Cascading failures are common phenomena in many of real-world networks,such as power grids,Internet,transportation networks and social networks.It's worth noting that once one or a few users on a social network ar...Cascading failures are common phenomena in many of real-world networks,such as power grids,Internet,transportation networks and social networks.It's worth noting that once one or a few users on a social network are unavailable for some reasons,they are more likely to influence a large portion of social network.Therefore,an effective mitigation strategy is very critical for avoiding or reducing the impact of cascading failures.In this paper,we firstly quantify the user loads and construct the processes of cascading dynamics,then elaborate the more reasonable mechanism of sharing the extra user loads with considering the features of social networks,and further propose a novel mitigation strategy on social networks against cascading failures.Based on the realworld social network datasets,we evaluate the effectiveness and efficiency of the novel mitigation strategy.The experimental results show that this mitigation strategy can reduce the impact of cascading failures effectively and maintain the network connectivity better with lower cost.These findings are very useful for rationally advertising and may be helpful for avoiding various disasters of cascading failures on many real-world networks.展开更多
Organelles are responsible for the efficient storage and transport of substances in living systems.A myriad of extracellular vesicles(EVs)acts as a bridge to exchange signaling molecules in cell-cell communication,and...Organelles are responsible for the efficient storage and transport of substances in living systems.A myriad of extracellular vesicles(EVs)acts as a bridge to exchange signaling molecules in cell-cell communication,and the highly dynamic tubulins and actins contribute to efficient intracellular substance transport.The inexhaustible cues of natural cargo delivery by organelles inspire researchers to explore the construction of biomimetic architectures for“smart”delivery carriers.Herein,we report a 10-hydroxycamptothecin(HCPT)-peptide conjugate HpYss that simulates the artificial EV-to-filament transformation process for precise liver cancer therapy.Under the sequential stimulus of extracellular alkaline phosphatase(ALP)and intracellular glutathione(GSH),HpYss proceeds via tandem self-assembly with a morphological transformation from nanoparticles to nanofibers.The experimental phase diagram elucidates the influence of ALP and GSH contents on the self-assembled nanostructures.In addition,the dynamic transformation of organelle-mimetic architectures that are formed by HpYss in HepG2 cells enables the efficient delivery of the anticancer drug HCPT to the nucleus,and the size-shape change from extracellular nanoparticles(50-100 nm)to intracellular nanofibers(4-9 nm)is verified to be of key importance for nuclear delivery.Nuclear targeting of HpYss amplifies apoptosis,thus significantly enhancing the inhibitory effect of HCPT(>10-fold)to HepG2 cells.Benefitting from the spatiotemporally controlled nanostructures,HpYss exhibited deep penetration,enhanced accumulation,and long-term retention in multicellular spheroid and xenograft models,potently abolishing liver tumor growth and preventing lung metastasis.We envision that our organelle-mimicking delivery strategy provides a novel paradigm for designing nanomedicine to cancer therapy.展开更多
基金supported by the National Key Technology R&D Program of China under Grant No.2012BAH46B04
文摘Cascading failures are common phenomena in many of real-world networks,such as power grids,Internet,transportation networks and social networks.It's worth noting that once one or a few users on a social network are unavailable for some reasons,they are more likely to influence a large portion of social network.Therefore,an effective mitigation strategy is very critical for avoiding or reducing the impact of cascading failures.In this paper,we firstly quantify the user loads and construct the processes of cascading dynamics,then elaborate the more reasonable mechanism of sharing the extra user loads with considering the features of social networks,and further propose a novel mitigation strategy on social networks against cascading failures.Based on the realworld social network datasets,we evaluate the effectiveness and efficiency of the novel mitigation strategy.The experimental results show that this mitigation strategy can reduce the impact of cascading failures effectively and maintain the network connectivity better with lower cost.These findings are very useful for rationally advertising and may be helpful for avoiding various disasters of cascading failures on many real-world networks.
基金We thank Prof.Chihua Fang from Zhujiang hospital of Southern Medical University for sharing the HepG2-luci cells and the c(RGDfC)peptide.We acknowledge the financial support from the National Science Fund for Distinguished Young Scholars(31825012)National Natural Science Foundation of China(21875116,31961143004,81921004,31900952,51973090)+2 种基金Tianjin Science Fund for Distinguished Young Scholars(17JCJQJC44900)Guangdong Basic and Applied Basic Research Foundation(2018A030313446,2019A1515011706,2019A1515110638)and the China Postdoctoral Science Foundation(BX20190149,2019M662972).
文摘Organelles are responsible for the efficient storage and transport of substances in living systems.A myriad of extracellular vesicles(EVs)acts as a bridge to exchange signaling molecules in cell-cell communication,and the highly dynamic tubulins and actins contribute to efficient intracellular substance transport.The inexhaustible cues of natural cargo delivery by organelles inspire researchers to explore the construction of biomimetic architectures for“smart”delivery carriers.Herein,we report a 10-hydroxycamptothecin(HCPT)-peptide conjugate HpYss that simulates the artificial EV-to-filament transformation process for precise liver cancer therapy.Under the sequential stimulus of extracellular alkaline phosphatase(ALP)and intracellular glutathione(GSH),HpYss proceeds via tandem self-assembly with a morphological transformation from nanoparticles to nanofibers.The experimental phase diagram elucidates the influence of ALP and GSH contents on the self-assembled nanostructures.In addition,the dynamic transformation of organelle-mimetic architectures that are formed by HpYss in HepG2 cells enables the efficient delivery of the anticancer drug HCPT to the nucleus,and the size-shape change from extracellular nanoparticles(50-100 nm)to intracellular nanofibers(4-9 nm)is verified to be of key importance for nuclear delivery.Nuclear targeting of HpYss amplifies apoptosis,thus significantly enhancing the inhibitory effect of HCPT(>10-fold)to HepG2 cells.Benefitting from the spatiotemporally controlled nanostructures,HpYss exhibited deep penetration,enhanced accumulation,and long-term retention in multicellular spheroid and xenograft models,potently abolishing liver tumor growth and preventing lung metastasis.We envision that our organelle-mimicking delivery strategy provides a novel paradigm for designing nanomedicine to cancer therapy.