Cognitive deficits induced by multi-walled carbon nanotubes via the autophagic pathway

This document is the Accepted Manuscript version, made available under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License CC BY NC-ND 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.Multi-walled carbon nanotubes (MWCNTs) have shown potential applications in many fields, especially in the field of biomedicine. Several studies have reported that MWCNTs induce apoptosis and oxidative damage in nerve cells during in vitro experiments. However, there are few studies focused on the neurotoxicity of MWCNTs used in vivo. Many studies have reported that autophagy, a cellular stress response to degrade damaged cell components, can be activated by diverse nanoparticles. In this study, we investigated the neurotoxic effects of MWCNTs on hippocampal synaptic plasticity and spatial cognition in rats. Then, we used an inhibitor of autophagy called chloroquine (CQ) to examine whether autophagy plays an important role in hippocampal synaptic plasticity, since this was damaged by MWCNTs. In this study, adult male Wister rats were randomly divided into three groups: a control group, a group treated with MWCNTs (2.5mg/kg/day) and a group treated with MWCNTs+CQ (20mg/kg/day). After two-weeks of intraperitoneal (i.p.) injections, rats were subjected to the Morris water maze (MWM) test, and the long-term potentiation (LTP) and other biochemical parameters were determined. Results showed that MWCNTs could induce cognitive deficits, histopathological alteration and changes of autophagy level (increased the ratio of LC3 II /LC3 I and the expression of Beclin-1). Furthermore, we found that CQ could suppress MWCNTs-induced autophagic flux and partly rescue the synapse deficits, which occurred with the down-regulation of NR2B (a subunit of NMDA receptor) and synaptophysin (SYP) in the hippocampus. Our results suggest that MWCNTs could induce cognitive deficits in vivo via the increased autophagic levels, and provide a potential strategy to avoid the adverse effects of MWCNTs.Peer reviewedFinal Accepted Versio

A novel coping metal material CoCrCu alloy fabricated by selective laser melting with antimicrobial and antibiofilm properties

This document is the Accepted Manuscript version of the following article: Ling Ren, Kaveh Memarzadeh, Shuyuan Zhang, Ziqing Sun, Chunguang Yang, Guogang Ren, Robert T. Allaker, Ke Yang, ‘A novel coping metal material CoCrCu alloy fabricated by selective laser melting with antimicrobial and antibiofilm properties’, Vol. 67: 461-467, October 2016, doi: http://dx.doi.org/10.1016/j.msec.2016.05.069. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ .OBJECTIVE: The aim of this study was to fabricate a novel coping metal CoCrCu alloy using a selective laser melting (SLM) technique with antimicrobial and antibiofilm activities and to investigate its microstructure, mechanical properties, corrosion resistance and biocompatibility. METHODS: Novel CoCrCu alloy was fabricated using SLM from a mixture of commercial CoCr based alloy and elemental Cu powders. SLM CoCr without Cu served as control. Antibacterial activity was analyzed using standard antimicrobial tests, and antibiofilm properties were investigated using confocal laser scanning microscope. Cu distribution and microstructure were determined using scanning electron microscope, optical microscopy and X-ray diffraction. Corrosion resistance was evaluated by potential dynamic polarization and biocompatibility measured using an MTT assay. RESULTS: SLM CoCrCu alloys were found to be bactericidal and able to inhibit biofilm formation. Other factors such as microstructure, mechanical properties, corrosion resistance and biocompatibility were similar to those of SLM CoCr alloys. SIGNIFICANCE: The addition of appropriate amounts of Cu not only maintains normal beneficial properties of CoCr based alloys, but also provides SLM CoCrCu alloys with excellent antibacterial and antibiofilm capabilities. This material has the potential to be used as a coping metal for dental applications.Peer reviewe

Bloch surface plasmon enhanced blue emission from InGaN/GaN light-emitting diode structures with Al-coated GaN nanorods

InGaN/GaN light-emitting diode structures with Al-coated GaN nanorods were fabricated by using soft ultraviolet nanoimprint lithography. The intensity of light emission was found to be greatly enhanced due to the strong near-fields confined at the interface of Al/GaN and extended to the multiple quantum wells (MQWs) active region. The dynamics of carrier recombination and plasmon-enhanced Raman scattering were also investigated, providing a progressive view on the effective energy transfer between MQWs and surface plasmons.This work was supported by Special Funds for Major State Basic Research Project (Nos. 2011CB301900 and 2012CB619304), the Hi-tech Research Project (No. 2014AA032605), National Nature Science Foundation of China (Nos. 11104130, 61274003, 60990311, 61176063, and 61422401), the Program for New Century Excellent Talents in University (No. NCET-11-0229), Nature Science Foundation of Jiangsu Province (Nos. BK2011556, BK2011010, BK2010385, BY2013077, and BE2011132), Funds of Key Laboratory (No. 9140C140102120C14), Scientific Innovation Research of College Graduate in Jiangsu Province (CXZZ12_0052), PAPD, the Fundamental Research Funds for the Central Universities, the Research Funds from NJUYangzhou Institute of Opto-electronics, and the Australian Research Council Discovery Early Career Researcher Award (DE130101700)

MOOCs as an Alternative for Teacher Professional Development. Examining Learner Persistence in One Chinese MOOC

Massive Open Online Courses (MOOCs) have developed into a significant international movement, showing great promise in addressing equity, quality, and efficiency issues in global education. To date, many MOOCs have been developed specifically for teacher professional development (TPD). In this regard, an important empirical question remains to be addressed: How and to what extent can MOOCs support equity, quality, and efficiency in teacher professional development? To help fill this knowledge gap, this study, conducted from 2014 to 2016, focused on persistent teacher-learners in a TPD MOOC that was offered for seven consecutive rounds by the X-Learning Center of Peking University. The study found that more than 15% of the 105,383 teachers who enrolled in this MOOC were persistent teacher-learners, defined as learners who enrolled in multiple rounds. Data analysis showed that these persistent Keywords: MOOC, teacher professional development, persistent teacher-learners, self-regulated learning teacher-learners had diverse motivations for re-enrollment, including refreshing conceptual understanding, achieving higher scores, earning course certification, and discussing practical problems. The study also found that the persistent teacher learners developed self-regulated learning skills in the course of multiple rounds of the MOOC and showed significantly higher learning achievement than one-time enrollees. Qualitative and quantitative analysis of both clicklog data and interview data revealed additional insights into the persistent teacherlearners’ learning within the MOOC and their real-world teaching practice beyond the MOOC. Overall, this study contributes to an improved understanding of the potential of MOOCs as an alternative TPD delivery mode in developing countries and sheds light on the future design of effective TPD through MOOCs.This work was created with financial support from the UK Government’s Department for International Development and the International Development Research Centre, Canada. The views expressed in this work are those of the authors and do not necessarily represent those of the UK Government’s Department for International Development; the International Development Research Centre, Canada or its Board of Governors; or the Foundation for Information Technology Education and Developmen

Inverse Problem Solution and Regularization Parameter Selection for Current Distribution Reconstruction in Switching Arcs by Inverting Magnetic Fields

Current density distribution in electric arcs inside low voltage circuit breakers is a crucial parameter for us to understand the complex physical behavior during the arcing process. In this paper, we investigate the inverse problem of reconstructing the current density distribution in arcs by inverting the magnetic fields. A simplified 2D arc chamber is considered. The aim of this paper is the computational side of the regularization method, regularization parameter selection strategies, and the estimation of systematic error. To address the ill-posedness of the inverse problem, Tikhonov regularization is analyzed, with the regularization parameter chosen by Morozov’s discrepancy principle, the L-curve, the generalized cross-validation, and the quasi-optimality criteria. The provided range of regularization parameter selection strategies is much wider than in the previous works. Effects of several features on the performance of these criteria have been investigated, including the signal-to-noise ratio, dimension of measurement space, and the measurement distance. The numerical simulations show that the generalized cross-validation and quasi-optimality criteria provide a more satisfactory performance on the robustness and accuracy. Moreover, an optimal measurement distance can be expected when using a planner sensor array to perform magnetic measurements

AVNP2 protects against cognitive impairments induced by C6 glioma by suppressing tumour associated inflammation in rats

© 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).Glioblastoma is a kind of malignant tumour and originates from the central nervous system. In the last century, some researchers and clinician have noticed that the psychosocial and neurocognitive functioning of patients with malignant gliomas can be impaired. Many clinical studies have demonstrated that part of patients, adults or children, diagnosed with glioblastoma will suffer from cognitive deficiency during their clinical course, especially in long-term survivors. Many nanoparticles (NPs) can inhibit the biological functions of tumours by modulating tumour-associated inflammation, which provokes angiogenesis and tumour growth. As one of the best antiviral nanoparticles (AVNPs), AVNP2 is the 2nd generation of AVNP2 that have been conjugated to graphite-graphene for improving physiochemical performance and reducing toxicity. AVNP2 inactivates viruses, such as the H1N1 and H5N1influenza viruses and even the SARS coronavirus, while it inhibits bacteria, such as MRSA and E. coli. As antimicrobials, nanoparticles are considered to be one of the vectors for the administration of therapeutic compounds. Yet, little is known about their potential functionalities and toxicities to the neurotoxic effects of cancer. Herein, we explored the functionality of AVNP2 on inhibiting C6 in glioma-bearing rats. The novel object-recognition test and open-field test showed that AVNP2 significantly improved the neuro-behaviour affected by C6 glioma. AVNP2 also alleviated the decline of long-term potentiation (LTP) and the decreased density of dendritic spines in the CA1 region induced by C6. Western blot assay and immunofluorescence staining showed that the expressions of synaptic-related proteins (PSD-95 and SYP) were increased, and these findings were in accordance with the results mentioned above. It revealed that the sizes of tumours in C6 glioma-bearing rats were smaller after treatment with AVNP2. The decreased expression of inflammatory factors (IL-1β, IL-6 and TNF-α) by Western blotting assay and ELISA, angiogenesis protein (VEGF) by Western blotting assay and other related proteins (BDNF, NF-ĸB, iNOS and COX-2) by Western blotting assay in peri-tumour tissue indicated that AVNP2 could control tumour-associated inflammation, thus efficiently ameliorating the local inflammatory condition and, to some extent, inhibiting angiogenesis in C6-bearing rats. In conclusion, our results suggested that AVNP2 could have an effect on the peri-tumor environment, obviously restraining the growth progress of gliomas, and eventually improving cognitive levels in C6-bearing rats.Peer reviewedProo

PRIMA-1Met suppresses colorectal cancer independent of p53 by targeting MEK

This work was supported by Grant No. 81201779 (Hua Xiong) from the National Natural Science Youth Foundation; Grant No. 81502118 (Yanmei Zou) from the National Natural Science Youth Foundation; Grant No. 2014CFB250 (Yanmei Zou) from the Natural Science Foundation of Hubei Province; Grant No. 81372434 (Huihua Xiong) from the National Natural Science Foundation.PRIMA-1Met is the methylated PRIMA-1 (p53 reactivation and induction of massive apoptosis) and could restore tumor suppressor function of mutant p53 and induce p53 dependent apoptosis in cancer cells harboring mutant p53. However, p53 independent activity of PRIMA-1Met remains elusive. Here we reported that PRIMA-1Met attenuated colorectal cancer cell growth irrespective of p53 status. Kinase profiling revealed that mitogen-activated or extracellular signal-related protein kinase (MEK) might be a potential target of PRIMA-1Met. Pull-down binding and ATP competitive assay showed that PRIMA-1Met directly bound MEK in vitro and in cells. Furthermore, the direct binding sites of PRIMA-1Met were explored by using a computational docking model. Treatment of colorectal cancer cells with PRIMA-1Met inhibited p53-independent phosphorylation of MEK, which in turn impaired anchorage-independent cell growth in vitro. Moreover, PRIMA-1Met suppressed colorectal cancer growth in xenograft mouse model by inhibiting MEK1 activity. Taken together, our findings demonstrate a novel p53-independent activity of PRIMA-1Met to inhibit MEK and suppress colorectal cancer growth.Publisher PDFPeer reviewe

Effects of nanoparticle zinc oxide on spatial cognition and synaptic plasticity in mice with depressive-like behaviors

Background: Nanomaterials, as a new kind of materials, have been greatly applied in different fields due to their special properties. With the industrialization of nanostructured materials and increasing public exposure, the biosafety and potential influences on central nervous system (CNS) have received more attention. Nanosized zinc oxide (nanoZnO) was suggested to up-regulate neuronal excitability and to induce glutamate release in vitro. Therefore, we hypothesized nanoparticles of nanoZnO may lead to changes in balance of neurotransmitter or neuronal excitability of CNS. This study was to investigate if there were effects of nanoZnO on animal model of depression. Methods: Male Swiss mice were given lipopolysaccharides (LPS, 100 mu g/kg, 100 mu g/ml, every other day, 8 times, i.p.) from weaning to induce depressive-like behaviors. NanoZnO (5.6 mg/kg, 5.6 mg/ml, every other day, 8 times, i.p.) was given as the interaction. The mouse model was characterized using the methods of open field test, tail suspension test and forced swim test. Furthermore, the spatial memory was evaluated using Morris water maze (MWM) and the synaptic plasticity was assessed by measuring the long-term potentiation (LTP) in the perforant pathway (PP) to dentate gyrus (DG) in vivo. Results: Results indicated that model mice showed disrupted spatial memory and LTP after LPS injections and the behavioral and electrophysiological improvements after nanoZnO treatment. Conclusion: Data suggested that nanoZnO may play some roles in CNS of mental disorders, which could provide some useful direction on the new drug exploring and clinical researches.Peer reviewe