Lamellar Hierarchical Porous Carbon Prepared from Coal Tar Pitch through a Lamellar Hard Template Combined with the Precarbonization and Activation Method for Supercapacitors

The lamellar porous carbon favors the diffusion and penetration of electrolyte ions and presents a fantastic advantage as an energy storage electrode material. In this work, the lamellar Mg5(OH)4(CO3)2·4H2O template is synthesized via a simple precipitation method in the low-temperature hydrothermal condition. Lamellar hierarchical porous carbon (LHPC) is successfully synthesized through the Mg5(OH)4(CO3)2·4H2O hard template and the KOH activation method using coal tar pitch (CTP) as the carbon source. The effects of activation temperature and activator dosage on the morphology, microstructure, and supercapacitor performance are researched at length. LHPCs-1–700 displays a good lamellar structure and an abundant mesoporous structure, so as to exhibit superior capacitive performance compared with other carbon electrodes. The specific capacitance for LHPCs-1–700 reaches 298 F g–1 at 1 A g–1 and still maintains 234 F g–1 at 50 A g–1 with a high capacitance retention of 78.5% in the three-electrode system. The kinetic behavior of the LHPCs-1–700 electrode was also analyzed according to the CV data obtained at different scan rates, and it was found that the fast kinetic capacitance contribution was up to 87% at 200 mV s–1. The assembled LHPCs-1–700 symmetric supercapacitor delivered an energy density of 16.73 W h kg–1 with a power density of 859.4 W kg–1 in 1 M Na2SO4 solution. Besides, the specific capacitance retention rate could still reach 95.8% after 8000 cycles

Molecular Mechanism Behind the Resistance of the G1202R-Mutated Anaplastic Lymphoma Kinase to the Approved Drug Ceritinib

Anaplastic lymphoma kinase (ALK) has been regarded as an essential target for the treatment of nonsmall cell lung cancer (NSCLC). However, the emergence of the G1202R solvent front mutation that confers resistance to the drugs was reported for the first as well as the second generation ALK inhibitors. It was thought that the G1202R solvent front mutation might hinder the drug binding. In this study, a different fact could be clarified by multiple molecular modeling methodologies through a structural analogue of ceritinib (compound 10, Cpd-10) that is reported to be a potent inhibitor against the G1202R mutation. Herein, molecular docking, accelerated molecular dynamics (aMD) simulations in conjunction with principal component analysis (PCA), and free energy map calculations were used to produce reasonable and representative initial conformations for the conventional MD simulations. Compared with Cpd-10, the binding specificity of ceritinib between ALK wild-type (ALK^WT) and ALK G1202R (ALK^G1202R) are primarily controlled by the conformational change of the P-loop- and A-loop-induced energetic redistributions, and the variation is nonpolar interactions, as indicated by conventional MD simulations, PCA, dynamic cross-correlation map (DCCM) analysis, and free energy calculations. Furthermore, the umbrella sampling (US) simulations were carried out to make clear the principle of the dissociation processes of ceritinib and Cpd-10 toward ALK^WT and ALK^G1202R. The calculation results suggest that Cpd-10 has similar dissociation processes from both ALK^WT and ALK^G1202R, but ceritinib is more easily dissociated from ALK^G1202R than from ALK^WT, thus less residence time is responsible for the ceritinib resistance. Our results suggest that both the binding specificity and the drug residence time should be emphasized in rational drug design to overcome the G1202R solvent front mutation of ALK resistance