Research on dust control technology and numerical simulation of conical guiding air curtain in fully mechanized excavation face.

The dust pollution caused by the operation of fully mechanized heading face poses a serious threat to the safety production of operators and working face. To reduce dust concentration at the fully mechanized heading face, this study analyzed dust samples collected from various positions to understand the particle size distribution characteristics. Based on these findings, a conical diversion air conditioning (CDAC) device was designed to create a radial air curtain for dust control in the roadway cross-section. Computational Fluid Dynamics (CFD) was then employed to investigate the airflow and particle dynamics when the cone-shaped deflector was in closed and open states. The results show that in the fully mechanized heading face, the dust distribution in the working area of the roadheader driver is relatively dense, and the dust particles with particle size ≤ 8 µm account for a large proportion. When the CDAC device is deployed, the axial airflow in the roadway is changed into a rotating airflow along the roadway wall, and an air screen is established in the working area of the roadheader driver to block the outward diffusion of dust. When the pressure air outlet is arranged 30 m away from the tunneling head, the pressure air volume is set to 400 m3/min, and the CDAC device can better form the air curtain barrier to block the dust particles. It provides a new method for effectively controlling the dust concentration of the fully mechanized heading face and directly ensuring the health of the roadheader driver.

Tumor microenvironment-responsive size-changeable and biodegradable HA-CuS/MnO2 nanosheets for MR imaging and synergistic chemodynamic therapy/phototherapy.

Tumor microenvironment (TME)-responsive size-changeable and biodegradable nanoplatforms for multimodal therapy possess huge advantages in anti-tumor therapy. Hence, we developed a hyaluronic acid (HA) modified CuS/MnO2 nanosheets (HCMNs) as a multifunctional nanoplatform for synergistic chemodynamic therapy (CDT)/photothermal therapy (PTT)/photodynamic therapy (PDT). The prepared HCMNs exhibited significant NIR light absorption and photothermal conversion efficiency because of the densely deposited ultra-small sized CuS nanoparticles on the surface of MnO2 nanosheet. They could precisely target the tumor cells and rapidly decomposed into small sized nanostructures in the TME, and then efficiently promote intracellular ROS generation through a series of cascade reactions. Moreover, the local temperature elevation induced by photothermal effect also promote the PDT based on CuS nanoparticles and the Fenton-like reaction of Mn2+, thereby enhancing the therapeutic efficiency. Furthermore, the T1-weighted magnetic resonance (MR) imaging was significantly enhanced by the abundant Mn2+ ions from the decomposition process of HCMNs. In addition, the CDT/PTT/PDT synergistic therapy using a single NIR light source exhibited considerable anti-tumor effect via in vitro cell test. Therefore, the developed HCMNs will provide great potential for MR imaging and multimodal synergistic cancer therapy.

Drug-Coated Balloon in Primary Percutaneous Coronary Intervention.

According to the latest coronary interventional guidelines, a drug-eluting stent is the recommended reperfusion therapy in primary percutaneous coronary intervention (pPCI). However, deficiencies and defects, such as in-stent restenosis (ISR), incomplete stent apposition, stent thrombosis, reinfarction after stent implantation, long-term dual antiplatelet drug use, and adverse reactions of metal implants, plague clinicians and patients. Drug-coated balloon (DCB), which delivers antiproliferative agents into the vessel wall without stent implantation and leaves no implants behind after the procedure, is a novel option for percutaneous coronary intervention and has proven to be a promising strategy in cases of ISR, small vessel coronary artery disease, and bifurcation lesions. However, most of the available experience has been gained in elective percutaneous coronary intervention, and experience in pPCI is lacking. The current evidence for the use of DCB-only in pPCI was discussed and analyzed in this review.

A time-series analysis of short-term ambient ozone exposure and hospitalizations from acute myocardial infarction in Henan, China.

Epidemiological studies in recent years have identified an association between exposure to air pollutants and acute myocardial infarction (AMI); however, the association between short-term ozone (O3) exposure and AMI hospitalization remains unclear, particularly in developing countries. Therefore, this study collected information on 24,489 AMI patients, including daily air pollutant and meteorological data in Henan, China, between 2016 and 2021. A distributed lagged nonlinear model combined with a Poisson regression model was used to estimate the nonlinear lagged effect of O3 on AMI hospitalizations. We also quantified the effects of O3 on the number of AMI hospitalizations, hospitalization days, and hospitalization costs. The results showed that single- and dual-pollution models of O3 at lag0, lag1, and lag (01-07) were risk factors for AMI hospitalizations, with the most significant effect at lag03 (RR = 1.132, 95% CI:1.083-1.182). Further studies showed that males, younger people (15-64 years), warm seasons, and long sunshine duration were more susceptible to O3. Hospitalizations attributable to O3 during the study period accounted for 11.66% of the total hospitalizations, corresponding to 2856 patients, 33,492 hospital days, and 90 million RMB. Maintaining O3 at 10-130 µg/m3 can prevent hundreds of AMI hospitalizations and save millions of RMB per year in Henan, China. In conclusion, we found that short-term exposure to O3 was significantly associated with an increased risk of hospitalization for AMI in Henan, China, and that further reductions in ambient O3 levels may have substantial health and economic benefits for patients and local healthcare facilities.

EZH2 can be used as a therapeutic agent for inhibiting endothelial dysfunction.

Enhancer of zeste homolog 2 (EZH2) is a catalytic subunit of polycomb repressor complex 2 and plays important roles in endothelial cell homeostasis. EZH2 functionally methylates lysine 27 of histone H3 and represses gene expression through chromatin compaction. EZH2 mediates the effects of environmental stimuli by regulating endothelial functions, such as angiogenesis, endothelial barrier integrity, inflammatory signaling, and endothelial mesenchymal transition. Numerous studies have been conducted to determine the significance of EZH2 in endothelial function. The aim of this review is to provide a concise summary of the roles EZH2 plays in endothelial function and elucidate its therapeutic potential in cardiovascular diseases.

Associations of Insomnia With Insulin Resistance Traits: A Cross-sectional and Mendelian Randomization Study.

CONTEXT: Insomnia is associated with insulin resistance (IR) in observational studies; however, whether insomnia is causally associated with IR remains unestablished. OBJECTIVE: This study aims to estimate the causal associations of insomnia with IR and its related traits. METHODS: In primary analyses, multivariable regression (MVR) and 1-sample Mendelian randomization (1SMR) analyses were performed to estimate the associations of insomnia with IR (triglyceride-glucose index and triglyceride to high-density lipoprotein cholesterol [TG/HDL-C] ratio) and its related traits (glucose level, TG, and HDL-C) in the UK Biobank. Thereafter, 2-sample MR (2SMR) analyses were used to validate the findings from primary analyses. Finally, the potential mediating effects of IR on the pathway of insomnia giving rise to type 2 diabetes (T2D) were examined using a 2-step MR design. RESULTS: Across the MVR, 1SMR, and their sensitivity analyses, we found consistent evidence suggesting that more frequent insomnia symptoms were significantly associated with higher values of triglyceride-glucose index (MVR, ß = 0.024, P < 2.00E-16; 1SMR, ß = 0.343, P < 2.00E-16), TG/HDL-C ratio (MVR, ß = 0.016, P = 1.75E-13; 1SMR, ß = 0.445, P < 2.00E-16), and TG level (MVR, ß = 0.019 log mg/dL, P < 2.00E-16, 1SMR: ß = 0.289 log mg/dL, P < 2.00E-16) after Bonferroni adjustment. Similar evidence was obtained by using 2SMR, and mediation analysis suggested that about one-quarter (25.21%) of the association between insomnia symptoms and T2D was mediated by IR. CONCLUSIONS: This study provides robust evidence supporting that more frequent insomnia symptoms are associated with IR and its related traits across different angles. These findings indicate that insomnia symptoms can be served as a promising target to improve IR and prevent subsequent T2D.

Salidroside Regulates Mitochondrial Homeostasis After Polarization of RAW264.7 Macrophages.

ABSTRACT: Salidroside has anti-inflammatory and antiatherosclerotic effects, and mitochondrial homeostasis imbalance is closely related to cardiovascular disease. The aim of this study was to investigate the effect of salidroside on mitochondrial homeostasis after macrophage polarization and elucidate its possible mechanism against atherosclerosis. RAW264.7 cells were stimulated with 1 µg·mL -1 Lipopolysaccharide and 50 ng·mL -1 IFN-γ establish M1 polarization and were also pretreated with 400 µM salidroside. The relative expression of proinflammatory genes was detected by RT-PCR whereas that of mitochondrial homeostasis-related proteins and nuclear factor kappa-B (NF-κB) was detected by WB. Levels of intracellular reactive oxygen species (ROS), mitochondrial membrane potential, and mass were measured by chemifluorescence whereas that of NF-κB nuclear translocation was detected by immunofluorescence. Compared with the Mφ group, the M1 group demonstrated increased mRNA expression of interleukin-1ß , inductible nitric oxide synthase (iNOS), and tumor necrosis factor-α ; increased protein expression of iNOS, NOD-like receptor protein 3, putative kinase 1 , and NF-κB p65 but decreased protein expression of MFN2, Tom20, and PGC-1α; decreased mitochondrial membrane potential and mass; and increased ROS levels and NF-κB p65 nuclear translocation. Salidroside intervention decreased mRNA expression of interleukin-1ß and tumor necrosis factor-α compared with the M1 group but did not affect that of iNOS. Furthermore, salidroside intervention prevented the changes in protein expression, mitochondrial membrane potential and mass, ROS levels, and NF-κB p65 nuclear translocation observed in the M1 group. In summary, salidroside ultimately inhibits M1 macrophage polarization and maintains mitochondrial homeostasis after macrophage polarization by increasing mitochondrial membrane potential, decreasing ROS levels, inhibiting NF-κB activation, and in turn regulating the expression of proinflammatory factors and mitochondrial homeostasis-associated proteins.

Construction of spider silk protein small-caliber tissue engineering vascular grafts based on dynamic culture and its performance evaluation.

Tissue engineering is an alternative method for preparing small-caliber (<6 mm) vascular grafts. Dynamic mechanical conditioning is being researched as a method to improve mechanical properties of tissue engineered blood vessels. This method attempts to induce unique reaction in implanted cells that regenerate the matrix around them, thereby improving the overall mechanical stability of the grafts. In this study, we used a bioreactor to seed endothelial cells and smooth muscle cells into the inner and outer layers of the electrospun spider silk protein scaffold respectively to construct vascular grafts. The cell proliferation, mechanical properties, blood compatibility and other indicators of the vascular grafts were characterized in vitro. Furthermore, the vascular grafts were implanted in Sprague Dawley rats, and the vascular grafts' patency, extracellular matrix formation, and inflammatory response were evaluated in vivo. We aimed to construct spider silk protein vascular grafts with the potential for in vivo implantation by using a pulsating flow bioreactor. The results showed that, when compared with the static culture condition, the dynamic culture condition improved cell proliferation on vascular scaffolds and enhanced mechanical function of vascular scaffolds. In vivo experiments also showed that the dynamic culture of vascular grafts was more beneficial for the extracellular matrix deposition and anti-thrombogenesis, as well as reducing the inflammatory response of vascular grafts. In conclusion, dynamic mechanical conditioning aid in the resolution of challenges impeding the application of electrospun scaffolds and have the potential to construct small-caliber blood vessels with regenerative function for cardiovascular tissue repair.

Risk Score for Prediction of Acute Kidney Injury in Patients with Acute ST-Segment Elevation Myocardial Infarction.

Background: Acute kidney injury (AKI) is an important comorbidity of ST-Segment Elevation Myocardial Infarction (STEMI) and worsens the prognosis. The purpose of this study was to investigate the relationship between clinical data, test results, surgical findings, and AKI in STEMI patients and to develop a simple, practical model for predicting the risk of AKI. Method: Prognostic prediction research with clinical risk score development was conducted. The data used for model development was derived from the database of the Henan Province Cardiovascular Disease Clinical Data and Sample Resource Bank Engineering Research Center. The data used for external validation was derived from the China Chest Pain Center database. The study endpoint was defined as the occurrence of AKI. Logistic regression analysis was used to identify independent predictors of AKI. Logistic coefficients of each predictor were used for score weighting and transformation. The predictive performance of the newly derived risk scores was validated, respectively, by receiver operating characteristic (ROC) regression in the development population and the external validation population. Result: A total of 364 patients, 57 (15.6%) with AKI and 307 (84.4%) without AKI, were included for score derivation. The validation crowd includes 88 STEMI patients in different institutions. A total of 11 potential predictors were explored under the multivariable logistic regression model. The new risk score was based on five final predictors which were age > 72 years, ejection fraction of no more than 40%, baseline serum creatinine > 102.7 mmol/L, red blood cell distribution width > 13.15, and culprit lesion located in the middistal segment. With only five predictor variables, the score predicted the risk of AKI with the effective discriminative ability (area under the receiver operating characteristic curve (AuROC): 0.721, 95% confidence interval (CI): 0.652-0.790). In the external validation, the newly developed score confirmed a similar discrimination as the crowd used for derivation (AuROC: 0.731, 95% CI: 0.624-0.838). Conclusion: The newly developed score was proved to have good predictive performance and could be practically applied for risk stratification of AKI in STEMI patients.

Advances in the study of nicotinamide adenine dinucleotide phosphate oxidase in myocardial remodeling.

Myocardial remodeling is a key pathophysiological basis of heart failure, which seriously threatens human health and causes a severe economic burden worldwide. During chronic stress, the heart undergoes myocardial remodeling, mainly manifested by cardiomyocyte hypertrophy, apoptosis, interstitial fibrosis, chamber enlargement, and cardiac dysfunction. The NADPH oxidase family (NOXs) are multisubunit transmembrane enzyme complexes involved in the generation of redox signals. Studies have shown that NOXs are highly expressed in the heart and are involved in the pathological development process of myocardial remodeling, which influences the development of heart failure. This review summarizes the progress of research on the pathophysiological processes related to the regulation of myocardial remodeling by NOXs, suggesting that NOXs-dependent regulatory mechanisms of myocardial remodeling are promising new therapeutic targets for the treatment of heart failure.

Long non-coding RNAs: Modulators of phenotypic transformation in vascular smooth muscle cells.

Long non-coding RNA (lncRNAs) are longer than 200 nucleotides and cannot encode proteins but can regulate the expression of genes through epigenetic, transcriptional, and post-transcriptional modifications. The pathophysiology of smooth muscle cells can lead to many vascular diseases, and studies have shown that lncRNAs can regulate the phenotypic conversion of smooth muscle cells so that smooth muscle cells proliferate, migrate, and undergo apoptosis, thereby affecting the development and prognosis of vascular diseases. This review discusses the molecular mechanisms of lncRNA as a signal, bait, stent, guide, and other functions to regulate the phenotypic conversion of vascular smooth muscle cells, and summarizes the role of lncRNAs in regulating vascular smooth muscle cells in atherosclerosis, hypertension, aortic dissection, vascular restenosis, and aneurysms, providing new ideas for the diagnosis and treatment of vascular diseases.

Celastrol: A Promising Agent Fighting against Cardiovascular Diseases.

Cardiovascular diseases (CVD) are leading causes of morbidity and mortality worldwide; therefore, seeking effective therapeutics to reduce the global burden of CVD has become increasingly urgent. Celastrol, a bioactive compound isolated from the roots of the plant Tripterygium wilfordii (TW), has been attracting increasing research attention in recent years, as it exerts cardiovascular treatment benefits targeting both CVD and their associated risk factors. Substantial evidence has revealed a protective role of celastrol against a broad spectrum of CVD including obesity, diabetes, atherosclerosis, cerebrovascular injury, calcific aortic valve disease and heart failure through complicated and interlinked mechanisms such as direct protection against cardiomyocyte hypertrophy and death, and indirect action on oxidation and inflammation. This review will mainly summarize the beneficial effects of celastrol against CVD, largely based on in vitro and in vivo preclinical studies, and the potential underlying mechanisms. We will also briefly discuss celastrol's pharmacokinetic limitations, which hamper its further clinical applications, and prospective future directions.

Proteomics-based evaluation of the mechanism underlying vascular injury via DNA interstrand crosslinks, glutathione perturbation, mitogen-activated protein kinase, and Wnt and ErbB signaling pathways induced by crotonaldehyde.

Crotonaldehyde (CRA)-one of the major environmental pollutants from tobacco smoke and industrial pollution-is associated with vascular injury (VI). We used proteomics to systematically characterize the presently unclear molecular mechanism of VI and to identify new related targets or signaling pathways after exposure to CRA. Cell survival assays were used to assess DNA damage, whereas oxidative stress was determined using colorimetric assays and by quantitative fluorescence study; additionally, cyclooxygenase-2, mitogen-activated protein kinase pathways, Wnt3a, ß-catenin, phospho-ErbB2, and phospho-ErbB4 were assessed using ELISA. Proteins were quantitated via tandem mass tag-based liquid chromatography-mass spectrometry and bioinformatics analyses, and 34 differentially expressed proteins were confirmed using parallel reaction monitoring, which were defined as new indicators related to the mechanism underlying DNA damage; glutathione perturbation; mitogen-activated protein kinase; and the Wnt and ErbB signaling pathways in VI based on Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and protein-protein interaction network analyses. Parallel reaction monitoring confirmed significant (p < 0.05) upregulation (> 1.5-fold change) of 23 proteins and downregulation (< 0.667-fold change) of 11. The mechanisms of DNA interstrand crosslinks; glutathione perturbation; mitogen-activated protein kinase; cyclooxygenase-2; and the Wnt and ErbB signaling pathways may contribute to VI through their roles in DNA damage, oxidative stress, inflammation, vascular dysfunction, endothelial dysfunction, vascular remodeling, coagulation cascade, and the newly determined signaling pathways. Moreover, the Wnt and ErbB signaling pathways were identified as new disease pathways involved in VI. Taken together, the elucidated underlying mechanisms may help broaden existing understanding of the molecular mechanisms of VI induced by CRA.

Effects of glycemic traits on left ventricular structure and function: a mendelian randomization study.

BACKGROUND: Adverse ventricular structure and function is a key pathogenic mechanism of heart failure. Observational studies have shown that both insulin resistance (IR) and glycemic level are associated with adverse ventricular structure and function. However, whether IR and glycemic level are causally associated with cardiac structure and function remains unclear. METHODS: Genetic variants for IR, fasting insulin, HbA1c, and fasting glucose were selected based on published genome-wide association studies, which included 188,577, 108,557, 123,665, and 133,010 individuals of European ancestry, respectively. Outcome datasets for left ventricular (LV) parameters were obtained from UK Biobank Cardiovascular Magnetic Resonance sub-study (n = 16,923). Mendelian randomization (MR) analyses with the inverse-variance weighted (IVW) method were used for the primary analyses, while weighted median, MR-Egger, and MR-PRESSO were used for sensitivity analyses. Multivariable MR analyses were also conducted to examine the independent effects of glycemic traits on LV parameters. RESULTS: In the primary IVW MR analyses, per 1-standard deviation (SD) higher IR was significantly associated with lower LV end-diastolic volume (ß = - 0.31 ml, 95% confidence interval [CI] - 0.48 to - 0.14 ml; P = 4.20 × 10-4), lower LV end-systolic volume (ß = - 0.34 ml, 95% CI - 0.51 to - 0.16 ml; P = 1.43 × 10-4), and higher LV mass to end-diastolic volume ratio (ß = 0.50 g/ml, 95% CI 0.32 to 0.67 g/ml; P = 6.24 × 10-8) after Bonferroni adjustment. However, no associations of HbA1c and fasting glucose were observed with any LV parameters. Results from sensitivity analyses were consistent with the main findings, but with a slightly attenuated estimate. Multivariable MR analyses provided further evidence for an independent effect of IR on the adverse changes in LV parameters after controlling for HbA1c. CONCLUSIONS: Our study suggests that genetic liability to IR rather than those of glycemic levels are associated with adverse changes in LV structure and function, which may strengthen our understanding of IR as a risk factor for heart failure by providing evidence of direct impact on cardiac morphology.

Transplantation of Gut Microbiota From High-Fat-Diet-Tolerant Cynomolgus Monkeys Alleviates Hyperlipidemia and Hepatic Steatosis in Rats.

Emerging evidence has been reported to support the involvement of the gut microbiota in the host's blood lipid and hyperlipidemia (HLP). However, there remains unexplained variation in the host's blood lipid phenotype. Herein a nonhuman primate HLP model was established in cynomolgus monkeys fed a high-fat diet (HFD) for 19 months. At month 19%, 60% (3/5) of the HFD monkeys developed HLP, but surprisingly 40% of them (2/5) exhibited strong tolerance to the HFD (HFD-T) with their blood lipid profiles returning to normal levels. Metagenomic analysis was used to investigate the compositional changes in the gut microbiota in these monkeys. Furthermore, the relative abundance of Megasphaera remarkably increased and became the dominant gut microbe in HFD-T monkeys. A validation experiment showed that transplantation of fecal microbiota from HFD-T monkeys reduced the blood lipid levels and hepatic steatosis in HLP rats. Furthermore, the relative abundance of Megasphaera significantly increased in rats receiving transplantation, confirming the successful colonization of the microbe in the host and its correlation with the change of the host's blood lipid profiles. Our results thus suggested a potentially pivotal lipid-lowering role of Megasphaera in the gut microbiota, which could contribute to the variation in the host's blood lipid phenotype.

Characterization of Changes and Driver Microbes in Gut Microbiota During Healthy Aging Using A Captive Monkey Model.

Recent population studies have significantly advanced our understanding of how age shapes the gut microbiota. However, the actual role of age could be inevitably confounded due to the complex and variable environmental factors in human populations. A well-controlled environment is thus necessary to reduce undesirable confounding effects, and recapitulate age-dependent changes in the gut microbiota of healthy primates. Herein we performed 16S rRNA gene sequencing, characterized the age-associated gut microbial profiles from infant to elderly crab-eating macaques reared in captivity, and systemically revealed the lifelong dynamic changes of the primate gut microbiota. While the most significant age-associated taxa were mainly found as commensals such as Faecalibacterium, the abundance of a group of suspicious pathogens such as Helicobacter was exclusively increased in infants, underlining their potential role in host development. Importantly, topology analysis indicated that the network connectivity of gut microbiota was even more age-dependent than taxonomic diversity, and its tremendous decline with age could probably be linked to healthy aging. Moreover, we identified key driver microbes responsible for such age-dependent network changes, which were further linked to altered metabolic functions of lipids, carbohydrates, and amino acids, as well as phenotypes in the microbial community. The current study thus demonstrates the lifelong age-dependent changes and their driver microbes in the primate gut microbiota, and provides new insights into their roles in the development and healthy aging of their hosts.

Role of oxidative stress in calcific aortic valve disease and its therapeutic implications.

Calcific aortic valve disease (CAVD) is the end result of active cellular processes that lead to the progressive fibrosis and calcification of aortic valve leaflets. In western populations, CAVD is a significant cause of cardiovascular morbidity and mortality, and in the absence of effective drugs, it will likely represent an increasing disease burden as populations age. As there are currently no pharmacological therapies available for preventing, treating, or slowing the development of CAVD, understanding the mechanisms underlying the initiation and progression of the disease is important for identifying novel therapeutic targets. Recent evidence has emerged of an important causative role for reactive oxygen species (ROS)-mediated oxidative stress in the pathophysiology of CAVD, inducing the differentiation of valve interstitial cells into myofibroblasts and then osteoblasts. In this review, we focus on the roles and sources of ROS driving CAVD and consider their potential as novel therapeutic targets for this debilitating condition.

Glyoxal damages human aortic endothelial cells by perturbing the glutathione, mitochondrial membrane potential, and mitogen-activated protein kinase pathways.

BACKGROUND: Exposure to glyoxal, the smallest dialdehyde, is associated with several diseases; humans are routinely exposed to glyoxal because of its ubiquitous presence in foods and the environment. The aim of this study was to examine the damage caused by glyoxal in human aortic endothelial cells. METHODS: Cell survival assays and quantitative fluorescence assays were performed to measure DNA damage; oxidative stress was detected by colorimetric assays and quantitative fluorescence, and the mitogen-activated protein kinase pathways were assessed using western blotting. RESULTS: Exposure to glyoxal was found to be linked to abnormal glutathione activity, the collapse of mitochondrial membrane potential, and the activation of mitogen-activated protein kinase pathways. However, DNA damage and thioredoxin oxidation were not induced by dialdehydes. CONCLUSIONS: Intracellular glutathione, members of the mitogen-activated protein kinase pathways, and the mitochondrial membrane potential are all critical targets of glyoxal. These findings provide novel insights into the molecular mechanisms perturbed by glyoxal, and may facilitate the development of new therapeutics and diagnostic markers for cardiovascular diseases.

Dual Role of Mitophagy in Cardiovascular Diseases.

ABSTRACT: Mitophagy is involved in the development of various cardiovascular diseases, such as atherosclerosis, heart failure, myocardial ischemia/reperfusion injury, and hypertension. Mitophagy is essential for maintaining intracellular homeostasis and physiological function in most cardiovascular origin cells, such as cardiomyocytes, endothelial cells, and vascular smooth muscle cells. Mitophagy is crucial to ensuring energy supply by selectively removing dysfunctional mitochondria, maintaining a balance in the number of mitochondria in cells, ensuring the integrity of mitochondrial structure and function, maintaining homeostasis, and promoting cell survival. Substantial research has indicated a "dual" effect of mitophagy on cardiac function, with inadequate and increased mitochondrial degradation both likely to influence the progression of cardiovascular disease. This review summarizes the main regulatory pathways of mitophagy and emphasizes that an appropriate amount of mitophagy can prevent endothelial cell injury, vascular smooth muscle cell proliferation, macrophage polarization, and cardiomyocyte apoptosis, avoiding further progression of cardiovascular diseases.

Causal associations of short and long sleep durations with 12 cardiovascular diseases: linear and nonlinear Mendelian randomization analyses in UK Biobank.

AIMS: Observational studies have suggested strong associations between sleep duration and many cardiovascular diseases (CVDs), but causal inferences have not been confirmed. We aimed to determine the causal associations between genetically predicted sleep duration and 12 CVDs using both linear and nonlinear Mendelian randomization (MR) designs. METHODS AND RESULTS: Genetic variants associated with continuous, short (≤6 h) and long (≥9 h) sleep durations were used to examine the causal associations with 12 CVDs among 404 044 UK Biobank participants of White British ancestry. Linear MR analyses showed that genetically predicted sleep duration was negatively associated with arterial hypertension, atrial fibrillation, pulmonary embolism, and chronic ischaemic heart disease after correcting for multiple tests (P < 0.001). Nonlinear MR analyses demonstrated nonlinearity (L-shaped associations) between genetically predicted sleep duration and four CVDs, including arterial hypertension, chronic ischaemic heart disease, coronary artery disease, and myocardial infarction. Complementary analyses provided confirmative evidence of the adverse effects of genetically predicted short sleep duration on the risks of 5 out of the 12 CVDs, including arterial hypertension, pulmonary embolism, coronary artery disease, myocardial infarction, and chronic ischaemic heart disease (P < 0.001), and suggestive evidence for atrial fibrillation (P < 0.05). However, genetically predicted long sleep duration was not associated with any CVD. CONCLUSION: This study suggests that genetically predicted short sleep duration is a potential causal risk factor of several CVDs, while genetically predicted long sleep duration is unlikely to be a causal risk factor for most CVDs.