DLK1 promoted ischemic angiogenesis through notch1 signaling in endothelial progenitor cells.

Delta like non-canonical Notch ligand 1 (DLK1), as a member of epidermal growth factor-like family, plays a critical role in somatic growth, tissue development and possibly tissue renewal. Though previous studies had indicated that DLK1 contributed to adipogenesis and myogenesis, it's still controversial whether DLK1 affects angiogenesis and how it interacts with Notch signaling with numerous conflicting reports from different models. Based on our preliminary finding that DLK1 expression was up-regulated in mice ischemic gastrocnemius and in the border zone of infarcted myocardium, we administered either recombinant DLK1 (rDLK1) or PBS in C57BL/6 mice after establishment of hindlimb ischemia (HLI) and myocardial infarction (MI), respectively. Exogenous rDLK1 administration significantly improved both blood perfusion of mice ischemic hindlimbs and muscle motor function on the 3rd, 7th day after HLI, by promoting neovascularization. Similar effect on neovascularization was verified in mice on the 28th day after MI as well as improvement of cardiac failure. Correspondingly, the number of CD34+KDR+ cells, indicated as endothelial progenitor cells (EPCs), was significantly in mice ischemic gastrocnemius by rDLK1 administration, which was abrogated by DAPT as the specific inhibitor of Notch intracellular domain (NICD). Furthermore, bone marrow mononuclear cells were obtained from C57BL/6 mice and differentiated to EPCs ex vivo. Incubation with rDLK1 triggered Notch1 mRNA and NICD protein expressions in EPCs as exposed to hypoxia and serum deprivation, promoting EPCs proliferation, migration, anti-apoptosis and tube formation. Otherwise, rDLK1 incubation significantly decreased intracellular and mitochondrial reactive oxygen species, increased ATP content and mitochondrial membrane potential, downregulated short isoform of OPA-1 expression whereas upregulated mitofusin (-1, -2) expression in EPCs by Notch1 signaling, which were all abrogated by DAPT. In summary, the present study unveils the pro-angiogenesis and its mechanism of rDLK1 through activation of Notch1 signaling in endothelial progenitor cells.

Cultural adaptation and evaluation of a school-based positive psychology intervention among Chinese middle school students: A mixed methods program design study.

With the recognition of positive psychology within China, there is a pressing need for evidence-based positive psychology interventions (PPIs) tailored to the cultural context of Chinese schools. The goals of the present study were to (a) culturally adapt the Well-Being Promotion Program using the ecological validity model and (b) conduct a preliminary evaluation of its effectiveness. Within a randomized controlled trial, we collected data from 107 eighth-grade students randomly assigned to the intervention (n = 55) or control group (n = 52). A mixed methods approach was used, with analysis of covariance to assess program effectiveness, and content analyses of students' short-answer responses collected from the intervention group. Qualitatively, more than half of students reported having positive feelings and an increase in happiness due to the program. Quantitatively, the study found that the intervention was associated with a significant increase in adaptability, a subcategory of psychological suzhi, following the intervention. Gender breakdown revealed that the intervention had a significant positive effect on boys' cognitive quality, but not girls'. Additionally, it marginally impacted girls' self-management and boys' adaptability quality. However, caution is warranted in interpreting the quantitative results due to limitations, such as a small sample size and a relatively low response rate at Time 2. This pilot study contributes to the literature by bridging the gap between evidence-based PPIs developed in Western contexts and their culturally responsive implementation in Chinese schools. Consequently, the results should be considered as initial evidence warranting further examination of effectiveness, yet with significant potential to advance future cultural adaptations of PPIs. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Adherence to oxidative balance score is inversely associated with the prevalence of stroke: results from National Health and Nutrition Examination Survey 1999-2018.

Introduction: The relationship between oxidative balance score (OBS), an emerging integrative metric for assessing individual redox homeostasis, and the prevalence of stroke in the general population remains unknown. We aimed to explore these relationships in the National Health and Nutrition Examination Survey (NHANES). We investigated the relationship between the oxidative balance score (OBS) and stroke prevalence using NHANES data from 1999-2018. Methods: We included eligible individuals from NHANES 1999-2018. OBS calculations were based on previously validated methods, and stroke diagnoses were based on self-reports in questionnaires. Multivariable logistic regression analyses were used to examine the independent associations of overall, dietary, and lifestyle OBS with stroke prevalence. In addition, restricted cubic spline (RCS), stratified analysis, and sensitivity analysis were used. Results: We included 25,258 participants aged 20-85 years, in which the prevalence of stroke was 2.66%. After adjusting for all confounders, overall and dietary OBS, but not lifestyle OBS, were inversely associated with the prevalence of stroke [odds ratios and 95% confidence intervals of 0.97 (0.96, 0.99) and 0.98 (0.96, 0.99) for overall and dietary OBS, respectively, both p < 0.05]. In addition, there was a dose-response relationship between overall and dietary OBS and stroke prevalence. The RCS showed that these relationships were linear. Stratified analyses indicated that socioeconomic status (SES) significantly influenced the relationship between all OBS and stroke prevalence. Conclusion: Dietary OBS, but not lifestyle OBS, had an inverse relationship with the prevalence of stroke in the general population. SES significantly influenced the protective effect of OBS against stroke. These findings emphasize the importance of integrated antioxidant properties from diet for stroke prevention.

Natural phytoalexins inspired the discovery of new biphenyls as potent antifungal agents for treatment of invasive fungal infections.

With the aim of discovering novel and effective antifungal agents derived from natural sources, a series of new biphenyls based on natural biphenyl phytoalexins were designed, synthesized and evaluated for their antifungal activities against four invasive fungi. By modifying the two benzene rings of noraucuparin, a well-known biphenyl phytoantitoxin, some promising compounds with remarkable antifungal activity were discovered. Notably, compounds 23a, 23e and 23h exhibited potent activities and a broad antifungal spectrum with low MICs of 0.25-16 µg/mL, which were 8-256-fold more potent than that of the lead compound noraucuparin. Particularly, they displayed comparable potency to the positive control amphotericin B against Cryptococcus neoformans. Some interesting structure-activity relationships have also been discussed. Preliminary mechanism studies revealed that compound 23h might achieve its rapid fungicidal activity by disrupting the fungal cell membrane. Moreover, compound 23h exhibited significant inhibition against some virulence factors of Cryptococcus neoformans, low toxicity to normal human cells, as well as favorable pharmacokinetic and drug-like properties. The above results evidenced that the development of new antifungal candidates derived from natural phytoalexins was a bright and promising strategy.

Effect of Traditional Chinese Exercises on Patients with Chronic Heart Failure (TCE-HF): A Systematic Review and Meta-Analysis.

Exercise-based cardiac rehabilitation is safe and effective for chronic heart failure (CHF) patients. The present study aimed to investigate the effects of traditional Chinese exercise (TCE) on patients with CHF and the impact of exercise types and duration. Evaluation of randomized controlled trials (RCTs) of TCE in patients with CHF published since 1997 from PubMed, Embase, Web of Science, the Cochrane Library, Chongqing VIP, Wanfang Databases, and the China National Knowledge was performed. A total of 41 RCTs, including 3209 patients with CHF, were included. It showed that TCE significantly increased 6-min walk distance (6MWD) [mean difference (MD) = 72.82 m, p < 0.001] and left ventricular ejection fraction (MD = 5.09%, p < 0.001), whereas reduced B-type natriuretic peptide (BNP) (MD = -56.80 pg/mL, p < 0.001), N-terminal pro-BNP (MD = -174.94 pg/mL, p < 0.05), and Minnesota Living with Heart Failure Questionnaire scores (MD = -11.31, p < 0.001). However, no significant difference was found in the effects of TCE on peak oxygen consumption. The increase in TCE weekly duration and program duration significantly improved 6MWD (MD = 71.91 m, p < 0.001; MD = 74.11 m, p < 0.001). The combination of TCE and conventional aerobic exercise significantly improved 6MWD (MD = 19.86 m, p < 0.005). TCE improves exercise capacity, cardiac function, and quality of life in patients with CHF, which might be an optimal and available pattern of exercise-based cardiac rehabilitation.

Global disease burden and its attributable risk factors of peripheral arterial disease.

Peripheral arterial disease (PAD) is a prevalent subtype of atherosclerotic cardiovascular diseases. It is crucial to assess the PAD-related burden and its attributable risk factors. We use the Global Burden of Disease study 2019 database to calculate the incidence, prevalence, mortality, disability-adjusted life years (DALY), attributable risk factors and estimated annual percentage change. The disease burden of PAD grows significantly with age accompanied by prominent heterogeneity between male and female. Despite the increase in the absolute numbers of disease burden from 1990 to 2019, the global PAD-related age-standardized death rate (ASDR) and age-standardized disability-adjusted life years rate (ASDALYR) have a mild downward trend from 1990 to 2019, which negatively correlated with sociodemographic index (SDI). Smoking and high systolic blood pressure (SBP) were the primary attributable risk factors for males (ASDR: 33.4%; ASDALYR: 43.4%) and females (ASDR: 25.3%; ASDALYR: 27.6%), respectively. High fasting plasma glucose (FPG) had become the second risk factor for ASDR (males: 28.5%; females: 25.2%) and ASDALYR (males: 29.3%; females: 26.3%) with an upward tendency. Low-middle SDI regions were predicted to have the most remarkable upward trend of PAD-related burden caused by high FPG. Smoking caused more disease burden in males before 85-90 years old and females before 65-70 years old, while high FPG and high SBP caused more burden after that. The patterns of PAD-related burden and its attributable risk factors are heterogeneous across ages, genders, and SDI regions. To reduce disease burden, tailored strategies should be implemented.

Global burden of calcific aortic valve disease and attributable risk factors from 1990 to 2019.

Background: Calcific aortic valve disease (CAVD) was highly prevalent among developed countries and caused numerous deaths. Based on the Global Burden of Disease 2019, this study was designed to present comprehensive epidemiological information, attributable risks, and relevant factors. Methods: All data were available online via the Global Health Data Exchange (GHDx). In this study, we analyzed the global incidence, prevalence, deaths, and disability-adjusted life years (DALYs) of CAVD across different regions from 1990 to 2019. We applied the estimated annual percentage changes (EAPCs) to evaluate the change trends and their attributable risks. In addition, we explored several relevant factors. Results: From 1990 to 2019, the incidence cases, prevalence cases, CAVD-related deaths, and DALYs of CAVD gradually increased globally. However, the age-standardized death rate (ASDR) was relatively stable, and the age-standardized DALYs rate gradually declined during the past 30 years. Males and elderly individuals were more likely to suffer from CAVD. High systolic blood pressure (SBP) was the predominant attributable risk of disease burden that presented a global downward trend (death: EAPC = -0.68, 95% CI -0.77~-0.59, P < 0.001; DALYs: EAPC = -0.99, 95% CI -1.09 to -0.89, P < 0.001). Alcohol consumption (R = 0.79, P < 0.001), smoking prevalence (R = 0.75, P < 0.001), and calcium (R = 0.72, P < 0.001) showed a positive correlation with the age-standardized incidence rate (ASIR), whereas classic monsoon region (R = -0.68, P < 0.001) and mean temperature (R = -0.7, P < 0.001) showed a negative correlation with age-standardized incidence rate (ASIR). Besides, medical and healthcare resources presented a positive correlation with ASIR. Meanwhile, similar relationships were found in age-standardized prevalence rate (ASPR), ASDR, and age-standardized DALY rate (ASDALYR). Conclusion: CAVD displays widely varied spatial distribution around the world, of which high SDI regions have the highest burdens. Age is a powerful factor and hypertension a predominant attributable risk factor. Moreover, controlling blood pressure, avoiding smoking, reducing alcohol consumption, and so on, could effectively reduce the burden of CAVD.

Burden of Aortic Aneurysm and Its Attributable Risk Factors from 1990 to 2019: An Analysis of the Global Burden of Disease Study 2019.

Background: Global and national estimates on the epidemiology of aortic aneurysms are prerequisites for disease management and policymaking. Based on the Global Burden of Disease (GBD) 2019, this study aimed to discern the global aortic aneurysm burden by systematically analyzing demographic data on mortality and exploring the attributable risks and relevant factors. Methods: The data analyzed in this study were available in the Global Health Data Exchange (GHDx) online query tool. The population in our study comprised individuals from 204 countries and territories from 1990 to 2019. The estimated annual percentage changes (EAPCs) were performed to assess the temporal trends of aortic aneurysms and their attributable risks. Spearman correlation analysis was performed to explore the relationship between the burden of aortic aneurysm and covariates. Results: Although aortic aneurysm-related deaths (82.1%) and disability-adjusted life years (DALYs) (67%) increased from 1990 to 2019, the global trend of age-standardized rate of death (ASRD) (EAPC: -1.34, 95% CI = -1.46 to -1.22, P < 0.001) and age-standardized rate of DALY (ASDALYR) (EAPC: -1.06, 95% CI = -1.17 to -0.95, P < 0.001) decreased, both of which presented age dependence and gender differences. Smoking and high systolic blood pressure (SBP) were the main attributable risks of disease burden and tend to decease globally (EAPC: -1.89, 95% CI = -2.03 to -1.89, P < 0.001; -1.31 95% CI = -1.43 to -1.19, P < 0.001, respectively). Alcohol abstinence (male: R = -0.71, P < 0.001; female: R = -0.73, P < 0.001), smoking age of initiation (male: R = -0.32, P < 0.001; female: R = -0.50, P < 0.001), physical activity (male: R = -0.50, P < 0.001; female: R = -0.55, P < 0.001), and mean temperature (R = -0.62, P < 0.001) had negative correlation with ASRD. However, cholesterol level (male: R = 0.62, P < 0.001; female: R = 0.39, P < 0.001), body mass index (BMI) (male: R = 0.30, P < 0.001; female R = -0.01, P > 0.05), and alcohol consumption (male: R = 0.46, P < 0.001; female: R = 0.42, P < 0.001) had a positive correlation with ASRM. Besides, standard of living and medical resources positively related to burden of aortic aneurysm. Conclusion: In this study, a decreasing trend of aortic aneurysm burden was found globally, especially in advanced regions. Aged men who smoke and women who have hypertension should pay close attention to, particularly in deprived economic groups, and many approaches can be performed to reduce the burden of aortic aneurysms.