Causal association of blood lipids with all-cause and cause-specific mortality risk: a Mendelian randomization study.

Dyslipidemia has long been implicated in elevating mortality risk; yet, the precise associations between lipid traits and mortality remained undisclosed. Our study aimed to explore the causal effects of lipid traits on both all-cause and cause-specific mortality. One-sample Mendelian randomization (MR) with linear and nonlinear assumptions was conducted in a cohort of 407,951 European participants from the UK Biobank. Six lipid traits, consisting of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), and lipoprotein(a), were included to investigate the causal associations with mortality. Two-sample MR was performed to replicate the association between each lipid trait and all-cause mortality. Univariable MR results showed that genetically predicted higher ApoA1 was significantly associated with a decreased all-cause mortality risk (HR[95% CI]:0.93 [0.89-0.97], P value = 0.001), which was validated by the two-sample MR analysis. Higher lipoprotein(a) was associated with an increased risk of all-cause mortality (1.03 [1.01-1.04], P value = 0.002). Multivariable MR confirmed the direct causal effects of ApoA1 and lipoprotein(a) on all-cause mortality. Meanwhile, nonlinear MR found no evidence for nonlinearity between lipids and all-cause mortality. Our examination into cause-specific mortality revealed a suggestive inverse association between ApoA1 and cancer mortality, a significant positive association between lipoprotein(a) and cardiovascular disease mortality, and a suggestive positive association between lipoprotein(a) and digestive disease mortality. High LDL-C was associated with an increased risk of cardiovascular disease mortality but a decreased risk of neurodegenerative disease mortality. The findings suggest that implementing interventions to raise ApoA1 and decrease lipoprotein(a) levels may improve overall health outcomes and mitigate cancer and digestive disease mortality.

Serum Olink Proteomics-Based Identification of Protein Biomarkers Associated with the Immune Response in Ischemic Stroke.

The immune response is considered essential for pathology of ischemic stroke (IS), but it remains unclear which immune response-related proteins exhibit altered expression in IS patients. Here, we used Olink proteomics to examine the expression levels of 92 immune response-related proteins in the sera of IS patients (n = 88) and controls (n = 88), and we found that 59 of these proteins were differentially expressed. Feature variables were screened from the differentially expressed proteins by the least absolute shrinkage and selection operator (LASSO) and the random forest and by determining whether their proteins had an area under the curve (AUC) greater than 0.8. Ultimately, we identified six potential protein biomarkers of IS, namely, MASP1, STC1, HCLS1, CLEC4D, PTH1R, and PIK3AP1, and established a logistic regression model that used these proteins to diagnose IS. The AUCs of the models in the internal validation and the test set were 0.962 (95% confidence interval (CI): 0.895-1.000) and 0.954 (95% CI: 0.884-1.000), respectively, and the same protein detection method was performed in an external independent validation set (AUC: 0.857 (95% CI: 0.801-0.913)). These proteins may play a role in immune regulation via the C-type lectin receptor signaling pathway, the PI3K-AKT signaling pathway, and the B-cell receptor signaling pathway.

AKT1 Promotes Tumorigenesis and Metastasis by Directly Phosphorylating Hexokinases.

The importance of protein kinase B (AKT) in tumorigenesis and development is well established, but its potential regulation of metabolic reprogramming via phosphorylation of the hexokinase (HK) isozymes remains unclear. There are two HK family members (HK1/2) and three AKT family members (AKT1/2/3), with varied distribution of AKTs exhibiting distinct functions in different tissues and cell types. Although AKT is known to phosphorylate HK2 at threonine 473, AKT-mediated phosphorylation of HK1 has not been reported. We examined direct binding and phosphorylation of HK1/2 by AKT1 and identified the phosphorylation modification sites using coimmunoprecipitation, glutathione pull-down, western blotting, and in vitro kinase assays. Regulation of HK activity through phosphorylation by AKT1 was also examined. Uptake of 2-[1,2-3H]-deoxyglucose and production of lactate were investigated to determine whether AKT1 regulates glucose metabolism by phosphorylating HK1/2. Functional assays, immunohistochemistry, and tumor experiments in mice were performed to investigate whether AKT1-mediated regulation of tumor development is dependent on its kinase activity and/or the involvement of HK1/2. AKT interacted with and phosphorylated HK1 and HK2. Serine phosphorylation significantly increased AKT kinase activity, thereby enhancing glycolysis. Mechanistically, the phosphorylation of HK1 at serine 178 (S178) by AKT significantly decreased the Km and enhanced the Vmax by interfering with the formation of HK1 dimers. Mutations in the AKT phosphorylation sites of HK1 or HK2 significantly abrogated the stimulatory characteristics of AKT on glycolysis, tumorigenesis, and cell migration, invasion, proliferation, and metastasis. HK1-S178 phosphorylation levels were significantly correlated with the occurrence and metastasis of different types of clinical tumors. We conclude that AKT not only regulates tumor glucose metabolism by directly phosphorylating HK1 and HK2, but also plays important roles in tumor progression, proliferation, and migration.

Ternary-Metal Sn-Pb-Zn Perovskite to Reconstruct Top Surface for Efficient and Stable Less-Pb Perovskite Solar Cells.

Though Sn-Pb alloyed perovskite solar cells (PSCs) achieved great progress, there is a dilemma to further increase Sn for less-Pb requirement. High Sn ratio (>70%) perovskite exhibits nonstoichiometric Sn:Pb:I at film surface to aggravate Sn2+ oxidation and interface energy mismatch. Here, ternary metal alloyed (FASnI3 )0.7 (MAPb1- x Znx I3 )0.3 (x = 0-3%) is constructed for Pb% < 30% perovskite. Zn with smaller ionic size and stronger ionic interaction than Sn/Pb assists forming high-quality perovskite film with ZnI6 4- enriched at surface to balance Sn:Pb:I ratio. Differing from uniform bulk doping, surface-rich Zn with lower lying orbits pushes down the energy band of perovskite and adjusts the interface energy for efficient charge transfer. The alloyed PSC realizes efficiency of 19.4% at AM1.5 (one of the highest values reported for Pb% < 30% PSCs). Moreover, stronger bonding of Zn─I and Sn─I contributes to better durability of ternary perovskite than binary perovskite. This work highlights a novel alloy method for efficient and stable less-Pb PSCs.

Improving Sedum plumbizincicola genetic transformation with the SpGRF4-SpGIF1 gene and the self-excision CRE/LoxP system.

MAIN CONCLUSION: S. plumbizincicola genetic transformation was optimized using a self-excision molecular-assisted transformation system by integrating the SpGRF4/SpGIF1 gene with XVE and Cre/loxP. Sedum plumbizincicola, despite being an excellent hyperaccumulator of cadmium and zinc with significant potential for soil pollution phytoremediation on farmland, has nonetheless trailed behind other major model plants in genetic transformation technology. In this study, different explants and SpGRF4-SpGIF1 genes were used to optimize the genetic transformation of S. plumbizincicola. We found that petiole and stem segments had higher genetic transformation efficiency than cluster buds. Overexpression of SpGRF4-SpGIF1 could significantly improve the genetic transformation efficiency and shorten the period of obtaining regenerated buds. However, molecular assistance with overexpression of SpGRF4-SpGIF1 leads to abnormal morphology, resulting in plant tissue enlargement and abnormal growth. Therefore, we combined SpGRF4-SpGIF1 with XVE and Cre/loxP to obtain DNA autocleavage transgenic plants induced by estradiol, thereby ensuring normal growth in transgenic plants. This study optimized the S. plumbizincicola genetic transformation system, improved the efficiency of genetic transformation, and established a self-excision molecular-assisted transformation system. This work also established the basis for studying S. plumbizincicola gene function, and for S. plumbizincicola breeding and germplasm innovation.

Plasma lipidomic profiling reveals six candidate biomarkers for the prediction of incident stroke in patients with hypertension.

INTRODUCTION: The burden of stroke in patients with hypertension is very high, and its prediction is critical. OBJECTIVES: We aimed to use plasma lipidomics profiling to identify lipid biomarkers for predicting incident stroke in patients with hypertension. METHODS: This was a nested case-control study. Baseline plasma samples were collected from 30 hypertensive patients with newly developed stroke, 30 matched patients with hypertension, 30 matched patients at high risk of stroke, and 30 matched healthy controls. Lipidomics analysis was performed by ultrahigh-performance liquid chromatography-tandem mass spectrometry, and differential lipid metabolites were screened using multivariate and univariate statistical methods. Machine learning methods (least absolute shrinkage and selection operator, random forest) were used to identify candidate biomarkers for predicting stroke in patients with hypertension. RESULTS: Co-expression network analysis revealed that the key molecular alterations of the lipid network in stroke implicate glycerophospholipid metabolism and choline metabolism. Six lipid metabolites were identified as candidate biomarkers by multivariate statistical and machine learning methods, namely phosphatidyl choline(40:3p)(rep), cholesteryl ester(20:5), monoglyceride(29:5), triglyceride(18:0p/18:1/18:1), triglyceride(18:1/18:2/21:0) and coenzyme(q9). The combination of these six lipid biomarkers exhibited good diagnostic and predictive ability, as it could indicate a risk of stroke at an early stage in patients with hypertension (area under the curve = 0.870; 95% confidence interval: 0.783-0.957). CONCLUSIONS: We determined lipidomic signatures associated with future stroke development and identified new lipid biomarkers for predicting stroke in patients with hypertension. The biomarkers have translational potential and thus may serve as blood-based biomarkers for predicting hypertensive stroke.

Projected Global Trends in Ischemic Stroke Incidence, Deaths and Disability-Adjusted Life Years From 2020 to 2030.

BACKGROUND: We projected global trends in ischemic stroke from 2020 to 2030 according to age, sex, and socio-demographic index (SDI) quintile. METHODS: Estimated annual percentage changes (EAPCs) were used to project trends in the incidence of deaths from and disability-adjusted life years (DALYs) due to ischemic stroke between 2020 and 2030. EAPCs were computed using generalized additive models and data from the Global Burden of Disease study during the 1990 to 2019 period. RESULTS: The global age-standardized incidence rate of ischemic stroke was projected to increase to 89.32 per 100 000 population in 2030 (EAPC=0.89), whereas the associated global age-standardized death and DALY rates were projected to decrease to 18.28 (EAPC, -3.58) and 500.37 per 100 000 (EAPC=-1.75), respectively, in 2030. The projections indicated a higher age-standardized incidence rate of ischemic stroke among women than among men in 2030 (90.70 versus 87.64 per 100 000). The incidence rate of ischemic stroke was projected to increase across all age groups and SDI quintiles between 2020 and 2030. At the national level, the greatest increase in the age-standardized incidence rate of ischemic stroke between 2020 and 2030 was projected to occur in Cyprus (EAPC=4.16), followed by Palestine (EAPC=3.50) and South Africa (EAPC=2.64). Additionally, the projections suggested increases in the age-standardized death and DALY rates due to ischemic stroke for countries in low-SDI quintiles (EAPC=3.68 and EAPC=5.30, respectively). CONCLUSIONS: The projections indicated that the incidence rate of ischemic stroke will increase both sexes, all age groups, and all SDI quintiles and in some countries between 2020 and 2030. Furthermore, countries with a low SDI should be aware of potential increases in the age-standardized death and DALY due to ischemic stroke.

Triglyceride-glucose index and triglyceride to high-density lipoprotein cholesterol ratio as potential cardiovascular disease risk factors: an analysis of UK biobank data.

BACKGROUND: The triglyceride-glucose (TyG) index and triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, two simple surrogate indicators of insulin resistance, have been demonstrated to predict cardiovascular disease (CVD). However, very few studies have investigated their associations with CVD in European populations. METHODS: A total of 403,335 participants from the UK Biobank with data for TyG index and TG/HDL-C ratio and free from CVD at baseline were included. Cox models were applied to evaluate the association between TyG index and TG/HDL-C ratio and incident CVD. Mediation analyses were performed to evaluate the contribution of prevalent diabetes, hypertension, and dyslipidemia to observed associations. RESULTS: During a median follow-up of 8.1 years, 19,754 (4.9%) individuals developed CVD, including 16,404 (4.1%) cases of CHD and 3976 (1.0%) cases of stroke. The multivariable-adjusted hazard ratios of total CVD in higher quartiles versus the lowest quartiles were 1.05, 1.05, and 1.19, respectively, for TyG index, and 1.07, 1.13, and 1.29, respectively, for TG/HDL-C ratio. There were significant trends toward an increasing risk of CVD across the quartiles of TyG index and TG/HDL-C ratio. In mediation analyses, dyslipidemia, type 2 diabetes, and hypertension explained 45.8%, 27.0%, and 15.0% of TyG index's association with CVD, respectively, and 40.0%, 11.8%, and 13.3% of TG/HDL-C ratio's association with CVD, respectively. CONCLUSIONS: Elevated baseline TyG index and TG/HDL-C ratio were associated with a higher risk of CVD after adjustment for the well-established CVD risk factors. These associations were largely mediated by greater prevalence of dyslipidemia, type 2 diabetes, and hypertension.

Functional analysis of transgenic cry1Ah-1 maize.

Maize is an important food crop in the world, but the yield and quality of maize have been significantly reduced due to the impact of insect pests. In order to address this issue, the cry1Ah gene was subjected to error-prone PCR for mutagenesis, and subsequently, the mutant cry1Ah-1 gene was introduced into maize inbred line GSH9901 callus using the Agrobacterium-mediated method. The T2 generation transformed plants were obtained by subculture, and 9 transgenic positive plants were obtained by molecular detection which was carried out by PCR, qRT-PCR, Bt gold-labeled immunoassay test strips, Western blot and ELISA. It was found that the Cry1Ah-1 gene could be transcribed normally in maize leaves, of which OE1 and OE3 had higher relative expression levels and could successfully express proteins of 71.94 KD size. They were expressed in different tissues at the 6-leaf stage, heading stage and grain-filling stage, and could ensure the protection of maize from corn borer throughout the growth period. The biological activities of OE1 and OE3 were tested indoors and in the field, and the results showed that in indoors, the corn borer that fed on OE1 and OE3 corn leaves had a mortality rate of 100 % after 3 days; in the field, OE1 and OE3 had strong insecticidal activity against corn borer, reaching a high resistance level. In conclusion, the transgenic cry1Ah-1 maize has a strong insecticidal effect on corn borer, and has a good prospect of commercialization.

Global Burden of Cardiovascular Disease from 1990 to 2019 Attributable to Dietary Factors.

BACKGROUND: Although dietary factors play a crucial role in the incidence of cardiovascular disease (CVD), the specific dietary risk factors vary across regions and require further investigation. OBJECTIVE: We aimed to analyze the burden of CVD due to different dietary factors by sex, age, and sociodemographic index (SDI) for 204 countries and territories between 1990 and 2019. METHODS: Data were extracted from the Global Burden of Disease 2019 and analyzed to determine population attributable fractions (PAFs), mortality, disability-adjusted life years (DALYs), and trends thereof, for CVDs attributable to dietary risk factors from 1990 to 2019. We used a generalized linear model with a Gaussian distribution to calculate the estimated annual percentage changes (EAPCs) in CVD mortality and DALY rates attributable to dietary risk factors. We also used a comparative risk-assessment framework to estimate CVD mortality and DALYs attributable to dietary risk factors. RESULTS: Approximately 40% of CVD mortality and DALY rates were attributable to dietary risk factors, with high-sodium intake, low whole grain intake, and low legume intake being the greatest dietary risk factors globally. Moreover, high SDI regions had the highest PAFs for CVD mortality and DALYs associated with high red and processed meat intake, middle SDI regions had the highest PAFs with high-sodium intake, and low SDI regions had the highest PAFs with low fruit and vegetable intake. The highest PAFs for CVD mortality and DALYs were associated with low whole grain intake in 13 and 9 regions, respectively. CONCLUSION: Reducing sodium intake and increasing whole grain and legume intake should be the top priority worldwide for improving regional diets and thereby decreasing CVD burdens. Other priorities should be set for regions with different SDIs, depending on the predominant dietary risk factors for CVDs in the respective regions.

Aurantimonas marianensis sp. nov., isolated from deep-sea sediment of the Mariana Trench.

A novel strain, designated as LRZ36T, was isolated from deep-sea sediment (from a depth of 5400 m) from the Mariana Trench. Cells of this strain are rod-shaped, Gram-stain-negative, strictly aerobic and non-motile. Phylogenetic analysis of LRZ36T based on 16S rRNA gene sequences revealed a lineage in the family Aurantimonadaceae but distinct from the most closely related species Aurantimonas marina CGMCC 1.17725T, 'Aurantimonas litoralis' KCTC 12094 and Aurantimonas coralicida DSM 14790T with sequence identities of 99.4 %, 98.0 and 97.9 %, respectively. The genome of LRZ36T was 3.8 Mbp in size with a DNA G+C content of 64.8 %, containing 3623 predicted coding genes. LRZ36T showed average nucleotide identity values of 89.8 %, 78.7 and 78.5 % and digital DNA-DNA hybridization values of 38.9 %, 21.7 and 21.6 % with A. marina CGMCC 1.17725T, 'A. litoralis' KCTC 12094 and A. coralicida DSM 14790T, respectively. The major respiratory quinone was ubiquinone-10 (Q-10), and the predominant fatty acids were C18 : 1ω7c (74.4 %) and C16 : 0 (12.1 %). The polar lipids in LRZ36T are diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine, phosphatidylcholine, phosphatidylinositol mannoside, an unidentified aminophospholipid, three unidentified lipids, three unidentified phospholipids and two unidentified aminolipids. On the basis of genotypic and phenotypic evidence, LRZ36T represents a novel species of the genus Aurantimonas, for which the name Aurantimonas marianensis sp. nov. is proposed. The type strain is LRZ36T (= KCTC 92065T = GDMCC 1.2985T=MCCC 1K07227T).

Characteristics of B cells and immunoglobulin profile in Takayasu's arteritis.

OBJECTIVES: Disorders of humoral immunity in Takayasu's arteritis (TAK) have not been well explored. This study describes the characteristics of B cells and immunoglobulin (Ig) profile in patients with TAK. METHODS: Peripheral B cell populations assessed using flow cytometry and serum Ig levels assessed using a biochemical analyser in 98 newly diagnosed patients with TAK were analysed and compared with those of 31 patients with systemic lupus erythematosus (SLE) and 60 healthy controls (HCs). CD19+ B cell and IgG infiltration to the aortic tissue was evaluated by immunohistochemical staining. RESULTS: The proportion of peripheral CD3-CD19+ B cells and levels of serum IgG in TAK were lower than those in SLE, but higher than those in HCs. CD3-CD19+ B cell counts were higher in TAK than in HCs. Serum IgG and IgG1 levels were higher in active TAK than in non-active TAK. In TAK, positive correlations of serum IgG levels with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, Kerr score, and Indian Takayasu Clinical Activity Score (ITAS2010, ITAS-A) were observed before immunotherapy. After 6 months of immunotherapy, serum Ig levels significantly decreased. Positive correlations between the changes in IgG levels and values of ESR, CRP, Kerr score, and ITAS-A were detected. Immunohistochemical staining confirmed CD19+ B cell and IgG infiltration to the aortic wall in patients with TAK. CONCLUSIONS: Enhanced B cells might contribute to the pathogenesis of TAK, and serum IgG levels could serve as a simple, useful biomarker to assess disease activity and monitor treatment response in TAK.

A solvent- and vacuum-free route to large-area perovskite films for efficient solar modules.

Recent advances in the use of organic-inorganic hybrid perovskites for optoelectronics have been rapid, with reported power conversion efficiencies of up to 22 per cent for perovskite solar cells. Improvements in stability have also enabled testing over a timescale of thousands of hours. However, large-scale deployment of such cells will also require the ability to produce large-area, uniformly high-quality perovskite films. A key challenge is to overcome the substantial reduction in power conversion efficiency when a small device is scaled up: a reduction from over 20 per cent to about 10 per cent is found when a common aperture area of about 0.1 square centimetres is increased to more than 25 square centimetres. Here we report a new deposition route for methyl ammonium lead halide perovskite films that does not rely on use of a common solvent or vacuum: rather, it relies on the rapid conversion of amine complex precursors to perovskite films, followed by a pressure application step. The deposited perovskite films were free of pin-holes and highly uniform. Importantly, the new deposition approach can be performed in air at low temperatures, facilitating fabrication of large-area perovskite devices. We reached a certified power conversion efficiency of 12.1 per cent with an aperture area of 36.1 square centimetres for a mesoporous TiO2-based perovskite solar module architecture.

Proteomic advance of ischemic stroke: preclinical, clinical, and intervention.

Ischemic stroke (IS) is the most common type of stroke and is characterized by high rates of mortality and long-term injury. The prediction and early diagnosis of IS are therefore crucial for optimal clinical intervention. Proteomics has provided important techniques for exploring protein markers associated with IS, but there has been no systematic evaluation and review of research that has used these techniques. Here, we review the differential proteins that have been found in cell- and animal- based studies and clinical trials of IS in the past 10 years; determine the key pathological proteins that have been identified in clinical trials; summarize the target proteins affected by interventions aimed at treating IS, with a focus on traditional Chinese medicine treatments. Overall, we clarify findings and problems that have been identified in recent proteomics research on IS and provide suggestions for improvements in this area. We also suggest areas that could be explored for determining the pathogenesis and developing interventions for IS.

Exploring Transcriptional Regulation of Hyperaccumulation in Sedum plumbizincicola through Integrated Transcriptome Analysis and CRISPR/Cas9 Technology.

The cadmium hyperaccumulator Sedum plumbizincicola has remarkable abilities for cadmium (Cd) transport, accumulation and detoxification, but the transcriptional regulation mechanisms responsible for its Cd hyperaccumulation remain unknown. To address this knowledge gap, we conducted a comparative transcriptome study between S. plumbizincicola and the non-hyperaccumulating ecotype (NHE) of Sedum alfredii with or without Cd treatment. Our results revealed many differentially expressed genes involved in heavy metal transport and detoxification that were abundantly expressed in S. plumbizincicola. Additionally, we identified a large number of differentially expressed transcription factor genes, highlighting the complexity of transcriptional regulatory networks. We further screened four transcription factor genes that were highly expressed in the roots of S. plumbizincicola as candidate genes for creating CRISPR/Cas9 knockout mutations. Among these, the SpARR11 and SpMYB84 mutant lines exhibited decreased Cd accumulation in their aboveground parts, suggesting that these two transcription factors may play a role in the regulation of the Cd hyperaccumulation in S. plumbizincicola. Although further research will be required to determine the precise targeted genes of these transcription factors, combined transcriptome analysis and CRISPR/Cas9 technology provides unprecedented opportunities for identifying transcription factors related to Cd hyperaccumulation and contributes to the understanding of the transcriptional regulation mechanism of hyperaccumulation in S. plumbizincicola.

Restricting the Formation of Pb-Pb Dimer via Surface Pb Site Passivation for Enhancing the Light Stability of Perovskite.

Poor light stability hinders the potential applications of perovskite optoelectronic devices. Recent experiments have demonstrated that the passivation surface via forming strong chemical bonds (SO4 -Pb, PO4 -Pb, Cl-Pb, O-Pb, and S-Pb) could effectively improve the light stability of perovskite solar cells. However, the underlying reasons are not clear. Herein, the elusive underlying mechanisms of light stability enhancement are explained in detail using first principles calculations. The small polaron model and self-trapped exciton model demonstrate that an iodine vacancy defect on the surface of perovskite could trap a free electron under light illumination, which leads to a significant rearrangement of the Pb-I lattice and creats a new chemical species, i.e., a Pb-Pb dimer bound in the typical perovskite of CH3 NH3 PbI3 . The Pb-Pb dimer distorts the Pb-I octahedral lattice and reduces the defect formation energy of the I atoms. The surface Pb site passivation can prevent the formation of the Pb-Pb dimer, thereby improving the light stability. In addition, the strong ionic bond could better stabilize the Pb site. The in-depth understanding of the light stability and the passivation mechanism in this study can promote the application of perovskite optoelectronic devices.

Educational level differences in the primary and secondary prevention of stroke.

The aim of this study is to estimate the educational level differences in the primary and secondary prevention of stroke among the Chinese population. Data were obtained from the China Kadoorie Biobank (CKB) survey of 512,891 people aged 30-79 years in 10 geographic regions of China, which was conducted from 2002 to 2008. The Prediction for Atherosclerotic Cardiovascular Disease Risk in China model was used to identify individuals with a high estimated 10-year stroke risk. A total of 8884 participants (1.7%) had established stroke and 218,972 (42.7%) had a high stroke risk. In both primary and secondary prevention, the participants' educational level was positively associated with the control of smoking, blood pressure, consuming a healthy diet, and the use of antiplatelet, BP-lowering medications but negatively associated with higher physical activity levels (all Ptrend < 0.001). In addition, the positive associations were observed with the control of drinking and use of anti-hyperglycaemia medication for primary prevention (all Ptrend < 0.001) and with the use of lipid-lowering medication for secondary prevention (Ptrend = 0.019). The results of the interaction between education level and prevention level showed that, compared with participants in primary prevention, educational level disparities in those with secondary prevention had significantly higher use of antiplatelets and lipid-lowering drugs, achieving the physical activity goal and non-current drinker (all Pfor interaction < 0.05). A higher education level was associated with an increased acceptance of primary and secondary prevention strategies (not smoking or drinking, consuming a healthier diet) except for engaging in a suitable level of physical activity.

Multivitamin/mineral supplementation and the risk of cardiovascular disease: a large prospective study using UK Biobank data.

PURPOSE: Despite the widespread use of multivitamin/mineral supplements, the effects of multivitamin/mineral on cardiovascular disease (CVD) remain inconclusive. We aimed to prospectively investigate how multivitamin/mineral use is associated with CVD. METHODS: This population-based cohort study included 465,278 men and women who participated in the UK Biobank and were free from CVD at baseline. Participants were enrolled between 2006 and 2010 and followed-up until the end of 2018. Data on supplement use including multivitamin/mineral were collected using self-reported questionnaires. Cox proportional hazards models were used to estimate the hazard ratios of CVD events in relation to multivitamin/mineral use. RESULTS: During the follow-up, we identified 25,772 cases of CVD events, 4754 cases of CVD mortality, 18,728 cases of coronary heart disease, 6726 cases of myocardial infarction, and 4561 cases of stroke. The multivariable-adjusted hazard ratios associated with multivitamin/mineral use were 0.96 (95% CI: 0.93, 0.99) for CVD events, 0.92 (0.86, 1.00) for CVD mortality, 0.96 (0.93, 0.99) for coronary heart disease, and 0.92 (0.86, 0.97) for myocardial infarction. Subgroup analysis suggested that multivitamin/mineral use was associated with a significantly lower risk of CVD events in participants aged < 60 years and in former and current smokers (P for interaction ≤ 0.01). Sensitivity analyses showed no substantial change in the results when we excluded participants who developed CVD events during the first 2 years of follow-up. CONCLUSION: Multivitamin/mineral supplementation was associated with very modest reductions in CVD events. Age and smoking might modify these associations.

Temporal and mediation relations of weight loss, and changes in insulin resistance and blood pressure in response to 2-year weight-loss diet interventions: the POUNDS Lost trial.

PURPOSE: Body weight and insulin resistance (IR) are closely correlated, and their temporal sequences in affecting blood pressure (BP) remain poorly defined. We examined the temporal sequences of weight loss and IR change, and their relations with BP in the Pounds Lost trial, a randomized weight-loss diet intervention study. METHODS: The present study included overweight/obese adults, who were randomized in a 2 × 2 factorial design to low-calorie diets containing 20 or 40% fat and 15 or 25% protein (diets with 65, 55, 45 and 35% carbohydrate). Weight, IR, systolic and diastolic BP levels were measured at baseline, 6 and 24 months. After excluding the subjects who took antihypertensive drugs, cross-lagged path and mediation analyses were performed among 540 participants. RESULTS: After adjusting for age, race, sex, and diet groups, the cross-lagged path coefficient from baseline weight to 24-month IR (ß1 = 0.135, P = 0.04) was significantly greater than the path coefficient (ß2 = 0.022, P > 0.05) from baseline IR to 24-month weight (P < 0.05 for the difference in ßs), indicating that weight-loss preceded change of IR. The mediation effects of 24-month IR on the 24-month systolic BP and diastolic BP were estimated at 20.94% (P = 0.004) and 17.03% (P = 0.034), respectively. CONCLUSIONS: Our data indicate that weight loss precedes change of IR, which mediates a significant proportion of the effects of weight loss on changes of BP in response to the diet interventions. TRIAL REGISTRATION: NCT00072995 First Posted November 17, 2003 Last Update Posted January 30, 2013 this study was not 'retrospectively registered'.

Metabolomics of ischemic stroke: insights into risk prediction and mechanisms.

Ischemic stroke (IS) is the most prevalent type of stroke. The early diagnosis and prognosis of IS are crucial for successful therapy and early intervention. Metabolomics, a tool in systems biology based on several innovative technologies, can be used to identify disease biomarkers and unveil underlying pathophysiological processes. Accordingly, in recent years, an increasing number of studies have identified metabolites from cerebral ischemia patients and animal models that could improve the diagnosis of IS and prediction of its outcome. In this paper, metabolomic research is comprehensively reviewed with a focus on describing the metabolic changes and related pathways associated with IS. Most clinical studies use biofluids (e.g., blood or plasma) because their collection is minimally invasive and they are ideal for analyzing changes in metabolites in patients of IS. We review the application of animal models in metabolomic analyses aimed at investigating potential mechanisms of IS and developing novel therapeutic approaches. In addition, this review presents the strengths and limitations of current metabolomic studies on IS, providing a reference for future related studies.