High-Resolution Modeling of Summertime Biogenic Isoprene Emissions in New York City.

As cities strive for ambitious increases in tree canopy cover and reductions in anthropogenic volatile organic compound (AVOC) emissions, accurate assessments of the impacts of biogenic VOCs (BVOCs) on air quality become more important. In this study, we aim to quantify the impact of future urban greening on ozone production. BVOC emissions in dense urban areas are often coarsely represented in regional models. We set up a high-resolution (30 m) MEGAN (The Model of Emissions of Gases and Aerosols from Nature version 3.2) to estimate summertime biogenic isoprene emissions in the New York City metro area (NYC-MEGAN). Coupling an observation-constrained box model with NYC-MEGAN isoprene emissions successfully reproduced the observed isoprene concentrations in the city core. We then estimated future isoprene emissions from likely urban greening scenarios and evaluated the potential impact on future ozone production. NYC-MEGAN predicts up to twice as much isoprene emissions in NYC as the coarse-resolution (1.33 km) Biogenic Emission Inventory System version 3.61 (BEIS) on hot summer days. We find that BVOCs drive ozone production on hot summer days, even in the city core, despite large AVOC emissions. If high isoprene emitting species (e.g., oak trees) are planted, future isoprene emissions could increase by 1.4-2.2 times in the city core, which would result in 8-19 ppbv increases in peak ozone on ozone exceedance days with current NOx concentrations. We recommend planting non- or low-isoprene emitting trees in cities with high NOx concentrations to avoid an increase in the frequency and severity of future ozone exceedance events.

Lipidomics Reveals the Effects of Detergents on Skin Surface Lipids in Young Adults.

BACKGROUND: Detergent is a chemical product commonly used in people's daily life. Contact with detergent solutions can damage the human skin barrier and cause skin diseases. Skin surface lipids (SSLs) play a decisive role in skin barrier function. This study aimed to observe the changes of SSLs in young adults after exposure to detergent solutions to explore the underlying mechanism of skin barrier function damage. METHODS: A self-controlled study on youth adults was conducted in Zhengzhou, China, in November 2020. The study lasted for a total of 1 week, and skin barrier function was assessed by trans-epidermal water loss (TEWL) values. The changes of SSLs before and after exposure to the detergent with subjects were measured using ultra-performance liquid chromatography quadrupole time of flight mass spectrometry. RESULTS: The skin barrier function of subjects' hands was impaired after exposure to detergent (TEWL value increased, p < 0.001). A total of 520 SSLs were detected, divided into 6 main categories. The average relative abundance of these 6 major lipids decreased after exposure. Sphingolipids (mainly ceramides), free fatty acids (mainly long-chain fatty acids), cholesterol lipids, and glycerophospholipids are the most severely damaged lipids. CONCLUSION: Detergent solutions can damage the skin barrier function and SSLs of young hands; interventions targeting SSLs to eliminate detergent damage to human skin may be of value.

Mitochondrial coding genes mediate insecticide tolerance in the oriental fruit fly, Bactrocera dorsalis (Hendel).

The oriental fruit fly, Bactrocera dorsalis (Hendel), an invasive insect pest infesting fruits and vegetables, possesses a remarkable capacity for environmental adaptation. The investigation of behind mechanisms of the stress adaptability in B. dorsalis holds significantly practical relevance. Previous studies on the molecular mechanism underlying stress resistance in B. dorsalis have predominantly focused on nuclear-coding genes, with limited exploration on organelle-coding genes. In this study, we assessed alterations in the mitochondrial physiological parameters of B. dorsalis under exposure to malathion, avermectin, and beta-cypermethrin at LD50 dosages. The results showed that all three insecticides were capable of reducing mitochondrial complex IV activity and ATP content. Expression patterns of mitochondrial coding genes across different developmental stages, tissues and insecticide exposures were analyzed by RT-qPCR. The results revealed that these mitochondrial coding genes were expressed in various tissues and at different developmental stages. Particularly noteworthy, atp6, cox2, and cytb exhibited substantial up-regulation in response to malathion and avermectin treatment. Furthermore, RNAi-mediated knockdown of atp6 and cox2 resulted in the increased toxicity of malathion and avermectin against B. dorsalis, and cox2 silencing was also associated with the decreased complex IV activity. These findings suggest that atp6 and cox2 most likely play pivotal roles in mediating tolerance or resistance to malathion and avermectin in B. dorsalis. Our results provide novel insights into the role of mitochondrial coding genes in conferring tolerance to insecticides in B. dorsalis, with practical implications for controlling this pest in the field.

The association of cortisol, testosterone, and cortisol/testosterone ratio with stroke: A cross-sectional study.

AIMS: We aimed to investigate the association between serum cortisol, testosterone, and cortisol/testosterone (C/T) ratio and stroke. MATERIALS AND METHODS: A total of 6157 subjects were included in this study. The serum levels of cortisol and testosterone were determined by liquid chromatography-tandem mass spectrometry method. The relationships of serum cortisol, testosterone, and C/T ratio levels with the odds ratios (ORs) of stroke were calculated using logistic regression analysis. The dose-response associations between serum cortisol, testosterone, and C/T ratio levels with stroke estimated by restricted cubic splines. RESULTS: After adjusting for multiple variables, serum testosterone levels were negactively associated with stroke in males (per 1 unit, odds ratio (OR) = 0.83, 95 % confidence interval (CI): 0.70, 0.97). The serum C/T ratio is positively associated with stroke in both males and females (OR = 1.16, 95 % CI:1.04,1.34 in males and OR = 1.15, 95 % CI:1.02,1.31 in females). Restricted cubic splines showed a significant linear dose-response relationship between testosterone and C/T ratio and stroke in males (P for overall association <0.05, P for nonlinearity >0.05). CONCLUSION: Our study findings show that serum testosterone levels are negatively correlated with stroke in males; meanwhile, serum C/T ratio is positively correlated with stroke in both males and females.

Proteomic Characterization of Peritoneal Extracellular Vesicles in a Mouse Model of Peritoneal Fibrosis.

Peritoneal fibrosis progression is regarded as a significant cause of the loss of peritoneal function, markedly limiting the application of peritoneal dialysis (PD). However, the pathogenesis of peritoneal fibrosis remains to be elucidated. Tissue-derived extracellular vesicles (EVs) change their molecular cargos to adapt the environment alteration, mediating intercellular communications and play a significant role in organ fibrosis. Hence, we performed, for the first time, four-dimensional label-free quantitative liquid chromatography-tandem mass spectrometry proteomic analyses on EVs from normal peritoneal tissues and PD-induced fibrotic peritoneum in mice. We demonstrated the alterations of EV concentration and protein composition between normal control and PD groups. A total of 2339 proteins containing 967 differentially expressed proteins were identified. Notably, upregulated proteins in PD EVs were enriched in processes including response to wounding and leukocyte migration, which participated in the development of fibrosis. In addition, EV proteins of the PD group exhibited unique metabolic signature compared with those of the control group. The glycolysis-related proteins increased in PD EVs, while oxidative phosphorylation and fatty acid metabolism-related proteins decreased. We also evaluated the effect of cell-type specificity on EV proteins, suggesting that mesothelial cells mainly cause the alterations in the molecular composition of EVs. Our study provided a useful resource for further validation of the key regulator or therapeutic target of peritoneal fibrosis.

Serum Progesterone is Negatively Associated with Hypertension and Blood Pressure Indicators Among Men and Postmenopausal Women.

Sex hormones have been shown to be negatively associated with hypertension, but the relationship between serum progesterone levels and hypertension has not been adequately studied. Therefore, we aimed to evaluate the association between progesterone and hypertension among Chinese rural adults. A total of 6222 participants were recruited, which included 2577 men and 3645 women. The concentration of serum progesterone was detected by liquid chromatography-mass spectrometer system (LC-MS/MS). Logistic regression and linear regression were used to assess the associations between progesterone levels and hypertension and blood pressure related indicators, respectively. Constrained splines were used to fit the dose-response relationships of progesterone with hypertension and blood pressure related indicators. Moreover, the interactive effects of several lifestyle factors and progesterone were identified by a generalized linear model. After fully adjusting the variables, progesterone levels were inversely associated with hypertension in men [odds ratio (OR): 0.851, 95% confidence interval (CI): 0.752, 0.964]. Among men, a 2.738 ng/ml increase in progesterone was associated with a 0.557 mmHg decrease in diastolic blood pressure (DBP) (95% CI: -1.007, -0.107) and a 0.541 mmHg decrease in mean arterial pressure (MAP) (95% CI: -1.049, -0.034), respectively. Similar results were observed in postmenopausal women. Interactive effect analysis showed that only a significant interaction was observed between progesterone and educational attainment on hypertension in premenopausal women (p=0.024). Elevated levels of serum progesterone were associated with hypertension in men. Except for premenopausal women, a negative association of progesterone with blood pressure related indicators was observed.

Enantioselective Fluorescence Recognition of Free α-Amino Acids by Ion-Type Ammonium Salt-Based Sensors.

Optically pure amino acids have extensive applications in pharmaceuticals, pesticides, food, materials, and other fields. Enantiomers recognition of chiral amino acids using optical methods with synthetic chiral sensors has attracted extensive attention. Most reported sensors typically identify guests by covalent or hydrogen bonding or hydrophobic interaction with amino acids and their derivatives. In this paper, a series of ion-type quaternary ammonium salt-based enantioselective fluorescent sensors were synthesized for chiral recognition of free α-amino acids via electrostatic interaction. The fluorescence intensity ratios ID/IL (ID, IL, fluorescence intensity of sensor when treated with D- or L-amino acid) were up to 2.1 and enantioselective fluorescence enhancement ratios ef (ef=[IL-I0]/[ID-I0] or [ID-I0]/[IL-I0]. (I0, fluorescence intensity of the sensor)) were up to 5.0. Among them, sensor 3 showed best enantioselective recognition performance toward tryptophan (Trp), and L-Trp significantly quenched the fluorescence of sensor 3, but D-Trp greatly enhanced the fluorescence of sensor 3, its ID/IL was 2.11 and ef was 1.8. The mechanistic investigation by NMR spectrum revealed that a tight three-point interaction, including electrostatic interaction, hydrogen bond, and π-π stacking, between sensor 3 and D-Trp was formed.

Changes in the Microbiota and their Roles in Patients with Type 2 Diabetes Mellitus.

An association between type 2 diabetes mellitus (T2DM) and gut microbiota is well established, but the results of related studies are inconsistent. The purpose of this investigation is to elucidate the characteristics of the gut microbiota in T2DM and non-diabetic subjects. Forty-five subjects were recruited for this study, including 29 T2DM patients and 16 non-diabetic subjects. Biochemical parameters, including body mass index (BMI), fasting plasma glucose (FPG), serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and hemoglobin A1c (HbA1c), were analyzed and correlated with the gut microbiota. Bacterial community composition and diversity were detected in fecal samples using direct smear, sequencing, and real-time polymerase chain reaction (PCR). In this study, it was observed that indicators such as BMI, FPG, HbA1c, TC, and TG in T2DM patients were on the rise, concurrent with dysbiosis of the microbiota. We observed an increase in Enterococci and a decrease in Bacteroides, Bifidobacteria, and Lactobacilli in patients with T2DM. Meanwhile, total short-chain fatty acids (SCFAs) and D-lactate concentrations were decreased in the T2DM group. In addition, FPG was positively correlated with Enterococcus and negatively correlated with Bifidobacteria, Bacteroides, and Lactobacilli. This study reveals that microbiota dysbiosis is associated with disease severity in patients with T2DM. The limitation of this study is that only common bacteria were noted in this study, and more in-depth related studies are urgently needed.

The miR-9b microRNA mediates dimorphism and development of wing in aphids.

Wing dimorphism is a phenomenon of phenotypic plasticity in aphid dispersal. However, the signal transduction for perceiving environmental cues (e.g., crowding) and the regulation mechanism remain elusive. Here, we found that aci-miR-9b was the only down-regulated microRNA (miRNA) in both crowding-induced wing dimorphism and during wing development in the brown citrus aphid Aphis citricidus We determined a targeted regulatory relationship between aci-miR-9b and an ABC transporter (AcABCG4). Inhibition of aci-miR-9b increased the proportion of winged offspring under normal conditions. Overexpression of aci-miR-9b resulted in decline of the proportion of winged offspring under crowding conditions. In addition, overexpression of aci-miR-9b also resulted in malformed wings during wing development. This role of aci-miR-9b mediating wing dimorphism and development was also confirmed in the pea aphid Acyrthosiphon pisum The downstream action of aci-miR-9b-AcABCG4 was based on the interaction with the insulin and insulin-like signaling pathway. A model for aphid wing dimorphism and development was demonstrated as the following: maternal aphids experience crowding, which results in the decrease of aci-miR-9b. This is followed by the increase of ABCG4, which then activates the insulin and insulin-like signaling pathway, thereby causing a high proportion of winged offspring. Later, the same cascade, "miR-9b-ABCG4-insulin signaling," is again involved in wing development. Taken together, our results reveal that a signal transduction cascade mediates both wing dimorphism and development in aphids via miRNA. These findings would be useful in developing potential strategies for blocking the aphid dispersal and reducing viral transmission.

Exposure to herbicides mixtures in relation to type 2 diabetes mellitus among Chinese rural population: Results from different statistical models.

BACKGROUND: Although it has been reported that herbicides exposure is related to adverse outcomes, available evidence on the associations of quantitatively measured herbicides with type 2 diabetes mellitus (T2DM) and prediabetes is still scant. Furthermore, the effects of herbicides mixtures on T2DM and prediabetes remain unclear among the Chinese rural population. AIMS: To assess the associations of plasma herbicides with T2DM and prediabetes among the Chinese rural population. METHODS: A total of 2626 participants were enrolled from the Henan Rural Cohort Study. Plasma herbicides were measured with gas chromatography coupled to triple quadrupole tandem mass spectrometry. Generalized linear regression analysis was employed to assess the associations of a single herbicide with T2DM, prediabetes, as well as indicators of glucose metabolism. In addition, the quantile g-computation and environmental risk score (ERS) structured by adaptive elastic net (AENET), and Bayesian kernel machine regression (BKMR) were used to estimate the effects of herbicides mixtures on T2DM and prediabetes. RESULTS: After adjusting for covariates, positive associations of atrazine, ametryn, and oxadiazon with the increased odds of T2DM were obtained. As for prediabetes, each 1-fold increase in ln-transformed oxadiazon was related to 8.4% (95% confidence interval (CI): 1.033, 1.138) higher odds of prediabetes. In addition, several herbicides were significantly related to fasting plasma glucose, fasting insulin, and HOMA2-IR (false discovery rates adjusted P value < 0.05). Furthermore, the quantile g-computation analysis showed that one quartile increase in multiple herbicides was associated with T2DM (OR (odds ratio): 1.099, 95%CI: 1.043, 1.158), and oxadiazon was assigned the largest positive weight, followed by atrazine. In addition, the ERS calculated by the selected herbicides from AENET were found to be associated with T2DM and prediabetes, and the corresponding ORs and 95%CIs were 1.133 (1.108, 1.159) and 1.065 (1.016, 1.116), respectively. The BKMR analysis indicated a positive association between mixtures of herbicides exposure and the risk of T2DM. CONCLUSIONS: Exposure to mixtures of herbicides was associated with an increased risk of T2DM among Chinese rural population, indicating that the impact of herbicides exposure on diabetes should be paid attention to and measures should be taken to avoid herbicides mixtures exposure.

Higher HDL-C levels attenuated the association of plasma polybrominated diphenyl ethers with prediabetes and type 2 diabetes mellitus in rural Chinese adults.

BACKGROUND: Plasma polybrominated diphenyl ethers (PBDE) were used as flame retardants widely, however, epidemiological evidence for the association between PBDEs and type 2 diabetes mellitus (T2DM) is inconsistent. Moreover, the combined effects of PBDEs and blood lipid indicators on impaired fasting glucose (IFG) and T2DM remains largely unknown in rural areas lacking good waste recycling infrastructure. METHODS: In this study, a total of 2607 subjects aged 18-79 years were included from the Henan Rural Cohort. Generalized linear and logistic regression models were applied to evaluate the associations of various PBDE pollutants on IFG and T2DM. Quantile g-computation regression and PBDE pollution score created by the adaptive elastic net were applied to evaluate the impact of PBDEs mixtures on IFG and T2DM. Interaction effects of individual PBDE pollutants and blood lipid indicators on IFG and T2DM were assessed by using Interaction plots. RESULTS: The geometric mean concentrations (detection rates) were 0.09 ng/mL (100.0%), 0.12 ng/mL (97.8%), 0.22 ng/mL (94.7%), 0.16 ng/mL (99.2%) and 0.28 ng/mL (100.0%) for PBDE-28, PBDE-47, PBDE-99, and PBDE-153 respectively. However, PBDE-28, PBDE-99, PBDE-100, and ΣPBDEs were positively associated with IFG (odds ratios (ORs) (95% confidence intervals (CIs)): 1.14 (1.06, 1.23), 1.16 (1.04, 1.29), 1.25 (1.14, 1.37), and 1.27 (1.08, 1.50)). Similarly, PBDE-28, PBDE-47, PBDE-99, PBDE-100, and ΣPBDEs were positively associated with T2DM (ORs (95% CIs): 1.30 (1.10, 1.54), 1.13 (1.06, 1.22), 1.27 (1.13, 1.43), 1.27 (1.15, 1.40), and 1.30 (1.10, 1.54)). Moreover, five PBDE mixtures or jointly as PBDE pollution score, were significantly associated with an increased risk of T2DM (P < 0.05 for all). In addition, the harmful effect of PBDE exposure on T2DM was decreased with accompanying high-density lipoprotein cholesterol (HDL-C) levels increased. CONCLUSIONS: Our findings highlight the importance of managing PBDEs contamination and suggest that HDL-C may be a novel way to prevent T2DM.

Overexpression of ABCB transporter genes confer multiple insecticide tolerances in Bactrocera dorsalis (Hendel) (Diptera: Tephritidae).

Bactrocera dorsalis is a notable invasive pest that has developed resistance to several commonly used insecticides in the field, such as avermectin, beta-cypermethrin and malathion. Investigating the mechanisms of insecticide resistance in this pest is of paramount importance for ensuring its effective control. The ATP-binding cassette transporter subfamily B (ABCB) genes, responsible for encoding transmembrane efflux transporters, represent a potential source of insecticide detoxification activity or transportation that remains largely unexplored in B. dorsalis. In this study, seven BdABCB genes were identified and comprehensive analyzed based on the latest genome and transcriptome dataset. Subsequently, we characterized the expression profiles of these genes across different development stages and tissues, as well as under different insecticide exposures. The results showed that the BdABCB genes were expressed at all stages in B. dorsalis, with BdABCB2 and BdABCB7 being highly expressed in the pupal stage, while BdABCB5 and BdABCB6 were highly expressed in the larval stage. Besides, the BdABCBs were highly expressed in the detoxification metabolic tissues. Among them, BdABCB5 and BdABCB6 were significantly overexpressed in the midgut and Malpighian tubules, respectively. Furthermore, with the exception of BdABCB6, the expression levels of the other six BdABCBs were significantly up-regulated following induction with avermectin, beta-cypermethrin and malathion. Six BdABCBs (BdABCB1-5 and BdABCB7) were knocked down by RNA interference, and the interference efficiencies were 46.58%, 39.50%, 45.60%, 33.74%, 66.37% and 63.83%, respectively. After injecting dsBdABCBs, the mortality of flies increased by 25.23% to 39.67% compared to the control upon exposure to the three insecticides. These results suggested that BdABCBs play crucial roles in the detoxification or tolerance of B. dorsalis to multiple insecticides.

Gender-specific associations between mixture of polycyclic aromatic hydrocarbons and telomere length.

Evidence shows the relationships of individual environmental PAHs by their urinary metabolites with relative telomere length (RTL), which may be affected by biological gender differences. Since plasma parent PAHs are not metabolized, it may reflect human exposure to PAHs more realistically in daily life. Thus, exploring joint associations between plasma parent PAHs and RTL is urgent, which may identify the major contributor to its adverse effect. In this study, 2577 participants were obtained from the Henan Rural Cohort. The level of PAHs in blood samples was detected by gas chromatography coupled with tandem mass spectrometry. RTL in blood samples was detected by quantitative polymerase chain reaction. Generalized linear models or quantile g-computation were performed to evaluate the associations between the individual or a mixture of PAHs and RTL. Results from generalized linear models showed that each unit increment in BghiP value corresponded to a 0.098 (95%CI: 0.067, 0.129) increment in RTL for men; each unit increment in BaP, BghiP and Flu value corresponded to a 0.041 (95%CI: 0.014, 0.068), 0.081 (95%CI: 0.055, 0.107) and 0.016 (95%CI: 0.005, 0.027) increment in RTL for women. Results from quantile-g computation revealed that each one-quantile increment in the mixture of 10 PAHs corresponded to a 0.057 (95%CI: 0.021, 0.094) and 0.047 (95%CI: 0.003, 0.091) increment in RTL values of women and men, but these associations were mainly ascribed to three PAHs for women (BaP, Flu and BghiP) and men (BaP, BghiP and Pyr), respectively. Similar results were found in smoking men and cooking women without smoking. Our study found that exposure to 10 PAHs mixture was positively associated with RTL across gender, mainly attributed to Flu, BaP and BghiP, implicating that gender-specific associations may be ascribed to tobacco and cooking smoke pollution. The findings provided clues for effective measures to control PAHs pollutants-related aging disease.Clinical trial registration The Henan Rural Cohort Study has been registered at the Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). Date of registration: 06 July 2015. http://www.chictr.org.cn/showproj.aspx?proj=11375 .

Nosocomial transmission and rearrangement of large resistance-virulence hybrid plasmids between two bacteremic ST11 carbapenem-resistant hypervirulent Klebsiella pneumoniae strains with low fitness cost.

OBJECTIVES: To characterize nosocomial transmission and rearrangement of the resistance-virulence plasmid between two ST11-K64 carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) strains (JX-CR-hvKP-10 and JX-CR-hvKP-9) with low fitness. METHODS: Phenotypic tests were used to assess the virulence of JX-CR-hvKP-10 and JX-CR-hvKP-9. Whole-genome sequencing was used to analyze JX-CR-hvKP-10 and JX-CR-hvKP-9 chromosomes and plasmids. Fitness and conjugation experiments were also conducted using these two CR-hvKP isolates. RESULTS: Phenotypic tests indicated that both JX-CR-hvKP-10 and JX-CR-hvKP-9 were multidrug-resistant and hypervirulent K. pneumoniae. Whole-genome sequencing and clinical information demonstrated that the super large resistance-virulence fusion plasmid pJX10-1 formed precisely by the fusion of pJX9-1 and pJX9-2 via the nosocomial transmission. Interestingly pJX9-1 itself was also a classic resistance-virulence fusion plasmid by way of the blaKPC-carrying resistance plasmid and pLVPK-like virulence plasmid. Compared with classic K. pneumoniae ATCC700603, fitness analysis revealed no significant difference in growth was observed between JX-CR-hvKP-10 and JX-CR-hvKP-9. CONCLUSION: Nosocomial transmission and rearrangement of a blaKPC-harboring plasmid and a pLVPK-like virulence plasmid with a low fitness cost in ST11 K. pneumoniae enhances drug resistance and virulence simultaneously. Thus, active surveillance of this hybrid plasmid is needed to prevent these efficient resistance-virulence plasmids from disseminating in hospital settings.

Ambient ozone exposure combined with residential greenness in relation to serum sex hormone levels in Chinese rural adults.

BACKGROUND: Long-term exposure to ambient ozone (O3) and residential greenness independently relate to altered hormones levels in urban settings and developed countries. However, independent and their joint associations with progestogen and androgen were sparsely studied in rural regions. MATERIALS AND METHODS: A total of 6211 individuals were recruited in this study. Random forest model was applied to predict the daily average concentrations of O3 using the satellites data. Residential greenness was reflected by the normalized difference vegetation index (NDVI). Liquid chromatography-tandem mass spectrometry was used to measure serum progestogen and androgen concentrations. Gender and menopausal status modified associations of long-term exposure to O3 and residential greenness with hormones levels were analyzed by generalized linear models. RESULTS: Long-term exposure to O3 was negatively related to 17-hydroxyprogesterone, testosterone, and androstenedione in both men and women (premenopausal and postmenopausal); the estimated ß and 95% CI of ln-progesterone in response to per 10 µg/m3 increment in O3 concentration was -0.560 (-0.965, -0.155) in postmenopausal women. Association of long-term exposure to O3 with serum androgen levels in premenopausal and postmenopausal women were alleviated by residing in places with higher greenness. Additionally, a prominent effect of long-term exposure to O3 related to decreased serum progestogen and androgen levels was found in participants with middle- or high-level of physical activity or lower education level. CONCLUSIONS: The results suggested that long-term exposure to high levels of O3 related to decreased serum androgen levels was attenuated by living in high greenness places in women regardless of menopause status. Future studies are needed to confirm the positive health effects of residential greenness on the potential detrimental effects due to exposure to O3.

Glycinebetaine mitigates tomato chilling stress by maintaining high-cyclic electron flow rate of photosystem I and stability of photosystem II.

KEY MESSAGE: Glycinebetaine alleviates chilling stress by protecting photosystems I and II in BADH-transgenic and GB-treated tomato plants, which can be an effective strategy for improving crop chilling tolerance. Tomato (Solanum lycopersicum) is one of the most cultivated vegetables in the world, but is highly susceptible to chilling stress and does not naturally accumulate glycinebetaine (GB), one of the most effective stress protectants. The protective mechanisms of GB on photosystem I (PSI) and photosystem II (PSII) against chilling stress, however, remain poorly understood. Here, we address this problem through exogenous GB application and generation of transgenic tomatoes (Moneymaker) with a gene encoding betaine aldehyde dehydrogenase (BADH), which is the key enzyme in the synthesis of GB, from spinach. Our results demonstrated that GB can protect chloroplast ultramicrostructure, alleviate PSII photoinhibition and maintain PSII stability under chilling stress. More importantly, GB increased the electron transfer between QA and QB and the redox potential of QB and maintained a high rate of cyclic electron flow around PSI, contributing to reduced production of reactive oxygen species, thereby mitigating PSI photodamage under chilling stress. Our results highlight the novel roles of GB in enhancing chilling tolerance via the protection of PSI and PSII in BADH transgenic and GB-treated tomato plants under chilling stress. Thus, introducing GB-biosynthetic pathway into tomato and exogenous GB application are effective strategies for improving chilling tolerance.

Associations of residential greenness, ambient air pollution, biological sex, and glucocorticoids levels in rural China.

AIMS: To evaluate the associations between residential greenness and glucocorticoid levels and whether air pollutants and sex modify the relationship between greenness and glucocorticoid level in Chinese rural adults. METHODS: We collected cross-sectional survey data from 6055 participants from the Henan Rural cohort. The three-year average residential greenness for participants was assessed using normalized difference vegetation index (NDVI) values from a satellite platform. Liquid chromatography-tandem mass spectrometry was employed to quantify the concentrations of glucocorticoids, which were measured by morning blood draw after at least 8 hr of fasting. A random forest model was employed to obtain the average concentrations of PM1, PM2.5, and PM10. A general linear regression model was performed to estimate the associations of NDVI500-m values with cortisol, 11-deoxycortisol, and cortisone. Furthermore, interaction plots were used to present the interaction effects of particulate matter, sex, and green space on glucocorticoid levels. RESULTS: After adjusting for multiple variables, an elevated average NDVI500-m value in the total population was associated with a decrease in cortisol levels (ß = -0.063, 95 % confidence interval (CI): - 0.118, - 0.008), and 11-deoxycortisol levels (ß = -0.118, 95 % CI: -0.190, -0.047), as well as an increase in cortisone levels (ß = 0.130, 95 % CI: 0.079, 0.181). By adding the interaction terms of air pollutants and residential greenness into the regression model, interaction effects between air pollutants and residential greenness were found (cortisol, PM2.5: P interaction=:0.018; PM10: P interaction=0.016; 11-deoxycortisol, all pollutants: P interaction< 0.001), suggesting that the protective effect of residential greenness on serum glucocorticoids disappeared accompanying with increased concentrations of particulate matter. Moreover, trends towards modification in the association between green space and glucocorticoid levels were also evident by sex, but these did not reach statistical significance (for all glucocorticoids: P interaction> 0.05). CONCLUSION: Long-term exposure to green space was negatively correlated with cortisol and 11-deoxycortisol levels, and positively correlated with cortisone levels. There may be sex differences in these associations. Moreover, the protective effect of residential greenness on serum glucocorticoids was altered by high levels of particulate matter.

The correlation between testosterone and stroke and the mediating role of blood pressure: The Henan rural cohort study.

AIMS: We aimed to investigate the association of serum testosterone with stroke and calculate the proportion explained by blood pressure on this association. MATERIALS AND METHODS: A total of 6175 subjects were included in this study. Serum testosterone was quantified by liquid chromatography-tandem mass spectrometry. The logistic regression model was used to evaluate the association between serum testosterone and stroke. Linear regression analysis was used to assess the associations of serum testosterone with blood pressure. In addition, mediation analysis was performed to identify the mediation effects of blood pressure on the association of serum testosterone with stroke. Sex-stratified analysis was employed throughout the research. RESULTS: After adjusting for multiple variables, serum testosterone levels were negatively associated with stroke in males (per 1 unit natural log-transformed, odds ratio (OR) = 0.81, 95% confidence interval (CI): 0.69-0.94; Tertile 3 vs Tertile 1, OR = 0.65, 95% CI:0.44-0.96). Furthermore, blood pressure played a partial mediating role in the relationship between testosterone and stroke in males. The indirect effect/total effect of systolic blood pressure, diastolic blood pressure and mean arterial pressure were 7.37%, 9.54% and 9.22%, respectively. Notably, the relationship between testosterone and stroke and the role of blood pressure in regulating them was not observed in females. CONCLUSION: This study describes that in rural Chinese males, testosterone can reduce the risk of stroke by affecting blood pressure. To some extent, we provide a new epidemiological evidence for the relationship between testosterone and stroke.

Tideglusib suppresses stem-cell-like features and progression of osteosarcoma by inhibiting GSK-3ß/NOTCH1 signaling.

Osteosarcoma is the most common primary bone tumor in children, teenagers and adolescents. Cancer stem cells (CSCs) have the function to self-renew and keep the phenotype of tumor, causing clinical treatment failure. Therefore, developing effective therapies to inhibit osteosarcoma progression is urgently necessary. Glycogen synthase kinase 3ß (GSK-3ß)is highly expressed in osteosarcoma. In the present study, we made an exploration on the anti-tumor effect of tideglusib (TID), a small-molecule inhibitor of GSK-3ß, and revealed the underlying mechanisms. Here, we found that TID markedly reduced the cell viability of different osteosarcoma cell lines. Cell cycle arrest distributed in G2/M was markedly up-regulated in TID-incubated osteosarcoma cells through enhancing p21 expression levels. Apoptosis was evidently induced in osteosarcoma cells via blocking Caspase-3 activation. Consistently, tumor growth was effectively suppressed in an established murine xenograft model with few toxicity and side effects in vivo. Furthermore, TID markedly repressed stem-cell-like activity in osteosarcoma cells through down-regulating NOTCH1 expression. Notably, rescuing NOTCH1 significantly abolished the role of TID in reducing cell proliferation and sarcosphere-formation. Mechanistically, we found that TID-inhibited NOTCH1 expression was associated with the blockage of AKT/GSK-3ß signaling pathway. In summary, we for the first time provided evidence that TID could effectively inhibit osteosarcoma progression through repressing cell proliferation, inducing apoptosis, suppressing stem-cell-like properties via down-regulating AKT/GSK-3ß/NOTCH1 signaling pathway. Thus, TID may be a promising therapeutic strategy for osteosarcoma treatment without side effects.

Associations of serum androgens with coronary heart disease and interaction with age: The Henan Rural Cohort Study.

BACKGROUND AND AIMS: We aimed to investigate the associations of testosterone and androstenedione with coronary heart disease, and the interaction effect of testosterone or androstenedione and age on coronary heart disease. METHODS AND RESULTS: A total of 6178 participants were included in this study. Serum testosterone and androstenedione were detected by liquid chromatography-tandem mass spectrometry. Logistic regression and restricted cubic splines were used to assess the independent effects of testosterone and androstenedione on coronary heart disease. Interactive plots were employed to examine the interaction effects of testosterone or androstenedione with age on coronary heart disease. After adjusting for multiple variables, serum testosterone and androstenedione levels were negatively associated with coronary heart disease in males (tertile 3 vs tertile 1, odd ratio (OR) = 0.56, 95% confidence interval (CI) (0.33, 0.96), and OR = 0.40, 95% CI (0.22, 0.74)). Per 1 unit increase in ln-testosterone and ln-androstenedione was associated with a 24% (OR = 0.76, 95% CI (0.63, 0.91)) and 30% (OR = 0.69, 95% CI (0.55, 0.86)) lower risk of coronary heart disease, respectively. Additionally, the positive association of age with coronary heart disease was attenuated by increasing concentrations of ln-testosterone and ln-androstenedione concentration in males. CONCLUSIONS: The results indicated that serum testosterone and androstenedione were negatively associated with coronary heart disease risk in Chinese rural males. To some extent, this study supports the application of hormone therapy in males with coronary heart disease, which can contribute to reducing the burden of coronary heart disease and related cardiovascular disease.