Cellular senescence in white matter microglia is induced during ageing in mice and exacerbates the neuroinflammatory phenotype

Cellular senescence, a state of irreversible cell-cycle arrest caused by a variety of cellular stresses, is critically involved in age-related tissue dysfunction in various organs. However, the features of cells in the central nervous system that undergo senescence and their role in neural impairment are not well understood as yet. Here, through comprehensive investigations utilising single-cell transcriptome analysis and various mouse models, we show that microglia, particularly in the white matter, undergo cellular senescence in the brain and spinal cord during ageing and in disease models involving demyelination. Microglial senescence is predominantly detected in disease-associated microglia, which appear in ageing and neurodegenerative diseases. We also find that commensal bacteria promote the accumulation of senescent microglia and disease-associated microglia during ageing. Furthermore, knockout of p16 INK4a, a key senescence inducer, ameliorates the neuroinflammatory phenotype in damaged spinal cords in mice. These results advance our understanding of the role of cellular senescence in the central nervous system and open up possibilities for the treatment of age-related neural disorders.Matsudaira T., Nakano S., Konishi Y., et al. Cellular senescence in white matter microglia is induced during ageing in mice and exacerbates the neuroinflammatory phenotype. Communications Biology 6, 665 (2023); https://doi.org/10.1038/s42003-023-05027-2

Analysis of grain boundary sinks and interstitial diffusion in neutron-irradiated SiC

The widths of the interstitial loop denuded zone (DZ) along grain boundaries were examined for 3C-SiC irradiated at 1010–1380 °C by transmission electron microscopy (TEM) in an effort to obtain the activation energy of interstitial migration. Denuded-zone widths as small as 17 nm were observed below 1130 °C, indicating that a substantial population of “TEM invisible” voids of diameter <0.7 significantly contribute to interstitial annihilation. By using the obtained loop DZ width and the matrix sink strength (including the invisible voids), the activation energy of interstitial diffusion was determined to be 1.5 eV for the slower moving Si interstitial of SiC by application of simple reaction-diffusion equations

Irradiation-induced β to α SiC transformation at low temperature

We observed that β-SiC, neutron irradiated to 9 dpa (displacements per atom) at ≈1440 °C, began transforming to α-SiC, with radiation-induced Frank dislocation loops serving as the apparent nucleation sites. 1440 °C is a far lower temperature than usual β → α phase transformations in SiC. SiC is considered for applications in advanced nuclear systems, as well as for electronic or spintronic applications requiring ion irradiation processing. β-SiC, preferred for nuclear applications, is metastable and undergoes a phase transformation at high temperatures (typically 2000 °C and above). Nuclear reactor concepts are not expected to reach the very high temperatures for thermal transformation. However, our results indicate incipient β → α phase transformation, in the form of small (~5–10 nm) pockets of α-SiC forming in the β matrix. In service transformation could degrade structural stability and fuel integrity for SiC-based materials operated in this regime. However, engineering this transformation deliberately using ion irradiation could enable new electronic applications

Effects of Cr and Si addition on the high-temperature oxidation resistance in high-Mn alumina-forming oxide dispersion strengthened austenitic steels

Oxide dispersion-strengthened (ODS) steels are promising candidates for constructing nuclear reactors. Considering a high-temperature environment, ODS austenitic steels could provide superior performance compared to the current ODS ferritic steels. To meet the reduced activation requirement, the compositions of ODS austenitic steels have to be carefully adjust. Currently, the authors focus on the ODS austenitic steels with the austenite stabilizer of Mn, and several amounts of Al are added to improve their high-temperature oxidation resistance. This study investigates the third-element effects of Cr and Si on the high-temperature oxidation resistance of high-manganese alumina-forming ODS austenitic steels. Generally, Si-containing steel exhibits superior oxidation resistance owing to the formation of a continuous inner layer of amorphous alumina. In contrast, the Cr-containing steel does not possess a continuous alumina layer, resulting in insufficient oxidation resistance. The reported phenomenon is believed to be a reference for the development of ODS austenitic steels in the future

Development of nano-oxide particles dispersed alumina scale formed on Zr-added FeCrAl ODS ferritic alloys

In order to develop a robust alumina scale dispersed with nano-oxide particles for FeCrAl oxide dispersion strengthened (ODS) ferritic alloys, the oxidation behavior of FeCrAl ODS ferritic alloys with zirconium and excessive oxygen (Ex. O) additions was investigated at 900 degrees C in air. Zirconia incorporation into alumina scale was not observed in the Ex. O-added FeCrAl ODS alloys at 900 degrees C, instead of this, a distribution with dense Y-Zr oxide particles inside the alumina scale was found, which is expected to enhance the stability of the alumina scale during service at elevated temperatures in nuclear applications. Preexisting large Zr-enriched precipitates formed during the alloy fabrication process are incorporated into the alumina scales during oxidation, which would increase the oxidation rate via providing a short-circuit paths for oxygen inward diffusion by themselves and associated porosity. In addition to a traditional spherical shape, a unique tadpole-like shape of the fine Y-Zr oxide particles in alumina was also observed, which is considered to be related to those incorporated coarse Zr-Y oxide inclusions in alumina scale

Development of Liquid Phase Sintering Silicon Carbide Composites for Light Water Reactor

Silicon carbide composites are expected for light water reactors. The objective is to understand the steam oxidation behavior and the high-temperature water corrosion behavior of the liquid phase sintering silicon carbide and to develop the liquid phase sintering silicon carbide composites, which are stable at the high-temperature water conditions in normal operation and the high-temperature steam conditions in a severe accident. The steam oxidation experiments were carried out at 1200 and 1400 &deg;C. The high-temperature water corrosion experiments were carried out at 320 and 360 &deg;C. The formation of the silicate, which is expected to have excellent resistance to the steam, was confirmed following the steam exposure at 1400 &deg;C. High-temperature water corrosion resistance was improved by the formation of Yttrium Aluminum Garnet at the grain boundary. The particle-dispersion silicon carbide composite tubes with the modified condition were developed, and the thermal shock experiments from 1200 &deg;C to ambient temperature were carried out. The composite tubes showed excellent oxidation and thermal shock resistance. The particle-dispersion liquid phase sintering silicon carbide composites with the modified condition are promising materials for light water reactors