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Abstract Background The cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) signaling pathway is closely associated with myocardial infarction (MI). Cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) is a key component of this pathway; however, there is currently a lack of clinical evidence linking plasma cGAMP levels to MI. Methods This study utilized clinical data from 270 patients diagnosed with coronary heart disease (CHD) at the Second Xiangya Hospital of Central South University. The outcomes included ST-segment elevation and non-ST-segment elevation MI. Univariate and multivariate logistic regression models were used to explore the relationships between plasma cGAMP levels and MI, while restricted cubic spline (RCS) using logistic regression to explore the dose-response relationship. Results Among the 270 patients, the mean plasma cGAMP level was 1352.58 ± 106.02 ng/L and 89 (32.96%) patients were diagnosed with MI. The RCS curves indicated a U-shape association between the cGAMP levels and MI; the risk of MI was negatively correlated with the cGAMP until it hit bottoms at 1352 ng/L. When the cGAMP level exceeded 1352 ng/L, the risk of MI increased significantly (adjusted OR, 1.02; 95% CI: 1.01–1.03). When considering cGAMP as a categorical variable, patients in Tertile 1 and Tertile 3 had a 167% (adjusted OR: 2.67, 95% CI: 1.23–5.78) and 155% (adjusted OR: 2.55, 95% CI: 1.17–5.55) higher risk of MI compared to those in Tertile 2, respectively. These results were consistent across subgroup analyses, notably, a significant interaction by age category was observed in patients with cGAMP ≥ 1352 ng/L, where the positive association was pronounced in the elderly. Conclusions A U-shaped association exists between cGAMP and MI in the CHD population, with a cutoff point at the cGAMP of 1352 ng/L. Both excessively high and low cGAMP levels are associated with an increased risk of MI, particularly among the elderly with cGAMP ≥ 1352 ng/L. This is the first clinical evidence of the cGAS-cGAMP-STING pathway in metabolic cardiovascular diseases. ClinicalTrials.gov Identifier NCT03363035 (Registration date: 2018-01-15).

Summary: Diabetic vascular aging is driven by macrophage senescence, which propagates senescence-associated secretory phenotypes (SASP), exacerbating vascular dysfunction. This study utilized a type 2 diabetes mellitus (T2DM) mouse model induced by streptozotocin injection and a high-fat diet to investigate the role of STING in macrophage senescence. Vascular aging markers and senescent macrophages were assessed in vivo, while in vitro, high glucose treatment induced macrophage senescence, enhancing senescence in co-cultured vascular smooth muscle cells. Mechanistic studies revealed that STING activation inhibits autophagy by phosphorylating ULK1 at S757, accelerating senescence. Pharmacological modulation showed that the STING inhibitor H-151 alleviates, while the agonist DMXAA enhances, senescence. These findings highlight the STING-autophagy axis as a critical driver of macrophage senescence, offering insights into the molecular mechanisms of diabetic vascular aging and identifying potential therapeutic targets to mitigate vascular complications in diabetes.

Abstract Background Worsening renal function (WRF) is a frequent comorbidity of heart failure with preserved ejection fraction (HFpEF). However, its relationship with abdominal obesity in terms of HFpEF remains unclear. This study aimed to evaluate the value of waist circumference (WC) and body mass index (BMI) in predicting WRF and examine the correlation between abdominal obesity and the risk of WRF in the HFpEF population. Methods Data were obtained from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial. Abdominal obesity was defined as WC ≥ 102 cm for men and ≥ 88 cm for women. WRF was defined as doubling of serum creatinine concentration from baseline. Restricted cubic splines and receiver operating characteristic curves were used to evaluate the value of WC and BMI in predicting WRF. Cumulative incidence curves and cox proportional-hazards models were used to compare patients with and without abdominal obesity. Results We included 2,806 patients with HFpEF in our study (abdominal obesity, n: 2,065). Although baseline creatinine concentrations did not differ, patients with abdominal obesity had higher concentrations during a median follow-up time of 40.9 months. Unlike BMI, WC exhibited a steady linear association with WRF and was a superior WRF predictor. Patients with abdominal obesity exhibited a higher risk of WRF after multivariable adjustment (hazard ratio: 1.632; 95% confidence interval: 1.015–2.621; P: 0.043). Conclusions Abdominal obesity is associated with an increased risk of WRF in the HFpEF population. Trial registration URL: https://beta.clinicaltrials.gov . Unique identifier: NCT00094302.

Introduction: Vascular smooth muscle cell (VSMC) senescence in the vasculature results in vascular aging as well as age-related diseases, while metformin improves the inflamm-aging profile by enhancing autophagy. However, metformin’s impact on VSMC senescence is largely undefined. Objectives: To test the hypothesis that metformin exerts an anti-senescence role by restoring autophagic activity in VSMCs and vascular tissues. Methods: Animal models established by angiotensin II (Ang II) induction and physiological aging and senescent primary VSMCs from the aortas of elderly patients were treated with metformin. Cellular and vascular senescence were assessed by measuring the amounts of senescence-associated β-galactosidase and senescence markers, including p21 and p53. Autophagy levels were assessed by autophagy-related protein expression, transmission electron microscope, and autolysosome staining. In order to explore the underlying mechanism of the anti-senescence effects of metformin, 4D label-free quantitative proteomics and bioinformatic analyses were conducted, with subsequent experiments validating these findings. Results: Ang II-dependent senescence was suppressed by metformin in VSMCs and vascular tissues. Metformin also significantly improved arterial stiffness and alleviated structural changes in aged arteries, reduced senescence-associated secretory phenotype (SASP), and improved proliferation and migration of senescent VSMCs. Mechanistically, the proteomic analysis indicated that autophagy might contribute to metformin’s anti-senescence effects. Reduced autophagic flux was observed in Ang II-induced cellular and vascular senescence; this reduction was reversed by metformin. Specifically, metformin enhanced the autophagic flux at the autophagosome-lysosome fusion level, whereas blockade of autophagosome-lysosome fusion inhibited the anti-senescence effects of metformin. Conclusions: Metformin prevents VSMC and vascular senescence by promoting autolysosome formation.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) clinically reduce atherosclerosis and lower blood pressure. However, their impact on endothelial dysfunction in type 2 diabetes (T2D) remains unclear. In this study, we investigated the protective effect and underlying mechanism of the SGLT2 inhibitor dapagliflozin in diabetes. Methods: Vascular reactivity was measured to assess the vasoprotective effect of dapagliflozin in a mouse model of high glucose (HG)-induced T2D. Pulse wave velocity was measured to quantify arterial stiffness. Protein expression was assessed by western blotting and immunofluorescence, oxidative stress was evaluated using dihydroethidium, nitric oxide was evaluated using the Griess reaction, and cellular senescence was assessed based on senescence-associated beta-galactosidase (SA‐β‐gal) activity and the expression of senescence markers. Furthermore, the endothelial nitric oxide synthase (eNOS) acetylation status was determined and eNOS interactions with SIRT1 were evaluated by coimmunoprecipitation assays. Results: Dapagliflozin protected against impaired endothelium-dependent vasorelaxation and improved arterial stiffness in the mouse model of T2D; mouse aortas had significantly reduced levels of senescence activity and senescence-associated inflammatory factors. HG-induced increases in senescence activity, protein marker levels, and oxidative stress in vitro were all ameliorated by dapagliflozin. The decreases in eNOS phosphorylation and nitric oxide (NO) production in senescent endothelial cells were restored by dapagliflozin. SIRT1 expression was reduced in HG-induced senescent endothelial cells, and dapagliflozin restored SIRT1 expression. SIRT1 inhibition diminished the antisenescence effects of dapagliflozin. Coimmunoprecipitation showed that SIRT1 was physically associated with eNOS, suggesting that the effects of dapagliflozin are dependent on SIRT1 activation. Conclusion: These findings indicate that dapagliflozin protects against endothelial cell senescence by regulating SIRT1 signaling in diabetic mice.

Abstract Background The triglyceride-glucose (TyG) index is a reliable surrogate marker of insulin resistance and is associated with major adverse cardiovascular events (MACEs) in patients with type 2 diabetes mellitus (T2DM). However, the long-term effect of the TyG index on the incidence of MACEs remains unclear. We aimed to investigate the association between the cumulative TyG index and the risk of MACEs in patients with T2DM. Methods This post-hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial assessed patients’ (T2DM > 3 months) cumulative TyG index and MACE data from the study database. Five fasting blood glucose and triglyceride measurements, at baseline and the first four visits, were taken from 5695 participants who had not experienced MACEs. Cumulative exposure to the TyG index was calculated as the weighted sum of the mean TyG index value for each time interval (value × time). Multivariable-adjusted Cox proportional hazard models and restricted cubic spline analysis were used to determine the association between the cumulative TyG index and MACEs. The incremental predictive value of the cumulative TyG index was further assessed. Results Over a median follow-up of 5.09 years, 673 (11.82%) MACEs occurred, including 256 (4.50%) cardiovascular disease (CVD) deaths, 288 (5.06%) non-fatal myocardial infarctions (MIs), and 197 (3.46%) strokes. The risk of developing MACEs increased with the cumulative TyG index quartile. After adjusting for multiple potential confounders, the hazard ratios for the very high cumulative TyG index group versus the low group were 1.59 (95% confidence interval [CI], 1.17–2.16), 1.97 (95% CI 1.19–3.26), and 1.66 (95% CI 1.02–2.70) for overall MACEs, CVD death, and non-fatal MI, respectively. Restricted cubic spline analysis also showed a cumulative increase in the risk of MACEs with an increase in the magnitude of the cumulative TyG index. The addition of the cumulative TyG index to a conventional risk model for MACEs improved the C-statistics, net reclassification improvement value, and integrated discrimination improvement value. Conclusions In patients with T2DM, the cumulative TyG index independently predicts the incidence of MACEs, and monitoring the long-term TyG index may assist with optimized-for-risk stratification and outcome prediction for MACEs. Trial registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT00000620.

Abstract Background Myocardial fibrosis after myocardial infarction (MI) is one of the leading causes of cardiovascular diseases. Cardiac fibroblasts (CFs) are activated and promoted by MI to undergo myofibroblast transformation (CMT). Urolithin A (UA) is an active and effective gut metabolite derived from polyphenolics of berries and pomegranate fruits, which has been reported to have anti-inflammatory and anti-oxidant functions. However, whether UA affects the CMT process during myocardial fibrosis remains unclear. Methods TGF-β1-treated primary rat cardiac fibroblasts were used for in vitro study. Cell proliferation ability was evaluated by MTT assay. Cell migration and invasion abilities were tested by wound healing and Transwell assays. The expression of CMT process-related markers were measured by qRT-PCR and western blot. The rat MI model was established by left anterior descending coronary artery (LAD) ligation and evaluated by H&E and Masson staining. Results Our data demonstrated that UA treatment could inhibit the CMT process in TGF-β1-induced CFs, including cell proliferation, migration and invasion abilities. Knocking down of Nrf2, which was activated by UA treatment, could mitigate the effects of UA treatment on CMT process. Moreover, in vivo administration of UA in rat MI model successfully up-regulated Nrf2 expression and improved the myocardial damage and fibrosis. Conclusions The study discovered the function and mechanism of UA on myocardial fibrosis and demonstrated the protective effects of UA administration through activation of Nrf2 pathway.

Abstract Background Previous studies reported the prognostic value of the atherogenic index of plasma (AIP) in the course of atherosclerosis and other cardiovascular diseases (CVDs). Still, the predictive utility of the AIP is unknown among patients with type 2 diabetes mellitus (T2DM). Methods This was a secondary analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, which randomized 10,251 patients with long-lasting T2DM. ROC curve analysis was used to determine an optimal threshold for AIP, and the study population was divided into high and low AIP groups. Univariable and multivariable Cox proportional hazards regression analyses were used to determine the association between AIP and primary (major adverse cardiovascular events [MACEs], including nonfatal myocardial infarction, nonfatal stroke, and/or death from cardiovascular causes) and secondary outcomes (all-cause mortality). Stratified analyses were performed to control for the confounding factors. Results AIP was an independent risk factor for the prognosis of T2DM (HR = 1.309; 95% CI 1.084–1.581; P = 0.005). The threshold for AIP was determined to be 0.34 in the study population. After adjustments for confounding factors, multivariable analysis showed that AIP was associated with the risk of MACEs (Model 1: HR = 1.333, 95% CI 1.205–1.474, P

Background: Vascular fibrosis is a universal phenomenon associated with aging, and oxidative stress plays an important role in the genesis of vascular damage in line with the aging process. However, whether antioxidants can ameliorate vascular fibrosis remains unclear. Objectives: The present study was to determine antioxidant N-acetylcysteine (NAC) could ameliorates aortic fibrosis in aging wild-type C57BL/6 mice. Methods: The aortas were harvested from both 12-week and 60-week wild-type mice. The 60-week mice were treated with and without the NAC for 12 weeks starting at the age of 48 weeks. Hematoxylin and eosin (H&E) staining and Masson's trichrome staining of aortic samples were performed, and the levels of reactive oxygen species (ROS), RNA expression of GAPDH, TNF-α, MCP-1, IL-6, IL-10, IL-4, SIRT-1, SIRT-3, FOXO-1, and macrophage polarization were determined. Results: There is a positive relationship between collagen deposition and the M1/M2 macrophage ratio in the aortic wall of aged wild-type C57BL/6 mice. The higher collagen area percentage in the aortas of 60-week-old mice than in 12-week-old mice was reversed by NAC. NAC could not impact the total number of macrophages, but partly promoted M2 macrophage polarization. By performing qRT-PCR using aortic samples from these mice, we identified that SIRT-1, SIRT-3, FOXO-1 could be somehow responsible for aging-related fibrosis. Conclusions: NAC ameliorates aortic fibrosis in aging wild type mice partly by promoting M2 macrophage polarization.

Background and AimsThis study aimed to evaluate the association of the triglyceride-glucose (TyG) index with the cardiovascular incidence in patients with type 2 diabetes mellitus (T2DM).Methods and ResultsSecondary analysis in patients with long-lasting T2DM from the Action to Control Cardiovascular Risk in Diabetes study was performed. The primary outcome was the first occurrence of major adverse cardiovascular events (MACEs). The association between the baseline and trajectories of the TyG index and MACEs was evaluated by Cox proportional hazards regression analysis. During a median follow-up period of 8.8 years, 1,815 (17.8%) patients developed MACEs. After traditional cardiovascular risk factor adjustments, each 1-standard deviation increase in the TyG index was associated with a 19.00% higher MACE risk, similar to that in the TyG index quartile characterization. Four distinct trajectories of TyG indexes were identified: low (16.17%), moderate (40.01%), high (34.60%), and very high (9.30%). In multivariate analysis, high and very high TyG index trajectories showed a greater risk of future MACE incidence than the low TyG index trajectory. A similar association was observed between the TyG index and the occurrence of coronary heart disease.ConclusionsThe baseline and trajectories of the TyG index were significantly associated with the occurrence of MACEs in patients with T2DM.Clinical Trial Registrationhttp://www.clinicaltrials.gov. Unique identifier: NCT00000620.

Diabetes mellitus (DM) is one of the most fast evolving global issues characterized by hyperglycemia. Patients with diabetes are considered to face with higher risks of adverse cardiovascular events. Those are the main cause of mortality and disability in diabetes patients. There are novel antidiabetic agents that selectively suppress sodium-glucose cotransporter-2 (SGLT-2). They work by reducing proximal tubule glucose reabsorption. Although increasing evidence has shown that SGLT-2 inhibitors can contribute to a series of cardiovascular benefits in diabetic patients, including a reduced incidence of major adverse cardiovascular events and protection of extracardiac organs, the potential mechanisms of SGLT2 inhibitors’ cardiovascular protective effects are still not fully elucidated. Given the important role of inflammation and metabolism in diabetic cardiovascular diseases, this review is intended to rationally compile the multifactorial mechanisms of SGLT-2 inhibitors from the point of immunity, inflammation and metabolism, depicting the fundamental cellular and molecular processing of SGLT-2 inhibitors exerting regulating immunity, inflammation and metabolism. Finally, future directions and perspectives to prevent or delay cardiovascular complications in DM by SGLT-2 inhibitors are presented.

BackgroundThere is a lack of studies evaluating the association between living status and subsequent outcomes in patients with type 2 diabetes (T2DM).ObjectivesThis study aimed to assess the association between living alone and the risk of all-cause mortality in T2DM patients.MethodsWe performed a secondary analysis in patients with long-lasting T2DM from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. The primary outcome was all-cause mortality. Multivariable Cox proportional hazard models was used to analyze and compare the hazard ratios (HRs) in patients living alone and with one or more adults.ResultsThis study included 10,249 patients with T2DM. Of these, 2,078 (20.28%) were living alone and 8,171 (79.72%) lived with one or more adults. Over a median total follow-up of 8.8 years, 1,958 patients developed the primary endpoint. The all-cause mortality rates in patients living alone or living with one or more adults were 23.24 and 18.05%, respectively. Cox proportional hazard analysis showed that T2DM patients living alone had significantly higher rate of all-cause mortality than those living with others (HR, 1.34; 95% confidence interval [CI], 1.20–1.48; p < 0.001). After multivariable adjustment, living alone was an independent risk factor for all-cause mortality in patients with T2DM (adjusted HR, 1.27; 95% CI, 1.14–1.41; p < 0.001). Furthermore, the risks of both congestive heart failure (CHF) and fatal coronary heart disease (CHD) among 4,050 propensity score-matched patients were higher for patients living alone (respectively HR, 1.37; 95% CI, 1.08–1.74; p = 0.010; and HR, 1.16; 95% CI, 1.00–1.34; p = 0.047).ConclusionsThe risk of all-cause mortality was significantly higher in T2DM patients living alone than in those living with one or more adults.

Background. Association between abdominal obesity and development of heart failure (HF) with preserved ejection fraction (HFpEF) between the sexes is not completely understood. Objectives. This study evaluated the association between abdominal obesity and the risk of all-cause mortality in patients with HFpEF while performing a gender outcome comparison. Methods. A post hoc analysis was undertaken from the American cohort of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT). The primary outcome (all-cause mortality) and the secondary outcomes (cardiovascular mortality, hospitalization for HF, stroke, and MI) were evaluated via Cox proportional hazards models to compare the hazard ratios (HRs) between sexes in HFpEF patients. Abdominal obesity was defined as a waist circumference of ≥102 cm in men and ≥88 cm in women. Results. A total of 3320 HFpEF patients (1620 men [48.80%] and 1700 women [51.20%]) were included in the analysis. The mean follow-up period was 3.4±1.7 years, with 503 patients dying during that time. After multivariable adjustment, abdominal obesity was significantly associated with an increased risk of all-cause mortality in males (adjusted HR: 1.32; 95% confidence interval [CI]: 1.02 to 1.71; p=0.038). Abdominal obesity was associated with hospitalization for HF in both male (adjusted HR: 1.39; 95% CI: 1.01 to 1.93; p=0.045) and female patients (adjusted HR: 1.15; 95% CI: 1.18 to 3.28; p=0.010). Conclusions. Abdominal obesity is associated with increased risks of all-cause mortality in the male but not the female HFpEF population and is associated with increased risks of hospitalization for HF in both sexes.

Introduction: Although the impact of sex on patient outcomes for heart failure (HF) with preserved ejection fraction (HFpEF) has been reported, it is still unclear whether this impact is applicable for elderly patients with HFpEF. This study was conducted as a secondary analysis from a large randomized controlled trial—The Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT)—to evaluate the impact of sex differences on the baseline characteristics and outcomes of HFpEF patients who were older than 70 years.Methods: Baseline characteristic of elderly patients were compared between men and women. Primary outcomes were cardiovascular (CV) mortality and HF-related hospitalization, whereas secondary outcomes were all-cause mortality and all-cause hospitalization. Cox regression models were used to determine the effect of sex differences on patient outcomes.Results: A total of 1,619 patients were included in the study: 898 (55.5%) women and 721 (44.5%) men. Age was similar between women and men. Women had fewer comorbidities but worse cardiac function than men. The rate of primary outcomes was lower in women than in men (18.4 vs. 27.5%; p < 0.001), including rate of CV mortality (8.9 vs. 14.8%; p < 0.001) and HF-related hospitalization (13.4 vs. 18.2%; p = 0.008). All-cause mortality was also lower in women than in men (15.6 vs. 25.4%; p < 0.001). After adjustment for baseline characteristics, Cox regression analysis showed that female sex was a protective factor for CV mortality [hazard ratio (HR): 0.53; 95% confidence interval (CI): 0.40–0.73], HF-related hospitalization (HR: 0.71; 95% CI: 0.55–0.93), and all-cause mortality (HR: 0.59; 95% CI: 0.47–0.75). Although spironolactone significantly reduced the rate of all-cause mortality in women even after adjusting for baseline characteristics (HR: 0.68; 95% CI: 0.48–0.96; p = 0.028), no significant multivariate association was noted between sex and treatment effects (p = 0.190).Conclusion: Among elderly patients with HFpEF, women had worse cardiac function but better survival and lower HF-related hospitalization rate than men.Clinical Trial Registration: NCT00094302 (TOPCAT). Registered October 15, 2004, https://www.clinicaltrials.gov/ct2/show/NCT00094302.

Background: The association between metabolic syndrome and the development of heart failure (HF) with preserved ejection fraction (HFpEF) has not been completely clarified.Aim: To evaluate the association between metabolic syndrome and the risk of HF hospitalization for patients with HFpEF.Methods: Patient data were obtained from the American cohort of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial database. Data for the primary outcome (hospitalization for HF) and secondary outcomes (all-cause mortality, cardiovascular mortality, and all-cause hospitalization) were collected, and hazard ratios (HRs) for the patients with and without metabolic syndrome were analyzed by applying a multivariable Cox proportional hazard model.Results: Among the 1,548 total participants, 1,197 had metabolic syndrome. The patients with metabolic syndrome exhibited worse heart function and a lower quality of life than those without metabolic syndrome. During the 3.3 years of follow-up, 351 patients were hospitalized for HF. After a multivariable adjustment, the risk of hospitalization for HF and all-cause hospitalization (adjusted HR = 1.42, 95% CI: 1.01–2.00; p = 0.042 and adjusted HR = 1.27; 95% CI: 1.04–1.54; p = 0.017, respectively) were independently associated with HFpEF for the patients with metabolic syndrome. In addition, the risks of HF hospitalization and all-cause hospitalization among 267 propensity score-matched patients were higher for patients with metabolic syndrome (HR = 1.53, 95% CI = 1.05–2.23, and p = 0.025 and HR = 1.34, 95% CI = 1.08–1.67, and p = 0.009, respectively).Conclusion: The risks of HF hospitalization and all-cause hospitalization were higher for patients with HFpEF having metabolic syndrome than for those without metabolic syndrome.

Recent studies demonstrated HMGB1, an extracellular inflammation molecule, played an important role on endothelial cells. This study aimed to define the role and related mechanism of HMGB1 in endothelial cells. Endothelial-specific deletion of HMGB1(HMGB1ECKO) was generated and Akt/eNOS signaling, reactive oxygen species (ROS) production, endothelium dependent relaxation (EDR), and angiogenesis were determined in vitro and in vivo. Decreased activation of Akt/eNOS signaling, sprouting, and proliferation, and increased ROS production were evidenced in endothelial cells derived from HMGB1ECKO mice as compared with wild type controls. Decreased EDR and retarded blood flow recovery after hind limb ischemia were also demonstrated in HMGB1ECKO mice. Both impaired EDR and angiogenesis could be partly rescued by superoxide dismutase in HMGB1ECKO mice. In conclusion, intracellular HMGB1 might be a key regulator of endothelial Akt/eNOS pathway and ROS production, thus plays an important role in EDR regulation and angiogenesis.

Vascular aging plays a pivotal role in the morbidity and mortality of elderly people. Decrease in autophagy leads to acceleration of vascular aging, while increase in autophagy leads to deceleration of vascular aging. And emerging evidence indicates that acetylation plays an important role in autophagy regulation; therefore, recent research has focused on an in-depth analysis of the mechanisms underlying this regulation. In this review, current knowledge on the role of acetylation of autophagy-related proteins and the mechanisms by which acetylation including non-autophagy-related acetylation and autophagy related acetylation regulate vascular aging have been discussed. We conclude that the occurrence of acetylation modification during autophagy is a fundamental mechanism underlying autophagy regulation and provides promising targets to retard vascular aging.

Abstract Objectives Asymptomatic and symptomatic patients may transmit severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), but their clinical features and immune responses remain largely unclear. We aimed to characterise the clinical features and immune responses of asymptomatic and symptomatic patients infected with SARS‐CoV‐2. Methods We collected clinical, laboratory and epidemiological records of patients hospitalised in a coronavirus field hospital in Wuhan. We performed qualitative detection of anti‐SARS‐CoV‐2 immunoglobulin M (IgM) and immunoglobulin G (IgG) using archived blood samples. Results Of 214 patients with SARS‐CoV‐2, 26 (12%) were asymptomatic at hospital admission and during hospitalisation. Most asymptomatic patients were ≤ 60 years (96%) and females (65%) and had few comorbidities (

Background. Information regarding the impact of cardiovascular (CV) conditions on disease progression among patients with mild coronavirus disease 2019 (COVID-19) is limited. Methods. This study evaluated the association of underlying CV conditions with disease progression in patients with mild COVID-19. The primary outcome was the need to be transferred to the designated hospital for intensive care due to COVID-19 disease progression. The patients were divided into with and without CV conditions as well as stable and intensive care groups. Results. Of the 332 patients with mild COVID-19, the median age was 51 years (IQR, 40-59 years), and 200 (61.2%) were female. Of the 48 (14.5%) patients with CV conditions, 23 (47.9%) progressed to severe disease status and required intensive care. Compared with patients without CV conditions, patients with CV conditions were older and more likely to have fatigue, chest tightness, and myalgia. The rate of requiring intensive care was significantly higher among patients with CV conditions than in patients without CV conditions (47.92% vs. 12.4%; P

Background. The impact of sex on the outcome of patients with acute coronary syndrome (ACS) has been suggested, but little is known about its impact on elderly patients with ACS. Methods. This study analyzed the impact of sex on in-hospital and 1-year outcomes of elderly (≥75 years of age) patients with ACS hospitalized in our department between January 2013 and December 2017. Results. A total of 711 patients were included: 273 (38.4%) women and 438 (61.6%) men. Their age ranged from 75 to 94 years, similar between women and men. Women had more comorbidities (hypertension (79.5% vs. 72.8%, p=0.050), diabetes mellitus (35.2% vs. 26.5%, p=0.014), and hyperuricemia (39.9% vs. 32.4%, p=0.042)) and had a higher prevalence of non-ST-segment elevation ACS (NSTE-ACS) (79.5% vs. 71.2%, p=0.014) than men. The prevalence of current smoking (56.5% vs. 5.4%, p

Background. Hyperuricemia is a risk factor for cardiovascular diseases, but the impact of hyperuricemia and sex-related disparities is not fully clear in elderly patients with acute coronary syndrome (ACS). Objective. To investigate the association between hyperuricemia and 1-year all-cause mortality in elderly patients with ACS. Methods. This retrospective cohort study included 711 consecutive ACS patients aged ≥75 years, hospitalized in our center between January 2013 and December 2017. Serum uric acid (sUA), in-hospital events, and 1-year follow-up were analyzed. Multivariable logistic regression models were used to explore the risk factors for in-hospital events and 1-year all-cause mortality. Results. sUA levels were higher in males than in females (381.4 ± 110.1 vs. 349.3 ± 119.1 μmol/l, P

Aims: During the COVID-19 epidemic, chest computed tomography (CT) has been highly recommended for screening of patients with suspected COVID-19 because of an unclear contact history, overlapping clinical features, and an overwhelmed health system. However, there has not been a full comparison of CT for diagnosis of heart failure or COVID-19 pneumonia. Methods: Patients with heart failure ( n=23) or COVID-19 pneumonia ( n=23) and one patient with both diseases were retrospectively enrolled. Clinical information and chest CT images were obtained and analyzed. Results: There was no difference in ground-glass opacity, consolidation, crazy paving pattern, the lobes affected, and septal thickening between heart failure and COVID-19 pneumonia. However, a less rounded morphology (4% vs. 70%, P=0.00092), more peribronchovascular thickening (70% vs. 35%, P=0.018) and fissural thickening (43% vs. 4%, P=0.002), and less peripheral distribution (30% vs. 87%, P=0.00085) were found in the heart failure group than in the COVID-19 group. Importantly, there were also more patients with upper pulmonary vein enlargement (61% vs. 4%, P=0.00087), subpleural effusion (50% vs. 0%, P=0.00058), and cardiac enlargement (61% vs. 4%, P=0.00075) in the heart failure group than in the COVID-19 group. Besides, more fibrous lesions were found in the COVID-19 group, although there was no statistical difference (22% vs. 4%, P=0.080). Conclusions: Although there is some overlap of CT features between heart failure and COVID-19, CT is still a useful tool for differentiating COVID-19 pneumonia.

Background: Convolutional neural networks have excellent modeling abilities to complex large-scale datasets and have been applied to genomics. It requires converting genotype data to image format when employing convolutional neural networks to genome-wide association studies. Existing studies converting the data into grayscale images have shown promising. However, the grayscale image may cause the loss of information of the genotype data. Methods: In order to make full use of the information, we proposed a new method, color-image-based convolutional neural networks, by converting the data into color images. Results: The experiments on simulation and real data show that our method outperforms the existing methods proposed by Yue and Chen for converting data into grayscale images, in which the model accuracy is improved by an average of 7.61%, and the ratio of disease risk genes is increased by an average of 18.91%. The new method has better robustness and generalized performance. [ABSTRACT FROM AUTHOR]

In this work, a high-throughput computation (HTC) and machine learning (ML) combined method was applied to identify the determining factors of the detonation velocity (vd) and detonation pressure (pd) of energetic molecules and screen potential high-energy molecules with acceptable stability in a high-throughput way. The HTC was performed based on 1725 sample molecules abstracted from a dataset of over 106 linear nitroaliphatics with 1- to 6-membered C backbones and three types of substituents, namely single nitro group (-NO2), nitroamine (-NNO2), and nitrate ester (-ONO2). ML models were established based on the HTC results to screen high-energy molecules and to identify the determining factors of vd and pd. Compared with quantum chemistry calculation results, the absolute relative errors of vd and pd obtained using the ML models were less than 3.63% and 5%, respectively. Furthermore, eight molecules with high energy and acceptable stability were selected as potential candidates. This study shows the high efficiency of the combination of HTC and ML in high-throughput screening. [ABSTRACT FROM AUTHOR]

C15H12O5, monoclinic, P21/c (no. 14), a = 16.1399(4) Å, b = 19.2950(5) Å, c = 8.2567(2) Å, β = 97.078(1)°, V = 2551.70(11) Å3, Z = 8, Rgt(F) = 0.0440, wRref(F2) = 0.1326, T = 299.15 K. [ABSTRACT FROM AUTHOR]

A new binuclear Gd(III) complex, [Gd2(L)6(Phen)2]·4H2O, was synthesized via the reaction of gadolinium(III) nitrate hexahydrate, 4-acetylphenoxyacetic acid (HL), NaOH, and 1,10-phenanthroline (Phen) in a solution of water–ethanol (v:v = 1:1). The Gd(III) complex was characterized using IR, UV–vis, TG-DSC, fluorescence, and single-crystal X-ray diffraction analyses. The results showed that the Gd(III) complex crystallizes in the triclinic system, space group P-1, and each Gd(III) ion was coordinated with two nitrogen atoms (N1, N2, or N1a, and N2a) from two Phen ligands and seven oxygen atoms (O1, O2, O7a, O9, O8, O8a, O10a, or O1a, O2a, O7, O8, O8a, O9a, and O10) from six L ligands, respectively, forming a nine-coordinated coordination mode. The Gd(III) complex molecules formed a one-dimensional chained and three-dimensional network structure via benzenering π-π stacking. The Hirschfeld surface analysis and the calculations of the electron density distributions of the frontier molecular orbitals of the Gd(III) complex were performed. The catalytic activities of the photocatalytic CO2 reduction and benzyl alcohol oxidation using the Gd(III) complex as a catalyst were performed. The results of the photocatalytic CO2 reduction showed that the yield and the selectivity of CO reached 41.5 μmol/g and more than 99% after four hours, respectively. The results of the benzyl alcohol oxidation showed that the yield of benzaldehyde was 45.7% at 120°C with THF as the solvent under 0.5 MPa O2 within 2 h. [ABSTRACT FROM AUTHOR]

C12H15NO9Cu, triclinic, P1̄ (no. 2), a = 7.3596(3) Å, b = 8.1735(2) Å, c = 12.0982(4) Å, α = 85.754(3)°, β = 80.318(3)°, γ = 84.852(2)°, V = 702.61(5) Å3, Z = 2, Rgt(F) = 0.0494, wRref(F2) = 0.1463, T = 298 K. [ABSTRACT FROM AUTHOR]

C48H108N9O18La, monoclinic, P21/n (no. 14), a = 16.5000(10) Å, b = 22.5924(14) Å, c = 17.4287(10) Å, β = 90.875(5)°, V = 6496.2(7) Å3, Z = 4, Rgt(F) = 0.0716, wRref(F2) = 0.1706, T = 100 K. [ABSTRACT FROM AUTHOR]