Mitochondrial and Autophagic Regulation of Adult Neurogenesis in the Healthy and Diseased Brain

Adult neurogenesis is a highly regulated process during which new neurons are generated from neural stem cells in two discrete regions of the adult brain: the subventricular zone of the lateral ventricle and the subgranular zone of the dentate gyrus in the hippocampus. Defects of adult hippocampal neurogenesis have been linked to cognitive decline and dysfunction during natural aging and in neurodegenerative diseases, as well as psychological stress-induced mood disorders. Understanding the mechanisms and pathways that regulate adult neurogenesis is crucial to improving preventative measures and therapies for these conditions. Accumulating evidence shows that mitochondria directly regulate various steps and phases of adult neurogenesis. This review summarizes recent findings on how mitochondrial metabolism, dynamics, and reactive oxygen species control several aspects of adult neural stem cell function and their differentiation to newborn neurons. It also discusses the importance of autophagy for adult neurogenesis, and how mitochondrial and autophagic dysfunction may contribute to cognitive defects and stress-induced mood disorders by compromising adult neurogenesis. Finally, I suggest possible ways to target mitochondrial function as a strategy for stem cell-based interventions and treatments for cognitive and mood disorders.     

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。     

Exosomes derived from osteoclasts under compression stress inhibit osteoblast differentiation

Orthodontic tooth movement is triggered by orthodontic force loading on the periodontal ligament and is achieved by alveolar bone remodeling, which is regulated by intimate crosstalk between osteoclastogenesis and osteoblast differentiation. Whether the communication between osteoclasts and osteoblasts is influenced by orthodontic compression stress requires further clarification. In this study, osteoclasts were differentiated for 10 days. On day 4 of differentiation, the number of pre-osteoclasts peaked, as determined by the increased expression of RANK and the number of multinucleated cells. After 24 h of compression stress loading, on day 4, the number of osteoclasts increased, and the optimal magnitude of stress to promote osteoclastogenesis was determined as 1 g/cm2. Moreover, the results of RNA-sequencing analysis showed that the miRNA expression profile changed markedly after compression loading and that many of the altered miRNAs were associated with cell communication functions. A series of indirect co-culture experiments showed an inhibitory effect of osteoclasts on osteoblast differentiation, especially after compression. Next, we added osteoclast-derived exosomes to hPDLSCs during osteoblast differentiation. Exosomes derived from osteoclasts under compression (cEXO) showed a greater inhibitory effect on osteoblast differentiation, compared to exosomes from osteoclasts without compression (EXO). Therefore, we analyzed differentially expressed miRNAs associated with bone development functions in exosomes: miR-223-5p and miR-181a-5p were downregulated, whereas miR-133a-3p, miR-203a-3p, miR-106a-5p, and miR-331-3p were upregulated; these altered expressions may explain the enhanced inhibitory effect of compression stress.     

Use of CFD-DEM to evaluate the effect of intermediate stress ratio on the undrained behaviour of granular materials

This study investigates the effect of intermediate stress ratio (b) on the mechanical behaviour of granular soil in true triaxial tests. A CFD-DEM solver with the ability to model compressible fluid and moving mesh has been developed and calibrated based on existing experimental test results on Nevada sand. The effect of b on the undrained true triaxial test, which has been neglected in the literature, was investigated using a reasonable number of models. The effects of the initial confining stress and initial void ratio also have been studied. The developed model was used to calculate the hydrodynamic forces on the particles and evaluate the ratio of the particle–fluid interaction force to the resultant force on the particles. It has been demonstrated that, in numerical studies, the effect of these forces cannot be neglected.     

地应力条件下的凿岩爆破数值模拟

为了研究地应力对凿岩爆破的影响,采用DDA方法模拟爆炸应力波作用下考虑地应力条件时的单孔和多孔凿岩爆破破岩过程。模拟发现,随着初始地应力水平的增加,裂纹扩展半径和破岩区域面积减小,裂纹发育主方向趋于地应力的最大主应力方向,初始地应力对裂纹的抑制和引导作用明显;初始地应力水平的增加,对拉伸裂纹的抑制作用更为显著,从而降低了拉伸破坏对爆破破岩的贡献。模拟也表明,在初始地应力存在的条件下,通过对爆破载荷和炮孔布置进行针对性的优化,可以克服地应力带来的影响,并取得预期的爆破效果。本研究对地应力条件下的凿岩爆破工程具有理论和参考意义。     

Analysis of surface and interior degradation of gas diffusion layer with accelerated stress tests for polymer electrolyte membrane fuel cell

The effects of surface and interior degradation of the gas diffusion layer (GDL) on the performance and durability of polymer electrolyte membrane fuel cells (PEMFCs) have been investigated using three freeze-thaw accelerated stress tests (ASTs). Three ASTs (ex-situ, in-situ, and new methods) are designed from freezing ?30 °C to thawing 80 °C by immersing, supplying, and bubbling, respectively. The ex-situ method is designed for surface degradation of the GDL. Change of surface morphology from hydrophobic to hydrophilic by surface degradation of GDL causes low capillary pressure which decreased PEMFC performance. The in-situ method is designed for the interior degradation of the GDL. A decrease in the ratio of the porosity to tortuosity by interior degradation of the GDL deteriorates PEMFC performance. Moreover, the new method showed combined effects for both surface and interior degradation of the GDL. It was identified that the main factor that deteriorated the fuel cell performance was the increase in mass transport resistance by interior degradation of GDL. In conclusion, this study aims to investigate the causes of degraded GDL on the PEMFC performance into the surface and interior degradation and provide the design guideline of high-durability GDL for the PEMFC.     

Adaptive response and tolerance to weak acids in Saccharomyces cerevisiae boulardii: a metabolomics approach

Weak acids inhibit the growth of probiotics, such as Saccharomyces boulardii. We explored the tolerance of S. boulardii to different weak acids. S. boulardii had better fermentation ability under lactic acid conditions compared with acetic and butyric acid conditions; however, the budding of S. boulardii was significantly stronger than that of Saccharomyces cerevisiae under acetic acid conditions. Although the surface structure of S. boulardii was destroyed, it produced more daughter cells. S. boulardii metabolites were also significantly different from S. cerevisiae under acidic stress. The growth of S. boulardii under weak acid conditions differed significantly from that of S. cerevisiae. S. boulardii-mediated fingerprints under weak acid conditions were identified as latent biomarkers, related to fructose and mannose metabolism, tricarboxylic acid cycle, and the glycolysis pathway. Identified biomarkers will aid in the genetic engineering of S. boulardii and other Saccharomyces strains for improved acid resistance and biomass yield.     

基于乙酰胆碱酯酶和氧化应激研究海胆酮对阿尔茨海默症的作用机制

海胆酮是一种酮式类胡萝卜素，主要从海胆及藻类等海洋生物中提取。本文研究海胆酮对乙酰胆碱酯酶（acetylcholinesterase，AChE）的抑制作用，应用酶动力学、荧光光谱、圆二色光谱和分子对接技术研究海胆酮对AChE的抑制机理，并用淀粉样β蛋白片段25～35（amyloid beta-peptide 25-35，Aβ25-35）诱导大鼠肾上腺嗜铬细胞瘤细胞（PC12细胞）建立阿尔茨海默症（Alzheimer’s disease，AD）模型，研究海胆酮对AD细胞模型氧化应激损伤的作用。结果表明，海胆酮有很强的AChE抑制活性，其半抑制质量浓度为（16.29±0.97）μg/mL，抑制常数Ki为3.82 μg/mL，表现为竞争性抑制；海胆酮可诱导AChE二级结构改变，更容易与AChE活性中心氨基酸Ser200、His440、Trp84和Tyr121结合，阻碍底物碘代硫代乙酰胆碱（acetylthiocholine iodide，ATCI）与酶结合，从而引起酶活力降低。海胆酮能有效抑制Aβ25-35诱导PC12细胞的AChE活力，降低丙二醛含量，增加超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶活力，减轻Aβ25-35诱导的PC12细胞氧化应激损伤。本研究基于AChE和氧化应激阐明了海胆酮对AD的潜在作用机制，为海胆酮在功能食品、生物医药等领域的应用提供了数据支持和理论根据。     

爆炸排淤填石法中淤泥的本构模型

以爆炸排淤填石法为背景 ,对不同应变率阶段淤泥的本构模型进行了分析 ,利用ANSYS/LS-DYNA动态有限元分析程序对所选择的模型进行验证和确认。计算和分析结果表明 :在形成爆炸空腔的高应变率阶段 ,淤泥表现为理想不可压缩流体的性质 ;在小药量小抵抗线条件下 ,甚至在淤泥自重作用下的较低应变率变形阶段 ,其黏性效应也可以忽略不计。