Inhibiting the death receptor 3(DR3)signaling pathway in group 3 innate lymphoid cells(ILC3s)presents a promising approach for promoting mucosal repair in individuals with ulcerative colitis(UC).Paeoniflorin,a promine...Inhibiting the death receptor 3(DR3)signaling pathway in group 3 innate lymphoid cells(ILC3s)presents a promising approach for promoting mucosal repair in individuals with ulcerative colitis(UC).Paeoniflorin,a prominent component of Paeonia lactiflora Pall.,has demonstrated the ability to restore barrier function in UC mice,but the precise mechanism remains unclear.In this study,we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s.C57BL/6 mice were subjected to random allocation into 7 distinct groups,namely the control group,the 2%dextran sodium sulfate(DSS)group,the paeoniflorin groups(25,50,and 100 mg/kg),the anti-tumor necrosis factor-like ligand 1A(anti-TL1A)antibody group,and the IgG group.We detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using Western blot and flow cytometry,respectively.Meanwhile,DR3-overexpressing MNK-3 cells and 2%DSS-induced Rag1^(-/-)mice were used for verification.The results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal barrier.Simultaneously,paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines(interleukin-17A,granulocyte-macrophage colony stimulating factor,and interleukin-22).Alternatively,paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage independently of the adaptive immune system.We additionally confirmed that paeoniflorin-conditioned medium(CM)restored the expression of tight junctions in Caco-2 cells via coculture.In conclusion,paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner,and its mechanism is associated with the inhibition of the DR3 signaling pathway.展开更多
Compared with conventional injection mold- ing, injection-compression molding can mold optical parts with higher precision and lower flow residual stress. However, the melt flow process in a closed cavity becomes more...Compared with conventional injection mold- ing, injection-compression molding can mold optical parts with higher precision and lower flow residual stress. However, the melt flow process in a closed cavity becomes more complex because of the moving cavity boundary during compression and the nonlinear problems caused by non-Newtonian polymer melt. In this study, a 3D simulation method was developed for injection-compres- sion molding. In this method, arbitrary Lagrangian- Eulerian was introduced to model the moving-boundary flow problem in the compression stage. The non-New- tonian characteristics and compressibility of the polymer melt were considered. The melt flow and pressure distribution in the cavity were investigated by using the proposed simulation method and compared with those of injection molding. Results reveal that the fountain flow effect becomes significant when the cavity thickness increases during compression. The back flow also plays an important role in the flow pattem and redistribution of cavity pressure. The discrepancy in pressures at different points along the flow path is complicated rather than monotonically decreased in injection molding.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.:82074092),Natural Science Foundation of Guangdong Province,China(Grant No.:2021A1515012219)Guangzhou University of Chinese Medicine“Double First-Class”and High-level University Discipline Collaborative Innovation Team Project,China(Grant No.:2021xk81) and Graduate Research Innovation Project of Guangzhou University of Chinese Medicine,China.
文摘Inhibiting the death receptor 3(DR3)signaling pathway in group 3 innate lymphoid cells(ILC3s)presents a promising approach for promoting mucosal repair in individuals with ulcerative colitis(UC).Paeoniflorin,a prominent component of Paeonia lactiflora Pall.,has demonstrated the ability to restore barrier function in UC mice,but the precise mechanism remains unclear.In this study,we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s.C57BL/6 mice were subjected to random allocation into 7 distinct groups,namely the control group,the 2%dextran sodium sulfate(DSS)group,the paeoniflorin groups(25,50,and 100 mg/kg),the anti-tumor necrosis factor-like ligand 1A(anti-TL1A)antibody group,and the IgG group.We detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using Western blot and flow cytometry,respectively.Meanwhile,DR3-overexpressing MNK-3 cells and 2%DSS-induced Rag1^(-/-)mice were used for verification.The results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal barrier.Simultaneously,paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines(interleukin-17A,granulocyte-macrophage colony stimulating factor,and interleukin-22).Alternatively,paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage independently of the adaptive immune system.We additionally confirmed that paeoniflorin-conditioned medium(CM)restored the expression of tight junctions in Caco-2 cells via coculture.In conclusion,paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner,and its mechanism is associated with the inhibition of the DR3 signaling pathway.
基金The authors would like to acknowledge the financial support from the National Natural Science Foundation of China （Grant Nos. 51635006 and 51675199）, the Fundamental Research Funds for the Central Universities （Grant Nos. 2016YXZD059 and 2015ZDTD028）, and the Beijing Engineering Research Center of Advanced Structural Transparencies for the Modem Traffic System.
文摘Compared with conventional injection mold- ing, injection-compression molding can mold optical parts with higher precision and lower flow residual stress. However, the melt flow process in a closed cavity becomes more complex because of the moving cavity boundary during compression and the nonlinear problems caused by non-Newtonian polymer melt. In this study, a 3D simulation method was developed for injection-compres- sion molding. In this method, arbitrary Lagrangian- Eulerian was introduced to model the moving-boundary flow problem in the compression stage. The non-New- tonian characteristics and compressibility of the polymer melt were considered. The melt flow and pressure distribution in the cavity were investigated by using the proposed simulation method and compared with those of injection molding. Results reveal that the fountain flow effect becomes significant when the cavity thickness increases during compression. The back flow also plays an important role in the flow pattem and redistribution of cavity pressure. The discrepancy in pressures at different points along the flow path is complicated rather than monotonically decreased in injection molding.
