Modeling Sialidosis with Neural Precursor Cells Derived from Patient-Derived Induced Pluripotent Stem Cells

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 NEU1^G227R and NEU1^V275A/R347Q mutations (sialidosis-iPSCs), and further differentiated them into neural precursor cells (iNPCs). Characterization of NEU1^G227R- and NEU1^V275A/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 NEU1^G227R- and NEU1^V275A/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.     

多模态影像学检查在诊断早期强直性脊柱炎骶髂关节疾病中的效果

目的:探究在早期强直性脊柱炎骶髂关节疾病诊断中不同放射影像学检查方法的应用效果。方法:抽取2018年5月-2020年1月本院收治的早期强直性脊柱炎骶髂关节疾病患者65例作为研究对象,所有患者均开展X线、CT、MRI影像学检查,对比三种不同影像学检查方法的检出率、影像学特征。结果:X线、CT、MRI检出率分别为38.46%(25/65)、60.00%(39/65)、76.92%(50/65),检出率相比,MRI、CT明显高于X线,P<0.05;X线、CT、MRI影像学特征,发现关节间隙出现不同的异常,如关节面出现侵蚀、骨质囊变现象,关节面下骨质出现硬化与关节软骨出现肿胀,其中MRI、CT检查,阳性率高于X线,P<0.05。而对于软组织肿胀、骨髓水肿、滑膜炎症、关节滑膜增厚等现象,只能通过MRI检查才能诊断。结论:在早期强直性脊柱炎骶髂关节疾病诊断中,X线、CT、MRI影像学检查均具有一定的指导意义,而MRI不仅可以提高检出率,还能准确反映微小病灶及其软组织病变,对于早期发现骶髂关节炎值得推荐。     

Inconel 690传热管GTAW对接焊接头组织及力学性能研究

对Inconel 690传热管材进行钨极气体保护焊(GTAW)对接焊,采用拉伸试验机、压扁试验机和光学显微镜测试和分析传热管焊接接头,同时利用ANSYS软件开展焊接接头在设计工况失压时的一次应力强度校核。研究结果表明:焊缝中心为树枝胞状晶,熔合线附近为粗大柱状晶。室温时接头的平均抗拉强度为619 MPa,平均屈服强度为292 MPa,350℃时接头平均抗拉强度为475 MPa,平均屈服强度为206 MPa,拉伸接头断裂从熔合区开始贯穿整个焊缝组织,呈塑性断裂。压扁试验和反向压扁试验结果表明管接头完好。通过ANSYS分析可知,设计工况下传热管接头350℃许用应力强度150 MPa限值可满足其一次应力强度要求,且裕量较大。     

剪切解络-超滤分离金属关键指标预测与验证

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。     

基于误差估值累加开环校正的诱导式欺骗检测方法

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。     

Experimental study on mitigating wind erosion of calcareous desert sand using spray method for microbially induced calcium carbonate precipitation

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.     

高应力软岩巷道锚注一体化联合支护技术应用

介绍了国家专利注锚剂、中空注浆锚索等产品,以国家能源麦朵山煤矿11采区2煤辅助运输巷为研究对象,采用数值模拟、理论分析、现场测试及井下试验相结合的综合研究方法,对11采区2煤辅助运输巷采用锚注一体联合支护技术,来实现对岩体裂隙注浆,使浆料与岩体结为一体,在围岩与支护体共同作用过程中,实现强岩增荷的作用,维护巷道的稳定性,实现工作面的安全生产。     

智能假肢膝关节的研发要点及其研究进展综述

目的 介绍国内外智能假肢膝关节研究的主要进展,为相关领域的研发提供可借鉴的思路.方法 基于机械结构、调控方式、驱动方式,对典型假肢膝关节进行了分类比较,并从假肢穿戴者的运动意图识别、驱动控制、人机协调控制等方面做了分析.此外,对假肢膝关节在智能化研究与安全性、个性化与通用性、人机共融技术、科学伦理、关键技术等方面需要注意的问题,提出了研发要点和技术思路.结论 智能假肢膝关节应注重安全性与稳定性,规避用户在使用过程中的潜在危险因素;实现假肢控制参数的自整定和灵活适配,在个性化与通用性上达到平衡;综合考虑人—机—环境因素,实现协调控制;坚持"以人为本",在技术方法和科学伦理两个方面开展医工结合的研究;突破关键技术限制,建立完善的社会医疗康复保障服务体系.     

混菌矿化增强再生粗骨料的物理力学性能

为克服单一微生物培养成本高且矿化鲁棒性不足的缺陷，提出了一种混菌矿化增强再生粗骨料物理力学性能的方法.通过筛选矿化效率较高的好氧嗜碱混菌，考察了混菌矿化对再生粗骨料物理力学性能和混凝土抗压强度的影响.结果表明：相同增强时间下，混菌比纯菌呈现出更优异的矿化增强效果；随着混菌矿化增强时间的延长，再生粗骨料吸水率和压碎指标呈现出先减小后增大的趋势，最优增强时间为15 d；采用矿化增强再生粗骨料制备的再生混凝土抗压强度提高幅度达到22.1%.     

Reversal of the Inflammatory Responses in Fabry Patient iPSC-Derived Cardiovascular Endothelial Cells by CRISPR/Cas9-Corrected Mutation

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.