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1.
Sialidosis, caused by a genetic deficiency of the lysosomal sialidase gene (NEU1), is a systemic disease involving various tissues and organs, including the nervous system. Understanding the neurological dysfunction and pathology associated with sialidosis remains a challenge, partially due to the lack of a human model system. In this study, we have generated two types of induced pluripotent stem cells (iPSCs) with sialidosis-specific NEU1G227R and NEU1V275A/R347Q mutations (sialidosis-iPSCs), and further differentiated them into neural precursor cells (iNPCs). Characterization of NEU1G227R- and NEU1V275A/R347Q- mutated iNPCs derived from sialidosis-iPSCs (sialidosis-iNPCs) validated that sialidosis-iNPCs faithfully recapitulate key disease-specific phenotypes, including reduced NEU1 activity and impaired lysosomal and autophagic function. In particular, these cells showed defective differentiation into oligodendrocytes and astrocytes, while their neuronal differentiation was not notably affected. Importantly, we found that the phenotypic defects of sialidosis-iNPCs, such as impaired differentiation capacity, could be effectively rescued by the induction of autophagy with rapamycin. Our results demonstrate the first use of a sialidosis-iNPC model with NEU1G227R- and NEU1V275A/R347Q- mutation(s) to study the neurological defects of sialidosis, particularly those related to a defective autophagy–lysosome pathway, and may help accelerate the development of new drugs and therapeutics to combat sialidosis and other LSDs. 相似文献
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Xiao-Lei Qiu Zi-Rui Fan Yang-Yang Liu Ding-Fu Wang Shi-Xin Wang Chun-Xia Li 《International journal of molecular sciences》2021,22(8)
A self-nanoemulsifying drug delivery system (SNEDDS) was developed to enhance the absorption of heparin after oral administration, in which heparin was compounded with phospholipids to achieve better fat solubility in the form of heparin-phospholipid (HEP-Pc) complex. HEP-Pc complex was prepared using the solvent evaporation method, which increased the solubility of heparin in n-octanol. The successful preparation of HEP-Pc complex was confirmed by differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR) spectroscopy, NMR, and SEM. A heparin lipid microemulsion (HEP-LM) was prepared by high-pressure homogenization and characterized. HEP-LM can enhance the absorption of heparin after oral administration, significantly prolong activated partial thromboplastin time (APTT) and thrombin time (TT) in mice, and reduce fibrinogen (FIB) content. All these outcomes indicate that HEP-LM has great potential as an oral heparin formulation. 相似文献
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Yujing Zhang Pin Liu Kumara Raja Kandula Wenru Li Yanfeng Qin Haibo Zhang Guangzu Zhang 《Journal of the European Ceramic Society》2021,41(1):360-367
The applications of antiferroelectric (AFE) materials in miniaturized and integrated electronic devices are limited by their low energy density. To address the above issue, the antiferroelectricity of the reinforced material was designed to improve its AFE-ferroelectric (FE) phase transition under electric fields. In this present study, the composition of Zr4+ (0.72 Å) and Ti4+ (0.605 Å) at B-site of Pb0.97La0.02(ZrxSn0.05Ti0.95-x)O3 ceramics with orthogonal reflections are synthesized via the tape-casting method. These ceramics are modified to enhance their antiferroelectricity by reducing their tolerance factor. A recoverable energy storage density Wrec 12.1 J/cm3 was obtained for x = 0.93 under 376 kV/cm, which is superior value than reported until now in lead-based energy storage systems. Moreover, the discharge energy density can reach 10.23 J/cm3, and 90 % of which can be released within 5.66 μs. This work provides a new window and potential materials for further industrialization of pulse power capacitors. 相似文献
5.
Novel lead-free (1-x)Ba0·9Ca0·1Ti0·9Zr0·1O3-xSrNb2O6 ceramics were synthesized via a two-step high energy ball milling process. The evolution of microstructural properties, phase transformation, and energy storage characteristics was comprehensively investigated to assess the applicability of material in multi-layered ceramic capacitors. The substitution of SrNb2O6 (SNO) in Ba0·9Ca0·1Ti0·9Zr0·1O3 (BTCZ) has resulted in substantial improvement in materials density along with a small increase in the grain size of the synthesized ceramic. A thorough microstructural investigation indicates an excellent dispersibility and compatibility between BTCZ and SNO phases. With an increase in SNO substitution, a transition from typical ferroelectric to relaxor ferroelectric has been observed, which has led to a significantly slimmer ferroelectric loop along with frequency dispersive dielectric properties. The optimized composition (i.e., x = 0.10) exhibits an ultra-high recoverable energy density of 2.68 J/cm3 along with a moderately high energy efficiency of 83.4%. Further, SNO substituted samples have also shown an enhancement in breakdown strength. The improvement in energy storage performance and breakdown strength of SNO substituted BTCZ composites are mainly attributed to relatively homogeneous grain morphology, optimum grain size, microstructural density, and improved grain boundary interface. 相似文献
6.
邓乐善 《中国水能及电气化》2021,(1):56-58
针对民乐县农村人饮机井水位自动供水系统控制中存在的可靠性低、成本高等问题,文章结合深井泵提取地下水进行供水的实际情况,提出了软启动控制柜+浮球开关+微电脑时间控制器改进的思路和方法,运用效果良好。 相似文献
7.
谭金军 《自动化技术与应用》2021,40(1):181-183
为进一步提升企业思想政治教育工作的信息化水平,本文详细介绍了企业思想政治教育系统的数据库设计方案,以便更加充分地发挥各种多媒体教学设备在企业思想政治教育工作方面的优势。 相似文献
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In this paper, a novel method is proposed for increasing the performance through coupling of top-down models adjusting the object detector based on a new loss function. Generally, object detectors and keypoint estimators are sequentially used in real-time multi-person pose estimations; however, these two models are separately trained. Therefore, the results of the object detector are not optimized for the keypoint estimator. To solve this problem, we analyze the relationship between the two models and propose a feedback-based loss optimization in the object detector, based on the estimation results of the keypoint estimator. In addition, the resulting bounding box of the object detector is readjusted to improve the accuracy of the keypoint estimation model. The experimental results demonstrate that the proposed approach can perform real-time operations with a high frame rate similar to that of the baseline model. Moreover, it achieved an accuracy of 74.2 average precision (AP), which is higher than the state-of-the-arts model including the human detector used in the experiment. 相似文献