Atrial remodeling is a major contributor to the onset of atrial fibrillation (AF) after myocardial infarction (MI). Tripartite motif-containing protein 21 (TRIM21), an E3 ubiquitin protein ligase, is ...associated with pathological cardiac remodeling and dysfunction. However, the role of TRIM21 in postmyocardial infarction atrial remodeling and subsequent AF remains unclear. This study investigated the role of TRIM21 in post myocardial infarction atrial remodeling using TRIM21 knockout mice and explored the underlying mechanisms by overexpressing TRIM21 in HL-1 atrial myocytes using a lentiviral vector. The expression of TRIM21 in the left atrium of the mouse MI model was significantly elevated. TRIM21 deficiency alleviated MI-induced atrial oxidative damage, Cx43 downregulation, atrial fibrosis and enlargement, and abnormalities in electrocardiogram parameters (prolongation of the P-wave and PR interval). TRIM21 overexpression in atrial myocyte HL-1 cells further enhanced oxidative damage and Cx43 downregulation, whereas these effects were reversed by the reactive oxygen species scavenger N-acetylcysteine. The findings suggest that TRIM21 likely induces Nox2 expression mechanistically by activating the NF-κB pathway, which in turn leads to myocardial oxidative damage, inflammation, and atrial remodeling.
•TRIM21 is up-regulated in the left atrium of mice following myocardial infarction (MI).•TRIM21 deficiency attenuates postmyocardial infarction oxidative stress and atrial remodeling.•TRIM21 promotes oxidative stress and atrial cardiomyocyte damage though upregulating Nox2.•TRIM21 promotes oxidative stress and Nox2 expression through activating the NF-κB pathway.
Macrophage polarization followed by myocardial infarction (MI) is essential for wound healing. Tripartite motif-containing protein 21 (TRIM21), a member of E3 ubiquitin ligases, is emerging as a ...mediator in cardiac injury and heart failure. However, its function in modulating post-MI macrophage polarization remains elusive. Here, we detected that the levels of TRIM21 significantly increased in macrophages of wild-type (WT) mice after MI. In contrast, MI was ameliorated in TRIM21 knockout (TRIM21
-/-
) mice with improved cardiac remodeling, characterized by a marked decrease in mortality, decreased infarct size, and improved cardiac function compared with WT-MI mice. Notably, TRIM21 deficiency impeded the post-MI apoptosis and DNA damage in the hearts of mice. Consistently, the accumulation of M1 phenotype macrophages in the infarcted tissues was significantly reduced with TRIM21 deletion. Mechanistically, the deletion of TRIM21 orchestrated the process of M1 macrophage polarization at least partly
via
a PI3K/Akt signaling pathway. Overall, we identify TRIM21 drives the inflammatory response and cardiac remodeling by stimulating M1 macrophage polarization through a PI3K/Akt signaling pathway post-MI.
An explicit topology optimization-based design paradigm is proposed for the design of photonic topological crystalline insulators (TCIs). To strictly guarantee the topological property, rational ...engineering of symmetry-indicators is carried out by mathematical programming, which simultaneously maximizes the width of nontrivial topological band gaps and achieves the desired quantized bulk polarization. Our approach is successfully applied to design photonic TCIs with time-reversal symmetry in two-dimensional point groups, higher-order magnetic TCIs, and higher-order photonic TCIs. This methodology paves the way for inverse design of optimized photonic/phononic, multiphysics, and multifunctional three-dimensional TCIs.
It is well-known that systemic inflammation plays a crucial role in the pathogenesis and prognosis of acute myocardial infarction (AMI). The systemic immune-inflammation index (SII, platelet × ...neutrophil/lymphocyte ratio) is a novel index that is used for the characterization of the severity of systemic inflammation. Recent studies have identified the high SII level as an independent predictor of poor outcomes in patients with AMI. We aimed to investigate the prognostic implications of SII in AMI patients with and without diabetes mellitus (DM).
We included 2111 patients with AMI from February 2014 to March 2018. Multivariable Cox regression analyses were performed to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause death and cardiovascular (CV) death. Multiple imputation was used for missing covariates.
Of 2111 patients (mean age: 65.2 ± 12.2 years, 77.5% were males) analyzed, 789 (37.4%) had DM. Generalized additive model analyses showed that as the SII increased, the C-reactive protein and peak TnT elevated while the LVEF declined, and these associations were similar in patients with and without DM. During a median of 2.5 years of follow-up, 210 all-cause deaths and 154 CV deaths occurred. When treating the SII as a continuous variable, a higher log-transformed SII was significantly associated with increased all-cause mortality (HR: 1.57, 95%CI: 1.02-2.43) and CV mortality (HR: 1.85, 95%CI 1.12-3.05), and such an association was also significant in the diabetics (HRs and 95%CIs for all-cause death and CV death were 2.90 1.40-6.01 and 3.28 1.43-7.57, respectively) while not significant in the nondiabetics (P
for all-cause death and CV death were 0.019 and 0.049, respectively). Additionally, compared to patients with the lowest tertiles of SII, those with the highest tertiles of SII possessed significantly higher all-cause mortality (HR: 1.82, 95%CI 1.19-2.79) and CV mortality (HR: 1.82, 95%CI 1.19-2.79) after multivariable adjustment, and this relationship remained pronounced in the diabetics (HRs and 95%CIs for all-cause death and CV death were 2.00 1.13-3.55 and 2.09 1.10-3.98, respectively) but was not observed in the nondiabetics (HRs and 95%CIs for all-cause death and CV death were 1.21 0.75-1.97 and 1.60 0.89-2.90, respectively). Our restricted cubic splines analyses indicated a pronounced linear association between SII and mortality only in diabetics.
In AMI patients with DM, high SII is an independent predictor of poor survival and may be helpful for patient's risk stratification.
Topological insulators supply robust edge states and can be used to compose novel waveguides to protect energy propagation against various defects. For practical applications, topological waveguides ...with a large working bandwidth and highly localized interface mode are desired. In the present work, mechanical valley Hall insulators are described by explicit geometry parameters using the moving morphable component method first. From the geometry parameters, artificial neural networks (ANN) are then well-trained to predict the topological property and the bounds of nontrivial bandgaps. Incorporating those ANN models, mathematical formulation for designing optimal mechanical topological waveguides can be solved efficiently, with an acceleration of more than 10,000 times than the traditional topology optimization approach.
Aims
New‐onset atrial fibrillation (NOAF) complicating acute myocardial infarction (AMI) has been associated with poor survival, but the clinical implication of NOAF on heart failure (HF) is still ...not well characterized. We aimed to investigate the relationship between NOAF complicating AMI and HF hospitalization.
Methods and results
Adult AMI patients identified in the New‐Onset Atrial Fibrillation Complicating Acute Myocardial Infarction in Shanghai registry who, discharged alive, had complete echocardiography and follow‐up data from February 2014 to March 2018 were included. Patients were divided according to the presence of NOAF. The outcome measures were HF hospitalization and death during the observational period (until 10 April 2019). Cox proportional hazard models were performed in the whole population and propensity score‐matched (PSM) cohort to assess the adjusted hazard ratio (HR) and 95% confidence interval (CI). Overall, 2075 patients (mean age: 65.2 ± 12.3 years, 77.3% were men) with AMI were analysed, of whom 228 (11.0%) developed NOAF. Advanced age, admission HF (Killip II–IV), impaired renal function, decreased left ventricular ejection fraction, increased heart rate, and left atrial enlargement were independent predictors of NOAF. Over a median observational period of 2.7 years, the annual incidence rates of HF hospitalization were 18.4% and 2.8% for patients with NOAF and sinus rhythm, respectively. After adjustment for confounders, NOAF was significantly associated with HF hospitalization (HR: 3.14, 95% CI: 2.30–4.28, P < 0.001). Similar results were obtained when accounting for the competing risk of all‐cause death (subdistribution HR: 3.06, 95% CI: 2.18–4.30, P < 0.001) or from the PSM cohort (HR: 2.82, 95% CI: 1.99–4.00, P < 0.001). Patients with persistent NOAF (HR: 5.81, 95% CI: 3.59–9.41) were at significantly higher risk of HF hospitalization when compared with those with transient one (HR: 2.61, 95% CI: 1.84–3.70, P interaction = 0.008). Although post‐MI NOAF was significantly related to cardiovascular death (annual incidence rates for NOAF and sinus rhythm were 9.4% and 2.3%, respectively; HR: 1.97, 95% CI: 1.36–2.85, P < 0.001), such an association was attenuated when HF hospitalization (modelled as a time‐varying covariate) and antithrombotic treatment were adjusted (HR: 1.37, 95% CI: 0.92–2.02, P = 0.121).
Conclusions
In patients with AMI, NOAF is strongly associated with an increased long‐term risk of HF hospitalization. Our findings suggest that strengthened secondary prevention of HF should be considered in this high‐risk population.
Dissolved organic matter plays a fundamental geochemical role in aquatic systems. However, not much is known about interactions of dissolved organic matter characteristics, source, and partial ...pressure of carbon dioxide in the monsoonal streams of Asia. The ultraviolet visible and fluorescence spectroscopic indices were used as proxies for dissolved organic matter quantity and quality, and consequently associations and controls of dissolved organic matter quality, nutrients and partial pressure of carbon dioxide were examined in a monsoonal headwater River Jinshui. The source, composition, and molecular weight of dissolved organic matter showed temporal variations, mainly contributable to hydrological seasonality and potentially biological productivity. The allochthonous (land-derived) high-molecular weight components (aromatic, humification and lignin substances) were the dominant source of dissolved organic matter in the River with more terrestrial contributions in the wet season (much higher absorption coefficient at a wavelength of 350 nm and specific ultraviolet–visible absorption at 254 nm, and lower biological index and freshness index). The autochthonous low-molecular weight fractions contributed more in the dry season (significantly higher biological index and freshness index). Dissolved organic matter quality indices rather than dissolved organic carbon concentration showed significant relationships with partial pressure of carbon dioxide, this observation coupled with correlation seasonality could demonstrate the origins and controls of partial pressure of carbon dioxide. The new findings advanced the interactions of dissolved organic matter geochemistry, nutrients and partial pressure of carbon dioxide in rivers. This is critical for water environmental assessment and regional sustainable development. Further studies on discrimination and controls of dissolved organic matter quality, dissolved carbon dioxide and nutrients remain to be conducted.
•DOM source and chemical compositions show significant seasonality.•Allochthonous land-derived DOM is dominant source of the overall DOM signal.•Terrestrial inputs contribute more in the wet season because of monsoonal rainfall.•Autochthonous DOM contributed more in the dry season than in the dry season.•DOC quality rather than DOC concentration is significantly related to pCO2.
Abstract Objectives To examine plasma protein Z (PZ) levels in acute myocardial infarction (AMI) and chronic coronary atherosclerosis disease (CCAD) patients without history of AMI and explore its ...potential clinical significance. Methods Plasma PZ concentrations were measured in 90 AMI patients (Group A), 87 CCAD patients without AMI history who remained free of major clinical events at least one year (Group B), and 88 clinically healthy controls (Group C). Results PZ was found to be significantly lower ( P < 0.001) in A (1508.5 ± 486.2 ng/mL) compared with B (1823.0 ± 607.8 ng/mL) and C (2001.7 ± 733.0 ng/mL) groups and in A + B compared with C Group (A + B 1663.1 ± 570.0, P < 0.001). No statistically significant difference was reached between B and C groups ( P = 0.081). PZ level was significantly correlated with concentration of creatine kinase MB, high sensitive-cardiac troponin T, high sensitive C reactive protein, D-dimer and coagulation factor II and may be a useful predictor for AMI (OR: 1.38, 95% CI: 1.13-1.77, P = 0.03). Subgroup analysis showed PZ concentration below the lowest tertile (< 1398 ng/mL) had a significantly increased risk for AMI and CCAD (OR: 3.39; 95% CI: 1.12-10.31; P = 0.03 and OR: 7.39; 95% CI: 2.62-20.79; P < 0.001 respectively). Conclusions PZ deficiency is found in AMI patients and could potentially reflect the myocardium injury, local coagulation activation and inflammation response during the acute phase of coronary atherosclerosis disease.
Panax notoginseng saponins (PNS) are among the most important compounds extracted from Panax notoginseng root, and have long been used in traditional Chinese medicine to control bleeding. PNS have ...recently garnered attention for the treatment of circulatory system diseases. The present study aimed to evaluate the effects of PNS on angiogenesis in vitro and to explore the molecular mechanisms underlying their actions. The present results demonstrated that the proliferative ability of human umbilical vein endothelial cells (HUVECs) was augmented following treatment with PNS. In addition, wound healing and Boyden chamber assays indicated that PNS may enhance HUVEC motility and increase the number of capillary‑like tube branches in HUVECs. These effects were suppressed by 5' adenosine monophosphate‑activated protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS) inhibitors. Furthermore, western blot analysis demonstrated that PNS stimulated the phosphorylation of AMPK and eNOS at Thr‑172 and Ser‑1179, respectively. These results suggested that PNS may promote tube formation in endothelial cells through AMPK‑ and eNOS‑dependent signaling pathways.
Background:
New-onset atrial fibrillation (NOAF) is a common complication during acute myocardial infarction (AMI) and sometimes can be completely asymptomatic, but the clinical implications of these ...asymptomatic episodes require further characterization. The objective of this study was to investigate the short- and long-term prognostic impact of post-MI NOAF based on the presence of AF-related symptoms.
Methods:
The New-Onset Atrial Fibrillation Complicating Acute Myocardial Infarction in ShangHai (NOAFCAMI-SH) registry was a retrospective cohort including participants with AMI without a documented history of AF. Patients with NOAF were divided into two groups according to the AF-related symptoms. The primary endpoint was all-cause mortality.
Results:
Of 2,399 patients included, 278 (11.6%) developed NOAF of whom 145 (6.0%) with asymptomatic episodes and 133 (5.5%) with symptomatic ones. During hospitalization, 148 patients died 106, 10, and 32 in the sinus rhythm (SR), asymptomatic, and symptomatic NOAF groups, respectively. After multivariable adjustment, only symptomatic NOAF was associated with in-hospital mortality odds ratio (OR): 2.32, 95% confidence interval (CI): 1.36–3.94 compared with SR. Over a median follow-up of 2.7 years, all-cause mortality was 3.2, 12.4, and 11.8% per year in the SR, asymptomatic, and symptomatic NOAF groups, respectively. After adjustment for confounders, it was the asymptomatic NOAF hazard ratio (HR): 1.61, 95% CI: 1.09–2.37) rather than the symptomatic one (HR: 1.37, 95% CI: 0.88–2.12) that was significantly related to mortality. Similar results were also observed for cardiovascular mortality HRs and 95% CI were 1.71 (1.10–2.67) and 1.25 (0.74–2.11) for asymptomatic and symptomatic NOAF, respectively. Both asymptomatic and symptomatic NOAF episodes were associated with heart failure, whereas only those with symptomatic NOAF were at heightened risk of ischemic stroke. Our exploratory analysis further identified patients with asymptomatic high-burden NOAF as the highest-risk population (mortality: 19.6% per year).
Conclusion:
Among patients with AMI, symptomatic NOAF is related to in-hospital mortality and asymptomatic NOAF is associated with poor long-term survival.
Registration:
URL:
https://clinicaltrials.gov/
; Unique identifier: NCT03533543.
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