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Recent studies have indicated that functional abnormalities in the KNa1.2 channel are linked to epileptic encephalopathies. However, the role of KNa1.2 channel in traumatic brain injury (TBI) remains limited. We collected brain tissue from the TBI mice and patients with post-traumatic epilepsy (PTE) to determine changes in KNa1.2 channel following TBI. We also investigated whether the MAPK pathway, which was activated by the released cytokines after injury, regulated KNa1.2 channel in in vitro. Finally, to elucidate the physiological significance of KNa1.2 channel in neuronal excitability, we utilized the null mutant-Kcnt2−/− mice and compared their behavior patterns, seizure susceptibility, and neuronal firing properties to wild type (WT) mice. TBI was induced in both Kcnt2−/− and WT mice to investigate any differences between the two groups under pathological condition. Our findings revealed that the expression of KNa1.2 channel was notably increased only during the acute phase following TBI, while no significant elevation was observed during the late phase. Furthermore, we identified the released cytokines and activated MAPK pathway in the neurons after TBI and confirmed that KNa1.2 channel was enhanced by the MAPK pathway via stimulation of TNF-α. Subsequently, compared to WT mice, neurons from Kcnt2−/− mice showed increased neuronal excitability and Kcnt2−/− mice displayed motor deficits and enhanced seizure susceptibility, which suggested that KNa1.2 channel may be neuroprotective. Therefore, this study suggests that enhanced KNa1.2 channel, facilitated by the inflammatory response, may exert a protective role in an acute phase of the TBI model. [ABSTRACT FROM AUTHOR]

A series of bisimidazolium tungstate ionic liquids were synthesized and applied to catalyze the reaction of ethylene carbonate (EC) with alcohols. A detailed investigation was carried out on the relationship between catalyst structures and catalytic activities. The result showed that 1-butyl-3-methyl-bisimidazolium tungstate ([Bmim]2WO4) containing double C2–H in bisimidazolium and WO42− had more effectively catalytic performance than other bisimidazolium tungstate and conventional imidazolium salt (OAc−, Cl−, Br−). Under the optimized conditions of 1:15 molar ratio of EC and ethanol, 5 mol% [Bmim]2WO4, 85 °C and 0.5 h, the yield of diethyl carbonate (DEC) was nearly 100%. The detailed DFT calculations and NMR spectroscopy indicated that the high catalytic activity of [Bmim]2WO4 was not only because the strong nucleophilic ability of WO42− could activate ethanol, but also the special structure of double C2–H in bisimidazolium could cooperatively activate EC. The reaction was catalyzed by synergistic effect in double C2–H and WO42− of [Bmim]2WO4. In addition, [Bmim]2WO4 could be used seven times without significant loss of catalytic activity. [ABSTRACT FROM AUTHOR]

Background and purpose: Although observational studies have reported a positive association between depression and ischemic stroke, causality remains inconclusive. We aimed to assess the causal relationship of major depressive disorder (MDD) with ischemic stroke, especially with the small vessel stroke (SVS) subtype. Methods: We used 72 independent single-nucleotide polymorphisms associated with MDD in a genome-wide association study (GWAS) from the Psychiatric Genetics Consortium as instrumental variables. The corresponding data for ischemic stroke and its subtypes of European ancestry were available from the MEGASTROKE consortium of 34,217 ischemic stroke cases and 406,111 controls. Primary Mendelian randomization estimates were calculated with inverse-variance weighted method, and several alternate methods and multiple sensitivity analyses were also performed. Results: We found that genetic predisposition to higher risk of MDD was associated with higher risk of SVS, with an odds ratio of 1.33 (95% confidence interval, 1.08–1.65; p = 0.009) per log-odds increment in MDD risk, but not with large artery stroke (OR, 1.08; 95% CI 0.83–1.41; p = 0.559), cardioembolic stroke (OR, 0.98; 95% CI 0.80–1.20; p = 0.833), or all ischemic stroke (OR, 1.03; 95% CI 0.92–1.15; p = 0.633). The association of MDD with SVS was overall robust to sensitivity analyses. Conclusions: We provided evidence for a possible causal effect of MDD on increased risk of SVS. Future researches are required to investigate whether rational intervention on depression may help to reduce societal burden of SVS. [ABSTRACT FROM AUTHOR]

In this study, stress deformation of Qingdao Jiaozhou Bay undersea tunnel terminal during high-rise building construction engineering was evaluated by real 3D numerical modeling using Midas software. The simulations were performed during high-rise building foundation pit blocks, stratified excavation unloading, and loading the whole building construction on adjacent existing tunnel. The influence of the whole process through tunnel convergence, tunnel vertical displacement and horizontal displacement, as well as deformation curvature changes of additional stress and lining were used to evaluate the tunnel safety. The results showed that excavation at depth of 6 m, the whole process of high-rise building construction on adjacent tunnel deformation was conform to requirements of control. As building load deformation reduced near tunnel ceiling, one side of foundation pit became bigger and far away from side of foundation pit but did not return to front of foundation pit excavation tunnel state. The construction load of adjacent tunnel excavation generated small additional stress with overall design no more than tunnel load values. Overall, the tunnel was in safe working conditions and the proposed research provide certain guidance and reference for similar projects. [ABSTRACT FROM AUTHOR]

Keshan disease (KD) is an endemic cardiomyopathy with high mortality. Selenium (Se) and zinc (Zn) deficiencies are closely related to KD. The molecular mechanism of KD pathogenesis is still unclear. There are only few studies on the interaction of trace elements and proteins associated with the pathogenesis of KD. In this study, isobaric tags for relative and absolute quantitation (iTRAQ)-coupled two-dimensional liquid chromatography tandem mass spectrometry (2DLC-MS/MS) technique analysis was used to analyze the differential expression of proteins from serum samples. Comparative Toxicogenomics Database (CTD) was used to screen Se- and Zn-associated proteins. Then, pathway and network analyses of Se- and Zn-associated proteins were constituted by Cytoscape ClueGO and GeneMANIA plugins. One hundred and five differentially expressed proteins were obtained by 2DLC-MS/MS, among them 19 Se- and 3 Zn-associated proteins. Fifty-two pathways were identified from ClueGO and 1 network from GeneMANIA analyses. The results showed that Se-associated proteins STAT3 and MAPK1 and Zn-associated proteins HIF1A and PARP1, the proteins involved in HIF-1 signaling pathway and apoptosis pathway, may play significant roles in the pathogenesis of KD. The approach of this study would be also beneficial for further dissecting molecular mechanism of other trace element-associated disease. [ABSTRACT FROM AUTHOR]