed because it is associated with greater health risks (4.5 × 10-4 for lifetime cancer risk and 8.3 for hazard quotient) than any other VOCs. The present study enriches the database of indoor VOC levels and provides scientific evidence for improving national indoor air quality standards as well as estimating the attributable disease burden caused by VOCs in China.

Health effects of exposure to indoor volatile organic compounds from 1980 to 2017: A systematic review and meta-analysis.

Exposure to volatile organic compounds (VOCs) indoors is thought to be associated with several adverse health effects. However, we still lack concentration-response (C-R) relationships between VOC levels in civil buildings and various health outcomes. For this paper, we conducted a systematic review and meta-analysis of observational studies to summarize related associations and C-R relationships. Four databases were searched to collect all relevant studies published between January 1980 and December 2017. A total of 39 studies were identified in the systematic review, and 32 of these were included in the meta-analysis. We found that the pooled relative risk (RR) for leukemia was 1.03 (95% CI: 1.01-1.05) per 1 µg/m3 increase of benzene and 1.25 (95%CI: 1.14-1.37) per 0.1 µg/m3 increase of butadiene. The pooled RRs for asthma were 1.08 (95% CI: 1.02-1.14), 1.02 (95% CI: 1.00-1.04), and 1.04 (95% CI: 1.02-1.06) per 1 µg/m3 increase of benzene, toluene, and p-dichlorobenzene, respectively. The pooled RR for low birth weight was 1.12 (95% CI: 1.05-1.19) per 1 µg/m3 increase of benzene. Our findings provide robust evidence for associations between benzene and leukemia, asthma, and low birth weight, as well as for health effects of some other VOCs.

Indoor exposure to phthalates and its burden of disease in China.

China's profoundly rapid modernization in the past two decades has resulted in dramatic changes in indoor environmental exposures. Among these changes, exposure to phthalates has attracted increasing attention. We aimed to characterize indoor phthalate exposure and to estimate the disease burden attributable to indoor phthalate pollution from 2000 to 2017 in China. We integrated the national exposure level of indoor phthalates from literature through systematic review and Monte Carlo simulation. Dose-response relationships between phthalate exposure and health outcomes were obtained by systematic review and meta-analysis. Based on existing models for assessing probabilities of causation and a comprehensive review of available data, we calculated the disability-adjusted life years (DALYs) among the general Chinese population resulting from exposure to indoor phthalate pollution. We found that DnBP, DiBP, and DEHP were the most abundant phthalates in indoor environments of residences, offices, and schools with medians of national dust phase concentration from 74.5 µg/g to 96.3 µg/g, 39.6 µg/g to 162.5 µg/g, 634.2 µg/g to 1,394.7 µg/g, respectively. The national equivalent exposure for children to phthalates in settled dust was higher than that of adults except for DiBP and DnOP. Dose-response relationships associated with DEP, DiBP, DnBP, BBzP, and DEHP exposures were established. Between 2000 and 2017, indoor phthalate exposure in China has led to 3.32 million DALYs per year, accounting for 0.90% of total DALYs across China. The annual DALY associated with indoor phthalate pollution in China was over 2000 people per million, which is about 2~3 times of the DALY loss due to secondhand smoke (SHS) in six European countries or the sum of the DALY loss caused by indoor radon and formaldehyde in American homes. Our study indicates a considerable socioeconomic impact of indoor phthalate exposure for a modernizing human society. This suggest the need for relevant national standard and actions to reduce indoor phthalate exposure.

Association between Lake Sediment Nutrients and Climate Change, Human Activities: A Time-Series Analysis.

Climate change and human activities are closely linked with the nutrient accumulation in sediments, but the role of influence factors and the driving mechanisms are unclear. Here, by using the generalized additive model (GAM), we investigated the contributions and driving mechanisms of climate change and human activities on TON, TN, and TP accumulation in sediments of typical lakes in the Huai River basin (Nansi Lake and Hongze Lake) from 1988 to 2018. The impacts of factors, such as air temperature (AT), real GDP per capita (GDP), population density (PD), crop sown area (CSA), artificial impervious area (AIA), and domestic sewage discharge (DSD) were considered in this study. The results of the multivariate GAM showed that the sediment variables were significantly affected by climate change in Nansi Lake, but not in Hongze Lake. AT and DSD contributed the most to the variation of sediment TOC in Nansi Lake, while the most critical factors affecting TN and TP were AT, PD and DSD. PD and CSA showed strong ability to explain the change of TOC in Hongze Lake, while CSA and DSD showed strong ability to explain the variations of TN and TP. The results show that the selected optimal multivariate GAM can well quantify the effects of climate change and human activities on nutrient enrichment in lake sediments. Effective recommendations are provided for decision-makers in developing water quality management plans to prevent eutrophication outbreaks in lake waters by targeting and controlling key factors.

[Meta-analysis of the Impact of Different Ozone Metrics on Total Mortality in China].

This study explores the effect of different ozone metrics on the total mortality risk in China. Using the CNKI, Wanfang, VIP, Web of Science, and PubMed databases, the time series studies and case crossover studies from the establishment of each database to December 31, 2020 were retrieved, and 22 eligible studies were included in this analysis. A meta-analysis was performed for the ozone metrics of O3-M1h, O3-M8h, and O3-24h. The results indicated that the increase in the total mortality risk is more closely associated with O3-M1h (RR #, 1.0052; 95%CI, 1.0031-1.0073) and is more weakly associated with O3-24h (RR #, 1.0036; 95%CI, 1.0025-1.0048) and O3-M8h (RR #, 1.0031; 95%CI, 1.0022-1.0041). A subgroup analysis of the three metrics revealed that the total mortality risk of ozone is higher in the cold season, the elderly (≥ 65) are more vulnerable to ozone pollution, and the total mortality risk in the north is higher than that in the south.

Indoor exposure levels of radon in dwellings, schools, and offices in China from 2000 to 2020: A systematic review.

After decades of development, the indoor environment in China has changed. A systematic review was conducted from peer-reviewed scientific papers with field test data of indoor radon in China from 2000 to 2020 for three types of buildings. The mean concentrations of indoor radon for dwellings, school buildings, and office buildings are 54.6, 56.1, and 54.9 Bq/m3 . The indoor radon concentration was related to seasons, climate regions, ventilation, decoration, and other factors such as soil and outdoor air. Colder seasons, especially in severe colder areas of China, newer decorated buildings, closed windows, and doors were all associated with higher indoor radon concentrations. Variables like climate region and ventilation showed statistical significance in the correlation analysis. Regarding the increasing trend of indoor radon concentration in China during the last two decades, further study of indoor radon is necessary especially for school buildings and office buildings, and will help access its environmental burden of disease in China more accurately.

Indoor exposure levels of ammonia in residences, schools, and offices in China from 1980 to 2019: A systematic review.

Indoor ammonia (NH3 ) pollution has been paid more and more attention in view of its health risk. However, few studies have investigated the exposure level in the non-occupational environment in China. This study systematically reviewed the indoor ammonia exposure level in different regions, the equivalent exposure concentration of different populations, and the factors that influence indoor air ammonia in residences, offices, and schools in China. The literature published in 1980-2019 from main databases was searched and detailed screened, and finally, 56 related studies were selected. The results illustrated that the median concentration of indoor air ammonia in residences, offices, and school buildings was 0.21 mg/m3 , 0.26 mg/m3 , and 0.15 mg/m3 . There were 46.4%, 71.4%, and 40% of these samples exceeding the NH3  standard, respectively. The national concentrations and the equivalent exposure levels of adults and children were calculated and found to be higher than 0.20 mg/m3 . The concentration of ammonia varied greatly in different climate zones and economic development regions. Higher concentrations were found in the severe cold zone and the regions with higher economic level. This review reveals a high exposure risk of indoor air ammonia and the crucial impact of human emission, indoor air temperature, new concrete, and economic level, suggesting further investigation on indoor air ammonia evaluation and health effects.

Indoor exposure levels of bacteria and fungi in residences, schools, and offices in China: A systematic review.

Microbes in buildings have attracted extensive attention from both the research community and the general public due to their close relationship with human health. However, there still lacks comprehensive information on the indoor exposure level of microbes in China. This study systematically reviews exposure levels, the community structures, and the impact factors of airborne bacteria and fungi in residences, schools, and offices in China. We reviewed the major literature databases between 1980 and 2019 and selected 55 original studies based on a set of criteria. Results show that the concentration of indoor bacteria varies from 72.5 to 7500 CFU/m3 , with a median value of 1000 CFU/m3 , and the concentration of fungi varies from 12 to 9730 CFU/m3 , with a median value of 526 CFU/m3 . The concentration level of microbes varies in different climate zones, with higher bacterial concentrations in the severe cold zone, and higher fungal concentrations in the hot summer and warm winter zone. Among different buildings, classrooms have the highest average bacteria and fungi levels. This review reveals that a unified assessment system based on health effects is needed for evaluating the exposure levels of bacteria and fungi.

Niclosamide ethanolamine-induced mild mitochondrial uncoupling improves diabetic symptoms in mice.

Type 2 diabetes (T2D) has reached an epidemic level globally. Most current treatments ameliorate the hyperglycemic symptom of the disease but are not effective in correcting its underlying cause. One important causal factor of T2D is ectopic accumulation of lipids in metabolically sensitive organs such as liver and muscle. Mitochondrial uncoupling, which reduces cellular energy efficiency and increases lipid oxidation, is an appealing therapeutic strategy. The challenge, however, is to discover safe mitochondrial uncouplers for practical use. Niclosamide is an anthelmintic drug approved by the US Food and Drug Administration that uncouples the mitochondria of parasitic worms. Here we show that niclosamide ethanolamine salt (NEN) uncouples mammalian mitochondria at upper nanomolar concentrations. Oral NEN increases energy expenditure and lipid metabolism in mice. It is also efficacious in preventing and treating hepatic steatosis and insulin resistance induced by a high-fat diet. Moreover, it improves glycemic control and delays disease progression in db/db mice. Given the well-documented safety profile of NEN, our study provides a potentially new and practical pharmacological approach for treating T2D.

Autophagy in adipose tissue biology.

Obesity, which predisposes individuals to type II diabetes and cardiovascular diseases, results from accumulation of white adipose tissue (WAT). WAT comprises mainly white adipocytes that have a unique cellular structure in which almost the entire intracellular space is occupied by one single lipid droplet. The cytoplasm envelopes this lipid droplet and occupies negligible space. Differentiation of WAT, or adipogenesis, requires dramatic cytoplasmic reorganization, including a dynamic change in mitochondrial mass. Autophagy is a major cytoplasmic degradation pathway and a primary pathway for mitochondrial degradation. Recent studies indicate that autophagy is implicated in adipogenesis. In this review, we summarize our current knowledge on autophagy in adipose tissue biology, with the emphasis on its role in mitochondrial degradation. Adipose tissue is a central component for whole-body energy homeostasis regulation. Advancement in this research area may provide novel venues for the intervention of obesity and obesity related diseases.

Design and stability of a novel coiled-coil peptide.

According to a template of natural protein, a novel peptide was designed with satisfied stability which came from the formation of coiled-coil dimer in vitro. The knowledge gained from this study is not only useful in antiparallel coiled-coil designing but also provide an ideal antiparallel coiled-coil model in future research.

Sodium barbital is a slow reversible inactivator of rabbit-muscle creatine kinase.

As a depressant of the central nervous system, the clinical effect of sodium barbital has been extensively studied. Here we report on sodium barbital as an inhibitor of rabbit-muscle creatine kinase (CK), which plays a significant role in energy homeostasis in the muscles. Although sodium barbital gradually inhibits the activity of CK with increased concentration, the inhibition effect can be completely reversed by dilution, indicating that the inactivation process is reversible. Detailed kinetics analysis, according to a previously presented theory, indicates that sodium barbital functions as a non complexing inhibitor, and its inhibition effect on CK is a slow reversible inactivation. In this study, a kinetic model of the substrate reaction is presented, and the microscopic rate constants for the reaction of sodium barbital with the free enzyme and the enzyme-substrate complexes are determined. Kinetic analysis reveals that sodium barbital might compete with both creatine and ATP, but mainly with creatine, to inhibit the activity of CK. The results suggest that CK might be a target for sodium barbital in vivo.

Conformational changes and inactivation of bovine carbonic anhydrase II in 2,2,2-trifluoroethanol solutions.

Changes in unfolding and enzymatic activity of bovine carbonic anhydrase II (BCA II) in different concentrations of 2,2,2-trifluoroethanol (TFE) were investigated by 1-anilino-8-naphthalenesulfonate (ANS) fluorescence emission spectra, far-UV CD spectra, and enzyme activity. The results showed that the activity and conformation of BCA II changed according to the concentration of TFE. Significant aggregation was observed when BCA II was denatured at TFE concentrations between 10 and 35% (v/v). When the concentration of TFE exceeded 40%, the aggregation of BCA II was not very obvious. The activity of BCA II decreased almost to zero as the TFE concentration reached 26%. The ANS fluorescence spectra indicated the tertiary conformations of BCA II were more stable in solutions with TFE concentrations lower than 15% (v/v) and higher than 40% (v/v). Far-UV CD spectra showed that high concentrations (higher than 25%) of TFE could induce BCA II to form more alpha-helix structures and caused these structures to be in relatively stable states. The native conformation of BCA II being destroyed after its inactivity indicated that the active sites of BCA II is situated in a limited region and has more flexibility than the whole enzyme molecule.