The therapeutic potential of umbilical cord-mesenchymal stem cell (UC-MSC) transplantation in liver fibrosis has been highlighted. However, the fate of transplanted MSCs in the fibrotic microenvironment remains unclear. In this study, we aim to uncover the fate of transplanted MSCs and develop targeting strategies that could enhance the therapeutic efficacy of MSC therapy in liver fibrosis. We used human UC-MSCs as the study object. For in vitro experiments, we stimulated UC-MSCs with several fibrotic-related factors (Liver fibrotic Factors, LF), including TGFβ, TNFα and IFNγ for downstream investigations. We co-cultured LF-treated UC-MSCs with hepatic stellate cell line LX-2 to assess the anti-fibrotic effect. We showed that upon LF stimulation, UC-MSCs exhibited reduced anti-fibrotic activity and underwent rapid senescence. Pathway analysis showed that JAK/STAT3 signaling was highly activated upon LF stimulation, which significantly elevated senescence-associated secretory phenotype (SASP) and senescence in UC-MSCs and could be reversed by a specific JAK inhibitor AG490. Moreover, using both carbon tetrachloride (CCl4) and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induce fibrosis models, we demonstrated that AG490 pretreatment promoted UC-MSCs survival within the fibrotic liver microenvironment and exhibited enhance therapeutic efficacy. Overall, we showed that targeting MSC senescence in vivo through AG490 pretreatment could enhance the anti-fibrotic activities of UC-MSCs.
To integrate DIgSILENT/PowerFactory into the core computing tool of the high-level application platform for dispatching operation and planning analysis, this paper studies the automation technology of importing online grid models to DIgSILENT and exporting calculation results to DIgSILENT. Based on IEEE9 node, it studies the data content and format of grid device models, topology models and graph models in DGS interface file. A test is conducted to verify the feasibility of using DGS interface to import the entire grid models. Then it compares and analyses the online grid models in E text and the grid models in DGS interface file, studies an approach to the automatic generation of grid graphic data in DGS format based on topology data, and designs a process of converting online grid models in E text into grid models in DGS interface file. At last, this paper develops a software and tests its function. It also analyses and summaries the debugging experience of setting the node type in flow calculation. The content and achievement of this paper will play a guiding role in promoting the application of DIgSILENT for online operation analysis and offline rapid prototyping.
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