Nanoplastics exacerbate Parkinson's disease symptoms in C. elegans and human cells.

The increasing prevalence of nanoplastics in our environment due to the widespread use of plastics poses potential health risks that are not yet fully understood. This study examines the physiological and neurotoxic effects of these minuscule nanoplastic particles on the nematode Caenorhabditis elegans as well as on human cells. Here, we find that 25 nm polystyrene nanoplastic particles can inhibit animal growth and movement at very low concentrations, with varying effects on their surface groups. Furthermore, these nanoplastic particles not only accumulate in the digestive tract but also penetrate further into extraintestinal tissues. Such nanoplastics significantly compromise the integrity of the intestinal barrier, leading to "leaky gut" conditions and cause mitochondrial fragmentation in muscles, which possibly explains the observed movement impairments. A striking discovery was that these nanoplastics exacerbate symptoms similar to those of Parkinson's disease (PD), including dopaminergic neuronal degeneration, locomotor dysfunction, and accumulation of α-Synuclein aggregates. Importantly, our study demonstrates that the detrimental effects of nanoplastics on the aggregation of α-Synuclein extend to both C. elegans and human cell models of PD. In conclusion, our research highlights the potential health hazards linked to the physicochemical properties of nanoplastics, underlining the urgency of understanding their interactions with biological systems. ENVIRONMENTAL IMPLICATION: The escalating prevalence of nanoplastics in the environment due to widespread plastic usage raises potential health risks. Studies conducted on C. elegans indicate that even low concentrations of 25 nm polystyrene nanoplastics can impair growth and movement. These particles accumulate in the digestive system, compromising the intestinal barrier, causing "leaky gut", as well as inducing Parkinson's-like symptoms. Importantly, in both C. elegans and human cell models of Parkinson's disease, such nanoplastics penetrate tissues or cells and increase α-Synuclein aggregates. This underscores the urgent need to understand the interactions of nanoplastics with biological systems and highlights potential environmental and health consequences.

European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation.

Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel). Eight variants from the multi-ancestry analysis replicated in at least one of the populations tested (European, Latino or African), while two may be specific to individuals of Japanese ancestry. AD loci showed enrichment for DNAse I hypersensitivity and eQTL associations in blood. At each locus we prioritised candidate genes by integrating multi-omic data. The implicated genes are predominantly in immune pathways of relevance to atopic inflammation and some offer drug repurposing opportunities.

Variability of the Human Serum Metabolome over 3 Months in the EXPOsOMICS Personal Exposure Monitoring Study.

Liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) and untargeted metabolomics are increasingly used in exposome studies to study the interactions between nongenetic factors and the blood metabolome. To reliably and efficiently link detected compounds to exposures and health phenotypes in such studies, it is important to understand the variability in metabolome measures. We assessed the within- and between-subject variability of untargeted LC-HRMS measurements in 298 nonfasting human serum samples collected on two occasions from 157 subjects. Samples were collected ca. 107 (IQR: 34) days apart as part of the multicenter EXPOsOMICS Personal Exposure Monitoring study. In total, 4294 metabolic features were detected, and 184 unique compounds could be identified with high confidence. The median intraclass correlation coefficient (ICC) across all metabolic features was 0.51 (IQR: 0.29) and 0.64 (IQR: 0.25) for the 184 uniquely identified compounds. For this group, the median ICC marginally changed (0.63) when we included common confounders (age, sex, and body mass index) in the regression model. When grouping compounds by compound class, the ICC was largest among glycerophospholipids (median ICC 0.70) and steroids (0.67), and lowest for amino acids (0.61) and the O-acylcarnitine class (0.44). ICCs varied substantially within chemical classes. Our results suggest that the metabolome as measured with untargeted LC-HRMS is fairly stable (ICC > 0.5) over 100 days for more than half of the features monitored in our study, to reflect average levels across this time period. Variance across the metabolome will result in differential measurement error across the metabolome, which needs to be considered in the interpretation of metabolome results.

Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk.

Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.

Air pollution, metabolites and respiratory health across the life-course.

Previous studies have explored the relationships of air pollution and metabolic profiles with lung function. However, the metabolites linking air pollution and lung function and the associated mechanisms have not been reviewed from a life-course perspective. Here, we provide a narrative review summarising recent evidence on the associations of metabolic profiles with air pollution exposure and lung function in children and adults. Twenty-six studies identified through a systematic PubMed search were included with 10 studies analysing air pollution-related metabolic profiles and 16 studies analysing lung function-related metabolic profiles. A wide range of metabolites were associated with short- and long-term exposure, partly overlapping with those linked to lung function in the general population and with respiratory diseases such as asthma and COPD. The existing studies show that metabolomics offers the potential to identify biomarkers linked to both environmental exposures and respiratory outcomes, but many studies suffer from small sample sizes, cross-sectional designs, a preponderance on adult lung function, heterogeneity in exposure assessment, lack of confounding control and omics integration. The ongoing EXposome Powered tools for healthy living in urbAN Settings (EXPANSE) project aims to address some of these shortcomings by combining biospecimens from large European cohorts and harmonised air pollution exposure and exposome data.

Residential exposure to greenspace and life satisfaction in times of COVID-19: a cross-sectional analysis of 9444 participants from a population-based study in Basel-Stadt and Basel-Landschaft.

BACKGROUND: Subjective well-being is an important target in the COVID-19 pandemic. Residential greenness may help cope with stress and hence influence subjective well-being during this mentally and physically challenging time. METHODS: We analysed the association between residential greenness and life satisfaction in 9,444 adults in the COVCO-Basel cohort. We assessed if the association is modified by age, sex, household income, financial worries, canton of residence, or month of study entry. In addition, we assessed if the association is attributed to specific types of greenspace or accessibility to greenspace. RESULTS: The association between residential greenness and life satisfaction varied by age groups, household income, and financial worries. Residential greenness was positively associated with life satisfaction in those with high household income and the least financially worried, and negatively associated with life satisfaction in the youngest age group (18-29 years) and the most financially worried. Living closer to a forest, but not to a park or an agricultural area, was associated with lower life satisfaction in the youngest age group. CONCLUSIONS: Residential greenness effects on life satisfaction vary according to sociodemographic characteristics. Living in a greener area does not benefit all dwellers in Basel and its region equally, with the most apparent benefit for those with high household income and without financial concerns.

Residential greenness-related DNA methylation changes.

BACKGROUND: Residential greenness has been associated with health benefits, but its biological mechanism is largely unknown. Investigation of greenness-related DNA methylation profiles can contribute to mechanistic understanding of the health benefits of residential greenness. OBJECTIVE: To identify DNA methylation profiles associated with greenness in the immediate surroundings of the residence. METHODS: We analyzed genome-wide DNA methylation in 1938 blood samples (982 participants) from the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA). We estimated residential greenness based on normalized difference vegetation index at 30 × 30 m cell (green30) and 500 m buffer (green500) around the residential address. We conducted epigenome-wide association study (EWAS) to identify differentially methylated CpGs and regions, and enrichment tests by comparing to the CpGs that previous EWAS identified as associated with allergy, physical activity, and allostatic load-relevant biomarkers. RESULTS: We identified no genome-wide significant CpGs, but 163 and 56 differentially methylated regions for green30 and green500, respectively. Green30-related DNA methylation profiles showed enrichments in allergy, physical activity, and allostatic load, while green500-related methylation was enriched in allergy and allostatic load. CONCLUSIONS: Residential greenness may have health impacts through allergic sensitization, stress coping, or behavioral changes. Exposure to more proximal greenness may be more health-relevant.

Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging.

BACKGROUND: Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. RESULTS: Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. CONCLUSION: This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.

Causal Effects of Body Mass Index on Airflow Obstruction and Forced Mid-Expiratory Flow: A Mendelian Randomization Study Taking Interactions and Age-Specific Instruments Into Consideration Toward a Life Course Perspective.

Obesity has complex links to respiratory health. Mendelian randomization (MR) enables assessment of causality of body mass index (BMI) effects on airflow obstruction and mid-expiratory flow. In the adult SAPALDIA cohort, recruiting 9,651 population-representative samples aged 18-60 years at baseline (female 51%), BMI and the ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) as well as forced mid-expiratory flow (FEF25-75%) were measured three times over 20 follow-up years. The causal effects of BMI in childhood and adulthood on FEV1/FVC and FEF25-75% were assessed in predictive (BMI averaged over 1st and 2nd, lung function (LF) averaged over 2nd and 3rd follow-up; N = 2,850) and long-term cross-sectional models (BMI and LF averaged over all follow-ups; N = 2,728) by Mendelian Randomization analyses with the use of weighted BMI allele score as an instrument variable and two-stage least squares (2SLS) method. Three different BMI allele scores were applied to specifically capture the part of BMI in adulthood that likely reflects tracking of genetically determined BMI in childhood. The main causal effects were derived from models containing BMI (instrumented by BMI genetic score), age, sex, height, and packyears smoked as covariates. BMI interactions were instrumented by the product of the instrument (BMI genetic score) and the relevant concomitant variable. Causal effects of BMI on FEV1/FVC and FEF25-75% were observed in both the predictive and long-term cross-sectional models. The causal BMI- LF effects were negative and attenuated with increasing age, and stronger if instrumented by gene scores associated with childhood BMI. This non-standard MR approach interrogating causal effects of multiplicative interaction suggests that the genetically rooted part of BMI patterns in childhood may be of particular relevance for the level of small airway function and airflow obstruction later in life. The methodological relevance of the results is first to point to the importance of a life course perspective in studies on the etiological role of BMI in respiratory health, and second to point out novel methodological aspects to be considered in future MR studies on the causal effects of obesity related phenotypes.

Short-term personal and outdoor exposure to ultrafine and fine particulate air pollution in association with blood pressure and lung function in healthy adults.

Studies reporting on associations between short-term exposure to outdoor fine (PM2.5), and ultrafine particles (UFP) and blood pressure and lung function have been inconsistent. Few studies have characterized exposure by personal monitoring, which especially for UFP may have resulted in substantial exposure measurement error. We investigated the association between 24-h average personal UFP, PM2.5, and soot exposure and dose and the health parameters blood pressure and lung function. We further assessed the short-term associations between outdoor concentrations measured at a central monitoring site and near the residences and these health outcomes. We performed three 24-h personal exposure measurements for UFP, PM2.5, and soot in 132 healthy adults from Basel (Switzerland), Amsterdam and Utrecht (the Netherlands), and Turin (Italy). Monitoring of each subject was conducted in different seasons in a one-year study period. Subject's activity levels and associated ventilation rates were measured using actigraphy to calculate the inhaled dose. After each 24-h monitoring session, blood pressure and lung function were measured. Contemporaneously with personal measurements, UFP, PM2.5 and soot were measured outdoor at the subject's residential address and at a central site in the research area. Associations between short-term personal and outdoor exposure and dose to UFP, PM2.5, and soot and health outcomes were tested using linear mixed effect models. The 24-h mean personal, residential and central site outdoor UFP exposures were not associated with blood pressure or lung function. UFP mean exposures in the 2-h prior to the health test was also not associated with blood pressure and lung function. Personal, central site and residential PM2.5 exposure were positively associated with systolic blood pressure (about 1.4 mmHg increase per Interquartile range). Personal soot exposure and dose were positively associated with diastolic blood pressure (1.2 and 0.9 mmHg increase per Interquartile range). No consistent associations between PM2.5 or soot exposure and lung function were observed. Short-term personal, residential outdoor or central site exposure to UFP was not associated with blood pressure or lung function. Short-term personal PM2.5 and soot exposures were associated with blood pressure, but not lung function.

SPHN - The Swiss Aging Citizen Reference (SACR).

In Switzerland by 2045, we expect 2.7 Mio citizens aged 65+ of whom 1.0 Mio. aged 80+. A priority and focus of personalized health research is therefore aging biology to extend healthy life expectancy. Novel molecular and imaging features will emerge as candidate targets for risk prediction and screening of chronic diseases. It is of utmost importance to test the clinical and public health utility of candidate biomarkers evolving from this research in citizen reference cohorts. We will build a Swiss Aging Citizen Reference (SACR), a testable and scalable reference cohort offering interoperable, searchable, and accessible data. 1000 participants from existing Swiss citizen cohorts will be combined and analyzed for DNA methylation and MRI brain imaging. SACR will serve as a testbed for clinical and public health utility of candidate biomarkers. As for a proof-of-concept study, we will conduct an agnostic search for structural and functional brain features associated with epigenetic aging acceleration to examine the potential of epigenetic age acceleration as the intermediate aging biomarker and to better understand the aging mechanism in brain.

Genome-Wide DNA Methylation in Peripheral Blood and Long-Term Exposure to Source-Specific Transportation Noise and Air Pollution: The SAPALDIA Study.

BACKGROUND: Few epigenome-wide association studies (EWAS) on air pollutants exist, and none have been done on transportation noise exposures, which also contribute to environmental burden of disease. OBJECTIVE: We performed mutually independent EWAS on transportation noise and air pollution exposures. METHODS: We used data from two time points of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) from 1,389 participants contributing 2,542 observations. We applied multiexposure linear mixed-effects regressions with participant-level random intercept to identify significant Cytosine-phosphate-Guanine (CpG) sites and differentially methylated regions (DMRs) in relation to 1-y average aircraft, railway, and road traffic day-evening-night noise (Lden); nitrogen dioxide (NO2); and particulate matter (PM) with aerodynamic diameter <2.5µm (PM2.5). We performed candidate (CpG-based; cross-systemic phenotypes, combined into "allostatic load") and agnostic (DMR-based) pathway enrichment tests, and replicated previously reported air pollution EWAS signals. RESULTS: We found no statistically significant CpGs at false discovery rate <0.05. However, 14, 48, 183, 8, and 71 DMRs independently associated with aircraft, railway, and road traffic Lden; NO2; and PM2.5, respectively, with minimally overlapping signals. Transportation Lden and air pollutants tendentially associated with decreased and increased methylation, respectively. We observed significant enrichment of candidate DNA methylation related to C-reactive protein and body mass index (aircraft, road traffic Lden, and PM2.5), renal function and "allostatic load" (all exposures). Agnostic functional networks related to cellular immunity, gene expression, cell growth/proliferation, cardiovascular, auditory, embryonic, and neurological systems development were enriched. We replicated increased methylation in cg08500171 (NO2) and decreased methylation in cg17629796 (PM2.5). CONCLUSIONS: Mutually independent DNA methylation was associated with source-specific transportation noise and air pollution exposures, with distinct and shared enrichments for pathways related to inflammation, cellular development, and immune responses. These findings contribute in clarifying the pathways linking these exposures and age-related diseases but need further confirmation in the context of mediation analyses. https://doi.org/10.1289/EHP6174.

Role of DNA methylation in the association of lung function with body mass index: a two-step epigenetic Mendelian randomisation study.

BACKGROUND: Low lung function has been associated with increased body mass index (BMI). The aim of this study was to investigate whether the effect of BMI on lung function is mediated by DNA methylation. METHODS: We used individual data from 285,495 participants in four population-based cohorts: the European Community Respiratory Health Survey, the Northern Finland Birth Cohort 1966, the Swiss Study on Air Pollution and Lung Disease in Adults, and the UK Biobank. We carried out Mendelian randomisation (MR) analyses in two steps using a two-sample approach with SNPs as instrumental variables (IVs) in each step. In step 1 MR, we estimated the causal effect of BMI on peripheral blood DNA methylation (measured at genome-wide level) using 95 BMI-associated SNPs as IVs. In step 2 MR, we estimated the causal effect of DNA methylation on FEV1, FVC, and FEV1/FVC using two SNPs acting as methQTLs occurring close (in cis) to CpGs identified in the first step. These analyses were conducted after exclusion of weak IVs (F statistic < 10) and MR estimates were derived using the Wald ratio, with standard error from the delta method. Individuals whose data were used in step 1 were not included in step 2. RESULTS: In step 1, we found that BMI might have a small causal effect on DNA methylation levels (less than 1% change in methylation per 1 kg/m2 increase in BMI) at two CpGs (cg09046979 and cg12580248). In step 2, we found no evidence of a causal effect of DNA methylation at cg09046979 on lung function. We could not estimate the causal effect of DNA methylation at cg12580248 on lung function as we could not find publicly available data on the association of this CpG with SNPs. CONCLUSIONS: To our knowledge, this is the first paper to report the use of a two-step MR approach to assess the role of DNA methylation in mediating the effect of a non-genetic factor on lung function. Our findings do not support a mediating effect of DNA methylation in the association of lung function with BMI.

Epigenome-wide association study of DNA methylation and adult asthma in the Agricultural Lung Health Study.

Epigenome-wide studies of methylation in children support a role for epigenetic mechanisms in asthma; however, studies in adults are rare and few have examined non-atopic asthma. We conducted the largest epigenome-wide association study (EWAS) of blood DNA methylation in adults in relation to non-atopic and atopic asthma.We measured DNA methylation in blood using the Illumina MethylationEPIC array among 2286 participants in a case-control study of current adult asthma nested within a United States agricultural cohort. Atopy was defined by serum specific immunoglobulin E (IgE). Participants were categorised as atopy without asthma (n=185), non-atopic asthma (n=673), atopic asthma (n=271), or a reference group of neither atopy nor asthma (n=1157). Analyses were conducted using logistic regression.No associations were observed with atopy without asthma. Numerous cytosine-phosphate-guanine (CpG) sites were differentially methylated in non-atopic asthma (eight at family-wise error rate (FWER) p<9×10-8, 524 at false discovery rate (FDR) less than 0.05) and implicated 382 novel genes. More CpG sites were identified in atopic asthma (181 at FWER, 1086 at FDR) and implicated 569 novel genes. 104 FDR CpG sites overlapped. 35% of CpG sites in non-atopic asthma and 91% in atopic asthma replicated in studies of whole blood, eosinophils, airway epithelium, or nasal epithelium. Implicated genes were enriched in pathways related to the nervous system or inflammation.We identified numerous, distinct differentially methylated CpG sites in non-atopic and atopic asthma. Many CpG sites from blood replicated in asthma-relevant tissues. These circulating biomarkers reflect risk and sequelae of disease, as well as implicate novel genes associated with non-atopic and atopic asthma.

microRNA expression profiles and personal monitoring of exposure to particulate matter.

An increasing number of findings from epidemiological studies support associations between exposure to air pollution and the onset of several diseases, including pulmonary, cardiovascular and neurodegenerative diseases, and malignancies. However, intermediate, and potentially mediating, biological mechanisms associated with exposure to air pollutants are largely unknown. Previous studies on the human exposome have shown that the expression of certain circulating microRNAs (miRNAs), regulators of gene expression, are altered upon exposure to traffic-related air pollutants. In the present study, we investigated the relationship between particulate matter (PM) smaller than 2.5 µm (PM2.5), PM2.5 absorbance (as a proxy of black carbon and soot), and ultrafine-particles (UFP, smaller than 0.1 µm), measured in healthy volunteers by 24 h personal monitoring (PEM) sessions and global expression levels of peripheral blood miRNAs. The PEM sessions were conducted in four European countries, namely Switzerland (Basel), United Kingdom (Norwich), Italy (Turin), and The Netherlands (Utrecht). miRNAs expression levels were analysed using microarray technology on blood samples from 143 participants. Seven miRNAs, hsa-miR-24-3p, hsa-miR-4454, hsa-miR-4763-3p, hsa-miR-425-5p, hsa-let-7d-5p, hsa-miR-502-5p, and hsa-miR-505-3p were significantly (FDR corrected) expressed in association with PM2.5 personal exposure, while no significant association was found between miRNA expression and the other pollutants. The results obtained from this investigation suggest that personal exposure to PM2.5 is associated with miRNA expression levels, showing the potential for these circulating miRNAs as novel biomarkers for air pollution health risk assessment.

Association of adult lung function with accelerated biological aging.

Lung function, strongly associated with morbidity and mortality, decreases with age. This study examines whether poor adult lung function is associated with age accelerations (AAs). DNA methylation (DNAm) based AAs, lifespan predictors (GrimAge and plasminogen activator inhibitor 1-PAI1) and their related age-adjusted measures were estimated from peripheral blood at two time points (8-to-11 years apart) in adults from two cohorts: SAPALDIA (n=987) and ECRHS (n=509). Within each cohort and stratified by gender (except for estimators from GrimAge and PAI1), AAs were used as predictors in multivariate linear regression with cross-sectional lung function parameters, and in covariate-adjusted mixed linear regression with longitudinal change in lung function and meta-analysed.AAs were found cross-sectionally associated with lower mean FEV1 (Forced Expiratory Volume in one second) (AA-residuals:P-value=4x10-4; Intrinsic Epigenetic AA:P-value=2x10-4) in females at the follow-up time point only, and the same trend was observed for FVC (Forced Vital Capacity). Both lifespan and plasma level predictors were observed strongly associated with lung function decline and the decline was stronger in the follow-up time points (strongest association between FEV1 and DNAmAge GrimAge:P-value=1.25x10-17).This study suggests that DNAm based lifespan and plasma level predictors can be utilised as important factors to assess lung health in adults.

Understanding of Fluorination Dependence on Electron Mobility and Stability of Naphthalenediimide-Based Polymer Transistors in Environment with 100% Relative Humidity.

A family of copolymers (P(NDIOD-T2Fx)) based on naphthalenediimide (NDI) and 2,2'-bithiophene (T2) units with different amounts of 3,3'-difluoro-2,2'-bithiophene (T2F) decoration were synthesized, characterized, and used in n-type organic field-effect transistors (OFETs). With increasing T2F content in the backbone, we observe increased melting and crystallization transitions, blue-shifted absorptions, and deeper-lying highest occupied molecular orbital (HOMO)/lowest unoccupied molecular orbital (LUMO) levels, together with improved hydrophobicity. The highest electron mobility of 4.48 × 10-1 cm2 V-1 s-1 was obtained for P(NDIOD-T2F0) without a T2F unit, which is attributed to the larger domain grains and crystallites, as well as a more tightly packed and oriented crystalline structure, as evidenced from the morphological study. In contrast, P(NDIOD-T2F100) with the highest T2F content has superior air stability, showing greater than 25% electron mobility retention after 30 days in wet conditions of 100% relative humidity without encapsulation. Even P(NDIOD-T2F100) is able to operate normally after 30 min of immersion in water, which is due to the synergistic contributions from the deep HOMO/LUMO levels and improved hydrophobicity. This study advances our fundamental understanding of how the morphology/crystallinity, device performance, and device stability of n-type copolymers are tuned by incorporating different concentrations of T2F in the backbone, shedding light on an important modification for air- and water-stable n-type materials for future OFET applications.

The mediating effect of immune markers on the association between ambient air pollution and adult-onset asthma.

We aim to investigate to what extent a set of immune markers mediate the association between air pollution and adult-onset asthma. We considered long-term exposure to multiple air pollution markers and a panel of 13 immune markers in peripheral blood samples collected from 140 adult cases and 199 controls using a nested-case control design. We tested associations between air pollutants and immune markers and adult-onset asthma using mixed-effects (logistic) regression models, adjusted for confounding variables. In order to evaluate a possible mediating effect of the full set of immune markers, we modelled the relationship between asthma and air pollution with a partial least square path model. We observed a strong positive association of IL-1RA [OR 1.37; 95% CI (1.09, 1.73)] with adult-onset asthma. Univariate models did not yield any association between air pollution and immune markers. However, mediation analyses indicated that 15% of the effect of air pollution on risk of adult-onset asthma was mediated through the immune system when considering all immune markers as a latent variable (path coefficient (ß) = 0.09; 95% CI: (-0.02, 0.20)). This effect appeared to be stronger for allergic asthma (22%; ß = 0.12; 95% CI: (-0.03, 0.27)) and overweight subjects (27%; ß = 0.19; 95% CI: (-0.004, 0.38)). Our results provides supportive evidence for a mediating effect of the immune system in the association between air pollution and adult-onset asthma.

Epigenome-wide association study of lung function level and its change.

Previous reports link differential DNA methylation (DNAme) to environmental exposures that are associated with lung function. Direct evidence on lung function DNAme is, however, limited. We undertook an agnostic epigenome-wide association study (EWAS) on pre-bronchodilation lung function and its change in adults.In a discovery-replication EWAS design, DNAme in blood and spirometry were measured twice, 6-15 years apart, in the same participants of three adult population-based discovery cohorts (n=2043). Associated DNAme markers (p<5×10-7) were tested in seven replication cohorts (adult: n=3327; childhood: n=420). Technical bias-adjusted residuals of a regression of the normalised absolute ß-values on control probe-derived principle components were regressed on level and change of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and their ratio (FEV1/FVC) in the covariate-adjusted discovery EWAS. Inverse-variance-weighted meta-analyses were performed on results from discovery and replication samples in all participants and never-smokers.EWAS signals were enriched for smoking-related DNAme. We replicated 57 lung function DNAme markers in adult, but not childhood samples, all previously associated with smoking. Markers not previously associated with smoking failed replication. cg05575921 (AHRR (aryl hydrocarbon receptor repressor)) showed the statistically most significant association with cross-sectional lung function (FEV1/FVC: pdiscovery=3.96×10-21 and pcombined=7.22×10-50). A score combining 10 DNAme markers previously reported to mediate the effect of smoking on lung function was associated with lung function (FEV1/FVC: p=2.65×10-20).Our results reveal that lung function-associated methylation signals in adults are predominantly smoking related, and possibly of clinical utility in identifying poor lung function and accelerated decline. Larger studies with more repeat time-points are needed to identify lung function DNAme in never-smokers and in children.