JZTX-V Targets the Voltage Sensor in Kv4.2 to Inhibit Ito Potassium Channels in Cardiomyocytes

Kv4 potassium channels are responsible for transient outward K+ currents in the cardiac action potential (AP). Previous experiments by our group demonstrated that Jingzhaotoxin-V (JZTX-V) selectively inhibits A-type potassium channels. However, the specific effects of JZTX-V on the transient outward (Ito) current of cardiomyocytes and underlying mechanism of action remain unclear. In the current study, 100 nM JZTX-V effectively inhibited the Ito current and extended the action potential duration (APD) of neonatal rat ventricular myocytes (NRVM). We further analyzed the effects of JZTX-V on Kv4.2, a cloned channel believed to underlie the Ito current in rat cardiomyocytes. JZTX-V inhibited the Kv4.2 current with a half-maximal inhibitory concentration (IC50) of 13 ± 1.7 nM. To establish the molecular mechanism underlying the inhibitory action of JZTX-V on Kv4.2, we performed alanine scanning mutagenesis of Kv4.2 and JZTX-V and assessed the effects of the mutations on binding activities of the proteins. Interestingly, the Kv4.2 mutations V285A, F289A, and V290A reduced the affinity for JZTX-V while I275A and L277A increased the affinity for JZTX-V. Moreover, mutation of positively charged residues (R20 and K22) of JZTX-V and the hydrophobic patch (formed by W5, M6, and W7) led to a significant reduction in toxin sensitivity, indicating that the hydrophobic patch and electrostatic interactions played key roles in the binding of JZTX-V with Kv4.2. Data from our study have shed light on the specific roles and molecular mechanisms of JZTX-V in the regulation of Ito potassium channels and supported its utility as a potential novel antiarrhythmic drug

State of Health Estimation Method for Lithium-Ion Batteries via Generalized Additivity Model and Transfer Component Analysis

Battery state of health (SOH) is a momentous indicator for aging severity recognition of lithium-ion batteries and is also an indispensable parameter of the battery management system. In this paper, an innovative SOH estimation algorithm based on feature transfer is proposed for lithium-ion batteries. Firstly, sequence features with battery aging information are sufficiently extracted based on the capacity increment curve. Secondly, transfer component analysis is employed to obtain the mapping that minimizes the data distribution difference between the training set and the test set in the shared feature space. Finally, the generalized additive model is investigated to estimate the battery health status. The experimental results demonstrate that the proposed algorithm is capable of forecasting the SOH for lithium-ion batteries, and the results are more outstanding than those of several comparison algorithms. The predictive error evaluation indicators for each battery are both less than 2.5%. In addition, satisfactory SOH estimation results can also be obtained by only relying on a small amount of data as the training set. The comparative experiments using traditional features and different machine learning methods also testify to the superiority of the proposed algorithm

LncRNA SNHG1: role in tumorigenesis of multiple human cancers

Abstract Small nucleolar RNA host gene 1 (SNHG1) is an important member of the SNHG family. This family is composed of a group of host genes that can be processed into small nucleolar RNAs and play important biological functions. In an oncogenic role, the SNHG1 expression is increased in various cancers, which has immense application prospects in the diagnosis, treatment, and prognosis of malignant tumors. In this review, we have summarized the role and molecular mechanism of SNHG1 in the development of various cancers. In addition, we have emphasized the clinical significance of SNHG1 in cancers in our article. This molecule is expected to be a new marker for potential usage in the diagnosis, prognosis, and treatment of cancer

Urethral calculi with a urethral fistula: a case report and review of the literature

Abstract Background To explore and summarize the reasons why urethral calculi cause a urethral fistula. Case presentation We retrospectively studied 1 patient in Xiangya hospital and all relevant literature published in English between 1989 and 2015. The patients (including those reported in the literature) were characterized by age, origin, location of calculus, size of calculus, fistulous track, and etiological factors. Most of urethral calculi associated with a urethral fistula were native generated. Urethral calculi can be formed in various locations of the urethra, and the size of the calculus ranged from small (multiple) calculi to giant stones. The fistula external orifice located at the root of the penis was relatively common, and there were various etiological factors, such as urethral strictures, urethral trauma induced by long-term catheterization, lumbar fractures, and congenital anomaly factors. They were managed by the excision of the fistulous tract, retrieval of the urethral stones, and/or debridement and pus drainage operations. Conclusion Some elements, such as trauma, recurrent urinary tract infections, abscess formation induced by long-term catheterization, and urethral calculus, may be the risk factors for a urethral fistula

Measuring the urban sprawl based on economic-dominated perspective: the case of 31 municipalities and provincial capitals

ABSTRACTAccurate measurement of urban sprawl is vital for urban planning and management. Urban planning-induced internal structure complexity affects the extent of urban sprawl. In addition, urban sprawl is closely linked to economic development. The study attempts to explore the impact of urban sprawl from an economic-dominated perspective. Thus a City-Ring road-County (CRC) scale framework based on top-down administrative divisions for urban sprawl measurement is proposed: 1) the single-index measurement based on economic activity is applied to calculate urban sprawl; 2) the spatiotemporal pattern of urban sprawl is investigated through a case study in 31 economy-dominated provincial capital cities across China from 2005 to 2015; 3) the impact of economy and land on urban sprawl is explored using correlation analysis. The results indicate that the degree of urban sprawl at the city scale shows an “inverted U-shaped” curve from 2005 to 2015, which represents that the phenomenon of urban sprawl was most severe in 2010. It finds that urban sprawl was more severe in the east and central regions relative to the provincial capitals in the western region, with the situation being most severe in the northeast region. Regions that have been transformed from suburban to urban built-up areas need to be given priority attention by the local government, including population movement, land layout, and fiscal policy, to meet the criteria of the urbanization process. Through correlation analysis, we also found that urban sprawl was influenced by the industry structure and the form of built-up area. The outcome of the study suggests that the data scale is sufficiently small in granularity to provide geographic boundaries for systematic analysis of urban sprawl in multiple administrative regions. Thus, the study helps provide a reference for differential planning policy formulation by governments at diverse economic levels

Design Method for Automatic Assembly Production Line of Electric Valves in Space Propulsion Systems

This article proposes a design method for a valve automatic assembly production line in response to the automation assembly requirements of electric valve products in space propulsion systems and the engineering problems of inaccurate loading force control and low valve measurement accuracy in existing process methods. This method can achieve five assembly processes during the assembly process of electric valves, including pre-tightening force control, valve-core stroke measurement, performance testing, and shell structure welding. The article introduces the design of platform components such as process execution, positioning, and transportation, as well as the design and operation process of workstations. By combining the design of a three-axis motion mechanism, a small turntable, and a robotic arm, the product can achieve professional, positioning, full process automation, and equipment miniaturization design across multiple workstations. Through the design of precise control of loading force and non-contact optical measurement method of moving structure, compared with the original method, the parameters affecting product performance are precisely controlled and the precision is improved. And the multivariable decoupling of valve product performance is realized by this method. Through application verification, this automatic assembly production line can significantly improve the assembly efficiency of electric valve products and solve difficult problems in product engineering

Selective Closed-State Nav1.7 Blocker JZTX-34 Exhibits Analgesic Effects against Pain

Jingzhaotoxin-34 (JZTX-34) is a selective inhibitor of tetrodotoxin-sensitive (TTX-S) sodium channels. In this study, we found that JZTX-34 selectively acted on Nav1.7 with little effect on other sodium channel subtypes including Nav1.5. If the DIIS3-S4 linker of Nav1.5 is substituted by the correspond linker of Nav1.7, the sensitivity of Nav1.5 to JZTX-34 extremely increases to 1.05 µM. Meanwhile, a mutant D816R in the DIIS3-S4 linker of Nav1.7 decreases binding affinity of Nav1.7 to JZTX-34 about 32-fold. The reverse mutant R800D at the corresponding position in Nav1.5 greatly increased its binding affinity to JZTX-34. This implies that JZTX-34 binds to DIIS3-S4 linker of Nav1.7 and the critical residue of Nav1.7 is D816. Unlike β-scorpion toxin trapping sodium channel in an open state, activity of JZTX-34 requires the sodium channel to be in a resting state. JZTX-34 exhibits an obvious analgesic effect in a rodent pain model. Especially, it shows a longer duration and is more effective than morphine in hot pain models. In a formalin-induced pain model, JZTX-34 at dose of 2 mg/kg is equipotent with morphine (5 mg/kg) in the first phase and several-fold more effective than morphine in second phase. Taken together, our data indicate that JZTX-34 releases pain by selectively binding to the domain II voltage sensor of Nav1.7 in a closed configuration