We investigate theoretically electron spin states in one dimensional (1D) and two dimensional (2D) hard-wall mesoscopic rings in the presence of both the Rashba spin-orbit interaction (RSOI) and the Dresselhaus spin-orbit interaction (DSOI) in a perpendicular magnetic field. The Hamiltonian of the RSOI alone is mathematically equivalent to that of the DSOI alone using an SU(2) spin rotation transformation. Our theoretical results show that the interplay between the RSOI and DSOI results in an effective periodic potential, which consequently leads to gaps in the energy spectrum. This periodic potential also weakens and smoothens the oscillations of the persistent charge current (CC) and spin current (SC) and results in the localization of electrons. For a 2D ring with a finite width, higher radial modes destroy the periodic oscillations of persistent currents.
A novel series of compounds obtained by fusing the cholinesterase inhibitor donepezil and the antioxidant ebselen were designed as multi-target-directed ligands against Alzheimer's disease. An in vitro assay showed that some of these molecules did not exhibit highly potent cholinesterase inhibitory activity but did have various other ebselen-related pharmacological effects. Among the molecules, compound 7d, one of the most potent acetylcholinesterase inhibitors (IC50 values of 0.042 μM for Electrophorus electricus acetylcholinesterase and 0.097 μM for human acetylcholinesterase), was found to be a strong butyrylcholinesterase inhibitor (IC50 = 1.586 μM), to possess rapid H2O2 and peroxynitrite scavenging activity and glutathione peroxidase-like activity (ν0 = 123.5 μM min(-1)), and to be a substrate of mammalian TrxR. A toxicity test in mice showed no acute toxicity at doses of up to 2000 mg/kg. According to an in vitro blood-brain barrier model, 7d is able to penetrate the central nervous system.
Spin-orbit coupled honeycomb magnets with the Kitaev interaction have received a lot of attention due to their potential of hosting exotic quantum states including quantum spin liquids. Thus far, the most studied Kitaev systems are 4d/5d-based honeycomb magnets. Recent theoretical studies predicted that 3d-based honeycomb magnets, including Na2Co2TeO6 (NCTO), could also be a potential Kitaev system. Here, we have used a combination of heat capacity, magnetization, electron spin resonance measurements alongside inelastic neutron scattering (INS) to study NCTO’s quantum magnetism, and we have found a field-induced spin disordered state in an applied magnetic field range of 7.5 T < B (⊥ b-axis) < 10.5 T. The INS spectra were also simulated to tentatively extract the exchange interactions. As a 3d-magnet with a field-induced disordered state on an effective spin-1/2 honeycomb lattice, NCTO expands the Kitaev model to 3d compounds, promoting further interests on the spin-orbital effect in quantum magnets.
Background
Centromere protein N (CENP-N) has been reported to be highly expressed in malignancies, but its role and mechanism in nasopharyngeal carcinoma (NPC) are unknown.
Methods
Abnormal CENP-N expression from NPC microarrays of GEO database was analyzed. CENP-N expression level was confirmed in NPC tissues and cell lines. Stable CENP-N knockdown and overexpression NPC cell lines were established, and transcriptome sequencing after CENP-N knockdown was performed. In vitro and in vivo experiments were performed to test the impact of CENP-N knockdown in NPC cells. ChIP and dual luciferase reporter assays were used to verify the combination of IRF2 and CENP-N. Western blot analysis, cellular immunofluorescence, immunoprecipitation and GST pulldown assays were used to verify the combination of CENP-N and AKT.
Results
CENP-N was confirmed to be aberrantly highly expressed in NPC tissues and cell lines and to be associated with high 18F-FDG uptake in cancer nests and poor patient prognosis. Transcriptome sequencing after CENP-N knockdown revealed that genes with altered expression were enriched in pathways related to glucose metabolism, cell cycle regulation. CENP-N knockdown inhibited glucose metabolism, cell proliferation, cell cycling and promoted apoptosis. IRF2 is a transcription factor for CENP-N and directly promotes CENP-N expression in NPC cells. CENP-N affects the glucose metabolism, proliferation, cell cycling and apoptosis of NPC cells in vitro and in vivo through the AKT pathway. CENP-N formed a complex with AKT in NPC cells. Both an AKT inhibitor (MK-2206) and a LDHA inhibitor (GSK2837808A) blocked the effect of CENP-N overexpression on NPC cells by promoting aerobic glycolysis, proliferation, cell cycling and apoptosis resistance.
Conclusions
The IRF2/CENP-N/AKT axis promotes malignant biological behaviors in NPC cells by increasing aerobic glycolysis, and the IRF2/CENP-N/AKT signaling axis is expected to be a new target for NPC therapy.
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