Background: The role of N6-methyladenosine (m6A) modification in abdominal aortic aneurysm (AAA) has not been extensively studied. This study therefore aimed to investigate m6A RNA methylation and the expressions of the corresponding modulators in AAA.Methods: A comparative study between AAA tissue samples (n=32) and healthy aortas (n=12) was performed using m6A methylation quantification for messenger RNA (mRNA) m6A status, quantitative polymerase chain reaction (qPCR), and western blot for the expressions of m6A modulators and immunohistochemistry (IHC) to detect locations of the modulators in AAA tissues.Results: The m6A level significantly increased in AAA as compared to healthy aorta tissues. Among AAA patients, the high m6A level represented an even greater risk of AAA rupture as compared to nonruptured AAA [odds ratio (OR), 1.370; 95% confidence interval (CI), 1.007-1.870]. The major N6adenosine modulators, including YTHDF1, YTHDF3, FTO, and METTL14, are the main factors involved in aberrant m6A modification and the expression of both was significantly correlated to the proportion of m6A in total mRNA. Clinically, YTHDF3 represented an even greater risk of rupture (OR, 1.036; 95% CI, 1.001-1.072). Regarding the cellular location, METTL14 seemed to be associated with inflammatory infiltrates and neovascularization. Furthermore, a strong correlation was seen between FTO and aneurysmal smooth muscle cells (SMCs), YTHDF3, and macrophage infiltrate. Conclusions:We were first to observe m6A modification in human AAA tissues. The results also reveal the important roles of m6A modulators, including YTHDF3, FTO, and METTL14, in the pathogenesis of human AAA and provide a new view on m6A modification in AAA. Our findings suggest a potential mechanism of epigenetic alterations in clinical AAA.
Background: Papillary thyroid cancer has been associated with chronic inflammation. A systematic understanding of immune cell infiltration in PTC is essential for subsequent immune research and new diagnostic and therapeutic strategies.Methods: Three different algorithms, single-sample gene set enrichment analysis (ssGSEA), immune cell marker and CIBERSORT, were used to evaluate immune cell infiltration levels (abundance and proportion) in 10 data sets (The Cancer Genome Atlas [TCGA], GSE3467, GSE3678, GSE5364, GSE27155, GSE33630, GSE50901, GSE53157, GSE58545, and GSE60542; a total of 799 PTC and 194 normal thyroid samples). Consensus unsupervised clustering divided PTC patients into low-immunity and high-immunity groups. Weighted gene coexpression network analysis (WGCNA) and gene set enrichment analysis (GSEA) were used to analyze the potential mechanisms causing differences in the immune response.Results: Compared with normal tissues, PTC tissues had a higher overall immune level and higher abundance levels and proportions of M2 macrophages, Tregs, monocytes, neutrophils, dendritic cells (DCs), mast cells (MCs), and M0 macrophages. Compared with early PTC, advanced PTC showed higher immune infiltration and higher abundance levels and proportions of M2 macrophages, Tregs, monocytes, neutrophils, DCs, MCs, and M0 macrophages. Compared to the low-immunity group, the high-immunity group exhibited more advanced stages, larger tumor sizes, greater lymph node metastases, higher tall-cell PTCs, lower follicular PTC proportions, more BRAF mutations, and fewer RAS mutations. Epstein-Barr virus (EBV) infection was the most significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway for key module genes. Conclusions:In human PTC, M2 macrophages, Tregs, monocytes, neutrophils, DCs, MCs, and M0 macrophages appear to play a tumor-promoting role, while M1 macrophages, CD8+ T cells, B cells, NK cells, and T follicular helper (T FH ) cells (including eosinophils, gd T cells, and Th17 cells with weak supporting evidence) appear to play an antitumor role. During the occurrence and development of PTC, the overall immune level was increased, and the abundance and proportion of tumorpromoting immune cells were significantly increased, indicating that immune escape
Floating-point arithmetic precision is limited in length the IEEE single (respectively double) precision format is 32-bit (respectively 64-bit) long. Extended precision formats can be up to 128-bit long. However some problems require a longer floating-point format, because of round-off errors. Such problems are usually solved in arbitrary precision, but round-off errors still occur and must be controlled. Interval arithmetic has been implemented in arbitrary precision, for instance in the MPFI library. Interval arithmetic provides guaranteed results, but it is not well suited for the validation of huge applications. The CADNA library estimates round-off error propagation using stochastic arithmetic. CADNA has enabled the numerical validation of real-life applications, but it can be used in single precision or in double precision only. In this paper, we present a library called SAM (Stochastic Arithmetic in Multiprecision). It is a multiprecision extension of the classic CADNA library. In SAM (as in CADNA), the arithmetic and relational operators are overloaded in order to be able to deal with stochastic numbers. As a consequence, the use of SAM in a scientific code needs only few modifications. This new library SAM makes it possible to dynamically control the numerical methods used and more particularly to determine the optimal number of iterations in an iterative process. We present some applications of SAM in the numerical validation of chaotic systems modeled by the logistic map.
BackgroundIn previous research, we found that cell secretion from the adult lamprey supraneural body tissues possesses cytocidal activity against tumor cells, but the protein with cytocidal activity was unidentified.MethodsA novel lamprey immune protein (LIP) as defense molecule was first purified and identified in jawless vertebrates (cyclostomes) using hydroxyapatite column and Q Sepharose Fast Flow column. After LIP stimulation, morphological changes of tumor cells were analysed and measured whether in vivo or in vitro.ResultsLIP induces remarkable morphological changes in tumor cells, including cell blebbing, cytoskeletal alterations, mitochondrial fragmentation and endoplasmic reticulum vacuolation, and most of the cytoplasmic and organelle proteins are released following treatment with LIP. LIP evokes an elevation of intracellular calcium and inflammatory molecule levels. Our analysis of the cytotoxic mechanism suggests that LIP can upregulate the expression of caspase 1, RIPK1, RIP3 to trigger pyroptosis and necroptosis. To examine the effect of LIP in vivo, tumor xenograft experiments were performed, and the results indicated that LIP inhibits tumor growth without damage to mice. In addition, the cytotoxic action of LIP depended on the phosphatidylserine (PS) content of the cell membrane.ConclusionsThese observations suggest that LIP plays a crucial role in tumor cell survival and growth. The findings will also help to elucidate the mechanisms of host defense in lamprey.Electronic supplementary materialThe online version of this article (10.1186/s12964-017-0198-6) contains supplementary material, which is available to authorized users.
Featured Application: The developed magnetostrictive FeNi coated Surface acoustic wave sensor with high sensitivity; fast response; strong anti-interference; good linearity and repeatability; and lower hysteresis error will be a potential candidate for current monitoring application in smart grid line testing; metallurgical and power supplies; rail transit safety warnings and rescue.Abstract: A magnetostrictive FeNi-coated surface acoustic wave (SAW)-based current sensor was proposed in this work. The weak remanence and hysteresis effect of the FeNi itself contributes to suppress the asymmetry in sensor response at increasing and decreasing current. The sensor response was simulated by solving the coupled electromechanical field equation in layered structure considering the magnetostrictive effect and an approach of effective dielectric constant. The effects from the aspect ratio and thickness of the FeNi film on sensor response were analyzed to determine the optimal design parameters. Differential oscillation structure was used to form the sensor, in which, the FeNi thin film was deposited along the SAW propagation of the sensor chip by using RF magnetron sputtering. The magnetostrictive effect of the FeNi coating induced by the magnetic loading generates the perturbation in SAW velocity, and corresponding oscillation frequency. High sensitivity of 10.7 KHz/A, good linearity and repeatability, lower hysteresis error of 0.97% were obtained from the developed prototype 150 MHz SAW FeNi coated current sensor.
Background: AHNAK2 has been recently reported as a biomarker in many cancers. However, a systematic investigation of AHNAK2 in papillary thyroid carcinoma (PTC) has not been conducted. Results: AHNAK2 is overexpressed in PTC tissues and could be an independent prognostic factor. AHNAK2 expression was significantly high in patients with advanced stage, advanced T classification, lymph node metastasis, increased BRAF mutations and decreased RAS mutations. Cell adhesion-, cell junction-, and immune-related pathways were the most frequently noted in gene set enrichment analysis. AHNAK2 expression in PTC was positively correlated with immune infiltration and negatively correlated with AHNAK2 methylation. AHNAK2 expression was significantly positively correlated with tumor progression and poor overall survival (OS) in pan-cancer patients. Conclusions: AHNAK2 is a good biomarker for the diagnosis and prognosis of PTC. AHNAK2 may promote thyroid cancer progression through cell adhesion-, cell junction-, and immune-related pathways. Methylation may act as an upstream regulator to inhibit the expression and biological function of AHNAK2 . Additionally, AHNAK2 has broad prognostic value in pan-cancer. Methods: Based on The Cancer Genome Atlas (TCGA) data, we screened AHNAK2 -related genes through weighted gene coexpression network analysis and explored the clinical value and the potential mechanism of AHNAK2 in PTC by multiomics analysis.
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