IntroductionThe migrasome is a newly discovered organelle that resembles extracellular vesicles in structure. However, the function of the migrasome in tumors, particularly in relation to tumor immunity and tumor microenvironment, is unclear.MethodsGene expression data, copy number variation raw data, and methylation data of 33 cancer types were downloaded from The Cancer Genome Atlas database. Immunohistochemistry (IHC) based on 114 case of colorectal cancer was used to validate the expression of the migrasome hub-gene. We analyzed the expression, prognosis, genetic variation, and drug sensitivity profiles of migrasome-related genes (MRGs) in pan-cancer datasets. A migrasome score was constructed based on gene set enrichment analysis, and the correlation of migrasomes with the tumor microenvironment was assessed. The CancerSEA was used to perform a single-cell level functional analysis of the migrasome. Additionally, we also analyzed the correlation between migrasomes and tumor mutational burden (TMB), microsatellite instability (MSI), and tumor immune dysfunction and exclusion scores. Single-cell transcriptome sequencing (scRNA-seq) data was used to assess the activation state of migrasomes in the tumor microenvironment.ResultsPIGK expression was significantly up-regulated in 22 of 33 tumors, and high expression of migrasome was estimated to have contributed to poor prognosis. Missense mutations are the most common type of mutation in MRGs. We identified piperlongumine as a potential drug targeting migrasomes. The migrasome score was significantly and positively correlated with the tumor immunity score and the stroma score. In most tumors, the abundance of macrophages in the tumor microenvironment was significantly and positively correlated with the migrasome score. Additionally, the migrasome scores were significantly correlated with the immune checkpoint genes in pan-cancer as well as immune checkpoint therapy-related markers including TMB and MSI. According to scRNA-seq analysis, migrasome differed significantly among cells of the tumor microenvironment. IHC confirmed low expression of ITGA5 and PIGK in colorectal cancer.DiscussionWe performed the first pan-cancer analysis of migrasomes and discovered that they play an important role in tumor development and immune escape. Our study provides new insights into the role of migrasomes in tumor prognosis and immunotherapy.
Medium-low-speed maglevs are increasingly used in the urban rail transit industry because of their advantages, such as low noise and low energy consumption. In this study, a finite element analysis of the responses of the subgrade that supports a medium-low-speed maglev structure under a dynamic maglev load is presented. First, the finite element analysis considers a low-lying structure with different elastic moduli. Then, the attenuation laws of the dynamic stress and dynamic deformation for different depth ranges of the subgrade under the rail beam are analyzed. In addition, the magnitude of the influence of the dynamic load is clarified. The results lead to a recommendation of a base bed thickness of 1.5 m, graded gravel or group A filler as the surface layer of filler, and gravel soil as the bottom layer. This study provides theoretical support for the construction design of a subgrade structure under the rail beam of a low-lying maglev line.
The experience needed to carry out engineering and construction in diatomaceous earth areas is currently lacking. This project studies the new Hang Shaotai high-speed railway passing through a diatomaceous earth area in Shengzhou, Zhejiang Province, and analyzes the hydrological and mechanical properties of diatomaceous earth on the basis of a field survey and laboratory. Moreover, a new antidrainage subgrade structure was proposed to address the rainy local environment, and field excitation tests were performed to verify the antidrainage performance and stability of the new subgrade structure. Finally, the dynamic characteristics and deformation of the diatomaceous earth roadbed were examined. The hydrophysical properties of diatomaceous earth in the area are extremely poor, and the disintegration resistance index ranges from 3.1% to 9.0%. The antidrainage subgrade structure has good water resistance and stability under dynamic loading while submerged in water. After 700,000 loading cycles, the dynamic stress and vibration acceleration of the surface of the subgrade bed stabilized at approximately 6.37 kPa and 0.94 m/s2, respectively. When the number of excitations reached 2 million, the settlement of the diatomaceous earth foundation was 0.08 mm, and there was basically negligible postwork settlement of the diatomaceous earth foundation. These results provide new insights for engineering construction in diatomaceous earth areas.
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