Gender- and Obesity-Specific Association of Co-Exposure to Personal Care Product and Plasticizing Chemicals and Short Sleep Duration among Adults: Evidence from the National Health and Nutrition Examination Survey 2011-2016.

There is limited evidence about the gender- and obesity-specific effects of personal care product and plasticizing chemicals (PCPPCs) on short sleep duration in adults. We evaluated the gender- and obesity-specific association of co-exposure to PCPPCs and short sleep duration among adults aged 20-60 years using the National Health and Nutrition Examination Survey (NHANES) 2011-2016, a secondary data source from the United States. Seventeen PCPPCs, including five phenols, two parabens, and ten phthalates, were detected, and sleep duration was assessed among 3012 adults. Logistic regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) were employed. We found that bisphenol A (BPA), mono (caboxy-isooctyl) phthalate (MCOP), and mono (3-carboxypropyl) phthalate (MCPP) were consistently positively associated with short sleep duration in both females and males regardless of obesity status, except for BPA with general obesity. In particular, mono benzyl phthalate (MBzP) revealed a positive association in females, mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) revealed a positive association in males, and MiBP revealed a positive association in abdominal obesity. Similar associations were observed in the mixture. Our study highlights that PCPPCs are independently associated with an increasing risk of short sleep duration in adults both individually and as a mixture; however, gender- and obesity-specific differences may have little effect on certain individual PCPPCs on short sleep duration.

Estimating lead-attributable mortality burden by socioeconomic status in the USA.

BACKGROUND: This study aimed to estimate population-level and state-level lead-attributable mortality burdens stratified by socioeconomic status (SES) class in the USA. METHODS: Based on the National Health and Nutrition Examination Survey (NHANES), we constructed individual-level SES scores from income, employment, education and insurance data. We assessed the association between the blood lead levels (BLL) and all-cause mortality by Cox regression in the NHANES cohort (n = 31 311, 4467 deaths). With estimated hazard ratios (HR) and prevalences of medium (2-5 µg/dL) and high (≥ 5 µg/dL) BLL, we computed SES-stratified population-attributable fractions (PAFs) of all-cause mortality from lead exposure across 1999-2019. We additionally conducted a systematic review to estimate the lead-attributable mortality burden at state-level. RESULTS: The HR for every 2-fold increase in the BLL decreased from 1.23 (1.10-1.38) for the lowest SES class to 1.05 (0.90-1.23) for the highest SES class. Across all SES quintiles, medium BLL exhibited a greater mortality burden. Individuals with lower SES had higher lead-attributable burdens, and such disparities haver persisted over the past two decades. In 2017-19, annually 67 000 (32 000-112 000) deaths in the USA were attributable to lead exposure, with 18 000 (2000-41 000) of these deaths occurring in the lowest SES class. Substantial disparities in the state-level mortality burden attributable to lead exposure were also highlighted. CONCLUSIONS: These findings suggested that disparities in lead-attributable mortality burden persisted within US adults, due to heterogeneities in the effect sizes of lead exposure as well as in the BLL among different SES classes.

Prenatal Parental Exposure to Metals and Birth Defects: A Prospective Birth Cohort Study.

While maternal exposure to high metal levels during pregnancy is an established risk factor for birth defects, the role of paternal exposure remains largely unknown. We aimed to assess the associations of prenatal paternal and maternal metal exposure and parental coexposure with birth defects in singletons. This study conducted within the Jiangsu Birth Cohort recruited couples in early pregnancy. We measured their urinary concentrations for 25 metals. A total of 1675 parent-offspring trios were included. The prevalence of any birth defects among infants by one year of age was 7.82%. Paternal-specific gravity-corrected urinary concentrations of titanium, vanadium, chromium, manganese, cobalt, nickel, copper, and selenium and maternal vanadium, chromium, nickel, copper, selenium, and antimony were associated with a 21-91% increased risk of birth defects after adjusting for covariates. These effects persisted after mutual adjustment for the spouse's exposure. Notably, when assessing the parental mixture effect by Bayesian kernel machine regression, paternal and maternal chromium exposure ranked the highest in relative importance. Parental coexposure to metal mixture showed a pronounced joint effect on the risk of overall birth defects, as well as for some specific subtypes. Our findings suggested a couple-based prevention strategy for metal exposure to reduce birth defects in offspring.

Effects of indoor air pollution from household solid fuel use on the risk of gastrointestinal and liver diseases in middle aged and elderly adults.

Solid fuels are widely used in China and increase the concentrations of indoor air pollutants. Nevertheless, there is limited longitudinal evidence linking solid fuel use and Gastrointestinal (GI) and liver diseases. This study aimed to prospectively investigate the association between household solid fuel use and the risk of GI and liver diseases in middle aged and elderly adults. This work was based on the China Health and Retirement Longitudinal Study (CHARLS). Longitudinal data incorporate with cross-sectional data were analyzed. Compared with individuals using clean fuel for cooking, solid fuel users were observed to have higher risk of GI diseases (OR in 2011, 2013, 2015, 2018 wave separately: 1.37, 95 % CI: 1.24-1.50, P < 0.001; 1.24, 95 % CI: 1.11-1.39, P < 0.001; 1.18, 95 % CI: 1.06-1.33, P < 0.001; 1.23, 95 % CI: 1.04-1.45, P < 0.05). The associations between solid fuel use and liver diseases were not significant in most of the groups. Participants transforming from solid to clean cooking fuels had lower risk of GI and liver diseases than persistent solid fuel users. Moreover, biomass cooking fuel users were at a significant higher risk of both liver and GI diseases compared with clean fuel users. Overall, household solid fuel use, especially for cooking, was related to higher risk of GI and liver diseases, while switching from solid to clean fuels could reduce this risk. Using biomass for cooking was identified to be more associated with the increasing risk of GI and liver diseases than cooking with coal.

Clonal expansion of shared T cell receptors reveals the existence of immune commonality among different lesions of synchronous multiple primary lung cancer.

The increase in the detection rate of synchronous multiple primary lung cancer (MPLC) has posed remarkable clinical challenges due to the limited understanding of its pathogenesis and molecular features. Here, comprehensive comparisons of genomic and immunologic features between MPLC and solitary lung cancer nodule (SN), as well as different lesions of the same patient, were performed. Compared with SN, MPLC displayed a lower rate of EGFR mutation but higher rates of BRAF, MAP2K1, and MTOR mutation, which function exactly in the upstream and downstream of the same signaling pathway. Considerable heterogeneity in T cell receptor (TCR) repertoire exists among not only different patients but also among different lesions of the same patient. Invasive lesions of MPLC exhibited significantly higher TCR diversity and lower TCR expansion than those of SN. Intriguingly, different lesions of the same patient always shared a certain proportion of TCR clonotypes. Significant clonal expansion could be observed in shared TCR clonotypes, particularly in those existing in all lesions of the same patient. In conclusion, this study provided evidences of the distinctive mutational landscape, activation of oncogenic signaling pathways, and TCR repertoire in MPLC as compared with SN. The significant clonal expansion of shared TCR clonotypes demonstrated the existence of immune commonality among different lesions of the same patient and shed new light on the individually tailored precision therapy for MPLC.

Inter- and trans-generational impacts of real-world PM2.5 exposure on male-specific primary hypogonadism.

Exposure to PM2.5, a harmful type of air pollution, has been associated with compromised male reproductive health; however, it remains unclear whether such exposure can elicit transgenerational effects on male fertility. Here, we aim to examine the effect of paternal exposure to real-world PM2.5 on the reproductive health of male offspring. We have observed that paternal exposure to real-world PM2.5 can lead to transgenerational primary hypogonadism in a sex-selective manner, and we have also confirmed this phenotype by using an external model. Mechanically, we have identified small RNAs (sRNAs) that play a critical role in mediating these transgenerational effects. Specifically, miR6240 and piR016061, which are present in F0 PM sperm, regulate intergenerational transmission by targeting Lhcgr and Nsd1, respectively. We have also uncovered that piR033435 and piR006695 indirectly regulate F1 PM sperm methylation by binding to the 3'-untranslated region of Tet1 mRNA. The reduced expression of Tet1 resulted in hypermethylation of several testosterone synthesis genes, including Lhcgr and Gnas, impaired Leydig cell function and ultimately led to transgenerational primary hypogonadism. Our findings provide insights into the mechanisms underlying the transgenerational effects of paternal PM2.5 exposure on reproductive health, highlighting the crucial role played by sRNAs in mediating these effects. The findings underscore the significance of paternal pre-conception interventions in alleviating the adverse effects of environmental pollutants on reproductive health.

Residential energy transition and chronic respiratory diseases.

Obtaining clean energy is of prime importance for planetary health and sustainable development. We aimed to assess the association between residential energy transition and the risk of chronic respiratory diseases. Using data from the Global Health Observatory and Global Burden of Diseases, Injuries, and Risk Factors Study, we delineated the spatial distribution and temporal trends of the population using clean fuels for cooking at a global scale. In the China Health and Retirement Longitudinal Study, we performed rigorous and well-structured multistage analyses incorporating both cross-sectional and prospective data analyses to examine the associations between solid fuel use, residential energy transition, duration of solid fuel use, and the risk of chronic respiratory diseases. Despite great progress, huge disparities in access to clean energy persist globally. Residential energy transition was associated with a lower risk of chronic respiratory diseases. In the period of 2011-2013, compared with persistent solid fuel users, both participants who switched from solid to clean fuels (adjusted risk ratio [RR] 0.78, 95% confidence interval [CI] 0.62-0.98) and persistent clean fuel users (adjusted RR 0.71, 95% CI 0.57-0.89) had significantly lower risk of chronic respiratory diseases (p < 0.001 for trend). Consistent associations were observed in the period of 2011-2015 and 2011-2018. Household energy transition from solid to clean fuels could reduce the risk of chronic respiratory diseases. This is a valuable lesson for policy-makers and the general public to accelerate energy switching to alleviate the burden of chronic respiratory diseases and achieve health benefits, particularly in low- and middle-income countries.

Evaluation of multiple organophosphate insecticide exposure in relation to altered thyroid hormones in NHANES 2007-2008 adult population.

The thyroid gland is susceptible to chemical exposure such as organophosphate insecticides (OPIs). With the ubiquitous nature of these products, humans are simultaneously exposed to a multitude of chemicals. This study aimed to evaluate the association between an individual and a mixture of OPI metabolites and changes in serum thyroid hormone (TH) concentrations. The analyzed data were 1,434 participants from the United States National Health and Nutrition Examination Surveys (NHANES) cycle 2007-2008. Generalized linear model (GLM) regression, weighted quantile sum (WQS), and adaptive least absolute shrinkage and selection operator (adaptive LASSO) regression were used to investigate the associations between urinary OPI metabolites and altered serum THs. In GLM, all of the five urinary OPI metabolites were inversely associated with free triiodothyronine (FT3) among the male subjects; meanwhile, higher thyroglobulin (Tg) was related to dimethylphosphate (DMP). Moreover, in WQS models, the metabolite mixture induced FT3 down-regulation (ß = -0.209 (95% CI: -0.310, -0.114)), and caused an increased Tg concentration (ß = 0.120 (95% CI: 0.024, 0.212)), however, any significant association was observed among female participants. Consistently, the weighted index and LASSO coefficient demonstrated dimethylthiophosphate (DMTP) as the strongest metabolite in the FT3 model (mean weight= 3.449e-01 and ß =-0.022, respectively), and dimethylphosphate (DMP) represented the highest association in the Tg model (mean weight= 9.873e-01 and ß =-0.020, respectively). Further research is required to confirm our results and investigate the clinical impacts of these disruptions.

Exposure to particulate matter may affect semen quality via trace metals: Evidence from a retrospective cohort study on fertile males.

Particulate matter (PM) exposure may be associated with male semen quality. Besides, PM exposure induces up and down levels of trace metals in tissues or organs. The levels of trace metals in semen are critical for adverse male semen quality. This study aims to evaluate the concentrations of seminal-level trace metals in fertile men and assess its associations with PM exposure and to explore the mediation role of trace metals in seminal plasma plays in the relationship between PM exposure and semen quality. Total 1225 fertile men who participated in a cohort study from 2014 to 2016 were finally recruited. Multivariate linear regression was applied to explore associations between each two of PM exposure, trace metals and semen parameters. 1-year PM2.5 and PM10 exposure levels were positively associated with arsenic (As), mercury (Hg), lanthanum (La), praseodymium (Pr), neodymium (Nd) but negatively associated with vanadium (V), magnesium (Mg), strontium (Sr), barium (Ba) in semen. It was also found that most of the elements were associated with total sperm number, followed by sperm concentration. Redundancy analysis (RDA) also determined several strong positive correlations or negative correlations between 1-year PM exposure and trace metals. Mediation analysis found that trace metals had a potentially compensatory or synergetic indirect effect on the total effect of the association between 1-year PM exposure and semen quality. The retrospective cohort study provides long-term PM exposure that may cause abnormal semen quality by affecting seminal plasma element levels.

[Relationship between Bacteria in the Lower Respiratory Tract/Lung Cancer 
and the Development of Lung Cancer as well as Its Clinical Application].

Due to the advancement of 16S rRNA sequencing technology, the lower respiratory tract microbiota, which was considered non-existent, has been revealed. The correlation between these microorganisms and diseases such as tumor has been a hot topic in recent years. As the bacteria in the surrounding can infiltrate the tumors, researchers have also begun to pay attention to the biological behavior of tumor bacteria and their interaction with tumors. In this review, we present the characteristic of the lower respiratory tract bacteria and summarize recent research findings on the relationship between these microbiota and lung cancer. On top of that, we also summarize the basic feature of bacteria in tumors and focus on the characteristic of the bacteria in lung cancer. The relationship between bacteria in lung cancer and tumor development is also been discussed. Finally, we review the potential clinical applications of bacterial communities in the lower respiratory tract and lung cancer, and summarize key points of sample collection, sequencing, and contamination control, hoping to provide new ideas for the screening and treatment of tumors.
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Contribution of serum elements to blood pressure during pregnancy by impacting gut microbiota: A prospective cohort study.

Exposure to environmental elements can alter gut microbiota, further affecting host health. Exploring the interrelationships among element exposure, gut microbiota and blood pressure (BP) during pregnancy, as well as the mediating roles of gut microbiota, is warranted, which holds implications for maternal and offspring health. In a prospective cohort study between 2017-2018, 733 pregnant women were included. The serum elements and gut microbiota during the second trimester were assessed, and BP was collected during the second and third trimester and before delivery. Fourteen associations were identified between serum elements and BP, including positive associations of zinc (Zn) and thallium (Tl) with systolic BP during the second trimester. Rubidium (Rb) showed a positive association with Pielou's evenness. Serum elements, such as Tl and Rb, were significantly associated with the relative abundance of bacteria and co-abundance groups (CAGs). Alpha diversity was negatively associated with BP levels and trajectories. Moreover, 15 associations between gut microbiota and BP were shown. Finally, mediation analysis confirmed that CAG2 and Pielou's evenness mediated the associations of Tl and Rb with BP, respectively. We concluded that serum elements can contribute to BP changes during pregnancy through gut microbiota, suggesting gut microbiota-targeted approach as a potential intervention.

Alterations in sperm DNA methylation may as a mediator of paternal air pollution exposure and offspring birth outcomes: Insight from a birth cohort study.

Paternal exposure to environmental risk factors influences the offspring health. This study aimed to evaluate the association between paternal air pollution exposure mediated by sperm DNA methylation and adverse birth outcomes in offspring. We recruited 1607 fertile men and their partners from 2014 to 2016 and collected semen samples to detect sperm DNA methylation. Multivariate linear regression and weighted quantile sum regression models were used to assess the associations between paternal air pollution exposure and offspring birth outcomes. A critical exposure window was identified. Reduced representation bisulfite sequencing was used to detect sperm DNA methylation. The results demonstrated that high paternal exposure to PM2.5 (ß = -211.31, 95% CI: (-386.37, -36.24)), PM10 (ß = -178.20, 95% CI: (-277.13, -79.27)), and NO2 (ß = -84.22, 95% CI: (-165.86, -2.57)) was negatively associated with offspring's birthweight, especially in boys. Additionally, an early exposure window of 15-69 days before fertilization was recognized to be the key exposure window, which increased the risk of low birth weight and small for gestational age. Furthermore, paternal co-exposure to six air pollutants contributed to lower birthweight (ß = -51.91, 95% CI: (-92.72, -11.10)) and shorter gestational age (ß = -1.72, 95% CI: (-3.26, -0.17)) and PM2.5 was the most weighted pollutant. Paternal air pollution exposure resulted in 10,328 differentially methylated regions and the IGF2R gene was the key gene involved in the epigenetic process. These differentially methylated genes were predominantly associated with protein binding, transcriptional regulation, and DNA templating. These findings indicate that spermatogenesis is a susceptible window during which paternal exposure to air pollution affects sperm DNA methylation and the birth outcomes of offspring.

Disentangling the age-related manner in the associations between gut microbiome and women's health: a multi-cohort microbiome study.

Women's health encompasses life-course healthcare, and mounting evidence emphasizes the pivotal contribution of gut microbiota. Therefore, understanding the temporal dynamics of gut microbiota and how age influences disease-gut microbiota associations is essential for improving women's health. By analyzing metagenomic data from 3625 healthy women, we revealed significant effects of age on gut microbiota and age-dependent patterns in microbial features, such as relative abundance, Shannon index, and microbial network properties. Additionally, declining trends in the predictive accuracy of gut microbiota for age groups were shown using iterative sub-sampling based random forest (ISSRF) model. Age-specific species markers were also identified, many of which were shared across age groups. To investigate the influence of age on disease-gut microbiota associations, metagenomic data from 681 women with various disease conditions and 491 matched healthy controls were collected. A substantial proportion of species markers for inflammatory bowel disease (IBD), type 2 diabetes (T2D), atherosclerotic cardiovascular disease (ACVD), and impaired glucose tolerance (IGT) differed in relative abundance across age groups, and were also age-specific species markers. Besides, the microbiota-based probabilities of IBD and ACVD were positively correlated with age. Furthermore, the age specificity of disease-gut microbiota associations was explored using the ISSRF model. Associations between IBD and gut microbiota were age-specific, with reduced stability of disease species markers in childhood and adolescence, possibly due to decrease in the effect size between patients and controls. Our findings provided valuable insights into promoting healthy aging and developing personalized healthcare strategies for women.

Association of maternal metals exposure, metabolites and birth outcomes in newborns: A prospective cohort study.

BACKGROUND: Maternal exposure to metals may pose a risk to the health of newborns, however, the underlying mechanisms remain ambiguous. Herein, we aimed to investigate the influence of metals exposure on birth outcomes and reveal the importance of metabolites in the exposure-outcomes association by using metabolomics methods. METHODS: In our study, 292 mother-pairs were included who were recruited from the affiliated hospitals of Nanjing Medical University between 2006 and 2011. We measured fifteen metals (mercury, lead, vanadium, arsenic, zinc, cadmium, rubidium, copper, cobalt, iron, molybdenum, strontium, thallium, magnesium and calcium) and metabolites in maternal second trimester serums by using inductively coupled plasma mass spectrometry and ultra-high performance liquid chromatography high resolution accurate mass spectrometry, respectively. A multi-step statistical analysis strategy including exposome-wide association study (ExWAS) model, variable selection models and multiple-exposure models were performed to systematically appraise the associations of individual and mixed metals exposure with birth outcomes. Furthermore, differential metabolites that associated with metals exposure and birth outcomes were identified using linear regression models. RESULTS: Metal's levels in maternal serums ranged from 0.05 µg/L to 1864.76 µg/L. In the ExWAS model, maternal exposure to arsenic was negatively associated with birth weight (ß = 188.83; 95% CI: -368.27, -9.39), while maternal mercury exposure showed a positive association (ß = 533.65; 95%CI: 179.40, 887.90) with birth weight. Moreover, each unit increase in mercury (1 ng/mL-log transformed) was associated with a 1.82 week-increase (95%CI: 0.85, 2.79) in gestational age. These findings were subsequently validated by variable selection models and multiple exposure models. Metabolomic analysis further revealed the significant role of 3-methyladenine in the relationship between arsenic exposure and birth weight. CONCLUSION: This study provides new epidemiological evidence indicating the associations of metals exposure and neonatal birth outcomes, and emphasizes the potential role of metabolite biomarkers and their importance in monitoring adverse birth outcomes.

Effect of short-term ambient air pollution exposure on early miscarriage and pregnancy hormones with critical window identification.

BACKGROUND: Pregnancy hormones are particularly important in early miscarriage, and some evidence suggests that exposure to air pollution is associated with pregnancy hormones and miscarriage. However, the effects of air pollution on pregnancy hormone-mediated miscarriages have not yet been investigated. METHODS: We collected air pollution exposure measurements and pregnancy hormone tests from the participants. Logistic regression models were used to investigate the association between air pollution and early miscarriages. A distributed lag nonlinear model (DLNM) was used to investigate non-linear and delayed associations and identify the crucial window. We performed mediation analysis to estimate the potential association that may exist between pregnancy hormone levels and early miscarriage. RESULTS: Short-term exposure to CO and SO2 was associated with early miscarriage. Lag 22-28 days of exposure to both CO and SO2 and lag 15-21 days of exposure to CO were significantly positively associated with early miscarriage, with an obvious exposure dose response. Serum progesterone concentration explained 36.79 % of the association between lag 15-28 days of CO exposure and early miscarriage. CONCLUSION: This study provides evidence for the association between short-term exposure to air pollution and early miscarriage, and provides clues for further exploration of biological mechanisms.

Maternal Exposure to Trace Elements, Toxic Metals, and Longitudinal Changes in Infancy Anthropometry and Growth Trajectories: A Prospective Cohort Study.

Exploration of stage-specific effects of maternal exposure to trace elements and toxic metals on infancy continuous growth and trajectories is critical for early-life health management. Within a Chinese prospective cohort in 2014-2015, a total of 919 mother-infant pairs were included, and the urinary levels of 17 elements including vanadium (V), chromium (Cr), manganese, iron, cobalt, nickel, copper, zinc, arsenic, molybdenum, palladium, cadmium, tin, gold, mercury, thallium, and lead in early (mean: 11.9 weeks), and late pregnancy (mean: 32.4 weeks) were assessed. Standardized anthropometric assessments of infants were conducted at 1, 3, 6, 8, and 12 months of age. A three-step longitudinal and high-dimensional data analysis procedure was carried out to estimate the impacts of exposome on dynamic growth. Early-pregnancy exposures to V and Cr were positively associated with repeated measurements of length-for-age z-scores (LAZ). Six trajectories were identified based on LAZ. Maternal single exposure to V and Cr as well as mixed exposure to trace elements in early pregnancy were associated with raised odds for the high-stable group. Our results suggested positive associations between maternal trace element exposome and infancy dynamic growth. V and Cr were the key elements and the early pregnancy might be the critical window.