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Dysregulated autophagy is associated with many pathological disorders such as cardiovascular diseases. Emerging evidence has suggested that circular RNAs (circRNAs) have important roles in some biological processes. However, it remains unclear whether circRNAs participate in the regulation of autophagy. Here we report that a circRNA, termed autophagy-related circular RNA (ACR), represses autophagy and myocardial infarction by targeting Pink1-mediated phosphorylation of FAM65B. ACR attenuates autophagy and cell death in cardiomyocytes. Moreover, ACR protects the heart from ischemia/reperfusion (I/R) injury and reduces myocardial infarct sizes. We identify Pink1 as an ACR target to mediate the function of ACR in cardiomyocyte autophagy. ACR activates Pink1 expression through directly binding to Dnmt3B and blocking Dnmt3B-mediated DNA methylation of Pink1 promoter. Pink1 suppresses autophagy and Pink1 transgenic mice show reduced myocardial infarction sizes. Further, we find that FAM65B is a downstream target of Pink1 and Pink1 phosphorylates FAM65B at serine 46. Phosphorylated FAM65B inhibits autophagy and cell death in the heart. Our findings reveal a novel role for the circRNA in regulating autophagy and ACR-Pink1-FAM65B axis as a regulator of autophagy in the heart will be potential therapeutic targets in treatment of cardiovascular diseases.

Cardiovascular disease (CVD) remains the most common cause of death worldwide. Carotid plaque is an indicator of subclinical CVDs. Metabolic dysfunction-associated steatotic liver disease (MASLD) is a risk factor for atherosclerotic CVDs. We aimed to develop and validate a predictive model for carotid plaque occurrence in annual health check-up populations, to integrate health check-up indicators with machine learning (ML) algorithms and LASSO-based feature selection and leverage advanced interpretability frameworks to elucidate the contribution of individual risk factors. In this retrospective cohort study, we enrolled 4,973 MASLD patients, among whom 1,178 were diagnosed with carotid plaques using carotid ultrasound. Collected baseline data included ​demographic indicators, ​clinical histories, blood ​biochemical parameters, and liver function test indicators. A predictive model for carotid plaques was developed and validated using five ML algorithms. Model performance was evaluated based on the​ area under the curve, ​sensitivity, ​specificity, ​accuracy, and ​F1 Score. For model interpretability, we adopted the ​Shapley Additive Explanations (SHAP) framework to quantify the contribution of individual features to the prediction outcomes. Among the five ML algorithm models, the support vectors machine model demonstrated superior discriminative capability, higher goodness-of-fit, and greater clinical utility compared to other ML algorithm models. Moreover, age, systolic blood pressure, total cholesterol, sex, and fasting plasma glucose were the most important risk factors associated with carotid plaques in the MASLD population. This study demonstrated the feasibility of constructing a predictive model for carotid plaques in MASLD populations using health check-up indicators combined with ML algorithms. The application of SHAP methods enhanced model interpretability by quantifying the contribution of individual risk factors to prediction outcomes, enabling clinicians to identify high risk MASLD patients prone to carotid plaque development, so that they can adjust interventions accordingly.

Increasing evidence suggests that long noncoding RNAs (lncRNAs) play crucial roles in various biological processes. However, little is known about the effects of lncRNAs on autophagy. Here we report that a lncRNA, termed cardiac autophagy inhibitory factor (CAIF), suppresses cardiac autophagy and attenuates myocardial infarction by targeting p53-mediated myocardin transcription. Myocardin expression is upregulated upon H 2 O 2 and ischemia/reperfusion, and knockdown of myocardin inhibits autophagy and attenuates myocardial infarction. p53 regulates cardiomyocytes autophagy and myocardial ischemia/reperfusion injury by regulating myocardin expression. CAIF directly binds to p53 protein and blocks p53-mediated myocardin transcription, which results in the decrease of myocardin expression. Collectively, our data reveal a novel CAIF-p53-myocardin axis as a critical regulator in cardiomyocyte autophagy, which will be potential therapeutic targets in treatment of defective autophagy-associated cardiovascular diseases. Little is known about the role of long lncRNAs in autophagy. The authors identify lncCAIF, and show that it suppresses cardiac autophagy and attenuates myocardial infarction by targeting p53 -mediated transcription of myocardin.

Background Heart failure (HF) remains a significant public health challenge globally. This study aims to systematically analyze the global HF disease burden from 1990 to 2021 across temporal, spatial, and demographic dimensions to provide evidence for targeted prevention and control strategies. Methods Using data from the Global Burden of Disease (GBD) 2021 study, we analyzed the global HF burden through prevalent cases, years lived with disability (YLDs), and age-standardized rates per 100,000 population. Temporal trends were evaluated using estimated annual percentage change (EAPC) and joinpoint regression analysis. The relationship between the Socio-demographic Index (SDI) and disease burden was explored through Pearson correlation analysis, while attribution analysis identified the main causes of HF. When appropriate, analyses were stratified by 5 SDI regions, 21 GBD regions, 204 countries and territories, 20 age groups, and both sexes. Results Global HF prevalence and YLDs burden showed substantial increases from 1990 to 2021, with age-standardized prevalence increasing from 641.14 to 676.68 per 100,000 population. Notably, high-SDI regions exhibited a declining burden since 2019, indicating a potential global turning point. High-income North America bears the heaviest burden while South Asia shows the fastest growth rate. The correlation between disease burden and SDI level was negligible. The disease burden in males consistently exceeded that in females, with prevalence and YLDs rates rising sharply after age 60. The main causes and their attributable proportions were: ischemic heart disease (34.53%), hypertensive heart disease (22.53%), other cardiomyopathies (7.61%), chronic obstructive pulmonary disease (6.51%), and congenital heart anomalies (5.69%), with their distribution patterns differing across age groups and regions. Conclusion Global burden of HF increased significantly over recent decades, with a potential turning point in 2019 and marked regional disparities. It is essential to prioritize regions with heavy burdens or rapid growth rates, strengthen the management of major causes, and monitor HF burden trends in the post-COVID era.

Mitochondrial dysfunction plays a major role in the pathogenesis of cardiovascular diseases. MicroRNAs (miRNAs) are small RNAs that act as negative regulators of gene expression, but how miRNAs affect mitochondrial function in the heart is unclear. Using a miRNA microarray assay, we found that miR-762 predominantly translocated in the mitochondria and was significantly upregulated upon anoxia/reoxygenation (A/R) treatment. Knockdown of endogenous miR-762 significantly attenuated the decrease in intracellular ATP levels, the increase in ROS levels, the decrease in mitochondrial complex I enzyme activity and the increase in apoptotic cell death in cardiomyocytes, which was induced by A/R treatment. In addition, knockdown of miR-762 ameliorated myocardial ischemia/reperfusion (I/R) injury in mice. Mechanistically, we showed that enforced expression of miR-762 dramatically decreased the protein levels of endogenous NADH dehydrogenase subunit 2 (ND2) but had no effect on the transcript levels of ND2. The luciferase reporter assay showed that miR-762 bound to the coding sequence of ND2. In addition, knockdown of endogenous ND2 significantly decreased intracellular ATP levels, increased ROS levels, reduced mitochondrial complex I enzyme activity and increased apoptotic cell death in cardiomyocytes, which was induced by A/R treatment. Furthermore, we found that the inhibitory effect of miR-762 downregulation was attenuated by ND2 knockdown. Thus, our findings suggest that miR-762 participates in the regulation of mitochondrial function and cardiomyocyte apoptosis by ND2, a core assembly subunit of mitochondrial complex I. Our results revealed that mitochondrial miR-762, as a new player in mitochondrial dysfunction, may provide a new therapeutic target for myocardial infarction.

Background Although the benefits of sodium–glucose cotransporter 2 inhibitors (SGLT2i) on cardiovascular events have been reported in patients with type 2 diabetes mellitus (T2DM) with or without heart failure (HF), the impact of SGLT2i on cardiac remodelling remains to be established. Methods We searched the PubMed, Embase, Cochrane Library and Web of Science databases up to November 16th, 2020, for randomized controlled trials reporting the effects of SGLT2i on parameters of cardiac structure, cardiac function, plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) level or the Kansas City Cardiomyopathy Questionnaire (KCCQ) score in T2DM patients with or without chronic HF. The effect size was expressed as the mean difference (MD) or standardized mean difference (SMD) and its 95% confidence interval (CI). Subgroup analyses were performed based on the stage A–B or stage C HF population and HF types. Results Compared to placebo or other antidiabetic drugs, SGLT2i showed no significant effects on left ventricular mass index, left ventricular end diastolic volume index, left ventricular end systolic volume index, or left atrial volume index. SGLT2i improved left ventricular ejection fraction only in the subgroup of HF patients with reduced ejection fraction (MD 3.16%, 95% CI 0.11 to 6.22, p = 0.04; I 2  = 0%), and did not affect the global longitudinal strain in the overall analysis including stage A–B HF patients. SGLT2i showed benefits in the E/e’ ratio (MD − 0.45, 95% CI − 0.88 to − 0.03, p = 0.04; I 2  = 0%), plasma NT-proBNP level (SMD − 0.09, 95% CI − 0.16 to − 0.03, p = 0.004; I 2  = 0%), and the KCCQ score (SMD 3.12, 95% CI 0.76 to 5.47, p  = 0.01; I 2  = 0%) in the overall population. Conclusion The use of SGLT2i was associated with significant improvements in cardiac diastolic function, plasma NT-proBNP level, and the KCCQ score in T2DM patients with or without chronic HF, but did not significantly affect cardiac structural parameters indexed by body surface area. The LVEF level was improved only in HF patients with reduced ejection fraction.

Background The Paenibacillus srains exhibit diverse abilities to secrete hydrolases capable of degrading biomacromolecules and to act as plant growth-promoting bacteria (PGPB) through the degradation of fungal cell walls and promotion the nutrient cycling of nitrogen (N) and phosphorus (P). Despite the well-acknowledged attributes of Paenibacillus , only limited studies have identified strains of it concurrently produce multiple hydrolytic enzymes and display strong phytobeneficial characteristics. The objective of this study was to isolate and functionally characterize a novel Paenibacillus strain that combines hydrolytic capabilities with plant growth-promoting potential. Methods Strain TH7-28 T was isolated and taxonomically classified through a polyphasic identification approach based on 16S rRNA gene phylogeny, genome analysis, and physiological and biochemical characteristics. Its metabolic capabilities were characterized using CAZy and KEGG pathway annotations, supplemented by Kofam-KOALA functional profiling. Genomic relatedness to reference strains was determined using OGRIs: ANI, dDDH, and tetra-nucleotide frequency signature analyses. Biophysical and biochemical properties were evaluated through enzymatic activity assays, antimicrobial susceptibility testing, respiratory quinone system identification, fatty acid methyl ester profiling, and polar lipid composition analysis. The wheat germination test was used to verify the plant growth-promoting ability. Results Strain TH7-28 T was Gram-stain-positive, aerobic, white and rod-shaped. Phylogenetic analysis based on the 16S rRNA gene and genomic sequence indicated that strain TH7-28 T was classified within the genus Paenibacillus . The ANI values of strain TH7-28 T with the closest related strains P . macerans ATCC 8244 T and P. oralis KCOM 3021 T were 91.00% and 92.85%, respectively. The dDDH values of strain TH7-28 T with P . macerans ATCC 8244 T and P. oralis KCOM 3021 T were 44.60% and 52.40%, respectively. The respiratory quinone was menaquinone 7 (MK-7). The major cellular fatty acids (> 10%) comprised anteiso-C 15:0 , anteiso-C 17:0 , iso-C 16:0 and C 16:0 . The genomic DNA G + C content was 52.1%. Phosphatidylethanolamine, two amino lipids and three phospholipids were the main polar lipids. Genomic sequencing revealed multifunctional gene clusters encoding carbohydrate-active enzymes (cellulase and amylase), proteases, and phospholipases, alongside antifungal chitinase and endo-β-1,3-glucanase. The biomolecular metabolic gene types and gene copy numbers of strain TH7-28 T were significantly higher than those of other Paenibacillus genus, indicating its robust capacity for macromolecule degradation. The nitrogen-fixing potential of strain TH7-28 T was confirmed via nifH/D/K genes. Phosphorus activation capacity was demonstrated through ps t S/C/A/B -mediated inorganic uptake and phospholipase-driven organic solubilization. Experimental assays further demonstrated significant enzymatic activities of chitinase (8.12 ± 0.66 × 10 –3 U/mL), β-1,3-glucanase (0.023 ± 0.004 U/mL), and nitrogenase (0.164 ± 0.006 U/mL), with concurrent hydrolysis of cellulose, starch, casein, chitin and lecithin. Through the wheat germination experiment, it has been confirmed that this strain significantly enhanced both the seed germination rate and stem length, thereby establishing a solid foundation for subsequent research on its practical applications. Conclusion Strain TH7-28 T , isolated from lake sediment, was identified to represent a novel species designated Paenibacillus lacisediminis sp. nov. The strain exhibits multifunctional hydrolase activities, antifungal enzyme synthesis, nitrogen fixation, phosphorus solubilization and plant growth promoting. The findings confirm Paenibacillus lacisediminis sp. nov. as a biotechnologically promising strain for sustainable agriculture, furthermore enriching the functional repertoire of Paenibacillus genus.

The aim of this study was to evaluate the accuracy of the single upper‐arm cuff oscillometric blood pressure (BP) monitor RBP‐9801 developed for office and home BP measurement in the general population according to the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization (AAMI/ESH/ISO) Universal Standard (ISO 81060–2:2018). Subjects were recruited to fulfil the age, gender, BP and cuff distribution criteria of the AAMI/ESH/ISO Universal Standard in general population using the same arm sequential BP measurement method. A total of 105 subjects were recruited and 85 were analyzed. For validation criterion 1, the mean ± SD of the differences between the test device and reference BP readings was 2.3 ± 6.4/3.1 ± 5.8 mmHg (systolic/diastolic). For criterion 2, the SD of the mean BP differences between the test device and reference BP per subject was 5.24/5.03 mmHg (systolic/diastolic). The conclusion is that the RBP‐9801 oscillometric device for office and home BP measurement fulfilled all the requirements of the AAMI/ESH/ISO Universal Standard (ISO 81060–2:2018) in the general population and can be recommended for clinic and self‐use at home.

Background Walnut ( Juglans regia ) is an important tree cultivated worldwide and is exposed to a series of both abiotic and biotic stress during their life-cycles. The heat stress transcription factors (HSFs) play a crucial role in plant response to various stresses by regulating the expression of stress-responsive genes. HSF genes are classified into 3 classes: HSFA , HSFB , and HSFC . HSFA gene has transcriptional activation function and is the main regulator of high temperature-induced gene expression. HSFB gene negatively regulates plant resistance to drought and NaCl. And HSFC gene may be involved in plant response to various stresses. There are some reports about the HSF family in herbaceous plants, however, there are no reports about the HSFs in walnut. Result In this study, based on the complete genome sequencing of walnut, the bioinformatics method was used and 29 HSF genes were identified. These HSF s covered 18 HSFA , 9 HSFB , and 2 HSFC genes. Phylogenetic analysis of these HSF proteins along with those from Arabidopsis thaliana showed that the HSFs in the two species are closely related to each other and have different evolutionary processes. The distribution of conserved motifs and the sequence analysis of HSF genes family indicated that the members of the walnut HSFs are highly conserved. Quantitative Real-Time PCR (qRT-PCR) analysis revealed that the most of walnut HSFs were expressed in the walnut varieties of ‘Qingxiang’ and ‘Xiangling’ under high temperature (HT), high salt and drought stress, and some JrHSFs expression pattern are different between the two varieties. Conclusion The complex HSF genes family from walnut was confirmed by genome-wide identification, evolutionary exploration, sequence characterization and expression analysis. This research provides useful information for future studies on the function of the HSF genes and molecular mechanism in plant stress response.

Aims Heart failure (HF) with supranormal ejection fraction (HFsnEF) represents a distinct clinical entity characterized by limited treatment options and an unfavourable prognosis. Revealing its phenotypic diversity is crucial for understanding disease mechanism and optimizing patient management. We aim to identify phenotypic subgroups in HFsnEF using unsupervised clustering analysis. Methods Consecutive hospitalized patients with a diagnosis of HF and a left ventricular ejection fraction ≥65% at baseline echocardiographic evaluations were included for analysis. We conducted unsupervised hierarchical clustering analysis on principal components (HCPC) to identify HFsnEF phenogroups using mixed data variables including demographics, HF duration, vital signs, anthropometrics, smoking/drinking status, HF aetiology, comorbid diseases, laboratory tests and echocardiographic parameters. We then employed decision tree modelling to identify parameters capable of distinguishing distinct clusters. Clinical outcomes, including all‐cause death, cardiovascular (CV) death and CV readmission for different clusters, were examined. Results Three mutually exclusive clusters were identified from the cohort of 221 HFsnEF patients. Cluster 1 (52.5%) predominantly consisted of patients with valvular heart disease, who had larger cardiac chambers and a higher prevalence of atrial fibrillation/atrial flutter. Cluster 2 (26.2%) primarily comprised older ischaemic patients with a higher prevalence of metabolic comorbidities. Cluster 3 (21.3%) were mainly hypertrophic cardiomyopathy patients. Two clinical variables were identified that could be used to group all HFsnEF patients into one of the clusters; they were HF aetiology and comorbid diabetes. During the median follow‐up of 53.4 months, 46 (20.8%) all‐cause deaths occurred, among them 39 of CV causes. Seventy (31.7%) patients experienced CV readmissions. Three clusters showed distinct differences in mortality outcomes, with Cluster 1 exhibiting the highest risk of all‐cause mortality [Cluster 1 vs. Cluster 2: adjusted hazard ratio (aHR) = 3.32, P = 0.022; Cluster 1 vs. Cluster 3: aHR = 3.81, P = 0.036; Cluster 2 vs. Cluster 3: aHR = 1.15, P = 0.865] and CV mortality (Cluster 1 vs. Cluster 2: aHR = 3.73, P = 0.022; Cluster 1 vs. Cluster 3: aHR = 4.27, P = 0.020; Cluster 2 vs. Cluster 3: aHR = 1.15, P = 0.870). CV readmission risk was comparable among the three clusters (Cluster 1 vs. Cluster 2: aHR = 0.82, P = 0.590; Cluster 1 vs. Cluster 3: aHR = 1.04, P = 0.900; Cluster 2 vs. Cluster 3: aHR = 1.28, P = 0.580). Conclusions In a heterogeneous HFsnEF cohort, three clusters were identified by unsupervised HCPC with distinct clinical characteristics and outcomes.