Apoe-knockout induces strong vascular oxidative stress and significant changes in the gene expression profile related to the pathways implicated in redox, inflammation, and endothelial function.

Apolipoprotein E (APOE) was recognized as a key regulator of lipid metabolism, which prompted the Apoe-knockout (Apoe-/-) mouse to be the most widely used atherosclerotic model. However, with more and more important physiological roles of APOE being revealed, it is necessary to reacquaint its comprehensive function in the aorta. In this study, we aimed to reveal how Apoe-knockout impacts the gene pathways and phenotypes in the aorta of mice. We performed transcriptome sequencing to acquire the gene expression profile (GEP) for C57BL/6J and Apoe-/- mouse aorta, and used enrichment analysis to reveal the signal pathways enriched for differentially expressed genes (DEGs). In addition, we used immunofluorescence and ELISA to detect the phenotypic differences of vascular tissues and plasma in the two-group mice. Apoe-knockout resulted in significant changes in the expression of 538 genes, among which about 75% were up-regulated and 134 genes were altered more than twice. In addition to the lipid metabolism pathways, DEGs were also mainly enriched in the pathways implicated in endothelial cell proliferation, migration of epithelial cells, immune regulatory, and redox. GSEA shows that the up-regulated genes are mainly enriched in 'immune regulation pathways' and 'signal regulation' pathways, while the down-regulated genes are enriched in lipid metabolism pathways, 'regulation_of_nitric_oxide_synthase_activity' and the pathways involved in redox homeostasis, including 'monooxygenase regulation', 'peroxisomes' and 'oxygen binding'. A significant increase of reactive oxygen species and a remarkable reduction of GSH/GSSG ratio were respectively observed in the vascular tissues and plasma of Apoe-/- mice. In addition, endothelin-1 significantly increased in the vascular tissue and the plasma of Apoe-/- mice. Taken together, our results suggest that besides functioning in lipid metabolism, APOE may be an important signal regulator that mediates the expression of the genes related to the pathways involved in redox, inflammation, and endothelial function. Apoe-knockout-induced strong vascular oxidative stress is also the key factor contributing to atherosclerosis.

Occurrence of microplastics in three types of household cleaning products and their estimated emissions into the aquatic environment.

Microplastics (MPs) in household cleaning products are a significant source of primary MPs. However, their presence in these products remain largely unknown. In this study, three types of common household cleaning products (laundry detergents, toilet bowl cleaners, and dishwashing detergents) were examined to assess the presence of MPs. The potential global emissions of MPs into aquatic environments resulting from the use of these products were estimated using statistics on global wastewater treatment plants (WWTPs) and household cleaning product markets. The average abundance of MPs in household cleaning products was 564.97 ± 327.83 n·kg-1, with toilet bowl cleaners having a significantly higher abundance than the other two products. The most commonly detected polymers in these products were polyamide (PA), silicone, polyurethane (PU), acrylate copolymer (ACR), polyethylene (PE), and polyethylene terephthalate (PET), while the size of the MPs ranged from 21.34 to 442.97 µm, with 81.52 % being <50 µm and 87.32 % being fragment-shaped. The estimated annual MP emissions from these three types of household cleaning products were 3.88 × 1013 ± 1.35 × 1013, with toilet bowl cleaners accounting for 56.44 % of the total emissions. MPs directly released without treatment in WWTPs (2.46 × 1013 n year-1) accounted for 63.40 % of the total emissions, highlighting the importance of increasing the treated rate of wastewater to reduce MP emissions. Sensitivity tests indicated that increasing the MP removal rates of secondary and tertiary WWTPs could also effectively reduce MP emissions. Moreover, gross and per capita MP emissions in 149 countries showed significant differences, which could be attributed to population, market size, demand for household cleaning products, and the level of MP removal among different countries. The findings of this study provide important insights into controlling MP contamination in household cleaning products.

MnO4--Triggered Immediate-Stable Real-Time Fluorescence Immunosensor with High Response Speed and Low Steady-State Error.

Real-time chemical and biological sensing in vitro is important for application in health and environmental monitoring. Thus, a more rapid and stable detection method is urgently needed. Herein, an immediate-stable real-time fluorescent immunosensor with a high response speed (∼100%, <1 s) and approximately zero steady-state error is constructed. The developed sensor is based on the MnO4--triggered in situ immediate-stable fluorogenic reaction between dopamine and orcinol monohydrate to produce azamonardine (DMTM). The obtained DMTM is identified and characterized by high-resolution mass spectrometry, 1H NMR spectroscopy, 13C NMR spectroscopy, and theoretical calculations. The present sensor achieves a highly sensitive detection of dopamine (DA) with a limit of detection (LOD) of 10 nM as well as alkaline phosphates (ALP) with an LOD of 0.1 mU/mL by using orcinol monohydrate phosphate sodium salt as a substrate. As a proof of concept, ALP-triggered fluorescence ELISA using cardiac troponin I (cTnI) as a model antigen target is further constructed. The developed real-time sensor achieves the detection of cTnI with an LOD of 0.05 ng/mL. Moreover, the sensor proposed by us is successfully applied to assess the cTnI level in clinical serum specimens and yields results consistent with those obtained by the commercial ELISA method. The immediate-stable real-time fluorescence immunosensor provides a promising and powerful platform for the trace detection of biomolecules in clinical diagnosis.

Potential risk of microplastics in processed foods: Preliminary risk assessment concerning polymer types, abundance, and human exposure of microplastics.

The occurrence of microplastics (MPs) has been widely reported in human foodstuffs, and their potential negative effects on human health have been brought into focus. Processed foods are more susceptible to MPs as contamination can be introduced during processing and packaging. However, the risk posed by MPs in processed foods remained unclear. This work aims to critically review the available data for MPs in 11 types of possessed foods and to conduct a preliminary risk assessment of MPs in processed foods. For a comprehensive evaluation, three indicators were selected and determined, namely chemical risk, pollution load, and estimated daily intake (EDI). Our results suggest that nori has the highest chemical risk, followed by canned fish, beverages, table salt, and other food items. In the case of pollution load, nori and milk fall into the risk category of Ⅳ and Ⅲ respectively. Table salts, bottled water, and sugar exhibited lower MPs pollution load (risk category of Ⅱ), whereas the pollution loads of other foods were calculated to be category Ⅰ. Moreover, a correlation between the pollution load of sea salts and MPs pollution level in ambient seawater was found. Regarding EDI of MPs from different processed foods, MPs intakes through bottled water (14.3 ± 3.4 n kg-1 d-1) and milk (6.6 ± 2.4 n kg-1 d-1) are significantly higher than that of the other foods (< 1 n kg-1 d-1). The probabilistic estimation of MPs daily intake indicated that children (19.7 n kg-1 d-1) are at a higher health risk than adults (female: 17.6 n kg-1 d-1, male: 12.6 n kg-1 d-1). Nevertheless, the exposure dose used in toxicological studies was about 10 times higher than the MPs intake via processed foods. Therefore, we argued that MPs in processed foods only carry limited risk. Overall, this study would provide the basis for risk management of MPs in processed food products.

The Acid Sphingomyelinase Inhibitor Amitriptyline Ameliorates TNF-α-Induced Endothelial Dysfunction.

PURPOSE: Inflammation associated endothelial cell (EC) dysfunction is key to atherosclerotic disease. Recent studies have demonstrated a protective role of amitriptyline in cardiomyocytes induced by hypoxia/reoxygenation. However, the mechanism by which amitriptyline regulates the inflammatory reaction in ECs remains unknown. Thus, the aim of this study was to investigate whether amitriptyline protects against inflammation in TNF-α-treated ECs. METHODS: HUVECs were incubated with amitriptyline (2.5 µM) or TNF-α (20 ng/ml) for 24 h. EdU, tube formation, transwell, DHE fluorescence staining, and monocyte adhesion assays were performed to investigate endothelial function. Thoracic aortas were isolated from mice, and vascular tone was measured with a wire myograph system. The levels of ICAM-1, VCAM-1, MCP-1, phosphorylated MAPK and NF-κB were detected using western blotting. RESULTS: Amitriptyline increased the phosphorylation of nitric oxide synthase (eNOS) and the release of NO. Amitriptyline significantly inhibited TNF-α-induced increases in ASMase activity and the release of ceramide and downregulated TNF-α-induced expression of proinflammatory proteins, including ICAM-1, VCAM-1, and MCP-1 in ECs, as well as the secretion of sICAM-1 and sVCAM-1. TNF-α treatment obviously increased monocyte adhesion and ROS production and impaired HUVEC proliferation, migration and tube formation, while amitriptyline rescued proliferation, migration, and tube formation and decreased monocyte adhesion and ROS production. Additionally, we demonstrated that amitriptyline suppressed TNF-α-induced MAPK phosphorylation as well as the activity of NF-κB in HUVECs. The results showed that the relaxation response of aortic rings to acetylcholine in the WT-TNF-α group was much lower than that in the WT group, and the sensitivity of aortic rings to acetylcholine in the WT-TNF-α group and WT-AMI-TNF-α group was significantly higher than that in the WT-TNF-α group. CONCLUSION: These results suggest that amitriptyline reduces endothelial inflammation, consequently improving vascular endothelial function. Thus, the identification of amitriptyline as a potential strategy to improve endothelial function is important for preventing vascular diseases.

Socioeconomic disparities and dementia in China.

OBJECTIVES: This study aimed to investigate the associations between individual-level SES, area-level SES, and their interaction with dementia in China. METHODS: This study used data from the Second China National Sample Survey on Disability and restricted our finalized analysis to 688,507 participants aged 50 years or older. Dementia was ascertained according to the International Statistical Classification of Diseases, Tenth Revision. Multilevel logistic regression models were fitted to examine the associations between individual-level SES, area-level SES, and their interaction with dementia. RESULTS: Participants with higher individual SES were less likely to develop dementia; the risk of dementia decreased by 18% for each standard deviation increase in individual SES (OR=0.82, 95% CI=0.77, 0.88). Advantaged areas were associated with an increased risk of dementia in Chinese adults by 1.52 (95% CI=1.43, 1.62). Analysis of the combination between individual-level SES and area-level SES revealed that as the level of area SES increased, the risk of dementia in lower SES people was significantly higher than in higher SES people (OR=1.09, 95% CI=1.04,1.14). DISCUSSION: This study found that people with lower SES living in high-SES areas had a higher risk of dementia than people with lower SES living in low-SES areas. Significant socioeconomic differences in the risk of dementia exist in China, and more attention should be given to low-SES populations living in high-SES areas.

Association of Urbanicity with Schizophrenia and Related Mortality in China: Association de l'urbanicité avec la schizophrénie et la mortalité qui y est reliée en Chine.

OBJECTIVE: Although higher prevalence of schizophrenia in Chinese urban areas was observed, studies focused on the association between schizophrenia and urbanicity were less in China. Using a national representative population-based data set, this study aimed to investigate the relationship between urbanicity and schizophrenia and its related mortality among adults aged 18 years old and above in China. METHODS: Data were obtained from the Second China National Sample Survey on Disability in 2006 and follow-up studies from 2007 to 2010 each year. We restricted our analysis to 1,909,205 participants aged 18 years or older and the 2,071 schizophrenia patients with information of survival and all-caused mortality of the follow-up surveys from 2007 to 2010.Schizophrenia was ascertained according to the International Statistical Classification of Diseases, 10th Revision. The degree of urbanicity and the region of residence were used to be the proxies of urbanicity. Of these, the degree of urbanicity measured by the ratio of nonagricultural population to total population and the region of residence measured by six categorical variables (first-tier cities, first-tier city suburbs, second-tier cities, second-tier city suburbs, other city areas, and rural areas). Logistics regression models and restricted polynomial splines were used to examine the linear/nonlinear relationship between urbanicity and the risk of schizophrenia. Cox proportional hazards regression models were used to test the role of urbanicity on mortality risk of schizophrenia patients. RESULTS: 10% increase in the degree of urbanicity was associated with increased risk of schizophrenia (OR = 1.44; 95% CI, 1.32 to 1.57). The nonlinear model further confirmed the association between the degree of urbanicity and the risk of schizophrenia. This association existed sex difference, as the level of urbanicity increased, schizophrenia risk of males grew faster than the risk of females. The hazard ratio (HR) of mortality in schizophrenia patients decreased with the elevated of urbanicity level, with a HR of 0.42 (95% CI, 0.21 to 0.84). CONCLUSIONS: This research suggested that incremental changes in the degree of urbanicity linked to higher risk of schizophrenia, and as the degree of urbanicity elevated, the risk of schizophrenia increased more for men than for women. Additionally, we found that schizophrenia patients in higher degree of urbanicity areas had lower risk of mortality. These findings contributed to the literature on schizophrenia in developing nations under a non-Western context and indicates that strategies to improve mental health conditions are needed in the progress of urbanicity.

MEF2A Is the Trigger of Resveratrol Exerting Protection on Vascular Endothelial Cell.

Both resveratrol and myocyte enhancer factor 2A (MEF2A) may protect vascular endothelial cell (VEC) through activating the expression of SIRT1. However, the relationship between resveratrol and MEF2A is unclear. We aimed to investigate the deeper mechanism of resveratrol in protecting vascular endothelial cells and whether MEF2A plays a key role in the protective function of resveratrol. Human umbilical vein endothelial cell (HUVEC) was used for in vitro study, and small interfere RNA was used for silencing MEF2A. Silencing MEF2A in the vascular endothelium (VE) of ApoE-/- mice was performed by tail injection with adeno associated virus expressing si-mef2a-shRNA. The results showed that treatment of HUVEC with resveratrol significantly up-regulated MEF2A, and prevented H2O2-induced but not siRNA-induced down-regulation of MEF2A. Under various experimental conditions, the expression of SIRT1 changed with the level of MEF2A. Resveratrol could rescue from cell apoptosis, reduction of cell proliferation and viability induced by H2O2, but could not prevent against that caused by silencing MEF2A with siRNA. Silencing MEF2A in VE of apoE-/- mice decreased the expression of SIRT1, increased the plasma LDL-c, and abrogated the function of resveratrol on reducing triglyceride. Impaired integrity of VE and aggravated atherosclerotic lesion were observed in MEF2A silenced mice through immunofluorescence and oil red O staining, respectively. In conclusion, resveratrol enhances MEF2A expression, and the upregulation of MEF2A is required for the endothelial protective benefits of resveratrol in vitro via activating SIRT1. Our work has also explored the in vivo relevance of this signaling pathway in experimental models of atherosclerosis and lipid dysregulation, setting the stage for more comprehensive phenotyping in vivo and further defining the molecular mechanisms.

The effects of indoor air pollution from solid fuel use on cognitive function among middle-aged and older population in China.

OBJECTIVES: Growing evidence has linked outdoor air pollution exposure with higher risk of cognitive impairments. However, the role of indoor air pollution in cognitive decline is not well elaborated. By using nationally representative longitudinal data, this study aimed to explore the effects of indoor air pollution from solid fuel use on cognitive function among middle-aged and older individuals in China. METHODS: Data were obtained from 2011 to 2015 waves of CHARLS (China Health and Retirement Longitudinal Study). Scores from the Telephone Interview of Cognitive Status and figure drawing/word recall tests were used to measure cognitive function in 39,482 individuals. Exposure to indoor air pollution was measured as use of solid fuel for cooking. Solid fuel was defined as coal, biomass charcoal, wood, and straw; clean fuel was defined as liquefied gas, natural gas, and electricity. Linear mixed effect models were applied to examine the effect of indoor air pollution from solid fuel use on cognitive function. RESULTS: Participants had an average global cognitive function of 9.67 (SD = 4.13). Solid fuel users made up 49.71% of participants, but this proportion was much greater among those living in rural areas (64.22%). Compared with clean fuel users, solid fuel users had worse cognitive function. On average, solid fuel users had a 0.81 (95%CI: -0.89, -0.73) lower global cognition score, 0.63 (95%CI: -0.69, -0.57) lower mental health score, and 0.16 (95%CI: -0.22, -0.14) lower episodic memory score. These effects were stronger among participants who are female, aged 65 years old and above, have education level of primary school and below, or have cardiovascular diseases. CONCLUSIONS: These results provide evidence for the role of indoor air pollution in neurobehavioral disorders in China. Promotion of practices like expanded use of clean fuel and improved stoves in households may be crucial to significantly reduce indoor air pollution and protect mental health.

Fluorescence copolymer-based dual-signal monitoring tyrosinase activity and its inhibitor screening via blue-green emission transformation.

Tyrosinase (TYR) is a crucial enzyme in melanin metabolism and catecholamine production, its abnormal overexpression is closely associated with many human diseases involving melanoma cancer, vitiligo, Parkinson's disease and so on. Herein, a dual-signal fluorescence sensing system for monitoring TYR activity is constructed depending on the transformation of blue-green fluorescence emission of copolymer. The developed sensing system is based on TYR catalyzing the hydroxylation of mono-phenol to o-diphenol and the conversion of fluorescence copolymer (FCP) blue emission (430 nm) and green emission (535 nm) in the presence of PEI. In the system, both blue and green emission exhibit a high selectivity and sensitivity (S/B up to 300 and 30 for blue and green emission, respectively) toward TYR in the range from 0.5 to 2.5 U/mL with the detection limit of 0.002 U/mL and 0.06 U/mL, respectively. Additionally, this assay is used to detect TYR in human serum with excellent recovery even at 30% human serum concentrations. Furthermore, it still has been successfully applied to TYR inhibitor screening by taking kojic acid as a model. We believe that our developed sensor has great potential application in TYR-associated disease diagnosis and treatment and drug discovery.

Association Between Urbanicity and Dementia in China: A Population-Based Study.

OBJECTIVES: This study investigated the relationship between urbanicity and dementia and predicted its nonlinear pattern among Chinese adults aged 50 years and older. METHODS: This study used data from the Second National Sample Survey on Disability, which was implemented from April 1 to May 31, 2006 across China. Dementia status was determined by a 2-stage process: the combination of self-reports or family members' reports and an onsite medical diagnosis by experienced specialists based on the International Statistical Classification of Diseases and Related Health Problems 10th Revision Symptom Checklist for Mental Disorders. Logistic regression models were used to examine the relationship between urbanicity and dementia, and restricted polynomial spline regression models were plotted to examine the nonlinear exposure-response relationship of urbanicity and dementia. RESULTS: Logistic regression results showed that an increase of 10% in the degree of urbanization was associated with a 73% decrease in the odds of dementia after adjusting for covariates, particularly area-level socioeconomic variables. This observed association was stronger in the younger age group, and this age group difference was only present in women. Spline regression findings suggested a nonlinear exposure-response relationship between urbanicity and the odds of dementia. Areas with very high levels of urbanization were associated with increased odds of dementia. CONCLUSIONS: These findings highlight the necessity to properly examine the nuanced relationship between urbanicity and mental health, especially for women in the younger age group. Notably, there were increased odds of dementia at very high levels of urbanicity.

Schizophrenia and education in Chinese metropolises: a population-based study.

OBJECTIVE: Schizophrenia is a public concern in metropolises. Increases in city size may strengthen the correlation between prevalence of schizophrenia and indices of socioeconomic status, such as education. This study used population-based data of adults to investigate the association between education and schizophrenia in Chinese metropolises and its differences between inner city areas and outer suburbs. METHODS: Data was obtained from the Second China National Sample Survey on Disability in 2006, and analysis was restricted to 189,143 participants aged 18 years or older in all counties (districts) of Beijing, Shanghai, and Tianjin. Schizophrenia diagnoses were ascertained according to the International Statistical Classification of Diseases, 10th Revision. Logistic regression models were fitted to examine the association between education and schizophrenia. RESULTS: An inverse U-shaped pattern between education and schizophrenia was found in inner city areas of Chinese metropolises. Compared with the primary school or below group, the odds ratios of junior high school group and senior high school or above group was 2.79 (95% CI 1.96, 3.96) and 1.45(95% CI 0.99, 2.13), respectively. In outer suburbs, junior high school (OR = 0.87, 95% CI 0.63, 1.19) and senior high school or above groups (0.58, 95% CI 0.38, 0.87) were less likely to develop schizophrenia than the primary school or below group. CONCLUSIONS: This study showed an association between education and schizophrenia in Chinese metropolises. In inner city areas, the association was an inverse U-shaped pattern between education and schizophrenia, whereas in suburban areas, the association was a negative linear pattern. Our findings can help identify high-risk populations of schizophrenia in Chinese metropolises. Programs for prevention and early intervention of schizophrenia will need to consider the socioeconomic disparities between inner city and outer suburban areas. Public policies can help improve mental health by developing social security for migrants in inner city areas and promoting regional equality.

Gender difference in the association between education and schizophrenia in Chinese adults.

BACKGROUND: Improving education level was evidenced to decrease the risk of schizophrenia, but whether this strength of education role depends on gender is not. This study aimed to investigate whether there was gender difference in the association between education and schizophrenia in Chinese adults. METHODS: Data were obtained from the Second China National Sample Survey on Disability in 2006, including 1,909,205 participants aged 18 years or older. Schizophrenia was ascertained according to the International Statistical Classification of Diseases, Tenth Revision. Logistics regression models were fitted to examine the combined effect of gender and education on schizophrenia. RESULTS: The lifetime prevalence of schizophrenia in female groups was higher than in male groups, with 0.44% (95%CI: 0.42-0.45%) and 0.36% (95%CI: 0.35-0.37%), respectively. Compared with schizophrenia male patients, more females with schizophrenia experienced severe or extreme difficulty in understanding and communicating. However, more males with schizophrenia suffered from severe or extreme difficulty in the function of daily activities. The combined effect of education and schizophrenia was statistically significant, indicating that, as the level of education increased, schizophrenia risk of females decreased faster than the risk of males. CONCLUSIONS: This study showed that additional years of education associated with lower risk of schizophrenia, and this association was stronger in females than in males. As education elevated, the risk of schizophrenia decreased more for women than for men. The findings indicate that improving education level may have an effect on reducing the gender disparities in mental health of China. Actions to prevent schizophrenia and address its gender disparities will require attention to the improving educational opportunities.

Sustainable and Transparent Fish Gelatin Films for Flexible Electroluminescent Devices.

In the past decades, various alternating current electroluminescent (ACEL) devices, especially the flexible ones, have been developed and used in flat panel display, large-scale decorating, logo display lighting, optical signaling, etc. Transparent plastics are usually used as substrates in ACEL devices; however, they are undegradable and may cause serious environmental pollution. Herein, we have developed a flexible transient ACEL device based on transparent fish gelatin (FG) films. The FG films were made from fish scales, which are sustainable, cost-efficient, and eco-friendly. These films could dissolve in water within seconds at 60 °C and degrade completely within 24 days in soil. The transmittance of these FG films was up to 91.1% in the visible spectrum, comparable to that of polyethylene terephthalate (PET) (90.4%). After forming a composite with silver nanowires (Ag NWs), the Ag NWs-FG film showed a transmittance up to 82.3% and a sheet resistance down to 22.4 Ω sq-1. The fabricated ACEL device based on the Ag NWs-FG film exhibited high flexibility and luminance up to 56.0 cd m-2. The device could be dissolved in water within 3 min. Our work demonstrates that the sustainable, flexible, and transparent FG films are a promising alternative for green and degradable substrates in the field of flexible electronics, including foldable displays, wearable devices, and health monitoring.

Urbanicity and autism of children in China.

OBJECTIVES: Increased risk of autism with the increment of urbanization has been documented in developed countries. However, very few studies in developing countries focused on this topic. By using Chinese nationally representative large dataset, we investigated the association between urbanicity and autism among children aged 0-17 years in China. Also, we analyzed whether there existed a sexually dimorphic effect on this association. METHODS: Data from the Second National Sample Survey on Disability (SNSSD) was used in this study, and 616,940 children was selected for analysis. Autism was measured by experienced psychiatrists according to The International Statistical Classification of Diseases and Related Health Problems 10th Revision Symptom Checklist for Mental Disorders. Logistic regression models allowing for multiple demographic and socioeconomic covariates were used to evaluate the association between the level of urbanization and autism in children. RESULTS: Compared with children in low level of urbanization areas, those in high urbanization level areas was 2.12 (95%CI: 1.28, 3.49) times more likely to develop autism, and 1.85 (95%CI: 1.21, 2.84) times for those in moderate level of urbanization areas. Stratified analyses found that all observed associations were only in male children, not in female children. CONCLUSIONS: Our findings suggested that higher level of urbanicity was associated with higher risk of autism in children. This association was only present in male children, not in female children.

Individual-level and area-level socioeconomic status (SES) and schizophrenia: cross-sectional analyses using the evidence from 1.9 million Chinese adults.

OBJECTIVES: Health disparities in schizophrenia are well established. However, it is less understood whether area-level socioeconomic status (SES) is differentially associated with schizophrenia depending on individual-level SES. Therefore, using a nationally large representative data, this study investigated the association between individual-level SES, area-level SES and their interaction with schizophrenia in Chinese adults from a multilevel perspective. SETTING: Household interviews in 734 counties (districts), 2980 towns (streets) and 5964 communities (villages) from 31 provinces, People's Republic of China, as part of the cross-sectional survey of Second China National Sample Survey on Disability. PARTICIPANTS: 1 909 205 men and women aged 18 years old and above. PRIMARY AND SECONDARY OUTCOME MEASURES: A screen followed by clinical diagnosis was used to identify schizophrenia, and schizophrenia was ascertained according to the International Statistical Classification of Diseases, 10th Revision (code F20). RESULTS: 1-SD increase in individual SES was associated with decreased risk of schizophrenia (OR=0.45, 95% CI 0.43 to 0.46). 1-SD increase in area-level SES was associated with increased risk of schizophrenia (OR=1.30, 95% CI 1.24 to 1.37). The interaction of individual SES and area-level SES was statistically significant (OR=1.05, 95% CI 1.02 to 1.08); as the level of area SES increased, schizophrenia risk of lower SES people grew faster than the risk of higher SES people. CONCLUSIONS: Area-level SES is particularly important to mental health of low SES individuals, with low SES people in high SES counties having the highest risk of schizophrenia than other groups. Action to reduce SES disparities in schizophrenia will require attention to the area-level context of low SES adults.

Unmarried Youth Pregnancy, Outcomes, and Social Factors in China: Findings From a Nationwide Population-Based Survey.

INTRODUCTION: Early pregnancies and their poor reproductive outcomes remain increasing concerns. AIM: This study aims to investigate the pregnancy rate and outcomes and to identify social factors associated with pregnancy among Chinese unmarried youths aged 15-24 years. METHODS: Data were obtained from the Survey of Youth Access to Reproductive Health in China, and 11,076 unmarried female youths were analyzed. Prevalence of pregnancy by various demographic and socioeconomic characteristics was calculated. Univariate and multivariable logistic regression models were used to identify factors associated with pregnancy. MAIN OUTCOME MEASURE: The main outcome is pregnancy among unmarried female youths during their lifetime. RESULTS: Among 11,076 female youths, 501 individuals reported 697 premarital pregnancies during their lifetime until the survey was conducted, approximately 62.9 (95% CI: 58.5-67.6) pregnancies per 1,000 female youths. Older age group (odds ratio [OR] = 4.49; 95% CI = 3.60-5.59), low education levels (primary school and below: OR = 1.78, 95% CI = 1.33-2.37; junior and senior high school: OR 1.44, 95% CI = 1.15-1.80), living in non-eastern regions (central: OR 1.34, 95% CI = 1.06-1.68; west: OR 1.62, 95% CI = 1.28-2.04), cigarette smoking (OR 3.60, 95% CI = 2.76-4.70), alcohol drinking (OR 1.59, 95% CI = 1.28-1.97), from family with mother's education of primary school and below (OR 1.65, 95% CI = 1.11-2.46), and the bottom economic status (OR 1.48, 95% CI = 1.14-1.91) were associated with higher risk of premarital pregnancy among female youths. CONCLUSION: The findings justify the national concern for pregnancy among unmarried youth in China. Strategies to improve sexual education in school and family, to enhance the reproductive services for youth, and to increase public awareness of the reproductive health of young people were warranted. Guo C, Pang L, Ding R, et al. Unmarried Youth Pregnancy, Outcomes, and Social Factors in China: Findings From a Nationwide Population-Based Survey. Sex Med 2019;7:396-402.

Myocyte enhancer factor 2A delays vascular endothelial cell senescence by activating the PI3K/p-Akt/SIRT1 pathway.

Myocyte enhancer factor 2A (MEF2A) dysfunction is closely related to the occurrence of senile diseases such as cardiocerebrovascular diseases, but the underlying molecular mechanism is unclear. Here, we studied the effects of MEF2A on the senescent phenotype of vascular endothelial cells (VEC) and downstream signaling pathway, and the association between plasma MEF2A levels and coronary artery disease (CAD). Results showed that MEF2A silencing promoted cell senescence and down-regulated PI3K/p-AKT/Sirtuin 1 (SIRT1) expression. MEF2A overexpression delayed cell senescence and up-regulated PI3K/p-AKT/SIRT1. Hydrogen peroxide (H2O2) treatment induced cellular senescence and down-regulated the expression of MEF2A and PI3K/p-AKT/SIRT1. MEF2A overexpression inhibited cellular senescence and the down-regulation of PI3K/p-AKT/SIRT1 induced by H2O2. Further study revealed that MEF2A directly up-regulated the expression of PIK3CA and PIK3CG through MEF2 binding sites in the promoter region. Pearson correlation and logistic regression analysis showed that the plasma level of MEF2A was negatively correlated with CAD, and with age in the controls. These results suggested that MEF2A can directly up-regulate PI3K gene expression, and one of the molecular mechanisms of delaying effect of MEF2A on VEC cell senescence was SIRT1-expression activation through the PI3K/p-Akt pathway. Moreover, the plasma MEF2A levels may be a potential biomarker for CAD risk prediction.

MEF2A alters the proliferation, inflammation-related gene expression profiles and its silencing induces cellular senescence in human coronary endothelial cells.

BACKGROUND: Myocyte enhancer factor 2A (MEF2A) plays an important role in cell proliferation, differentiation and survival. Functional deletion or mutation in MEF2A predisposes individuals to cardiovascular disease mainly caused by vascular endothelial dysfunction. However, the effect of the inhibition of MEF2A expression on human coronary artery endothelial cells (HCAECs) is unclear. In this study, expression of MEF2A was inhibited by specific small interference RNA (siRNA), and changes in mRNA profiles in response to MEF2A knockdown were analyzed using an Agilent human mRNA array. RESULTS: Silencing of MEF2A in HCAECs accelerated cell senescence and suppressed cell proliferation. Microarray analysis identified 962 differentially expressed genes (DEGs) between the MEF2A knockdown group and the negative control group. Annotation clustering analysis showed that the DEGs were preferentially enriched in gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to proliferation, development, survival, and inflammation. Furthermore, 61 of the 578 downregulated DEGs have at least one potential MEF2A binding site in the proximal promoter and were mostly enriched in the GO terms "reproduction" and "cardiovascular." The protein-protein interaction network analyzed for the downregulated DEGs and the DEGs in the GO terms "cardiovascular" and "aging" revealed that PIK3CG, IL1B, IL8, and PRKCB were included in hot nodes, and the regulation of the longevity-associated gene PIK3CG by MEF2A has been verified at the protein level, suggesting that PIK3CG might play a key role in MEF2A knockdown induced HCAEC senescence. CONCLUSIONS: MEF2A knockdown accelerates HCAEC senescence, and the underlying molecular mechanism may be involved in down-regulation of the genes related with cell proliferation, development, inflammation and survival, in which PIK3CG may play a key role.