Association of sleep characteristics with cardiovascular disease risk in adults over 40 years of age: a cross-sectional survey.

Background: The relationship between sleep characteristics and cardiovascular disease (CVD) risk has yet to reach a consistent conclusion, and more research needs to be carried out. This study aimed to explore the relationship between snoring, daytime sleepiness, bedtime, sleep duration, and high-risk sleep patterns with CVD risk. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 2015-2018 were collected and analyzed. Multivariable logistic regression was used to evaluate the relationship between snoring, daytime sleepiness, bedtime, sleep duration, high-risk sleep patterns, and CVD risk. Stratified analysis and interaction tests were carried out according to hypertension, diabetes and age. Results: The final analysis contained 6,830 participants, including 1,001 with CVD. Multivariable logistic regression suggested that the relationship between snoring [OR = 7.37,95%CI = (6.06,8.96)], daytime sleepiness [OR = 11.21,95%CI = (9.60,13.08)], sleep duration shorter than 7 h [OR = 9.50,95%CI = (7.65,11.79)] or longer than 8 h [OR = 6.61,95%CI = (5.33,8.19)], bedtime after 0:00 [OR = 13.20,95%CI = (9.78,17.80)] compared to 22:00-22:59, high-risk sleep patterns [OR = 47.73,95%CI = (36.73,62.04)] and CVD risk were statistically significant. Hypertension and diabetes interacted with high-risk sleep patterns, but age did not. Conclusions: Snoring, daytime sleepiness, excessive or short sleep duration, inappropriate bedtime, and high-risk sleep patterns composed of these factors are associated with the CVD risk. High-risk sleep patterns have a more significant impact on patients with hypertension and diabetes.

Association between different insulin resistance surrogates and all-cause mortality in patients with coronary heart disease and hypertension: NHANES longitudinal cohort study.

BACKGROUND: Studies on the relationship between insulin resistance (IR) surrogates and long-term all-cause mortality in patients with coronary heart disease (CHD) and hypertension are lacking. This study aimed to explore the relationship between different IR surrogates and all-cause mortality and identify valuable predictors of survival status in this population. METHODS: The data came from the National Health and Nutrition Examination Survey (NHANES 2001-2018) and National Death Index (NDI). Multivariate Cox regression and restricted cubic splines (RCS) were performed to evaluate the relationship between homeostatic model assessment of IR (HOMA-IR), triglyceride glucose index (TyG index), triglyceride glucose-body mass index (TyG-BMI index) and all-cause mortality. The recursive algorithm was conducted to calculate inflection points when segmenting effects were found. Then, segmented Kaplan-Meier analysis, LogRank tests, and multivariable Cox regression were carried out. Receiver operating characteristic (ROC) and calibration curves were drawn to evaluate the differentiation and accuracy of IR surrogates in predicting the all-cause mortality. Stratified analysis and interaction tests were conducted according to age, gender, diabetes, cancer, hypoglycemic and lipid-lowering drug use. RESULTS: 1126 participants were included in the study. During the median follow-up of 76 months, 455 participants died. RCS showed that HOMA-IR had a segmented effect on all-cause mortality. 3.59 was a statistically significant inflection point. When the HOMA-IR was less than 3.59, it was negatively associated with all-cause mortality [HR = 0.87,95%CI (0.78, 0.97)]. Conversely, when the HOMA-IR was greater than 3.59, it was positively associated with all-cause mortality [HR = 1.03,95%CI (1.00, 1.05)]. ROC and calibration curves indicated that HOMA-IR was a reliable predictor of survival status (area under curve = 0,812). No interactions between HOMA-IR and stratified variables were found. CONCLUSION: The relationship between HOMA-IR and all-cause mortality was U-shaped in patients with CHD and hypertension. HOMA-IR was a reliable predictor of all-cause mortality in this population.

Natural compounds from botanical drugs targeting mTOR signaling pathway as promising therapeutics for atherosclerosis: A review.

Atherosclerosis (AS) is a chronic inflammatory disease that is a major cause of cardiovascular diseases (CVDs), including coronary artery disease, hypertension, myocardial infarction, and heart failure. Hence, the mechanisms of AS are still being explored. A growing compendium of evidence supports that the activity of the mechanistic/mammalian target of rapamycin (mTOR) is highly correlated with the risk of AS. The mTOR signaling pathway contributes to AS progression by regulating autophagy, cell senescence, immune response, and lipid metabolism. Various botanical drugs and their functional compounds have been found to exert anti- AS effects by modulating the activity of the mTOR signaling pathway. In this review, we summarize the pathogenesis of AS based on the mTOR signaling pathway from the aspects of immune response, autophagy, cell senescence, and lipid metabolism, and comb the recent advances in natural compounds from botanical drugs to inhibit the mTOR signaling pathway and delay AS development. This review will provide a new perspective on the mechanisms and precision treatments of AS.

Dl-3-n-Butylphthalide Alleviates Behavioral and Cognitive Symptoms Via Modulating Mitochondrial Dynamics in the A53T-α-Synuclein Mouse Model of Parkinson's Disease.

BACKGROUND: Aggregation and neurotoxicity of the presynaptic protein α-synuclein and the progressive loss of nigral dopaminergic neurons are believed to be the key hallmarks of Parkinson's disease (PD). A53T mutant α-synuclein causes early onset PD and more severe manifestations. A growing body of evidence shows that misfolding or deposition of α-synuclein is linked to the maintenance of mitochondrial dynamics, which has been proven to play an important role in the pathogenesis of PD. It has been observed that Dl-3-n-butylphthalide (NBP) may be safe and effective in improving the non-tremor-dominant PD. However, the potential mechanism remains unclear. This study aimed to investigate whether NBP could decrease the loss of dopaminergic neurons and α-synuclein deposition and explore its possible neuroprotective mechanisms. METHODS: A total of 20 twelve-month-old human A53T α-synuclein transgenic mice and 10 matched adult C57BL/6 mice were included in the study; 10 adult C57BL/6 mice were selected as the control group and administered with saline (0.2 ml daily for 14 days); 20 human A53T α-synuclein transgenic mice were randomly divided into A53T group (treated in the same manner as in the control group) and A53T + NBP group (treated with NBP 0.2 ml daily for 14 days). Several markers of mitochondrial fission and fusion and mitophagy were determined, and the behavioral, olfactory, and cognitive symptoms were assessed as well. RESULTS: In the present study, it was observed that the A53T-α-synuclein PD mice exhibited anxiety-like behavioral disturbance, impairment of coordination ability, memory deficits, and olfactory dysfunction, loss of dopaminergic neurons, and α-synuclein accumulation. Meanwhile, the mitofusin 1 expression was significantly decreased, and the mitochondrial number and dynamin-related protein 1, Parkin, and LC3 levels were increased. The detected levels of all markers were reversed by NBP treatment, and the mitochondrial morphology was partially recovered. CONCLUSION: In the present study, a valuable neuropharmacological role of NBP has been established in the A53T-α-synuclein PD mouse model. Possible neuroprotective mechanisms might be that NBP is involved in the maintenance of mitochondrial dynamics including mitochondrial fission and fusion and clearance of damaged mitochondria. It is essential to perform further experiments to shed light on the precise mechanisms of NBP on mitochondrial homeostasis.

Comparison of the expression and toxicity of AAV2/9 carrying the human A53T α-synuclein gene in presence or absence of WPRE.

Woodchuck Hepatitis Virus Post-transcriptional Regulatory Element (WPRE) is thought to enhance transgene expression of target genes delivered by adeno-associated viral (AAV) vectors. This study assessed the protein expression of α-synuclein, phosphorylated α-synuclein at Serine 129, extent of nigrostriatal degeneration as well as subsequent behavioral deficits induced by unilateral intranigral stereotactic injection in male adult C57BL/6J mice of an AAV2/9 expressing A53T human α-synuclein under the control of the synapsin promoter in presence or absence of the WPRE. The presence of WPRE enabled to achieve greater nigrostriatal degeneration and synucleinopathy which was concomitant with worsened forelimb use asymmetry. This work refines a mouse Parkinson's disease model in which anatomo-pathology is related to behavioral deficits.

Drilling high aspect ratio holes by femtosecond laser filament with aberrations.

A near-infrared femtosecond laser is focused by a 100 mm-focal-length plano-convex lens to form a laser filament, which is employed to drill holes on copper targets. By shifting or rotating the focusing lens, additional aberration is imposed on the focused laser beam, and significant influence is produced on the aspect ratio and cross-sectional shape of the micro-holes. Experimental results show that when proper aberration is introduced, the copper plate with a thickness of 3 mm can be drilled through with an aspect ratio of 30, while no through-holes can be drilled on 3-mm-thickness copper plates by femtosecond laser with minimized aberration. In addition, when femtosecond laser filament with large astigmatism is used, micro-holes that had a length to width ratio up to 3.3 on the cross-section are obtained. Therefore, the method proposed here can be used to fabricate long oval holes with high aspect ratios.