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.     

珠江口盆地珠一坳陷古近系高自然伽马砂岩形成机制及油气地质意义

运用放射性元素寻找油气是一种非常规油气勘探手段。近年来,在珠江口盆地珠一坳陷富烃凹陷周边古近系钻遇高自然伽马(GR)砂岩,其GR值(100~300 API)甚至大于同区泥岩的GR值(100~200 API)。为了弄清该特殊现象背后的地质意义,对珠江口盆地珠一坳陷古近系高自然伽马砂岩开展了铀(U)、钍(Th)、钾(K)等3种元素含量与GR值的相关趋势线分析,从井震特征、岩性特征及矿物成分特征等入手分析了砂岩GR值增高的主要原因及成因机制,探讨了放射性元素聚集的条件、运移通道、驱动力以及油气意义。结果表明:西江、惠州地区由U含量增高导致砂岩GR值偏高,恩平、番禺地区由K,Th含量增高导致砂岩GR值偏高;砂岩GR值增高有两大成因机制,一是地下流体带来的放射性元素离子U4+在氧化-还原面处富集后导致地层GR值偏高,这种特殊现象说明在具有连通基底大断裂旁的圈闭中,U4+的富集指示了曾经油气的存在,证实了研究区油气运移通道的有效性,对于油气藏的预测有着非常重要的指导性意义,二是地表流体带来的含放射性元素的矿物大量沉积后导致地层GR值偏高,含放射性元素矿物性质不稳定,可指示近源供给的存在,对于判断物源及沉积环境有着非常重要的意义。该研究成果为预测研究区油气成藏有利区带提供了依据。     

Achieving excellent energy storage density of Pb0.97La0.02(ZrxSn0.05Ti0.95-x)O3 ceramics by the B-site modification

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 Pb_0.97La_0.02(Zr_xSn_0.05Ti_0.95-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 W_rec 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.     

Microstructure induced ultra-high energy storage density coupled with rapid discharge properties in lead-free Ba0.9Ca0.1Ti0.9Zr0.1O3–SrNb2O6 ceramics

Novel lead-free (1-x)Ba_0·9Ca_0·1Ti_0·9Zr_0·1O₃-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 Ba_0·9Ca_0·1Ti_0·9Zr_0·1O₃ (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.     

Effects of upholstery materials on the burning behavior of real‐scale residential upholstered furniture mock‐ups

Fire spread and growth on real‐scale four cushion mock‐ups of residential upholstered furniture (RUF) were investigated with the goal of identifying whether changes in five classes of materials (barrier, flexible polyurethane foam, polyester fiber wrap, upholstery fabric, and sewing thread), referred to as factors, resulted in statistically significant changes in burning behavior. A fractional factorial experimental design plus practical considerations yielded a test matrix with 20 material combinations. Experiments were repeated a minimum of two times. Measurements included fire spread rates derived from video recordings and heat release rates (HRRs). A total of 13 experimental parameters (3 based on the videos and 10 on the HRR results), referred to as responses, characterized the measurements. Statistical analyses based on Main Effects Plots (main effects) and Block Plots (main effects and factor interactions) were used. The results showed that three of the factors resulted in statistically significant effects on varying numbers of the 13 responses. The Barrier and Fabric factors had the strongest main effects with roughly comparable magnitudes. Foam was statistically significant for fewer of the responses and its overall strength was weaker than for Barrier and Fabric. No statistically significant main effects were identified for Wrap or Thread. Multiple two‐term interactions between factors were identified as being statistically significant. The Barrier*Fabric interaction resulted in the highest number of and strongest statistically significant effects. The existence of two‐term interactions means that it will be necessary to consider their effects in approaches designed to predict the burning behavior of RUF.     

Reduced‐scale test to assess the effect of fire barriers on the flaming combustion of cored composites: An upholstery‐material case study

Herein, we describe a reduced‐scale test (“Cube” test), measuring the fire performance of specimens including a fire barrier (FB) and a flammable core material, which acts as the main fuel load. The specimen is intended to reproduce a cross‐section of a composite product where heat/mass transfer occurs primarily in a direction perpendicular to the FB. The Cube test procedure and benefits are discussed in this work by adopting residential upholstery furniture as an exemplary study. One flexible polyurethane foam, one polypropylene cover fabric, and 10 commercially available FBs were selected. They were used to compare the fire performance of FBs, measured in terms of peak of heat release rate, in the ASTM E1474‐14 standard test and the newly developed Cube test. Edge effects severely affected the performance of FBs in the ASTM E1474‐14 standard test but not in the Cube test. Furthermore, appropriate test conditions were determined in the Cube test to measure the so‐called “wetting point,” that is, the time and value of heat release rate measured when flammable liquid products were first observed on the bottom of the specimen. The relevance of the “wetting point” in terms of full‐scale fire performance and failure mechanism of FBs is discussed.     

一类分数阶微积分的中值定理及应用

Riemann-Liouville分数阶微积分算子是一类带有一个函数的分数阶微积分算子的特殊情形，以Riemann-Liouville分数阶微积分算子的积分中值定理和微分中值定理为基础，我们得到了一类带有一个函数的分数阶微积分算子的积分中值定理和微分中值定理，并给出其在计算方面的一些应用。     

Alterations in the Genomic Distribution of 5hmC in In Vivo Aged Human Skin Fibroblasts

5-Hydroxymethylcytosine (5hmC) is a functionally active epigenetic modification. We analyzed whether changes in DNA 5-hydroxymethylation are an element of age-related epigenetic drift. We tested primary fibroblast cultures originating from individuals aged 22–35 years and 74–94 years. Global quantities of methylation-related DNA modifications were estimated by the dot blot and colorimetric methods. Regions of the genome differentially hydroxymethylated with age (DHMRs) were identified by hMeDIP-seq and the MEDIPS and DiffBind algorithms. Global levels of DNA modifications were not associated with age. We identified numerous DHMRs that were enriched within introns and intergenic regions and most commonly associated with the H3K4me1 histone mark, promoter-flanking regions, and CCCTC-binding factor (CTCF) binding sites. However, only seven DHMRs were identified by both algorithms and all of their settings. Among them, hypo-hydroxymethylated DHMR in the intron of Rab Escort Protein 1 (CHM) coexisted with increased expression in old cells, while increased 5-hydroxymethylation in the bodies of Arginine and Serine Rich Protein 1 (RSRP1) and Mitochondrial Poly(A) Polymerase (MTPAP) did not change their expression. These age-related differences were not associated with changes in the expression of any of the ten-eleven translocation (TET) enzymes or their activity. In conclusion, the distribution of 5hmC in DNA of in vivo aged human fibroblasts underwent age-associated modifications. The identified DHMRs are, likely, marker changes.     

往复活塞式压缩机活塞杆温度高故障分析及改造

针对2台2D40型空气压缩机在实际试机过程中,活塞杆温度过高,导致连锁报警,压缩机不能正常工作的问题进行了详细的故障原因分析;对压缩机技术性能参数进行介绍;对压缩机的损伤情况进行说明并找到改造方案,解决机组运行中活塞杆温度过高的问题,从而提高机组的运行效率,使机组运行安全、稳定。