Purpose: Following major trauma, genes involved in adaptive immunity are downregulated, which accompanies the upregulation of genes involved in systemic inflammatory responses. This study ...investigated microRNA (miRNA)-mRNA interactome dysregulation in circulating T cells of patients with major trauma. Patients and Methods: This study included adult trauma patients who had an injury severity score greater than or equal to16 and required ventilator support for more than 48 h in the intensive care unit. Next-generation sequencing was used to profile the miRNAs and mRNAs expressed in CD3.sup.+ T cells isolated from patient blood samples collected during the injury and recovery stages. Results: In the 26 studied patients, 9 miRNAs (hsa-miR-16-2-3p, hsa-miR-16-5p, hsa-miR-185-5p, hsa-miR-192-5p, hsa-miR-197-3p, hsa-miR-23a-3p, hsa-miR-26b-5p, hsa-miR-223-3p, and hsa-miR-485-5p) were significantly upregulated, while 58 mRNAs were significantly downregulated in T cells following major trauma. A network consisting of 8 miRNAs and 22 mRNAs interactions was revealed by miRWalk, with three miRNAs (hsa-miR-185-5p, hsa-miR-197-3p, and hsa-miR-485-5p) acting as hub genes that regulate the network. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggested that "chemokine signaling pathway" was the predominant pathway. Conclusion: The study revealed a miRNA-mRNA interactome consisting of 8 miRNAs and 22 mRNAs that are predominantly involved in chemokine signaling in circulating T cells of patients following major trauma. Keywords: miRNA, next-generation sequencing, T cells, adaptive immunity, major trauma, critical illness
In this paper, an experiment has been used to study the effect of pyrolysis stage (from injection to combustion) to dioxin exhaust from diesel engine. The characteristics of diesel fuel pyrolysis ...have been applied in order to calculate the mean molecular weight in varied temperatures and measure the concentration of inorganic chlorine (HCl). On the other hand, measuring the chlorine content of these particles after diesel pyrolysis enables researchers to find out the pyrolysis temperature that has the lowest possibility to produce dioxin. Additionally, the post-pyrolysis carbon particle diameter has been observed through electronic microscope so as to evaluate the combustion condition of the combustion stage. Result from this study would be helpful for researchers to understand the probability of dioxin formation.
Benzyl alcohol (BA) is the preservative in triamcinolone acetonide (TA) suspensions, which are used in treating vitreoretinal diseases and during surgery. This paper investigates the molecular ...mechanisms and signaling pathways underlying BA toxicity in human retinal pigment epithelial (RPE) cells.
Cultured human RPE cells from the ARPE-19 cell line were exposed to culture medium alone (control) or with BA (0.0225, 0.225, 0.9, 3, or 9 mg/mL) for up to 6 hours. BA toxicity was assessed by TUNEL assay, propidium iodide/annexin V-FITC staining and flow cytometry, caspase activation assay, caspase and apoptosis inhibition assays, mitochondrial transmembrane potential by rhodamine staining and flow cytometry, reactive oxygen species by chemiluminescence, and apoptosis-inducing factor staining.
BA caused RPE cell death not only by necrosis but also by apoptosis, evidenced by exposure to 9 mg/mL BA for 6 hours leading to 19.0% early apoptotic cells and 64.2% apoptotic necrotic cells. Apoptotic signaling involved the immediate production of reactive oxygen species, activation of caspase-8, impairment of the mitochondrial transmembrane potential, and further activation of caspase-9 and -3. In addition, BA induced translocation of apoptosis-inducing factor into the nucleus, indicating caspase-independent apoptosis.
BA leads to necrosis of RPE cells and triggers mitochondrial apoptosis through both caspase-dependent and - independent pathways. Extreme caution is suggested in the intraocular use of TA suspensions and meticulous evaluation before adoption of BA as a preservative in the future development of ophthalmic formulations.
Background: A significant proportion of acute coronary syndrome (ACS) patients experience high on-treatment platelet reactivity (HPR) on clopidogrel-based dual antiplatelet therapy (DAPT) after ...percutaneous coronary intervention (PCI). ＜br＞
Objectives: This study assessed key independent risk factors associated with significant HPR risk on clopidogrel, but not prasugrel, in the Switch Study cohort of 200 Taiwanese ACS patients who switched from clopidogrel to low-dose prasugrel for maintenance DAPT after PCI. ＜br＞
Methods: Univariate analysis and stepwise multivariate logistic regression analysis were conducted to identify key independent risk factors for HPR on clopidogrel, but not prasugrel. ＜br＞
Results: A HANC H: low hemoglobin (＜ 13 g/dL for men and ＜ 12 g/dL for women); A: age ≥ 65 years; N: non-ST elevation myocardial infarction; C: chronic kidney disease as defined by estimated glomerular filtration rate ＜ 60 mL/min risk stratification score was developed, and demonstrated optimal sensitivity and sp
This study proposes a flux-splitting Maxwellas equations solver for modeling electromagnetic waves in two-dimensional non-staggered grids. A fifth-order spatially accurate dual-compact upwind scheme ...was developed in a three-point grid stencil to approximate the first-order derivative term. The integrity of the proposed finite-difference time-domain method for solving TM-mode Maxwellas equations verified using two-dimensional test problems. The benchmark Mie-scattering problem was also shown to be in good agreement with the semi-analytic result.
In recent years, cyber security threats have become increasingly dangerous. Hackers have fabricated fake emails to spoof specific users into clicking on malicious attachments or URL links in them. ...This kind of threat is called a spear-phishing attack. Because spear-phishing attacks use unknown exploits to trigger malicious activities, it is difficult to effectively defend against them. Thus, this study focuses on the challenges faced, and we develop a Cloud-threat Inspection Appliance (CIA) system to defend against spear-phishing threats. With the advantages of hardware-assisted virtualization technology, we use the CIA to develop a transparent hypervisor monitor that conceals the presence of the detection engine in the hypervisor kernel. In addition, the CIA also designs a document pre-filtering algorithm to enhance system performance. By inspecting PDF format structures, the proposed CIA was able to filter 77% of PDF attachments and prevent them from all being sent into the hypervisor monitor for deeper analysis. Finally, we tested CIA in real-world scenarios. The hypervisor monitor was shown to be a better anti-evasion sandbox than commercial ones. During 2014, CIA inspected 780,000 mails in a company with 200 user accounts, and found 65 unknown samples that were not detected by commercial anti-virus software.
Abstract Uterine sarcoma is a very aggressive and highly lethal disease. Even after a comprehensive staging surgery or en block cytoreduction surgery followed by multimodality therapy (often ...chemotherapy and/or radiation therapy), many patients relapse or present with distant metastases, and finally die of diseases. The worst outcome of uterine sarcomas is partly because of their rarity, unknown etiology, and highly divergent genetic aberration. Uterine sarcomas are often classified into four distinct subtypes, including uterine leiomyosarcoma, low-grade uterine endometrial stromal sarcoma, high-grade uterine endometrial stromal sarcoma, and undifferentiated uterine sarcoma. Currently, evidence from tumor biology found that these tumors showed alternation and/or mutation of genomes and the intracellular signal pathway. In addition, some preclinical studies showed promising results for targeting receptor tyrosine kinase signaling, phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway, various kinds of growth factor pathways, Wnt/beta-catenin signaling pathway, transforming growth factor β/bone morphogenetic protein signal pathway, aurora kinase A, MDM2 proto-oncogene, histone deacetylases, sex hormone receptors, certain types of oncoproteins, and/or loss of tumor suppressor genes. The current review is attempted to summarize the recurrent advance of targeted therapy for uterine sarcomas.
The heterogeneity of exosome populations presents a great challenge to their study. The current study was designed to investigate the potential heterogeneity miRNA contents in circulating exosomes ...purified via different exosomal markers. In this study, exosomes from the serum of C57BL/6 mice after cecum ligation and perforation (CLP) or sham operation were isolated by precipitation using ExoQuick-TC and affinity purified with anti-Rab5b, anti-CD9, anti-CD31, and anti-CD44 antibodies using the Exo-Flow Exosome Capture kit to collect exosome subpopulations. RNA extracted from the exosomes isolated by ExoQuick-TC were profiled by next-generation sequencing (NGS). Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was also employed to determine the expression profiles of four representative exosomal miRNAs (mmu-miR-486-5p, mmu-miR-10a-5p, mmu-miR-143-3p, and mmu-miR-25-3p) selected from the NGS analysis. The results revealed that the expression patterns of these miRNAs in exosomes isolated by ExoQuick-TC as determined by RT-qPCR and NGS were similar, showing upregulation of mmu-miR-10a-5p and mmu-miR-143-3p but downregulation of mmu-miR-25-3p and mmu-miR-486-5p following CLP when compared to the levels in exosomes from sham control mice. However, their expression levels in the antibody-captured exosome subpopulations varied. The miRNAs in the exosomes captured by anti-Rab5b or anti-CD9 antibodies were more similar to those isolated by ExoQuick-TC than to those captured by anti-CD44 antibodies. However, there were no significant differences in these four miRNAs in CD31-captured exosomes. This study demonstrated that purification with different exosomal markers allows the collection of different exosome subpopulations with various miRNA contents. The results of this study demonstrate the heterogeneity of circulating exosomes and suggest the importance of stratifying exosome subpopulations when using circulating exosomes as biomarkers or investigating exosome function. In addition, this study also emphasized the necessity of using a consistent exosome marker across different samples as detecting biomarkers.
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