Decoding 11-oxygenated androgen synthesis: insights from enzyme gene expression and LC-MS/MS quantification.

BACKGROUND: Adrenal-origin and peripheral tissue-transformed 11-oxygenated androgens are recognized as significant androgens. However, our current understanding of the synthesis of 11-oxygenated androgens, including the organs and cell types involved, remains limited. METHODS: We performed comprehensive analyses on an extensive dataset of normal human tissues, which included bulk RNA data from 30 tissues, single-cell RNA sequencing (scRNA) data from 16 tissues and proteomics data from 29 tissues, to characterize the expression profiles of enzyme-encoding genes. To validate the findings, immunohistochemical and liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques were employed. RESULTS: Our investigation revealed that the gene expression levels of the enzymes HSD11B2 and AKR1C3 were notably elevated in the kidney and intestines. Intriguingly, within these organs, we observed an increasing trend in enzyme expression with age in women, while a decreasing trend was apparent in men. scRNA analysis revealed that HSD11B2 was predominantly expressed in collecting duct principal cells in the kidney, while AKR1C3 was primarily expressed in the proximal tubules. Intriguingly, nearly all epithelial cells in the intestine expressed these key enzymes. Further analysis using LC-MS/MS revealed that the kidney exhibited the highest levels of 11-ketoandrostenedione (11KA4) and 11-ketotestosterone (11KT) among the seven tissues examined, and substantial synthesis of 11KA4 and 11KT was also observed in the intestine. Finally, we developed the TransMap website (http://gxmujyzmolab.cn:16245/TransMap/) to provide comprehensive visualization of all currently available transcriptome data. CONCLUSION: This study offers an overarching perspective on tracing the synthesis of 11-oxygenated androgens in peripheral tissues, thereby providing valuable insights into the potential role of these androgens in humans.

A biocompatible polydopamine platform for targeted delivery of nicotinamide mononucleotide and boosting NAD+ levels in the brain.

Nicotinamide mononucleotide (NMN), a precursor of the coenzyme nicotinamide adenine dinucleotide (NAD+), has gained wide attention as an anti-aging agent, which plays a significant role in intracellular redox reactions. However, its effectiveness is limited by easy metabolism in the liver and subsequent excretion as nicotinamide, resulting in low bioavailability, particularly in the brain. Additionally, the blood-brain barrier (BBB) further hinders NMN supply to the brain, compromising its potential anti-aging effects. Herein, we developed a biocompatible polydopamine (PDA) platform to deliver NMN for boosting NAD+ levels in the brain for the first time. The lactoferrin (Lf) ligand was covalently attached to the PDA spheres to improve BBB transport efficiency. The resultant PDA-based system, referred to as PDA-Lf-NMN, not only exhibited superior BBB penetration ability but also improved the utilization rate of brain NMN in elevating NAD+ levels compared to NMN alone for both young (3 months) and old (21 months) mice. Moreover, after the old mice were treated with low-dose PDA-Lf-NMN (8 mg kg-1 day-1), they exhibited improved spatial cognition. Importantly, these nanomedicines did not induce any cellular necrosis or apoptosis. It provides a promising avenue for delivering NMN specifically to the brain, boosting NAD+ levels for promoting longevity and treating brain aging-related diseases.

Green space modified the association between air pollutants and hypertension in China.

Evidence regarding the combined effects of green space and air pollutants on hypertension remains limited and complex. This study aims to investigate the varying effects of greenness under different air pollution levels in China, using data from the wave 2018 China Health and Retirement Longitudinal Study (CHARLS) involving 17 468 adults (aged ≥ 45 years). As a result, the prevalence rate of hypertension was 42.04%. Logistic regression analyses revealed the positive associations between air pollution concentrations at the city level and prevalent hypertension and the negative associations between NDVI and prevalent hypertension, all of which were more prominent in the populations of the eastern and rural regions. Notably, the negative effect of green space was greater at the lowest quartiles of each air pollutant (OR for PM2.5 quartiles = 0.724, 0.792, 0.740, and 0.931) . Improving air quality and greenness could potentially reduce hypertension risk, and minimizing air pollution might optimize the protective effects of greenness.

Effects of ambient air pollution on cause-specific hospitalizations in Wuhan during 2017-2019.

BACKGROUND: Few studies have focused on the associations between air pollutants and multiple organ system diseases in the entire hospitalized population. The present study aims to explore the short-term effects of six routinely monitored air pollutants on the broad causes of hospital admissions and estimate the resulting hospital admission burdens. METHODS: Daily hospital admission records from 2017 to 2019 were obtained from the Wuhan Information center of Health and Family Planning. Generalized additive models (GAMs) were employed to evaluate the effects of air pollutants on the percent increase in the cause-specific daily number of hospital admissions. Increased hospital admission numbers, days, and expenses were also estimated. RESULTS: A total of 2636,026 hospital admissions were identified. We found that both PM2.5 and PM10 increased the risk of hospital admissions for most disease categories. Short-term exposure to PM2.5 was positively associated with hospitalizations of several rarely studied disease categories, such as diseases of the eye and adnexa (2.83%, 95%CI: 0.96-4.73%, P < 0.01) and diseases of the musculoskeletal system and connective tissue (2.17%, 95% CI: 0.88-3.47%, P < 0.001). NO2 was observed to have a robust effect on diseases of the respiratory system (1.36%, 95%CI: 0.74-1.98%, P < 0.001). CO was significantly associated with hospital admissions for six disease categories. Furthermore, each 10-µg/m3 increase in PM2.5 was associated with an annual increase of 13,444 hospital admissions (95% CI: 6239-20,649), 124,344 admission days (95% CI: 57,705-190,983), and 166-million-yuan admission expenses (95% CI: 77-255). CONCLUSION: Our study suggested that particulate matter (PM) had a short-term effect on hospital admissions of most major disease categories and resulted in a considerable hospital admission burden. In addition, the health effects of NO2 and CO emissions require more attention in megacities.

Effects of green spaces on alleviating mortality attributable to PM2.5 in China.

Increasing research suggested that green spaces are associated with many health benefits, but evidence for the quantitative relationship between green spaces and mortality attributable to particulate matter with an aerodynamic diameter of 2.5 µm or less (PM2.5) is limited. We collected disease-specific mortality and PM2.5 data for a period of 4 years (2015-2018) along with green space data for an 8-year duration (2010-2017) in 31 provincial-level administrative regions of China. First, this study used the Integrated Exposure-Response model to estimate the mortality of four diseases attributable to PM2.5, including chronic obstructive pulmonary diseases (COPD), lung cancer (LC), ischemic heart disease (IHD), and cerebrovascular disease (CBVD). Then we performed linear regression and mixed-effects model to investigate the counteracting effect of green spaces on death caused by PM2.5 exposure. The differences in impacts among the Eastern, Central, and Western regions were explored using stratified analysis. The most significant results from linear regression analysis indicated that per 100 km2 of green spaces increase, there was a decreased total mortality (10-5) (COPD, LC, IHD, and CBVD) attributable to PM2.5 by - 4.012 [95% confidence interval (CI): - 5.535, - 2.488], while the reduction by mixed-linear regression analysis was - 2.702/105 (95% CI = - 3.645, - 1.759). Of all hysteresis analyses, the effect estimates (ß) at lag3 and lag4 were the largest. The effect of green spaces was more advantageous when targeting CBVD and the Eastern region. We found a negative correlation between green space exposure and mortality attributable to PM2.5, which can provide further support for city planners, government personnel, and others to build a healthier city and achieve national health goals.

Association between smoking and hypertension under different PM2.5 and green space exposure: A nationwide cross-sectional study.

Background: Smoking has been widely reported to have a significant relationship with hypertension, but the past description of this relationship has not been uniform. In addition, there has been a lack of research to discuss the impact of environmental exposure on the relationship between smoking and hypertension. Therefore, this study estimates the association between smoking and hypertension in middle aged and elderly people in China under different PM2.5 (fine particulate matter) concentrations and the green space exposure conditions. Methods: Individual sample data from the China Health and Retirement Longitudinal Study in 2018 and the long-term average exposure concentration of fine particles and green space exposure for all participants were used with a multilevel binary logistic mixed effects model. Adjustments were made for sociodemographic characteristics and other health behaviors including drinking, physical activity, and social activity. The normalized difference vegetation index (NDVI) and PM2.5 concentration stratification were assigned with the median of the population exposure concentration as the dividing line, and the dual environmental factor stratification was assigned in combination with the two types of environmental exposure. The analysis was also stratified using age groups. Results: A total of 10,600 participants over the age of 45 were included in the study. The effects of smoking on hypertension were diverse under different environmental exposure conditions. There was a significant relationship between smoking behavior and hypertension in the Low-NDVI group, and the effect value of this relationship was significantly different from that in the High-NDVI group. Furthermore, for respondents exposed to low green spaces and high PM2.5 environments at the same time (Low-NDVI/High-PM2.5 group), their smoking behavior may lead to an increase in the risk of hypertension. In addition, the risk of hypertension caused by smoking in the middle-aged (45-64) was significant under low green space exposure, but the effect difference between the different age groups was not significant. Conclusions: The relationship between smoking and hypertension was different under different environmental exposure conditions. Exposure to low green spaces may strengthen the association between smoking and hypertension risk. When participants were exposed to both low green spaces and high PM2.5 concentrations, the risk of hypertension caused by smoking was significantly higher than that of those who were exposed to high green spaces and low PM2.5 concentrations.

Association of NO2 with daily hospital admissions for mental disorders: Investigation of the modification effects of green spaces and long-term NO2 exposure.

Air pollution is a risk factor for increased hospital admissions due to mental disorders, while green spaces have been linked with better mental health. We linked daily hospital admission records from Wuhan's 74 municipal hospitals from 2017 to 2019 with modeled annual average NO2 concentrations and added data on the residential surrounding green spaces with 250 m and 500 m buffers based on the normalized difference vegetation index (NDVI) using a land use regression model (LUR). The conditional logistic regression model was used to estimate the acute effect of short-term NO2 exposure, and stratification analyses were applied to explore the modification effect of long-term NO2 exposure and green spaces by estimating the odds ratios in the single- and dual-environmental factor groups. A total of 42,705 hospital admissions for mental disorders were identified. Short-term exposure to NO2 was associated with an increased risk of hospital admission for mental disorders. A 10 µg/m3 increase in NO2 (lag01 day) was associated with an increase in hospital admissions of 2.86% (95% CI, 2.05-3.68) for the total mental disorders. Compared with patients in the "low-NDVI/low-NO2" group (ER = 2.27%, 95% CI, 0.27-4.31), patients in the "high-NDVI/low-NO2" group (ER = 1.93%, -0.10-3.99) showed a lower and insignificant increase in hospitalizations for the total mental disorders, while greenness had a slight moderating effect in the high-level long-term NO2 exposure areas. This study suggested that green spaces may moderate the acute effect of NO2 exposure for mental disorder hospitalizations, especially in low-level long-term NO2 exposure areas.

Roc, the G-domain of the Parkinson's disease-associated protein LRRK2.

Mutation in leucine-rich repeat (LRR) kinase 2 (LRRK2) is a common cause of Parkinson's disease (PD). Aberrant LRRK2 kinase activity is associated with disease pathogenesis and thus it is an attractive drug target for combating PD. Intense efforts in the past nearly two decades have focused on the development of small-molecule inhibitors of the kinase domain of LRRK2 and have identified potent kinase inhibitors. However, most LRRK2 kinase inhibitors have shown adverse effects; therefore, alternative-mechanism-based strategies are desperately needed. In this review, we discuss the new insights gleaned from recent cryoelectron microscope (cryo-EM) structures of LRRK2 towards understanding the mechanisms of actions of LRRK2 and explore the potential new therapeutic avenues.

Association Between Grip Strength and Cognitive Function in US Older Adults of NHANES 2011-2014.

BACKGROUND: The relationship between grip strength and cognitive function remains no consensus in the older adults. OBJECTIVE: To investigate the association of grip strength with cognitive function and cognitive performance in different domains. METHODS: Participants of the present cross-sectional study were from the National Health and Nutrition Examination Survey 2011-2014. Grip strength was measured by grip dynamometer, and combined handgrip strength was the sum of the largest reading from each hand. Four cognitive domains (immediate and delayed memory, language, and attention) were assessed by a set of neuropsychological tests. The subjective cognitive decline was determined via self-report. RESULTS: Among 2,618 participants, combined grip strength was positively associated with scores on global cognitive function and each cognitive domain after controlling for demographic characteristics, lifestyle factors, and history of disease. In addition, compared to those with grip strength < 46.7 kg, participants with grip strength≥75.3 kg had odds ratios of 0.36 (95% CI: 0.21 to 0.63) for poor global cognitive function, 0.66 (95% CI: 0.38 to 1.13) for poor immediate memory, 0.53 (95% CI: 0.30 to 0.93) for poor delayed memory, 0.48 (95% CI: 0.27 to 0.86) for poor language function, 0.20 (95% CI: 0.11 to 0.35) for poor attention, and 0.36 (95% CI: 0.18 to 0.73) for subjective cognitive decline in fully adjusted model. CONCLUSION: Older adults with higher grip strength were significantly associated with better performance on cognition function included global and various domains such as memory, language, attention, and subjective cognitive decline.

Short-term effects of air pollution on respiratory diseases among young children in Wuhan city, China.

BACKGROUND: The high risks for childhood respiratory diseases are associated with exposure to ambient air pollution. However, there are few studies that have explored the association between air pollution exposure and respiratory diseases among young children (particularly aged 0-2 years) based on the entire population in a megalopolis. METHODS: Daily hospital admission records were obtained from 54 municipal hospitals in Wuhan city, China. We included all children (aged 0-2 years) hospitalized with respiratory diseases between January 2017 and December 2018. Individual air pollution exposure assessment was used in Land Use Regression model and inverse distance weighted. Case-crossover design and conditional logistic regression models were adopted to estimate the hospitalization risk associated with air pollutants. RESULTS: We identified 62,425 hospitalizations due to respiratory diseases, of which 36,295 were pneumonia. Particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5) and nitrogen dioxide (NO2) were significantly associated with respiratory diseases and pneumonia. ORs of pneumonia were 1.0179 (95% CI 1.0097-1.0260) for PM2.5 and 1.0131 (95% CI 1.0042-1.0220) for NO2 at lag 0-7 days. Subgroup analysis suggested that NO2, Ozone (O3) and sulfur dioxide (SO2) only showed effects on pneumonia hospitalizations on male patients, but PM2.5 had effects on patients of both genders. Except O3, all pollutants were strongly associated with pneumonia in cold season. In addition, children who aged elder months and who were in central urban areas had a higher hospitalization risk. CONCLUSIONS: Air pollution is associated with higher hospitalization risk for respiratory diseases, especially pneumonia, among young children, and the risk is related to gender, month age, season and residential location.

PM2.5-Associated Hospitalization Risk of Cardiovascular Diseases in Wuhan: Cases Alleviated by Residential Greenness.

PM2.5, a type of particulate matter with an aerodynamic diameter of less than 2.5 µm, is associated with the occurrence of cardiovascular diseases (CVDs), while greenness seems to be associated with better cardiovascular health. We identified 499,336 CVD cases in Wuhan's 74 municipal hospitals between 2017 and 2019. A high-resolution PM2.5 model and a normalized difference vegetation index (NDVI) map were established to estimate individual exposures. The time-stratified case-crossover design and conditional logistic regression models were applied to explore the associations between PM2.5 and CVDs under different levels of environmental factors. Greenness could alleviate PM2.5-induced hospitalization risks of cardiovascular diseases. Compared with patients in the low-greenness group (ER = 0.99%; 95% CI: 0.71%, 1.28%), patients in the high-greenness group (ER = 0.45%; 95% CI: 0.13%, 0.77%) showed a lower increase in total CVD hospitalizations. After dividing the greenness into quartiles and adding long-term PM2.5 exposure as a control factor, no significant PM2.5-associated hospitalization risks of CVD were identified in the greenest areas (quartile 4), whether the long-term PM2.5 exposure level was high or low. Intriguingly, in the least green areas (quartile 1), the PM2.5-induced excess risk of CVD hospitalization was 0.58% (95% CI: 0.04%, 1.11%) in the long-term high-level PM2.5 exposure group, and increased to 1.61% (95% CI: 0.95%, 2.27%) in the long-term low-level PM2.5 exposure group. In the subgroup analysis, males and participants aged 55-64 years showed more significant increases in the PM2.5-induced risk of contracting CVDs with a reduction in greenness and fine particle exposure conditions. High residential greenness can greatly alleviate the PM2.5-induced risk of cardiovascular admission. Living in the areas with long-term low-level PM2.5 may make people more sensitive to short-term increases in PM2.5, leading to CVD hospitalization.

Trends in Mortality From Parkinson Disease in the United States, 1999-2019.

BACKGROUND AND OBJECTIVES: The mortality from Parkinson disease (PD) and its long-term trends in the United States in recent decades remains unknown. This study aimed to describe the trends in PD mortality in the United States from 1999 to 2019. METHODS: We used data from the National Vital Statistics System, a nationwide, population-based death registry, to determine national trends in PD mortality, overall and by age, sex, race/ethnicity, urban-rural classification, and geographic location. Analyses focused on the data from 479,059 deaths due to PD from 1999 to 2019. Joinpoint regression was performed to examine temporal trends in age-adjusted death rates. RESULTS: The age-adjusted mortality from PD increased from 5.4 (95% confidence interval [CI] 5.3-5.5) per 100,000 population in 1999 to 8.8 (95% CI, 8.7-8.9) per 100,000 population in 2019, with an average annual percent change of 2.4% (95% CI, 1.8%-3.0%). From 1999 to 2019, PD mortality increased significantly across all age groups, both sexes, various racial/ethnic groups, and different urban-rural classifications. The US states and District of Columbia with reported death rates all experienced an increase in PD mortality. Significant differences by sex and race/ethnicity were noted. Age-adjusted PD mortality rates were twice as high in men as in women and were greater in White individuals than those from other racial/ethnic groups. DISCUSSION: From 1999 to 2019, the mortality from PD in the United States has increased significantly. The increase was regardless of age, sex, race/ethnicity, urban-rural classification, and geographic location. A comprehensive evaluation of long-term trends in PD mortality is important for health care priority setting.

The Association between Preterm Birth and Ambient Air Pollution Exposure in Shiyan, China, 2015-2017.

Shortening of the gestational duration has been found associated with ambient air pollution exposure. However, the critical exposure windows of ambient air pollution for gestational duration remain inconsistent, and the association between ambient air pollution and early term births (ETB, 37 to 38 weeks) has rarely been studied relative to preterm births (PTB, 28-37 weeks). A time-series study was conducted in Shiyan, a medium-sized city in China. Birth information was collected from the Shiyan Maternity and Child Health Hospital, and 13,111 pregnant women who gave birth between 2015 and 2017 were included. Data of the concentrations of air pollutants, including PM10, PM2.5, NO2, and SO2 and meteorological data, were collected in the corresponding gestational period. The Cox regression analysis was performed to estimate the relationship between ambient air pollution exposure and the risk of preterm birth after controlling the confounders, including maternal age, education, Gravidity, parity, fetal gender, and delivery mode. Very preterm birth (VPTB, 28-32 weeks) as a subtype of PTB was also incorporated in this study. The risk of VPTB and ETB was positively associated with maternal ambient air pollution exposure, and the correlation of gaseous pollutants was stronger than particulate matter. With respect to exposure windows, the critical trimester of air pollutants for different adverse pregnancy outcomes was different. The exposure windows of PM10, PM2.5, and SO2 for ETB were found in the third trimester, with HRs (hazard ratios) of 1.06 (95%CI: 1.04, 1.09), 1.07 (95%CI: 1.04, 1.11), and 1.28 (95%CI: 1.20, 1.35), respectively. However, for NO2, the second and third trimesters exhibited similar results, the HRs reaching 1.10 (95%CI: 1.03, 6.17) and 1.09 (95%CI: 1.03,1.15), respectively. This study extends and strengthen the evidence for a significant correlation between the ambient air pollution exposure during pregnancy and the risk of not only PTB but, also, ETB. Moreover, our findings suggest that the exposure windows during pregnancy vary with different air pollutants and pregnancy outcomes.

Effect of ambient fine particulates (PM2.5) on hospital admissions for respiratory and cardiovascular diseases in Wuhan, China.

BACKGROUND: Positive associations between ambient PM2.5 and cardiorespiratory disease have been well demonstrated during the past decade. However, few studies have examined the adverse effects of PM2.5 based on an entire population of a megalopolis. In addition, most studies in China have used averaged data, which results in variations between monitoring and personal exposure values, creating an inherent and unavoidable type of measurement error. METHODS: This study was conducted in Wuhan, a megacity in central China with about 10.9 million people. Daily hospital admission records, from October 2016 to December 2018, were obtained from the Wuhan Information center of Health and Family Planning, which administrates all hospitals in Wuhan. Daily air pollution concentrations and weather variables in Wuhan during the study period were collected. We developed a land use regression model (LUR) to assess individual PM2.5 exposure. Time-stratified case-crossover design and conditional logistic regression models were adopted to estimate cardiorespiratory hospitalization risks associated with short-term exposure to PM2.5. We also conducted stratification analyses by age, sex, and season. RESULTS: A total of 2,806,115 hospital admissions records were collected during the study period, from which we identified 332,090 cardiovascular disease admissions and 159,365 respiratory disease admissions. Short-term exposure to PM2.5 was associated with an increased risk of a cardiorespiratory hospital admission. A 10 µg/m3 increase in PM2.5 (lag0-2 days) was associated with an increase in hospital admissions of 1.23% (95% CI 1.01-1.45%) and 1.95% (95% CI 1.63-2.27%) for cardiovascular and respiratory diseases, respectively. The elderly were at higher PM-induced risk. The associations appeared to be more evident in the cold season than in the warm season. CONCLUSIONS: This study contributes evidence of short-term effects of PM2.5 on cardiorespiratory hospital admissions, which may be helpful for air pollution control and disease prevention in Wuhan.

Characteristics of Sleep Structure Assessed by Objective Measurements in Patients With Amnestic Mild Cognitive Impairment: A Meta-Analysis.

Objectives: This study aims to explore the differences of sleep structure between patients with amnestic mild cognitive impairment (aMCI) and elderly people with normal cognition, which will help to provide evidence for the relationship between sleep disturbances and cognitive impairment. Methods: A systematic review and meta-analysis were conducted on the literature on sleep parameters obtained by polysomnography or actigraphy in patients with aMCI. The PubMed and EMBASE databases were searched up to April 2020. Inclusion and exclusion criteria were established according to evidence-based medicine methods, and data of all eligible studies were meta-analyzed using the Review Manager 5.3 software. Results: Among the 1,171 literature articles on sleep structure of patients with MCI, eight case-control studies met the inclusion criteria and were included in this meta-analysis. A total of 278 subjects were included, of which 103 were patients with aMCI and 175 were elderly people with normal cognition. The results showed that sleep efficiency (SE) and slow wave sleep (SWS) of patients with aMCI were significantly lower than those of healthy elderly people. Compared with the control group, the percentage of stage 1 of non-rapid eye movement (N1%) in the aMCI patients group increased, and the percentage of stage 2 of non-rapid eye movement (N2%) decreased. Conclusions: Patients with aMCI may experience more severe sleep disturbances than normal cognitive elderly people. There were specific changes, especially in SE and SWS, in the sleep structure of patients with aMCI when compared to those with normal cognition.

Maternal PM2.5 exposure triggers preterm birth: a cross-sectional study in Wuhan, China.

Background: Most of the studies regarding air pollution and preterm birth (PTB) in highly polluted areas have estimated the exposure level based on fixed-site monitoring. However, exposure assessment methods relying on monitors have the potential to cause exposure misclassification due to a lack of spatial variation. In this study, we utilized a land use regression (LUR) model to assess individual exposure, and explored the association between PM2.5 exposure during each time window and the risk of preterm birth in Wuhan city, China. Methods: Information on 2101 singleton births, which were ≥ 20 weeks of gestation and born between November 1, 2013 and May 31, 2014; between January 1, 2015 and August 31, 2015, was obtained from the Obstetrics Department in one 3A hospital in Wuhan. Air quality index (AQI) data were accessed from the Wuhan Environmental Protection Bureau website. Individual exposure during pregnancy was assessed by LUR models and Kriging interpolation. Logistic regression analyses were conducted to determine the association between women exposure to PM2.5 and the risk of different subtypes of PTB. Results: During the study period, the average individual exposure concentration of PM2.5 during the entire pregnancy was 84.54 µg/m3. A 10 µg/m3 increase of PM2.5 exposure in the first trimester (OR: 1.169; 95% CI: 1.077, 1.262), the second trimester (OR: 1.056; 95% CI: 1.015, 1.097), the third trimester (OR: 1.052; 95% CI: 1.002, 1.101), and the entire pregnancy (OR: 1.263; 95% CI: 1.158, 1.368) was significantly associated with an increased risk of PTB. For the PTB subgroup, the hazard of PM2.5 exposure during pregnancy was stronger for very preterm births (VPTB) than moderate preterm births (MPTB). The first trimester was the most susceptible exposure window. Moreover, women who had less than 9 years of education or who conceived during the cold season tended to be more susceptible to the PM2.5 exposure during pregnancy. Conclusions: Maternal exposure to PM2.5 increased the risk of PTB, and this risk was stronger for VPTB than for MPTB, especially during the first trimester.

The association between ambient temperature and sperm quality in Wuhan, China.

BACKGROUND: Few epidemiological investigations have focused on the influence of environmental temperature on human sperm quality. Here, we evaluated the potential association between ambient temperature and human sperm quality in Wuhan, China, and examined the interactive effect of particulate matter (PM2.5) and temperature. METHODS: 1780 males who had been living in Wuhan for no less than three months and received semen analysis at the Department of Reproductive Medicine in Renmin Hospital of Wuhan University between April 8, 2013 and June 30, 2015 were recruited. Daily mean meteorological data and air pollution data (PM2.5, O3 and NO2) in Wuhan between 2013 and 2015 were collected. A generalized linear model was used to explore the associations between ambient temperature and sperm quality (including sperm concentration, percentage of normal sperm morphology, and progressive motility) at 0-9, 10-14, 15-69, 70-90, and 0-90 days before semen examination, and the interaction between temperature and PM2.5. RESULTS: The associations between ambient temperature and sperm quality were an inverted U-shape at five exposure windows, except for a lag of 0-9 days for sperm concentration. A 1 °C increase in ambient temperature above the thresholds was associated with a 2.038 (1.292 ~ 2.783), 1.814 (1.217 ~ 2.411), 1.458 (1.138 ~ 1.777), 0.934(0.617 ~ 1.251) and 1.604 (1.258 ~ 1.951) decrease in the percentage of normal sperm morphology at lag 0-9, lag 10-14, lag 15-69, lag 70-90, and lag 0-90 days, respectively. The interaction p-values of PM2.5 and temperature were mostly less than 0.05 at five exposure windows. When ambient temperature exposure levels were above the thresholds, a 0.979 (0.659-1.299) and 3.559 (0.251 ~ 6.867) decrease in percentage of normal sperm morphology per 1 °C increase in temperature at lag 0-90 days was observed in the PM2.5 ≤ P50 group and PM2.5 > P50 group, respectively. CONCLUSIONS: Our results indicate that exposure to ambient temperature has a threshold effect on sperm quality, and PM2.5 enhances the effect of temperature on sperm quality when temperatures are above the threshold.

Association between ambient air pollution exposure and infants small for gestational age in Huangshi, China: a cross-sectional study.

Small for gestational age (SGA) is defined as intrauterine growth retardation or small sample, referring to the 10th percentile of birth weight lower or two standard deviations less than the average weight at the same gestational age. SGA infants bring great economic and psychological burdens to families and society. The association between exposure to air pollution and SGA in underdeveloped cities with poor air quality remains unclear. Thus, this study is conducted to estimate the effects of maternal exposure to air pollutants on SGA numbers. Birth information was collected from the Huangshi Maternity and Children's Health Hospital from January 1st to December 31st in 2017. Data of pregnancy exposure were accessed using stationary monitors. These data included particulate matter less than or equal to 10 µm in aerodynamic diameter (PM10), particulate matter less than or equal to 2.5 µm in aerodynamic diameter (PM2.5), nitrogen dioxide (NO2), and sulfur dioxide (SO2). Multivariate logistic regression models were performed to estimate the association between ambient air pollution and the risk of SGA during different exposure windows. It was found that a 1 µg/m3 increase in air pollution concentrations during the entire pregnancy was associated with a higher risk of SGA, with an adjusted odds ratio (OR) and 95% confidence interval (CI) of 1.055 (1.035-1.076), 1.084 (1.053-1.116), 1.000 (0.953-1.049), and 1.051 (0.968-1.141) for PM10, PM2.5, NO2, and SO2, respectively. Thus, it is suggested that exposure to air pollution is associated with an increased risk of SGA. The effects of PM10 and PM2.5 were more stable than NO2 and SO2.

Short-Term Effects of Carbonaceous Components in PM2.5 on Pulmonary Function: A Panel Study of 37 Chinese Healthy Adults.

OBJECTIVES: To explore the health effects of indoor/outdoor carbonaceous compositions in PM2.5 on pulmonary function among healthy students living in the local university campus. METHODS: Daily peak expiratory flow (PEF) and forced expiratory volume in 1 second (FEV1) were measured among 37 healthy students in the morning and evening for four two-week periods. Concurrent concentrations of indoor and outdoor PM2.5 (particulate matter with an aerodynamic diameter ≤ 2.5µm), carbonaceous components in PM2.5, ambient temperature, and relative humidity in the study area were also obtained. Mixed-effects model was applied to evaluate the associations between carbonaceous components and lung function. Different lags for the carbonaceous components were investigated. RESULTS: In single-pollutant model, a 10 µg/m3 increase of indoor and outdoor EC (elemental carbon) associated with -3.93 (95%CI: -6.89, -0.97) L/min and -3.21 (95%CI: -5.67, -0.75) L/min change in evening PEF at lag 0 day, respectively. Also, a 10 µg/m3 increase of indoor and outdoor POC (primary organic carbon) concentration was significantly associated with -5.82 (95%CI: -10.82, -0.81) L/min and -7.32 (95%CI: -12.93, -1.71) L/min change of evening PEF at lag 0 day. After adjusting total mass of PM2.5, indoor EC consistently had a significant adverse impact on evening PEF and FEV1 at lag3 day and a cumulative effect at lag0-3 day. CONCLUSIONS: This study suggests that carbonaceous components in PM2.5 indeed have impacts on pulmonary function among healthy young adults especially on evening PEF. Thus, the local mitigation strategies on pollution are needed.

Parkinson's disease-associated mutations in the GTPase domain of LRRK2 impair its nucleotide-dependent conformational dynamics.

Mutation in leucine-rich repeat kinase 2 (LRRK2) is a common cause of familial Parkinson's disease (PD). Recently, we showed that a disease-associated mutation R1441H rendered the GTPase domain of LRRK2 catalytically less active and thereby trapping it in a more persistently "on" conformation. However, the mechanism involved and characteristics of this on conformation remained unknown. Here, we report that the Ras of complex protein (ROC) domain of LRRK2 exists in a dynamic dimer-monomer equilibrium that is oppositely driven by GDP and GTP binding. We also observed that the PD-associated mutations at residue 1441 impair this dynamic and shift the conformation of ROC to a GTP-bound-like monomeric conformation. Moreover, we show that residue Arg-1441 is critical for regulating the conformational dynamics of ROC. In summary, our results reveal that the PD-associated substitutions at Arg-1441 of LRRK2 alter monomer-dimer dynamics and thereby trap its GTPase domain in an activated state.