Kidney function decline mediates the adverse effects of per- and poly-fluoroalkyl substances (PFAS) on uric acid levels and hyperuricemia risk.

Previous studies indicated per- and poly-fluoroalkyl substances (PFAS) were related to uric acid and hyperuricemia risk, but evidence for the exposure-response (E-R) curves and combined effect of PFAS mixture is limited. Moreover, the potential mediation effect of kidney function was not assessed. Hence, we conducted a national cross-sectional study involving 13,979 US adults in NHANES 2003-2018 to examine the associations of serum PFAS with uric acid and hyperuricemia risk, and the mediation effects of kidney function. Generalized linear models and E-R curves showed positive associations of individual PFAS with uric acid and hyperuricemia risk, and nearly linear E-R curves indicated no safe threshold for PFAS. Weighted quantile sum regression found positive associations of PFAS mixture with uric acid and hyperuricemia risk, and PFOA was the dominant contributor to the adverse effect of PFAS on uric acid and hyperuricemia risk. Causal mediation analysis indicated significant mediation effects of kidney function decline in the associations of PFAS with uric acid and hyperuricemia risk, with the mediated proportion ranging from 19 % to 57 %. Our findings suggested that PFAS, especially PFOA, may cause increased uric acid and hyperuricemia risk increase even at low levels, and kidney function decline plays a crucial mediation effect.

Reconsidering gas as clean energy: Switching to electricity for household cooking to reduce NO2-attributed disease burden.

Nitrogen dioxide (NO2) is a prevalent air pollutant in urban areas, originating from outdoor sources, household gas consumption, and secondhand smoke. The limited evaluation of the disease burden attributable to NO2, encompassing different health effects and contributions from various sources, impedes our understanding from a public health perspective. Based on modeled NO2 exposure concentrations, their exposure-response relationships with lung cancer, chronic obstructive pulmonary disease, and diabetes mellitus, and baseline disability-adjusted life years (DALYs), we estimated that 1,675 (655-2,624) thousand DALYs were attributable to NO2 in urban China in 2019 [138 (54-216) billion Chinese yuan (CNY) economic losses]. The transition from gas to electricity for household cooking was estimated to reduce the attributable economic losses by 35%. This reduction falls within the range of reductions achieved when outdoor air meets the World Health Organization interim target 3 and air quality guidelines for annual NO2, highlighting the significance of raising awareness of gas as a polluting household energy for cooking. These findings align with global sustainable development initiatives, providing a sustainable solution to promote public health while potentially mitigating climate change.

Greenness and its composition and configuration in association with allergic rhinitis in preschool children.

BACKGROUND: Few studies focus on the associations of green space composition and configuration with children's allergic rhinitis (AR). METHODS: A multi-center population-based cross-sectional study was performed in 7 cities in mainland of China between 2019 and 2020, recruiting 36,867 preschool children. Information on the current AR symptoms and demographics were collected by questionnaire. Exposure to residential greenness was estimated by Normalized Difference Vegetation Index (NDVI, 1000 m buffer) around the residences. Greenness composition was estimated in 3 main categories: forest, grassland, shrubland. Configuration of each category and total greenness (a spatial resolution of 10 m × 10 m) was estimated by 6 landscape pattern metrics to quantify their area, shape complexity, aggregation, connectivity, and patch density. Exposure to daily ambient particulate matter (PM1, PM2.5 and PM10, a spatial resolution of 1 km × 1 km) was estimated. Multilevel logistic regression models were applied to analyze the associations of greenness and its composition and configuration with AR, and mediation effects by PMs were examined by mediation analysis models. RESULTS: The prevalence of self-reported current AR in preschool children was 33.1%. Two indicators of forest, Aggregation Index of forest patches (AIforest) (odds ratio (OR):0.92, 95% Confidential Interval (CI): 0.88-0.97), and Patch Cohesion of forest (COHESIONforest) (OR: 0.93, 95% CI:0.89-0.98) showed significantly negative associations with AR symptoms. Mediation analyses found the associations were partially mediated by PMs. Age, exclusive breastfeed duration and season were the potential effect modifiers. The associations varied across seven cities. CONCLUSION: Our findings suggest the inverse associations of the aggregation and connectivity of forest patches surrounding residence addresses with AR symptoms. Since the cross-sectional study only provides associations rather than causation, further studies are needed to confirm our results as well as the underlying mechanisms.

Intrauterine and early postnatal exposures to submicron particulate matter and childhood allergic rhinitis: A multicity cross-sectional study in China.

BACKGROUND: Airborne particulate matter pollution has been linked to occurrence of childhood allergic rhinitis (AR). However, the relationships between exposure to particulate matter with an aerodynamic diameter ≤1 µm (PM1) during early life (in utero and first year of life) and the onset of childhood AR remain largely unknown. This study aims to investigate potential associations of in utero and first-year exposures to size-segregated PMs, including PM1, PM1-2.5, PM2.5, PM2.5-10, and PM10, with childhood AR. METHODS: We investigated 29286 preschool children aged 3-6 years in 7 Chinese major cities during 2019-2020 as the Phase II of the China Children, Families, Health Study. Machine learning-based space-time models were utilized to estimate early-life residential exposure to PM1, PM2.5, and PM10 at 1 × 1-km resolutions. The concentrations of PM1-2.5 and PM2.5-10 were calculated by subtracting PM1 from PM2.5 and PM2.5 from PM10, respectively. Multiple mixed-effects logistic models were used to assess the odds ratios (ORs) and 95% confidence intervals (CIs) of childhood AR associated with per 10-µg/m3 increase in exposure to particulate air pollution during in utero period and the first year of life. RESULTS: Among the 29286 children surveyed (mean ± standard deviation, 4.9 ± 0.9 years), 3652 (12.5%) were reported to be diagnosed with AR. Average PM1 concentrations during in utero period and the first year since birth were 36.3 ± 8.6 µg/m3 and 33.1 ± 6.9 µg/m3, respectively. Exposure to PM1 and PM2.5 during pregnancy and the first year of life was associated with an increased risk of AR in children, and the OR estimates were higher for each 10-µg/m3 increase in PM1 than for PM2.5 (e.g., 1.132 [95% CI: 1.022-1.254] vs. 1.079 [95% CI: 1.014-1.149] in pregnancy; 1.151 [95% CI: 1.014-1.306] vs. 1.095 [95% CI: 1.008-1.189] in the first year of life). No associations were observed between AR and both pre- and post-natal exposure to PM1-2.5, indicating that PM1 rather than PM1-2.5 contributed to the association between PM2.5 and childhood AR. In trimester-stratified analysis, childhood AR was only found to be associated with exposure to PM1 (OR = 1.077, 95% CI: 1.027-1.128), PM2.5 (OR = 1.048, 95% CI: 1.018-1.078), and PM10 (OR = 1.032, 95% CI: 1.007-1.058) during the third trimester of pregnancy. Subgroup analysis suggested stronger PM-AR associations among younger (<5 years old) and winter-born children. CONCLUSIONS: Prenatal and postnatal exposures to ambient PM1 and PM2.5 were associated with an increased risk of childhood AR, and PM2.5-related hazards could be predominantly attributed to PM1. These findings highlighted public health significance of formulating air quality guideline for ambient PM1 in mitigating children's AR burden caused by particulate air pollution.

Modification of Food Allergy on the Associations between Early Life Exposure to Size-Specific Particulate Matter and Childhood Allergic Rhinitis.

Previous studies have reported the association between particulate matter (PM) and childhood allergic rhinitis (AR). However, it is unclear whether food allergy (FA) modifies the PM-AR association. We aimed at evaluating the effect of the modification of FA on PM-AR association in preschool children. We adopted a cross-sectional study and conducted a questionnaire survey among preschool children aged 3-6 years in 7 cities in China from June 2019 to June 2020 to collect information on AR and FA. We used a combination of multilevel logistic regression and restricted cubic spline functions to quantitatively assess whether FA modifies the associations between size-specific PM exposure (1 × 1 km) and the risk of AR. The adjusted odds ratios (ORs) for AR among the children with FA as per a 10 µg/m3 increase in early life PM1, PM2.5, and PM10 were significantly higher than the corresponding ORs among the children without FA [e.g., OR: 1.58, 95% CI: (1.32, 1.90) vs 1.29, 95% CI: (1.18, 1.41), per 10 µg/m3 increase in PM1]. The interactions between FA and size-specific PM exposure and their effects on AR were statistically significant (all p-int < 0.001). FA, as an important part of the allergic disease progression, may modify the PM-AR association in preschool children.

Associations between home environmental factors and childhood eczema and related symptoms in different cities in China.

Previous studies have shown significant associations between home environmental factors and childhood eczema. However, few studies have compared how associations differ in different regions. This study investigated associations between home environmental factors and childhood eczema ever, and related symptoms including itchy rash (IR) and being awakened by itchy rash at night (awake by IR) in 4 cities located in different regions of China, based on cross-sectional investigations during 2010-2012. We used two-step analysis to explore the associations between influencing factors and eczema/related symptoms: first, group Least Absolute Shrinkage and Selection Operator (LASSO) was conducted to identify important factors among a list of candidates; then, the associations in total study population and in each city were estimated using logistic regression. We found these home environmental factors to be risk factors for eczema or related symptoms: large residence size, shared room, air cleaner at home, abnormal smell, perceived dry air, visible mold or damp stains, cooking with coal or wood, painted wall, incense, mice, new furniture during pregnancy, abnormal smell at birth, window condensation at birth and environmental tobacco smoke at birth. Environmental protective factors were rural house location and window ventilation. Associations of factors with eczema/related symptoms differed across cities. For example, air conditioning was protective for eczema in Beijing and awakening by IR in Shanghai with ORs of 0.70 (95%CI: 0.52, 0.95) and 0.33 (95%CI: 0.14, 0.81) respectively, but not significant in other cities. Our results have implications for improving home environments to reduce the risk of childhood eczema/related symptoms in different regions of China.

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.

The Role of Indoor Microbiome and Metabolites in Shaping Children's Nasal and Oral Microbiota: A Pilot Multi-Omic Analysis.

Maintaining a diverse and well-balanced nasal and oral microbiota is vital for human health. However, the impact of indoor microbiome and metabolites on nasal and oral microbiota remains largely unknown. Fifty-six children in Shanghai were surveyed to complete a questionnaire about their personal and environmental characteristics. The indoor microbiome and metabolites from vacuumed indoor dust were profiled via shotgun metagenomics and untargeted liquid chromatography-mass spectrometry (LC-MS). The nasal and oral microbiota in children was characterized using full-length 16S rRNA sequencing from PacBio. Associations between personal/environmental characteristics and the nasal/oral microbiota were calculated using PERMANOVA and regression analyses. We identified 6247, 431, and 342 microbial species in the indoor dust, nasal, and oral cavities, respectively. The overall nasal and oral microbial composition showed significant associations with environmental tobacco smoke (ETS) exposure during pregnancy and early childhood (p = 0.005 and 0.03, respectively), and the abundance of total indoor flavonoids and two mycotoxins (deoxynivalenol and nivalenol) (p = 0.01, 0.02, and 0.03, respectively). Notably, the abundance of several flavonoids, such as baicalein, eupatilin, isoliquiritigenin, tangeritin, and hesperidin, showed positive correlations with alpha diversity and the abundance of protective microbial taxa in nasal and oral cavities (p < 0.02), suggesting their potential beneficial roles in promoting nasal/oral health. Conversely, high carbohydrate/fat food intake and ETS exposure diminished protective microorganisms while augmenting risky microorganisms in the nasal/oral cavities. Further, potential microbial transfer was observed from the indoor environment to the childhood oral cavity (Moraxella catarrhalis, Streptococcus mitis, and Streptococcus salivarius), which could potentially increase virulence factors related to adherence and immune modulation and vancomycin resistance genes in children. This is the first study to reveal the association between the indoor microbiome/metabolites and nasal/oral microbiota using multi-omic approaches. These findings reveal potential protective and risk factors related to the indoor microbial environment.

Metabolomic alterations in healthy adults traveling to low-pollution areas: A natural experiment with ozone exposure.

Numerous epidemiological studies have demonstrated links between short-term ozone exposure to various adverse health outcomes, but some ozone-induced pathological mechanisms remain unclear. To fill this knowledge gap, we enrolled 36 healthy young adults living in high-ozone areas and performed an untargeted metabolomic analysis in serum collected before, during, and after their travel to a low-ozone scenic area. Reviewing the literature, we found 16 metabolites significantly associated with ozone, pointing to neurological health, type 2 diabetes (T2D) risk, and cardiovascular health. Notably, we observed significant changes in these 16 metabolites from the ozone reduction when participants traveled from the campus to the scenic area (adjusted p-value < 0.05). However, when ozone increased after participants returned to campus from the scenic area, we observed that T2D risk and cardiovascular health-related metabolites returned to their original state (adjusted p-value < 0.05), but neurological health-related metabolites did not change significantly with ozone exposure. Our study showed that ozone exposure was linked to prompt alterations in serum metabolites related to cardiovascular health and T2D risk but less sensitive changes in neurological health-related metabolites. Among many lipids, free fatty acids and acylcarnitines were the most sensitive compounds positively associated with changes in ozone exposure.

Improved ambient air quality is associated with decreased prevalence of childhood asthma and infancy shortly after weaning is a sensitive exposure window.

BACKGROUND: The urban ambient air quality has been largely improved in the past decade. It is unknown whether childhood asthma prevalence is still increasing in ever top-ranking city of Shanghai, whether the improved air quality is beneficial for children's asthma and what time window of exposure plays critical roles. METHODS: Using a repeat cross-sectional design, we analyzed the association between early life exposure to particles and wheezing/asthma in each individual and combined surveys in 2011 and 2019, respectively, in 11,825 preschool children in Shanghai. RESULTS: A significantly lower prevalence of doctor-diagnosed asthma (DDA) (6.6% vs. 10.5%, p < 0.001) and wheezing (10.5% vs. 23.2%, p < 0.001) was observed in 2019 compared to 2011. Exposure to fine particulate matter (PM2.5 ), coarse particles (PM2.5-10 ) and inhalable particles (PM10 ) was decreased in 2019 by 6.3%, 35.4%, and 44.7% in uterus and 24.3%, 20.2%, and 31.8% in infancy, respectively. Multilevel log-binomial regression analysis showed exposure in infancy had independent association with wheezing/DDA adjusting for exposure in uterus. For each interquartile range (IQR) increase of infancy PM2.5 , PM2.5-10 and PM10 exposure, the odds ratios were 1.39 (95% confidence interval (CI): 1.24-1.56), 1.51 (95% CI:1.15-1.98) and 1.53 (95% CI:1.27-1.85) for DDA, respectively. The distributed lag non-linear model showed the sensitive exposure window (SEW) was 5.5-11 months after birth. Stratified analysis showed the SEWs were at or shortly after weaning, but only in those with <6 months of exclusive breastfeeding. CONCLUSIONS: Improved ambient PM benefits in decreasing childhood asthma prevalence. We firstly reported the finding of SEW to PM at or closely after weaning on childhood asthma.

Prevalence, risk factors, impact and management of pneumonia among preschool children in Chinese seven cities: a cross-sectional study with interrupted time series analysis.

BACKGROUND: Pneumonia is a common disease worldwide in preschool children. Despite its large population size, China has had no comprehensive study of the national prevalence, risk factors, and management of pneumonia among preschool children. We therefore investigated the prevalence of pneumonia among preschool children in Chinese seven representative cities, and explore the possible risk factors of pneumonia on children, with a view to calling the world's attention to childhood pneumonia to reduce the prevalence of childhood pneumonia. METHODS: Two group samples of 63,663 and 52,812 preschool children were recruited from 2011 and 2019 surveys, respectively. Which were derived from the cross-sectional China, Children, Homes, Health (CCHH) study using a multi-stage stratified sampling method. This survey was conducted in kindergartens in seven representative cities. Exclusion criteria were younger than 2 years old or older than 8 years old, non-permanent population, basic information such as gender, date of birth and breast feeding is incomplete. Pneumonia was determined on the basis of parents reported history of clearly diagnosed by the physician. All participants were assessed with a standard questionnaire. Risk factors for pneumonia, and association between pneumonia and other respiratory diseases were examined by multivariable-adjusted analyses done in all participants for whom data on the variables of interest were available. Disease management was evaluated by the parents' reported history of physician diagnosis, longitudinal comparison of risk factors in 2011 and 2019. RESULTS: In 2011 and 2019, 31,277 (16,152 boys and 15,125 girls) and 32,016 (16,621 boys and 15,395 girls) preschool children aged at 2-8 of permanent population completed the questionnaire, respectively, and were thus included in the final analysis. The findings showed that the age-adjusted prevalence of pneumonia in children was 32.7% in 2011 and 26.4% in 2019. In 2011, girls (odds ratio [OR] 0.91, 95%CI [confidence interval]0.87-0.96; p = 0.0002), rural (0.85, 0.73-0.99; p = 0.0387), duration of breastfeeding ≥ 6 months(0.83, 0.79-0.88; p < 0.0001), birth weight (g) ≥ 4000 (0.88, 0.80-0.97; p = 0.0125), frequency of putting bedding to sunshine (Often) (0.82, 0.71-0.94; p = 0.0049), cooking fuel type (electricity) (0.87, 0.80-0.94; p = 0.0005), indoor use air-conditioning (0.85, 0.80-0.90; p < 0.0001) were associated with a reduced risk of childhood pneumonia. Age (4-6) (1.11, 1.03-1.20; p = 0.0052), parental smoking (one) (1.12, 1.07-1.18; p < 0.0001), used antibiotics (2.71, 2.52-2.90; p < 0.0001), history of parental allergy (one and two) (1.21, 1.12-1.32; p < 0.0001 and 1.33, 1.04-1.69; p = 0.0203), indoor dampness (1.24, 1.15-1.33; p < 0.0001), home interior decoration (1.11, 1.04-1.19; p = 0.0013), Wall painting materials (Paint) (1.16, 1.04-1.29; p = 0.0084), flooring materials (Laminate / Composite wood) (1.08, 1.02-1.16; p = 0.0126), indoor heating mode(Central heating)(1.18, 1.07-1.30, p = 0.0090), asthma (2.38, 2.17-2.61; p < 0.0001), allergic rhinitis (1.36, 1.25-1.47; p < 0.0001), wheezing (1.64, 1.55-1.74; p < 0.0001) were associated with an elevated risk of childhood pneumonia; pneumonia was associated with an elevated risk of childhood asthma (2.53, 2.31-2.78; p < 0.0001), allergic rhinitis (1.41, 1.29-1.53; p < 0.0001) and wheezing (1.64, 1.55-1.74; p < 0.0001). In 2019, girls (0.92, 0.87-0.97; p = 0.0019), duration of breastfeeding ≥ 6 months (0.92, 0.87-0.97; p = 0.0031), used antibiotics (0.22, 0.21-0.24; p < 0.0001), cooking fuel type (Other) (0.40, 0.23-0.63; p = 0.0003), indoor use air-conditioning (0.89, 0.83-0.95; p = 0.0009) were associated with a reduced risk of childhood pneumonia. Urbanisation (Suburb) (1.10, 1.02-1.18; p = 0.0093), premature birth (1.29, 1.08-1.55; p = 0.0051), birth weight (g) < 2500 (1.17, 1.02-1.35; p = 0.0284), parental smoking (1.30, 1.23-1.38; p < 0.0001), history of parental asthma (One) (1.23, 1.03-1.46; p = 0.0202), history of parental allergy (one and two) (1.20, 1.13-1.27; p < 0.0001 and 1.22, 1.08-1.37; p = 0.0014), cooking fuel type (Coal) (1.58, 1.02-2.52; p = 0.0356), indoor dampness (1.16, 1.08-1.24; p < 0.0001), asthma (1.88, 1.64-2.15; p < 0.0001), allergic rhinitis (1.57, 1.45-1.69; p < 0.0001), wheezing (2.43, 2.20-2.68; p < 0.0001) were associated with an elevated risk of childhood pneumonia; pneumonia was associated with an elevated risk of childhood asthma (1.96, 1.72-2.25; p < 0.0001), allergic rhinitis (1.60, 1.48-1.73; p < 0.0001) and wheezing (2.49, 2.25-2.75; p < 0.0001). CONCLUSIONS: Pneumonia is prevalent among preschool children in China, and it affects other childhood respiratory diseases. Although the prevalence of pneumonia in Chinese children shows a decreasing trend in 2019 compared to 2011, a well-established management system is still needed to further reduce the prevalence of pneumonia and reduce the burden of disease in children.

Impact of environmental characteristics on children's gut microbiota - A pilot study in assessing the role of indoor microbiome and metabolites.

BACKGROUND: A diverse and balanced human gut microbiota is crucial for maintaining normal human physiological functions. However, the impact of indoor microbiome and metabolites on gut microbiota is not well understood. METHODS: A self-administered questionnaire was used to collect information on more than 40 personal and environmental characteristics and dietary habits from 56 children in Shanghai, China. Shotgun metagenomics and untargeted liquid chromatography-mass spectrometry (LC-MS) were used to characterize the indoor microbiome and metabolomic/chemical exposure in children's living rooms. PacBio full-length 16 S rRNA sequencing was used to characterize children's gut microbiota. Associations between environmental characteristics and gut microbiota diversity/composition were assessed using PERMANOVA and regression. RESULTS: In total, 6247 and 318 indoor and gut microbial species and 1442 indoor metabolites were characterized. Age of children (R2 = 0.033, p = 0.008), age start kindergarten (R2 = 0.029, p = 0.03), living adjacent to heavy traffic (R2 = 0.031, p = 0.01) and drinking soft drinks (R2 = 0.028, p = 0.04) significantly impacted overall gut microbial composition, consistent with previous studies. Having pets/plants and frequent vegetable intake were positively associated with gut microbiota diversity and the Gut Microbiome Health Index (GMHI), while frequent juice and fries intake decreased gut microbiota diversity (p < 0.05). The abundance of indoor Clostridia and Bacilli was positively associated with gut microbial diversity and GMHI (p < 0.01). Total indoor indole derivatives and 6 indole metabolites (L-tryptophan, indole, 3-methylindole, indole-3-acetate, 5-hydroxy-L-tryptophan and indolelactic acid, p < 0.05) were positively associated with the abundance of total protective gut bacteria, suggesting a potential role in promoting gut health. Neural network analysis revealed that these indole derivatives were derived from indoor microorganisms. CONCLUSIONS: The study is the first to report associations between indoor microbiome/metabolites and gut microbiota, highlighting the potential role of indoor microbiome in shaping human gut microbiota.

Microbial Virulence Factors, Antimicrobial Resistance Genes, Metabolites, and Synthetic Chemicals in Cabins of Commercial Aircraft.

Passengers are at a higher risk of respiratory infections and chronic diseases due to microbial exposure in airline cabins. However, the presence of virulence factors (VFs), antimicrobial resistance genes (ARGs), metabolites, and chemicals are yet to be studied. To address this gap, we collected dust samples from the cabins of two airlines, one with textile seats (TSC) and one with leather seats (LSC), and analyzed the exposure using shotgun metagenomics and LC/MS. Results showed that the abundances of 17 VFs and 11 risk chemicals were significantly higher in TSC than LSC (p < 0.01). The predominant VFs in TSC were related to adherence, biofilm formation, and immune modulation, mainly derived from facultative pathogens such as Haemophilus parainfluenzae and Streptococcus pneumoniae. The predominant risk chemicals in TSC included pesticides/herbicides (carbofuran, bromacil, and propazine) and detergents (triethanolamine, diethanolamine, and diethyl phthalate). The abundances of these VFs and detergents followed the trend of TSC > LSC > school classrooms (p < 0.01), potentially explaining the higher incidence of infectious and chronic inflammatory diseases in aircraft. The level of ARGs in aircraft was similar to that in school environments. This is the first multi-omic survey in commercial aircraft, highlighting that surface material choice is a potential intervention strategy for improving passenger health.

Prevalence and influencing factors of wheeze and asthma among preschool children in Urumqi city: a cross-sectional survey.

To investigate the prevalence and indoor environmental influencing factors of wheeze and asthma among preschool children in Urumqi, Xinjiang, China to provide a strong basis for prevention and control. In August 2019, a cross-sectional study involving 8153 preschool children was conducted in 60 kindergartens in Urumqi. The ALLHOME-2 questionnaire was used for childhood wheeze and asthma survey, and the dampness in buildings and health (DBH) questionnaire was used for the childhood home dwelling and living environment survey. Multivariate unconditional logistic regression was then used to analyze the potential influencing factors of childhood asthma and wheeze. The prevalence of wheeze and asthma in children was 4.7% and 2.0%, respectively. Multivariate unconditional logistic regression results suggested that ethnicity other than the Han Chinese (odds ratio (OR) 1.39, 95% confidence interval (CI) 1.05-1.84), caesarean section (OR 1.24, 95% CI 1.00-1.53), family history of asthma (OR 5.00, 95% CI 3.36-7.44), carpet or floor bedding at home (OR 1.40, 95% CI 1.05-1.87), purchasing new furniture in the mother's residence during pregnancy (OR 1.58, 95% CI 1.06-2.36), pet keeping in the residence at aged 0-1 year (OR 1.55, 95% CI 1.13-2.13), passive smoking by child in the current residence (OR 1.35, 95% CI 1.01-1.80), and having mould or hygroma in the child's residence at aged 0-1 year (OR 1.72, 95% CI 1.12-2.64) were risk factors for wheeze. In addition, Girls (OR 0.73, 95% CI 0.59-0.90) was a protective factor for wheeze. Caesarean section (OR 1.46, 95% CI 1.06-2.00), family history of asthma (OR 7.06, 95% CI 4.33-11.53), carpet or floor bedding at home (OR 2.20, 95% CI 1.50-3.23), and pet keeping in the residence at aged 0-1 year (OR 1.64, 95% CI 1.04-1.83) were risk factors for asthma, whereas Girls (OR 0.58, 95% CI 0.42-0.80) was a protective factor for asthma. This survey indicates that the purchase of new furniture, the placement of carpet or floor bedding in the child's residence, the pets keeping, room dampness or moldy phenomena, and passive smoking may all contribute to an elevated risk of wheeze or asthma in children.

Coronarin A modulated hepatic glycogen synthesis and gluconeogenesis via inhibiting mTORC1/S6K1 signaling and ameliorated glucose homeostasis of diabetic mice.

Promotion of hepatic glycogen synthesis and inhibition of hepatic glucose production are effective strategies for controlling hyperglycemia in type 2 diabetes mellitus (T2DM), but agents with both properties were limited. Herein we report coronarin A, a natural compound isolated from rhizomes of Hedychium gardnerianum, which simultaneously stimulates glycogen synthesis and suppresses gluconeogenesis in rat primary hepatocytes. We showed that coronarin A (3, 10 µM) dose-dependently stimulated glycogen synthesis accompanied by increased Akt and GSK3ß phosphorylation in rat primary hepatocytes. Pretreatment with Akt inhibitor MK-2206 (2 µM) or PI3K inhibitor LY294002 (10 µM) blocked coronarin A-induced glycogen synthesis. Meanwhile, coronarin A (10 µM) significantly suppressed gluconeogenesis accompanied by increased phosphorylation of MEK, ERK1/2, ß-catenin and increased the gene expression of TCF7L2 in rat primary hepatocytes. Pretreatment with ß-catenin inhibitor IWR-1-endo (10 µM) or ERK inhibitor SCH772984 (1 µM) abolished the coronarin A-suppressed gluconeogenesis. More importantly, we revealed that coronarin A activated PI3K/Akt/GSK3ß and ERK/Wnt/ß-catenin signaling via regulation of a key upstream molecule IRS1. Coronarin A (10, 30 µM) decreased the phosphorylation of mTOR and S6K1, the downstream target of mTORC1, which further inhibited the serine phosphorylation of IRS1, and subsequently increased the tyrosine phosphorylation of IRS1. In type 2 diabetic ob/ob mice, chronic administration of coronarin A significantly reduced the non-fasting and fasting blood glucose levels and improved glucose tolerance, accompanied by the inhibited hepatic mTOR/S6K1 signaling and activated IRS1 along with enhanced PI3K/Akt/GSK3ß and ERK/Wnt/ß-catenin pathways. These results demonstrate the anti-hyperglycemic effect of coronarin A with a novel mechanism by inhibiting mTORC1/S6K1 to increase IRS1 activity, and highlighted coronarin A as a valuable lead compound for the treatment of T2DM.

Indoor metabolites and chemicals outperform microbiome in classifying childhood asthma and allergic rhinitis.

Indoor microorganisms impact asthma and allergic rhinitis (AR), but the associated microbial taxa often vary extensively due to climate and geographical variations. To provide more consistent environmental assessments, new perspectives on microbial exposure for asthma and AR are needed. Home dust from 97 cases (32 asthma alone, 37 AR alone, 28 comorbidity) and 52 age- and gender-matched controls in Shanghai, China, were analyzed using high-throughput shotgun metagenomic sequencing and liquid chromatography-mass spectrometry. Homes of healthy children were enriched with environmental microbes, including Paracoccus, Pseudomonas, and Psychrobacter, and metabolites like keto acids, indoles, pyridines, and flavonoids (astragalin, hesperidin) (False Discovery Rate < 0.05). A neural network co-occurrence probability analysis revealed that environmental microorganisms were involved in producing these keto acids, indoles, and pyridines. Conversely, homes of diseased children were enriched with mycotoxins and synthetic chemicals, including herbicides, insecticides, and food/cosmetic additives. Using a random forest model, characteristic metabolites and microorganisms in Shanghai homes were used to classify high and low prevalence of asthma/AR in an independent dataset in Malaysian schools (N = 1290). Indoor metabolites achieved an average accuracy of 74.9% and 77.1% in differentiating schools with high and low prevalence of asthma and AR, respectively, whereas indoor microorganisms only achieved 51.0% and 59.5%, respectively. These results suggest that indoor metabolites and chemicals rather than indoor microbiome are potentially superior environmental indicators for childhood asthma and AR. This study extends the traditional risk assessment focusing on allergens or air pollutants in childhood asthma and AR, thereby revealing potential novel intervention strategies for these diseases.

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.

Associations of Early-Life Exposure to Submicron Particulate Matter With Childhood Asthma and Wheeze in China.

Importance: Exposure to particulate matter (PM) has been associated with childhood asthma and wheeze. However, the specific associations between asthma and PM with an aerodynamic equivalent diameter of 1 µm or less (ie, PM1), which is a contributor to PM2.5 and potentially more toxic than PM2.5, remain unclear. Objective: To investigate the association of early-life (prenatal and first year) exposure to size-segregated PM, including PM1, PM1-2.5, PM2.5, PM2.5-10, and PM10, with childhood asthma and wheeze. Design, Setting, and Participants: This cross-sectional study was based on a questionnaire administered between June 2019 and June 2020 to caregivers of children aged 3 to 6 years in 7 Chinese cities (Wuhan, Changsha, Taiyuan, Nanjing, Shanghai, Chongqing, and Urumqi) as the second phase of the China, Children, Homes, Health study. Exposures: Exposure to PM1, PM1-2.5, PM2.5, PM2.5-10, and PM10 during the prenatal period and first year of life. Main Outcomes and Measures: The main outcomes were caregiver-reported childhood asthma and wheeze. A machine learning-based space-time model was applied to estimate early-life PM1, PM2.5, and PM10 exposure at 1 × 1-km resolution. Concentrations of PM1-2.5 and PM2.5-10 were calculated by subtracting PM1 from PM2.5 and PM2.5 from PM10, respectively. Multilevel (city and child) logistic regression models were applied to assess associations. Results: Of 29 418 children whose caregivers completed the survey (15 320 boys [52.1%]; mean [SD] age, 4.9 [0.9] years), 2524 (8.6%) ever had wheeze and 1161 (3.9%) were diagnosed with asthma. Among all children, 18 514 (62.9%) were breastfed for more than 6 months and 787 (2.7%) had parental history of atopy. A total of 22 250 children (75.6%) had a mother with an educational level of university or above. Of the 25 422 children for whom information about cigarette smoking exposure was collected, 576 (2.3%) had a mother who was a current or former smoker during pregnancy and 7525 (29.7%) had passive household cigarette smoke exposure in early life. Early-life PM1, PM2.5, and PM10 exposure were significantly associated with increased risk of childhood asthma, with higher estimates per 10-µg/m3 increase in PM1 (OR, 1.55; 95% CI, 1.27-1.89) than in PM2.5 (OR, 1.14; 95% CI, 1.03-1.26) and PM10 (OR, 1.11; 95% CI, 1.02-1.20). No association was observed between asthma and PM1-2.5 exposure, suggesting that PM1 rather than PM1-2.5 contributed to the association between PM2.5 and childhood asthma. There were significant associations between childhood wheeze and early-life PM1 exposure (OR, 1.23; 95% CI, 1.07-1.41) and PM2.5 exposure (OR, 1.08; 95% CI, 1.01-1.16) per 10-µg/m3 increase in PM1 and PM2.5, respectively. Conclusions and Relevance: In this cross-sectional study, higher estimates were observed for the association between PM with smaller particles, such as PM1, vs PM with larger particles and childhood asthma. The results suggest that the association between PM2.5 and childhood asthma was mainly attributable to PM1.