No abstract

Understanding subclonal architecture and their biological functions poses one of the key challenges to deeply portray and investigative the cause of triple-negative breast cancer (TNBC). Here we combine single-cell and bulk sequencing data to analyze tumor heterogeneity through characterizing subclone compositions and proportions. Based on sing-cell RNA-seq data (GSE118389) we identified five distinct cell subpopulations and characterized their biological functions based on their gene markers. It is worth noting that C1 and C2 relate to immune functions, while C5 relates to programmed cell death. Then based on subclonal basis gene expression matrix, we applied CBS deconvolution algorithm on TCGA tissue RNA-seq data, and found that patients with low and high C1 proportions have different immune microenvironment;and high C5 proportions would led to poor survival outcome, p-value and HR [95%CI] for five years overall survival in TCGA dataset were 0.0326 and 1.664 [1.038-2.667], and in GSE96058 dataset were 0.0158 and 2.557 [1.160-5.636]. Collectively, our analysis reveals the both intra-tumor and inter-tumor heterogeneity and their association with subclonal microenvironment in TNBC (subclone compositions and proportions), and uncovers the organic combination of subclones dictating poor outcomes in this disease.

Background: As reliable intercellular transporters, exosomes for the diagnosis and function of various disease are fully explored. Also, exosomes extracted from tear film have been used as indictors for various eye disease, even systemic disease due to the easy and non-invasive collection nature with microRNAs variation. However, there still no reports focus the change and function of on exosomes and exosomal microRNAs during diabetes ocular dysfunction.Methods: Paired diabetes and health tear film-derived exosomes were collected by test strips and identified according standard regimens. Different expression microRNAs were profiled by microarray. The function of exosomes to cornea epithelium was detected by cornea wound model in vivo and cell viability and migration assay in vitro. Bioinformatics analysis, including GO and KEGG were conducted to explore the potential biological signaling pathway.Results: We confirmed diabetic tear film derived exosomes contribute to delay cornea wound healing and aggravate diabetic dry eye-like syndrome. Total 12 differential expression microRNAs were confirmed compared with paired controls, may participate in glycosphingolipid biosynthesis; mucin type O-Glycan biosynthesis; Ras signaling pathway; AMPK signaling pathway; bacterial invasion of epithelial cells; ErbB signaling pathway; cGMP-PKG signaling pathwayConclusion: This study provides evidence that diabetic tear film derived exosomes can affect the ocular surface health during diabetes, while healthy exosomes have no similar effects. Thus, the different expression of microRNAs existed in the exosomes from diabetes and healthy volunteer may be the reason of different function.

Background Chronic inflammatory infiltration is a common process for atherosclerosis development. However, autopsy studies reveal that incidence rate of inflammatory infiltrates are less abundant in plaque erosion compared with plaque rupture. Purpose Studies performed by optical coherence tomography (OCT) have allowed to establish the severity of plaque inflammation by assessing macrophage infiltration (MØI). In this study, we aimed at assessing the impaction of MØI in plaque erosion among patients with STEMI by using OCT. Methods A total of 1561 patients with ST-segment elevation myocardial infarctions (STEMI) who underwent OCT imaging were enrolled in this study. According to the exclusion criteria, 312 patients with STEMI exhibiting plaque erosion were classified as MØI or no MØI. Results 163 (52.2%) patients had MØI at the site of plaque erosion, whereas 149 (47.8%) patients had no evidence of MØI and patients of MØI group were significantly older (P=0.015). The result of angiography showed the prevalence of multi-vessel disease appeared more frequency (P=0.021) and diameter stenosis% were higher (P=0.031) in MØI group. OCT results showed the minimum fibrous-cap thickness was thinner (P<0.001) and the maximum lipid arc was larger (P=0.005) in MØI group. Some patients underwent imaging follow-up at 1 year. There was no significant difference in the culprit plaque morphology progress among two groups (Figure 1A-1D). Conclusions This study demonstrated that plaque inflammation can increase culprit lesion severity and plaque vulnerability in patients with STEMI caused by plaque erosion. Figure 1 Funding Acknowledgement Type of funding source: None

Many studies have provided valuable information about genomic and transcriptomic changes that occur in colorectal cancer (CRC). However, protein abundance cannot be reliably predicted by DNA alteration or mRNA expression, which can be partially attributed to post-transcriptional and/or translational regulation of gene expression. In this study, we identified increased translational efficiency (TE) as a hallmark of CRC by evaluating the transcriptomic and proteomic features of CRC patients, along with comparative transcriptomic and ribosome-protected mRNA analysis in colon epithelial cells and colon cancer cells. COPS7B was among the key genes that consistently showed both significant TE increase and protein elevation without transcriptional alteration in CRC. IGF2BP3 enhanced the TE of COPS7B mRNA to promote CRC growth and metastasis. COPS7B was found to be a component of the ribo-interactome that interacted with ribosomes to facilitate ribosome biogenesis and mRNA translation initiation. Collectively, this study revealed the proteomic features of CRC and highlighted elevated mRNA translation as a hallmark of CRC. The identification of the IGF2BP3-COPS7B axis underlying the increased protein synthesis rate in CRC provided a promising therapeutic target to treat this aggressive disease.