No abstract

Non-invasive ultrasonic neural modulation (UNM), a non-invasive technique with enhanced spatial focus compared to conventional electrical neural modulation, has attracted much attention in recent decades and might become the mainstream regimen for neurological disorders. However, as ultrasonic bioeffects and its adjustments are still unclear, it remains difficult to be extensively applied for therapeutic purpose, much less in the setting of human skull. Hence to comprehensively understand the way ultrasound exerts bioeffects, we explored UNM from a basic perspective by illustrating the parameter settings and the underlying mechanisms. In addition, although the spatial resolution and precision of UNM are considerable, UNM is relatively non-specific to tissue or cell type and shows very low specificity at the molecular level. Surprisingly, Ibsen et al. (2015) first proposed the concept of sonogenetics, which combined UNM and mechanosensitive (MS) channel protein. This emerging approach is a valuable improvement, as it may markedly increase the precision and spatial resolution of UNM. It seemed to be an inspiring tool with high accuracy and specificity, however, little information about sonogenetics is currently available. Thus, in order to provide an overview of sonogenetics and prompt the researches on UNM, we summarized the potential mechanisms from a molecular level.

Objectives. The gut microbiota and its metabolites are linked to inflammation and contribute to the progression of atrial fibrillation (AF), but the predictive value of the gut microbiota-derived metabolite lipopolysaccharide (LPS) for AF recurrence (RAF) is unknown. This study is aimed at investigating (1) the correlation between LPS and RAF and (2) its relationship with inflammation and atrial fibrosis. Method. We performed a single-centre retrospective analysis in 159 AF patients. Fasting plasma samples were collected, and an enzyme-linked immunosorbent assay was used to determine the levels of serum LPS, interleukin-6 (IL-6), collagen type-1 C-terminal telopeptide (CITP), and transforming growth factor-β1 (TGFβ1). The cumulative risk for RAF was evaluated with Kaplan–Meier analysis. Cox proportional hazard analysis was carried out to predict the hazard of RAF. The correlations among LPS and IL-6, CITP, TGFβ1, and left atrial diameter (LAD) were analysed by Pearson’s correlation coefficient. Subsequent univariate and multivariable linear regression analyses were carried out to evaluate the connection between clinical variables and Log-LPS. Results. All 159 AF patients were included in this study. The proportion of persistent atrial fibrillation was 40.3%, the mean age was 61.9 ± 10.1 years, the proportion of males was 61.6%, and the mean LPS was 56.5 ± 29.5  pg/mL. After all patients were divided into tertiles according to the circulating LPS level, a total of 44 RAF occurred: 10 in the first tertile, 15 in the second tertile, and 19 in the third tertile (log-rank test P = 0.037 ). Heart failure (hazard ratio 2.029, P = 0.041 ), LAD (hazard ratio 1.064, P = 0.022 ), Log-LPS (hazard ratio 5.686, P = 0.043 ), and CITP (hazard ratio 6.841, P = 0.033 ) independently predicted the risk of RAF. In all patients, univariate analysis showed that heart failure, LAD, hs-CRP, IL-6, CITP, and TGF-β1 were connected with Log-LPS. Multivariate linear regression analysis indicated that IL-6 and hs-CRP were independently and positively connected with Log-LPS. Conclusions. Our results indicated that circulating LPS was a predictor of RAF and may contribute to RAF incidence after ablation by increasing systemic inflammation and atrial fibrosis.

Purpose. Recent studies have indicated that N-acetylneuraminic acid (Neu5Ac) plays a key role in severe coronary artery diseases, involving RhoA signaling pathway activation, which is critically involved in cardiac fibrosis. There is convincing evidence from many studies that left atrium fibrosis is involved in the pathophysiology of AF. Therefore, we speculated that Neu5Ac may be associated with atrial fibrillation (AF) and involved in the development of AF. This study aims to investigate the clinical relationship between Neu5Ac and AF and left atrial enlargement. Methods. Forty-five patients with AF (AF group) and forty-five patients with non-AF (control group) matched for age, sex, and hospitalization date were recruited for our study. Plasma concentrations of Neu5Ac from peripheral venous blood were analyzed using enzyme-linked immunosorbent assay (ELISA). The baseline characteristics, plasma level of Neu5Ac, and echocardiographic characteristics were evaluated. Results. The plasma level of Neu5Ac was significantly higher in the AF group than in the control group (107.66 ± 47.50 vs 77.87 ± 39.09  ng/ml; P<0.05); the left atrial diameters were positively correlated with the plasma Neu5Ac level (R = 0.255; P<0.05). The plasma Neu5Ac level (R = 0.368; P<0.05) and the left atrial diameters (R = 0.402; P<0.05) were positively correlated with AF history times. Neu5Ac (odds ratio 1.018, 95% CI 1.003–1.032; P<0.05) and the left atrial diameter (odds ratio 1.142, 95% CI 1.020–1.280; P<0.05) were independent risk factors for AF in multivariate regression analysis. Conclusions. Serum Neu5Ac is associated with atrial fibrillation, and the mechanism may involve left atrial enlargement.