Exploring nature's battlefield: organismic interactions in the discovery of bioactive natural products.

Covering: up to March 2024.Microbial natural products have historically been a cornerstone for the discovery of therapeutic agents. Advanced (meta)genome sequencing technologies have revealed that microbes harbor far greater biosynthetic capabilities than previously anticipated. However, despite the application of CRISPR/Cas-based gene editing and high-throughput technologies to activate silent biosynthetic gene clusters, the rapid identification of new natural products has not led to a proportional increase in the discovery rate of lead compounds or drugs. A crucial issue in this gap may be insufficient knowledge about the inherent biological and physiological functions of microbial natural products. Addressing this gap necessitates recognizing that the generation of functional natural products is deeply rooted in the interactions between the producing microbes and other (micro)organisms within their ecological contexts, an understanding that is essential for harnessing their potential therapeutic benefits. In this review, we highlight the discovery of functional microbial natural products from diverse niches, including those associated with humans, nematodes, insects, fungi, protozoa, plants, and marine animals. Many of these findings result from an organismic-interaction-guided strategy using multi-omic approaches. The current importance of this topic lies in its potential to advance drug discovery in an era marked by increasing antimicrobial resistance.

An Azulene-Based Crystalline Porous Covalent Organic Framework for Efficient Photothermal Conversion.

The designed synthesis of a crystalline azulene-based covalent organic framework (COF-Azu-TP) is presented and its photothermal property is investigated. Azulene, a distinctive 5-7 fused ring non-benzenoid aromatic compound with a large intramolecular dipole moment and unique photophysical characteristics, is introduced as the key feature in COF-Azu-TP. The incorporation of azulene moiety imparts COF-Azu-TP with broad-spectrum light absorption capability and interlayer dipole interactions, which makes COF-Azu-TP a highly efficient photothermal conversion material. Its polyurethane (PU) composite exhibits a solar-to-vapor conversion efficiency (97.2%) and displays a water evaporation rate (1.43 kg m-2 h-1) under one sun irradiation, even at a very low dosage of COF-Azu-TP (2.2 wt%). Furthermore, COF-Azu-TP is utilized as a filler in a polylactic acid (PLA)/polycaprolactone (PCL) composited shape memory material, enabling rapid shape recovery under laser stimulation. A comparison study with a naphthalene-based COF isomer further emphasizes the crucial role of azulene in enhancing photothermal conversion efficiency. This study demonstrates the significance of incorporating specific building blocks into COFs for the development of functional porous materials with enhanced properties, paving the way for future applications in diverse fields.

Sweetened beverages and atrial fibrillation in people with prediabetes or diabetes.

AIM: To assess the association of intake of sugar-sweetened beverages (SSBs), artificially sweetened beverages (ASBs) and natural juices (NJs) with new-onset atrial fibrillation (AF) in people with prediabetes or diabetes. METHODS: A total of 31 433 participants with prediabetes and diabetes from the UK Biobank were included. Information on the intake of SSBs, ASBs and NJs was accessed by 24-hour dietary recalls from 2009 to 2012. The study outcome was new-onset AF. RESULTS: During a median follow-up of 12.0 years, 2470 (7.9%) AF cases were documented. Both the intake of SSBs (per 1 unit/day increment; adjusted hazard ratio [HR] = 1.11; 95% confidence interval [CI]: 1.04-1.18) and ASBs (per 1 unit/day increment; adjusted HR = 1.08; 95% CI: 1.02-1.14) were linearly and positively associated with new-onset AF, while NJ intake was not significantly associated with new-onset AF (per 1 unit/day increment; adjusted HR = 1.00; 95% CI: 0.93-1.08). Accordingly, compared with non-consumers, participants who consumed more than one unit per day of SSBs (adjusted HR = 1.30; 95% CI: 1.11-1.53) or ASBs (adjusted HR = 1.21; 95% CI:1.05-1.40) had an increased risk of AF. Substituting 1 unit/day of NJs for SSBs was associated with a 9% (adjusted HR = 0.91; 95% CI: 0.83-0.99) lower risk of new-onset AF, while replacing SSBs with ASBs was not significantly associated with new-onset AF (adjusted HR = 0.97; 95% CI: 0.89-1.06). CONCLUSIONS: Both the intake of SSBs and ASBs were linearly and positively associated with new-onset AF, while NJ intake did not show a significant association with AF in people with prediabetes or diabetes. Replacing an equivalent amount of SSB intake with NJs, but not ASBs, was associated with a lower risk of AF.

Base-Promoted Nucleophilic Phosphorylation of Benzyl Fluorides via C(sp3)-F Cleavage.

Herein, a transition-metal-free phosphorylation of benzyl fluorides with P(O)-H compounds is disclosed. In the presence of tBuOK, various benzyl fluorides react with P(O)-H compounds to produce the corresponding benzyl phosphine oxides, phosphinates, and phosphonates in good to high yields. This base-promoted phosphorylation reaction offers a facile and general strategy for the construction of a C(sp3)-P bond.

Visible Light-Induced, Nickel-Catalyzed Late-Stage 4-Alkylation of Hantzsch Esters with Alkyl Bromide.

Herein, visible light-induced, nickel-catalyzed direct functionalization of the Hantzsch esters (HEs) with readily accessible alkyl bromides has been successfully achieved by taking advantage of HE as the reductant and substrate through an aromatization-dearomatization process. In this strategy, the single electron reduction of alkyl bromides by reactive Ni(I) species is essential for the success of this late-stage transformation. A wide range of 4-alkyl-1,4-dihydropyridines were rapidly assembled in moderate to good yields under mild conditions, rendering this photoinduced approach attractive for synthetic and medicinal chemistry.

Amine-Borane-Mediated, Nickel/Photoredox-Catalyzed Cross-Electrophile Coupling between Alkyl and Aryl Bromides.

Nickel/photoredox catalysis has emerged as a powerful platform for exploring nontraditional and challenging cross-couplings. Herein, a metallaphotoredox catalytic protocol has been developed on the basis of a tertiary amine-ligated boryl radical-induced halogen atom transfer process under blue-light irradiation. A wide variety of aryl and heteroaryl bromides featuring different functional groups and pharmaceutical moieties were facilely coupled to rapidly install C(sp3)-enriched aromatic scaffolds. The compatibility of Lewis base-ligated borane with nickel catalysis was well exemplified to extend the chemical space for Ni-catalyzed cross-electrophile coupling.

Association of accelerometer-derived "weekend warrior" moderate to vigorous physical activity, chronic kidney disease and acute kidney injury.

OBJECTIVE: To examine the relationship between an accelerometer-derived "weekend warrior" pattern, characterized by achieving the most moderate to vigorous physical activity (MVPA) over 1-2 days, as opposed to more evenly distributed patterns, with risk of chronic kidney disease (CKD) and acute kidney injury (AKI). METHODS: 77,977 participants without prior kidney diseases and with usable accelerometer data (collected between 2013 and 2015) were included from the UK Biobank. Three physical activity patterns were compared: active weekend warrior pattern (achieving ≥150 min MVPA per week and accumulating ≥50 % of total MVPA in 1-2 days), active regular pattern (achieving ≥150 min MVPA but not meeting active weekend warrior criteria per week), and inactive pattern (<150 min MVPA per week). The study outcomes included incident CKD and AKI, ascertained through self-report data and data linkage with primary care, hospital admissions, and death registry records. RESULTS: During a median follow-up of 6.8 years, 1324 participants developed CKD and 1515 developed AKI. In multivariable-adjusted models, when compared with inactive participants, individuals with active weekend warrior pattern (CKD: hazard ratio [HR], 0.79, 95 % confidence interval [CI], 0.69-0.89; AKI: HR, 0.70, 95 %CI, 0.62-0.79) and those with active regular pattern (CKD: HR, 0.81, 95 %CI, 0.69-0.95; AKI: HR, 0.79, 95 %CI, 0.68-0.91) exhibited a similar and significantly lower risk of incident CKD and AKI. Similar findings were observed at the median threshold of ≥230.4 min of MVPA per week. CONCLUSION: Concentrated MVPA within 1 to 2 days is as effective as distributed ones in decreasing the risk of renal outcomes.

Interaction between Extreme Temperature Events and Fine Particulate Matter on Cardiometabolic Multimorbidity: Evidence from Four National Cohort Studies.

Accumulating evidence linked extreme temperature events (ETEs) and fine particulate matter (PM2.5) to cardiometabolic multimorbidity (CMM); however, it remained unknown if and how ETEs and PM2.5 interact to trigger CMM occurrence. Merging four Chinese national cohorts with 64,140 free-CMM adults, we provided strong evidence among ETEs, PM2.5 exposure, and CMM occurrence. Performing Cox hazards regression models along with additive interaction analyses, we found that the hazards ratio (HRs) of CMM occurrence associated with heatwave and cold spell were 1.006-1.019 and 1.063-1.091, respectively. Each 10 µg/m3 increment of PM2.5 concentration was associated with 17.9% (95% confidence interval: 13.9-22.0%) increased risk of CMM. Similar adverse effects were also found among PM2.5 constituents of nitrate, organic matter, sulfate, ammonium, and black carbon. We observed a synergetic interaction of heatwave and PM2.5 pollution on CMM occurrence with relative excess risk due to the interaction of 0.999 (0.663-1.334). Our study provides novel evidence that both ETEs and PM2.5 exposure were positively associated with CMM occurrence, and the heatwave interacts synergistically with PM2.5 to trigger CMM.

Association between community walkability and hypertension: Evidence from the Wuhan Chronic Disease Cohort Study.

While community walkability is recognized as a key environmental factor for health status, evidence linking it specifically to hypertension is rather limited. To fill the knowledge gap, we concluded a cross-sectional study among 6421 eligible participants from the Wuhan Chronic Disease Cohort. A well-developed algorithm was performed to evaluate community walkability across Wuhan, quantified as Walk Score. We then calculated each participant residential Walk Score using the geographic information system. The logistic and linear regression models were conducted to determine the relationship between walkability, hypertension and blood pressure, respectively. We further performed the mediation analysis to explore potential mechanisms. After adjusting for extra confounders, we observed a higher community walk score was associated with a lower hypertension risk (OR = 0.73; 95% CI: 0.63, 0.84), a lower systolic blood pressure (ß = -3.152 mmHg; 95% CI: -4.25, -2.05), a lower diastolic blood pressure (ß = -2.237 mmHg; 95% CI: -2.95, -2.53) and a lower mean arterial pressure (ß = -2.976 mmHg; 95% CI: -3.75, -2.20). The effect of community walkability on hypertension was partially mediated by body fat rate. Our study indicates a positive correlation between high walkability and a reduced odds of hypertension in China. This highlights the potential role of urban design in hypertension prevention, emphasizes the need for walkability-focused planning strategies to foster healthier communities, and guides future interventions and research to mitigate hypertension.

Inverse association between lung function and nonalcoholic fatty liver disease: An observational and mendelian randomization study.

BACKGROUND AND AIM: The association between lung function with non-alcoholic fatty liver disease (NAFLD) in the general population remains unknown. We aimed to examine the association between lung function and NAFLD among the general population in an observational and Mendelian randomization (MR) study. METHODS AND RESULTS: 340, 253 participants without prior liver diseases were included from the UK Biobank. Of these, 30,397 participants had liver proton density fat fraction (PDFF) measurements by magnetic resonance image (MRI). Lung function parameters included forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC). The primary outcome was the presence of NAFLD, defined as a PDFF greater than 5.5%. The secondary outcome included incident severe NAFLD and severe liver diseases (including liver cirrhosis, liver failure, hepatocellular carcinoma and liver-related death), defined by the International Classification of Disease codes with different data sources. During a media follow-up duration of 9.3 years, 7335 (24.1%) the presence of NAFLD cases were documented. There was an inverse association of FEV1 (% predicted) (Per SD increment, adjusted OR = 0.91, 95%CI: 0.88-0.94) and FVC (% predicted) (Per SD increment, adjusted OR = 0.90, 95%CI: 0.87-0.92) with the presence of NAFLD. Similar results were found for incident severe NAFLD, severe liver disease, liver cirrhosis, liver failure and liver-related death. MR analyses showed that the genetically predicted FEV1 (adjusted OR = 0.63, 95%CI: 0.46-0.87) and FVC (adjusted OR = 0.69, 95%CI: 0.51-0.95) were both inversely associated with the presence of NAFLD. CONCLUSIONS: There was an inverse causal relationship between lung function and NAFLD in the general population.

Cohort profile: China undergraduate cohort for environmental health study.

The China Undergraduate Cohort (CUC) is an ambispective cohort study with its major purpose to better understand the effects of lifetime environmental exposures on health outcomes. We recruited 5322 college students with an average age of 18.3 ± 0.7 years in China from August 23, 2019 to October 28, 2019. Follow-up surveys were conducted annually. The dataset comprises individual demographic data (e.g. age, sex, height, weight, birth date, race, home address, annual family income, contact information), health-related behavior data (smoking status, smoking cessation, passive smoking exposure, drinking habit, physical activity, dietary status), lifestyle data (physical exercise, dietary habit, length of time spent outdoors), disease history (respiratory disease history, cardiovascular disease history, urinary system disease history, etc.), mental health status data (sleep quality, self-reported stress, anxiety and depression symptoms), lung function and blood samples data. Preliminary results from our cohort have found the association between air pollution, summer heat and mercury exposure and lung function among young adults in China.

Ambient ozone pollution impairs glucose homeostasis and contributes to renal function decline: Population-based evidence.

Particulate matter pollution could increase the risk of kidney disease, while evidence for ozone exposure is less well-established. Here, we aimed to evaluate the effect of ozone pollution on renal function and explore mechanisms. We first conducted a cross-sectional study based on Wuhan Chronic Disease Cohort Study baseline information. We recruited 2699 eligible participants, estimated their residential ozone concentrations, collected fasting peripheral blood samples for biochemical analysis and calculated the estimated glomerular filtration rate (eGFR). The linear regression model was applied to evaluate the long-term association between ozone pollution and eGFR. Then, we recruited another 70 volunteers as a panel with 8 rounds follow-up visits. We calculated the eGFR and measured fasting blood glucose and lipid levels. The linear mixed-effect model along with mediation analysis were performed to confirm the short-term association and explore potential mechanisms, respectively. For the long-term association, a 10.95 µg/m3 increment of 3-year ozone exposure was associated with 2.96 mL/min/1.73 m2 decrease in eGFR (95%CI: -4.85, -1.06). Furthermore, the drinkers exhibited a pronounced declination of eGFR (-7.46 mL/min/1.73 m2, 95%CI: -11.84, -3.08) compared to non-drinkers in relation to ozone exposure. Additionally, a 19.02 µg/m3 increase in 3-day ozone concentrations was related to 2.51 mL/min/1.73 m2 decrease in eGFR (95%CI: -3.78, -1.26). Hyperglycemia and insulin resistance mediated 12.2% and 16.5% of the aforementioned association, respectively. Our findings indicated that higher ozone pollution could affect renal function, and the hyperglycemia and insulin resistance linked to ozone might be the underlying mechanisms.

Mechanism Behind the Programmed Biosynthesis of Heterotrimeric Fungal Depside Thielavin A.

Thielavin A (1) is a fungal depside composed of one 3-methylorsellinic acid and two 3,5-dimethylorsellinic acid units. It displays diverse biological activities. However, the mechanism underlying the assembly of the heterotrimeric structure of 1 remains to be clarified. In this study, we identified the polyketide synthase (PKS) involved in the biosynthesis of 1. This PKS, designated as ThiA, possesses an unusual domain organization with the C-methyltransferase (MT) domain situated at the C-terminus following the thioesterase (TE) domain. Our findings indicated that the TE domain is solely responsible for two rounds of ester bond formation, along with subsequent chain hydrolysis. We identified a plausible mechanism for TE-catalyzed reactions and obtained insights into how a single PKS can selectively yield a specific heterotrimeric product. In particular, the tandem acyl carrier protein domains of ThiA are critical for programmed methylation by the MT domain. Overall, this study highlighted the occurrence of highly optimized domain-domain communication within ThiA for the selective synthesis of 1, which can advance our understanding of the programming rules of fungal PKSs.

Ketoreductase Domain-Catalyzed Polyketide Chain Release in Fungal Alkyl Salicylaldehyde Biosynthesis.

Alkyl salicylaldehyde derivatives are polyketide natural products, which are widely distributed in fungi and exhibit great structural diversity. Their biosynthetic mechanisms have recently been intensively studied; however, how the polyketide synthases (PKSs) involved in the fungal alkyl salicylaldehyde biosyntheses release their products remained elusive. In this study, we discovered an orphan biosynthetic gene cluster of salicylaldehyde derivatives in the fungus Stachybotrys sp. g12. Intriguingly, the highly reducing PKS StrA, encoded by the gene cluster, performs a reductive polyketide chain release, although it lacks a C-terminal reductase domain, which is typically required for such a reductive release. Our study revealed that the chain release is achieved by the ketoreductase (KR) domain of StrA, which also conducts cannonical ß-keto reductions during polyketide chain elongation. Furthermore, we found that the cupin domain-containing protein StrC plays a critical role in the aromatization reaction. Collectively, we have provided an unprecedented example of a KR domain-catalyzed polyketide chain release and a clearer image of how the salicylaldehyde scaffold is generated in fungi.

Integrated analysis of intratumoral biomarker and tumor-associated macrophage to improve the prognosis prediction in cancer patients.

BACKGROUND: The lack of effective and accurate predictive indicators remains a major bottleneck for the improvement of the prognosis of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Hepatitis B virus X (HBx) has been widely suggested as a critical pathogenic protein for HBV-driven liver carcinogenesis, while tumor-associated macrophage (TAM) infiltration is also closely related to the tumorigenesis and progression of HCC. However, few studies have determined whether combining HBx expression with TAM populations could increase the accuracy of prognostic prediction for HBV-related HCC. METHODS: The study cohort enrolling 251 patients with HBV-related HCC was randomly split into a training and a validation group (ratio 1:1). The expression levels of HBx and TAM marker CD68 in HCC samples were detected by immunohistochemistry. Kaplan-Meier curves, Cox regression and Harrell's concordance index (C-index) analysis were conducted to evaluate the prognostic significance of these indicators alone or in combination. RESULTS: The expression level of HBx was strongly correlated with CD68+ TAM infiltration in HCC tissues. Elevated HBx or CD68 expression indicated poorer overall survival (OS) and progression-free survival (PFS) after hepatectomy, and both of them were independent risk factors for postoperative survival. Meanwhile, patients with both high HBx and CD68 levels had worst clinical outcomes. Moreover, integrating HBx and CD68 expression with clinical indicators (tumor size and micro-vascular invasion) showed the best prognostic potential with highest C-index value for survival predictivity, and this proposed model also performed better than several conventional classifications of HCC. CONCLUSION: Combining the expression of intratumoral HBx, CD68+ TAM population and clinical variables could enable better prognostication for HBV-related HCC after hepatectomy, thus providing novel insights into developing more effective clinical prediction model based on both molecular phenotypes and tumor-immune microenvironment.

Photocatalyzed Defluorinative Dichloromethylation of α-CF3 Alkenes Using CHCl3 as the Radical Source.

A visible-light-induced defluorinative dichloromethylation of α-CF3 alkenes was developed with cheap and readily accessible chloroform simultaneously as a dichloromethylation reagent and reaction medium, leading to the facile preparation of new polyhalogenated scaffolds. Notably, the change from CHCl3 to CDCl3 offers a straightforward pathway for accessing the deuterated analogues with excellent degrees of D incorporation. Mechanistic studies suggested the reaction underwent a radical addition of the dichloromethyl radical with alkenes, followed by sequential single-electron transfer and defluorination. This protocol features mild conditions, easy operation, facile scalability, and high efficiency, allowing convenient access to dichloronated gem-difluoroalkenes.

Inverse association of glucosamine use and risk of new-onset kidney stones in UK adults with less sedentary time.

OBJECTIVE: To assess the association of different sedentary behaviors and glucosamine use with the risk of kidney stones and examine the modification of genetic risk of kidney stones on this association. METHODS: 473,225 participants free of kidney stones at baseline from the UK Biobank were included. Total sedentary time was calculated as the sum of the duration of TV-watching, driving, and non-occupational computer using. The primary outcome was new-onset kidney stones. RESULTS: During a median follow-up of 12.0 years, 5528 cases of kidney stones were documented. All major sedentary behaviors and total sedentary time were significantly positively related to the risk of kidney stones (All P for trend<0.05). Participants with total sedentary time ≥ 3.5 h/day had a significantly higher risk of new-onset kidney stones (vs. <3.5 h/day [tertile 1]; HR, 1.18; 95%CI,1.10-1.27). Compared with non-users, participants who regularly used glucosamine had a significantly lower risk of new-onset kidney stones in those with total sedentary time < 3.5 h/day (HR, 0.72; 95%CI,0.59-0.86), but not in those with total sedentary time ≥ 3.5 h/day (HR, 0.99; 95%CI,0.91-1.08; P-interaction = 0.001). Among participants with total sedentary time < 3.5 h/day, there was a dose-response relationship of glucosamine use with new-onset kidney stones (P for trend<0.001). Genetic risks of kidney stones did not significantly modify the association. CONCLUSIONS: TV-watching, driving and non-occupational computer using were all positively associated with the risk of new-onset kidney stones. Glucosamine use was associated with a lower risk of new-onset kidney stones in participants with total sedentary time < 3.5 h/day, following a dose-response relationship.

Associations of fine particulate matter and its metal constituents with blood pressure: A panel study during the seventh World Military Games.

Evidence is needed to elucidate the association of blood pressure (BP) changes with metal constituents in fine particulate matter (PM2.5). Therefore, we designed a longitudinal panel study enrolling 70 healthy students from Wuhan University in the context of the seventh World Military Games (the 7th WMG) from September 2019 to January 2020. A total of eight visits were conducted before, during, and after the 7th WMG. During every visit, each participant was asked to carry a personal PM2.5 monitor to measure hourly PM2.5 levels for three consecutive days. Questionnaire investigation and physical examination were completed on the fourth day. We analyzed ten metal constituents of ambient PM2.5 collected from the fixed station, and blood pressure was recorded during each visit. The linear mixed-effects models were performed to evaluate associations of metal constituents and blood pressure measurements. We observed a dramatic variation of PM2.5 concentration ranging from 7.38 to 132.04 µg/m3. A 10 µg/m3 increment of PM2.5 was associated with an increase of 0.64 mmHg (95% CI: 0.44, 0.84) in systolic BP (SBP), 0.40 mmHg (0.26, 0.54) in diastolic BP (DBP), 0.31 mmHg (0.15, 0.47) in pulse pressure (PP) and 0.44 mmHg (0.26, 0.62) in mean artery pressure (MAP), respectively. For metal constituents in PM2.5, robust positive associations were observed between BP and selenium, manganese, arsenic, cadmium, and thallium. For example, for an IQR (0.93 ng/m3) increment of selenium, SBP and MAP elevated by 0.98 mmHg (0.09, 1.87) and 0.71 mmHg (0.03, 1.39), respectively. Aluminum was found to be robustly associated with decreased SBP, DBP, and MAP. The study indicated that exposure to PM2.5 total mass and metal constituents including selenium, manganese, arsenic, cadmium, and thallium were associated with the elevated BP.

Independent and interactive associations between greenness and ambient pollutants on novel glycolipid metabolism biomarkers: A national repeated measurement study.

This study aims to investigate the independent and interactive effects of greenness and ambient pollutants on novel glycolipid metabolism biomarkers. A repeated national cohort study was conducted among 5085 adults from 150 counties/districts across China, with levels of novel glycolipid metabolism biomarkers of TyG index, TG/HDL-c, TC/HDL-c, and non-HDL-c measured. Exposure levels of greenness and ambient pollutants (including PM1, PM2.5, PM10, and NO2) for each participant were determined based on their residential location. Linear mixed-effect and interactive models were used to evaluate the independent and interactive effects between greenness and ambient pollutants on the four novel glycolipid metabolism biomarkers. In the main models, the changes [ß (95% CIs)] of TyG index, TG/HDL-c, TC/HDL-c, and non-HDL-c were -0.021 (-0.036, -0.007), -0.120 (-0.175, -0.066), -0.092 (-0.122, -0.062), and -0.445 (-1.370, 0.480) for every 0.1 increase in NDVI, and were 0.004 (0.003, 0.005), 0.014 (0.009, 0.019), 0.009 (0.006, 0.011), and 0.067 (-0.019, 0.154) for every 1 µg/m3 increase in PM1. Results of interactive analyses demonstrated that individuals living in low-polluted areas could get greater benefits from greenness than those living in highly-polluted areas. Additionally, the results of mediation analyses revealed that PM2.5 mediated 14.40% of the association between greenness and the TyG index. Further research is needed to validate our findings.

Effects of air pollution and residential greenness on sleep disorder: A 8-year nationwide cohort study.

BACKGROUND: Sleep disorder influencing the quality of life, however, its contributing factors have not been fully identified yet. Recently the potential effects of environmental exposures like air pollution and greenness on sleep disorder have attracted attention, but the evidence in China is limited, particularly in the middle-aged and elderly. METHODS: We conducted a nationwide prospective study that included 21,878 Chinese citizens aged 45 years or above. For each participant, the 3-year averaged exposure concentrations of air pollutants (including PM10, PM2.5, PM1, NO2) and greenness (assessed by NDVI) were estimated based on residential address. We used mixed-effects logistic models to examine the associations of sustained air pollutants and greenness exposures with the occurrence of sleep disorder, and used linear mixed-effects models to assess the associations with sleep duration. Specifically, interaction effects models were employed to identify potential modificators of the above associations. RESULTS: A total of 39,580 survey responses were received, with the overall occurrence rate of sleep disorder was 25.7%. A 10 µg/m3 increment in PM10 and PM2.5 were associated with increased occurrence of sleep disorder at 2% (aOR = 1.02, 95%CI:1.01, 1.04) and 7% (aOR = 1.07, 95%CI: 1.04, 1.11), and were associated with reduced sleep duration by 0.07 (95% CI: 0.08, 0.05) and 0.04 (95% CI: 0.05, 0.03) hours, respectively. Residential greenness appears to the potential protective factor for sleep disorder, that a 0.1 higher of the NDVI was associated a 9% (aOR = 0.91, 95%CI: 0.86, 0.96) decreased occurrence of sleep disorder and 0.09 h (95% CI: 0.05, 0.13) longer of sleep duration. Age and residence were identified as modificators of the above significant associations. CONCLUSION: Sustained exposure to air pollutants can increase the occurrence of sleep disorder and can reduce sleep duration, while exposure to higher levels of greenness can protect sleep health from the side effects of air pollutants.