Effect of pinocembrin pre-treatment on expressions of Cx43 protein and claudin 1 in myocardial ischemia cardiomyocytes of arrhythmic rats

Purpose: To investigate the effects of pinocembrin on ventricular rhythm and the expression of cardiomyocyte ligament junction protein (Cx43) and claudin 1 (ZO-1) in ischemia/reperfusion (I/R) rats.Methods: Ischemia/reperfusion (I/R) model rats (n = 15) were divided into 5 groups: IR group, control group, and 3 pinocembrin groups (3, 10 and 30 mg/kg). The serum levels of creatine kinase-MB isoenzyme (CK-MB) and troponin I (cTnI) were measured by enzyme-linked immunosorbent assay (ELISA). Changes in myocardial tissue were detected by H & E staining, while mRNA and protein levels of Cx43, ZO-1 and Kir2.1 were measured by reverse transcriotion-polymerase chain reaction (RT-PCR) and Western blotting, respectively.Results: In pinocembrin groups, heart rate (HR), mean arterial pressure (MAP) and rate-pressure product (RPP) levels were significantly higher compared with IR group (p < 0.05). Moreover, the extent of arrhythmia and the levels of CK-MB and cTnI in pinocembrin groups were lower relative to IR group, while Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities, as well as Cx43 mRNA, ZO-1 mRNA, and protein levels of Cx43, ZO-1 and Kir2.1 were significantly higher than the corresponding values for IR group (p < 0.05).Conclusion: These results suggest that pinocembrin reduces ventricular arrhythmias in I/R rats by upregulation of expressions of Cx43, ZO-1 and Kir21, and inhibition of re-distribution of ZO-1 and Cx43. These findings provide the basis for the clinical application of pinocembrin in the treatment of arrhythmia.Keywords: Pinocembrin, Ventricular arrhythmia, Ligament junction protein, Recombinant human Kir2.1 protein, Arterial pressure, Protein levels, Claudin, Cardiomyocyt

A parameter optimization method for stress simulation of double horse head pumping unit dynamics model with cable

Some components in Double horse head (DHH) pumping unit may occur cracking failure due to high cycle alternating stress, and this makes the research on dynamic stress simulation for them more interesting topic in its maintenance operation. This paper aims to improve the accuracy of dynamic stress simulation model through a parameter optimization method for the cable joints in DHH pumping unit. A series of cylinders was employed to model the steel cable, and the back horse head was also transformed to flexible body, then a rigid-flexible multibody dynamics model with cable was constructed to simulate the dynamic stress of components in DHH pumping unit. Stiffness and damping coefficient in cable joints have a significant effect on the model performance, and an unreasonable value may cause a strong vibrational and undesirable model response, therefore, a Memetic Algorithms based method was proposed to optimize them for improving the simulation accuracy using tested stress as objective function. Results show that the dynamic stress simulated from improved model is much closer to the experimental test compared with the original model, and these optimized parameters are also valid for the model in other working condition

A novel SCN5A mutation, F1344S, identified in a patient with Brugada syndrome and fever-induced ventricular fibrillation

Objective Brugada syndrome (BS) is an inherited electrical cardiac disorder characterized by right bundle branch block pattern and ST segment elevation in leads V1 to V3 on surface electrocardiogram that can potentially lead to malignant ventricular tachycardia and sudden cardiac death. About 20% of patients have mutations in the only so far identified gene, SCN5A, which encodes the α-subunit of the human cardiac voltage-dependent sodium channel (hNav1.5). Fever has been shown to unmask or trigger the BS phenotype, but the associated molecular and the biophysical mechanisms are still poorly understood. We report on the identification and biophysical characterization of a novel heterozygous missense mutation in SCN5A, F1344S, in a 42-year-old male patient showing the BS phenotype leading to ventricular fibrillation during fever. Methods The mutation was reproduced in vitro using site-directed mutagenesis and characterized using the patch clamp technique in the whole-cell configuration. Results The biophysical characterization of the channels carrying the F1344S mutation revealed a 10mV mid-point shift of the G/V curve toward more positive voltages during activation. Raising the temperature to 40.5°C further shifted the mid-point activation by 18mV and significantly changed the slope factor in Nav1.5/F1344S mutant channels from − 6.49 to − 10.27mV. Conclusions Our findings indicate for the first time that the shift in activation and change in the slope factor at a higher temperature mimicking fever could reduce sodium currents' amplitude and trigger the manifestation of the BS phenotyp

An improved local mean decomposition method and its application for fault diagnosis of reciprocating compressor

Local mean decomposition (LMD) is a new time–frequency analysis method which can decompose a signal adaptively into a set of product function (PF) components, and the construction of local mean function and envelope function plays an important role in the accuracy of its PF components. Aiming at the strong nonstationarity, nonlinearity and multi-component coupling characteristics of reciprocating compressor vibration signals, an improved LMD was proposed by a novel construction method of local mean function and envelope function. By introducing an extreme symmetrical point between two extreme points and using the Monotone Piecewise Cubic Hermite Interpolation (MPCHI) instead of Cubic Spline Interpolation (CSI) to construct the envelopes, a novel construction method of local mean function and envelope function was proposed, and then the improved LMD algorithm was given based on this novel construction method. The improved LMD was applied to decompose the vibration signals of reciprocating compressor fault states, and the comparison of details between different LMD decomposition results verified the superiority of this improved method. The envelope frequency spectrum of PF component gives a more significant peak of fault frequency than that of original signal, which further indicates that this proposed method is competent for the diagnosis of reciprocating compressor oversized bearing clearance fault

Metanetwork Transmission Model for Predicting a Malaria-Control Strategy

Background: Mosquitoes are the primary vectors responsible for malaria transmission to humans, with numerous experiments having been conducted to aid in the control of malaria transmission. One of the main approaches aims to develop malaria parasite resistance within the mosquito population by introducing a resistance (R) allele. However, when considering this approach, some critical factors, such as the life of the mosquito, female mosquito fertility capacity, and human and mosquito mobility, have not been considered. Thus, an understanding of how mosquitoes and humans affect disease dynamics is needed to better inform malaria control policymaking.Methods: In this study, a method was proposed to create a metanetwork on the basis of the geographic maps of Gambia, and a model was constructed to simulate evolution within a mixed population, with factors such as birth, death, reproduction, biting, infection, incubation, recovery, and transmission between populations considered in the network metrics. First, the same number of refractory mosquitoes (RR genotype) was introduced into each population, and the prevalence of the R allele (the ratio of resistant alleles to all alleles) and malaria were examined. In addition, a series of simulations were performed to evaluate two different deployment strategies for the reduction of the prevalence of malaria. The R allele and malaria prevalence were calculated for both the strategies, with 10,000 refractory mosquitoes deployed into randomly selected populations or selection based on nodes with top-betweenness values. The 10,000 mosquitoes were deployed among 1, 5, 10, 20, or 40 populations.Results: The simulations in this paper showed that a higher RR genotype (resistant-resistant genes) ratio leads to a higher R allele prevalence and lowers malaria prevalence. Considering the cost of deployment, the simulation was performed with 10,000 refractory mosquitoes deployed among 1 or 5 populations, but this approach did not reduce the original malaria prevalence. Thus, instead, the 10,000 refractory mosquitoes were distributed among 10, 20, or 40 populations and were shown to effectively reduce the original malaria prevalence. Thus, deployment among a relatively small fraction of central nodes can offer an effective strategy to reduce malaria.Conclusion: The standard network centrality measure is suitable for planning the deployment of refractory mosquitoes.Importance: Malaria is an infectious disease that is caused by a plasmodial parasite, and some control strategies have focused on genetically modifying the mosquitoes. This work aims to create a model that takes into account mosquito development and malaria transmission among the population and how these factors influence disease dynamics so as to better inform malaria-control policymaking