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Exploring non-noble and high-performance metal catalysts to replace platinum-based catalysts for the hydrogen evolution reaction (HER) via electrochemical water splitting significantly alleviates environmental pollution and the energy crisis. However, the synthetic approaches of such electrocatalysts are generally complex and challenging for large-scale production. Herein, a facile and green solid-state synthesis of Ni nanoparticles decorated with N-doped porous carbon is presented. These materials are derived from chitosan as carbon, nitrogen sources, and nickel acetate as a nickel source with NaCl as a template. The synthesis procedure is simple to scale up without an organic solvent. Benefiting from its porous structure, splendid conductivity, and the synergistic effect of Ni nanoparticles and holey N-doped carbon, the as-prepared Ni@CN exhibits superior HER performance in 1 M KOH with a low potential of 121 mV at 10 mA cm -2 . These findings indicate that the convenient and environmentally friendly synthesis approach provides a novel method for large-scale synthesis of HER electrocatalysts for industrial electrolytic water splitting applications.

Background: Increased level of serum cholic acid (CA) is often accompanied with decreased CYP2E1 expression in hepatocellular carcinoma (HCC) patients. However, the roles of CA and CYP2E1 in hepatocarcinogenesis have not been elucidated. This study aimed to investigate the roles and the underlying mechanisms of CYP2E1 and CA in HCC cell growth., Methods: The proteomic analysis of liver tumors from DEN-induced male SD rats with CA administration was used to reveal the changes of protein expression in the CA treated group. The growth of CA-treated HCC cells was examined by colony formation assays. Autophagic flux was assessed with immunofluorescence and confocal microscopy. Western blot analysis was used to examine the expression of CYP2E1, mTOR, AKT, p62, and LC3II/I. A xenograft tumor model in nude mice was used to examine the role of CYP2E1 in CA-induced hepatocellular carcinogenesis. The samples from HCC patients were used to evaluate the clinical value of CYP2E1 expression., Results: CA treatment significantly increased the growth of HCC cells and promoted xenograft tumors accompanied by a decrease of CYP2E1 expression. Further studies revealed that both in vitro and in vivo, upregulated CYP2E1 expression inhibited the growth of HCC cells, blocked autophagic flux, decreased AKT phosphorylation, and increased mTOR phosphorylation. CYP2E1 was involved in CA-activated autophagy through the AKT/mTOR signaling. Finally, decreased CYP2E1 expression was observed in the tumor tissues of HCC patients and its expression level in tumors was negatively correlated with the serum level of total bile acids (TBA) and gamma-glutamyltransferase (GGT)., Conclusions: CYP2E1 downregulation contributes to CA-induced HCC development presumably through autophagy regulation. Thus, CYP2E1 may serve as a potential target for HCC drug development., (© 2024. The Author(s).)

Covalent organic frameworks (COFs) with controlled porosity, high crystallinity, diverse designability and excellent stability are very attractive in metal-free heterogeneous photocatalysis of volatile organic compounds (VOCs) degradation. In order to construct the high optimal performance COFs under feasible and universal conditions, herein, the visible light-driven hollow COF TAPB-PDA (H-COF TAPB-PDA ) microcapsule was designed by a facile dual-ligand regulated sacrificial template method. The H-COF TAPB-PDA microcapsule possesses improved surface area, high crystallinity, broad absorption range and high stability, which enables enhanced substrates and visible light adsorption, photogenerated electrons-holes separation and transfer, and facilitate the generation of reactive radicals. Importantly, it was found to be a highly efficient photocatalyst for toluene degradation under visible-light irradiation compared with the solid COF TAPB-PDA , and the degradation efficiency of toluene reached 91.8 % within 180 min with the conversion rate of CO 2 was 68.9 %. Additionally, the H-COF TAPB-PDA presented good recyclability and long-term stability after multiple photocatalytic reuses. Furthermore, the active sites of H-COF TAPB-PDA in photocatalytic degradation of toluene was proposed by XPS and DFT calculations, and the degradation pathway and mechanism was proposed and analyzed. The result presented great prospect of morphologic design of hollow COFs in metal-free heterogeneous photocatalysis for VOCs degradation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The design of efficient, stable and cost-effective electrocatalysts for the hydrogen evolution reaction holds substantial significance in water electrolysis, but it remains challenging. Tremella-like nickel-molybdenum bimetal phosphide encapsulated cobalt phosphide (NiMoP/CoP) with hierarchical architectures has been effectively synthesized on nickel foam (NF) via a straightforward hydrothermal followed by low-temperature phosphating method. Based on the unique structural benefits, it significantly increases the number of redox active centers, enhances the electrical conductivity of materials, and diminishes the ion diffusion path lengths, thereby promoting efficient electrolyte penetration and reducing the inherent resistance. The as-obtained NiMoP/CoP/NF electrocatalyst exhibited remarkable catalytic activity with an ultralow overpotential of 38 mV (10 mA cm -2 ) and low Tafel slope of 83 mV dec -1 . The straightforward synthesis process and exceptional electrocatalytic properties of NiMoP/CoP/NF demonstrate great potential for the HER to replace the precious metal catalyst.

Background: Alzheimer's disease (AD) and related Tauopathies are characterised by the pathologically hyperphosphorylated and aggregated microtubule-associated protein Tau, which is accompanied by neuroinflammation mediated by activated microglia. However, the role of Tau pathology in microglia activation or their causal relationship remains largely elusive., Methods: The levels of nucleotide-binding oligomerisation domain (NOD)-like receptor pyrin domain containing 3 (NLRP3) acetylation and inflammasome activation in multiple cell models with Tau proteins treatment, transgenic mice with Tauopathy, and AD patients were measured by Western blotting and enzyme-linked immunosorbent assay. In addition, the acetyltransferase activity of Tau and NLRP3 acetylation sites were confirmed using the test-tube acetylation assay, co-immunoprecipitation, immunofluorescence (IF) staining, mass spectrometry and molecular docking. The Tau-overexpressing mouse model was established by overexpression of human Tau proteins in mouse hippocampal CA1 neurons through the adeno-associated virus injection. The cognitive functions of Tau-overexpressing mice were assessed in various behavioural tests, and microglia activation was analysed by Iba-1 IF staining and [18F]-DPA-714 positron emission tomography/computed tomography imaging. A peptide that blocks the interaction between Tau and NLRP3 was synthesised to determine the in vitro and in vivo effects of Tau-NLRP3 interaction blockade on NLRP3 acetylation, inflammasome activation, microglia activation and cognitive function., Results: Excessively elevated NLRP3 acetylation and inflammasome activation were observed in 3xTg-AD mice, microtubule-associated protein Tau P301S (PS19) mice and AD patients. It was further confirmed that mimics of 'early' phosphorylated-Tau proteins which increase at the initial stage of diseases with Tauopathy, including TauT181E, TauS199E, TauT217E and TauS262E, significantly promoted Tau-K18 domain acetyltransferase activity-dependent NLRP3 acetylation and inflammasome activation in HEK293T and BV-2 microglial cells. In addition, Tau protein could directly acetylate NLRP3 at the K21, K22 and K24 sites at its PYD domain and thereby induce inflammasome activation in vitro. Overexpression of human Tau proteins in mouse hippocampal CA1 neurons resulted in impaired cognitive function, Tau transmission to microglia and microgliosis with NLRP3 acetylation and inflammasome activation. As a targeted intervention, competitive binding of a designed Tau-NLRP3-binding blocking (TNB) peptide to block the interaction of Tau protein with NLRP3 inhibited the NLRP3 acetylation and downstream inflammasome activation in microglia, thereby alleviating microglia activation and cognitive impairment in mice., Conclusions: In conclusion, our findings provide evidence for a novel role of Tau in the regulation of microglia activation through acetylating NLRP3, which has potential implications for early intervention and personalised treatment of AD and related Tauopathies., (© 2024 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Background: Methamphetamine (METH) addiction causes a huge burden on society. The prefrontal cortex (PFC), associated with emotion and cognitive behaviours, is also involved in addiction neurocircuitry. Although bulk RNA sequencing has shown METH-induced gene alterations in the mouse PFC, the impact on different cell types remains unknown., Aims: To clarify the effects of METH treatment on different cell types of the PFC and the potential pathways involved in METH-related disorders., Methods: We performed single-nucleus RNA sequencing (snRNA-seq) to examine the transcriptomes of 20 465 nuclei isolated from the PFC of chronic METH-treated and control mice. Main cell types and differentially expressed genes (DEGs) were identified and confirmed by RNA fluorescence in situ hybridization(FISH)., Results: Six main cell types were identified depending on the single-cell nucleus sequencing; of particular interest were the mature oligodendrocytes in the PFC. The DEGs of mature oligodendrocytes were enriched in the myelin sheath, adenosine triphosphate (ATP) metabolic process, mitochondrial function and components, and so on. The messenger RNA levels of Aldoc and Atp5l (FISH) and the protein level of the mitochondrial membrane pore subunit TOM40 (immunofluorescence) decreased in the mature oligodendrocytes. Fast blue staining and transmission electron microscopy image indicated myelin damage, and the myelin thickness decreased in METH brains., Conclusions: snRNA-seq reveals altered transcriptomes of different cell types in mouse PFC induced by chronic METH treatment, underscoring potential relationships with psychiatric disorders., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Reducing the environmental problems caused by nitrogen loss and nitrogen pollution is of great significance. The addition of biochar to soil is a new method for increasing nitrogen interception due to the special structural and physicochemical properties of biochar. The optimal modified biochar was screened out after acid-base modification and batch adsorption test in this paper. And then the effects of different soil and biochar mixing methods on soil physicochemical properties and nitrogen adsorption and retention were explored through soil column leaching test. The results showed that the biochar with a pyrolysis temperature of 700 °C had the best adsorption effect on nitrogen after being modified by 0.1 mol/L HCI, and the adsorption capacity of nitrate nitrogen reached 121.46 mg/g. The adsorption process of ammonia nitrogen and nitrate nitrogen conformed to the Langmuir model and was mainly homogeneous monolayer. After mixing the selected modified biochar with black soil, the pH increased by 4.77%, the content of ammonia nitrogen increased by 4.89%, and the nitrate content increased by 16.62%. In this study, the adsorption effect of biochar on nitrogen in black soil was discussed, so as to explore the optimal use of biochar in soil, which provided some reference basis for the relevant research., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The preparation of an electrocatalyst for the oxygen evolution reaction (OER) with high catalytic activity, good long-term durability and rapid reaction kinetics through interface engineering is of great significance. Herein, we have developed a bimetallic sulfide particle cluster-supported three-dimensional graphene aerogel (FeNiS@GA), which serves as an efficient electrocatalyst for OER, by a one-step hydrothermal method. Profiting from the synergy of the FeNiS particle cluster with high capacitance and GA with its three-dimensional porous nanostructure, FeNiS@GA shows a high specific surface area, large pore volume, low contact resistance, and decreases the electron and ion transport routes. FeNiS@GA exhibits outstanding OER activity (when the current density is 50 mA cm -2 , the overpotential is 341 mV), low Tafel slope (63.87 mV dec -1 ) and remarkable stability in alkaline solutions, outperforming FeNiS, NiS@GA, FeS@GA and RuO 2 . Due to its simple synthesis process and excellent electrocatalytic performance, FeNiS@GA shows great potential to replace noble metal-based catalysts in practical applications.

Efficient non-noble metal bifunctional electrocatalysts can increase the conversion rate of electric energy in the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER). Herein, a ball & sheet MoS 2 /Ni 3 S 2 composite with wide-layer-spacing and high 1T-rich MoS 2 is assembled on nickel foam (NF) via a two-step solvothermal method with polymeric sulfur (S-r-DIB) as the sulfur source. The obtained material serves as both the cathode and the anode toward overall water splitting in an alkaline electrolyte. The results proved that the interpenetration of MoS 2 /Ni 3 S 2 -p with a ball and sheet structure increased the material active surface area and exposed more catalytic active sites, which contributed to the penetration of solution and the transfer of charge/hydrion. Meanwhile, two different semiconductors of MoS 2 and Ni 3 S 2 along with the presence of ample active sulfur edge sites and few-layer, wide-layer-spacing structures of MoS 2 lead to an outstanding electrocatalytic activity. In particular, the electrodes of MoS 2 /Ni 3 S 2 -p only need a battery voltage of 1.55 V at 10 mA cm -2 . The bifunctional electrocatalyst MoS 2 /Ni 3 S 2 -p also shows excellent stability at large current densities during the electrochemical test.

The novel photocatalytic advanced oxidation catalyst, ZIF-67@MXene-TA-CNF (ZIF-67@MTC) aerogels, was prepared via introducing tannic acid-coated cellulose nanofibril (TA-CNF), two-dimensional layered MXene, and ZIF-67 into a composite aerogel network. Specially, TA assisted the crosslinking of CNF through hydrogen bonds to construct the flexible aerogel skeleton, accompanied by assembly of MXene and ZIF-67. MXene not only provided sufficient attachment sites for the anchoring of ZIF-67, but also can be used as a repository for electron transfer to facilitate the separation of photogenerated electrons and holes. In the peroxymonosulfate (PMS)/aerogels/visible light system, the SO 4 - , OH and 1 O 2 were generated, and 1 O 2 was the main reactive species. As a result, 99.9 % of Tetrabromobisphenol A (TBBPA) can be degraded and the total organic carbon (TOC) removal efficiency reached 81.8 % within 40 min in this system. The results might provide a new concept for the design of biomass aerogels for applications in organic pollutant removal., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled, “Ternary ZIF-67/MXene/CNF aerogels for enhanced photocatalytic TBBPA degradation via peroxymonosulfate activation”., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Alzheimer's disease is a global public health problem and the most common form of dementia. Due to the failure of many single therapies targeting the two hallmarks, Aβ and Tau, and the multifactorial etiology of AD, there is now more and more interest in nutraceutical agents with multiple effects such as Moringa oleifera (MO) that have strong anti-oxidative, anti-inflammatory, anticholinesterase, and neuroprotective virtues. In this study, we treated APP/PS1 mice with a methanolic extract of MO for four months and evaluated its effect on AD-related pathology in these mice using a multitude of behavioral, biochemical, and histochemical tests. Our data revealed that MO improved behavioral deficits such as anxiety-like behavior and hyperactivity and cognitive, learning, and memory impairments. MO treatment abrogated the Aβ burden to wild-type control mice levels via decreasing BACE1 and AEP and upregulating IDE, NEP, and LRP1 protein levels. Moreover, MO improved synaptic plasticity by improving the decreased GluN2B phosphorylation, the synapse-related proteins PSD95 and synapsin1 levels, the quantity and quality of dendritic spines, and neurodegeneration in the treated mice. MO is a nutraceutical agent with promising therapeutic potential that can be used in the management of AD and other neurodegenerative diseases.

The aim of this study was to investigate the therapeutic value of neoadjuvant chemotherapy for breast cancer (BC) based on magnetic resonance imaging (MRI) and to evaluate its effect on depressive mood and immune function in patients. 70 female patients with BC who received neoadjuvant chemotherapy were selected for the experiment to comprehensively evaluate the MRI image findings, immune cell levels before and after chemotherapy, as well as the depression score and influencing factors of the patients during chemotherapy. The results showed that 49 patients (70%) responded to treatment, and MRI showed that the breast mass after chemotherapy was significantly reduced. 55 patients experienced depressive mood during chemotherapy, and the incidence of depression was 78.5%. Adverse symptoms such as pain, worry, sadness, vertigo, and nausea are important factors in the development of depression in patients. However, there were no significant changes in the levels of CD4+, CD8+, CD4+/CD8+, and killer cells before and after chemotherapy, and only B cells showed a significant decrease (9.78 ± 3.65% and 7.63 ± 3.65%) ( P   <  0.05). In summary, neoadjuvant chemotherapy can effectively shrink the breast mass and provide favorable conditions for subsequent surgery, and its clinical efficacy can be more accurately assessed by MRI. Neoadjuvant chemotherapy has little effect on the immune function of patients, but it will promote patients to experience depression. It provides a reference for the clinical treatment and prognosis of BC patients., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Ying Nie et al.)

Surface electromyography (sEMG) is commonly used to observe the motor neuronal activity within muscle fibers. However, decoding dexterous body movements from sEMG signals is still quite challenging. In this paper, we present a high-density sEMG (HD-sEMG) signal database that comprises simultaneously recorded sEMG signals of intrinsic and extrinsic hand muscles. Specifically, twenty able-bodied participants performed 12 finger movements under two paces and three arm postures. HD-sEMG signals were recorded with a 64-channel high-density grid placed on the back of hand and an 8-channel armband around the forearm. Also, a data-glove was used to record the finger joint angles. Synchronisation and reproducibility of the data collection from the HD-sEMG and glove sensors were ensured. The collected data samples were further employed for automated recognition of dexterous finger movements. The introduced dataset offers a new perspective to study the synergy between the intrinsic and extrinsic hand muscles during dynamic finger movements. As this dataset was collected from multiple participants, it also provides a resource for exploring generalized models for finger movement decoding., (© 2022. The Author(s).)

Co-doped magnetic Mn 3 O 4 was synthesized by the solvothermal method and adopted as an effective catalyst for the degradation of oxytetracycline (OTC) in water. Synergistic interactions between Co-Mn 3 O 4 and Fe 3 O 4 not only resulted in the enhanced catalytic activity through the activation of peroxymonosulfate (PMS) to degrade OTC but also made Fe 3 O 4 /Co-Mn 3 O 4 easy to be separated and recovered from aqueous solution. 94.2% of OTC could be degraded within 60 min at an initial OTC concentration of 10 mg L -1 , catalyst dosage of 0.2 g L -1 , and PMS concentration of 10 mM. The high efficiency of OTC removal was achieved in a wider pH range of 3.0-10.0. Co (II), Co (III), Fe (II), Fe (III), Mn (II), Mn (III), and Mn (IV) on Fe 3 O 4 /Co-Mn 3 O 4 were identified as catalytic sites based on XPS analysis. The free radical quenching experiments showed that O 2 •- radicals and 1 O 2 played the main role in the degradation process and the catalytic degradation of OTC involved both free radical and non-free radical reactions. Eventually, the intermediates of OTC degradation were examined, and the possible decomposition pathways were proposed. The excellent catalytic performances of Fe 3 O 4 /Co-Mn 3 O 4 came from the fact that the large specific surface area could provide abundant active sites for the activation of PMS and the redistribution of inter-atomic charges accelerated the redox reactions of metal ions. The high degradation efficiency and rate constant of OTC in actual water samples indicated that Fe 3 O 4 /Co-Mn 3 O 4 had a good practical application potential., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Alzheimer's disease (AD) is the most common neurodegenerative disease with limited therapeutic strategies. Cell cycle checkpoint protein kinase 1 (Chk1) is a Ser/Thr protein kinase which is activated in response to DNA damage, the latter which is an early event in AD. However, whether DNA damage-induced Chk1 activation participates in the development of AD and Chk1 inhibition ameliorates AD-like pathogenesis remain unclarified. Here, we demonstrate that Chk1 activity and the levels of protein phosphatase 2A (PP2A) inhibitory protein CIP2A are elevated in AD human brains, APP/PS1 transgenic mice, and primary neurons with Aβ treatment. Chk1 overexpression induces CIP2A upregulation, PP2A inhibition, tau and APP hyperphosphorylation, synaptic impairments, and cognitive memory deficit in mice. Moreover, Chk1 inhibitor (GDC0575) effectively increases PP2A activity, decreases tau phosphorylation, and inhibits Aβ overproduction in AD cell models. GDC0575 also reverses AD-like cognitive deficits and prevents neuron loss and synaptic impairments in APP/PS1 mice. In conclusion, our study uncovers a mechanism by which DNA damage-induced Chk1 activation promotes CIP2A-mediated tau and APP hyperphosphorylation and cognitive dysfunction in Alzheimer's disease and highlights the therapeutic potential of Chk1 inhibitors in AD., (© 2022. The Author(s).)

Background: Obesity is a worldwide health problem that has been implicated in many diseases, including Alzheimer's disease (AD). AD is one of the most common neurodegenerative disorders and is characterized by two pathologies, including extracellular senior plaques composed of amyloid-β (Aβ) and intracellular neurofibrillary tangles (NFTs) consisting of abnormally hyperphosphorylated tau. According to current research, a high-fat diet (HFD) could exacerbate Aβ accumulation, oxidative damage, and cognitive defects in AD mice. However, the accurate role of HFD in the pathogenesis of AD is far more unclear., Objective: To explore the accurate role of HFD in the pathogenesis of AD., Methods: Open Field, Barns Maze, Elevated zero-maze, Contextual fear condition, Tail suspension test, western blotting, immunofluorescence, Fluoro-Jade C Labeling, Perls' Prussian blue staining, and ELISA were used., Results: HFD caused nonheme iron overload in the brains of APPswe/PS1dE9 (APP/PS1) mice. Furthermore, the administration of M30 (0.5 mg/kg) for iron chelation once every 2 days per os (p.o.) for 1 month remitted memory deficits caused by HFD in APP/PS1 mice. Notably, a variety of hematological parameters in whole blood had no difference after iron chelation. In addition, iron chelation effectively reduced synaptic impairment in hippocampus and neuronal degeneration in cortex in the HFD-fed APP/PS1 mice. Meanwhile, iron chelation decreased Aβ1-40 and Aβ1-42 level as well as neuroinflammation in HFD-fed APP/PS1 mice., Conclusion: These data enhance our understanding of how HFD aggravates AD pathology and cognitive impairments and might shed light on future preclinical studies.

Smart nanomaterials that can simultaneously detect and eliminate contaminants in water environment are significant for health protection. To achieve such goal, Co-MOF-74 was in-situ assembled on regenerated cellulose membranes followed by calcination process, thus achieving dual-functional Co 3 O 4 /cellulose derivative membrane (Co 3 O 4 /CDM) catalyst. The Co 3 O 4 morphology was readily controlled by further recrystallization of the deposited MOF precursor. Combining the high enrichment ability of cellulose membrane and outstanding peroxidase-active of Co 3 O 4 , the fast color reaction for phenol was accomplished within 10 min by Co 3 O 4 /CDM with the assistance of H 2 O 2 and 4-aminoantipyrine (4-AAP). Moreover, the Co 3 O 4 /CDM also portrayed an excellent degradation property for phenol elimination via sulfate radical-advanced oxidation processes (SR-AOPs). The degradation efficiency of phenol reached 93% in 20 min, and the possible mineralization mechanism was proposed based on the XPS and LC-MS analysis. Thus, Co-MOF-74 derived Co 3 O 4 /CDM shows excellent properties in aiding the colorimetric detection and degradation of phenol in aqueous solutions., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Few-layer and 1T-rich MoS 2 is synthesized by a one-step solvothermal process using a rigid segment-containing polysulfide as a concomitant sulfur source and in situ intercalator. The prepared MoS 2 displays superior hydrogen evolution reaction activity, providing a facile and mild approach for the development of high performing MoS 2 and other two-dimensional lamellar materials.

The development of non-precious metal electrocatalysts with high activity, good durability and low cost to replace precious metal electrocatalysts is highly demanded for oxygen evolution reaction (OER). However, the higher overpotential, less catalytic sites and lower catalytic rate of precious metal electrocatalysts affect their practical application, which needs to be optimized from the aspects of structural design (e.g., specific morphology/particle size, geometric/electronic structures). In this study, we reported a high topological tri-metal phosphide of CoP@FeNiP derived from the composite structure of ZIF-67 twined on a FeNi-LDH shelled with ultrathin carbon networks (ZIF-67/FeNi-LDH) grown on a nickel foam. In the synthesis process of FeNi-LDH, the addition of polyvinylpyrrolidone (PVP) promoted the self-assembly of the topological structure of FeNi-LDH and further nucleation of the topological structure of the ZIF-67 precursor on FeNi-LDH. Besides, CoP@FeNiP inherits the topological structure of ZIF-67/FeNi-LDH. The obtained CoP@FeNiP/NF shows superior OER performance with a low overpotential of ∼283 mV at 100 mA cm-2, a low Tafel slope of ∼31.8 mV dec-1 and a conservation rate of catalytic activity of ∼98% after 110 h of continuous electrolysis at 10 mA cm-2. The remarkable activity of CoP@FeNiP/NF can be attributed to its unique structural features, such as the hierarchical morphology, large surface area, ultrathin carbon networks and the feature of phosphide, all of which simultaneously promote the OER process. The extraordinary catalytic activities and stability of CoP@FeNiP/NF are significant to meet the industrial requirements for bulk water electrocatalysis.

Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) share some pathological features, including tau hyperphosphorylation and deficits in insulin signaling, but the underlying mechanism and effective drugs for treating AD are unknown. The AD-like brain impairments are almost same in both of mouse type 2 DM models induced by the multiple low-dose intraperitoneal (i.p.) streptozotocin (STZ) injection and twice intracerebroventricular (i.c.v.) STZ injection. We found that memory disorders, impairment of insulin signaling, and AD-like tauopathies were exhibited in two different STZ-induced mouse models and that the level of Advanced Glycation End Products (AGEs) was increased in two STZ mouse models. Inhibition of mTORC1 with rapamycin reversed the deficits of insulin signaling associated kinases activity, decreased levels of AGEs and AD-like tau phosphorylation, and also improved memory deficit in both STZ mice. Rapamycin attenuated HG-induced tau hyperphosphorylation via the AKT/AMPK/GSK-3β pathways and p70S6K in SH-SY5Y cells. Taken together, these data demonstrated that rapamycin improved STZ-induced AD-like tauopathies and memory deficit in mice via improving p70S6K and AKT/AMPK/GSK-3β signaling and decreasing AGEs. Therefore, regulating insulin signaling via mTORC1 is a new strategy for preventing T2DM-associated AD, and mTORC1 is a potential drug target., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

AgO nanoparticles were successfully integrated into NiCo2O4 nanosheets for enhanced electrochemical catalysis ability and stability in the oxygen evolution reaction (OER). The chrysanthemum-like NiCo2O4/AgO composites mounted on nickel foam (NF) were synthesized by a hydrothermal-calcination method. AgO upgraded the ratio of Co3+/Co2+ and thus regulated the intrinsic activity of the species. The highly hierarchical structure of NiCo2O4/AgO composed of 0D AgO nanoparticles, 1D NiCo2O4 needles, 2D NiCo2O4 nanosheets, and 3D chrysanthemum-like bundles grown on NF bestowed the high surface area and mesoporous structure for the easy evolution of O2. The Ni atoms in NiCo2O4 originating in situ from NF in the process of AgO formation produced an integrated electrode of the active component of NiCo2O4 bound on NF with a superb highway for charge transfer. AgO significantly tuned the structure and physicochemical properties of NiCo2O4. As a result, NiCo2O4/AgO/NF exhibited excellent OER performance with an overpotential of 232 mV to obtain a current density of 10 mAcm-2 in an alkaline electrolyte, and the catalyst showed a small loss of the initial catalyst activity for 50 h and over 5000 cycles. This study provides a pathway for developing high-performance OER electrocatalysts.

A nitrogen doped bio-carbon catalyst with high specific surface area and a hierarchical interconnected porous structure was fabricated by an in situ gas-foaming strategy from sodium alginate and ammonium chloride. The optimized catalyst displays a fabulous ORR activity, providing a facile approach for the mass production of metal-free bio-carbon catalysts in fuel cells and metal-air batteries.

The sustained release of antimicrobial therapeutics for wound dressing has become an attractive design strategy for prolonging the timespan of wound dressings and for reducing the risk of chronic wound infection. Recently, cellulose-based membrane has become a preferred option of wound dressings for the treatment of burn wounds and skin ulcers. In this work, novel cellulose membrane incorporated with mesoporous silica particles (SBA-15) was developed as an antimicrobial wound dressing with desirable sustained release functionality for targeting persistent bacterial pathogens. Attributed to a coated layer of calcium carbonate (CaCO 3 ), SBA-15 particles were free from corrosion in alkaline condition during the preparation of cellulose-based composite membranes. SEM, TEM and BET results showed that the morphology, specific surface area, pore size and pore volume of pristine SBA-15 were preserved after the incorporation of CaCO 3 -coated SBA-15 into the cellulose matrix, while the mesoporous structure of SBA-15 was significantly disrupted without the use of CaCO 3 coating. The resultant composite membranes containing 30 wt% SBA-15 (denoted as CM-Ca2-SBA(30%)) achieved 3.6 wt% of antimicrobial drug loading. Interestingly, CM-Ca2-SBA(30%) demonstrated the sustained release property of chloramphenicol for 270 h, driven by a two-stage drug release processes of SBA-15/cellulose. The water vapor permeability (WVTR) and swelling properties of composite membranes were shown to have complied with the primary requirements of wound dressing. Antibacterial assays revealed that strong antibacterial activities (144 h) of the composite membranes against Staphylococcus aureus and Eschericia coli were achieved. All results displayed that the strategy of coating silica with CaCO 3 helps to obtain cellulose-silica composite membranes with desirable sustained release profiles and strong antibacterial activities. The antibacterial SBA-15/cellulose composite membranes show potential for the application of wound dressing.

A three-dimensional MIL-100(Fe)/graphene hybrid aerogel (MG-HA) was fabricated via in situ decoration of graphene oxide with MIL-100(Fe) nanoparticles. The resulting MG-HA with interconnected pore structure was applied as both adsorbent and catalyst for the removal of methylene blue (MB) from aqueous solutions. The result shows that the saturation adsorption capacity of the MG-HA was as high as 333.33 mg g -1 , exceeding that of both the corresponding pristine graphene aerogel and MIL-100(Fe) nanoparticles. In the presence of hydrogen peroxide, MG-HA further exhibited catalytic degradation ability. The dual functions achieved a synergistic effect leading to the quick and complete removal of MB. The benefit was revealed in the treatment of high concentration of pollutants without leaving secondary pollution. The merit was intuitively demonstrated in the instant removal of MB through a model separation device in comparison with a series of common adsorbents. A feasible mathematic model was built based on the synergistic adsorption/catalysis process, which perfectly fitted the experimental data. A pseudo-second-order adsorption process and pseudo-first-order catalytic degradation kinetics were revealed. Additionally, the MG-HA was able to retain 93.4% of its initial removal efficiency after 5 cycles of application. The macro-material body can be easily separated and reused without a time-consuming and high-cost recycling process., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The performance of a chemosensor is closely related to its structure. A new Schiff bass (DFSB) based on 4,5-diazafluorene units has been synthesized in this work. The interaction of DFSB with different metal ions has been studied using UV-vis absorption spectra and fluorescent spectra. The results show that DFSB is a highly selective and sensitive probe for Al 3+ ions over other commonly coexisting metal ions in ethanol. A very obvious fluorescence enhancement effect was observed, and a turn-on ratio over 1312-fold was triggered with the addition of 10 equiv. of Al 3+ ions. What is more, such fluorescent responses could be detected by the naked eye under a UV-lamp. The lowest detection limit for Al 3+ was determined as 3.7 × 10 -8 M. The complex solution (DFSB-Al 3+ ) exhibited reversibility with EDTA. These results may be caused by the unique molecular structure., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

We report the discovery of two new forms (II and III) of a potential non-steroidal anti-inflammatory and thyroid drug, 2-((2,6-dimethylphenyl)amino)benzoic acid (HDMPA) through solution growth and thermal treatment of crystals. Form II has been discovered through crystal growth in a variety of solvents, and characterized by single-crystal X-ray diffraction, powder X-ray diffraction (PXRD), FT-IR, and Raman spectroscopy. Form II converts into form III upon thermal treatment, as indicated by the phase behavior study of form II with differential scanning calorimetry (DSC). Form III has been characterized by IR, Raman and PXRD. Conformational flexibility of the molecule seems to lead to the polymorphism of the system. A conformational scan shows the conformational minima correspond to the conformers in the polymorphs. Lattice energy calculations show energies of -48.14 and -50.31 kcal mol -1 for forms I and II, providing information on the relative stability for each form. Hirshfeld analysis revealed that intermolecular interactions such as C⋯C, H⋯H, C⋯H, and H⋯O contribute to the stability of the crystal forms., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

A new 4,5-diazafluorene-based fluorescent chemosensor has been synthesized by Schiff base condensation of 9,9-bis(3,5-dimethyl-4-aminophenyl)-4,5-diazafluorene with salicylaldehyde. The interaction of Schiff base with different metal ions has been studied over photofluorescent spectra. The results showed that Schiff base exhibited 194-fold enhancements in fluorescence at 465 nm after Zn(2+) ions. Such fluorescent responses could be detected by naked eye under UV-lamp. The complex solution (L-Zn(2+)) exhibited reversibility with EDTA.

FexOy@FexOy/C nanoparticles with a soap-bubble-like shell have been synthesized, and the materials exhibit excellent Fenton catalytic performance. More importantly, FexOy@FexOy/C nanoparticles as catalysts and precursors could catalyze organic dye molecules to form iron oxide@organic dye polymer core-shell nanospheres.

Functionalized magnetic adsorbents (FMAs) were synthesized by a facile and surfactant-free one-pot solvothermal approach, using iron(III) chloride hexahydrate as the precursor, ethylene glycol as the reducing agent, ammonium acetate, and EDTA-2Na as an electrostatic stabilization agent. The self-assembly process of the functionalized magnetic adsorbents has been investigated and a plausible mechanism is proposed. The resulting functionalized magnetic adsorbents have relatively high specific surface areas (71.6 m(2) g(-1)), excellent magnetic properties and rich functional groups (carboxyl groups, hydroxyl groups and hydrophobic groups). Meanwhile, the resulting FMAs were employed in the adsorption of dyes and heavy metal ions from aqueous solution. Herein, we took two types of typical pollutants, dyes (methylene blue (MB) and malachite green (MG)) and toxic heavy metal ions (Cr(VI) and Pb(II)) as examples of organic and inorganic pollutants in environmental water. The excellent intrinsic properties of the FMAs led to a stronger adsorption ability than a solid Fe3O4 adsorbent for MB, MG, Cr(VI) and Pb(II). Especially, the simultaneous adsorption of the functionalized flower-like magnetic adsorbents for MG and Pb(II) was also determined in a binary system. Finally, it was demonstrated that the resulting flower-like magnetic adsorbents are expected to be a good candidate as an adsorbent for water treatment.

We report a facile fabrication of a host-metal-guest coordination-bonding system in a mesostructured Fe3O4/chitosan nanoparticle that can act as a pH-responsive drug-delivery system. The mesostructured Fe3O4/chitosan was synthesized by a solvothermal approach with iron(III) chloride hexahydrate as a precursor, ethylene glycol as a reducing agent, ammonium acetate as a porogen, and chitosan as a surface-modification agent. Subsequently, doxorubicin (DOX), acting as a model drug (guest), was loaded onto the mesostructured Fe3O4/chitosan nanoparticles, with chitosan acting as a host molecule to form the NH2-Zn(II)-DOX coordination architecture. The release of DOX can be achieved through the cleavage of coordination bonds that are sensitive to variations in external pH under weakly acidic conditions. The pH-responsive nature of the nanoparticles was confirmed by in vitro releases and cell assay tests. Furthermore, the relaxation efficiency of the nanoparticles as high-performance magnetic resonance imaging contrast agents was also investigated. Experimental results confirm that the synthesized mesostructured Fe3O4/chitosan is a smart nanovehicle for drug delivery owing to both its pH-responsive nature and relaxation efficiency., (Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Hypoxia was shown to be associated with an increased risk of Alzheimer's disease (AD). The effects of hypoxia on the development of AD pathology and spatial memory ability and the possible molecular mechanisms remain poorly understood. In this study, we demonstrate that rats exposed to a hypoxic condition (10% oxygen concentration) for 1, 2, 4 and 8 weeks (6 h each day) displayed spatial memory impairment and increased tau phosphorylation at Ser198/199/202, Thr205, Ser262, Ser396 and Ser404 in the hippocampus. Concomitantly, the levels of Tyr216-phosphorylated glycogen synthase kinase (GSK)-3β (activated form of GSK-3β) and Tyr307-phosphorylated protein phosphatase 2A (inactivated form of PP2A) were significantly increased in the hippocampus of the rats with 1, 2, 4 and 8 weeks of hypoxia exposure, while the levels of methylated PP2A (activated form of PP2A) were significantly decreased in the hippocampus of the rats with 4 and 8 weeks of hypoxia exposure. In addition, the content of malondialdehyde, an indicator of oxidative stress, was elevated, whereas the activity of superoxide dismutase was not significantly changed in the hippocampus of the rats exposed to hypoxia. Taken together, these data demonstrated that hypoxia induced tau hyperphosphorylation and memory impairment in rats, and that the increased tau phosphorylation could be attributed to activation of GSK-3β and inactivation of PP2A. These data suggest that interventions to improve hypoxia may be helpful to prevent the development of AD pathology and cognitive impairment., (© 2014 S. Karger AG, Basel.)

Aim. This study aimed to analyze blood lipid levels, temporal trend, and age distribution of dyslipidemia in civil aviators in China. Methods. The 305 Chinese aviators were selected randomly and followed up from 2006 to 2011. Their total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were evaluated annually. Mean values for each parameter by year were compared using a linear mixed-effects model. The temporal trend of borderline high, high, and low status for each index and of overall borderline high, hyperlipidemia, and dyslipidemia by year was tested using a generalized linear mixed model. Results. The aviators' TC (F = 4.33, P < 0.01), HDL-C (F = 23.25, P < 0.01), and LDL-C (F = 6.13, P < 0.01) values differed across years. The prevalence of dyslipidemia (F = 5.53, P < 0.01), borderline high (F = 6.52, P < 0.01), and hyperlipidemia (F = 3.90, P < 0.01) also differed across years. The prevalence rates for hyperlipidemia and dyslipidemia were the highest in the 41-50-year-old and 31-40-year-old groups. Conclusions. Civil aviators in China were in high dyslipidemia and borderline high level and presented with dyslipidemia younger than other Chinese populations.

Glycogen synthase kinase-3 beta (GSK-3β) dysfunction may play an essential role in the pathogenesis of psychiatric, metabolic, neurodegenerative diseases, in which oxidative stress exists concurrently. Some studies have shown that GSK-3β activity is up-regulated under oxidative stress. This study evaluated how oxidative stress regulates GSK-3β activity in human embryonic kidney 293 (HEK293)/Tau cells treated with hydrogen peroxide (H₂O₂). Here, we show that H₂O₂ induced an obvious increase of GSK-3β activity. Surprisingly, H₂O₂ dramatically increased phosphorylation of GSK-3β at Ser9, an inactive form of GSK-3β,while there were no changes of phosphorylation of GSK-3β at Tyr216. Moreover, H₂O₂ led to a transient [Ca²⁺](i) elevation, and simultaneously increased the truncation of GSK-3β into two fragments of 40 kDa and 30 kDa, whereas inhibition of calpain decreased the truncation and recovered the activity of GSK-3β. Furthermore, tau was hyperphosphorylated at Ser396, Ser404, and Thr231, three most common GSK-3β targeted sites after 100 μM H₂O₂ administration in HEK293/Tau cells, whereas inhibition of calpain blocked the tau phosphorylation. In addition, we found that there were no obvious changes of Cyclin-dependent kinase 5 (CDK5) expression (responsible for tau phosphorylation) and of p35 cleavage, the regulatory subunit of CDK5 in H₂O₂-treated HEK293/Tau cells. In conclusion, Ca²⁺-dependent calpain activation leads to GSK-3β truncation, which counteracts the inhibitory effect of Ser9 phosphorylation, up-regulates GSK-3β activity, and phosphorylates tau in H₂O₂-treated HEK293/Tau cells., (© 2013 International Society for Neurochemistry.)

A simple preparation process for the monodispersed pH-sensitive core-shell magnetic microspheres was carried out consisting of chitosan self-assembled on magnetic iron oxide nanoparticles. Meanwhile, glucoamylase was immobilized as a model enzyme on this carrier of Fe(3)O(4)/CS microspheres by ionic adsorption. The morphology, inner structure, and high magnetic sensitivity of the resulting magnetic chitosan microspheres were studied, respectively, with a field emission scanning electron microscope (SEM), transmission electron microscope (TEM), FT-IR spectroscopy, thermogravimetric analysis (TGA), and a vibrating sample magnetometer (VSM). Subsequently, the properties of glucoamylase immobilized on the regenerated supports were also investigated by determining storage stability, pH stability, reusability, magnetic response, and regeneration of supports. The results from characterization and determination remarkably indicated that the immobilized glucoamylase obtained presents excellent storage stability, pH stability, reusability, magnetic response, and regeneration of supports. Therefore, this kind of magnetic Fe(3)O(4)/CS microspheres with perfect monodispersity should be an ideal support for enzyme immobilization.

Accumulation of unfolded proteins can disturb the functions of the endoplasmic reticulum (ER), leading to ER-stress or unfolded protein response (UPR). Recent data have shown that activation of UPR can be found in postmortem brains of Alzheimer's disease (AD) patients; and biological markers for activation of UPR are abundant in neurons with diffuse phosphorylated tau. Although these observations suggest a linkage between ER-stress and tau pathology, little is known of their relationship. In this study, we found that high levels of phosphorylated PKR-like ER-resident kinase (p-PERK) and phosphorylated eukaryotic initiation factor 2 alpha (p-eIF2α) as markers for activation of UPR in the hippocampus of aged P301L mutant tau transgenic mice. The immunoreactivity of p-PERK was found to co-localize with that of phosphorylated tau. We then hypothesized that phosphorylation of tau could induce ER-stress and vice versa in promoting AD-like pathogenesis. By using the protein phosphatase 2A inhibitor okadaic acid (OA) as an inducer for phosphorylation of tau, we found that primary cultures of rat cortical neurons treated with OA triggered UPR as indicated by increased levels of p-PERK and p-eIF2α, splicing of mRNA for xbp-1 and elevated levels of mRNA for GADD153. On the other hand, thapsigargin as an ER-stress inducer stimulated phosphorylation of tau at Thr231, Ser262 and Ser396. Thapsigargin also induced activation of caspase-3 and cleavage of tau. These findings suggested that ER-stress and hyperphosphorylation of tau could be induced by each other to form a vicious cycle to propagate AD-like neurodegeneration.

Brain iron deposition has been proposed to play an important role in the pathophysiology of Alzheimer disease (AD). The aim of this study was to investigate the correlation of brain iron accumulation with the severity of cognitive impairment in patients with AD by using quantitative MR relaxation rate R2' measurements. Fifteen patients with AD, 15 age- and sex-matched healthy controls, and 30 healthy volunteers underwent 1.5T MR multi-echo T2 mapping and T2* mapping for the measurement of transverse relaxation rate R2' (R2'=R2*-R2). We statistically analyzed the R2' and iron concentrations of bilateral hippocampus (HP), parietal cortex (PC), frontal white matter (FWM), putamen (PU), caudate nucleus (CN), thalamus (TH), red nucleus (RN), substantia nigra (SN), and dentate nucleus (DN) of the cerebellum for the correlation with the severity of dementia. Two-tailed t-test, Student-Newman-Keuls test (ANOVA) and linear correlation test were used for statistical analysis. In 30 healthy volunteers, the R2' values of bilateral SN, RN, PU, CN, globus pallidus (GP), TH, and FWM were measured. The correlation with the postmortem iron concentration in normal adults was analyzed in order to establish a formula on the relationship between regional R2' and brain iron concentration. The iron concentration of regions of interest (ROI) in AD patients and controls was calculated by this formula and its correlation with the severity of AD was analyzed. Regional R2' was positively correlated with regional brain iron concentration in normal adults (r=0.977, P<0.01). Iron concentrations in bilateral HP, PC, PU, CN, and DN of patients with AD were significantly higher than those of the controls (P<0.05); Moreover, the brain iron concentrations, especially in parietal cortex and hippocampus at the early stage of AD, were positively correlated with the severity of patients' cognitive impairment (P<0.05). The higher the R2' and iron concentrations were, the more severe the cognitive impairment was. Regional R2' and iron concentration in parietal cortex and hippocampus were positively correlated with the severity of AD patients' cognitive impairment, indicating that it may be used as a biomarker to evaluate the progression of AD.

Magnetic carbon nanotubes (MCNTs) with necklace-like nanostructures was prepared via hydrothermal method, and hyperbranched poly(amidoamine) (PAMAM) was grafted on the surface of MCNTs on the basis of the Michael addition of methyl acrylate and the amidation of the resulting ester with a large excess of ethylenediamine (EDA), which could achieve generational growth under such uniform stepwise reactions. The terminal -NH(2) groups from the dendritic PAMAM were reacted with differently functionalized groups to form functionalized MCNTs. Subsequently, enzyme was immobilized on the functionalized MCNTs through adsorption, covalent bond, and metal-ion affinity interactions. The immobilization of glucoamylase, hereby chosen as model enzyme, onto the differently functionalized MCNTs is further demonstrated and assessed based on its activity, thermal stability, as well as reusability. Besides ease in recovery by magnetic separation, the immobilized glucoamylase on functionalized MCNTs offers superior stability and reusability, without compromising the substrate specificity of free glucoamylase. Furthermore, the results indicate that the metal-chelate dendrimer offers an efficient route to immobilize enzymes via metal-ion affinity interactions. The applicability of the regenerated supports in the current study is relevant for the conjugation of other enzymes beyond glucoamylase.

Neurofilaments (NFs) are hyperphosphorylated and accumulate in Alzheimer's disease (AD) brains. In this study, employing the transgenic mouse model, we explored the effect of presenilin 1 (PS-1) mutation on the phosphorylation and distribution of NFs. Western blot analysis showed that there was a significant increase in the phosphorylation of NF-H and NF-M subunits with a concomitant increase in phosphorylated c-Jun N-terminal protein kinase 1/2 (JNK1/2) mitogen-activated protein kinase (MAPK) in hippocampus of PS-1 transgenic mice compared to that of wild-type littermates. Immunohistochemical analysis revealed that phosphorylated NFs accumulated throughout the hippocampal neurons of the transgenic mice. These findings suggest that PS-1 mutation may induce hyperphosphorylation and accumulation of NFs via a JNK1/2-involved mechanism.

Huntington's disease (HD) is an autosomal dominant inheritable neurodegenerative disorder caused by expansion of a polyglutamine repeat in the amino-terminal region of huntingtin. Polyglutamine expansion causes mutant huntingtin to aggregate and accumulate in the nuclei and cytoplasm of neurons. The aggregated amino-terminal fragments of mutant huntingtin are toxic to neuronal cells and may be involved in the neurodegeneration in HD patient brains. Although nuclear mutant huntingtin has been found to affect gene expression, the effect of cytoplasmic mutant huntingtin remains to be investigated. We established stably transfected mouse neuroblastoma (N2a) cells that express soluble amino-terminal fragments of huntingtin containing 20 (20Q) or 150 (150Q) glutamine repeats. In these stable cell lines, both 20Q and 150Q are diffusely distributed in the cytoplasm without aggregate formation. However, the stable 150Q cells are deficient in neurite outgrowth. Compared with wild-type N2a cells and cells stably expressing 20Q, stable 150Q cells also have decreased viability and are more susceptible to apoptotic stimulation. These findings suggest that the cytoplasmic soluble mutant huntingtin is also toxic to cells.

DDPH (1-(2, 6-dimethylphenoxy)-2-(3, 4-dimethoxyphenylethylamino) propane hydrochloride), a candidate drug known to be an alpha(1)-adrenoceptor antagonist, can efficiently penetrate through blood brain barrier and inhibit the contraction of vascular smooth muscle in the brain. In rats with chronic cerebral hypoperfusion after permanent bilateral carotid artery ligation, we found that DDPH treatment at 6 or 12 mg/kg per day for 30 days significantly reversed pathological changes such as glial cell proliferation and nuclei shrinkage and reduced neuronal cell loss. In vivo electrophysiological studies revealed that DDPH increased long-term potentiation that was inhibited in these animals. In water maze tests, the percentage of time spent in the target quadrant (Q3) for ischemic rats (20.17+/-2.87%) was much shorter than that for the sham rats (45.39+/-3.68%), but DDPH at 12 mg/kg increased the time (39.58+/-3.77%) spent in Q3 in ischemic rats by 96.23%. These data suggested that DDPH improved the learning and memory performance significantly in rats with ischemia induced by bilateral carotid artery ligation. DDPH also lowered the levels of malondialdehyde (MDA), which was increased in the hypoperfused rats, and enhanced the activities of superoxide dismutase (SOD) and glutathione peroxidase, which were decreased in these rats. Further more, immunohistochemistry, RT-PCR assays and Western blot study demonstrated that DDPH attenuated the decreased expression of NMDAR2B (NR2B) in cortex and hippocampal CA1 region of the rats after bilateral carotid artery ligation. Our results suggest that DDPH may have favorable effects for the subjects in cerebrovascular insufficiency state following ischemic stroke.

One of the neuropathological features of Alzheimer's disease (AD) is the deposition of senile plaques containing beta-amyloid (A beta). There is limited evidence for the treatment to arrest A beta pathology of AD. In our present study, we tested the effect of coenzyme Q10 (CoQ10), an endogenous antioxidant and a powerful free radical scavenger, on A beta in the aged transgenic mice overexpressing Alzheimer presenilin 1-L235P (leucine-to-proline mutation at codon 235, 16-17 months old). The treatment by feeding the transgenic mice with CoQ10 for 60 days (1,200 mg kg(-1) day(-1)) partially attenuated A beta overproduction and intracellular A beta deposit in the cortex of the transgenic mice compared with the age-matched untreated transgenic mice. Meanwhile, an increased oxidative stress reaction was detected as evidenced by elevated level of malondialdehyde (MDA) and decreased activity of superoxide dismutase (SOD) in the transgenic mice relative to the wild-type mice, and supplementation of CoQ10 partially decreased MDA level and upregulated the activity of SOD. The results indicate that oxidative stress is enhanced in the brain of the transgenic mice, that this enhancement may further promote A beta 42 overproduction in a vicious formation, and that CoQ10 would be beneficial for the therapy of AD.

Epidemiological and clinical data suggest that homocysteine (Hcy) may increase the risk of Alzheimer's disease, but the underlying mechanisms are elusive. To investigate the effect of Hcy on phosphorylation of tau, we injected Hcy into the lateral cerebral ventricle of rats. We found that level of the hyperphosphorylated tau at PHF-1 (Ser396/404) and tau-1 (Ser198/199/202) epitopes was elevated prominently at 6, 9, and 12 h after the injection, and it was recovered to normal at 24 h. Simultaneously, the level of protein phosphatase-2A catalytic subunit (PP-2Ac) was reduced markedly as compared with control. These results imply that Hcy may induce hyperphosphorylation of tau with PP-2Ac involved mechanism.

The aim of this study is to investigate the effects of baicalein on cognitive impairment and neuronal degeneration in a rat model of chronic cerebral hypoperfusion induced by permanent occlusion of bilateral common carotid arteries (2VO). It was found that baicalein (2 or 4 mg/kg/day, i.p.) significantly improved 2VO-induced cognitive deficits and neuropathological changes. Biochemical and histological examinations revealed that baicalein reduced the increased activities of superoxide dismutase (SOD) and malondialdehyde (MDA), and attenuated the decreased activities of glutathione peroxidase (GPx) and catalase in 2VO rats. The results of the present observation suggest that baicalein has therapeutic potential for the treatment of vascular dementia, which is most likely related, at least in part, to its antioxidant action.

Parkinson's disease (PD) is the most frequent neurodegenerative movement disorder. Mutations in the PINK1 gene are linked to the autosomal recessive early onset familial form of PD. The physiological function of PINK1 and pathological abnormality of PD-associated PINK1 mutants are largely unknown. We here show that inactivation of Drosophila PINK1 (dPINK1) using RNAi results in progressive loss of dopaminergic neurons and in ommatidial degeneration of the compound eye, which is rescued by expression of human PINK1 (hPINK1). Expression of human SOD1 suppresses neurodegeneration induced by dPINK1 inactivation. Moreover, treatment of dPINK1 RNAi flies with the antioxidants SOD and vitamin E significantly inhibits ommatidial degeneration. Thus, dPINK1 plays an essential role in maintaining neuronal survival by preventing neurons from undergoing oxidative stress, thereby suggesting a potential mechanism by which a reduction in PINK1 function leads to PD-associated neurodegeneration.

Breviscapine, a traditional Chinese medicine, is extensively used in clinic to treat cardiovascular diseases and cerebrovascular injury. In this study, we demonstrated the effects of breviscapine on vascular dementia (VD) rats, which were mimicked by permanent occlusion of bilateral common carotid arteries. Breviscapine (2 mg/kg for 14 d) improved the performance of learning and memory of VD rats in Morris water maze, decreased the level of lipid peroxidation and free radicals, and attenuated the pathological alterations, such as nuclear shrink, cellular edema and irregular arrangement of pyramidal layer in the hippocampal CA(1) area. In vitro experiment, breviscapine (50 microg/l) protected cortical neuron from injury and decreased intracellular calcium overloading induced by H2O2 (10 mM). The results suggest that breviscapine has therapeutic effect on cerebral ischemia and vascular dementia.

The abnormal hyperphosphorylation of tau protein is one of the hallmarks of Alzheimer disease and other tauopathies; as yet the exact role of various tau kinases in this pathology is not fully understood. Here, we show that injection of isoproterenol, an activator of cAMP-dependent kinase (PKA), into rat hippocampus bilaterally results in the activation of PKA, calcium/calmodulin-dependent kinase II and cyclin-dependent kinase-5, inhibition of protein phosphatase-2A, hyperphosphorylation of tau at several Alzheimer-like epitopes and a disturbance of spatial memory retention 48 h after the drug injection. These findings suggest the involvement of PKA and PKA-mediated signaling pathway in the Alzheimer-like tau hyperphosphorylation and memory impairment.

In this study, we studied the effect of glycogen synthase kinase-3 (GSK-3) overactivation on neurofilament phosphorylation in cultured cells. After N2a cells were treated with the specific inhibitor (wortmannin) of phosphoinositol-3 kinase (PI-3K) or treated with wortmannin and the specific inhibitor (LiCl) of glycogen synthase kinase-3 (GSK-3), GSK-3 activity and neurofilament phosphorylation were detected by using GSK-3 activity assay, Western blots and immunofluoresence. Our results showed that after treatment of N2a cells with wortmannin for 1 h, overactivation of GSK-3 caused a reduced staining with antibody SMI32 and an enhanced staining with antibody SMI31. When N2a cells were treated with wortmannin and LiCl, the activity of GSK-3 was reduced substantially. At the same time, the phosphorylation of neurofilament was also reduced. The study demonstrated that overactivation of GSK-3 induced hyperphosphorylation of neurofilament and suggested that in vitro overactivation of GSK-3 resulted in neurofilament hyperphosphorylation and this may be the underlying mechanism for Alzheimer's disease.

In Alzheimer's disease (AD), hyperphosphorylation of tau may be the underlying mechanism for the cytoskeletal abnormalities and neuronal death. It was reported that cyclin-dependent kinase5 (cdk-5) could phosphorylate tau at most AD-related epitopes in vitro. In this study, we investigated the effect of cdk-5 overexpression on tau phosphorylation and spatial memory in rat. We demonstrated that 24 h after transfection into rat hippocampus, cdk-5 was overexpressed and induced a reduced staining with antibody tau-1 and an enhanced staining with antibodies 12e8 and PHF-1, suggesting hyperphosphorylation of tau at Ser199/202, Ser262/356 and Ser396/404 sites. Additionally, the cdk-5 transfected rats showed long latency to find the hidden platform in Morris water maze compared to the control rat. 48 h after transfection, the level of cdk-5 was decreased significantly, and the latency of rats to find the hidden platform was prolonged. It implies that in vivo overexpression of cdk-5 leads to impairment of spatial memory in rat and tau hyperphosphorylation may be the underlying mechanism.

Accumulating evidence indicates that serine/threonine (Ser/Thr) protein phosphatases (PPs), such as PP1, PP2A and PP2B, participate in the neurodegenerative progress in Alzheimer's disease (AD). The general characteristics and pathologic changes of PP1, PP2A and PP2B in AD, and their relations with microtubule-associated proteins, focusing mainly on tau protein, neurofilament (NF), amyloid precursor protein (APP) processing and synaptic plasticity are discussed. Deriving novel insight into the particular topic will attract greater attention to more active investigation and effective therapeutic intervention in the future., (Copyright 2003 S. Karger AG, Basel)