The fatigue life prediction of high strength steel SUS 630 （H900） under high cycle loading is conducted with consideration of a characteristic fatigue length of material. Based on the WShler curve of smooth material...The fatigue life prediction of high strength steel SUS 630 （H900） under high cycle loading is conducted with consideration of a characteristic fatigue length of material. Based on the WShler curve of smooth materials, a modified method for fatigue life prediction is approached. The characteristic fatigue length of material under cyclic loading is associated with the polycrystalline material. Rather than the stress at a point, the average stress within the characteristic fatigue length is implemented for the fatigue life prediction. The method can be applied to both the smooth and the defected material. The fatigue life prediction is also verified experimentally by specimens with various small circular holes. Through the comparison, it is found that the method can be adopted to predict the fatigue lives with different size effects.展开更多
Doxorubicin(DOX)-mediated cardiotoxicity can exacerbate mortality in oncology patients,but related pharmacotherapeutic measures are relatively limited.Ferroptosis was recently identified as a major mechanism of DOX-in...Doxorubicin(DOX)-mediated cardiotoxicity can exacerbate mortality in oncology patients,but related pharmacotherapeutic measures are relatively limited.Ferroptosis was recently identified as a major mechanism of DOX-induced cardiotoxicity.Idebenone,a novel ferroptosis inhibitor,is a well-described clinical drug widely used.However,its role and pathological mechanism in DOX-induced cardiotoxicity are still unclear.In this study,we demonstrated the effects of idebenone on DOX-induced cardiotoxicity and elucidated its underlying mechanism.A single intraperitoneal injection of DOX(15 mg/kg)was administrated to establish DOX-induced cardiotoxicity.The results showed that idebenone significantly attenuated DOX-induced cardiac dysfunction due to its ability to regulate acute DOX-induced Fe^(2+)and ROS overload,which resulted in ferroptosis.CESTA and BLI further revealed that idebenone's anti-ferroptosis effect was mediated by FSP1.Interestingly,idebenone increased FSP1 protein levels but did not affect Fsp1 mRNA levels in the presence of DOX.Idebenone could form stable hydrogen bonds with FSP1 protein at K355,which may influence its association with ubiquitin.The results confirmed that idebenone stabilized FSP1 protein levels by inhibiting its ubiquitination degradation.In conclusion,this study demonstrates idebenone attenuated DOX-induced cardiotoxicity by inhibiting ferroptosis via regulation of FSP1,making it a potential clinical drug for patients receiving DOX treatment.展开更多
基金supported by the National Natural Science Foundation of China(Nos.10772116,10772115 and 10932007)by the JST program ‘Development of Technology for Promoting Food Quality Project’
文摘The fatigue life prediction of high strength steel SUS 630 （H900） under high cycle loading is conducted with consideration of a characteristic fatigue length of material. Based on the WShler curve of smooth materials, a modified method for fatigue life prediction is approached. The characteristic fatigue length of material under cyclic loading is associated with the polycrystalline material. Rather than the stress at a point, the average stress within the characteristic fatigue length is implemented for the fatigue life prediction. The method can be applied to both the smooth and the defected material. The fatigue life prediction is also verified experimentally by specimens with various small circular holes. Through the comparison, it is found that the method can be adopted to predict the fatigue lives with different size effects.
基金supported by the following grants:the Regional Innovation and Development Joint Fund of the National Natural Science Foundation of China(No.U22A20269)the National Key R&D Program of China(No.2018YFC1311300)the National Natural Science Foundation of China(Nos.82200262 and 82000229).
文摘Doxorubicin(DOX)-mediated cardiotoxicity can exacerbate mortality in oncology patients,but related pharmacotherapeutic measures are relatively limited.Ferroptosis was recently identified as a major mechanism of DOX-induced cardiotoxicity.Idebenone,a novel ferroptosis inhibitor,is a well-described clinical drug widely used.However,its role and pathological mechanism in DOX-induced cardiotoxicity are still unclear.In this study,we demonstrated the effects of idebenone on DOX-induced cardiotoxicity and elucidated its underlying mechanism.A single intraperitoneal injection of DOX(15 mg/kg)was administrated to establish DOX-induced cardiotoxicity.The results showed that idebenone significantly attenuated DOX-induced cardiac dysfunction due to its ability to regulate acute DOX-induced Fe^(2+)and ROS overload,which resulted in ferroptosis.CESTA and BLI further revealed that idebenone's anti-ferroptosis effect was mediated by FSP1.Interestingly,idebenone increased FSP1 protein levels but did not affect Fsp1 mRNA levels in the presence of DOX.Idebenone could form stable hydrogen bonds with FSP1 protein at K355,which may influence its association with ubiquitin.The results confirmed that idebenone stabilized FSP1 protein levels by inhibiting its ubiquitination degradation.In conclusion,this study demonstrates idebenone attenuated DOX-induced cardiotoxicity by inhibiting ferroptosis via regulation of FSP1,making it a potential clinical drug for patients receiving DOX treatment.
