LINC00543 promotes colorectal cancer metastasis by driving EMT and inducing the M2 polarization of tumor associated macrophages.

BACKGROUND: The interaction between the tumor-microenvironment (TME) and the cancer cells has emerged as a key player in colorectal cancer (CRC) metastasis. A small proportion of CRC cells which undergo epithelial-mesenchymal transition (EMT) facilitate the reshaping of the TME by regulating various cellular ingredients. METHODS: Immunohistochemical analysis, RNA immunoprecipitation (RIP), RNA Antisense Purification (RAP), dual luciferase assays were conducted to investigate the biological function and regulation of LINC00543 in CRC. A series in vitro and in vivo experiments were used to clarify the role of LINC00543 in CRC metastasis. RESULTS: Here we found that the long non-coding RNA LINC00543, was overexpressed in colorectal cancer tissues, which correlated with advanced TNM stage and poorer prognosis of CRC patients. The overexpression of LINC00543 promoted tumorigenesis and metastasis of CRC cells by enhancing EMT and remodeling the TME. Mechanistically, LINC00543 blocked the transport of pre-miR-506-3p across the nuclear-cytoplasmic transporter XPO5, thereby reducing the production of mature miR-506-3p, resulting in the increase in the expression of FOXQ1 and induction of EMT. In addition, upregulation of FOXQ1 induced the expression of CCL2 that accelerated the recruitment of macrophages and their M2 polarization. CONCLUSIONS: Our study showed that LINC00543 enhanced EMT of CRC cells through the pre-miR-506-3p/FOXQ1 axis. This resulted in the upregulation of CCL2, leading to macrophages recruitment and M2 polarization, and ultimately stimulating the progression of CRC.

Exploration of dilated cardiomyopathy for biomarkers and immune microenvironment: evidence from RNA-seq.

BACKGROUND: The pathogenic mechanism of dilated cardiomyopathy (DCM) remains to be defined. This study aimed to identify hub genes and immune cells that could serve as potential therapeutic targets for DCM. METHODS: We downloaded four datasets from the Gene Expression Omnibus (GEO) database: GSE141910, GSE3585, GSE42955 and GSE79962. Weighted gene coexpression network analysis (WGCNA) and differential expression analysis were performed to identify gene panels related to DCM. Meanwhile, the CIBERSORT algorithm was used to estimate the immune cells in DCM tissues. Multiple machine learning approaches were used to screen the hub genes and immune cells. Finally, the diagnostic value of the hub genes was assessed by receiver operating characteristic (ROC) analysis. An experimental mouse model of dilated cardiomyopathy was used to validate the bioinformatics results. RESULTS: FRZB and EXT1 were identified as hub biomarkers, and the ROC curves suggested an excellent diagnostic ability of the above genes for DCM. In addition, naive B cells were upregulated in DCM tissues, while eosinophils, M2 macrophages, and memory CD4 T cells were downregulated in DCM tissues. The increase in two hub genes and naive B cells was validated in animal experiments. CONCLUSION: These results indicated that FRZB and EXT1 could be used as promising biomarkers, and eosinophils, M2 macrophages, resting memory CD4 T cells and naive B cells may also affect the occurrence of DCM.

Causal effect of iron status on lung function: A Mendelian randomization study.

Background: The association between systemic iron status and lung function was conflicting in observational studies. We aim to explore the potential causal relationships between iron status and the levels of lung function using the two-sample Mendelian randomization (MR) design. Methods: Genetic instruments associated with iron status biomarkers were retrieved from the Genetics of Iron Status (GIS) consortium (N = 48,972). Summary statistics of these genetic instruments with lung function were extracted from a meta-analysis of UK Biobank and SpiroMeta consortium (N = 400,102). The main analyses were performed using the inverse-variance weighted method, and complemented by multiple sensitivity analyses. Results: Based on conservative genetic instruments, MR analyses showed that genetically predicted higher iron (beta: 0.036 per 1 SD increase, 95% confidence interval (CI): 0.016 to 0.056, P = 3.51 × 10-4), log10-transformed ferritin (beta: 0.081, 95% CI: 0.047 to 0.116, P = 4.11 × 10-6), and transferrin saturation (beta: 0.027, 95% CI: 0.015 to 0.038, P = 1.09 × 10-5) were associated with increased forced expiratory volume in 1 s (FEV1), whereas higher transferrin was associated with decreased FEV1 (beta: -0.036, 95% CI: -0.064 to -0.008, P = 0.01). A significant positive association between iron status and forced vital capacity (FVC) was also observed. However, there is no causal association between iron status and FEV1-to-FVC ratio (P = 0.10). Similar results were obtained from the liberal instruments analyses and multiple sensitivity analyses. Conclusion: Our study provided strong evidence to support that higher iron status is causally associated with higher levels of FEV1 and FVC, but has no impact on airway obstruction, confirming iron status as an important target for lung function management.

Approach to breech face impression comparison based on the robust estimation of a correspondence function.

Forensic firearm analysis concerns an attempt to determine if ammunition is associated with a specific firearm based on tool-marks produced by it. A feature-based method using the Scale Invariant Feature Transform (SIFT) and RANdom SAmple Consensus (RANSAC) integration algorithm had been suggested to allow the automated comparison of breech face impressions. In this paper, an estimation method is proposed to establish a correspondence function among the features of comparison impression pairs, aiming to further improve the robustness and repeatability of automated feature matching. During the application of the iterative establishment algorithm, the Support Vector Regression (SVR) method is repeated to estimate the correspondence function based on current feature correspondences, and a robust weighting method excludes egregious outliers among putative correspondences by updating additional weightings. Moreover, the consistency detection method is adopted to overcome the over-fitting problem in SVR. Validation tests of the proposed method are conducted on three sets of cartridge case's breech face impressions; namely the Fadul set consisting of 40 cartridge cases ejected from 10 Ruger P95PR15 pistols, the Weller sets containing 95 cartridge cases obtained from 11 Ruger P95DC firearms and the Lightstone set containing 30 cartridge cases from 10 SW40VE S&W Sigma pistol slides. Test results show that most known matching (KM) pairs possess no less than 20 matching feature points while the non-matching (KNM) pairs all maintain 3-8 correspondences. It also indicates that the feature-based method has apparent advantages in dealing with granular impressions with local peaks and valleys features, and poor performance on the striation marks. The clear distinction between KM and KNM impression pairs demonstrates the feasibility of the proposed method in ballistic feature comparison. Compared to the random hypothesize-and-verify modeling of RANSAC, this method can retain more reliable matching feature points of the impression pair to ensure the repeatability of feature correspondence selection.

Pyroptosis Patterns Are Involved in Immune Microenvironment Regulation of Dilated Cardiomyopathy.

The importance of cell pyroptosis in immunity regulation is becoming increasingly obvious, especially in diseases of the cardiovascular system. Nevertheless, it is unknown whether the pyroptosis signalling pathway is involved in the immune microenvironment regulation of dilated cardiomyopathy (DCM). Therefore, the purpose of the study was to investigate the influence of pyroptosis on the immune environment in dilated cardiomyopathy. We found that expression of 19 pyrolysis-related genes (PRGs) in DCM samples was altered compared to healthy samples. Subsequently, based on these 12 hub pyrolysis-related genes, we developed a classifier that can distinguish between healthy samples and DCM samples. Among the hub pyrolysis-related genes, RT-PCR analyses demonstrated that five of them exhibited significant differential expression in DCM. Interestingly, we observed that immune characteristics are correlated with pyroptosis: higher expression of GSDMD is positively correlated with infiltrating activated pDCs; GSDMD is negatively correlated with Tregs; CASP1 is positively related to parainflammation; and CASP9 is negatively related to the type II IFN response. In addition, distinct pyroptosis-mediated patterns were identified, and immune characteristics under distinct patterns were revealed: pattern B mediates an active immune response, and pattern A leads to a relatively mild immune response to DCM. We also compared the biological functions between these patterns. Compared with pattern A, pattern B had more abundant pathways, such as the NOTCH signalling pathway and pentose phosphate pathway. In summary, this study proves the important influence of pyrolysis on the immune microenvironment of dilated cardiomyopathy and provides new clues for understanding the pathogenesis of dilated cardiomyopathy.

Ditetraalkylammonium amino acid ionic liquids as CO2 absorbents of high capacity.

By grafting butyl or ethyl onto tetramethylethylenediamine, quaternary ammonium salts with two positive charge centers were formed at the first step. Metathesis with Ag(2)O followed. Through neutralization with glycine, l-alanine, or valine, a series of new ditetraalkylammonium amino acid ionic liquids (DILs) for CO(2) capture were generated. The structures of DILs, as shown in Figure 1, were verified by using (1)H NMR and EA. These DILs were found to be of quite high viscosity which militated against their industrial application in CO(2) removal. Drawing on the experience of mixed amines' aqueous solutions, these DILs were blended with water or N-methyldiethanolamine (MDEA) aqueous solutions to act as special absorbents of CO(2). Using a Double-Tank Absorption System, the absorption performance of these DIL solutions was investigated in detail. The experimental results indicated that among the three aqueous solutions of DILs (20%, 40%, and 80 wt %), the solution of 40% DIL had a higher absorption rate of CO(2) than the other two, demonstrating the different effects of concentration and viscosity on the absorption. The solution of 40% DIL or the 15% DIL + 15% MDEA had much higher capacity for CO(2) than the corresponding monocation tetraalkylammonium AAILs, due to the special structure of the dication which could influence the solubility of CO(2) in the aqueous solution.