The gene kcnma1 encodes the α-subunit of high-conductance calcium- and voltage-dependent K+ (BK) potassium channel. With the development of generation gene sequencing technology, many KCNMA1 mutants have been identified and are more closely related to generalized epilepsy and paroxysmal dyskinesia. Here, we performed a genetic screen of 26 patients with febrile seizures and identified a novel mutation of KCNMA1 (E155Q). Electrophysiological characterization of different KCNMA1 mutants in HEK 293T cells, the previously-reported R458T and E884K variants (not yet determined), as well as the newly-found E155Q variant, revealed that the current density amplitude of all the above variants was significantly smaller than that of the wild-type (WT) channel. All the above variants caused a positive shift of the I-V curve and played a role through the loss-of-function (LOF) mechanism. Moreover, the β4 subunit slowed down the activation of the E155Q mutant. Then, we used kcnma1 knockout (BK KO) mice as the overall animal model of LOF mutants. It was found that BK KO mice had spontaneous epilepsy, motor impairment, autophagic dysfunction, abnormal electroencephalogram (EEG) signals, as well as possible anxiety and cognitive impairment. In addition, we performed transcriptomic analysis on the hippocampus and cortex of BK KO and WT mice. We identified many differentially expressed genes (DEGs). Eight dysregulated genes [i.e., (Gfap and Grm3 associated with astrocyte activation) (Alpl and Nlrp10 associated with neuroinflammation) (Efna5 and Reln associated with epilepsy) (Cdkn1a and Nr4a1 associated with autophagy)] were validated by RT-PCR, which showed a high concordance with transcriptomic analysis. Calcium imaging results suggested that BK might regulate the autophagy pathway from TRPML1. In conclusion, our study indicated that newly-found point E155Q resulted in a novel loss-of-function variant and the dysregulation of gene expression, especially astrocyte activation, neuroinflammation and autophagy, might be the molecular mechanism of BK-LOF meditated epilepsy.

Ameliorating the high-temperature performance of cast Al-Si alloys used as engine components is essential. The effects of different T6 heat-treatment processes on the microstructure and mechanical properties of cast Al-Si-Cu-Mg-Ni-Cr alloys were investigated in the present study. The results demonstrate that, under the optimal solution treatment conditions of 500 °C for 2 h and 540 °C for 4 h, the T-Al9FeNi phase was present in the alloy, and the roundness of primary Si and the aspect ratio of eutectic Si in the alloy reached valley values of 1.46 and 2.56, respectively. With increasing ageing time at 180 °C, the tensile strength significantly improved, while the microhardness first increased and then decreased. When the ageing time was 4 h, microhardness reached a peak value of 155.82 HV. The fracture characteristics changed from quasi-cleavage to the coexistence of quasi-cleavage and dimples. After heat treatment, the high-temperature tensile properties of the alloy improved, which is a significant advantage compared to the as-cast alloy. The stable Al3Ni and Al9FeNi phases inhibited the cracking of the alloy at 350 °C.

To improve the wear resistance of high-strength and high-conductivity Cu–Cr–Zr alloys in high-speed and heavy load friction environments, coatings including Ni–Cu, Ni–Cu-10(W,Si), Ni–Cu–10(Mo,W,Si), and Ni–Cu–15(Mo,W,Si) (with an atomic ratio of Mo,W to Si of 1:2) were prepared using coaxial powder-feeding laser cladding technology. The microstructure and wear performance of coatings were chiefly investigated. The results revealed that (Mo,W)Si2 and MoNiSi phases are found in the Ni–Cu–10(Mo,W,Si) and Ni–Cu–15(Mo,W,Si) coating. WSi2 phases are found in the Ni–Cu–10(W,Si) coating. The degree of grain refinement in Ni–Cu–10(Mo,W,Si) was greater than that of the Ni–Cu–10(W,Si) coating after the effect of Mo. The excellent wear resistance and micro-hardness of the Ni–Cu–15(Mo,W,Si) coating were attributed to the increase in its dispersion phase, which were approximately 34.72 mg/km and 428 HV, 27.1% and 590% higher than the Cu–Cr–Zr substrate, respectively. The existence of silicide plays an important role in grain refinement due to the promotion of nucleation and the inhibition of grain growth. In addition, the wear mechanism transformed from adhesive wear in the Ni–Cu coating with no silicides to abrasive wear in the Ni–Cu–15(Mo,W,Si) coating with high levels of silicides.

Cu-Ni-W alloy coating was electroplated on the surface of mild steel and the effect of Cl- concentration on its corrosion behavior was evaluated in this paper. Polarization techniques and electrochemical impedance spectroscopy (EIS) have been used to investigate the corrosion behavior in aqueous solution contain various Cl-. The results showed that The increased Cl- is prejudice for the Cu-Ni-W coating from 0.01 to 0.3 mol/L, and the critical value of Cl- content is 0.3 mol/L, the coating corrosion present better resistance when immerse in the solution with Cl- content exceeds the critical value or more .

Nucleation kinetics of Ni-nanoCr2O3composite coating during early electro-crystallization was investigated. The results showed that, the early electro-crystallization processes of Ni-nanoCr2O3composite coating and pure Ni coating followed a Scharifker-Hill nucleation/growth mechanism. At the low potential, the nucleation process of pure Ni and Ni-Cr2O3composite system may approach to the progressive nucleation model; With the overpotential increasing, the nucleation model of Pure Ni and Ni-Cr2O3composite system converts into the instantaneous nucleation mechanism controlled; at the same overpotential, Cr2O3powder promotes the electro-crystallization nucleation of Ni. But at high negative potential, Cr2O3powder in composite system promotes the electro-crystal nucleation of Ni weakly; the nanoCr2O3powder added reduces the current efficiency in the nucleation process of Ni.