Transcriptome-wide association study reveals novel susceptibility genes for coronary atherosclerosis

BackgroundGenetic risk factors substantially contributed to the development of coronary atherosclerosis. Genome-wide association study (GWAS) has identified many risk loci for coronary atherosclerosis, but the translation of these loci into therapeutic targets is limited for their location in non-coding regions. Here, we aimed to screen the potential coronary atherosclerosis pathogenic genes expressed though TWAS (transcriptome wide association study) and explore the underlying mechanism association.MethodsFour TWAS approaches (PrediXcan, JTI, UTMOST, and FUSION) were used to screen genes associated with coronary atherosclerosis. Enrichment analysis of TWAS-identified genes was applied through the Metascape website. The summary-data-based Mendelian randomization (SMR) analysis was conducted to provide the evidence of causal relationship between the candidate genes and coronary atherosclerosis. At last, the cell type-specific expression of the intersection genes was examined by using human coronary artery single-cell RNA-seq, interrogating the immune microenvironment of human coronary atherosclerotic plaque at different stages of maturity.ResultsWe identified 19 genes by at least three approaches and 1 gene (NBEAL1) by four approaches. Enrichment analysis enriching the genes identified at least by two TWAS approaches, suggesting that these genes were markedly enriched in asthma and leukocyte mediated immunity reaction. Further, the summary-data-based Mendelian randomization (SMR) analysis provided the evidence of causal relationship between NBEAL1 gene and coronary atherosclerosis, confirming the protecting effects of NBEAL1 gene and coronary atherosclerosis. At last, the single cell cluster analysis demonstrated that NBEAL1 gene has differential expressions in macrophages, plasma cells and endothelial cells.ConclusionOur study identified the novel genes associated with coronary atherosclerosis and suggested the potential biological function for these genes, providing insightful guidance for further biological investigation and therapeutic approaches development in atherosclerosis-related diseases

Optimization of roadway layout in ultra-close coal seams: A case study.

Most coal mines in China are currently mining close coal seams. Roadways in close coal seams, especially ultra-close coal seams, confronted difficulties in maintaining, including large deformation of the roadway, roof caving, rib spalling and floor heaving. This is mainly caused by the complicated stress and geological conditions, shattered roof, improper layout and support. To explore the issues mentioned above, the theoretical analysis was used to build a mechanical model and study the stress distribution under coal pillars, and FLAC3D modelling was adopted to build numerical models with different staggered distances. The optimal roadway layout was brought forward combining the result of numerical simulation and coal recovery rate. The field practice was carried out in the tailgate of panel 25301 to investigate the effect of the layout scheme. The results of field monitoring show that the roadway's stability is well maintained in the mining process

Upper crustal structure beneath the Qin-Hang and Wuyishan metallogenic belts in Southeast China as revealed by a joint active and passive seismic experiment

Southeast China is one of the most important polymetallic metallogenic provinces in the world. However, distinct differences in the type and origin of the mineral deposits are present between the major metallogenic belts in this province. To deepen our knowledge of this regional metallogenic setting, investigate the factors controlling its metallogenic differences and explore the feasibility of active and passive seismic imaging, we performed a multibatch seismic experiment using active and passive sources with the help of 437 short-period seismographs deployed across the Qin-Hang and Wuyishan metallogenic belts in Southeast China. We resolved the S-wave velocity structure beneath the profile using ambient noise tomography and derived a Vp/Vs model by combining with a published P-wave model. A good correlation between the obtained seismic velocity models and geological observations is observed. The Proterozoic volcanic-sedimentary rock series and the Fuzhou-Yongfeng sedimentary basin are identified by low P- and S-wave velocities, high Vp/Vs ratios and low S-wave velocity perturbations. Within the core of the Wuyishan Metallogenic Belt, several narrow, elongated and low seismic velocity anomalies are considered to be signs of the nearby fault zones, and these anomalies provide reference information on the extension and pattern of these faults at depth. Combined with the geological and mineralogical evidence, we propose that theses faults function as ore-guiding structures and facilitate the formation of regionally representative mineral species and metal assemblages