Klotho Regulates Epithelial-to-Mesenchymal Transition In Vitro via Wnt/ß-Catenin Pathway and Attenuates Chronic Allograft Dysfunction in a Rat Renal Transplant Model.

BACKGROUND Klotho deficiency has been implicated in various kidney diseases and has been associated with renal fibrosis. However, the role of Klotho in renal allograft fibrosis still remains undetermined. MATERIAL AND METHODS A 24-week-old rat renal transplant model with chronic allograft dysfunction (CAD) was carried out by orthotopic kidney transplantation using F344 donor rats to Lewis recipient rats. Successful establishment of the model was verified by HE and Masson staining and renal allograft function assessment. HK-2 cells were cultured and treated with TGF-ß1 and/or siRNA-Klotho at various time points. Total proteins and RNA were extracted from the cultured cells and kidney tissues. Western blot assay and quantitative RT-PCR were used to analyze the expression of Klotho, fibronectin, and ß-catenin pathways. RESULTS We successfully established and identified a 24-week-old rat renal transplant model with CAD. Loss of Klotho was identified to be associated with epithelial-to-mesenchymal transition (EMT), renal allograft fibrosis, and CAD. In HK-2 cells, a significant decrease of Klotho protein was observed in the renal fibrosis induced by TGF-ß1 in a time-dependent manner. Moreover, intervention of siRNA-Klotho remarkably promoted the progression of renal fibrosis and activation of the Wnt/ß-catenin signaling pathway. CONCLUSIONS Our results show that Klotho has a significant protective role against EMT, renal allograft fibrosis, and CAD following kidney transplantation, which is mediated by inhibition of the Wnt/ß-catenin signaling pathway.

Multistage implementation framework for smart supply chain management under industry 4.0.

The true potential of the industry 4.0, which is a byproduct of the fourth industrial revolution, cannot be actually realized. This is, of course true, until the smart factories in the supply chains get connected to each other, with their systems and the machines linked to a common networking system. The last few years have experienced an increase in the adoption and acceptance of the industry 4.0's components. However, the next stage of smart factories, which will be the smart supply chains, is still in its period of infancy. Moreover, there is a simultaneous need to maintain a focus on the supply chain level implementation of the concept that industry 4.0 puts forth. This is important in order to gain the end to end benefits, while also avoiding the organization to organization compatibility issues that may follow later on. When considering this concept, limited research exists on the issues related to the implementation of industry 4.0, at the supply chain level. Hence, keeping in mind this lack of literature and research available, on a phenomenon that will define the future of business and industry, this study uses an exploratory approach to capture the implementation of industry 4.0 concepts across multiple tiers of the supply chain. Based on this research, the study proposes a multistage implementation framework that highlights the organizational enablers such as culture, cross-functional approach, and the continuous improvement activities. Furthermore, it also highlights the staged implementation of the advanced tools, starting from the focal organization with the subsequent integration with the partner organizations.

Trade and technological innovation: The catalysts for climate change and way forward for COP21.

Following the adaptation of the Paris Agreement at COP21, it was noted that the traditional measures of carbon emissions have several limitations; and a reliable and relevant carbon emissions measurement is important to formulate a response to the challenge of climate change. This study, therefore, explores the relationship between international trade and consumption-based carbon emissions, which is a trade adjusted indicator; and measures the outflow and the inflow of emissions through exports and imports separately. We also include technological innovation in the model to understand its impact on consumption-based carbon emissions. The results show that exports and consumption-based carbon emissions are negatively associated, and technological innovation helps reducing the adverse effect of CO2 growth. In contrast, Imports and gross domestic product are positively linked with consumption-based carbon emissions. The findings also suggest the countries which embraced the Paris Climate Agreement must focus on consumption-based carbon emissions rather than the production-based carbon emissions.