The lipid mediator platelet-activating factor(PAF)and its receptor(PAFR)signaling play critical roles in a wide range of physiological and pathophysiological conditions,including cancer growth and metastasis.The abili...The lipid mediator platelet-activating factor(PAF)and its receptor(PAFR)signaling play critical roles in a wide range of physiological and pathophysiological conditions,including cancer growth and metastasis.The ability of PAFR to interact with other oncogenic signaling cascades makes it a promising target for cancer treatment.Moreover,numerous natural and synthetic compounds,characterized by diverse pharmacological activities such as anti-inflammatory and anti-tumor effects,have been explored for their potential as PAF and PAFR antagonists.In this review,we provide comprehensive evidence regarding the PAF/PAFR signaling pathway,highlighting the effectiveness of various classes of PAF and PAFR inhibitors and antagonists across multiple cancer models.Notably,the synergistic effects of PAF and PAFR antagonists in enhancing the efficacy of chemotherapy and radiation therapy in several experimental cancer models are also discussed.Overall,the synthesis of literature review indicates that targeting the PAF/PAFR axis represents a promising approach for cancer treatment and also exerts synergy with chemotherapy and radiation therapy.展开更多
Reducing the peak actuating force(PAF)and parasitic displacement is of high significance for improving the performance of compliant parallel mechanisms(CPMs).In this study,a 2-DOF 4-4R compliant parallel pointing mech...Reducing the peak actuating force(PAF)and parasitic displacement is of high significance for improving the performance of compliant parallel mechanisms(CPMs).In this study,a 2-DOF 4-4R compliant parallel pointing mechanism(4-4R CPPM)was used as the object,and the actuating force of the mechanism was optimized through redundant actuation.This was aimed at minimizing the PAF and parasitic displacement.First,a kinetostatic model of the redundantly actuated 4-4R CPPM was established to reveal the relationship between the input forces/displacements and the output displacements of the mobile platform.Subsequently,based on the established kinetostatic model,methods for optimizing the actuating force distribution with the aim of minimizing the PAF and parasitic displacement were introduced successively.Second,a simulated example of a mobile platform’s spatial pointing trajectory validated the accuracy of the kinetostatic model.The results show a less than 0.9%relative error between the analytical and finite element(FE)results,and the high consistency indicates the accuracy of the kinetostatic model.Then,the effectiveness of the method in minimizing the PAF and parasitic displacement was validated using two simulated examples.The results indicate that compared with the non-redundant actuation case,the PAF of the mechanism could be reduced by up to 50%,and the parasitic displacement was reduced by approximately three-four orders of magnitude by means of redundant actuation combined with the optimal distribution of the actuating force.As expected,with the reduction in parasitic displacement,the FE-results of the output angular displacements(θ_(x) andθ_(z))of the mobile platform were closer to the target oscillation trajectory.This further verified that the reduction in parasitic displacement is indeed effective in improving the motion accuracy of the mechanism.The advantage of this proposed method is that it reduces the PAF and parasitic displacement from the perspective of the actuating force control strategy,without the requirement of structural changes to the original mechanism.展开更多
基金support from the National Institutes of Health grants R21 ES033806(RPS)is greatly acknowledged.
文摘The lipid mediator platelet-activating factor(PAF)and its receptor(PAFR)signaling play critical roles in a wide range of physiological and pathophysiological conditions,including cancer growth and metastasis.The ability of PAFR to interact with other oncogenic signaling cascades makes it a promising target for cancer treatment.Moreover,numerous natural and synthetic compounds,characterized by diverse pharmacological activities such as anti-inflammatory and anti-tumor effects,have been explored for their potential as PAF and PAFR antagonists.In this review,we provide comprehensive evidence regarding the PAF/PAFR signaling pathway,highlighting the effectiveness of various classes of PAF and PAFR inhibitors and antagonists across multiple cancer models.Notably,the synergistic effects of PAF and PAFR antagonists in enhancing the efficacy of chemotherapy and radiation therapy in several experimental cancer models are also discussed.Overall,the synthesis of literature review indicates that targeting the PAF/PAFR axis represents a promising approach for cancer treatment and also exerts synergy with chemotherapy and radiation therapy.
基金Supported by Key Project of Hubei Provincial Department of Education Research Program(Grant No.D20211401).
文摘Reducing the peak actuating force(PAF)and parasitic displacement is of high significance for improving the performance of compliant parallel mechanisms(CPMs).In this study,a 2-DOF 4-4R compliant parallel pointing mechanism(4-4R CPPM)was used as the object,and the actuating force of the mechanism was optimized through redundant actuation.This was aimed at minimizing the PAF and parasitic displacement.First,a kinetostatic model of the redundantly actuated 4-4R CPPM was established to reveal the relationship between the input forces/displacements and the output displacements of the mobile platform.Subsequently,based on the established kinetostatic model,methods for optimizing the actuating force distribution with the aim of minimizing the PAF and parasitic displacement were introduced successively.Second,a simulated example of a mobile platform’s spatial pointing trajectory validated the accuracy of the kinetostatic model.The results show a less than 0.9%relative error between the analytical and finite element(FE)results,and the high consistency indicates the accuracy of the kinetostatic model.Then,the effectiveness of the method in minimizing the PAF and parasitic displacement was validated using two simulated examples.The results indicate that compared with the non-redundant actuation case,the PAF of the mechanism could be reduced by up to 50%,and the parasitic displacement was reduced by approximately three-four orders of magnitude by means of redundant actuation combined with the optimal distribution of the actuating force.As expected,with the reduction in parasitic displacement,the FE-results of the output angular displacements(θ_(x) andθ_(z))of the mobile platform were closer to the target oscillation trajectory.This further verified that the reduction in parasitic displacement is indeed effective in improving the motion accuracy of the mechanism.The advantage of this proposed method is that it reduces the PAF and parasitic displacement from the perspective of the actuating force control strategy,without the requirement of structural changes to the original mechanism.
