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Oxylipins are highly bioactive lipid mediators derived from polyunsaturated fatty acids (PUFAs) and have fundamental roles in a diverse set of homeostatic and inflammatory processes. Current targeted methods of analyzing oxylipins require long runtimes and laborious sample preparation, limiting their application to epidemiological studies. Here, we report the development of an online solid-phase extraction-liquid chromatography-triple quadrupole mass spectrometry (online SPE-LC-MS/MS) method to quantify 49 non-esterified oxylipins and PUFAs, including prostanoids, leukotrienes, lipoxins, resolvins, hydroxy PUFAs, epoxy PUFAs, and their PUFA precursors, in 50-μL samples of human serum. The new method was validated in terms of linearity, lower limits of quantification, recovery, precision, and matrix effects. The limits of quantification were in the range of 0.18 to 9 pg for oxylipins. A single 11.5-min analysis enabled the accurate (80–120% recovery), precise, and reproducible (RSD < 15%) quantification of 32 analytes at three spiked concentrations (0.1, 1, 5 ng/mL), demonstrating the suitability of this method for large-scale epidemiological studies. We successfully applied it to rapidly analyze a total of 565 serum samples from prediabetic and healthy individuals in a nested case-control panel study. Oxylipin concentrations were quantified within a range similar to those of previously published articles. Application of this approach to both healthy and prediabetic subjects found that several circulating hydroxy PUFAs, including LTB4, 12-HEPE, 15(S)-HETE, and 17-HDHA, were negatively associated with fasting glucose levels, indicating decreased anti-inflammatory activity and impaired glucose tolerance in diabetes progression. This new approach provides a means for high-throughput analyses of non-esterified oxylipins for epidemiological studies and will help unravel the intricate interactions of the oxylipin cascade and accelerate our understanding of the biological regulation of these important lipid mediators in human disease. [ABSTRACT FROM AUTHOR]

[Display omitted] • Identification of changes in land use and ESV in Hubei. • Coupling analysis between environment and economy based on EEC evaluation. • Assessment of the impacts of relevant driving factors on EEC. • Detection of spatial clustering characteristics of EEC in Hubei. • Our research model improves existing model's ease of applicability. Environmental and economic coordination (EEC) is an essential indicator of sustainability and plays a vital role in human well-being. Quantifying trends in EEC and identifying the contributing factors are important to understand the relative impacts of human activities on ecological environment. For our case-study of 74 cities and counties in Hubei Province of China from 2000 to 2020, based on the changes of ecosystem service value (ESV), the coupling coordination degree (CCD) model was applied to calculate the EEC. The spatial–temporal differentiation characteristics of EEC were detected through spatial correlation analysis. By the spatial Durbin model and panel data, we quantified the impacts of driving factors on EEC. Our results indicated that the number of cities and counties in a coordinated state in Hubei Province declined from 2000 to 2010 and then gradually rose from 2010 to 2020, while 87.84% of the cities and counties showed an overall decreasing trend in EEC values. Hubei's EEC had obvious spatial clustering characteristics, with over 84.57% of cities and counties with medium to high EEC concentrated in the Wuhan City Circle and Yichang region, while those with low EEC were mainly concentrated in northwest, northeast and southwest of Hubei. For the driving factors, the promotion effects of industrial structure optimization and precipitation were evident, whereas the inhibition effects of increase in general public budget expenditure, population growth, urban expansion and rising temperatures were observed. The results provide important background understanding for achieving coordinated development of the ecological environment and socio-economy at regional and global scales. [ABSTRACT FROM AUTHOR]

Individuals with metabolic disorders exhibit enhanced susceptibility to the cardiovascular health effects of particulate air pollution, but the underlying mechanisms are not yet understood. We aim to assess whether changes in proinflammatory lipid signals are associated with fine particulate matter (PM 2.5) exposure in individuals with and without prediabetes. A longitudinal panel study was conducted in Beijing, China, and included 120 participants followed up over 589 clinical visits from August 2013 to February 2015. We measured 12 lipids derived from arachidonic acid pathways in blood samples of the participants via targeted lipidomic analyses. Ambient PM 2.5 concentrations were continuously monitored at a station for associations with the lipids. Among the 120 participants, 110 (mean [SD] age at recruitment, 56.5 [4.2] years; 31 prediabetics) who visited the clinic at least twice over the follow-up period were assigned exposure values of the outdoor residential PM 2.5 concentrations during the 1–14 days preceding each clinical visit. With an interquartile range increase in the 1-day-lag PM 2.5 exposure (64.0 μg/m3), the prediabetic group had consistently greater increases in the concentration of arachidonate metabolites derived from the cytochrome P450 (CYP450) pathway (5,6-DHET, 15.8% [95% CI, 3.5–29.7%]; 8,9-DHET, 9.7% [95% CI, 0.6–19.6%]; 11,12-DHET, 8.3% [95% CI, 1.9–15.1%]; 14,15-DHET, 7.4% [95% CI, 0.9–14.4%]; and 20-HETE, 8.9% [95% CI, 1.0–17.5%]), compared with the healthy group. Among CYP450-derived lipids, 14,15-DHET and 20-HETE significantly mediated 8% and 8% of the PM 2.5 -associated increase in white blood cells, 10% and 13% of that in neutrophils, and 20% and 23% of that in monocytes, respectively, in the prediabetic group. In conclusion, proinflammatory lipid signals from CYP450 pathways triggered the health effects of particulate air pollution in individuals with prediabetes, suggesting that targeting lipid metabolism has therapeutic potential to attenuate or prevent the cardiovascular effects of air pollution in susceptible populations. [Display omitted] • Prediabetes exhibit enhanced susceptibility to the cardiovascular effects of PM 2.5. • A longitudinal panel study (SCOPE) was conducted in Beijing, China. • 12 bioactive lipids from arachidonic acid were measured via targeted lipidomic analyses. • Prediabetes may enhance proinflammatory lipid signaling following exposure to air pollution. • CYP450-derived eicosanoids mediated the proinflammatory effects of air pollution. [ABSTRACT FROM AUTHOR]

Growing evidence supports that air pollution exposure has become a risk factor of type II diabetes mellitus through the induction of insulin resistance (IR), but the presented findings did not provide a consistent relationship between air pollution exposure and IR in the temporal scale and the magnitude. Reported associated with IR and air pollution exposure, branched-chain amino acids (BCAAs) in blood might modify the association between air pollution exposure and IR. We took advantage of an existing panel study on elderly people who were healthy or with pre-diabetes. Amino acids were analyzed from the serum samples using a UPLC-QQQ-MS, and the homeostasis model assessment of insulin resistance (HOMA-IR) values were calculated to represent the levels of IR in each visit. Exposures to PM 2.5 , NO 2 , SO 2 , CO, O 3 , and black carbon (BC) were estimated using data from a monitoring station. Linear mixed-effects models were applied to estimate the associations between the air pollution and HOMA-IR, as well as the modifying effects of BCAAs. We found significantly higher concentrations of BCAAs in the pre-diabetic subjects than healthy ones. The concentrations of BCAAs were all significantly associated with HOMA-IR. For subjects with high-level BCAAs, HOMA-IR was positively associated with an IQR increase in PM 2.5 , NO 2 , BC, and CO at lag day 2 and in PM 2.5 , SO 2 , NO 2 , BC, and CO at lag day 7. While for subjects with low-level BCAAs, there was no significant association observed at any lag day except for CO at lag day 5. The study provided evidence that circulating BCAAs may modify the relationship between air pollution exposure and the level of insulin resistance in humans. [Display omitted] • Serum BCAAs appeared negatively associated with air pollution exposure. • Serum BCAAs modified the associations between air pollution and insulin resistance. • Serum BCAAs increased the risk of air pollution exposure on insulin resistance. [ABSTRACT FROM AUTHOR]

Background: Recent studies suggest that people with diabetes or who are at risk of developing diabetes, i.e. prediabetic (preDM), are potentially susceptible to air pollution, but the underlying mechanisms remain unclear because the existing epidemiological studies did not include healthy control groups and only focused on limited health outcomes. We hypothesized that acute exposure to ambient fine particles (PM2.5) will lead to enhanced pulmonary and cardiometabolic changes in preDM than healthy individuals.Methods: We recruited 60 preDM and 60 healthy individuals from a community of 22,343 adults in Beijing China, and arranged each subject to complete up to seven repeated clinical visits with measures of 6 cardiopulmonary biomarkers, 6 cytokines, 4 blood pressure and endothelial function outcomes and 4 glucose metabolism biomarkers.. Moving averaged daily ambient PM2.5 in preceding 1-14 days was matched to each subject and the PM2.5 associated effect on multiple biomarkers was estimated and compared between PreDM and healthy subjects based on linear mixed effect model.Results: All the subjects exhibited significant acute elevation of exhaled nitric oxide, white blood cells, neutrophils, interleukin-1α, and glycated haemoglobin with increased exposure to PM2.5. PreDM subjects had significant stronger adverse changes compared to healthy subjects in 6 cardiometabolic biomarkers, namely, interleukin-2, interleukin-8, systolic and diastolic blood pressure, augmentation pressure, and glucose. The maximum elevation of these 6 biomarkers in PreDM subjects were 8.6% [CI: 4.1-13.3%], 10.0% [CI: 3.9-16.4%], 1.9% [CI: 0.2-3.6%], 1.2% [CI: - 0.1-2.4%], 5.7% [CI: - 0.1-11.8%], 2.4% [CI: 0.7-4.2%], respectively, per an interquartile increase of ambient PM2.5 (61.4 μg m- 3) throughout the exposure window of the preceding 1-14 days. No significant difference was observed for the changes in pulmonary biomarkers between the two groups.Conclusions: PreDM individuals are more susceptible to the acute cardiometabolic effect of air pollution than the healthy individuals. A considerable public health burden can be inferred, given the high prevalence of prediabetes and the ubiquity of air pollution in China and worldwide. [ABSTRACT FROM AUTHOR]

Atmospheric oxidation can produce electrophilic compounds, altering the health effects induced by fine particulate matter (PM 2.5); however, little is known about these electrophilic compounds or their health effects. Using electron capture negative ionization, we systematically detected 301 electrophilic compounds from personal PM 2.5 samples in a panel study in urban Beijing. Most were oxygen-containing compounds with 3–17 double bond equivalents (DBE), suggesting the dominance of oxidized aromatic structures. Over 64% of the species, mostly outdoor-originated, were associated with inflammatory cytokines in both exhaled breath condensate and serum. Primary components of polycyclic aromatic hydrocarbons (PAHs) and high-DBE oxygenated PAHs, mainly from fossil fuel combustion, were positively associated with interleukin (IL)− 6, a cytokine related to oxidative homeostasis. Oxidized secondary species, particularly maleic and phthalic anhydrides, were negatively associated with IL-2/IL-8, which changed by − 3.8% to − 16.4% per one-fold increase in the abundance of the secondary source, indicating the immune disorders in response to the oxidized aerosols. Mediation analysis demonstrated the necessity of transformation products between atmospheric oxidation capacity and IL-2/IL-8 inhibition. This study provides new information on particulate electrophilic compounds and highlights the role of atmospheric chemistry in specific immune disorders. [Display omitted] • 301 electrophilic compounds were characterized in personal PM 2.5 in urban Beijing. • Over 64% of the electrophilic species were associated with inflammatory cytokines. • Secondary species of aromatic anhydrides showed association on IL-2/IL-8 inhibition. • Secondary oxidation compounds mediated the immune inhibition of ambient ozone. [ABSTRACT FROM AUTHOR]

The exposome overhauls conventional environmental health impact research paradigms and provides a novel methodological framework that comprehensively addresses the complex, highly dynamic interplays of exogenous exposures, endogenous exposures, and modifiable factors in humans. Holistic assessments of the adverse health effects and systematic elucidation of the mechanisms underlying environmental exposures are major scientific challenges with widespread societal implications. However, to date, few studies have comprehensively and simultaneously measured airborne pollutant exposures and explored the associated biomarkers in susceptible healthy elderly subjects, potentially resulting in the suboptimal assessment and management of health risks. To demonstrate the exposome paradigm, we describe the rationale and design of a comprehensive biomarker and biomonitoring panel study to systematically explore the association between individual airborne exposure and adverse health outcomes. We used a combination of personal monitoring for airborne pollutants, extensive human biomonitoring, advanced omics analysis, confounding information, and statistical methods. We established an exploratory panel study of Biomarkers of Air Pollutant Exposure in Chinese people aged 60–69 years (China BAPE), which included 76 healthy residents from a representative community in Jinan City, Shandong Province. During the period between September 2018 and January 2019, we conducted prospective longitudinal monitoring with a 3-day assessment every month. This project: (1) leveraged advanced tools for personal airborne exposure monitoring (external exposures); (2) comprehensively characterized biological samples for exogenous and endogenous compounds (e.g., targeted and untargeted monitoring) and multi-omics scale measurements to explore potential biomarkers and putative toxicity pathways; and (3) systematically evaluated the relationships between personal exposure to air pollutants, and novel biomarkers of exposures and effects using exposome-wide association study approaches. These findings will contribute to our understanding of the mechanisms underlying the adverse health impacts of air pollution exposures and identify potential adverse clinical outcomes that can facilitate the development of effective prevention and targeted intervention techniques. [ABSTRACT FROM AUTHOR]

• We conducted the first investigation of personal black carbon (BC) exposure among elderly adults in urban China. • The personal BC exposure level in our study is higher than those in developed countries or regions. • Temperature could significantly affect personal BC exposure by affecting individual activity patterns. • Individuals' education level may be a potential determinant of personal BC exposure among elderly adults. Personal exposure to air pollution is affected by its concentration in the microenvironment and individual time-activity patterns. To investigate personal black carbon (BC) exposure levels and identify their potential determinants, we conducted a panel study among 67 elderly residents aged 60–69 years in Jinan, China. Personal BC exposure was measured using portable real-time monitors, while corresponding ambient BC concentrations and meteorological conditions were also collected from the local central site. Time-activity and household characteristics were recorded. A linear mixed-effects model was used to identify potential determinants of personal BC exposure. The daily average personal BC exposure concentration was 4.1 ± 2.0 μg/m3 (±standard deviation, SD), which was significantly lower than the ambient concentration (4.6 ± 2.5 μg/m3) (p < 0.001). Strong correlation (Spearman's r = 0.63 , p < 0.001) was found between personal and ambient BC concentrations. The fixed-site monitoring ambient concentration cannot fully reflect the actual personal exposure concentration. Ambient BC concentration, ambient temperature, relative humidity, education level and air purifier use were significant determinants of personal BC exposure. Our findings highlight the need for detailed assessment of personal exposure on health risk assessment of BC and also help develop strategies for targeted risk reduction. [ABSTRACT FROM AUTHOR]