Explore the vast range of titles available.

Background METTL3 is the core catalytic enzyme in m6A and is involved in a variety of cardiovascular diseases. However, whether and how METTL3 plays a role during angiotensin II (Ang-II)-induced myocardial hypertrophy is still unknown. Methods Neonatal rat cardiomyocytes (NRCMs) and C57BL/6J mice were treated with Ang-II to induce myocardial hypertrophy. qRT-PCR and western blots were used to detect the expression of RNAs and proteins. Gene function was verified by knockdown and/or overexpression, respectively. Luciferase and RNA immunoprecipitation (RIP) assays were used to verify interactions among multiple genes. Wheat germ agglutinin (WGA), hematoxylin and eosin (H&E), and immunofluorescence were used to examine myocardial size. m6A methylation was detected by a colorimetric kit. Results METTL3 and miR-221/222 expression and m6A levels were significantly increased in response to Ang-II stimulation. Knockdown of METTL3 or miR-221/222 could completely abolish the ability of NRCMs to undergo hypertrophy. The expression of miR-221/222 was positively regulated by METTL3, and the levels of pri-miR-221/222 that bind to DGCR8 or form m6A methylation were promoted by METTL3 in NRCMs. The effect of METTL3 knockdown on hypertrophy was antagonized by miR-221/222 overexpression. Mechanically, Wnt/β-catenin signaling was activated during hypertrophy and restrained by METTL3 or miR-221/222 inhibition. The Wnt/β-catenin antagonist DKK2 was directly targeted by miR-221/222, and the effect of miR-221/222 inhibitor on Wnt/β-catenin was abolished after inhibition of DKK2. Finally, AAV9-mediated cardiac METTL3 knockdown was able to attenuate Ang-II-induced cardiac hypertrophy in mouse model. Conclusions Our findings suggest that METTL3 positively modulates the pri-miR221/222 maturation process in an m6A-dependent manner and subsequently activates Wnt/β-catenin signaling by inhibiting DKK2, thus promoting Ang-II-induced cardiac hypertrophy. AAV9-mediated cardiac METTL3 knockdown could be a therapeutic for pathological myocardial hypertrophy.

Ventricular arrhythmias (VAs) are critical cardiovascular diseases that require rapid and accurate detection. Conventional approaches relying on multi-lead ECG or deep learning models have limitations in computational cost, interpretability, and real-time applicability on wearable devices. To address these issues, a lightweight and interpretable framework based on multiple complex networks was proposed for the detection of life-threatening VAs using short-term single-lead ECG signals. The input signals were decomposed using the fixed-frequency-range empirical wavelet transform, and sub-bands were subsequently analyzed through multiscale visibility graphs, recurrence networks, cross-recurrence networks, and joint recurrence networks. Eight topological features were extracted and input into an XGBoost classifier for VA identification. Ten-fold cross-validation results on the MIT-BIH VFDB and CUDB databases demonstrated that the proposed method achieved a sensitivity of 99.02 ± 0.53%, a specificity of 98.44 ± 0.43%, and an accuracy of 98.73 ± 0.02% for 10 s ECG segments. The model also maintained robust performance on shorter segments, with 97.23 ± 0.76% sensitivity, 98.85 ± 0.95% specificity, and 96.62 ± 0.02% accuracy on 2 s segments. The results outperformed existing feature-based and deep learning approaches while preserving model interpretability. Furthermore, the proposed method supports mobile deployment, facilitating real-time use in wearable healthcare applications.

Background Studies in populations with or without cardiovascular disease have shown that very high HDL-C levels are associated with an increased risk of cardiovascular events. However, the exact relationship between HDL-C levels and long-term prognosis remains unknown in patients with myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI). Methods This was a post hoc secondary analysis of long-term follow-up results in patients undergoing PCI open-label, observational cohort study. Patients with MI who had undergone PCI were enrolled. Restricted cubic spline (RCS) analysis and logistic regression analysis were performed to assess the relationship between HDL-C levels and the risk of cardiovascular events. Results A total of 1934 patients with MI undergoing PCI were enrolled in our analysis and our population was divided in 3 groups according to the HDL-C plasma levels: HDL-C < 40 mg/dL (low HDL-C); HDL-C between 40 and 80 mg/ dL (medium HDL-C); and HDL-C > 80 mg/dL (high HDL-C). RCS analysis showed a nonlinear U-shaped association between HDL-C levels and major adverse cardiac and cerebrovascular events (MACCE) in patients with NSTEMI with adjusted variables. After adjusting for potential confounders, the follow-up analysis indicated that high risk group had elevated occurrence of MACCE than low risk group (HDL-C 35 and 55 mg/dL) (OR:1.645, P = 0.006). Conclusions Our analysis demonstrated that there is a U-shaped association between HDL-C and MACCE in patients with NSTEMI undergoing PCI.

Doxorubicin is one of the most common antitumor drugs. However, cardiotoxicity’s side effect limits its clinical applicability. In the present study, Gene Expression Omnibus (GEO) datasets were applied to reanalyze differentially expressed genes (DEGs) and construct weighted correlation network analysis (WGCNA) modules of doxorubicin-induced cardiotoxicity in wild-type mice. Several other bioinformatics analyses were performed to pick out the hub gene, and then the correlation between the hub gene and immune infiltration was evaluated. In total, 120 DEGs were discovered in a mouse model of doxorubicin-induced cardiotoxicity, and PF-04217903, propranolol, azithromycin, etc. were found to be potential drugs against this pathological condition. Among all the DEGs, 14 were further screened out by WGCNA modules, of which Limd1 was upregulated and finally regarded as the hub gene after being validated in other GEO datasets. Limd1 was upregulated in the peripheral blood mononuclear cell (PBMC) of the rat model, and the area under curve (AUC) of the receiver operating characteristic curve (ROC) in diagnosing cardiotoxicity was 0.847. The GSEA and PPI networks revealed a potential immunocyte regulatory role of Limd1 in cardiotoxicity. The proportion of “dendritic cells activated” in the heart was significantly elevated, while “macrophage M1” and “monocytes” declined after in vivo doxorubicin application. Finally, Limd1 expression was significantly positively correlated with “dendritic cells activation’ and negatively correlated with “monocytes” and “macrophages M1’. In summary, our results suggested that limd1 is a valuable biomarker and a potential inflammation regulator in doxorubicin-induced cardiotoxicity.

Objective: To explore the role of neutrophil-to-lymphocyte ratio (NLR) in predicting the short-term prognosis of NSTEMI and STEMI. Methods: This study was a single-center, retrospective and observational study. 2618 patients including 1289 NSTMI and 1329 STEMI patients were enrolled from June 2013 to February 2018 in Zhongda Hospital, Southeast University. The demographic information, clinical characteristics, medical history, laboratory examination, treatment, and outcome of individuals at admission and during hospitalization were extracted from the electronic medical record system. Outcome was defined as the all-cause death during hospitalization. Results: (1) In the NSTEMI group, the ability of NLR in predicting in-hospital death (AUC = 0.746) was higher than the neutrophil-monocyte ratio (NMR) (AUC = 0.654), the platelet-lymphocyte ratio (PLR) (AUC = 0.603) and the lymphocyte-monocyte ratio (LMR) (AUC = 0.685), and also higher than AST (AUC = 0.621), CK (AUC = 0.595), LDH (AUC = 0.653) and TnI (AUC = 0.594). The AUC of NLR in the STEMI group was only 0.621. (2) The optimal cut-off value of NLR in NSTEMI group was 5.509 (Youden index = 0.447, sensitivity = 77.01%, specificity = 67.72%). After adjusting variables including age, sex, diabetes history, smoking history, LDL-C and Cr, the logistic regression showed that the patients with NLR>5.509 had higher hazard risk of death (HR4.356; 95%CI 2.552–7.435; P < 0.001) than the patients with NLR ≤ 5.509. (3) Stratification analysis showed that the in-hospital mortality of patients with NLR > 5.509 was 14.611-fold higher than those with NLR ≤ 5.509 in patients aged <76, much higher than the ratio in patients aged ≥ 76. For patients with creatinine levels ≤ 71, the in-hospital death risk in high NLR group was 10.065-fold higher than in low NLR group (95%CI 1.761–57.514, P = 0.009), while the HR was only 4.117 in patients with creatinine levels > 71. The HR in patients with or without diabetes were 6.586 and 3.375, respectively. The HR in smoking or no smoking patients were 6.646 and 4.145, respectively. The HR in patients with LDL-C ≥ 2.06 or <2.06 were 5.526 and 2.967 respectively. Conclusion: Compared to NMR, PLR, and LMR, NLR had the best ability in predicting in-hospital death after NSTEMI. Age, creatinine, LDL-C, diabetes and smoking history were all important factors affecting the predictive efficiency in NSTEMI. NLR had the limited predictive ability in STEMI.

Dyslipidemia plays a pivotal role in the pathogenesis of acute coronary syndrome (ACS). This study aims to investigate the value of two indices associated with lipid metabolism, low-density lipoprotein cholesterol to apolipoprotein B ratio (LBR) and high-density lipoprotein cholesterol to apolipoprotein A-1 ratio (HAR), to predict in-hospital death in patients with ACS. This single-center, retrospective, observational study included 3,366 consecutive ACS patients in Zhongda Hospital, Southeast University from July 2013 to January 2018. The clinical and laboratory data were extracted, and the in-hospital death and hospitalization days were also recorded. All patients were equally divided into four groups according to quartiles of HAR: Q1 (HAR < 1.0283), Q2 (1.0283 ≤ HAR < 1.0860), Q3 (1.0860 ≤ HAR < 1.1798), and Q4 (HAR ≥ 1.1798). Overall, HAR was positively associated with the counts of neutrophils and monocytes, whereas negatively correlated to lymphocyte counts. HAR was negatively correlated to left ventricular ejection fraction (LVEF). Compared to other three groups, in-hospital mortality (vs. Q1, Q2, and Q3, p < 0.001) and hospitalization length (vs. Q1, Q2, and Q3, p < 0.001) were significantly higher in the Q4 group. When grouped by LBR, however, there was no significant difference in LVEF, in-hospital mortality, and hospitalization length among groups. After adjusting potential impact from age, systolic blood pressure, creatine, lactate dehydrogenase, albumin, glucose, and uric acid, multivariate analysis indicated that HAR was an independent factor predicting in-hospital death among ACS patients. HAR had good predictive value for patients' in-hospital death after the occurrence of acute coronary events, but LBR was not related to in-hospital adverse events.

Acute myocardial infarction (AMI) is one of the fatal cardiac emergencies. The detection of triggering receptor expressed on myeloid cells 1 (TREM1), a cell surface immunoglobulin that amplifies pro-inflammatory responses, screened by bioinformatics was shown to be significant in diagnosing and predicting the prognosis of AMI. GSE66360, GSE61144 and GSE60993 were downloaded from the Gene Expression Omnibus (GEO) database to explore the differentially expressed genes (DEGs) between AMI and control groups using R software. A total of 147 patients in total were prospectively enrolled from October 2018 to June 2019 and divided into two groups, the normal group ( = 35) and the AMI group ( = 112). Plasma was collected from each patient at admission and all patients received 6-month follow-up care. According to bioinformatic analysis, TREM1 was an important DEG in patients with AMI. Compared with the normal group, TREM1 expression was markedly increased in the AMI group ( < 0.001). TREM1 expression was positively correlated with fasting plasma glucose (FPG), glycosylated hemoglobin (HbAC), and the number of lesion vessels, although it had no correlation with Gensini score. TREM1 expression in the triple-vessels group was significantly higher than that of the single-vessel group ( < 0.05). Multiple linear regression showed that UA and HbAC were two factors influencing TREM1 expression. The ROC curve showed that TREM1 had a diagnostic significance in AMI ( < 0.001), especially in AMI patients without diabetes. Cox regression showed increased TREM1 expression was closely associated with 6-month major adverse cardiac events (MACEs) ( < 0.001). TREM1 is a potentially significant biomarker for the diagnosis of AMI and may be closely associated with the severity of coronary lesions and diabetes. TREM1 may also be helpful in predicting the 6-month MACEs after AMI.

Articular cartilage regeneration is still a difficult task due to the cartilage’s weak capacity for self-healing and the effectiveness of the available therapies. The engineering of cartilage tissue has seen widespread use of stem cell-based therapies. However, efficient orientation of line-specific bone marrow mesenchymal stem cells (BMSCs) to chondrogenesis and maintenance of chondrogenic differentiation challenged stem cell-based therapy. Herein, we developed a Fe-based metal-organic framework (MOF) loaded with hematoporphyrin monomethyl ether (HMME) and cartilage-targeting arginine-aspartate-glycine (RGD) peptide to form MOF-HMME-RGD sonosensitizer to regulate BMSCs chondrogenic differentiation for cartilage regeneration via the modulation of reactive oxygen species (ROS). By using sonodynamic therapy (SDT), the MOF-HMME-RGD demonstrated favorable biocompatibility, could generate a modest amount of ROS, and enhanced BMSCs chondrogenic differentiation through increased accumulation of glycosaminoglycan, an ECM component specific to cartilage, and upregulated expression of key chondrogenic genes ( ACAN , SOX9 , and Col2a1 ). Further, transplanted BMSCs loading MOF-HMME-RGD combined with SDT enhanced cartilage regeneration for cartilage defect repair after 8 weeks into treatment. This synergistic strategy based on MOF nanoparticles provides an instructive approach to developing alternative sonosensitizers for cartilage regeneration combined with SDT.

Background: This study aimed to examine whether quantitative flow ratio (QFR), an angiography-based computation of fractional flow reserve, was associated with intravascular imaging-defined vulnerable plaque features, such as thin cap fibroatheroma (TCFA) in patients with stable angina, and non-ST-segment elevation acute coronary syndrome. Methods: Patients undergoing optical coherence tomography (OCT) or intravascular ultrasound (IVUS) examinations were identified from two prospective studies and their interrogated vessels were assessed with QFR. Lesions in the OCT cohort were classified into tertiles: QFR-T1 (QFR ≤ 0.85), QFR-T2 (0.85 < QFR ≤ 0.93), and QFR-T3 (QFR > 0.93). Lesions in the IVUS cohort were classified dichotomously as low or high QFR groups. Results: This post-hoc analysis included 132 lesions (83 for OCT and 49 for IVUS) from 126 patients. The prevalence of OCT-TCFA was significantly higher in QFR-T1 (50%) than in QFR-T2 (14%) and QFR-T3 (19%) ( p = 0.003 and 0.018, respectively). Overall significant differences were also observed among tertiles in maximum lipid arc, thinnest fibrous cap thickness, and minimal lumen area ( p = 0.017, 0.040, and <0.001, respectively). Thrombus was more prevalent in QFR-T1 (39%) than in QFR-T2 (3%), and QFR-T3 (12%) ( p = 0.001 and 0.020, respectively). In the multivariable analysis, QFR ≤ 0.80 remained as a significant determinant of OCT-TCFA regardless of the presence of NSTE-ACS and the level of low-density lipoprotein cholesterol (adjusted OR: 4.387, 95% CI 1.297–14.839, p = 0.017). The diagnostic accuracy of QFR was moderate in identifying lesions with OCT-TCFA (area under the curve: 0.72, 95% CI 0.58–0.86, p = 0.003). In the IVUS cohort, significant differences were found between two groups in minimal lumen area and plaque burden but not in the distribution of virtual histology (VH)-TCFA ( p = 0.025, 0.036, and 1.000, respectively). Conclusions: Lower QFR was related to OCT-defined plaque vulnerability in angiographically mild-to-intermediate lesions. The QFR might be a useful tool for ruling out high-risk plaques without using any pressure wire or vasodilator.

Rationale: Bone defects pose a persistent challenge in orthopedic medicine due to their limited self-repair capacity. Although guided bone regeneration scaffolds have shown therapeutic potential, their clinical efficacy remains constrained by their suboptimal osteoinductive capability. Methods: Herein, we developed biodegradable piezoelectric polyhydroxybutyrate-barium titanate (PHB-BT) nanofiber scaffolds capable of generating synergistic piezoelectric stimulation for bone repair when integrated with low-intensity pulsed ultrasound (LIPUS). Results: Compared with conventional PHB scaffolds, ​PHB-BT nanofiber scaffolds​ ​showed enhanced piezoelectric properties​ and ​excellent biocompatibility, ​thereby facilitating​ sustained osteogenic activity. ​In vitro​ studies revealed that these scaffolds ​significantly promoted​ the osteogenic differentiation of bone marrow mesenchymal stem cells under LIPUS stimulation. ​Notably, ​in vivo​ evaluations ​demonstrated​ that these scaffolds ​substantially accelerated bone defect repair​, with complete scaffold degradation observed after eight weeks. Mechanistically, PHB-BT nanofibers improved osteogenesis via activating the Ca2+/calcineurin/nuclear factor of activated T-cells signaling pathway in response to ultrasound stimulation. Conclusions: These findings have significant implications for the design of next-generation, implantable electrical stimulators capable of providing sustained electromechanical cues for personalized bone tissue engineering applications.Rationale: Bone defects pose a persistent challenge in orthopedic medicine due to their limited self-repair capacity. Although guided bone regeneration scaffolds have shown therapeutic potential, their clinical efficacy remains constrained by their suboptimal osteoinductive capability. Methods: Herein, we developed biodegradable piezoelectric polyhydroxybutyrate-barium titanate (PHB-BT) nanofiber scaffolds capable of generating synergistic piezoelectric stimulation for bone repair when integrated with low-intensity pulsed ultrasound (LIPUS). Results: Compared with conventional PHB scaffolds, ​PHB-BT nanofiber scaffolds​ ​showed enhanced piezoelectric properties​ and ​excellent biocompatibility, ​thereby facilitating​ sustained osteogenic activity. ​In vitro​ studies revealed that these scaffolds ​significantly promoted​ the osteogenic differentiation of bone marrow mesenchymal stem cells under LIPUS stimulation. ​Notably, ​in vivo​ evaluations ​demonstrated​ that these scaffolds ​substantially accelerated bone defect repair​, with complete scaffold degradation observed after eight weeks. Mechanistically, PHB-BT nanofibers improved osteogenesis via activating the Ca2+/calcineurin/nuclear factor of activated T-cells signaling pathway in response to ultrasound stimulation. Conclusions: These findings have significant implications for the design of next-generation, implantable electrical stimulators capable of providing sustained electromechanical cues for personalized bone tissue engineering applications.