RESUMEN
Biological aging can be defined as a gradual loss of homeostasis across various aspects of molecular and cellular function. Aging is a complex and dynamic process which influences distinct cell types in a myriad of ways. The cellular architecture of the mammalian brain is heterogeneous and diverse, making it challenging to identify precise areas and cell types of the brain that are more susceptible to aging than others. Here, we present a high-resolution single-cell RNA sequencing dataset containing ~1.2 million high-quality single-cell transcriptomic profiles of brain cells from young adult and aged mice across both sexes, including areas spanning the forebrain, midbrain, and hindbrain. We find age-associated gene expression signatures across nearly all 130+ neuronal and non-neuronal cell subclasses we identified. We detect the greatest gene expression changes in non-neuronal cell types, suggesting that different cell types in the brain vary in their susceptibility to aging. We identify specific, age-enriched clusters within specific glial, vascular, and immune cell types from both cortical and subcortical regions of the brain, and specific gene expression changes associated with cell senescence, inflammation, decrease in new myelination, and decreased vasculature integrity. We also identify genes with expression changes across multiple cell subclasses, pointing to certain mechanisms of aging that may occur across wide regions or broad cell types of the brain. Finally, we discover the greatest gene expression changes in cell types localized to the third ventricle of the hypothalamus, including tanycytes, ependymal cells, and Tbx3+ neurons found in the arcuate nucleus that are part of the neuronal circuits regulating food intake and energy homeostasis. These findings suggest that the area surrounding the third ventricle in the hypothalamus may be a hub for aging in the mouse brain. Overall, we reveal a dynamic landscape of cell-type-specific transcriptomic changes in the brain associated with normal aging that will serve as a foundation for the investigation of functional changes in the aging process and the interaction of aging and diseases.
RESUMEN
This study focuses on the assessment of possible hypereutectoid steel carbide mesh crushing. It is used for tools production, including forming rolls of various diameters, with modification and cyclic heat treatment methods. For steel containing 1.79-1.83% C, we studied the effect of 0.35-1.15% Si on the possible crushing of the cementite mesh within crystallization by introducing modifiers Ti, V, N, as well as simultaneously modifying V with N and Ti with N. The obtained castings of Ø200 mm, 400 mm high were cut into discs, from which we made samples for tests on wear, determining mechanical properties, thermal resistance, and susceptibility to brittle fracture. The assessment was performed in the as-cast and after double and triple normalizing and annealing with drawback. With additional fans blowing, we changed the cooling rate from 25 °C/h to 100-150 °C/h. We performed the microstructure analyses using traditional metallographic, micro-X-ray spectral analyses, and also used the segmentation process based on 2D image markers. It was found that the as-cast modifying additives infusion is insufficient for carbide mesh crushing. It can be made by multi-stage normalizing with accelerated cool-down for products up to 600 mm in diameter to cycle temperatures above the steel transfer from a plastic to elastic state (above 450 °C).
