Mixed-linker strategy for suppressing structural flexibility of metal-organic framework membranes for gas separation.

Structural flexibility is a critical issue that limits the application of metal-organic framework (MOF) membranes for gas separation. Herein we propose a mixed-linker approach to suppress the structural flexibility of the CAU-10-based (CAU = Christian-Albrechts-University) membranes. Specifically, pure CAU-10-PDC membranes display high separation performance but at the same time are highly unstable for the separation of CO2/CH4. A partial substitution (30 mol.%) of the linker PDC with BDC significantly improves its stability. Such an approach also allows for decreasing the aperture size of MOFs. The optimized CAU-10-PDC-H (70/30) membrane possesses a high separation performance for CO2/CH4 (separation factor of 74.2 and CO2 permeability of 1,111.1 Barrer under 2 bar of feed pressure at 35°C). A combination of in situ characterization with X-ray diffraction (XRD) and diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy, as well as periodic density functional theory (DFT) calculations, unveils the origin of the mixed-linker approach to enhancing the structural stability of the mixed-linker CAU-10-based membranes during the gas permeation tests.

Cognitive deficits and Alzheimer-like neuropathological impairments during adolescence in a rat model of type 2 diabetes mellitus.

Numerous studies have shown that many patients who suffer from type 2 diabetes mellitus exhibit cognitive dysfunction and neuronal synaptic impairments. Therefore, growing evidence suggests that type 2 diabetes mellitus has a close relationship with occurrence and progression of neurodegeneration and neural impairment in Alzheimer's disease. However, the relationship between metabolic disorders caused by type 2 diabetes mellitus and neurodegeneration and neural impairments in Alzheimer's disease is still not fully determined. Thus, in this study, we replicated a type 2 diabetic animal model by subcutaneous injection of newborn Sprague-Dawley rats with monosodium glutamate during the neonatal period. At 3 months old, the Barnes maze assay was performed to evaluate spatial memory function. Microelectrodes were used to measure electrophysiological function in the hippocampal CA1 region. Western blot assay was used to determine expression levels of glutamate ionotropic receptor NMDA type subunit 2A (GluN2A) and GluN2B in the hippocampus. Enzyme-linked immunosorbent assay was used to determine levels of interleukin-1ß, tumor necrosis factor α, and interleukin-6 in the hippocampus and cerebral cortex, as well as hippocampal amyloid beta (Aß)1-40 and Aß1-42 levels. Our results showed that in the rat model of type 2 diabetes mellitus caused by monosodium glutamate exposure during the neonatal period, latency was prolonged and the number of errors increased in the Barnes maze. Further, latency was increased and time in the escape platform quadrant shortened. Number of times crossing the platform was also reduced in the Morris water maze. After high frequency stimulation of the hippocampus, synaptic transmission was inhibited, expression of GluN2A and GluN2B were decreased in the hippocampus, expression of interleukin 1ß, interleukin 6, and tumor necrosis factor α was increased in the hippocampus and cortex, and levels of Aß1-40 and Aß1-42 were increased in the hippocampus. These findings confirm that type 2 diabetes mellitus induced by neonatal monosodium glutamate exposure results in Alzheimer-like neuropathological changes and further causes cognitive deficits and neurodegeneration in young adulthood.

Dendritic cell nuclear protein-1 regulates melatonin biosynthesis by binding to BMAL1 and inhibiting the transcription of N-acetyltransferase in C6 cells.

Dendritic cell nuclear protein-1 (DCNP1) is a protein associated with major depression. In the brains of depression patients, DCNP1 is up-regulated. However, how DCNP1 participates in the pathogenesis of major depression remains unknown. In this study, we first transfected HEK293 cells with EGFP-DCNP1 and demonstrated that the full-length DCNP1 protein was localized in the nucleus, and RRK (the residues 117-119) composed its nuclear localization signal (NLS). An RRK-deletion form of DCNP1 (DCNP1ΔRRK) and truncated form (DCNP11-116), each lacking the RRK residues, did not show the specific nuclear localization like full-length DCNP1 in the cells. A rat glioma cell line C6 can synthesize melatonin, a hormone that plays important roles in both sleep and depression. We then revealed that transfection of C6 cells with full-length DCNP1 but not DCNP1ΔRRK or DCNP11-116 significantly decreased the levels of melatonin. Furthermore, overexpression of full-length DCNP1, but not DCNP1ΔRRK or DCNP11-116, in C6 cells significantly decreased both the mRNA and protein levels of N-acetyltransferase (NAT), a key enzyme in melatonin synthesis. Full-length DCNP1 but not DCNP1ΔRRK or DCNP11-116 was detected to interact with the Nat promoter and inhibited its activity through its E-box motif. Furthermore, full-length DCNP1 but not the mutants interacted with and repressed the transcriptional activity of BMAL1, a transcription factor that transactivates Nat through the E-box motif. In conclusion, we have shown that RRK (the residues 117-119) are the NLS responsible for DCNP1 nuclear localization. Nuclear DCNP1 represses NAT expression and melatonin biosynthesis by interacting with BMAL1 and repressing its transcriptional activity. Our study reveals a connection between the major depression candidate protein DCNP1, circadian system and melatonin biosynthesis, which may contribute to the pathogenesis of depression.

Vitamin K2 suppresses rotenone-induced microglial activation in vitro.

AIM: Increasing evidence has shown that environmental factors such as rotenone and paraquat induce neuroinflammation, which contributes to the pathogenesis of Parkinson's disease (PD). In this study, we investigated the molecular mechanisms underlying the repression by menaquinone-4 (MK-4), a subtype of vitamin K2, of rotenone-induced microglial activation in vitro. METHODS: A microglial cell line (BV2) was exposed to rotenone (1 µmol/L) with or without MK-4 treatment. The levels of TNF-α or IL-1ß in 100 µL of cultured media of BV2 cells were measured using ELISA kits. BV2 cells treated with rotenone with or without MK4 were subjected to mitochondrial membrane potential, ROS production, immunofluorescence or immunoblot assays. The neuroblastoma SH-SY5Y cells were treated with conditioned media (CM) of BV2 cells that were exposed to rotenone with or without MK-4 treatment, and the cell viability was assessed using MTT assay. RESULTS: In rotenone-treated BV2 cells, MK-4 (0.5-20 µmol/L) dose-dependently suppressed the upregulation in the expression of iNOS and COX-2 in the cells, as well as the production of TNF-α and IL-1ß in the cultured media. MK-4 (5-20 µmol/L) significantly inhibited rotenone-induced nuclear translocation of NF-κB in BV2 cells. MK-4 (5-20 µmol/L) significantly inhibited rotenone-induced p38 activation, ROS production, and caspase-1 activation in BV2 cells. MK-4 (5-20 µmol/L) also restored the mitochondrial membrane potential that had been damaged by rotenone. Exposure to CM from rotenone-treated BV2 cells markedly decreased the viability of SH-SY5Y cells. However, this rotenone-activated microglia-mediated death of SH-SY5Y cells was significantly attenuated when the BV2 cells were co-treated with MK-4 (5-20 µmol/L). CONCLUSION: Vitamin K2 can directly suppress rotenone-induced activation of microglial BV2 cells in vitro by repressing ROS production and p38 activation.