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Novel circular ssDNA genomes have recently been detected in animals and in the environment using metagenomic and high-throughput sequencing approaches. In this study, five full-length circular ssDNA genomes were recovered from bat faecal samples using inverse PCR with sequences designed based on circovirus-related sequences obtained from Solexa sequencing data derived from a random amplification method. These five sequences shared a similar genomic organization to circovirus or the recently proposed cyclovirus of the family Circoviridae. The newly obtained circovirus/cyclovirus-like genomes ranged from 1741 to 2177 bp, and each consisted of two major ORFs, ORF1 and ORF2, encoding putative replicase (Rep) and capsid (Cap) proteins, respectively. The potential stem-loop region was predicted in all five genomes, and three of them had the typical conserved nonanucleotide motif of cycloviruses. A set of primers targeting the conserved Rep region was designed and used to detect the prevalence of circovirus/ cyclovirus sequences in individual bats. Among 199 samples tested, 47 were positive (23.6 %) for the circovirus genome and two (1.0 %) were positive for the cyclovirus genome. In total, 48 partial Rep sequences plus the five full-length genomes were obtained in this study. Detailed analysis indicated that these sequences are distantly related to known circovirus/cyclovirus genomes and may represent 22 novel species that belong to the family Circoviridae.

Objectives: Left ventricular remodeling is a frequent complication of hypertension with no therapeutic treatment available for the subsequent onset of myocardial fibrosis. Pirfenidone is an antifibrotic small-molecular-size drug with anti-inflammatory properties that is used as a treatment for fibrotic diseases, but its effects on hypertension-induced myocardial fibrosis are unknown. Therefore, we tested whether pirfenidone could ameliorate hypertension-induced left ventricular remodeling and whether hypertension-induced NLRP3 (Nod-like receptor pyrin domain containing 3), a critical protein in NLRP3 inflammasome formation, is involved in the therapeutic mechanism. Methods: A TAC-induced mouse model of hypertension and left ventricular hypertrophy was treated with pirfenidone, and survival, collagen deposition by histopathologic examination, heart function by echocardiography, concentrations of fibrosis-related inflammatory cytokines TGF-β₁, IL-1β in heart homogenate and in vitro cell cultures by ELISA, levels of ROS and inflammatory cells by flow cytometry, and levels of NLRP3 by Western blotting and immunohistochemistry were measured. Results: Pirfenidone increased the survival rate and attenuated myocardial fibrosis and inflammatory mediators in the TAC-induced hypertension-complicated left ventricular remodeling mouse model. The inhibition of NLRP3 expression by pirfenidone attenuated the expression of IL-1β and IL-1β-induced inflammatory and profibrotic responses. Conclusions: Pirfenidone may be useful in the treatment of hypertension-induced myocardial fibrosis by inhibiting NLRP3-induced inflammation and fibrosis.

Background Left bundle branch area pacing (LBBaP) is a new physiological pacing strategy that produces comparable clinical effects to His bundle pacing (HBP). Objective The purpose of this study was to investigate the immediate clinical outcomes of LBBaP vs RVP. Methods and Results From April 2018 to September 2018, we included 44 patients under continuous pacemaker implantation. Patients were randomly divided into the LBBaP group and conventional RVP group. Compared to the RVP group, the LBBaP group displayed significantly increased operative (90.10 ± 19.68 minutes vs 61.57 ± 6.62 minutes, P < .001) and X‐ray exposure times (15.55 ± 5.62 minutes vs 4.67 ± 2.06 minutes, P < .001). The lead threshold of the LBBaP group was increased (0.68 ± 0.20 mV vs 0.51 ± 0.0 mV, P = .001), while the R‐wave amplitude and ventricular impedance did not significantly differ between the two groups. The conventional RVP procedure significantly widened the QRS complex (93.62 ± 8.28 ms vs 135.19 ± 12.21 ms, P = .001), whereas the LBBaP had no effect on QRS complex (130.13 ± 43.30 ms vs 112.63 ± 12.14 ms, P = .904). Furthermore, the LBBaP procedure significantly narrowed the QRS complex in patients with left bundle branch block (LBBB) (168.43 ± 38.870 ms vs 119.86 ± 6.69 ms, P = .019). Conclusion LBBaP is a new physiological, safe and effective pacing procedure with a high overall success rate. Compared to conventional RVP, LBBaP can correct LBBB, thereby improving cardiac electrical dyssynchrony.

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Coronary artery disease (CAD) isbaseline data for each patient. All patients underwent cardioangiography and were divided into four groups according to their Gensini scores: a control group, and groups with a mild, moderate, or severe degree of stenosis. One hundred and five of these patients simultaneously underwent angiography of the lower extremities and were divided into four groups according to the degree of artery stenosis: a control group, and groups with a mild, moderate, or severe degree of stenosis. Grouping of baPWV levels was made according to Japanese surveys. Bilateral baPWV and ABI were measured using non-invasive arterial atherosclerosis measuring equipment. In the coronary artery groups based on Gensini score, ABI in the group with a high degree of stenosis was significantly lower than that in the control and moderate stenosis groups, while the baPWV was significantly higher than that in the control and mild stenosis groups. In the grouping of baPWV levels, it was indicated that the ABI level was significantly different between each group. The ABI <0.9 in groups with baPWV <1,400 cm/s and >2,100 cm/s was higher than that in other groups. In the grouping by angiography of the lower extremities, the ABI level was decreased with increasing degree of artery stenosis while the baPWV levels were increased under the same circumstance (p <0.05 or p <0.01). Logistic regression analysis indicated that relatively low ABI, high baPWV, abnormal fasting blood glucose, and smoking were independent risk factors for the development of cardiovascular diseases. The simultaneous measurement of bilateral baPWV and ABI using the newly developed equipment presented herein is

BackgroundCardiac dysfunction in diabetic cardiomyopathy may be associated with abnormal Ca2+ homeostasis. This study investigated the effects of alterations in Ca2+ homeostasis and sarcoplasmic reticulum Ca2+-associated proteins on cardiac function in the development of diabetic cardiomyopathy.MethodsSprague–Dawley rats were divided into 4 groups (n = 12, each): a control group, and streptozotocin-induced rat models of diabetes groups, examined after 4, 8, or 12 weeks. Evaluations on cardiac structure and function were performed by echocardiography and hemodynamic examinations, respectively. Cardiomyocytes were isolated and spontaneous Ca2+ spark images were formed by introducing fluorescent dye Fluo-4 and obtained with confocal scanning microscopy. Expressions of Ca2+-associated proteins were assessed by Western blotting.ResultsEchocardiography and hemodynamic measurements revealed that cardiac dysfunction is associated with the progression of diabetes, which also correlated with a gradual but significant decline in Ca2+ spark frequency (in the 4-, 8- and 12-week diabetic groups). However, Ca2+ spark decay time constants increased significantly, relative to the control group. Expressions of ryanodine receptor 2 (RyR2), sarcoplasmic reticulum Ca2+-2ATPase (SERCA) and Na+/Ca2+ exchanger (NCX1) were decreased, together with quantitative alterations in Ca2+regulatory proteins, FKBP12.6 and phospholamban progressively and respectively in the diabetic rats.ConclusionsCa2+ sparks exhibited a time-dependent decay with progression of diabetic cardiomyopathy, which may partly contribute to cardiac dysfunction. This abnormality may be attributable to alterations in the expressions of some Ca2+-associated proteins.

Background Ablation index (AI) has been evaluated as guidance quality marker for pulmonary vein isolation, but not for linear ablation of the cavotricuspid isthmus (CTI) for typical right atrial flutter (AFL). We thus studied the feasibility and effectiveness of AI‐guided CTI for AFL. Methods Procedural and 6‐month outcomes of ablation for AFL were retrospectively compared between consecutive patients undergoing either AI‐guided ablation of CTI (n = 43; AI target of 500 for anterior 2/3 segments and 400 for posterior 1/3 segments) or contact force (CF)‐guided ablation (n = 42) at a single center. Each Visitag dataset from all patients in each group was analyzed. Results AI guidance vs CF guidance was associated with: higher first‐pass conduction block of CTI (93.0% vs 76.2%, P = .03) with similar ablation time; similar acute spontaneous CTI reconnection 2.3% vs 9.5%, P = .343); fewer radiofrequency (RF) applications (10.1 ± 2.8 vs 11.5 ± 3.0, P = .031) needed to achieve CTI directional block; significantly higher mean ablation time, impedance drop, force time integral and AI and similar mean CF and power of each VisiTag point. One inguinal hematoma and one pseudoaneurysm developed in the AI and CF groups, respectively. Recurrent AFL was recorded in two (4.7%) AI‐group patients and four (9.5%) CF‐group patients (P = .650). Conclusion AI‐guided ablation of CTI line for AFL appears feasible and effective with similar ablation time, fewer RF applications, a higher rate of first‐pass conduction block, and no additional complications.