MicroRNA-125b (miR-125b) reduces myocardial infarct area and restrains myocardial ischemia reperfusion injury (I/R). In this study, we aimed to investigate the effect of bone marrow mesenchymal stem ...cell (BMSC)-derived exosomes carrying miR-125b on I/R rats. The myocardial I/R model in rats was constructed by ligation of the left anterior descending coronary artery (LAD). Rats were randomly divided into I/R and Sham group. Lv-cel-miR-67 (control) or Lv-miR-125b was transfected into BMSCs. Exosomes were extracted from transfected BMSCs, and separately named BMSC-Exo-67, BMSC-Exo-125b, and BMSC-Exo. MTT assay and flow cytometry were used to detect the viability and apoptosis of I/R myocardium cells, respectively. The expression of cell apoptosis proteins and the levels of inflammatory factors were examined by Western blot and ELISA assay, respectively. The target relationship between miR-125b and SIRT7 was predicted by using StarBase3.0, and was confirmed by using dual-luciferase reporter gene assay. qRT-PCR, immunohistochemistry staining, and Western blot were used to evaluate the expression of SIRT7 in myocardium tissues in I/R rats. BMSC-derived exosomes were successfully isolated and identified by TEM and positive expression of CD9 and CD63. The expression of miR-125b was down-regulated in I/R myocardium tissues and cells. BMSC-Exo-125b significantly up-regulated miR-125b in I/R myocardium cells. The intervention of BMSC-Exo-125b significantly increased the cell viability, decreased the apoptotic ratio, down-regulated Bax and caspase-3, up-regulated Bcl-2, and decreased the levels of IL-1β, IL-6, and TNF-α in I/R myocardium cells. SIRT7 was a target of miR-125b, and BMSC-Exo-125b significantly down-regulated SIRT7 in myocardium cells. In addition, the injection of BMSC-Exo-125b alleviated the pathological damages and down-regulated SIRT7 in myocardium tissues of I/R rats. BMSC-derived exosomes carrying miR-125b protected against myocardial I/R by targeting SIRT7.
We introduce a new troubled-cell indicator for the discontinuous Galerkin (DG) methods for solving hyperbolic conservation laws. This indicator can be defined on unstructured meshes for high order DG ...methods and depends only on data from the target cell and its immediate neighbors. It is able to identify shocks without PDE sensitive parameters to tune. Extensive one- and two-dimensional simulations on the hyperbolic systems of Euler equations indicate the good performance of this new troubled-cell indicator coupled with a simple minmod-type TVD limiter for the Runge–Kutta DG (RKDG) methods.
Layered double hydroxides (LDH) have been extensively investigated for charge storage, however, their development is hampered by the sluggish reaction dynamics. Herein, triggered by mismatching ...integration of Mn sites, we configured wrinkled Mn/NiCo-LDH with strains and defects, where promoted mass & charge transport behaviors were realized. The well-tailored Mn/NiCo-LDH displays a capacity up to 518 C g
(1 A g
), a remarkable rate performance (78%@100 A g
) and a long cycle life (without capacity decay after 10,000 cycles). We clarified that the moderate electron transfer between the released Mn species and Co
serves as the pre-step, while the compressive strain induces structural deformation with promoted reaction dynamics. Theoretical and operando investigations further demonstrate that the Mn sites boost ion adsorption/transport and electron transfer, and the Mn-induced effect remains active after multiple charge/discharge processes. This contribution provides some insights for controllable structure design and modulation toward high-efficient energy storage.
de Winter syndrome, also termed anterior ST-segment elevation myocardial infarction (STEMI) equivalent, is estimated to be present in approximately 2% of patients with acute myocardial infarction, ...but is often under-recognized by clinicians. Therefore, de Winter syndrome is associated with increased morbidity and mortality. We report a 51-year-old man with typical chest tightness and a characteristic electrocardiographic pattern without classic ST-segment elevation, but with acute nearly total occlusion of the left anterior descending coronary artery. Although the patient presented as a non-STEMI case, the definite diagnosis of de Winter syndrome was made on the basis of clinical and electrocardiographic findings. The patient’s symptom of chest tightness was relieved immediately after acute percutaneous coronary intervention and the left ventricular ejection fraction had not deteriorated at 1 month of follow-up.
We introduce the concept of an M-decomposition and show how to use it to systematically construct hybridizable discontinuous Galerkin and mixed methods for steady-state diffusion methods with ...superconvergence properties on unstructured meshes.
Despite coronary re-vascularization, the common complications of acute myocardial infarction (AMI), cardiac remodeling, and heart failure (HF), is increasing globally. Sacubitril valsartan (SV), an ...angiotensin receptor-neprilysin inhibitor (ARNI), has been previously demonstrated to improve HF. We further hypothesize that ultra-early SV treatment is also effective in preventing cardiac remodeling for patients with AMI following primary percutaneous coronary intervention (PCI).
The Assessment of ultra-early administration of Sacubitril Valsartan to improve cardiac remodeling in patients with Acute Myocardial Infarction following primary PCI (ASV-AMI) trial is a prospective, multicenter, randomized controlled trial in China planning to enroll at least 1,942 eligible patients from 10 centers. After successful primary PCI of culprit artery within 24 h, AMI patients are randomized to 2 h group or 3-7 days group with SV treatment. The major endpoints are echocardiographic measurement, cardiothoracic ratio, and N-Terminal pro-B-Type Natriuretic Peptide (NT pro-BNP) at baseline, 1, 3, 6, and 12 months. The secondary endpoints included MACE (cardiac arrest, cardiogenic death, myocardial infarction, and target vessel re-vascularization), in-/out-patient HF, EuroQol Five Dimensions Questionnaire (EQ-5D), and Kansas City Cardiomyopathy Questionnaire (KCCQ).
The ASV-AMI trial is the first clinical trial of ultra-early administration of SV in the treatment of post-PCI AMI, adding more clinical evidence. Early application of SV to prevent cardiac remodeling in AMI patient is a major focus of this trial.
Trial registration Chinese Clinical Trial Registry (http://www.chictr.org.cn; ChiCTR2100051979). Registered on 11 October 2021.
Objective: Given the psychosocial and ethical burden, patients with hypertrophic cardiomyopathy (HCMs) could benefit from the establishment of genetic probability prior to the test. This study aimed ...to develop a simple tool to provide genotype prediction for HCMs.
Methods: A convolutional neural network (CNN) was built with the 12-lead electrocardiogram (ECG) of 124 HCMs who underwent genetic testing (GT), externally tested by predicting the genotype on another HCMs cohort (n = 54), and compared with the conventional methods (the Mayo and Toronto score). Using a third cohort of HCMs (n = 76), the role of the network in risk stratification was explored by calculating the sudden cardiac death (SCD) risk scorers (HCM risk-SCD) across the predicted genotypes. Score-CAM was employed to provide a visual explanation of the network.
Results:
Overall, 80 of 178 HCMs (45%) were genotype-positive. Using the 12-lead ECG as input, the network showed an area under the curve (AUC) of 0.89 (95% CI, 0.83-0.96) on the test set, outperforming the Mayo score (0.69 95% CI, 0.65-0.78, p < 0.001) and the Toronto score (0.69 95% CI, 0.64-0.75, p < 0.001). The network classified the third cohort into two groups (predicted genotype-negative vs. predicted genotype-positive). Compared with the former, patients predicted genotype-positive had a significantly higher HCM risk-SCD (0.04 ± 0.03 vs. 0.03 ± 0.02, p <0.01). Visualization indicated that the prediction was heavily influenced by the limb lead.
Conclusions: The network demonstrated a promising ability in genotype prediction and risk assessment in HCM.
Patients with genotype-positive hypertrophic cardiomyopathy (HCM) have a higher risk of severe heart failure and sudden cardiac death (SCD). A deep learning-derived 12-lead electrocardiogram was developed, outperformed the conventional methods in genotype prediction, and showed a promising future in SCD risk assessment in HCM.
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