Low-level ambient ozone exposure associated with neutrophil extracellular traps and pro-atherothrombotic biomarkers in healthy adults.

BACKGROUND AND AIMS: Uncertainty of the causality determinations for ambient ozone (O3) on cardiovascular events is heightened by the limited understanding of the mechanisms involved in humans. We aimed to examine the pro-atherothrombotic impacts of O3 exposure and to explore the potential mediating roles of dysfunctional neutrophils, focusing on neutrophil extracellular traps (NETs). METHODS: A longitudinal panel study of 152 healthy adults was conducted in the cool to cold months with relatively low levels of O3 between September 2019 and January 2020 in Beijing, China. Four repeated measurements of indicators reflecting atherothrombotic balance and NETs were performed for each participant. RESULTS: Daily average exposure levels of ambient O3 were 16.6 µg/m3 throughout the study period. Per interquartile range increase in average concentrations of O3 exposure at prior up to 7 days, we observed elevations of 200.1-276.3% in D-dimer, 27.2-36.8% in thrombin-antithrombin complex, 10.8-60.3% in plasminogen activator inhibitor 1, 13.9-21.8% in soluble P-selectin, 16.5-45.1% in matrix metalloproteinase-8, and 2.4-12.4% in lipoprotein-associated phospholipase A2. These pro-atherothrombotic changes were accompanied by endothelial activation, lung injury, and immune inflammation. O3 exposure was also positively associated with circulating NETs indicators, including citrullinated histone H3, neutrophil elastase, myeloperoxidase, and double-stranded DNA. Mediation analyses indicated that NETs could mediate O3-associated pro-atherothrombotic responses. The observational associations remained significant and robust after controlling for other pollutants, and were generally greater in participants with low levels of physical activity. CONCLUSIONS: Ambient O3 exposure was associated with significant increases in NETs and pro-atherothrombotic potential, even at exposure levels well below current air quality guidelines of the World Health Organization.

Augmentation of scleral glycolysis promotes myopia through histone lactylation.

Myopia is characterized of maladaptive increases in scleral fibroblast-to-myofibroblast transdifferentiation (FMT). Scleral hypoxia is a significant factor contributing to myopia, but how hypoxia induces myopia is poorly understood. Here, we showed that myopia in mice and guinea pigs was associated with hypoxia-induced increases in key glycolytic enzymes expression and lactate levels in the sclera. Promotion of scleral glycolysis or lactate production induced FMT and myopia; conversely, suppression of glycolysis or lactate production eliminated or inhibited FMT and myopia. Mechanistically, increasing scleral glycolysis-lactate levels promoted FMT and myopia via H3K18la, and this promoted Notch1 expression. Genetic analyses identified a significant enrichment of two genes encoding glycolytic enzymes, ENO2 and TPI1. Moreover, increasing sugar intake in guinea pigs not only induced myopia but also enhanced the response to myopia induction via the scleral glycolysis-lactate-histone lactylation pathway. Collectively, we suggest that scleral glycolysis contributes to myopia by promoting FMT via lactate-induced histone lactylation.

Association between interleg systolic blood pressure difference and apparent peripheral neuropathy in US adults with diabetes: a cross-sectional study.

BACKGROUND: Interleg systolic blood pressure difference (ILSBPD) is associated with peripheral artery disease, but the relationship between ILSBPD and apparent peripheral neuropathy in diabetic patients remains unclear. We explored the relationship between ILSBPD and apparent peripheral neuropathy and examined the possible effect modifiers in US adults with diabetes. METHODS: One thousand and fifty-one diabetic participants were included in the study with complete data on systolic blood pressure of the lower extremities and Semmes-Weinstein 10-g monofilament testing from the 1999-2004 National Health and Nutritional Examination Surveys. Systolic blood pressure in the lower extremities was measured using an oscillometric blood pressure device with the patient in the supine position. Apparent peripheral neuropathy was defined as the presence of monofilament insensitivity. RESULTS: Every 5-mmHg increment in ILSBPD is associated with an about 14% increased risk of apparent peripheral neuropathy in crude model, but after adjustment for covariates, the correlation became nonsignificant (P = 0.160). When participants were divided into groups based on ILSBPD cutoffs of 5, 10 and 15 mmHg in different analyses, there was a significantly increased risk of apparent peripheral neuropathy in the ILSBPD ≥ 15 mmHg group (OR 1.79, 95% CI 1.11-2.91, P = 0.018), even after adjusting for confounders. In subgroup analysis, no interaction effect was found (all P for interaction > 0.05). CONCLUSIONS: In US adults with diabetes, an increase in the ILSBPD (≥ 15 mmHg) was associated with a higher risk of apparent peripheral neuropathy.

The mediating role of vascular inflammation in traffic-related air pollution associated changes in insulin resistance in healthy adults.

AIM: The precise pathophysiologic pathway linking traffic-related air pollution (TRAP) to diabetes mellitus is not well elucidated. We aimed to investigate whether activation of vascular inflammation can be a mechanistic linkage between ambient TRAP and insulin resistance. METHODS: Study outcomes were determined by assessing a series of circulating biomarkers indicative of insulin resistance and vascular inflammation among 73 healthy adults who underwent repeated clinical visits in Beijing, China, 2014-2016. Concomitantly, concentrations of ambient TRAP indices, including particulate matter in diameter <2.5 µm (PM2.5), particles in size fractions of 5-560 nm, black carbon, carbon monoxide, nitrogen dioxide, and oxides of nitrogen, were continuously monitored. RESULTS: Participants experienced extremely high levels of TRAP exposures, with mean (standard deviation) PM2.5 concentrations of 91.8 (48.3) µg/m3, throughout the study. We found that interquartile range increases in exposure to moving average concentrations of various TRAP indices at prior up to 7 days were associated with significant elevations of 8.9-49.6% in insulin levels. Higher pollutant levels were also related to worsening metrics of insulin resistance (soluble insulin receptor ectodomain, adipokines, and homeostasis model assessment of insulin resistance) and heightened vascular inflammatory responses, particularly disruptions of the receptor activator of nuclear factor κB ligand/osteoprotegerin system balance and elevations of monocyte/macrophage and T cell activation markers. Mediation analyses showed that activation of vascular inflammation could explain up to 66% of the alterations in metrics of insulin resistance attributable to air pollution. CONCLUSION: Our results suggest that ambient traffic pollution exposure was capable of promoting insulin resistance possibly via generating vascular inflammation.

Joint Predictive Value of cTnI and NT-proBNP on Mortality in Patients with Coronavirus Disease 2019: A Retrospective Research in Wuhan, China.

BACKGROUND AND OBJECTIVES: The pandemic of coronavirus disease 2019 (COVID-19) remains to be the biggest public threat all over the world. Because of the rapid deterioration in some patients, markers that could predict poor clinical outcomes are urgently required. This study was to evaluate the predictive values of cardiac injury parameters, including cardiac troponin I (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, on mortality in COVID-19 patients. METHODS: COVID-19 patients in Zhongfaxincheng branch of Tongji Hospital (Wuhan, China) from February 8-28, 2020, were enrolled in this study. We followed up the patients for 30 days after admission. RESULTS: A total of 134 patients were included in the study. Multivariate Cox regression showed that 1) patients with elevated cTnI levels had a higher risk of death (hazard ratio [HR] 7.33, 95% confidence interval [CI] 2.56-21.00) than patients with normal cTnI levels; 2) patients with elevated NT-proBNP levels had a higher risk of death (HR 27.88, 95% CI 3.55-218.78) than patients with normal NT-proBNP levels; 3) patients with both elevated cTnI and NT-proBNP levels had a significantly higher risk of death (HR 53.87, 95% CI 6.31-459.91, P < 0.001) compared to patients without elevated cTnI or NT-proBNP levels; 4) the progressions of cTnI and NT-proBNP levels were also correlated with death (HR 12.70, 95% CI 3.94-40.88, P < 0.001 and HR 51.09, 95% CI 5.82-448.26, P < 0.001). CONCLUSIONS: In COVID-19 patients, cTnI and NT-proBNP levels could be monitored to identify patients at a high risk of death in their later course of disease.

Combustion-derived particulate organic matter associated with hemodynamic abnormality and metabolic dysfunction in healthy adults.

Epidemiological evidence on cardiometabolic health of particulate organic matter (POM) and its sources is sparse. In a panel of 73 healthy adults in Beijing, China, daily concentrations of ambient fine particulate matter-bound polycyclic aromatic hydrocarbons (PAHs) and n-alkanes were measured throughout the study period, and Positive Matrix Factorization approach was used to identity PAHs sources. Linear mixed-effect models and mediation analyses were applied to examine the associations and potential interlink pathways between POM and biomarkers indicative of hemodynamics, insulin resistance, vascular calcification and immune inflammation. We found that significant alterations in cardiometabolic measures were associated with POM exposures. In specific, interquartile range increases in PAHs concentrations at prior up to 9 days were observed in association with significant elevations of 2.6-2.9% in diastolic blood pressure, 6.6-8.1% in soluble ST2, 10.5-14.5% in insulin, 40.9-45.7% in osteoprotegerin, and 36.3-48.7% in interleukin-17A. Greater associations were generally observed for PAHs originating from traffic emissions and coal burning. Mediation analyses revealed that POM exposures may prompt the genesis of hemodynamic abnormalities, possibly via worsening insulin resistance and calcification potential. These findings suggested that cardiometabolic health benefits would be achieved by reducing PM from combustion emissions.

Perturbation of amino acid metabolism mediates air pollution associated vascular dysfunction in healthy adults.

The molecular mechanisms of air pollution-associated adverse cardiovascular effects remain largely unknown. In the present study, we investigated the impacts of ambient air pollution on vascular function and the potential mediation effects of amino acids in a longitudinal follow-up of 73 healthy adults living in Beijing, China, between 2014 and 2016. We estimated associations between air pollutants and serum soluble intercellular adhesion molecule 1 (sICAM-1) and plasma levels of amino acids using linear mixed-effects models, and elucidated the biological pathways involved using mediation analyses. Higher air pollutant levels were significantly associated with increases in sICAM-1 levels. Metabolomics analysis showed that altered metabolites following short-term air pollution exposure were mainly involved in amino acid metabolism. Significant reductions in levels of plasma alanine, threonine and glutamic acid of 2.1 µM [95% confidence interval (CI): -3.8, -0.3] to 62.0 µM (95% CI: -76.1, -47.9) were associated with interquartile range increases in moving averages of PM2.5, BC, CO and SO2 in 1-7 days prior to clinical visits. Mediation analysis also showed that amino acids can mediate up to 48% of the changes in sICAM-1 associated with increased air pollution exposure. Our results indicated that air pollution may prompt vascular dysfunction through perturbing amino acid metabolism.

Association Between Average Plasma Potassium Levels and 30-day Mortality During Hospitalization in Patients with COVID-19 in Wuhan, China.

Background: Coronavirus disease 2019 (COVID-19) has resulted in more than 610,000 deaths worldwide since December 2019. Given the rapid deterioration of patients' condition before death, markers with efficient prognostic values are urgently required. During the treatment process, notable changes in plasma potassium levels have been observed among severely ill patients. We aimed to evaluate the association between average plasma potassium (Ka +) levels during hospitalization and 30-day mortality in patients with COVID-19. Methods: Consecutive patients with COVID-19 hospitalized in the Zhongfaxincheng branch of Tongji Hospital in Wuhan, China from February 8 to 28, 2020 were enrolled in this study. We followed patients up to 30 days after admission. Results: A total of 136 patients were included in the study. The average age was 62.1±14.6 years and 51.5% of patients were male. The median baseline potassium level was 4.3 (3.9-4.6) mmol/L and Ka + level during hospitalization was 4.4 (4.2-4.7) mmol/L; the median number of times that we measured potassium was 4 (3-5). The 30-day mortality was 19.1%. A J-shaped association was observed between Ka + and 30-day mortality. Multivariate Cox regression showed that compared with the reference group (Ka + 4.0 to <4.5 mmol/L), 30-day mortality was 1.99 (95% confidence interval [CI]=0.54-7.35, P=0.300), 1.14 (95% CI=0.39-3.32, P=0.810), and 4.14 (95% CI=1.29-13.29, P=0.017) times higher in patients with COVID-19 who had Ka + <4.0, 4.5 to <5.0, and ≥5.0 mmol/L, respectively. Conclusion: Patients with COVID-19 who had a Ka + level ≥5.0 mmol/L had a significantly increased 30-day mortality compared with those who had a Ka + level 4.0 to <4.5 mmol/L. Plasma potassium levels should be monitored routinely and maintained within appropriate ranges in patients with COVID-19.

Elevated resting heart rates are a risk factor for mortality among patients with coronavirus disease 2019 in Wuhan, China.

BACKGROUND: We evaluated the association between higher resting heart rates (RHRs) and adverse events in COVID-19 patients. METHODS: One hundred and thirty-six patients with laboratory-confirmed COVID-19 were admitted. Outcomes of patients with different RHRs were compared. RESULTS: Twenty-nine patients had RHRs of <80 bpm (beat per min), 85 had 80-99 bpm and 22 had ≥100 bpm as tachycardia. Those with higher RHRs had lower pulse oxygen saturation (SpO2) and higher temperatures, and there was a higher proportion of men upon admission (all P < 0.05). Patients with higher RHRs showed higher white blood cell counts and D-dimer, cardiac troponin I (TnI), N-terminal pro-B-type natriuretic peptide and hypersensitive C-reactive protein levels, but lower albumin levels (all P < 0.05) after admission. During follow-up, 26 patients died (mortality rate, 19.1%). The mortality rate was significantly higher among patients with tachycardia than among the moderate and low RHR groups (all P < 0.001). Kaplan-Meier survival curves showed that the risks of death and ventilation use increased for patients with tachycardia (P < 0.001). Elevated RHR as a continuous variable and a mean RHR as tachycardia were independent risk factors for mortality and ventilator use (all P < 0.05) in the multivariable adjusted Cox proportional hazards regression model. CONCLUSIONS: Elevated average RHRs during the first 3 days of hospitalisation were associated with adverse outcomes in COVID-19 patients. Average RHRs as tachycardia can independently predict all-cause mortality.

Protein biomarkers associated with frozen Japanese puffer fish (Takifugu rubripes) quality traits.

This study was designed to investigate proteome changes in Japanese puffer fish (Takifugu rubripes) during short- and long-term frozen storage. In total, 1484 proteins were quantified, and 164 proteins were identified as differential abundance proteins (DAPs) in Japanese puffer fish from two frozen storage treatment groups (14 days and 60 days) compared with the fresh control group. Correlation analysis between the DAPs and quality traits of the puffer fish muscle showed that 106 proteins were correlated closely with colour and texture (hardness, elasticity, and chewiness). Bioinformatics analysis revealed and Western blot analysis verified that Putative prothymosin alpha species, Bridging integrator 3, NADH: the ubiquinone oxidoreductase subunit and Mx species are candidate biomarkers for puffer fish properties. This study offers valuable evidence to improve the quality control and monitoring of Japanese puffer fish during transportation and storage.

The association between total homocysteine and blood pressure in two independent Chinese populations.

Hypertension and hyperhomocystinemia have a joint effect on the risk of stroke. We aimed to evaluate the relationship between plasma total homocysteine (tHcy) and blood pressure in two independent Chinese populations. Four thousand five hundred and fifty-five participants who underwent health examinations between March 2016 and September 2016 at Peking University First Hospital were enrolled as 'Population 1', and 2689 participants who were admitted to Peking University First Hospital between January 2014 and December 2015 were enrolled as 'Population 2'. None of the study participants were taking antihypertensive medication or vitamins, or had cardio-cerebrovascular disease or chronic kidney disease stages 4 or 5. In Population 1, a 5 µmol/L increase in tHcy was associated with a 0.47 mmHg (95% confidence interval [CI]: 0.23-0.70 mmHg, p < 0.01) increase in systolic blood pressure (SBP) and a 0.14 mmHg (95% CI: -0.02 to 0.30 mmHg, p = 0.08) increase in diastolic blood pressure (DBP). In Population 2, a 5 µmol/L increase in tHcy was associated with a 0.42 mmHg (95% CI: 0.13-0.72 mmHg, p < 0.01) increase in SBP and a 0.29 mmHg (95% CI: 0.09-0.49 mmHg, p < 0.01) increase in DBP. The prevalence of hypertension was significantly higher in Population 1 (by 47%; odds ratio [OR] 1.47, 95% CI: 1.09-1.98, p = 0.01) and in Population 2 (by 55%;OR 1.55, 95% CI: 1.15-2.08, p < 0.01) in participants with tHcy ≥ 15 µmol/l than in those with tHcy < 10 µmol/L. Stratified analysis showed that the association was stronger in women than in men.

Ambient Air Pollution Is Associated With HDL (High-Density Lipoprotein) Dysfunction in Healthy Adults.

Objective- We aimed to assess whether exposure to higher levels of ambient air pollution impairs HDL (high-density lipoprotein) function and to elucidate the underlying biological mechanisms potentially involved. Approach and Results- In the Beijing AIRCHD study (Air Pollution and Cardiovascular Dysfunction in Healthy Adults), 73 healthy adults (23.3±5.4 years) were followed-up with 4 repeated study visits in 2014 to 2016. During each visit, ambient air pollution concentrations, HDL function metrics, and parameters of inflammation and oxidative stress were measured. Average daily concentrations of ambient particulate matter in diameter <2.5 µm were 62.9 µg/m3 (8.1-331.0 µg/m3). We observed significant decreases in HDL cholesterol efflux capacity of 2.3% (95% CI, -4.3 to -0.3) to 5.0% (95% CI, -7.6 to -2.4) associated with interquartile range increases in moving average concentrations of particulate matter in diameter <2.5 µm and traffic-related air pollutants (black carbon, nitrogen dioxide, and carbon monoxide) during the 1 to 7 days before each participant's clinic visit. Higher ambient air pollutant levels were also associated with significant reductions in circulating HDL cholesterol and apoA-I (apolipoprotein A-I), as well as elevations in HDL oxidation index, oxidized LDL (low-density lipoprotein), malondialdehyde, and high-sensitivity C-reactive protein. Conclusions- Higher ambient air pollution concentrations were associated with impairments in HDL functionality, potentially because of systemic inflammation and oxidative stress. These novel findings further our understanding of the mechanisms whereby air pollutants promote cardiometabolic disorders.

Ambient air pollution is associated with cardiac repolarization abnormalities in healthy adults.

BACKGROUND: Ambient air pollution has been associated with acute cardiovascular events; however, the underlying mechanisms remain incompletely understood. We aimed to examine the impacts of ambient air pollutants on cardiac ventricular repolarization in a highly polluted urban region. METHODS: Seventy-three healthy non-smoking young adults (66% female, mean age of 23.3 ±â€¯5.4 years) were followed with four repeated 24-h electrocardiogram recordings in 2014-2016 in Beijing, China. Continuous concentrations of ambient particulates in size fractions of 5-560 nm diameter, black carbon (BC), nitrogen dioxide (NO2), carbon monoxide (CO), sulfur dioxide (SO2), and ozone (O3) were measured at a fixed-location air pollution monitoring station. Generalized linear mixed models, with adjustment for individual risk factors, time-varying factors and meteorological parameters, were used to evaluate the effects of air pollution on 5-min segments of heart rate-corrected QT interval (QTc), an index of cardiac ventricular repolarization. RESULTS: During the study period, the mean levels of number concentrations of particulates in size range of 5-560 nm (PNC5-560) were 20,711 particles/cm3. Significant increases in QTc of 0.56% (95% CI: 0.27, 0.84) to 1.76% (95% CI: 0.73, 2.79) were associated with interquartile range increases in PNC50-560 at prior 1-5 moving average days. Significant increases in QTc were also associated with increases in exposures to traffic-related air pollutants (BC, NO2 and CO), a combustion pollutant SO2, and the secondary pollutant O3. The associations were stronger in participants who were male, overweight, with abdominal obesity, and with higher levels of high-sensitivity C-reactive protein. CONCLUSIONS: Our findings suggest that exposures to higher levels of ambient particulates in small size fractions and traffic pollutants were associated with cardiac repolarization abnormalities in healthy adults, and the cardio-metabolic risks may modify the adverse cardiac effects attributable to air pollution.

Extreme Levels of Air Pollution Associated With Changes in Biomarkers of Atherosclerotic Plaque Vulnerability and Thrombogenicity in Healthy Adults.

RATIONALE: The pathophysiologic mechanisms of air pollution-associated exacerbation of cardiovascular events remain incompletely understood. OBJECTIVE: To assess whether ambient air pollution can be a trigger of the vulnerable plaque and heightened thrombogenicity through systemic inflammatory pathways. METHODS AND RESULTS: In Beijing AIRCHD study (Air Pollution and Cardiovascular Dysfunctions in Healthy Adults Living in Beijing), 73 healthy adults (mean±SD, 23.3±5.4 years) were followed up in 2014 to 2016. We estimated associations between air pollutants and biomarkers relevant to atherosclerotic plaque vulnerability, thrombogenicity, and inflammation using linear mixed-effects models and elucidated the biological pathways involved using mediation analyses. Receiver operating characteristic analyses were conducted to assess the ability of each biomarker to predict ambient air pollution exposures. High average concentrations of particulate matter in diameter <2.5 µm (91.8±63.8 µg/m3) were observed during the study period. Significant increases in circulating biomarkers of plaque vulnerability, namely MMPs (matrix metalloproteinases; MMP-1, 2, 3, 7, 8, and 9), of 8.6% (95% CI, 0.1-17.8) to 141.4% (95% CI, 111.8-171.0) were associated with interquartile range increases in moving averages of particulate matter in diameter <2.5 µm, number concentrations of particles in sizes of 5 to 560 nm and black carbon, during the last 1 to 7 days before each participant's clinic visit. Higher air pollutant levels were also significantly associated with decreases in TIMP (tissue inhibitors of MMPs; TIMP-1 and 2), heightened thrombogenicity (shortened prothrombin time and increases in sCD40L [soluble CD40 ligand], sCD62P [soluble P-selectin], and fibrinogen/fibrin degradation products), and elevations in systemic inflammation (IL-1ß [interleukin-1ß], CRP [C-reactive protein], MIP-1α/ß [macrophage inflammatory protein-1α/ß], sRAGE [soluble receptor for advanced glycation end products], and IGFBP [insulin-like growth factor-binding protein]-1 and 3). Receiver operating characteristic curves showed that several biomarkers can serve as robust pollutant-specific predictors with high versus low black carbon exposure (area under the receiver operating characteristic curve of 0.974 [95% CI, 0.955-0.992] for MMP-8 and 0.962 [95% CI, 0.935-0.988] for sRAGE). Mediation analysis further showed that systemic inflammation can mediate ≤46% of the changes in MMPs and thrombogenicity associated with interquartile range increases in air pollutants. CONCLUSIONS: Our results suggest that air pollution may prompt cardiovascular events by triggering vulnerable plaque along with heightened thrombogenicity possibly through systemic inflammatory pathways.

Short-term effects of ambient air pollution and outdoor temperature on biomarkers of myocardial damage, inflammation and oxidative stress in healthy adults.

The mechanisms whereby ambient air pollution and temperature changes promote cardiac events remain incompletely described. Seventy-three nonsmoking healthy adults (mean age 23.3, SD 5.4 years) were followed with up to four repeated visits across 15 months in Beijing in 2014-2016. Biomarkers relevant to myocardial damage (high-sensitivity cardiac troponin I [hs-cTnI]), inflammation (growth differentiation factor-15 [GDF-15]), and oxidative stress (8-hydroxy-2'-deoxyguanosine [8-OHdG]) were measured at each visit, while ambient air pollution and temperature were monitored throughout the study. Linear mixed-effects models coupled with distributed lag nonlinear models were used to assess the impacts of each exposure measure on study outcomes. During follow-up, average daily concentrations of fine particulate matter and outdoor temperature were 62.9 µg/m3 (8.1-331.0 µg/m3) and 10.1 °C (-6.5°C to 29.5°C). Serum hs-cTnI levels were detectable in 18.2% of blood samples, with 27.4% of individuals having ≥1 detectable values. Higher levels of ambient particulates and gaseous pollutants (per interquartile range) up to 14 days before clinical visits were associated with significant alterations in hs-cTnI levels of 22.9% (95% CI, 6.4, 39.4) to 154.7% (95% CI, 94.4, 215.1). These changes were accompanied by elevations of circulating GDF-15 and urinary 8-OHdG levels. Both low (5th percentile, -2.5 °C) and high (95th percentile, 24.8°C) outdoor temperatures, with breakpoint at ~13.0°C as the reference level, were also associated with elevations of hs-cTnI levels. Short-term exposure to ambient air pollution and temperature was associated with cardiac troponin, a biomarker of myocardial damage, along with increased inflammation and oxidative stress responses. These findings extend our understanding of the biological mechanisms linking pervasive environmental exposure to adverse cardiac events.

Short-Term Blood Pressure Responses to Ambient Fine Particulate Matter Exposures at the Extremes of Global Air Pollution Concentrations.

BACKGROUND: Fine particulate matter (PM2.5) air pollution is a leading cause of global cardiovascular mortality. A key mechanism may be PM2.5-induced blood pressure (BP) elevations. Whether consistent prohypertensive responses persist across the breadth of worldwide pollution concentrations has never been investigated. METHODS: We evaluated the hemodynamic impact of short-term exposures to ambient PM2.5 in harmonized studies of healthy normotensive adults (4 BP measurements per participant) living in both a highly polluted (Beijing) and clean (Michigan) location. RESULTS: Prior 7-day outdoor-ambient and 24-hour personal-level PM2.5 concentration averages were much higher in Beijing (86.7 ± 52.1 and 52.4 ± 79.2 µg/m3) compared to Michigan (9.1 ± 1.8 and 12.2 ± 17.0 µg/m3). In Beijing (n = 73), increased outdoor-ambient exposures (per 10 µg/m3) during the prior 1-7 days were associated with significant elevations in diastolic BP (0.15-0.17 mm Hg). In overweight adults (body mass index ≥25 kg/m2), significant increases in both systolic (0.34-0.44 mm Hg) and diastolic (0.22-0.66 mm Hg) BP levels were observed. Prior 24-hour personal-level exposures also significantly increased BP (0.41/0.61 mm Hg) in overweight participants. Conversely, low PM2.5 concentrations in Michigan (n = 50), on average within Air Quality Guidelines, were not associated with BP elevations. CONCLUSIONS: Our findings demonstrate that short-term exposures to ambient PM2.5 in a highly polluted environment can promote elevations in BP even among healthy adults. The fact that no adverse hemodynamic responses were observed in a clean location supports the key public health importance of international efforts to improve air quality as part of the global battle against hypertension.

Comparative RNA-Seq analysis of differentially expressed genes in the testis and ovary of Takifugu rubripes.

Takifugu rubripes is a classical model organism for studying the role of gonad organogenesis in such physiological processes as fertilization, sex determination, and sexual development. To explicitly investigate the mechanism associated with gonad organogenesis in T. rubripes, we obtained 44.3 million and 55.2 million raw reads from the testis and ovary, respectively, by RNA-seq and from these, 18,523 genes were identified. A total of 680 differentially expressed genes were obtained from comparison transcriptome analysis between the testis and ovary, and of these, 556 genes were up-regulated in the testis, whereas only 124 genes were upregulated in the ovary. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that many of these genes encode proteins involved in signal transduction and gonad development. We mainly focused on the differentially expressed genes that have the potential to develop into the gonad. The generation of large scale transcriptomic data presented in this work would enrich the genetic resources of T. rubripes, which should be valuable to the comparative and evolutionary studies of teleosts.