ABSTRACT
Inorganic pyrophosphatase (PPA1) encoded by PPA1 gene belongs to Soluble Pyrophosphatases (PPase) family and is expressed widely in various tissues of Homo sapiens, as well as significantly in a variety of malignancies. The hydrolysis of inorganic pyrophosphate (PPi) to produce orthophosphate (Pi) not only dissipates the negative effects of PPi accumulation, but the energy released by this process also serves as a substitute for ATP. PPA1 is highly expressed in a variety of tumors and is involved in proliferation, invasion, and metastasis during tumor development, through the JNK/p53, Wnt/ß-catenin, and PI3K/AKT/GSK-3ß signaling pathways. Because of its remarkable role in tumor development, PPA1 may serve as a biological target for adjuvant therapy of tumor malignancies. Further, PPA1 is a potential biomarker to predict survival in patients with cancer, where the assessment of its transcriptional regulation can provide an in-depth understanding. Herein, we describe the signaling pathways through which PPA1 regulates malignant tumor progression and provide new insights to establish PPA1 as a biomarker for tumor diagnosis.
ABSTRACT
In order to explore the clamping fatigue properties of shrink-fit holders, ANSYS software was used in this study to analyze the thermal and contact stresses during the clamping process of the shrink-fit holder, and the fatigue analysis was performed by selecting the dangerous areas based on the two stresses. A numerical control shrink-fit holder clamping fatigue test device was manufactured, and the automatic clamping of the shrink-fit holder was executed in this study. After 500 clamping repetitions, a milling test was carried out on the shrink-fit bracket. By collecting the vibration signal of the workpiece during processing and measuring the change in the surface roughness of the workpiece, and then analyzing the change in the machining performance of the shrink-fit holder under different clamping times, we were able to compare and verify the accuracy of the finite element fatigue analysis.
ABSTRACT
INTRODUCTION: High platelet reactivity (HPR) caused by clopidogrel tolerance is an adverse reaction of acute coronary syndrome (ACS) patients who receive clopidogrel antiplatelet therapy after percutaneous coronary intervention (PCI) surgery. Platelet microRNA (miRNA) is related to platelet reactivity. This study explored the mechanism of platelet miRNA in regulating platelet reactivity. METHODS: We recruited 50 ACS/PCI patients and divided them into the HPR group (P2Y12 reaction units [PRU] ≥300) and the LPR group (PRU < 170) according to the PRU through the VerifyNow P2Y12 assay. P2Y12-related miRNAs were screened by TargetScan, miRWalk, and Gene Expression Omnibus. The expressions of P2Y12 and miRNAs in the HPR group and the LPR group were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Pearson correlation analysis was used to determine the correlation between P2Y12 and miRNAs. The interactions between P2Y12 and miR-107 were predicted by TargetScan and verified by dual-luciferase reporter assay. The regulation of miR-107 mimic or inhibitor on P2Y12 expression was detected by qRT-PCR and Western blot. RESULTS: There were 22 patients in the LPR group and 28 patients in the HPR group. PY212 was highly expressed in the HPR group compared with the LPR group. We screened the P2Y12-related miRNAs (miR-145-5p, miR-4701-3p, miR-107, and miR-15b-5p), but only miR-107 and miR-15b-5p expressions were downregulated in the HPR group and were negatively correlated with PY212 expression. P2Y12 was the target gene of miR-107. PY212 expression was inhibited by miR-107 overexpression but suppressed by miR-107 silencing. CONCLUSION: Platelet miR-107 participated in clopidogrel resistance in ACS/PCI patients by regulating P2Y12 expression.
