Mkk4 is a negative regulator of the transforming growth factor beta 1 signaling associated with atrial remodeling and arrhythmogenesis with age.

BACKGROUND: Atrial fibrillation (AF), often associated with structural, fibrotic change in cardiac tissues involving regulatory signaling mediators, becomes increasingly common with age. In the present study, we explored the role of mitogen-activated protein kinase kinase 4 (Mkk4), a critical component of the stress-activated mitogen-activated protein kinase family, in age-associated AF. METHODS AND RESULTS: We developed a novel mouse model with a selective inactivation of atrial cardiomyocyte Mkk4 (Mkk4(ACKO)). We characterized and compared electrophysiological, histological, and molecular features of young (3- to 4-month), adult (6-month), and old (1-year) Mkk4(ACKO) mice with age-matched control littermates (Mkk4(F/F)). Aging Mkk4(ACKO) mice were more susceptible to atrial tachyarrhythmias than the corresponding Mkk4(F/F) mice, showing characteristic slow and dispersed atrial conduction, for which modeling studies demonstrated potential arrhythmic effects. These differences paralleled increased interstitial fibrosis, upregulated transforming growth factor beta 1 (TGF-β1) signaling and dysregulation of matrix metalloproteinases in Mkk4(ACKO), compared to Mkk4(F/F), atria. Mkk4 inactivation increased the sensitivity of cultured cardiomyocytes to angiotensin II-induced activation of TGF-β1 signaling. This, in turn, enhanced expression of profibrotic molecules in cultured cardiac fibroblasts, suggesting cross-talk between these two cell types in profibrotic signaling. Finally, human atrial tissues in AF showed a Mkk4 downregulation associated with increased production of profibrotic molecules, compared to findings in tissue from control subjects in sinus rhythm. CONCLUSIONS: These findings together demonstrate, for the first time, that Mkk4 is a negative regulator of the TGF-β1 signaling associated with atrial remodeling and arrhythmogenesis with age, establishing Mkk4 as a new potential therapeutic target for treating AF

Seismic Hazard Analysis of China’s Mainland Based on a New Seismicity Model

Abstract Based on the seismic source model in the Fifth Generation Seismic Ground Motion Parameters Zonation Map of China (FGSGMPZMC), a new seismic fault model, the new zonation of seismic risk areas (SRAs), and the estimation of seismicity rates for 2021–2030, this study constructed a new time-dependent seismic source model of China’s mainland, and used the probabilistic seismic hazard analysis method to calculate seismic hazard by selecting the ground motion models (GMMs) suitable for seismic sources in China. It also provided the probabilities of China’s mainland being affected by earthquakes of modified Mercalli intensity (MMI) VI, VII, VIII, IX, and ≥ X in 2021–2030. The spatial pattern of seismic hazards presented in this article is similar to the pattern of the FGSGMPZMC, but shows more details. The seismic hazards in this study are higher than those in the FGSGMPZMC in the SRAs and fault zones that can produce large earthquakes. This indicates that the seismic source model construction in this study is scientific and reasonable. There are certain similarities between the results in this study and those of Rong et al. (2020) and Feng et al. (2020), but also disparities for specific sites due to differences in seismic source models, seismicity parameters, and GMMs. The results of seismic hazard may serve as parameter input for future seismic risk assessments. The hazard results can also be used as a basis for the formulation of earthquake prevention and mitigation policies for China’s mainland

A novel method for multiple bowel injuries: a pilot canine experiment

Abstract Background Intestinal ligation is the cornerstone for damage control in abdominal emergency, yet it may lead to bowel ischemia. Although intestinal ligation avoids further peritoneal cavity pollution, it may lead to an increased pressure within the bowel segments and rapid bacterial translocation. In this study, we showed that severed intestine could be readily reconnected by using silicon tubes and be secured by using rubber bands in a canine model. Methods Adult Beagle dogs, subject to multiple intestinal transections and hemorrhagic shock by exsanguination, randomly received conventional ligation vs. silicon tubes reconnecting (n = 5 per group). Intestinal transections were carried out under general anesthesia after 24-h fasting. The abdomen was opened with a midline incision. The small intestine was severed at 50, 100, and 150 cm below the Treitz ligament. Hemorrhagic shock was established by streaming blood from the left carotid artery until the mean arterial pressure reached 40 mmHg in 20 min. Fluid resuscitation and surgery began 30 min after the establishment of hemorrhagic shock. Severed intestines were ligated or connected with silicon tubes. Definitive repair was conducted in subjects surviving for at least 48 h. Results Operation time was comparable between the two groups (39.6 ± 8.9 vs. 36.6 ± 7.8 min in ligation and reconnecting groups, respectively; p = 0.56). The time spent in managing each resection was also comparable (4.6 ± 1.1 vs. 3.8 ± 0.84 min; p = 0.24). Blood loss (341.2 ± 28.6 vs. 333.8 ± 34.6 ml; p = 0.48), and fluid resuscitation within the first 24 h (1676 ± 200.6 vs. 1594 ± 156.5 ml; p = 0.46) were similar. One subject in the ligation group was sacrificed at 36-h due to severe vomiting that led to aspiration. Four remaining dogs in the ligation group received definitive surgery, but two out of four had to be sacrificed at 24-h after definitive repair due to imminent death. All five dogs in the reconnecting group survived for at least a week. Radiographic examination confirmed the integrity of the GI tract in the reconnecting group. In both groups, plasma endotoxin concentration increased after damage control surgery, but the increase was much more pronounced in the ligation group. Microscopic examination of the involved segment of the intestine revealed much more severe pathology in the ligation group. Conclusion The current study showed that the reconnecting resected intestine by using silicon tubes is feasible under emergency. Such a method could decrease short-term mortality and minimize endotoxin translocation

A Novel Method for Fatigue Detection Based on Fuzzy Logic

The problem of fatigue is becoming one of the factors impacting on the working and studying people. Therefore, how to detect whether the people are tired simply and effectively is paid attention to by more and more researchers. A novel method of fatigue testing based on fuzzy logic and image processing is proposed in this paper. Firstly, positive map and side elevation are extracted through camera device. Then motion detection determined to locate human faces and the frequency of eyes opening and closing is derived by using image processing techniques. Finally the angle between the head and the shoulder is calculated combined with a representation of time function and a fatigue threshold is set up. All of these are determined to estimate the degree of fatigue. Experimental results show that, the method can quickly detect the degree of fatigue simply

Oxidative Stress Induced by Metal Ions in Bioleaching of LiCoO2 by an Acidophilic Microbial Consortium

© Copyright © 2020 Liu, Liu, Wu, Zhang, Gu, Zhu and Tan. An acidophilic microbial consortium (AMC) was used to investigate the fundamental mechanism behind the adverse effects of pulp density increase in the bioleaching of waste lithium ion batteries (WLIBs). Results showed that there existed the effect of metal-ion stress on the bio-oxidative activity of AMC. The Li+ and Co2+ accumulated in the leachate were the direct cause for the decrease in lithium and cobalt recovery yields under a high pulp density. In a simulated bioleaching system with 4.0% (w ⋅v–1) LiCoO2, the intracellular reactive oxygen species (ROS) content in AMC increased from 0.82 to 6.02 within 24 h, which was almost three times higher than that of the control (2.04). After the supplementation of 0.30 g⋅L–1 of exogenous glutathione (GSH), the bacterial intracellular ROS content decreased by 40% within 24 h and the activities of intracellular ROS scavenging enzymes, including glutathione peroxidase (GSH-Px) and catalase (CAT), were 1.4- and 2.0-folds higher in comparison with the control within 24 h. In the biofilms formed on pyrite in the bioleaching of WLIBs, it was found that metal-ion stress had a great influence on the 3-D structure and the amount of biomass of the biofilms. After the exogenous addition of GSH, the structure and the amount of biomass of the biofilms were restored to some extent. Eventually, through ROS regulation by the exogenous addition of GSH, very high metal recovery yields of 98.1% Li and 96.3% Co were obtained at 5.0% pulp density

Effects of doping FeCl3 on hydrogen storage properties of Li-N-H system

The effects of doping FeCl3 on the LiNH2- 2LiH system were investigated systematically. FeCl(3)was prior to react with LiH during ball milling their mixtures. The metallic Fe, which is generated from metathesis reaction between FeCl3 and LiH, plays an important role on improving the dehydrogenation kinetics of LiNH2-2LiH system. The results indicated that the dehydrogenation peak and ending temperatures of the doped 1 mol% FeCl3 sample shifted to low temperatures, and the dehydrogenation active energy changed from 102.45 kJ/mol to 87.52 kJ/mol. While increasing the amount of FeCl3, an excess of LiCl, the by-product of metathesis reaction between FeCl3 and LiH, can stabilize LiNH2 and thus hinder hydrogen desorption. The dehydrogenation product is a new solid cubic phase solution of lithium imide-chloride. The high limit of the solid solution of LiCl and Li2NH is near the molar ratio of 1:1

Research on Fuzzy Clustering Validity

The evaluation of clustering validity is important for clustering analysis, and is one of the hottest spots of cluster analysis. The quality of the evaluation of clustering is that optimal number of clusters is reasonable. For fuzzy clustering, the paper surveys the widely known fuzzy clustering validity evaluation based on the methods of fuzzy partition, geometry structure and statistics