Association of total sleep duration variability with risk of new stroke in the middle-aged and elderly Chinese population.

OBJECTIVE: To investigate the association between total sleep duration variability and stroke in the middle-aged and elderly population in China. METHODS: Data were collected from the 2011, 2013, 2015, and 2018 surveys of the China Health and Retirement Longitudinal Study (CHARLS). A total of 3485 participants, who had not experienced a stroke until 2015 and completed the follow-up in 2018, were enrolled to analyze the relationship between total sleep duration variability and new stroke. Total sleep duration was calculated by summing self-reported nocturnal sleep duration and daytime napping. The variability was determined by calculating the standard deviation (SD) of total sleep duration across the first three waves. A binary logistic regression model was utilized to analyze this association. RESULTS: Of the 3485 participants, 183 (5.25%) sustained a stroke event. A dose-response relationship was observed, indicating an increased stroke risk of 0.2 per unit (hours) increase in total sleep duration variability [OR (95% CI): 1.20 (1.01-1.42)]. Upon stratification by sex groups, this increased risk was significant only in men [OR (95% CI): 1.44 (1.12-1.83)]. CONCLUSION: Increased total sleep duration variability was associated with an increased risk of stroke in the middle-aged and elderly, independent of factors such as age, nocturnal sleep duration, napping habits, region of residence, hypertension, diabetes mellitus, dyslipidemia, BMI, smoking, drinking habits, and marital status. However, a more notable correlation was observed in males.

Early use of PCSK9 inhibitors in the prognosis of patients with acute coronary syndrome by protecting vascular endothelial function.

INTRODUCTION: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) has a protective effect on acute coronary syndrome (ACS). However, most studies have shown that this protective effect is based on a decrease in low-density lipoprotein cholesterol (LDL-C), while other mechanisms remain limited. This study aimed to determine whether PCSK9i can improve the prognosis of ACS patients by protecting endothelial function. METHODS: A total of 113 ACS patients were enrolled and randomly assigned to PCSK9i group (PCSK9i combined with statins) and control group (statins only). Blood lipids and endothelial function indicators were measured and analyzed 6 weeks before and after treatment. The effect of PCSK9i on the expression and secretion of endothelial function indicators in vascular endothelial cells were studied by cell experiments. RESULTS: After 6 weeks of treatment, endothelial function indicators such as NO, TM, ICAM-1, ET-1, and flow-mediated vasodilation (FMD) were significantly improved in PCSK9i group compared with control group. Only the changes of NO and vWF were associated with blood lipid levels, whereas the changes of other endothelial function indicators were not significantly associated with blood lipid levels. PCSK9i reduced the incidence of MACEs in patients with ACS compared to those in the control group. In cell experiments, PCSK9i treatment significantly ameliorated LPS induced endothelial injury in HUVECs. CONCLUSION: PCSK9i can protect vascular endothelial function partly independently of its lipid-lowering effect and ameliorate the prognosis of patients with ACS within 6 weeks. This mechanism may involve HSF1/HSPs related signaling pathways. Early use of PCSK9i in patients with ACS should be strongly considered in clinical practice.

Adsorption-desorption of Atrazine with 9 Agricultural Soils in China.

In this work, the characteristics and mechanisms for atrazine adsorption-desorption with 9 types of soils were investigated with batch equilibrium studies, elemental analyses, infrared spectroscopy, and UV‒visible spectroscopy. The atrazine sorption data for the 9 soils showed better fits with the Freundlich model than the Langmuir model, except with Red earth in Jiangxi (REJ) The results showed that the adsorption capacity was positively correlated with the organic matter (OM) content and negatively correlated with cation-exchange capacity (CEC) and pH. UV‒visible spectroscopy showed that dissolved organic matter (DOM) in the soil enhanced atrazine adsorption, but the adsorption on different DOM fractions was quite different. In addition, the infrared spectra revealed differences in the functional groups of soils and these functional groups may drive the adsorption process via hydrogen bonding and coordination with the -NH2 groups in atrazine.

Attractive serial dependence in heading perception from optic flow occurs at the perceptual and postperceptual stages.

Previous work has revealed that the heading perception from optic flow can be either attracted to the straight-ahead direction showing a center bias or repelled away from the previously seen heading (i.e., repulsive serial dependence) after ruling out the center bias accounting for perceptual errors. Recent studies have debated whether the serial dependence occurs at the perceptual or postperceptual stages (e.g., working memory). Our current study reexamined the serial dependence in heading perception and investigated whether the serial dependence occurred at perceptual or postperceptual stages. Additionally, an ideal observer model was developed to explore whether observers optimally combined the straight-ahead direction and previous and current headings to perceive headings. Our results showed that after ruling out the center bias, the perceived heading was biased toward the previous heading, suggesting an attractive serial dependence in heading perception. This attractive serial dependence occurred at both perceptual and postperceptual stages. Importantly, the perceived heading was well predicted by an ideal observer model, suggesting that observers could optimally combine their perceptual observations (current heading) with their prior information about the straight-ahead direction and previous headings to estimate their heading.

PCSK9 inhibitors ameliorate arterial stiffness in ACS patients: evidences from Mendelian randomization, a retrospective study and basic experiments.

Background: Current evidences suggest that Proprotein Convertase Subtilisin/kexin Type 9 inhibitors (PCSK9i) exhibit a protective influence on acute coronary syndrome (ACS). Nevertheless, further investigation is required to comprehend the impact and mechanisms of these pharmaceutical agents on inflammatory factors and arterial stiffness (AS) in patients with ACS. Consequently, the objective of this study is to ascertain the influence of PCSK9i on arterial stiffness in ACS patients and elucidate the underlying mechanisms behind their actions. Methods: This study employed Mendelian randomization (MR) analysis to examine the association between genetic prediction of PCSK9 inhibition and arterial stiffness. Data of 71 patients with ACS were retrospectively collected, including PCSK9i group (n = 36, PCSK9 inhibitors combined with statins) and control group (n = 35, statins only). Blood lipid levels, inflammatory markers and pulse wave velocity (PWV) data were collected before treatment and at 1 and 6 months after treatment for analysis. Additionally, cell experiments were conducted to investigate the impact of PCSK9i on osteogenesis of vascular smooth muscle cells (VSMCs), utilizing western blot (WB), enzyme-linked immunosorbent assay (ELISA), and calcification index measurements. Results: The results of the MR analysis suggest that genetic prediction of PCSK9 inhibition has potential to reduce the PWV. Following treatment of statins combined with PCSK9 inhibitors for 1 and 6 months, the PCSK9i group exhibited significantly lower levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), C-reactive protein (CRP), interleukin-6 (IL-6), fibrinogen (FIB) and procalcitonin (PCT) compared to the control group (p < 0.05). Additionally, PWV in the PCSK9i group demonstrated significant reduction after 6 months of treatment and was found to be associated with the circulating CRP level. In cell experiments, PCSK9i pretreatment ameliorated osteogenesis of VSMCs through reducing the deposition of calcium ions, alkaline phosphatase (ALP) activity, and expression of runt-related transcription factor 2 (RUNX2). Conclusion: PCSK9i have potential to enhance arterial stiffness in ACS patients. Specifically, at the clinical level, this impact may be attributed to alterations in circulating CRP levels. At the cellular level, it is associated with the signaling pathway linked to RUNX2.

miRNAs Influence m6A RNA Methylation through FTO and IGF2BP2 in Pressure Overload-Induced Heart Failure.

BACKGROUND: N6-adenosine methylation (m6A) is a prevalent RNA modification associated with heart failure, alongside aberrant miRNA expression. Despite indications of miRNAs regulating m6A modification, their specific influence on m6A in heart failure remains unclear. METHODS: The initial analysis utilized transcriptome and methylation sequencing data from GSE131296 in mice to identify key m6A methylation enzymes in heart failure and construct an associated network. Integration of miRNA sequencing data from GSE231700 revealed miRNAs influencing m6A methylation enzymes, contributing to the formation of a comprehensive network. Furthermore, differential miRNA levels in human serum were assessed via qPCR, and the expression of m6A methyltransferases in the heart was confirmed using proteomic databases. RESULTS: In pressure overload-induced heart failure mice, 217 mRNAs showed differential expression, with FTO and IGF2BP2 identified as m6A methylation enzymes. Subsequent methylation sequencing revealed 884 highly-methylated and 178 lowly-methylated peaks, establishing a network linking Fto and Igf2bp2 with these peaks. Additionally, miRNA sequencing identified 156 differentially expressed miRNAs, including let-7b-5p and miR-23b-3p, predicted as m6Aregulating miRNAs, both elevated in heart failure patients. CONCLUSION: miR-23b-3p and let-7b-5p are identified as potential regulators of RNA methylation in heart failure, acting via FTO and IGF2BP2, offering new insights into the role of miRNA-mediated RNA methylation and its potential therapeutic avenues for heart failure.

Axitinib targets cardiac fibrosis in pressure overload-induced heart failure through VEGFA-KDR pathway.

Background: There are no specific clinical medications that target cardiac fibrosis in heart failure (HF). Recent studies have shown that tyrosine kinase inhibitors (TKIs) may benefit fibrosis in various organs. However, there is limited research on their application in cardiac fibrosis. Axitinib, an FDA-approved tyrosine kinase inhibitor, was used to evaluate its effects on cardiac fibrosis and function in pressure overload-induced heart failure. Methods: To build a pharmacological network, the pharmacological targets of axitinib were first retrieved from databases and coupled with key heart failure gene molecules for analysis and prediction. To validate the results outlined above, 8-week-old male C57BL/6 J mice were orally administrated of axitinib (30 mg/kg) daily for 8 weeks after Transverse Aortic Constriction (TAC) surgery. Mouse cardiomyocytes and cardiac fibroblasts were used as cell lines to test the function and mechanism of axitinib. Results: We found that the pharmacological targets of axitinib could form a pharmacological network with key genes involved in heart failure. The VEGFA-KDR pathway was found to be closely related to the differential gene expression of human heart-derived primary cardiomyocyte cell lines treated with axitinib, based on analysis of the publicly available dataset. The outcomes of animal experiments demonstrated that axitinib therapy greatly reduced cardiac fibrosis and improved TAC-induced cardiac dysfunction. Further research has shown that the expression of transforming growth factor-ß(TGF-ß) and other fibrosis genes was significantly reduced in vivo and in vitro. Conclusion: Our study provides evidence for the repurposing of axitinib to combat cardiac fibrosis, and offers new insights into the treatment of patients with HF.