Mitochondrial plasticity implicates their new purpose in therapy-induced senescence

Cellular senescence and mitochondrial dysfunction are regarded as pillars of aging and age-related diseases such as cancer. As a result, there have been great efforts to understand the role of the two phenomena in such pathological settings. However, the exact relationship between the two is not fully understood due in part to conflicting results. A thorough understanding of their relationship warrants revealing greater therapeutic targets in age-related diseases. Here, I report mitochondrial states with their accurate quantity in a senescent cell. Mitochondria were found to be bioenergetically hypoactive in senescent cells demonstrated by lower membrane potential, lower superoxide level, and lower respiration compared to proliferating cells. However, a profound increase of mitochondrial volume in a senescent cell led to enhanced outputs of the bioenergetic parameters on a cellular base. This largely resolves the paradoxical states of mitochondria in senescent cells and agrees with their age-related dysfunctions. In subsequent analyses combined with time-resolved quantitative proteomics and metabolomics, it was found that metabolic rewiring is the main signature amongst all mitochondrial pathways in senescent cells. In detail, branched-chain amino acid catabolism was increased while one carbon-folate metabolism was rapidly blocked upon the induction of cellular senescence. Such rewired mitochondrial metabolisms orchestrated a synthesis of non-essential amino acids, nucleotides, and translation of mitochondrial RNAs in senescent cells. Besides, a mitochondrial orphan gene OCIAD2 was identified as a pan-senescence marker. The inner mitochondrial membrane protein OCIAD2 regulated the formation of perinuclear mitochondrial clumps in senescent cells. Moreover, bulk RNA-seq analyses discovered its potential crosstalk with TGF-b signaling in senescent cells. However, OCIAD2 neither regulated respiration and superoxide generation, nor oxidation of glucose, glutamine, and fatty acids in mitochondria of senescent cells. Thus, the function of OCIAD2 remains to be determined other than those. These data collectively demonstrate the mitochondrial plasticity in senescent cells and warrant future investigation into their regulatory roles in senescent cells

Experimental and Numerical Investigations on Microcoining of Stainless Steel 304

Increasing demands for miniature metallic parts have driven the application of microforming in various industries. Only a limited amount of research is, however, available on the forming of miniature features in high strength materials. This study investigated the forming of microfeatures in Type 304 stainless steel by using the coining process. Experimental work was performed to study the effects of workpiece thickness, preform shape, grain size, and feature size on the formation of features ranging from 320μmto800μm. It was found that certain preform shapes enhance feature formation by allowing a favorable flow of the bulk material. In addition, a flow stress model for Type 304 stainless steel that took into consideration the effects of the grain and feature sizes was developed to accurately model and better understand the coining process. Weakening of the material, as the grain size increased at the miniature scale, was explained by the Hall–Petch relationship and the feature size effect

Effect of dimension reduction on prediction performance of multivariate nonlinear time series

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Fabrication of High Aspect Ratio Porous Microfeatures Using Hot Compaction Technique

High aspect ratio porous microfeatures are becoming more important in the modern industry. However, the fabrication of such features under a mass production environment remains a challenge when robustness, cost effectiveness, and high productivity requirements are required. In this study, the forming of such porous microfeatures using hot compaction was investigated. A hot compaction experimental setup was designed and fabricated that is capable of performing high temperature operation (700°C), quick heatup, and avoiding oxidation. 3D thermal simulation of the experimental setup was conducted to investigate the heat transfer performance and internal temperature distribution, which was then used as a reference for the experiment. Hot compaction experiments were carried out, and the effects of compression force and temperature on the quality in terms of powder consolidation strength and porosity were investigated. In addition, the achievable aspect ratio and taper angle were also discussed