The Wnt/β-catenin pathway comprises a family of proteins that play critical roles in embryonic development and adult tissue homeostasis. The deregulation of Wnt/β-catenin signalling often leads to various serious diseases, including cancer and non-cancer diseases. Although many articles have reviewed Wnt/β-catenin from various aspects, a systematic review encompassing the origin, composition, function, and clinical trials of the Wnt/β-catenin signalling pathway in tumour and diseases is lacking. In this article, we comprehensively review the Wnt/β-catenin pathway from the above five aspects in combination with the latest research. Finally, we propose challenges and opportunities for the development of small-molecular compounds targeting the Wnt signalling pathway in disease treatment.

Tumor microenvironment plays very important roles in the carcinogenesis. A variety of stromal cells in the microenvironment have been modified to support the unique needs of the malignant state. This study was to discover stromal differentially expressed proteins (DEPs) that were involved in colon carcinoma carcinogenesis. Laser capture microdissection (LCM) was captured and isolated the stromal cells from colon adenocarcinoma (CAC) and non-neoplastic colon mucosa (NNCM) tissues, respectively. Seventy DEPs were identified between the pooled LCM-enriched CAC and NNCM stroma samples by iTRAQ-based quantitative proteomics. Gene Ontology (GO) relationship analysis revealed that DEPs were hierarchically grouped into 10 clusters, and were involved in multiple biological functions that were altered during carcinogenesis, including extracellular matrix organization, cytoskeleton, transport, metabolism, inflammatory response, protein polymerization, and cell motility. Pathway network analysis revealed 6 networks and 56 network eligible proteins with Ingenuity pathway analysis. Four significant networks functioned in digestive system development and its function, inflammatory disease, and developmental disorder. Eight DEPs (DCN, FN1, PKM2, HSP90B1, S100A9, MYH9, TUBB, and YWHAZ) were validated by Western blotting, and four DEPs (DCN, FN1, PKM2, and HSP90B1) were validated by immunohistochemical analysis. It is the first report of stromal DEPs between CAC and NNCM tissues. It will be helpful to recognize the roles of stromas in the colon carcinoma microenvironment, and improve the understanding of carcinogenesis in colon carcinoma. The present data suggest that DCN, FN1, PKM2, HSP90B1, S100A9, MYH9, TUBB, and YWHAZ might be the potential targets for colon cancer prevention and therapy.

Oxaliplatin is widely used in the frontline treatment of colorectal cancer (CRC), but an estimated 50% of patients will eventually stop responding to treatment due to acquired resistance. This study revealed that diminished MEIS1 expression was detected in CRC and harmed the survival of CRC patients. MEIS1 impaired CRC cell viabilities and tumor growth in mice and enhanced CRC cell sensitivity to oxaliplatin by preventing DNA damage repair. Mechanistically, oxaliplatin resistance following MEIS1 suppression was critically dependent on enhanced FEN1 expression. Subsequently, we confirmed that EZH2-DNMT3a was assisted by lncRNA ELFN1-AS1 in locating the promoter of MEIS1 to suppress MEIS1 transcription epigenetically. Based on the above, therapeutics targeting the role of MEIS1 in oxaliplatin resistance were developed and our results suggested that the combination of oxaliplatin with either ELFN1-AS1 ASO or EZH2 inhibitor GSK126 could largely suppress tumor growth and reverse oxaliplatin resistance. This study highlights the potential of therapeutics targeting ELFN1-AS1 and EZH2 in cell survival and oxaliplatin resistance, based on their controlling of MEIS1 expression, which deserve further verification as a prospective therapeutic strategy.

Abstract:Inclusions entrapped by the solidifying front during continuous casting would deteriorate the properties of the final steel products. In order to investigate the inclusion motion and the entrapment during the full solidification in curved billet caster, the present work has developed a three-dimensional numerical model coupling the flow, solidification, and inclusion motion. The predicted result indicates that the inclusion distribution inside the liquid pool of the mold is not perfectly symmetrical. Furthermore, the motion and the entrapment of micro inclusions in the mold are mainly affected by the molten steel flow pattern, however, those of macro inclusions depend both on the molten steel flow pattern and the buoyancy force of the inclusions. In the curved part of the strand, macro inclusions shift to the solidifying front of the inner radius as time goes on, while the solidifying front of the outer radius cannot entrap inclusions. The distributions of inclusions smaller than 5 µm in the solidified strand are even. However, for inclusions that are larger than 5 µm, their distributions become uneven. To validate the model, measurement of the strand surface temperature and the detection of inclusions in samples obtained from a plant have been performed. Good agreement is found between the predicted and experimental results.

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This paper realizes global stabilization for probabilistic Boolean control networks (PBCNs) with event-triggered state feedback control (ETSFC). Via the semitensor product (STP) of matrices, PBCNs with ETSFC are converted into discrete-time algebraic systems, based on which a necessary and sufficient condition is derived for global stabilization of PBCNs. Furthermore, an algorithm is presented to design a class of feasible event-triggered state feedback controllers for global stabilization. Finally, an illustrative example shows the effectiveness of the obtained result.

In this paper, output tracking problem for the Boolean control networks (BCNs) under constant reference signal is investigated. A theorem is presented for solving the output tracking problem of BCNs. A set, named the maximum invariant set, is obtained to solve the output tracking problem under shortest time, and based on the invariant set, the number of state feedback matrices which make the output tracking successful is obtained. Compare with the existing results, the computational cost can be dramatically reduced by using our method. Finally, the results presented in this brief is verified by a biological network.INDEX TERMS Semi-tensor product, optimal control design, Boolean networks, output tracking control.