Hematopoietic stem cells (HSCs) are responsible for the continuous regeneration of all types of blood cells, including themselves. To ensure the functional and genomic integrity of blood tissue, a network of regulatory pathways tightly controls the proliferative status of HSCs. Nevertheless, normal HSC aging is associated with a noticeable decline in regenerative potential and possible changes in other functions. Myelodysplastic syndrome (MDS) is an age-associated hematopoietic malignancy, characterized by abnormal blood cell maturation and a high propensity for leukemic transformation. It is furthermore thought to originate in a HSC and to be associated with the accrual of multiple genetic and epigenetic aberrations. This raises the question whether MDS is, in part, related to an inability to adequately cope with DNA damage. Here we discuss the various components of the cellular response to DNA damage. For each component, we evaluate related studies that may shed light on a potential relationship between MDS development and aberrant DNA damage response/repair.
In order to study the characteristics of pile–rock action of steel pipe driven pile in coral reef limestone stratum, coral reef limestone at the China–Maldives Friendship Bridge site was selected to carry out indoor physical and model tests with red sandstone as the control group. The test outcomes indicate the following: (1) when substantial deformation is permitted, the coral reef limestone has a considerable strength dispersion, a low post-peak stress decrease rate, and a high residual strength, roughly 30% of the peak strength; (2) when the steel pipe pile penetrates the coral reef limestone, the pile top load shows an obvious sawtooth shape, and with the increase in penetration depth, the pile end load of the high-porosity rock sample gradually decreases, and the pile end load of the low-porosity rock sample gradually increases; (3) when the steel pipe pile is penetrated, the strain value of the red sandstone is about twice that of the coral reef limestone at the same position from the steel pipe pile. These findings indicate that the high porosity and heterogeneity cementation characteristics of the coral reef limestone make the extrusion effect during piling significantly less than that of the red sandstone. In addition, the steel pipe pile penetration process is numerically simulated using a four-dimensional discrete spring model method based on the multi-body damage criterion. The numerical simulation results further demonstrate that the pile-side rock fragmentation during steel pipe pile penetration is the primary reason for the lower bearing capacity of steel pipe piles in coral reef limestone stratums. This method provides a novel approach for studying the mechanical properties of reef limestone. The findings can serve as a guide for the design and construction of steel pipe piles in the reef limestone stratum.
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