Fangchinoline alleviates cognitive impairments through enhancing autophagy and mitigating oxidative stress in Alzheimer’s disease models

Introduction: Alzheimer’s disease (AD) is a debilitating, progressive, neurodegenerative disorder characterized by the deposition of amyloid-β (Aβ) peptides and subsequent oxidative stress, resulting in a cascade of cytotoxic effects. Fangchinoline (Fan), a bisbenzylisoquinoline alkaloid isolated from traditional Chinese herb Stephania tetrandra S. Moorec, has been reported to possess multiple potent biological activities, including anti-inflammatory and antioxidant properties. However, the potential neuroprotective efficacy of Fan against AD remains unknown.Methods: N2AAPP cells, the mouse neuroblastoma N2A cells stably transfected with human Swedish mutant APP695, were served as an in vitro AD model. A mouse model of AD was constructed by microinjection of Aβ1–42 peptides into lateral ventricle of WT mice. The neuroprotective effects of Fan on AD were investigated through a combination of Western blot analysis, immunoprecipitation and behavioral assessments.Results and discussion: It was found that Fan effectively attenuated the amyloidogenic processing of APP by augmenting autophagy and subsequently fostering lysosomal degradation of BACE1 in N2AAPP cells, as reflected by the decrease in P62 levels, concomitant with the increase in Beclin-1 and LC3-II levels. More importantly, Fan significantly ameliorated cognitive impairment in an Aβ1–42-induced mouse model of AD via the induction of autophagy and the inhibition of oxidative stress, as evidenced by an increase in antioxidants including glutathione reductase (GR), total antioxidant capacity (T-AOC), nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and superoxide dismutase-1 (SOD-1) and a decrease in pro-oxidants including hydrogen peroxide (H2O2) and inducible nitric oxide synthase (i-NOS), coupled with a reduction in apoptosis marker, cleaved caspase-3. Taken together, our study demonstrate that Fan ameliorates cognitive dysfunction through promoting autophagy and mitigating oxidative stress, making it a potential therapeutic agent for AD

Formation of robust and completely tunable resonant photonic band gaps

We identify different types of the photonic band gaps (PBGs) of two dimensional magnetic photonic crystals (MPCs) consisting of arrays of magnetic cylinders and study the different tunability (by an external static magnetic field) of these PBGs. One type of the band gaps comes from infinitely degenerate flat bands and is closely related to those in the study of plasmonics. In addition, such PBGs are magnetically tunable and robust against position disorder. We calcualte the transmission of the PBG's and found excellent agreement with the results of the photonic band structure calculation. Positional disorder of the lattice structure affects the different types of PBGs differently.Comment: 4 pages, 5 figure

Effect of rs1344706 in the ZNF804A gene on the brain network.

ZNF804A rs1344706 (A/C) was the first SNP that reached genome-wide significance for schizophrenia. Recent studies have linked rs1344706 to functional connectivity among specific brain regions. However, no study thus far has examined the role of this SNP in the entire functional connectome. In this study, we used degree centrality to test the role of rs1344706 in the whole-brain voxel-wise functional connectome during the resting state. 52 schizophrenia patients and 128 healthy controls were included in the final analysis. In our whole-brain analysis, we found a significant interaction effect of genotype × diagnosis at the precuneus (PCU) (cluster size = 52 voxels, peak voxel MNI coordinates: x = 9, y = - 69, z = 63, F = 32.57, FWE corrected P < 0.001). When we subdivided the degree centrality network according to anatomical distance, the whole-brain analysis also found a significant interaction effect of genotype × diagnosis at the PCU with the same peak in the short-range degree centrality network (cluster size = 72 voxels, F = 37.29, FWE corrected P < 0.001). No significant result was found in the long-range degree centrality network. Our results elucidated the contribution of rs1344706 to functional connectivity within the brain network, and may have important implications for our understanding of this risk gene's role in functional dysconnectivity in schizophrenia

Element Replacement Approach by Reaction with Lewis Acidic Molten Salts to Synthesize Nanolaminated MAX Phases and MXenes

Nanolaminated materials are important because of their exceptional properties and wide range of applications. Here, we demonstrate a general approach to synthesize a series of Zn-based MAX phases and Cl-terminated MXenes originating from the replacement reaction between the MAX phase and the late transition metal halides. The approach is a top-down route that enables the late transitional element atom (Zn in the present case) to occupy the A site in the pre-existing MAX phase structure. Using this replacement reaction between Zn element from molten ZnCl2 and Al element in MAX phase precursors (Ti3AlC2, Ti2AlC, Ti2AlN, and V2AlC), novel MAX phases Ti3ZnC2, Ti2ZnC, Ti2ZnN, and V2ZnC were synthesized. When employing excess ZnCl2, Cl terminated MXenes (such as Ti3C2Cl2 and Ti2CCl2) were derived by a subsequent exfoliation of Ti3ZnC2 and Ti2ZnC due to the strong Lewis acidity of molten ZnCl2. These results indicate that A-site element replacement in traditional MAX phases by late transition metal halides opens the door to explore MAX phases that are not thermodynamically stable at high temperature and would be difficult to synthesize through the commonly employed powder metallurgy approach. In addition, this is the first time that exclusively Cl-terminated MXenes were obtained, and the etching effect of Lewis acid in molten salts provides a green and viable route to prepare MXenes through an HF-free chemical approach.Comment: Title changed; experimental section and discussion revise

Assessment of the three-dimensional flow field in the reactor pressure vessel in Hualong One nuclear power plants

This study uses computational fluid dynamics (CFD) to investigate the three-dimensional flow field under normal operating conditions in the reactor pressure vessel (RPV) in the Hualong One nuclear power plants (NPPs). With a particular focus on the flowrate distribution at the core inlet, the numerical framework is validated against the integral hydraulic experiment in a 1:4-scaled RPV of CNP1000, the prototype of the Hualong One reactor. The simulation results of the normalized flowrate at the core inlet agree reasonably well with the measured data. Based on the experimental data, several methods of calibrating the CFD turbulence model coefficients are suggested by introducing the concepts of data assimilation and machine learning. The flow field in a realistic RPV for Hualong One is predicted using the validated numerical framework, showing that the flowrate distribution at the core inlet is nearly homogeneous and that the turbulent intensity is acceptably low for each fuel assembly. It can provide essential information for the reactor core thermal–hydraulic design and the fuel assembly mechanical assessment

Low-Frequency Repetitive Transcranial Magnetic Stimulation Ameliorates Cognitive Function and Synaptic Plasticity in APP23/PS45 Mouse Model of Alzheimer’s Disease

Alzheimer’s disease (AD) is a chronic neurodegenerative disease leading to dementia, which is characterized by progressive memory loss and other cognitive dysfunctions. Recent studies have attested that noninvasive repetitive transcranial magnetic stimulation (rTMS) may help improve cognitive function in patients with AD. However, the majority of these studies have focused on the effects of high-frequency rTMS on cognitive function, and little is known about low-frequency rTMS in AD treatment. Furthermore, the potential mechanisms of rTMS on the improvement of learning and memory also remain poorly understood. In the present study, we reported that severe deficits in spatial learning and memory were observed in APP23/PS45 double transgenic mice, a well known mouse model of AD. Furthermore, these behavioral changes were accompanied by the impairment of long-term potentiation (LTP) in the CA1 region of hippocampus, a brain region vital to spatial learning and memory. More importantly, 2-week low-frequency rTMS treatment markedly reversed the impairment of spatial learning and memory as well as hippocampal CA1 LTP. In addition, low-frequency rTMS dramatically reduced amyloid-β precursor protein (APP) and its C-terminal fragments (CTFs) including C99 and C89, as well as β-site APP-cleaving enzyme 1 (BACE1) in the hippocampus. These results indicate that low-frequency rTMS noninvasively and effectively ameliorates cognitive and synaptic functions in a mouse model of AD, and the potential mechanisms may be attributed to rTMS-induced reduction in Aβ neuropathology