The pancreas of vertebrates is separately derived from both the dorsal and ventral endodermal domains. However, the difference between these two programs has been unclear. Here, using a pancreatic determination gene, , driven GFP transgenic mouse strain, we identified Pdx1-GFP highly expressing cells (Pdx1) and Pdx1-GFP lowly expressing cells (Pdx1) in both embryonic dorsal Pdx1-expressing region (DPR) and ventral Pdx1-expressing region (VPR). We analyzed the transcriptomes of single Pdx1 and Pdx1 cells from the DPR and VPR. In the VPR, Pdx1 cells have an intermediate progenitor identity and can generate hepatoblasts, extrahepatobiliary cells, and Pdx1 pancreatic progenitor cells. In the DPR, Pdx1 cells are directly specified as pancreatic progenitors, whereas Pdx1 cells are precocious endocrine cells. Therefore, our study defines distinct road maps for dorsal and ventral pancreatic progenitor specification. The findings provide guidance for optimization of current β-cell induction protocols by following the dorsal pancreatic specification program.

Wnt/β-catenin is an important signaling pathways involved in the tumorgenesis, progression and maintenance of cancer stem cells (CSCs). In the present study, the role of Wnt/β-catenin signaling in CSC-mediated tumorigenesis and invasion in liver CSCs was investigated. A small population of cancer stem-like side population (SP) cells (3.6%) from liver cancer samples were identified. The cells were highly resistant to drug treatment due to the enhanced expression of drug efflux pumps, such as ABC subfamily G member 2, multidrug resistance protein 1 and ATP-binding cassette subfamily B member 5. Furthermore, using TOPflash and reverse transcription-quantitative polymerase chain reaction analysis, Wnt/β-catenin signaling and the transcriptional regulation of Wnt/β-catenin target genes including dickkopf Wnt signaling pathway inhibitor 1, axis inhibition protein 2 and cyclin D1 were observed to be markedly upregulated in liver cancer SP cells. As a consequence, SP cells possessed infinite cell proliferation potential and the ability to generating tumor spheres. In addition, upon reducing Wnt/β-catenin signaling, the rates of proliferation, tumor sphere formation and tumor invasion of SP cells were markedly reduced. Therefore, these data suggest that Wnt/β-catenin signaling is a potential therapeutic target to reduce CSC-mediated tumorigenicity and invasion in liver cancer.

This paper investigates the effectiveness of pre-training for few-shot intent classification. While existing paradigms commonly further pre-train language models such as BERT on a vast amount of unlabeled corpus, we find it highly effective and efficient to simply finetune BERT with a small set of labeled utterances from public datasets. Specifically, fine-tuning BERT with roughly 1,000 labeled data yields a pre-trained model -IntentBERT, which can easily surpass the performance of existing pre-trained models for few-shot intent classification on novel domains with very different semantics. The high effectiveness of IntentBERT confirms the feasibility and practicality of few-shot intent detection, and its high generalization ability across different domains suggests that intent classification tasks may share a similar underlying structure, which can be efficiently learned from a small set of labeled data. The source code can be found at https://github.com/ hdzhang-code/IntentBERT.

Mycobacterium tuberculosis ( M. tb ) is a highly successful pathogen that has co-existed with humans for 1,000's of years. As the cornerstone of the immune system, macrophages are a key part of innate immunity. They ingest and degrade foreign substances including aging cells and microorganisms, coordinate the inflammatory process, and are the first line of defense against M. tb infection. Recent advances in cellular mycobacteriology have indicated that M. tb uses an remarkably complex strategy to disrupt macrophage function, in order to counteract the antimicrobial mechanisms of the innate and adaptive immune responses, thereby achieving immune escape. With the popularity of microarray technology, a variety of public platforms have provided a variety of gene expression data associated with physiological and disease conditions. Meta-analysis can systematically and quantitatively analyze multiple independent data concerning the same disease, greatly improving the statistical significance and credibility of the gene expression data analysis performed. In the present study, 6 microarray expression datasets of human acute monocytic leukemia THP-1 cell line infected by M. tb H37Rv strain were collected from the GEO database. A total of 4 high-quality datasets were identified using meta-analysis methods in R language, and 306 differentially expressed genes with statistical significance were obtained. Then, a protein-protein interaction (PPI) network of these differentially expressed genes was constructed on the Search Tool for the Retrieval of Interacting Genes/Proteins Database online tool and visualized by Cytoscape v. 3.6.1 software. Using CentiScape and MCODE plugin in the Cytoscape software to mine the functional modules associated with M. tb infection process, 32 characteristic genes were identified. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis was performed on the 32 characteristic genes, and it was demonstrated that these genes were primarily associated with the type I interferon (IFN) pathway. In the established model of THP-1-derived macrophages infected by M. tb , the actual differential expression levels of IFN-stimulated gene 15 ( ISG15 ), 2′-5-oligoadenylate synthetase like ( OASL ), IFN regulatory factor 7 ( IRF7 ) and DExD/H-box helicase 58 ( DDX58 ), the first 4 genes of the 32 characteristic genes, were verified by reverse transcription quantitative polymerase chain reaction. The results were consistent with the results of microarray analysis. The association between ISG15 , OASL and IRF7 and TB infection was also verified. Although a number of studies have identified that the type I IFN pathway may assist M. tb to achieve immune escape, the pres...

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