Melatonin has been indicated to ameliorate tau hyperphosphorylation in the pathogenesis of tau diseases, but the role of melatonin-receptor signal transduction has not been clearly discovered. In this study, we found intensive tau hyperphosphorylation in melatonin receptor knockout mice. Bielschowsky silver staining showed ghostlike neurofibrillary tangles in melatonin receptor-2 knockout (MT2KO) as well as melatonin receptors-1 and -2 knockout (DKO) mice, and an argyrophilic substance was deposited in melatonin receptor-1 knockout (MT1KO) mice. Furthermore, we found significantly decreased activity of protein phosphatase 2A (PP2A) by Western blot and enzyme-linked immunosorbent assay (ELISA), which was partly due to the overexpression of protein phosphatase methylesterase-1 (PME-1), but not glycogen synthase kinase-3β (GSK-3β), cyclin-dependent kinase 5 (CDK5) or protein kinase B (Akt). Finally, we observed a significant increase in cyclic adenosine monophosphate (cAMP) and a decrease in miR-125b-5p levels in MT1KO, MT2KO and DKO mice. Using a luciferase reporter assay, we discovered that miR-125b-5p largely decreased the expression of firefly luciferase by interfering with the 3′UTR of PME-1. Furthermore, miR-125b-5p mimics significantly decreased the expression of PME-1, while miR-125b-5p inhibitor induced tau hyperphosphorylation. These results show that melatonin-receptor signal transduction plays an important role in tau hyperphosphorylation and tangle formation.
Although dry cutting is the most common method used in machining of compacted graphite cast iron (CGI), it sharply reduces the durability of the cutting tool, incurring the need to change tools frequently, and has high operating costs. This work proposes the use of oil-on-water (OoW), specifically external oil-on-water (EOoW), internal oil-on-water (IOoW) and cryogenic air with oil-on-water (CAOoW) droplets, as an eco-friendly cooling method for the turning of CGI. The results show that, because of better combination of cooling and lubrication effect, EOoW rf (spray-to-rake and flank faces EOoW) and IOoW (with 1.2 L/h water content) had the least adhesion on both tool rake and flank faces and the lowest tool wear rate among EOoW and IOoW, respectively. Furthermore, OoW condition and coated tool should be matched in order to carry out the best cutting performance. EOoW rf gave the best tool wear resistance in the machining of CGI by using a CVD Al 2 O 3-based coated tool (Tiger). The penetrability of the OoW conditions depends on machined material, setup conditions of OoW, et al. In order to improve the tool resistance in the case of turning CGI, a newly developed OoW condition (CAOoW), was proposed. CAOoW (-50°C cryogenic air) gave 3 times lower tool wear rate and 0.2-0.3 times lower surface roughness than that of EOoW rf .
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