Platelet miR-107 Participates in Clopidogrel Resistance after PCI Treatment by Regulating P2Y12.

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.

Ultrasonic signal enhancement for coarse grain materials by machine learning analysis.

This paper aims at dealing with the dilemma of examining the existence of a defect in ultrasonic detection of coarse grain materials. In such cases, defect echoes can be drowned in a strong noise background resulting from intricate coarse grain scattering, that is, grain noise. To this end, we develop an innovative signal reconstruction methodology from polluted measurements which combines basic statistical analysis with a series of machine learning algorithms. The proposed methodology analyzes abundant information from numerous raw signals to distinguish the desired signal from grain noise, avoiding the limitation of information provided only by a single signal. The technique is achieved by collecting similar signals together through a clustering algorithm and subsequently inputting these similar signals to a denoising autoencoder to suppress the grain noise. It is successfully employed to ultrasonic signals obtained from an as-cast stainless steel specimen with coarse equiaxed grains, a stainless steel specimen with relatively homogeneous dendrite fabricated by additive manufacturing and a stainless steel weld with heterogeneous columnar grains having variation of grain sizes in various locations. The influence of material microstructure and probe frequency on denoising performance is investigated in detail. Based on this, the proposed methodology is applied to defect detection. Desired A-scan results and B-scan imaging are achieved by the proposed method, where defects are well revealed. The experimental results demonstrate the developed methodology has stable excellent performance and superior denoising capabilities for defect detection with respect to conventional techniques, especially in the case where the noise is almost the same as the desired signal.

Stiff Self-Healing Coating Based on UV-Curable Polyurethane with a "Hard Core, Flexible Arm" Structure.

Two series of ultraviolet (UV)-cured self-healing polyurethane (PU) oligomers were synthesized through a prepolymer process from isophorone diisocyanate (IPDI) or 1,6-hexamethylene diisocyanate (HDI), polycarbonate diol (PCDL) of varying molecular weight (500, 1000, and 2000 Da), and chemically modified cyclotriphosphazene as hard cores were introduced. The synthesized oligomers contained rigid aromatic rings as "hard cores" and long fatty chains as "flexible arms". Nuclear magnetic resonance spectrometer (H NMR) and Fourier transform infrared spectroscopy were used to characterize the structures of the oligomers. In addition, the UV-cured self-healing PU coatings were prepared by designing some coating formulations with the PU oligomers. The self-healing properties and mechanical properties of the UV-cured coatings were investigated. The results revealed that the coatings had self-healing properties based on hydrogen bonds. As the molecular weight of PCDL decreased, the coatings exhibited increased hardness, tensile strength, and glass transition temperature. Furthermore, the coatings exhibited excellent thermostability. The results proved the application prospects of the self-healing coatings with high repair efficiency and excellent mechanical properties.

Aberrant promoter methylation of multiple genes in VSMC proliferation induced by Hcy.

Vascular smooth muscle cell (VSMC) proliferation is a primary pathological event in atherosclerosis (AS), and homocysteine (Hcy) is an independent risk factor for AS. However, the underlying mechanisms are still lagging. Studies have used the combination of methylation of promoters of multiple genes to diagnose tumors, thus the aim of the current study was to investigate the role of methylation status of several genes in VSMCs treated with Hcy. CpG islands were identified in the promoters of platelet­derived growth factor (PDGF), p53, phosphatase and tensin homologue on chromosome 10 (PTEN) and mitofusin 2 (MFN2). Hypomethylation was observed to occur in the promoter region of PDGF, hypermethylation in p53, PTEN and MFN2, and hypomethylation in two global methylation indicators, aluminium (Alu) and long interspersed nucleotide element­1 (Line­1). This was accompanied by an increase in the expression of PDGF, and reductions of p53, PTEN and MFN2, both in mRNA and protein levels. An elevation of S­adenosylmethionine (SAM) and a reduction of S­adenosylhomocysteine (SAH) and the SAM/SAH ratio were also identified. In conclusion, Hcy impacted methylation the of AS­associated genes and global methylation status that mediate the cell proliferation, which may be a character of VSMCs treated with Hcy. The data provided evidence for mechanisms of VSMCs proliferation in AS induced by Hcy and may provide a new perspective for AS induced by Hcy.