BackgroundLong-term infections by Clonorchis sinensis are associated with cholangitis, cholecystitis, liver fibrosis, cirrhosis, and even liver cancer. Molecules from the worm play vital roles in disease progress. In the present study, we identified and explored molecular characterization of C. sinensis granulin (CsGRN), a growth factor-like protein from C. sinensis excretory/secretory products (CsESPs).MethodsThe encoding sequence and conserved domains of CsGRN were identified and analysed by bioinformatics tools. Recombinant CsGRN (rCsGRN) protein was expressed in Escherichia coli BL21 (DE3). The localisation of CsGRN in adult worms and Balb/c mice infected with C. sinensis was investigated by immunofluorescence and immunohistochemistry, respectively. Stable CsGRN-overexpressed cell lines of hepatoma cells (PLC-GRN cells) and cholangiocarcinoma cells (RBE-GRN cells) were constructed by transfection of eukaryotic expression plasmid of pEGFP-C1-CsGRN. The effects on cell migration and invasion of CsGRN were assessed through the wound-healing assay and transwell assay. The levels of matrix metalloproteinase 2 and 9 (MMP2 and MMP9) in PLC-GRN or RBE-GRN cells were detected by real-time PCR (qRT-PCR). The levels of E-cadherin, vimentin, N-cadherin, zona occludens proteins (ZO-1), β-catenin, phosphorylated ERK (p-ERK) and phosphorylated AKT (p-AKT) were analysed by Western blotting.Results CsGRN, including the conserved GRN domains, was confirmed to be a member of the granulin family. CsGRN was identified as an ingredient of CsESPs. CsGRN was localised in the tegument and testes of the adult worm. Furthermore, it appeared in the cytoplasm of hepatocytes and biliary epithelium cells from infected Balb/c mouse. The enhancement of cell migration and invasion of PLC-GRN and RBE-GRN cells were observed. In addition, CsGRN upregulated the levels of vimentin, N-cadherin, β-catenin, MMP2 and MMP9, while it downregulated the level of ZO-1 in PLC-GRN/RBE-GRN cells. In total proteins of liver tissue from rCsGRN immunised Balb/c mice, vimentin level decreased, while E-cadherin level increased when compared with the control groups. Meanwhile, the levels of p-ERK reached a peak at 4 weeks post immunisation and the level of p-AKT did at 2 weeks after immunisation.ConclusionsThe encoding sequence and molecular characteristics of CsGRN were identified. As a member of granulin superfamily, CsGRN induced mesenchymal characteristics of PLC and RBE cells and was found to regulate the activities of the downstream molecules of the ERK and PI3K/AKT signalling pathways, which could contribute to the enhancement of cell migration and invasion.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-017-2179-4) contains supplementary material, which is available to authorized users.

The fast-growing motion capturing/monitoring technique has raised a great demand for flexible strain sensors. For capturing complex motions (e.g., facial motion), both the strain amplitude and direction should be accurately detected. Although some reported sensors based on anisotropic conductive networks are proved to show accurate localization of strain directions, it is still a great challenge to achieve both high sensitivity and a high sensing range in these designs. Here, a self-assembled Ti 3 C 2 T x MXene film with parallel and periodic wrinkles is fabricated on a stretchable poly(dimethylsiloxane) substrate for constructing multidirectional strain sensors. During stretching, relative slip and crack will occur between the stacked MXene nanosheets, which contribute to high structural sensitivity in the MXene film. Meanwhile, the wrinkled structure contributes to high stretchability. As a result, the sensor based on the film with one-dimensional periodic wrinkles shows a large sensing range (>50%) and a gauge factor of 45. Furthermore, the sensor can accurately detect both the strain amplitude and direction by using the MXene film with two-dimensional wrinkles. It shows distinguishable electrical responses when detecting different-amplitude human/robot motions such as joint bending and walking. Additionally, the directions in complex human motions (e.g., facial motion) can also be well-tracked. This work provides an effective strategy to detect multi-directional motions.

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