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To investigate the effect of HSP70-hom+2437 single nucleotide polymorphisms (SNPs) on hypoxia and ischemia condition, we constructed the neuronal hypoxic injury model and the rat middle cerebral artery occlusion (MCAO) model to compare the inhibition rate of neurons and detect the infarct volume as well as the expression of related apoptotic proteins in order to explore the possible mechanisms. The neuroblastoma cells SHSY5Y were divided into the OE (transfected with the C allele) group, OEmu (transfected with the T allele) group and negative control (NC, transfected with the empty lentiviral vector CON195) group. Varying degrees of hypoxia were induced by deferoxamine (DFO). The inhibition rate of hypoxic neurons and the expression of related apoptotic proteins were detected in the three genotype groups. While in the rat MCAO model, we built five groups including the sham group, the blank control group (injected with physiological saline), the negative control group (injected with lentivirus and physiological saline), the C allele group and the T allele group (injected with lentivirus overexpressing C and T allele). The MCAO model operation was then underwent in all five groups, the infarct volume by TTC staining and the expression of related apoptotic proteins were detected after 24 h. The results in neuronal hypoxic injury model showed a significant difference in the inhibition rate between the three groups (P < 0.05), and the average inhibition rates for the OEmu, OE and NC groups were 13.2%, 19.2% and 23.3%, respectively. The inhibition rates also differed between lower and higher DFO concentrations (P < 0.05). Compared with the NC group, Bax decreased significantly in the OE and OEmu groups, whereas PI3K and HSPA1L (HSP70-hom) increased. However, the expression of Bax in the OEmu group decreased significantly more than in the OE group, whereas PI3K and HSPA1L levels showed no difference between the two groups. Corresponding with the results above, overexpressing HSP70-hom could reduce the infarct volume of ischemic injury by TTC staining in rat MCAO model and the T allele group also had less infarct volume than C allele group. Compared with the sham group, blank control group and negative control group, Bax decreased significantly in the C and T allele groups, while HSPA1L and p- AKT increased. Furthermore, the expression of Bax in the T allele group decreased significantly more than that in the C allele group, while there were no significant differences in HSPA1L and p-AKT levels between the two groups. Therefore, the overexpression of HSP70-hom+2437 could play a protective role in hypoxic neurons and ischemic brain tissue by upregulating the expression of HSPA1L and PI3K/p-AKT and downregulating the expression of BAX. The neuroprotective effect of the T allele was stronger than that of the C allele, which may be related to the strengthened downregulation of BAX. • The overexpression of the HSP70-hom gene (C or T allele) may take a neuroprotective role in vitro and in vivo. • Our experimental results suggest that the neuroprotective effect of the T allele is stronger than that of the C allele. • The HSP70-hom gene may protect hypoxic neurons by downregulating the expression level of BAX. • The HSP70-hom gene may protect hypoxic neurons by upregulating the expression levels of HSPA1L and PI3K/p-AKT. [ABSTRACT FROM AUTHOR]

Silicon carbide (SiC) is extremely hard and brittle, posing challenges for traditional abrasive machining. This study used molecular dynamics simulations to investigate synchronous versus asynchronous force-torque effects on SiC abrasive machining. Multi-grit diamond abrasion of 4H-SiC was modeled by applying controlled sinusoidal forces and torques. Asynchronous force-torque increased material removal rates up to 2X versus synchronous conditions by promoting particle agglomeration and enabling trapped particles to contribute. However, asynchronous operation also produced higher surface roughness and subsurface cracking from greater penetration. The alternating forces generated larger stresses that may have driven more plastic deformation and brittle fracture. The study provided atomic-scale insights into force-torque effects, establishing guidelines to potentially enhance efficiency through asynchronous operation despite drawbacks. [ABSTRACT FROM AUTHOR]