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1.
Zhenzhen Sun Yujie Xie Yintong Chen Qinghu Yang Zhenzhen Quan Rongji Dai Hong Qing 《Molecular neurobiology》2018,55(5):3841-3855
γ-Secretase has been a therapeutical target for its key role in cleaving APP to generate β-amyloid (Aβ), the primary constituents of senile plaques and a hallmark of Alzheimer’s disease (AD) pathology. Recently, γ-secretase-associating proteins showed promising role in specifically modulating APP processing while sparing Notch signaling; however, the underlying mechanism is still unclear. A co-immunoprecipitation (Co-IP) coupled with mass spectrometry proteomic assay for Presenilin1 (PS1, the catalytic subunit of γ-secretase) was firstly conducted to find more γ-secretase-associating proteins. Gene ontology analysis of these results identified Rab21 as a potential PS1 interacting protein, and the interaction between them was validated by reciprocal Co-IP and immunofluorescence assay. Then, molecular and biochemical methods were used to investigate the effect of Rab21 on APP processing. Results showed that overexpression of Rab21 enhanced Aβ generation, while silencing of Rab21 reduced the accumulation of Aβ, which resulted due to change in γ-secretase activity rather than α- or β-secretase. Finally, we demonstrated that Rab21 had no effect on γ-secretase complex synthesis or metabolism but enhanced PS1 endocytosis and translocation to late endosome/lysosome. In conclusion, we identified a novel γ-secretase-associating protein Rab21 and illustrate that Rab21 promotes γ-secretase internalization and translocation to late endosome/lysosome. Moreover, silencing of Rab21 decreases the γ-secretase activity in APP processing thus production of Aβ. All these results open new gateways towards the understanding of γ-secretase-associating proteins in APP processing and make inhibition of Rab21 a promising strategy for AD therapy. 相似文献
2.
Nguyen Huu Quan Vu Van Hanh Le Phuong Dung Chu Hoang Mau 《Molecular biology reports》2018,45(5):1067-1075
Molecular Biology Reports - Chitinases play the key role in hydrolysis of chitin, a huge organic carbon reservoir on earth, into monomeric sugars and their eventual conversion into valuable... 相似文献
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Xiaodong Chen Vikram Sadineni Mita Maity Yong Quan Matthew Enterline Rao V. Mantri 《AAPS PharmSciTech》2015,16(6):1317-1326
Lyophilization is an approach commonly undertaken to formulate drugs that are unstable to be commercialized as ready to use (RTU) solutions. One of the important aspects of commercializing a lyophilized product is to transfer the process parameters that are developed in lab scale lyophilizer to commercial scale without a loss in product quality. This process is often accomplished by costly engineering runs or through an iterative process at the commercial scale. Here, we are highlighting a combination of computational and experimental approach to predict commercial process parameters for the primary drying phase of lyophilization. Heat and mass transfer coefficients are determined experimentally either by manometric temperature measurement (MTM) or sublimation tests and used as inputs for the finite element model (FEM)-based software called PASSAGE, which computes various primary drying parameters such as primary drying time and product temperature. The heat and mass transfer coefficients will vary at different lyophilization scales; hence, we present an approach to use appropriate factors while scaling-up from lab scale to commercial scale. As a result, one can predict commercial scale primary drying time based on these parameters. Additionally, the model-based approach presented in this study provides a process to monitor pharmaceutical product robustness and accidental process deviations during Lyophilization to support commercial supply chain continuity. The approach presented here provides a robust lyophilization scale-up strategy; and because of the simple and minimalistic approach, it will also be less capital intensive path with minimal use of expensive drug substance/active material. 相似文献
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Lei Qin Yu Lei Huwei Wang Jiahui Dong Yiying Wu Dengyun Zhai Feiyu Kang Ying Tao Quan‐Hong Yang 《Liver Transplantation》2019,9(29)
Metallic potassium (K) is a desirable anode for potassium secondary batteries due to its low electrode potential in nonaqueous electrolytes and high theoretical capacity. Nevertheless, instability caused by dendritic growth, large volume changes, and parasitic side reactions hamper its practical application. Here, an anode containing metallic K is fabricated by infiltrating an aligned carbon nanotube membrane (ACM) with molten K because of its good wettability to molten K due to the strong capillary forces. The K metal is spatially distributed on the 3D ACM framework, which offers sufficient electrode/electrolyte contact for charge transfer. The robust ACM host provides a large number of K nucleation sites and physically confines the K deposited there, thus mitigating dimensional changes during cycling. The pathways for electrons and ions in the anode are associated to form a mixed conducting network, which is beneficial for the electrochemical redox. Consequently, the anode shows stable plating/stripping profiles with low polarization in symmetric cells using conventional carbonate‐based electrolytes. In addition, dendrite growth is suppressed, and the anode demonstrates excellent suitability when paired with a Prussian blue cathode in a full cell. This design strategy is expected to provide a way to address the problems with using metallic K anodes. 相似文献
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Yu‐Zuo Wang Xu‐Yi Shan Li‐Po Ma Jia‐Wei Wang Da‐Wei Wang Zhang‐Quan Peng Hui‐Ming Cheng Feng Li 《Liver Transplantation》2019,9(12)
Understanding the electric double layer is essential for achieving efficient electrochemical energy storage technologies. A conventional solid–liquid electrode interface suffers from serious self‐discharge and a narrow voltage window, which makes the development of a solid–solid interface imperative. However, an in‐depth understanding of the electric double layer with a solid–solid interface is lacking. Here, a solid–solid interfacial electric double layer is proposed with excellent electrochemical performance. The solid layer is constructed by the electrochemical decomposition of lithium difluoro(oxalate)borate, which provides a desolvated environment for the establishment of a electric double layer. This makes a stronger interaction between the electrode surface and the ions. Based on this unique property, it is found that the solid–solid interfacial electric double layer has an increased capacitance, which suggests a way to develop high‐energy electrochemical capacitors. 相似文献
9.
Huan Li Changsheng Qi Ying Tao Huabo Liu Da‐Wei Wang Feng Li Quan‐Hong Yang Hui‐Ming Cheng 《Liver Transplantation》2019,9(21)
Nanostructured materials have greatly improved the performance of electrochemical energy storage devices because of the increased activity and surface area. However, nanomaterials (e.g., nanocarbons) normally possess low packing density, and thus occupy more space which restricts their suitability for making electrochemical devices as compact as possible. This has resulted in their low volumetric performance (capacitance, energy density, and power density), which is a practical obstacle for the application of nanomaterials in mobile and on‐board energy storage devices. While rating electrode materials for supercapacitors, their volumetric performance is equally important as the gravimetric metrics and more reliable in particular for systems with limited space. However, the adopted criteria for measuring the volumetric performance of supercapacitors vary in the literature. Identifying the appropriate performance criteria for the volumetric values will set a universal ground for valid comparison. Here, the authors discuss the rationale for quantifying the volumetric performance metrics of supercapacitors from the three progressive levels of materials, electrodes, and devices. It is hoped that these thoughts will be of value for the general community in energy storage research. 相似文献
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