In this paper,an incremental contact model is developed for the elastic self-affine fractal rough surfaces under plane strain condition.The contact between a rough surface and a rigid plane is simplified by the accumu...In this paper,an incremental contact model is developed for the elastic self-affine fractal rough surfaces under plane strain condition.The contact between a rough surface and a rigid plane is simplified by the accumulation of identical line contacts with half-width given by the truncated area divided by the contact patch number at varying heights.Based on the contact stiffness of two-dimensional flat punch,the total stiffness of rough surface is estimated,and then the normal load is calculated by an incremental method.For various rough surfaces,the approximately linear load-area relationships predicted by the proposed model agree well with the results of finite element simulations.It is found that the real average contact pressure depends significantly on profile properties.展开更多
Glioblastoma multiforme(GBM)is a lethal primary brain cancer with limited treatment options.Systemic and local immunosuppression induced by GBMs contributes to malignancy aggressiveness and resistance to immune checkp...Glioblastoma multiforme(GBM)is a lethal primary brain cancer with limited treatment options.Systemic and local immunosuppression induced by GBMs contributes to malignancy aggressiveness and resistance to immune checkpoint blockade(ICB)therapy.Herein,we demonstrated that a novel oncolytic virus,M1(OVM),reversed GBM-driven systemic immunosuppression and promoted T lymphocyte infiltration within the tumor microenvironment(TME).Intravenous administration of OVM suppressed glioma progression in a spleen-dependent manner.Mechanistically,OVM enhanced B-cell–T-cell interactions in the spleen through the formation of immune synapses.A subset of B cells positive for bone marrow stromal cell antigen 2(Bst2)was enriched in the splenic marginal zone following OVM treatment and exhibited superior capacity for antigen cross-presentation.These splenic Bst2^(+)B cells activated cognate CD8^(+)T cells to mediate adaptive antitumor immunity against intracranial gliomas.Moreover,OVM treatment synergized with anti-PD-1 therapy and further extended the survival of glioma-bearing animals.Collectively,our findings highlight the therapeutic potential of intravenous OVM for GBM management and reveal a novel immunomodulatory mechanism underlying oncolytic virotherapy.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.12372100,12302126,and 12302141)the China Postdoctoral Science Foundation(Grant No.2023M732799)+1 种基金the Fundamental Research Funds for the Central Universities(Grant No.xzy012024020)Sihe Wang also thanks the support from the China Scholarship Council(CSC).
文摘In this paper,an incremental contact model is developed for the elastic self-affine fractal rough surfaces under plane strain condition.The contact between a rough surface and a rigid plane is simplified by the accumulation of identical line contacts with half-width given by the truncated area divided by the contact patch number at varying heights.Based on the contact stiffness of two-dimensional flat punch,the total stiffness of rough surface is estimated,and then the normal load is calculated by an incremental method.For various rough surfaces,the approximately linear load-area relationships predicted by the proposed model agree well with the results of finite element simulations.It is found that the real average contact pressure depends significantly on profile properties.
基金funded by grants from the National Natural Science Foundation of China(82373284 and 82373903).
文摘Glioblastoma multiforme(GBM)is a lethal primary brain cancer with limited treatment options.Systemic and local immunosuppression induced by GBMs contributes to malignancy aggressiveness and resistance to immune checkpoint blockade(ICB)therapy.Herein,we demonstrated that a novel oncolytic virus,M1(OVM),reversed GBM-driven systemic immunosuppression and promoted T lymphocyte infiltration within the tumor microenvironment(TME).Intravenous administration of OVM suppressed glioma progression in a spleen-dependent manner.Mechanistically,OVM enhanced B-cell–T-cell interactions in the spleen through the formation of immune synapses.A subset of B cells positive for bone marrow stromal cell antigen 2(Bst2)was enriched in the splenic marginal zone following OVM treatment and exhibited superior capacity for antigen cross-presentation.These splenic Bst2^(+)B cells activated cognate CD8^(+)T cells to mediate adaptive antitumor immunity against intracranial gliomas.Moreover,OVM treatment synergized with anti-PD-1 therapy and further extended the survival of glioma-bearing animals.Collectively,our findings highlight the therapeutic potential of intravenous OVM for GBM management and reveal a novel immunomodulatory mechanism underlying oncolytic virotherapy.
