Grape Seed Proanthocyanidins Protect Pancreatic ß Cells Against Ferroptosis via the Nrf2 Pathway in Type 2 Diabetes.

Pancreatic ß cell damage is the primary contributor to type 2 diabetes mellitus (T2DM); however, the underlying mechanism remains nebulous. This study explored the role of ferroptosis in pancreatic ß cell damage and the protective effects of grape seed proanthocyanidin extract (GSPE). In T2DM model rats, the blood glucose, water intake, urine volume, HbA1c, and homeostasis model assessment-insulin resistance were significantly increased, while the body weight and the insulin level were significantly decreased, indicating the successful establishment of the T2DM model. MIN6 mouse insulinoma ß cells were cultured in high glucose and sodium palmitate conditions to obtain a glycolipid damage model, which was administered with GSPE, ferrostatin-1 (Fer-1), or nuclear factor erythroid 2-related factor 2 (Nrf2) small interfering (si) RNA. GSPE and Fer-1 treatment significantly improved pancreatic ß-cell dysfunction and protected against cell death. Both treatments increased the superoxide dismutase and glutathione activity, reduced the malondialdehyde and reactive oxygen species levels, and improved iron metabolism. Furthermore, the treatments reversed the expression of ferroptosis markers cysteine/glutamate transporter (XCT) and glutathione peroxidase 4 (GPX4) caused by glycolipid toxicity. GSPE treatments activated the expression of Nrf2 and related proteins. These effects were reversed when co-transfected with si-Nrf2. GSPE inhibits ferroptosis by activating the Nrf2 signaling pathway, thus reducing ß-cell damage and dysfunction in T2DM. Therefore, GSPE is a potential treatment strategy against T2DM.

Comparison of the effects of imputation methods for missing data in predictive modelling of cohort study datasets.

BACKGROUND: Missing data is frequently an inevitable issue in cohort studies and it can adversely affect the study's findings. We assess the effectiveness of eight frequently utilized statistical and machine learning (ML) imputation methods for dealing with missing data in predictive modelling of cohort study datasets. This evaluation is based on real data and predictive models for cardiovascular disease (CVD) risk. METHODS: The data is from a real-world cohort study in Xinjiang, China. It includes personal information, physical examination data, questionnaires, and laboratory biochemical results from 10,164 subjects with a total of 37 variables. Simple imputation (Simple), regression imputation (Regression), expectation-maximization(EM), multiple imputation (MICE) , K nearest neighbor classification (KNN), clustering imputation (Cluster), random forest (RF), and decision tree (Cart) were the chosen imputation methods. Root Mean Square Error (RMSE) and Mean Absolute Error (MAE) are utilised to assess the performance of different methods for missing data imputation at a missing rate of 20%. The datasets processed with different missing data imputation methods were employed to construct a CVD risk prediction model utilizing the support vector machine (SVM). The predictive performance was then compared using the area under the curve (AUC). RESULTS: The most effective imputation results were attained by KNN (MAE: 0.2032, RMSE: 0.7438, AUC: 0.730, CI: 0.719-0.741) and RF (MAE: 0.3944, RMSE: 1.4866, AUC: 0.777, CI: 0.769-0.785). The subsequent best performances were achieved by EM, Cart, and MICE, while Simple, Regression, and Cluster attained the worst performances. The CVD risk prediction model was constructed using the complete data (AUC:0.804, CI:0.796-0.812) in comparison with all other models with p<0.05. CONCLUSION: KNN and RF exhibit superior performance and are more adept at imputing missing data in predictive modelling of cohort study datasets.

Stability Enhancement in All-Inorganic Perovskite Light Emitting Diodes via Dual Encapsulation.

Addressing the challenge of lighting stability in perovskite white light emitting diodes (WLEDs) is crucial for their commercial viability. CsPbX3 (X = Cl, Br, I, or mixed) nanocrystals (NCs) are promising for next-generation lighting due to their superior optical and electronic properties. However, the inherent soft material structure of CsPbX3 NCs is particularly susceptible to the elevated temperatures associated with prolonged WLED operation. Additionally, these NCs face stability challenges in high humidity environments, leading to reduced lighting performance. This study introduces a two-step dual encapsulation method, resulting in CsPbBr3 @SiO2 /Al2 SiO5 composite fibers (CFs) with enhanced optical stability under extreme conditions. In testing, WLEDs incorporating these CFs, even under prolonged operation at high power (100 mA for 9 h), maintain consistent electroluminescence (EL) intensity and optoelectronic parameters, with surface temperatures reaching 84.2 °C. Crucially, when subjected to 85 °C and 85% relative humidity for 200 h, the WLEDs preserve 97% of their initial fluorescence efficiency. These findings underscore the efficacy of the dual encapsulation strategy in significantly improving perovskite material stability, marking a significant step toward their commercial application in optoelectronic lighting.

Regulating interfacial thermal conductance with commensurate-incommensurate transitions at atomic-scale silicon/silicon interfaces.

Interfacial thermal conductance (ITC) between two contact surfaces is an important factor in accurately measuring energy transfer and heat dissipation at the interface; however, it is still not fully resolved how to more effectively modulate the ITC and unravel the related inner mechanisms. In this study, the contribution of commensurability and normal load to ITC at the atomic-scale silicon/silicon interface is disclosed. The results manifest that the ITC gradually reduces with the transition from commensurability to incommensurability. This is because the reduced force constant at the incommensurate interface decreases the transmittance of phonons, leading to the suppression of high-frequency phonon excitation and a red shift in the phonon spectrum, thereby weakening the ITC. We further discovered that increasing the normal loads can significantly enhance the ITC in both contact states, and the reason is that the interlayer distance decreases with increasing normal loads, which strengthens the interfacial potential and force constant, consequently resulting in greater heat transfer efficiency. This paper reveals that interfacial thermal transport can be regulated by applying normal loads and changing the interfacial contact states.

Phonon mechanism of angle-dependent superlubricity between black phosphorus layers.

Based on a combination of molecular dynamics simulations and quantum theories, this study discloses the phonon mechanism of angle-dependent superlubricity between black phosphorus layers. Friction exhibits 180° periodicity, i.e., the highest friction at 0° and 180° and lowest at 90°. Thermal excitation reduces friction at 0° due to thermal lubrication. However, at 90°, high temperature increases friction caused by thermal collision owing to lower interfacial constraints. Phonon spectra reveal that with 0°, energy dissipation channels can be formed at the interface, thus enhancing dissipation efficiency, while the energy dissipation channels are destroyed, thus hindering frictional dissipation at 90°. Besides, for both commensurate and incommensurate cases, more phonons are excited on atoms adjacent to the contact interface than those excited from nonadjacent interface atoms.

Studies on the optical stability of CsPbBr3 with different dimensions (0D, 1D, 2D, 3D) under thermal environments.

The thermal stability of phosphor materials had long been a bottleneck in their commercialization. Nowadays, cesium lead halide perovskite CsPbBr3 has been considered a potential replacement for the next generation of optoelectronic devices due to its excellent optical and electronic properties, however, the devices inevitably generate high temperatures on the surface under prolonged energization conditions in practical applications, which can be fatal to CsPbBr3. Despite the various strategies that have been employed to improve the thermal stability of CsPbBr3, systematic studies of the thermal stability of the basis CsPbBr3 are lacking. In this study, CsPbBr3 with different dimensions (0D quantum dots (QDs), 1D nanowires (NWs), 2D nanoplate (NPs), 3D micron crystals (MCs)) was prepared by traditional high-temperature thermal injection, and a systematic study was carried out on their optical properties and thermal stability. The results revealed that the dimensional change will directly influence the optical properties as well as the thermal stability of CsPbBr3. In particular, 3D CsPbBr3 MCs maintained relatively high thermal stability under high-temperature environments, which will bring interest for the commercialization of next-generation perovskite optoelectronic devices.

Decoding the phonon transport of structural lubrication at silicon/silicon interface.

Although the friction characteristics under different contact conditions have been extensively studied, the mechanism of phonon transport at the structural lubrication interface is not extremely clear. In this paper, we firstly promulgate that there is a 90°-symmetry of friction force depending on rotation angle at Si/Si interface, which is independent of normal load and temperature. It is further found that the interfacial temperature difference under incommensurate contacts is much larger than that in commensurate cases, which can be attributed to the larger interfacial thermal resistance (ITR). The lower ITR brings greater energy dissipation in commensurate sliding, and the reason for that is more effective energy dissipation channels between the friction surfaces, making it easier for the excited phonons at the washboard frequency and its harmonics to transfer through the interface. Nevertheless, the vibrational frequencies of the interfacial atoms between the tip and substrate during the friction process do not match in incommensurate cases, and there is no effective energy transfer channel, thus presenting the higher ITR and lower friction. Eventually, the number of excited phonons on contact surfaces reveals the amount of frictional energy dissipation in different contact states.

Updating Framingham CVD risk score using waist circumference and estimated cardiopulmonary function: a cohort study based on a southern Xinjiang population.

PURPOSE: To explore the association between waist circumference (WC), estimated cardiopulmonary function (eCRF), and cardiovascular disease (CVD) risk in southern Xinjiang. Update the Framingham model to make it more suitable for the southern Xinjiang population. METHODS: Data were collected from 7705 subjects aged 30-74 years old in Tumushuke City, the 51st Regiment of Xinjiang Production and Construction Corps. CVD was defined as an individual's first diagnosis of non-fatal acute myocardial infarction, death from coronary heart disease, and fatal or non-fatal stroke. The Cox proportional hazards regression analysis was used to analyze the association between WC, eCRF and CVD risk. Restricted cubic spline plots were drawn to describe the association of the two indicators with CVD risk. We update the model by incorporating the new variables into the Framingham model and re-estimating the coefficients. The discrimination of the model is evaluated using AUC, NRI, and IDI metrics. Model calibration is evaluated using pseudo R2 values. RESULTS: WC was an independent risk factor for CVD (multivariate HR: 1.603 (1.323, 1.942)), eCRF was an independent protective factor for CVD (multivariate HR: 0.499 (0.369, 0.674)). There was a nonlinear relationship between WC and CVD risk (nonlinear χ2 = 12.43, P = 0.002). There was a linear association between eCRF and CVD risk (non-linear χ2 = 0.27, P = 0.6027). In the male, the best risk prediction effect was obtained when WC and eCRF were added to the model (AUC = 0.763((0.734,0.792)); pseudo R2 = 0.069). In the female, the best risk prediction effect was obtained by adding eCRF to the model (AUC = 0.757 (0.734,0.779); pseudo R2 = 0.107). CONCLUSION: In southern Xinjiang, WC is an independent risk factor for CVD. eCRF is an independent protective factor for CVD. We recommended adding WC and eCRF in the male model and only eCRF in the female model for better risk prediction.

Comparison of obesity-related indicators for identifying metabolic syndrome among normal-weight adults in rural Xinjiang, China.

BACKGROUND: This study aimed to compare the ability of certain obesity-related indicators to identify metabolic syndrome (MetS) among normal-weight adults in rural Xinjiang. METHODS: A total of 4315 subjects were recruited in rural Xinjiang. The questionnaire, biochemical and anthropometric data were collected from them. Binary logistic regression was used to analyze the association between the z-score of each index and MetS. The area under the receiver-operating characteristic (ROC) curves were used to compare the diagnostic ability of each index. According to the cut-off value of each index, nomogram models were established and their diagnostic ability were evaluated. RESULTS: After adjusting for confounding factors, each indicator in different genders was correlated with MetS. Triglyceride-glucose index (TyG index) showed the strongest association with MetS in both males (OR = 3.749, 95%CI: 3.173-4.429) and females (OR = 3.521,95%CI: 2.990-4.148). Lipid accumulation product (LAP) showed the strongest diagnostic ability in both males (AUC = 0.831, 95%CI: 0.806-0.856) and females (AUC = 0.842, 95%CI: 0.820-0.864), and its optimal cut-off values were 39.700 and 35.065, respectively. The identification ability of the TyG index in different genders (males AUC: 0.817, females AUC: 0.817) was slightly weaker than LAP. Waist-to-height ratio (WHtR) had the similar AUC (males: 0.717, females: 0.747) to conicity index (CI) (males: 0.734, females: 0.749), whereas the identification ability of a body shape index (ABSI) (males AUC: 0.700, females AUC: 0.717) was relatively weak. Compared with the diagnostic ability of a single indicator, the AUC of the male nomogram model was 0.876 (95%CI: 0.856-0.895) and the AUC of the female model was 0.877 (95%CI: 0.856-0.896). The identification ability had been significantly improved. CONCLUSION: LAP and TyG index are effective indicators for identifying MetS among normal-weight adults in rural Xinjiang. Nomogram models including age, CI, LAP, and TyG index can significantly improve diagnostic ability.

Tuning the interfacial friction force and thermal conductance by altering phonon properties at contact interface.

Controlling friction force and thermal conductance at solid/solid interface is of great importance but remains a significant challenge. In this work, we propose a method to control the matching degree of phonon spectra at the interface through modifying the atomic mass of contact materials, thereby regulating the interfacial friction force and thermal conductance. Results of Debye theory and molecular dynamics simulations show that the cutoff frequency of phonon spectrum decreases with increasing atomic mass. Thus, two contact surfaces with equal atomic mass have same vibrational characteristics, so that more phonons could pass through the interface. In these regards, the coupling strength of phonon modes on contact surfaces makes it possible to gain insight into the nonmonotonic variation of interfacial friction force and thermal conductance. Our investigations suggest that the overlap of phonon modes increases energy scattering channels and therefore phonon transmission at the interface, and finally, an enhanced energy dissipation in friction and heat transfer ability at interface.

Nanosized Titanium Dioxide Induced Apoptosis and Abnormal Expression of Blood-Testis Barrier Junction Proteins Through JNK Signaling Pathway in TM4 Cells.

Nanosized titanium dioxide (nano-TiO2) has been widely used in consumer products. It can cross the blood-testis barrier (BTB), and it has adverse effects on the male reproductive system. However, the specific mechanism has not been fully elucidated. The purpose of this study was to understand the role of the JNK signaling pathway in the apoptosis and abnormal expression of BTB junction proteins induced by nano-TiO2 in TM4 cells. After different concentration of nano-TiO2 treatments, the cell viability, apoptosis, mitochondrial membrane potential (Δψm), BTB junction proteins (Claudin-11, ZO-1, ß-catenin), apoptosis-related proteins (Bax, Bcl-2, cleaved caspase-9, cleaved caspase-3), and phosphorylated (p)-JNK protein were examined. The results showed that cell viability, apoptosis rates, Δψm, and apoptosis-related protein levels changed in a concentration-dependent manner. Cell viability decreased significantly from 100 µg/mL nano-TiO2 group. Apoptosis rates increased significantly from 150 µg/mL nano-TiO2 group, and Δψm decreased significantly from 150 µg/mL nano-TiO2 group. The protein levels of Bax, cleaved caspase-9, and cleaved caspase-3 increased significantly from 150 µg/mL nano-TiO2 group, and the protein level of Bcl-2 decreased significantly from 100 µg/mL nano-TiO2 group. The protein level of p-JNK increased significantly from 100 µg/mL nano-TiO2 group. Abnormal expression of ZO-1 and ß-catenin started from 150 µg/mL nano-TiO2 group, and abnormal expression of Claudin-11 started from 100 µg/mL nano-TiO2 group. Cells were treated with JNK inhibitor SP100625 to determine whether the changes of the above indicators in the concentration of 150 µg/mL nano-TiO2 group can be reversed. We found that SP100625 at 20 µM significantly reversed these effects. These results highlighted that nano-TiO2 could activate the JNK signaling pathway to induce mitochondria-mediated apoptosis and abnormal expression of BTB junction proteins in TM4 cells.

Visceral Obesity-Related Indices in the Identification of Individuals with Metabolic Syndrome Among Different Ethnicities in Xinjiang, China.

BACKGROUND: Few studies have focused on the predictive ability of visceral obesity-related indices for metabolic syndrome (MetS), especially in different ethnic groups. This study aimed to evaluate the applicability of visceral obesity-related indices for MetS screening among three major ethnic groups living in remote rural areas of Xinjiang. METHODS: Based on multistage stratified cluster random sampling method, 3,192 Uyghurs, 3,054 Kazakhs, and 3,658 Hans were recruited from Xinjiang, China. The Joint Interim Statement (JIS) criteria were used to define MetS. The receiver operating characteristic curve (ROC), area under the ROC curve (AUC), and predictive value of each visceral obesity-related index were used to evaluate the predictive ability of MetS. RESULTS: After adjusting for potential confounding factors, the lipid accumulation product (LAP), Chinese visceral adiposity index (CVAI), waist-to-height ratio (WHtR), and atherogenic index of plasma (AIP) were significantly correlated with MetS for each ethnic group, and the odds ratios (ORs) for MetS increased across quartiles. LAP was best able to identify MetS status in Kazakhs (AUC=0.853) and Uyghurs (AUC=0.851), with optimal cut-offs being 36.3 and 28.2, respectively. Both LAP (AUC=0.798) and CVAI (AUC=0.791) most accurately identified MetS status in Hans, with the optimal cut-offs being 27.3 and 85.0, respectively. Moreover, the AUC of the combination of these visceral obesity-related indices is higher for each ethnic group. However, compared with LAP, the improved value of combined screening was not significant. CONCLUSION: LAP had the best discriminative capability for the screening of MetS among Kazakhs, Uyghurs, and Hans. The screening ability of CVAI for MetS was similar to that of LAP in Hans. Thus, LAP may be a complementary indicator for assessing MetS in various ethnic groups.

Protective Effects of Grape Seed Proanthocyanidins on the Kidneys of Diabetic Rats through the Nrf2 Signalling Pathway.

BACKGROUND: Diabetic nephropathy (DN) is the most common cause of end-stage renal failure. Grape seed proanthocyanidin extract (GSPE) is a powerful antioxidant that is believed to protect the kidney through antioxidant action. However, the underlying mechanism of GSPE protection against DN remains unclear. OBJECTIVE: To explore if GSPE can improve DN by activating nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response element signalling and to clarify its possible mechanism. Materials and methods. Ten healthy Sprague-Dawley rats were randomly selected as controls. Rats with streptozotocin-induced diabetes were randomly divided into three groups (10 animals/group): type 2 diabetes mellitus (T2DM) group (untreated), L-GSPE group (treated with 125-mg/kg/day GSPE for 8 weeks), and H-GSPE group (treated with 250 mg/kg/day GSPE for 8 weeks). RESULTS: Renal histopathological results indicated limited pathological damage in GSPE-treated groups. Compared with the T2DM group, the H-GSPE group had significantly reduced kidney weight and renal index. Similarly, the levels of fasting blood glucose, serum creatinine, blood urea nitrogen, uric acid, urinary albumin, and renal malondialdehyde (p < 0.05) were also significantly decreased. In addition, GSPE significantly increased the levels of superoxide dismutase, total antioxidative capability, and glutathione (p < 0.05) as well as the protein levels of Nrf2, HO-1, glutathione S-transferase, and NAD (P)H quinone oxidoreductase 1 (p < 0.05). CONCLUSION: The results indicate that GSPE reduced renal damage in rats with diabetes by activating the Nrf2 signalling pathway, which consequently increased the antioxidant capacity of the tissue. Therefore, GSPE is a potential natural agent for the treatment of diabetic nephropathy.

Construction and Investigation of an LINC00284-Associated Regulatory Network in Serous Ovarian Carcinoma.

The low survival rate associated with serous ovarian carcinoma (SOC) is largely due to the lack of relevant molecular markers for early detection and therapy. Increasing experimental evidence has demonstrated that long noncoding RNAs (lncRNAs) are involved in cancer initiation and development, and a competitive endogenous RNA (ceRNA) hypothesis has been formulated. Therefore, the characterization of new lncRNA and lncRNA-related networks is crucial for early diagnosis and targeted therapy of SOC. Data on lncRNAs, mRNAs, and miRNAs with differential expression in SOC, compared to normal ovarian tissue, were obtained from the Gene Expression Omnibus (GEO) database. Data on lncRNA expression and clinical data in SOC were obtained from The Cancer Genome Atlas (TCGA). lncRNA-miRNA interactions were predicted by the miRBase database. Different online tools, i.e., TargetScan, RNA22, miRmap, microT, miRanda, StarBase, and PicTar, were cooperatively utilized to predict the mRNAs targeted by miRNAs. The plugin of BiNGO in Cytoscape and KOBAS 3.0 were used to conduct the functional and pathway enrichment analyses. The lncRNA, miRNAs, and mRNAs identified to be expressed at statistically significant and different levels between SOC and healthy fallopian tube tissues were further validated using qRT-PCR. A total of 4 lncRNAs (LINC00284, HAGLR, HCAT158, and BLACAT1) and 111 mRNAs were found to be upregulated in SOC tissues compared to normal tissues, based on the GEO database. LINC00284 was found to be highly expressed in SOC, in association with the upregulation of the transcription factor SOX9. The high LINC00284 expression was associated with poor prognosis and proved to be an independent risk factor in patients with SOC, based on TCGA database. The qRT-PCR validation results closely recapitulated the expression profiles and prognostic scores of the aforementioned bioinformatic analyses. The LINC00284-related ceRNA network was found to be associated with SOC carcinogenesis by biofunctional analysis. In conclusion, the LINC00284-related ceRNA network may provide valuable information on the mechanisms of SOC initiation and progression. Importantly, LINC00284 proved to be a new potential prognostic biomarker for SOC.

Overexpression of ICAM-1 Predicts Poor Survival in High-Grade Serous Ovarian Carcinoma: A Study Based on TCGA and GEO Databases and Tissue Microarray.

Intercellular cell adhesion molecule-1 (ICAM-1), an important adhesion molecule in the immunoglobulin superfamily, is expressed on many cell types. Recent studies have identified ICAM-1 as a potential oncogene that promotes the development of epithelial ovarian cancer (EOC); it was also found to be associated with poor survival. However, the clinical significance of its expression in high-grade serous ovarian carcinoma (HGSOC) is unclear. Thus, this study aimed to investigate the significance of ICAM-1 expression in HGSOC. Data on ICAM1 expression and mutations in serous ovarian carcinoma (SOC) were obtained from the Cancer Genome Atlas (TCGA), and ICAM1 mRNA expression data in HGSOC were obtained from the Gene Expression Omnibus (GEO) database. ICAM-1 expression was evaluated by immunohistochemistry in HGSOC and normal fallopian tube tissues microarray. In TCGA data, amplification/mutation of ICAM1 was identified in 12% of serous ovarian carcinoma samples, and overexpression of ICAM1 mRNA predicted reduced overall survival in SOC. From TCGA and GEO data, SOC patients with ICAM1 mRNA overexpression treated with chemotherapeutic drugs that contained taxol or taxol and platin together had significantly reduced progression-free survival. According to GEO data, ICAM1 mRNA expression was found significantly higher in HGSOC than in control samples. In our study, ICAM-1 overexpression was observed in 63.1% (65/103) of HGSOCs. As a prognostic biomarker, overexpression of ICAM-1 predicted reduced recurrence-free and overall survival and is an independent risk factor for poor prognosis. These findings suggest that overexpression of ICAM-I is an independent indicator of poor prognosis for HGSOC and that it can serve as an effective clinical prognostic biomarker for this disease.

Patterns of Life Lost to Cancers with High Risk of Death in China.

To inform public health policy and research, we analyzed the patterns of life lost to cancers and evaluated the cancer burden in China. Based on the published Chinese Cancer Registry Annual Report and related literature in 2013, we calculated the cancer-related mortality and potential years of life lost (PYLL) by age, sex, districts (urban or rural), to describe the patterns of life lost to cancers. The high death-risk cancers in China were lung, liver, stomach, esophageal, colorectal, breast, pancreatic, brain and nervous system, and ovarian cancers, and leukemia. Liver and esophageal cancers were more prominent among males, while breast and colorectal cancers were more prevalent among females. The most obvious differences of mortality between urban and rural areas were found in liver, esophageal, and colorectal cancers. Cancer-related mortality increased significantly after the age of 30 years, and peaking at 70-79 years. The PYLL rate of cancer in urban areas was higher than that in rural areas (21.49 vs. 19.20/1000), and significant regional and gender differences of PYLL ranks can be observed. For people aged over 60 years, cancer PYLL mainly came from lung, stomach, and esophageal cancers; for middle-aged people, it was mainly induced by liver, colorectal, and female reproductive systems' cancers; and for those under 30 years, life lost to cancer was mainly caused by leukemia and brain, nervous system cancers. Moreover, disparities in age distribution of PYLL from different regions and sexes can be found. In short, three categories of people, including those in urban areas, males and people over 60 years, were suffering from more serious cancer deaths and life lost. These variations pose considerable challenges for the Chinese health care system, and comprehensive measures are required for cancer prevention and treatment.

Correction: Metabolic syndrome in Xinjiang Kazakhs and construction of a risk prediction model for cardiovascular disease risk.

[This corrects the article DOI: 10.1371/journal.pone.0202665.].

The Variable Regulatory Effect of Arsenic on Nrf2 Signaling Pathway in Mouse: a Systematic Review and Meta-analysis.

Arsenic is known to cause oxidative damage. Nuclear factor E2-relate factor-2 (Nrf2) can resist this toxicity. Scholars demonstrated that Nrf2 pathway was activated by arsenic. In contrast, other articles established arsenic-induced inhibition of Nrf2 pathway. To resolve the contradiction and elucidate the mechanism of Nrf2 induced by arsenic, 39 publications involving mouse models were identified through exhaustive database retrieval and were analyzed. The pooled results suggested that arsenic obviously elevated transcription and translation levels of Nrf2 and its downstream genes, NAD(P)H dehydrogenase 1 (NQO1), heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC), and GST-glutathione-S-transferase1/2 (GSTO1/2). Arsenic increased the level of reactive oxygen species (ROS), but reduced the level of glutathione (GSH). Subgroup analysis between arsenic and control groups showed that the levels of Nrf2 and its downstream genes are greater in high dose than that in the low dose, higher in short-term exposure than long term, female subjects tolerated better than males, higher in mice than the rats, and greater in other organs than the liver. However, the contents of genes of Nrf2 pathway between the arsenic and control groups were lower in rats than in mice and were less for long-term exposure than the short term (P < 0.05). Conclusively, a variable regulation of arsenic on Nrf2 pathway is noted. Higher dose and short-term exposure of female mice organs except for liver promoted Nrf2 pathway. On the other hand, arsenic inhibited Nrf2 pathway for long-term exposure on rats.

Comparison Between Metabolic Syndrome and the Framingham Risk Score as Predictors of Cardiovascular Diseases Among Kazakhs in Xinjiang.

Metabolic syndrome (MS) and Framingham risk score (FRS) can be used for predicting the risk of developing cardiovascular diseases (CVD). Previous studies that compared FRS and MS have focused on high-income urban areas. This study focused on the comparison between FRS and MS when used in nomadic minorities in mountain areas. Moreover, an applicable tool for predicting the risk of developing CVD was identified. 2,286 participants who were recruited from the far west of China were followed-up for a median of 5.49 years. MS and FRS were compared in terms of their ability in predicting development of CVD using Cox regression and receiver operating characteristic curve. After each component of MS was appraised, its area under the curve (AUC) was 0.647. When age was included, the AUC of MS risk score increased from 0.647 to 0.758 (P < 0.001). After adjusting for age, the AUC of FRS decreased from 0.732 to 0.582 (P < 0.001). The association between CVD and each quintile of MS risk score that included age was more significant than that between FRS and CVD under the same exposed condition. In conclusion, MS risk score that included age may be a better predictor of CVD among Kazakhs.

Impact of interactions among metabolic syndrome components on the development of cardiovascular disease among Kazakhs in Xinjiang.

BACKGROUND: Few prospective studies have explored the effect of interactions among metabolic syndrome (MS) components on the development of cardiovascular disease (CVD) in the Kazakh population in Xinjiang Province of China. METHOD: As of December 2016, 2,644 participants who completed a baseline survey over a period of 5 years or more were included in the study. The multiplicative interactions among MS components were evaluated by incorporation of the product terms into a logistic regression model. The additive interactions among MS components were evaluated by calculating the additive interaction index. Logistic regression was used to construct a predictive model, and CVD risk level was divided according to the risk probability of the population that did not eventually have CVD. RESULTS: When we analyzed the independent risk of MS and its components on developing CVD, only blood pressure(BP) and waist circumference(WC) were associated with CVD. A linear association was found between the risk of CVD, BP/WC, and the number of other components (trend, P<0.001). The risk of developing CVD increased when BP and WC coexisted, or when combined BP/WC with MS (≥3 components except for BP and WC) was present; however, there were no significant interactions among MS components. After the CVD hazards were divided into four levels, it was showed that over 19.92% of the incidence probability was in the population under mediate-risk while over 35.24% of them was in the high-risk group, respectively. CONCLUSIONS: BP and WC were independent risk factors for CVD in the Kazakh population. The risk of CVD was greatly increased when BP and WC coexisted or when combined BP/WC with MS (≥3 components except for BP and WC) was present, but no significant interactions were found among MS components.