Transcriptome Analysis Revealed a Highly Connected Gene Module Associated With Cirrhosis to Hepatocellular Carcinoma Development

IntroductionCirrhosis is one of the most important risk factors for development of hepatocellular carcinoma (HCC). Recent studies have shown that removal or well control of the underlying cause could reduce but not eliminate the risk of HCC. Therefore, it is important to elucidate the molecular mechanisms that drive the progression of cirrhosis to HCC.Materials and MethodsMicroarray datasets incorporating cirrhosis and HCC subjects were identified from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were determined by GEO2R software. Functional enrichment analysis was performed by the clusterProfiler package in R. Liver carcinogenesis-related networks and modules were established using STRING database and MCODE plug-in, respectively, which were visualized with Cytoscape software. The ability of modular gene signatures to discriminate cirrhosis from HCC was assessed by hierarchical clustering, principal component analysis (PCA), and receiver operating characteristic (ROC) curve. Association of top modular genes and HCC grades or prognosis was analyzed with the UALCAN web-tool. Protein expression and distribution of top modular genes were analyzed using the Human Protein Atlas database.ResultsFour microarray datasets were retrieved from GEO database. Compared with cirrhotic livers, 125 upregulated and 252 downregulated genes in HCC tissues were found. These DEGs constituted a liver carcinogenesis-related network with 272 nodes and 2954 edges, with 65 nodes being highly connected and formed a liver carcinogenesis-related module. The modular genes were significantly involved in several KEGG pathways, such as “cell cycle,” “DNA replication,” “p53 signaling pathway,” “mismatch repair,” “base excision repair,” etc. These identified modular gene signatures could robustly discriminate cirrhosis from HCC in the validation dataset. In contrast, the expression pattern of the modular genes was consistent between cirrhotic and normal livers. The top modular genes TOP2A, CDC20, PRC1, CCNB2, and NUSAP1 were associated with HCC onset, progression, and prognosis, and exhibited higher expression in HCC compared with normal livers in the HPA database.ConclusionOur study revealed a highly connected module associated with liver carcinogenesis on a cirrhotic background, which may provide deeper understanding of the genetic alterations involved in the transition from cirrhosis to HCC, and offer valuable variables for screening and surveillance of HCC in high-risk patients with cirrhosis

Multi-turn Inference Matching Network for Natural Language Inference

Natural Language Inference (NLI) is a fundamental and challenging task in Natural Language Processing (NLP). Most existing methods only apply one-pass inference process on a mixed matching feature, which is a concatenation of different matching features between a premise and a hypothesis. In this paper, we propose a new model called Multi-turn Inference Matching Network (MIMN) to perform multi-turn inference on different matching features. In each turn, the model focuses on one particular matching feature instead of the mixed matching feature. To enhance the interaction between different matching features, a memory component is employed to store the history inference information. The inference of each turn is performed on the current matching feature and the memory. We conduct experiments on three different NLI datasets. The experimental results show that our model outperforms or achieves the state-of-the-art performance on all the three datasets

Robust high-temperature topological excitonic insulator of transition-metal carbides (MXenes)

Topological excitonic insulators combine topological edge states and spontaneous exciton condensation, with dual functionality of topological insulators and excitonic insulators. Yet, they are very rare and little is known about their formation. In this work, we find that a mechanism dubbed as parity frustration prevents excitonic instability in usual topological insulators, and those whose band inversion is independent of spin-orbit coupling are possible candidates. We verify this by first-principles calculations on monolayer transition-metal carbides (MXenes), which show a robust thermal-equilibrium exciton condensation, being sufficient for topological applications at room temperature. Such a state can be identified by angle-resolved photoemission spectroscopy and transport measurement. Our work provides not only a guide for finding more topological excitonic insulators, but also a new platform for studying the interplay between non-trivial band topology and quantum many-body effects