ABSTRACT
Microglia-mediated neuroinflammation plays a significant role in the pathogenesis of Parkinson's disease (PD). Down-regulation of DJ-1, a PD-associated protein, has been recently found to increase microglial sensitivity to lipopolysaccharides (LPS). However, the role of DJ-1 in microglia-mediated neuroinflammation in PD remains unclear. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to establish a PD model with mice and tyrosine hydroxylase (TH) staining was performed to validate the model. Adenovirus strategy and shRNA was employed to knockdown the expression of DJ-1 in mice and BV2 microglia, respectively. Western Blot and quantitative PCR were carried out to determine the expression of cytokines, DJ-1, Nrf2, Trx1 and NRLP3. Immunoprecipitation was used to examine the potential interaction between DJ-1 and Nrf2 or Trx1. Flow cytometry-based Annexin V/7-AAD assay were performed to evaluate cell apoptosis. We found that down-regulation of DJ-1 exacerbated neuroinflammation in PD mice. DJ-1 and Nrf2 knockdown promoted inflammation and cell apoptosis in BV2 microglia, while NLRP3 knockdown had opposite effects. Furthermore, DJ-1 regulated the expression of NLRP3 by upregulating Nrf2/Trx1 axis. Taken together, these data suggested that down-regulation of DJ-1 accelerated microglia-mediated neuroinflammation and cell apoptosis via Nrf2/Trx1/NLRP3 axis. Thus, our results demonstrated the important role of DJ-1 in PD pathogenesis and warranted further investigation of DJ-1 as a therapeutic target for PD.
Subject(s)
NF-E2-Related Factor 2 , Parkinson Disease , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine , Animals , Disease Models, Animal , Down-Regulation , Mice , Mice, Inbred C57BL , Microglia/metabolism , NF-E2-Related Factor 2/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolismABSTRACT
Two-dimensional (2D) B-C-N alloys have recently attracted much attention but unfortunately, Chemical Vapor Deposition (CVD) B-C-N alloys typically phase separate. In spite of that, our analysis of the B-C-N alloy fabricated by electron-beam irradiation suggests that non-phase-separated B-C-N may in fact exist with a carbon concentration up to 14 at%. While this analysis points to a new way to overcome the phase-separation in 2D B-C-N, by first-principles calculations, we show that these B-C-N alloys are made of motifs with even numbers of carbon atoms, in particular, dimers or six-fold rings (in a molecule-like form), embedded in a 2D BN network. Moreover, by tuning the carbon concentration, the band gap of the B-C-N alloys can be reduced by 35% from that of BN. Due to a strong overlap of the wavefunctions at the conduction band and valance band edges, the non-phase-separated B-C-N alloys maintain the strong optical absorption of BN.
ABSTRACT
The organic-inorganic hybrid perovskite has become a new type of semiconductor for low cost and highly efficient solar cells. However, the mechanism of interactions between the organic cation and the inorganic framework is still not completely clear under optical electronic excitation. In this work, we employ first-principles molecular dynamics with electronic excitation effects to prove that the hydrogen-bond interaction between the molecular cation and the inorganic lattice can be readily adjusted by several-percentage-valence-electron excitations in cubic CH3NH3PbI3. While the hydrogen-bond interaction causes serious lattice distortions, the electronic excitation can recover the lattice symmetry largely by weakening hydrogen bonding. The study offers atomic dynamics to understand the excitation process in the organic-inorganic hybrid perovskite semiconductor.
