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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
2.
Zhuolong Tu Mi Chen Min Wang Zhenxuan Shao Xiaoqi Jiang Kangyan Wang Zhe Yao Shiwei Yang Xingxing Zhang Weiyang Gao Cai Lin Bo Lei Cong Mao 《Advanced functional materials》2021,31(30):2100924
Diabetic wound healing still faces great challenges due to the excessive inflammation, easy infection, and impaired angiogenesis in wound beds. The immunoregulation of macrophages polarization toward M2 phenotype that facilitates the transition from inflammation to proliferation phase has been proved to be an effective way to improve diabetic wound healing. Herein, an M2 phenotype-enabled anti-inflammatory, antioxidant, and antibacterial conductive hydrogel scaffolds (GDFE) for producing rapid angiogenesis and diabetic wound repair are reported. The GDFE scaffolds are fabricated facilely through the dynamic crosslinking between polypeptide and polydopamine and graphene oxide. The GDFE scaffolds possess thermosensitivity, self-healing behavior, injectability, broad-spectrum antibacterial activity, antioxidant and anti-inflammatory ability, and electronic conductivity. GDFE effectively activates the polarization of macrophages toward M2 phenotype and significantly promotes the proliferation of dermal fibroblasts, the migration, and in vitro angiogenesis of endothelial cells through paracrine mechanisms. The in vivo results from a full-thickness diabetic wound model demonstrate that GDFE can rapidly promote the diabetic wound repair and skin regeneration, through fast anti-inflammation and angiogenesis and M2 macrophage polarization. This study provides highly efficient strategy for treating diabetic wound repair through designing the M2 polarization-enabled anti-inflammatory, antioxidant, and antibacterial bioactive materials. 相似文献
3.
根据剪切解络-超滤过程中金属离子的动态浓度关系和质量守恒定律,采用CodeBlocks17.12软件编写程序,建立了剪切解络-超滤工艺关键指标预测模型,实现了金属离子浓度、回收率、体积稀释倍数等指标的预测,并用实验加以验证。依次在转速800 r/min、1 400 r/min、3 000 r/min下回收模拟废水中43 μg/L的Co2+、995 μg/L的Ni2+和88 μg/L的La3+,3种金属的回收率均达99.8%以上时,超滤过程体积稀释倍数的预测值分别为7.0、7.5、5.75,实验值分别为7.5、7.25、6.25,可见预测值与实验值基本一致。本模型对研究方案制定和调整有实际指导意义。 相似文献
4.
诱导式卫星欺骗干扰可诱导航空器逐渐偏离预定航迹,难以被发现,因此及时有效地检测干扰是飞行安全的保障。在现有紧组合导航体制基础上,设计了一种基于误差估值累加开环校正的紧组合导航结构,并证明了其性能与传统闭环校正紧组合导航性能等效。在此结构中,将紧组合导航系统与自适应序贯概率比检测方法结合,提出了一种基于误差估值累加开环校正的诱导式欺骗检测方法,融合紧组合导航信息与其他不受欺骗影响的导航信息,构建欺骗检测统计量进行诱导式欺骗检测。仿真结果表明,开环校正结构可避免随时间累加的惯性导航系统误差所导致的组合导航滤波器发散问题,同时欺骗检测方法可进一步提高算法对“最坏”情形下微小诱导式欺骗的检测效果。 相似文献
5.
《岩石力学与岩土工程学报(英文版)》2022,14(5):1556-1567
Wind erosion is one of the significant natural calamities worldwide, which degrades around one-third of global land. The eroded and suspended soil particles in the environment may cause health hazards, i.e. allergies and respiratory diseases, due to the presence of harmful contaminants, bacteria, and pollens. The present study evaluates the feasibility of microbially induced calcium carbonate precipitation (MICP) technique to mitigate wind-induced erosion of calcareous desert sand (Thar desert of Rajasthan province in India). The temperature during biotreatment was kept at 36 °C to stimulate the average temperature of the Thar desert. The spray method was used for bioaugmentation of Sporosarcina (S.) pasteurii and further treatment using chemical solutions. The chemical solution of 0.25 pore volume was sprayed continuously up to 5 d, 10 d, 15 d, and 20 d, using two different concentration ratios of urea and calcium chloride dihydrate viz 2:1 and 1:1. The biotreated samples were subjected to erosion testing (in the wind tunnel) at different wind speeds of 10 m/s, 20 m/s, and 30 m/s. The unconfined compressive strength of the biocemented crust was measured using a pocket penetrometer. The variation in calcite precipitation and microstructure (including the presence of crystalline minerals) of untreated as well as biotreated sand samples were determined through calcimeter, scanning electron microscope (SEM), and energy-dispersive X-ray spectroscope (EDX). The results demonstrated that the erosion of untreated sand increases with an increase in wind speeds. When compared to untreated sand, a lower erosion was observed in all biocemented sand samples, irrespective of treatment condition and wind speed. It was observed that the sample treated with 1:1 cementation solution for up to 5 d, was found to effectively resist erosion at a wind speed of 10 m/s. Moreover, a significant erosion resistance was ascertained in 15 d and 20 d treated samples at higher wind speeds. The calcite content percentage, thickness of crust, bulk density, and surface strength of biocemented sand were enhanced with the increase in treatment duration. The 1:1 concentration ratio of cementation solution was found effective in improving crust thickness and surface strength as compared to 2:1 concentration ratio of cementation solution. The calcite crystals formation was observed in SEM analysis and calcium peaks were observed in EDX analysis for biotreated sand. 相似文献
6.
《International Journal of Hydrogen Energy》2022,47(90):38114-38123
High-temperature water electrolysis through solid oxide electrolysis cells (SOEC) will play a key role in building a hydrogen economy in the future. However, the delamination between the air electrode and the electrolyte remains a critical issue to be addressed. Previously, it was hypothesized that Co migration may improve the catalytic activity of the SrZrO3 second phase at the LSCF-YSZ interface, eventually leading to the delamination. In this work, the LSCF-YSZ interfaces sintered at different temperatures were examined in detail. The activation behaviors of the LSCF electrodes upon application with electrolysis current were characterized under different conditions. Further, samples containing purposely added SrZrO3 interlayer with and without cobalt were fabricated and compared. The activation process is less significant for the sample with cobalt-added SrZrO3 interlayer than the sample with pure SrZrO3 layer, supporting the hypothesis that Co migration may lead to the activation behavior. 相似文献
7.
8.
四元数调制(Quaternion Modulation,QMod)是一种新型高传输速率的极化调制(Polarized Modulation,PMod)技术,是未来卫星通信系统中极具潜力的多元调制方案之一。QMod将数据块分成4块,其中两块是传输数据信号,另外两块则映射到极化状态部分。每个极化状态块均有一位比特,那么它们可以产生4个极化状态组合。这些状态组合可以用来确定传输数据块在四元数4个不同维度中的位置,从而获得两位额外的传输比特。相比于传统的PMod技术,QMod有着更高的频谱效率。为了进一步挖掘QMod的潜力,介绍了由可重构智能表面(Reconfigurable Intelligent Surface,RIS)辅助的QMod系统,同时推导了该系统的平均误码率理论上界,并在瑞利信道下进行了BER性能仿真。仿真结果表明,RIS辅助的PMod或者QMod系统即便在较低的SNR情况下仍有良好的BER性能,并且随着RIS单元数的增多,其BER性能会逐步提升。 相似文献
9.
Mingqiang Cheng Erding Zhao Fangjian Jiang Xiaodong Jiang Ze Fang Feng Li Wanneng Ye Yalin Qin Yongcheng Zhang 《Ceramics International》2021,47(13):18417-18423
The materials processing history has a great influence on their properties and finally determines their application effect. In this paper, the ferroelectric, polarization-switching current, and strain properties of Mn-doped 0.75Pb(Mg1/3Nb2/3)O3-0.25PbTiO3 ceramics were studied in fresh state, aged state, and poled state, respectively. Compared with the symmetric polarization-electric-field (P-E) hysteresis loops, current-density-electric-field (J-E) curves, and bipolar electric-field-induced strain (S-E) curves in fresh state samples, asymmetric P-E loops, J-E curves, and bipolar S-E curves were obtained in poled state samples. Well-aged-state samples exhibit double hysteresis P-E loop, four peaks J-E curves, and symmetric S-E curves without negative strain. The symmetry-conforming short-range order (SC-SRO) principle of point defects and internal electric field Ei is employed to clarify the different phenomenon of three states. Results indicated that randomly oriented defect polarization PD in aged samples can reverse the spontaneous polarization PS back and result in the double hysteresis P-E loop and four peaks J-E curves. The oriented PD and resulting Ei in poled-state samples will lead to the asymmetric loops and strain memory effect. 相似文献
10.
Hui-Yung Song Yi-Ping Yang Yueh Chien Wei-Yi Lai Yi-Ying Lin Shih-Jie Chou Mong-Lien Wang Chien-Ying Wang Hsin-Bang Leu Wen-Chung Yu Chian-Shiu Chien 《International journal of molecular sciences》2021,22(5)
The late-onset type of Fabry disease (FD) with GLA IVS4 + 919G > A mutation has been shown to lead to cardiovascular dysfunctions. In order to eliminate variations in other aspects of the genetic background, we established the isogenic control of induced pluripotent stem cells (iPSCs) for the identification of the pathogenetic factors for FD phenotypes through CRISPR/Cas9 genomic editing. We adopted droplet digital PCR (ddPCR) to efficiently capture mutational events, thus enabling isolation of the corrected FD from FD-iPSCs. Both of these exhibited the characteristics of pluripotency and phenotypic plasticity, and they can be differentiated into endothelial cells (ECs). We demonstrated the phenotypic abnormalities in FD iPSC-derived ECs (FD-ECs), including intracellular Gb3 accumulation, autophagic flux impairment, and reactive oxygen species (ROS) production, and these abnormalities were rescued in isogenic control iPSC-derived ECs (corrected FD-ECs). Microarray profiling revealed that corrected FD-derived endothelial cells reversed the enrichment of genes in the pro-inflammatory pathway and validated the downregulation of NF-κB and the MAPK signaling pathway. Our findings highlighted the critical role of ECs in FD-associated vascular dysfunctions by establishing a reliable isogenic control and providing information on potential cellular targets to reduce the morbidity and mortality of FD patients with vascular complications. 相似文献