Emerging Roles and Therapeutic Applications of Arachidonic Acid Pathways in Cardiometabolic Diseases.

Cardiometabolic disease has become a major health burden worldwide, with sharply increasing prevalence but highly limited therapeutic interventions. Emerging evidence has revealed that arachidonic acid derivatives and pathway factors link metabolic disorders to cardiovascular risks and intimately participate in the progression and severity of cardiometabolic diseases. In this review, we systemically summarized and updated the biological functions of arachidonic acid pathways in cardiometabolic diseases, mainly focusing on heart failure, hypertension, atherosclerosis, nonalcoholic fatty liver disease, obesity, and diabetes. We further discussed the cellular and molecular mechanisms of arachidonic acid pathway-mediated regulation of cardiometabolic diseases and highlighted the emerging clinical advances to improve these pathological conditions by targeting arachidonic acid metabolites and pathway factors.

Viscosity of Ionic Liquids: Theories and Models.

Ionic liquids (ILs) offer a wide range of promising applications due to their unique and designable properties compared to conventional solvents. Further development and application of ILs require correlating/predicting their pressure-viscosity-temperature behavior. In this review, we firstly introduce methods for calculation of thermodynamic inputs of viscosity models. Next, we introduce theories, theoretical and semi-empirical models coupling various theories with EoSs or activity coefficient models, and empirical and phenomenological models for viscosity of pure ILs and IL-related mixtures. Our modelling description is followed immediately by model application and performance. Then, we propose simple predictive equations for viscosity of IL-related mixtures and systematically compare performances of the above-mentioned theories and models. In concluding remarks, we recommend robust predictive models for viscosity at atmospheric pressure as well as proper and consistent theories and models for P-η-T behavior. The work that still remains to be done to obtain the desired theories and models for viscosity of ILs and IL-related mixtures is also presented. The present review is structured from pure ILs to IL-related mixtures and aims to summarize and quantitatively discuss the recent advances in theoretical and empirical modelling of viscosity of ILs and IL-related mixtures.

Lower contact force predicts right pulmonary vein carina breakthrough after ablation index-guided pulmonary vein isolation using high-power short-duration.

INTRODUCTION: Carina breakthrough (CB) at the right pulmonary vein (RPV) can occur after circumferential pulmonary vein isolation (PVI) due to epicardial bridging or transient tissue edema. High-power short-duration (HPSD) ablation may increase the incidence of RPV CB. Currently, the surrogate of ablation parameters to predict RPV CB is not well established. This study investigated predictors of RPV CB in patients undergoing ablation index (AI)-guided PVI with HPSD. METHODS: The study included 62 patients with symptomatic atrial fibrillation (AF) who underwent AI-guided PVI using HPSD. Patients were categorized into two groups based on the presence or absence of RPV CB. Lesions adjacent to the RPV carina were assessed, and CB was confirmed through residual voltage, low voltage along the ablation lesions, and activation wavefront propagation. RESULTS: Out of the 62 patients, 21 (33.87%) experienced RPV CB (Group 1), while 41 (66.13%) achieved first-pass RPV isolation (Group 2). Despite similar AI and HPSD, patients with RPV CB had lower contact force (CF) at lesions adjacent to the RPV carina. Receiver operating characteristic (ROC) curve analysis identified CF < 10.5 g as a predictor of RPV CB, with 75.7% sensitivity and 56.2% specificity (area under the curve: 0.714). CONCLUSION: In patients undergoing AI-guided PVI with HPSD, lower CF adjacent to the carina was associated with a higher risk of RPV CB. These findings suggest that maintaining higher CF during ablation in this region may reduce the occurrence of RPV CB.

Fibroblasts Drive Metabolic Reprogramming in Pacemaker Cardiomyocytes.

BACKGROUND: The sino atrial node (SAN) is characterized by the microenvironment of pacemaker cardiomyocytes (PCs) encased with fibroblasts. An altered microenvironment leads to rhythm failure. Operable cell or tissue models are either generally lacking or difficult to handle. The biological process behind the milieu of SANs to evoke pacemaker rhythm is unknown. We explored how fibroblasts interact with PCs and regulate metabolic reprogramming and rhythmic activity in the SAN. METHODS: Tbx18 (T-box transcription factor 18)-induced PCs and fibroblasts were used for cocultures and engineered tissues, which were used as the in vitro models to explore how fibroblasts regulate the functional integrity of SANs. RNA-sequencing, metabolomics, and cellular and molecular techniques were applied to characterize the molecular signals underlying metabolic reprogramming and identify its critical regulators. These pathways were further validated in vivo in rodents and induced human pluripotent stem cell-derived cardiomyocytes. RESULTS: We observed that rhythmicity in Tbx18-induced PCs was regulated by aerobic glycolysis. Fibroblasts critically activated metabolic reprogramming and aerobic glycolysis within PCs, and, therefore, regulated pacemaker activity in PCs. The metabolic reprogramming was attributed to the exclusive induction of Aldoc (aldolase c) within PCs after fibroblast-PC integration. Fibroblasts activated the integrin-dependent mitogen-activated protein kinase-E2F1 signal through cell-cell contact and turned on Aldoc expression in PCs. Interruption of fibroblast-PC interaction or Aldoc knockdown nullified electrical activity. Engineered Tbx18-PC tissue sheets were generated to recapitulate the microenvironment within SANs. Aldoc-driven rhythmic machinery could be replicated within tissue sheets. Similar machinery was faithfully validated in de novo PCs of adult mice and rats, and in human PCs derived from induced pluripotent stem cells. CONCLUSIONS: Fibroblasts drive Aldoc-mediated metabolic reprogramming and rhythmic regulation in SANs. This work details the cellular machinery behind the complex milieu of vertebrate SANs and opens a new direction for future therapy.

Feasibility of Auto-Quantified Epicardial Adipose Tissue in Predicting Atrial Fibrillation Recurrence After Catheter Ablation.

BACKGROUND: The aim of this study was to build an auto-segmented artificial intelligence model of the atria and epicardial adipose tissue (EAT) on computed tomography (CT) images, and examine the prognostic significance of auto-quantified left atrium (LA) and EAT volumes for AF.Methods and Results: This retrospective study included 334 patients with AF who were referred for catheter ablation (CA) between 2015 and 2017. Atria and EAT volumes were auto-quantified using a pre-trained 3-dimensional (3D) U-Net model from pre-ablation CT images. After adjusting for factors associated with AF, Cox regression analysis was used to examine predictors of AF recurrence. The mean (±SD) age of patients was 56±11 years; 251 (75%) were men, and 79 (24%) had non-paroxysmal AF. Over 2 years of follow-up, 139 (42%) patients experienced recurrence. Diabetes, non-paroxysmal AF, non-pulmonary vein triggers, mitral line ablation, and larger LA, right atrium, and EAT volume indices were linked to increased hazards of AF recurrence. After multivariate adjustment, non-paroxysmal AF (hazard ratio [HR] 0.6; 95% confidence interval [CI] 0.4-0.8; P=0.003) and larger LA-EAT volume index (HR 1.1; 95% CI 1.0-1.2; P=0.009) remained independent predictors of AF recurrence. CONCLUSIONS: LA-EAT volume measured using the auto-quantified 3D U-Net model is feasible for predicting AF recurrence after CA, regardless of AF type.

Polo-like Kinase-1 Regulates Myc Stabilization and Activates a Feedforward Circuit Promoting Tumor Cell Survival.

MYCN amplification in human cancers predicts poor prognosis and resistance to therapy. However, pharmacological strategies that directly target N-Myc, the protein encoded by MYCN, remain elusive. Here, we identify a molecular mechanism responsible for reciprocal activation between Polo-like kinase-1 (PLK1) and N-Myc. PLK1 specifically binds to the SCFFbw7 ubiquitin ligase, phosphorylates it, and promotes its autopolyubiquitination and proteasomal degradation, counteracting Fbw7-mediated degradation of N-Myc and additional substrates, including cyclin E and Mcl1. Stabilized N-Myc in turn directly activates PLK1 transcription, constituting a positive feedforward regulatory loop that reinforces Myc-regulated oncogenic programs. Inhibitors of PLK1 preferentially induce potent apoptosis of MYCN-amplified tumor cells from neuroblastoma and small cell lung cancer and synergistically potentiate the therapeutic efficacies of Bcl2 antagonists. These findings reveal a PLK1-Fbw7-Myc signaling circuit that underlies tumorigenesis and validate PLK1 inhibitors, alone or with Bcl2 antagonists, as potential effective therapeutics for MYC-overexpressing cancers.

Tripartite motif 38 alleviates the pathological process of NAFLD-NASH by promoting TAB2 degradation.

Nonalcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease worldwide, without any Food and Drug Administration-approved pharmacological intervention in clinic. Trim38, as an important member of the TRIM (tripartite motif-containing) family, was largely reported to be involved in the regulation of innate immune and inflammatory responses. However, the functional roles of TRIM38 in NAFLD remain largely unknown. Here, the expression of TRIM38 was first detected in liver samples of both NAFLD mice model and patients diagnosed with NAFLD. We found that TRIM38 expression was downregulated in NAFLD liver tissues compared with normal liver tissues. Genetic Trim38-KO in vivo showed that TRIM38 depletion deteriorated the high-fat diet and high fat and high cholesterol diet-induced hepatic steatosis and high fat and high cholesterol diet-induced liver inflammation and fibrosis. In particular, we found that the effects of hepatocellular lipid accumulation and inflammation induced by palmitic acid and oleic acid were aggravated by TRIM38 depletion but mitigated by TRIM38 overexpression in vitro. Mechanically, RNA-Seq analysis demonstrated that TRIM38 ameliorated nonalcoholic steatohepatitis progression by attenuating the activation of MAPK signaling pathway. We further found that TRIM38 interacted with transforming growth factor-ß-activated kinase 1 binding protein 2 and promoted its protein degradation, thus inhibiting the transforming growth factor-ß-activated kinase 1-MAPK signal cascades. In summary, our study revealed that TRIM38 could suppress hepatic steatosis, inflammatory, and fibrosis in NAFLD via promoting transforming growth factor-ß-activated kinase 1 binding protein 2 degradation. TRIM38 could be a potential target for NAFLD treatment.

Insights into ZmWAKL in maize kernel development: genome-wide investigation and GA-mediated transcription.

BACKGROUND: The functional roles of the Wall Associated Kinase (WAK) and Wall Associated Kinase Like (WAKL) families in cellular expansion and developmental processes have been well-established. However, the molecular regulation of these kinases in maize development is limited due to the absence of comprehensive genome-wide studies. RESULTS: Through an in-depth analysis, we identified 58 maize WAKL genes, and classified them into three distinct phylogenetic clusters. Moreover, structural prediction analysis showed functional conservation among WAKLs across maize. Promoter analysis uncovered the existence of cis-acting elements associated with the transcriptional regulation of ZmWAKL genes by Gibberellic acid (GA). To further elucidate the role of WAKL genes in maize kernels, we focused on three highly expressed genes, viz ZmWAKL38, ZmWAKL42 and ZmWAKL52. Co-expression analyses revealed that their expression patterns exhibited a remarkable correlation with GA-responsive transcription factors (TF) TF5, TF6, and TF8, which displayed preferential expression in kernels. RT-qPCR analysis validated the upregulation of ZmWAKL38, ZmWAKL42, ZmWAKL52, TF5, TF6, and TF8 following GA treatment. Additionally, ZmWAKL52 showed significant increase of transcription in the present of TF8, with ZmWAKL52 localizing in both the plasma membrane and cell wall. TF5 positively regulated ZmWAKL38, while TF6 positively regulated ZmWAKL42. CONCLUSIONS: Collectively, these findings provide novel insights into the characterization and regulatory mechanisms of specific ZmWAKL genes involved in maize kernel development, offering prospects for their utilization in maize breeding programs.

Switch-associated protein 70 protects against nonalcoholic fatty liver disease through suppression of TAK1.

BACKGROUND AND AIMS: NAFLD is a progressive disease without known effective drug treatments. Switch-associated protein 70 (SWAP70) is a guanine nucleotide exchange factor that participates in the regulation of many cellular processes. However, the role of SWAP70 in NAFLD remains unclear. This study aimed to identify the function and mechanism of SWAP70 in NAFLD. APPROACH AND RESULTS: The results showed that the expression of SWAP70 was significantly increased in mice and hepatocytes after metabolic stimulation. Overexpression of SWAP70 in hepatocytes suppressed lipid deposition and inflammation, and SWAP70 knockdown created the inverse effect. Using hepatocyte-specific Swap70 knockout and overexpression mice fed a high-fat, high-cholesterol diet, we demonstrated that SWAP70 suppressed the progression of nonalcoholic steatohepatitis by inhibiting lipid accumulation, inflammatory response, and fibrosis. Mechanically, RNA sequencing analysis and immunoprecipitation assays revealed that SWAP70 inhibited the interaction between transforming growth factor ß-activated kinase 1 (TAK1) binding protein 1 and TAK1 and sequentially suppressed the phosphorylation of TAK1 and subsequent c-Jun N-terminal kinase/P38 signaling. Inhibition of TAK1 activation blocked hepatocyte lipid deposition and inflammation caused by SWAP70 knockdown. CONCLUSIONS: SWAP70 is a protective molecule that can suppress the progression of NAFLD by inhibiting hepatic steatosis and inflammation. SWAP70 may be important for mitigating the progression of NAFLD.

N-acetylgalactosaminyltransferase-4 protects against hepatic ischemia/reperfusion injury by blocking apoptosis signal-regulating kinase 1 N-terminal dimerization.

BACKGROUND AND AIMS: Ischemia-reperfusion (I/R) injury is an inevitable complication of liver transplantation (LT) and compromises its prognosis. Glycosyltransferases have been recognized as promising targets for disease therapy, but their roles remain open for study in hepatic I/R (HIR) injury. Here, we aim to demonstrate the exact function and molecular mechanism of a glycosyltransferase, N-acetylgalactosaminyltransferase-4 (GALNT4), in HIR injury. APPROACH AND RESULTS: By an RNA-sequencing data-based correlation analysis, we found a close correlation between GALNT4 expression and HIR-related molecular events in a murine model. mRNA and protein expression of GALNT4 were markedly up-regulated upon reperfusion surgery in both clinical samples from subjects who underwent LT and in a mouse model. We found that GALNT4 deficiency significantly exacerbated I/R-induced liver damage, inflammation, and cell death, whereas GALNT4 overexpression led to the opposite phenotypes. Our in-depth mechanistic exploration clarified that GALNT4 directly binds to apoptosis signal-regulating kinase 1 (ASK1) to inhibit its N-terminal dimerization and subsequent phosphorylation, leading to a robust inactivation of downstream c-Jun N-terminal kinase (JNK)/p38 and NF-κB signaling. Intriguingly, the inhibitory capacity of GALNT4 on ASK1 activation is independent of its glycosyltransferase activity. CONCLUSIONS: GALNT4 represents a promising therapeutic target for liver I/R injury and improves liver surgery prognosis by inactivating the ASK1-JNK/p38 signaling pathway.

Characterization and identification of atrial fibrillation drivers in patients with nonparoxysmal atrial fibrillation using simultaneous amplitude frequency electrogram transform.

INSTRUCTION: We hypothesized that real-time simultaneous amplitude frequency electrogram transform (SAFE-T) during sinus rhythm (SR) is able to identify and characterize the drivers of atrial fibrillation (AF) in nonparoxysmal (NP) AF. METHODS: Twenty-one NPAF patients (85.71% males, mean age 52 years old) underwent substrate mapping during SR (SAFE-T and voltage) and during AF (complex fractionated atrial electrograms [CFAE] and similarity index [SI]). After pulmonary veins isolation, extensive substrate ablation was performed with the endpoint of procedural termination or elimination of all SI sites (>63% similarities). Sites with procedural termination and non-termination sites were tagged for postablation SR analysis using SAFE-T. RESULTS: In 74 CFAE sites identified (average of 3 ± 2 sites per person), 28 (37.84%) were identified as termination sites demonstrating a high SI compared with the non-termination sites (80.11 ± 9.57% vs. 45.96 ± 13.38%, p < .001) during AF. During SR, these termination sites have high SAFE-T values and harbor a highly resonant, localized, repetitive high frequency components superimposed in the low frequency components compared with non-termination sites (5.70 ± 3.04 vs. 1.49 ± 1.66 Hz·mV, p < .001). In the multivariate analysis, the termination sites have higher SAFE-T and SI value (p < .001). CONCLUSION: AF procedural termination sites harbored signal characteristics of repetitive, high frequency component of individualized electrogram during SR, which can be masked by the low frequency fractionated electrogram and are difficult to see from the bipolar electrogram. Thus, SAFE-T mapping is feasible in identifying and characterizing sites of AF drivers.

Insight of electrocardiographic and electrophysiological parameters on the left ventricular function in patients with ventricular arrhythmia from left ventricular summit.

INTRODUCTION: Ventricular arrhythmia (VA) commonly originate from the left ventricular summit (LVS) and results in left ventricular (LV) dysfunction in some patients; however, factors related to LV cardiomyopathy have not been well elucidated. Therefore, this study aimed to investigate the risk factors for LV cardiomyopathy and the outcomes of patients with LVS VA. METHODS: Between 2013 and 2018, a total of 139 patients (60.7% men; mean age 53.2 ± 13.9 years old) underwent catheter ablation for LVS VA in two centers. Detailed patient demographics, electrocardiograms, electrophysiological characteristics, and clinical outcomes were analyzed. LV cardiomyopathy was defined as left ventricular ejection fraction (LVEF) <50%. RESULTS: Acute procedural success was achieved in 92.8% of patients. There were 40 patients (28.8%) with LV cardiomyopathy, and the mean LVEF improved from 37.5 ± 9.3% to 48.5 ± 10.2% after ablation (p < .001). After multivariate analysis, the independent factors of LV dysfunction were wider QRS duration (QRSd) of the VA (odds ratio [OR] 1.02; 95% confidence interval [CI]: 1.00-1.04; p = .046) and the absolute earliest activation time discrepancy (AEAD) between epicardium and endocardium (OR 1.05; 95% CI: 1.00-1.09; p = .048). After ablation, the LV function was completely recovered in 20 patients (50%). The factors for LV dysfunction without recovery included wider premature ventricular complex (PVC) QRSd (OR 1.09; 95% CI: 1.02-1.17; p = .012) and poorer LVEF (OR 0.85; 95% CI: 0.74-0.97; p = .020). CONCLUSION: In patients with VA from the LVS, PVC QRSd and AEAD are factors associated with deteriorating LV systolic function. Catheter ablation can reverse LV remodeling. Narrower QRSd and better LVEF are associated with better recovery of LV function after ablation.

Factors predicting the progression from paroxysmal to persistent atrial fibrillation despite an index catheter ablation.

INTRODUCTION: Despite undergoing an index ablation, some patients progress from paroxysmal atrial fibrillation (PAF) to persistent AF (PersAF), and the mechanism behind this is unclear. The aim of this study was to investigate the predictors of progression to PersAF after catheter ablation in patients with PAF. METHODS: This study included 400 PAF patients who underwent an index ablation between 2015 and 2019. The patients were classified into three groups based on their outcomes: Group 1 (PAF to sinus rhythm, n = 226), Group 2 (PAF to PAF, n = 146), and Group 3 (PAF to PersAF, n = 28). Baseline and procedural characteristics were collected, and predictors for AF recurrence and progression were evaluated. RESULTS: The mean age of the patients was 58.4 ± 11.1 years, with 272 males. After 3 years of follow-up, 7% of the PAF cases recurred and progressed to PersAF despite undergoing an index catheter ablation. In the multivariable analysis, a larger left atrial (LA) diameter and the presence of non-pulmonary vein (PV) triggers during the index procedure independently predicted recurrence. Moreover, a larger LA diameter, the presence of non-PV triggers, and a history of thyroid disease independently predicted AF progression. CONCLUSION: The progression from PAF to PersAF after catheter ablation is associated with a larger LA diameter, history of thyroid disease, and the presence of non-PV triggers. Meticulous preprocedural evaluation, patient selection, and comprehensive provocation tests during catheter ablation are recommended.

Harnessing cell reprogramming for cardiac biological pacing.

Electrical impulses from cardiac pacemaker cardiomyocytes initiate cardiac contraction and blood pumping and maintain life. Abnormal electrical impulses bring patients with low heart rates to cardiac arrest. The current therapy is to implant electronic devices to generate backup electricity. However, complications inherent to electronic devices remain unbearable suffering. Therefore, cardiac biological pacing has been developed as a hardware-free alternative. The approaches to generating biological pacing have evolved recently using cell reprogramming technology to generate pacemaker cardiomyocytes in-vivo or in-vitro. Different from conventional methods by electrical re-engineering, reprogramming-based biological pacing recapitulates various phenotypes of de novo pacemaker cardiomyocytes and is more physiological, efficient, and easy for clinical implementation. This article reviews the present state of the art in reprogramming-based biological pacing. We begin with the rationale for this new approach and review its advances in creating a biological pacemaker to treat bradyarrhythmia.

Ablation of atrial fibrillation and dementia risk reduction during long-term follow-up: a nationwide population-based study.

AIMS: This study investigated the epidemiological characteristics of new-onset dementia in patients with atrial fibrillation (AF) and the association of catheter ablation with different subtypes of dementia. METHODS AND RESULTS: We conducted a population-based, retrospective cohort study using data from the Taiwan National Health Insurance Research Database. In total, 136 774 patients without a history of dementia were selected after 1:1 propensity score matching based on age (with AF vs. without AF). A competing risk model was used to investigate the three subtypes of dementia: Alzheimer's disease, vascular dementia, and other/mixed dementia. Inverse probability of treatment weighting (IPTW) was performed to minimize the impact on dementia risk due to the imbalanced baseline characteristics. After a median follow-up period of 6.6 years, 8704 events of new-onset dementia occurred. Among all AF patients developing dementia, 73% were classified as having Alzheimer's disease, 16% as having vascular dementia, and 11% as having other/mixed dementia. The cumulative incidence of dementia in AF patients was higher than those without AF (log-rank test: P < 0.001 for both before and after IPTW). In patients with AF undergoing catheter ablation, the total dementia risk decreased significantly [P = 0.015, hazard ratio (HR): 0.74, 95% confidence interval (CI): 0.58-0.94] after multivariable adjustment, but not for the subtype of vascular dementia (P = 0.59, HR: 0.86, 95% CI: 0.49-1.50). CONCLUSION: Patients with AF have a higher incidence of all types of dementia, including Alzheimer's disease, vascular dementia, and a mixed type of dementia. Alzheimer's disease is less likely to occur in patients with AF undergoing catheter ablation.

Comparison of Long-Term Clinical Outcomes Between Segmental and Circumferential Pulmonary Vein Isolation in Patients Undergoing Repeat Atrial Fibrillation Ablation.

BACKGROUND: Circumferential pulmonary vein isolation (CPVI) has supplanted segmental PVI (SPVI) as standard procedure for atrial fibrillation (AF). However, there is limited evidence examining the efficacy of these strategies in redo ablations. In this study, we investigated the difference in recurrence rates between SPVI and CPVI in redo ablations for PV reconnection.Methods and Results: This study retrospectively enrolled 543 patients who had undergone AF ablation between 2015 and 2017. Among them, 167 patients (30.8%, including 128 male patients and 100 patients with paroxysmal AF) underwent redo ablation for recurrent AF. Excluding 26 patients without PV reconnection, 141 patients [90 patients of SPVI (Group 1) and 51 patients of CPVI (Group 2)] were included. The AF-free survival rates were 53.3% and 56.9% in Group 1 and Group 2, respectively (P=0.700). The atrial flutter (AFL)-free survival rates were 90% and 100% in Group 1 and Group 2, respectively (P=0.036). The ablation time was similar between groups, and there no major complications were observed. CONCLUSIONS: For redo AF ablation procedures, SPVI and CPVI showed similar outcomes, except for a higher AFL recurrence rate for SPVI after long-term follow-up (>2 years). This may be due to a higher probability of residual PV gaps causing reentrant AFL.

Fractal complexity alternations in paroxysmal atrial fibrillation patients with and without recurrence after pulmonary vein isolation.

BACKGROUND: Pulmonary vein isolation (PVI) is a cornerstone therapy for paroxysmal atrial fibrillation (PAF). The variations in nonlinear heart rate variability (HRV) between patients with and without recurrences remain unclear. We aimed to characterize the nonlinear HRV before and after PVI in patients with and without recurrence. METHODS: Twenty-five drug-refractory PAF patients (56.0 ± 9.1 years old, 20 males) who received PVI were enrolled. Holter electrocardiography were performed before, 1-3, and 6-12 months after PVI. After 8.2 ± 2.5 months of follow-ups after PVI, patients were divided into two groups: the recurrence (n = 8) and non-recurrence (n = 17) groups. Linear and nonlinear HRV variables were analyzed, including the Poincaré Plot analysis and the Detrended Fluctuation Analysis (DFA). RESULTS: The non-recurrence group, but not the recurrence group, had decreased high-frequency component (HF), the root mean square of successive RR interval differences (RMSSD), and the Poincaré Plot index SD1 1-3 months after PVI and increased DFAslope2 6-12 months after PVI. The non-recurrence group's LF/HF ratio and DFAslope1 decreased significantly 1-3 and 6-12 months after PVI, respectively, whereas there was no significant change in the recurrence group after PVI. CONCLUSIONS: Significantly reduced vagal tone 1-3 months after PVI, increased long-term fractal complexity 6-12 months after PVI, and decreased sympathetic tone as well as short-term fractal complexity 1-3 and 6-12 months after PVI led to a better AF-free survival after PVI. These findings suggest that neuromodulation and heart rate dynamics play crucial roles in AF recurrence following PVI.

The Role of Large Animal Models in Cardiac Regeneration Research Using Human Pluripotent Stem Cell-Derived Cardiomyocytes.

PURPOSE OF REVIEW: Heart failure leads to high mortality. The failing myocardium cannot often be rescued as heart regeneration is mostly compromised by disease progress. Stem cell therapy is a strategy under development to replace the impaired myocardium for recovery after heart injury. RECENT FINDINGS: Many studies have provided evidence of the beneficial effects of pluripotent stem cell-derived cardiomyocyte (CM) implantation into diseased rodent hearts, but there are still many challenges and limitations to replicating the same effects in large animal models for preclinical validation. In this review, we summarize progress in the use of pluripotent stem cell-derived CMs in large animal models based on three key parameters: species selection, cell source, and delivery. Most importantly, we discuss the current limitations and challenges that need to be solved to advance this technology to the translational stage.

Shared decision making for anticoagulation reduces anxiety and improves adherence in patients with atrial fibrillation.

BACKGROUND: Treatment with oral anticoagulants (OACs) could prevent stroke in atrial fibrillation (AF), but side effects developed due to OACs may cause patients anxiety during decision making. This study aimed to investigate whether shared decision making (SDM) reduces anxiety and improves adherence to stroke prevention measures in patients with AF. METHODS: A one-group pretest-posttest design using a questionnaire survey was applied at the outpatient cardiology clinic between July 2019 until September 2020. A Patient Decision Aid (PDA) tool was used for the completion of the questionnaire survey after health education and counseling. Ten questions were included for patients' recognition of SDM, and a 5-point scoring method was used, where "very much" was scored as 5 points, and "totally not" was scored as 1 point. RESULTS: Fifty-two patients with AF were enrolled. In terms of patients' recognition of SDM, points of more than 4.17 out of 5 were noted, indicating recognition above the level of "very much." The patients' anxiety scores before SDM were 3.56 (1.2), with a decrease of 0.64 points (p < 0.001) to 2.92 (1.3) after SDM. After SDM, the number of patients who decided to take OAC increased from 76.9% to 88.5%, and the 15.4% answering "unclear" decreased to 1.9% (p = 0.006). The patients' anxiety levels after SDM were associated with gender (p = 0.025). CONCLUSIONS: The approach using SDM enhanced our understanding of the pros and cons of OAC treatment and, in patients with AF, decreased anxiety about therapeutic decisions and increased willingness to accept treatment options.

The role of apoptosis in the pathogenesis of osteoarthritis.

PURPOSE: Apoptosis is an important physiological process, making a great difference to development and tissue homeostasis. Osteoarthritis (OA) is a chronic joint disease characterized by degeneration and destruction of articular cartilage and bone hyperplasia. This purpose of this study is to provide an updated review of the role of apoptosis in the pathogenesis of osteoarthritis. METHODS: A comprehensive review of the literature on osteoarthritis and apoptosis was performed, which mainly focused on the regulatory factors and signaling pathways associated with chondrocyte apoptosis in osteoarthritis and other pathogenic mechanisms involved in chondrocyte apoptosis. RESULTS: Inflammatory mediators such as reactive oxygen species (ROS), nitric oxide (NO), IL-1ß, tumor necrosis factor-α (TNF-α), and Fas are closely related to chondrocyte apoptosis. NF-κB signaling pathway, Wnt signaling pathway, and Notch signaling pathway activate proteins and gene targets that promote or inhibit the progression of osteoarthritis disease, including chondrocyte apoptosis and ECM degradation. Long non-coding RNAs (LncRNAs) and microRNAs (microRNAs) have gradually replaced single and localized research methods and become the main research approaches. In addition, the relationship between cellular senescence, autophagy, and apoptosis was also briefly explained. CONCLUSION: This review offers a better molecular delineation of apoptotic processes that may help in designing new therapeutic options for OA treatment.