Despite demonstrating significant anti-tumor potential as an artemisinin derivative,artesunate faces delivery efficiency challenges due to low water solubility and insufficient targeting specificity.To improve the del...Despite demonstrating significant anti-tumor potential as an artemisinin derivative,artesunate faces delivery efficiency challenges due to low water solubility and insufficient targeting specificity.To improve the delivery efficiency,we engineered three artesunate(ART) derivatives,AC_(15)-L(linear),AC_(15)-B(branched),and AC_(15)-C(cyclic) with distinct aliphatic chain architectures.Unexpectedly,we observed that AC_(15)-C exhibited superior cytotoxicity against 4T1 breast cancer cells,and had the highest binding affinity for Lon protease 1(LONP1)(-72.6 kcal/mol).Subsequently,disulfide bond-containing lipid-PEG(DSPESS-PEG2K) modified chain architecture-engineered ART derivatives nanoassemblies(NAs) were developed to mitigate solubility-related limitations while enhancing targeting precision.Molecular docking and experimental validation demonstrated that ART derivatives inhibited LONP1 through hydrophobic interactions while preserved Fe^(2+)-mediated Fenton-like reaction activity.In vitro and in vivo evaluations demonstrated that AC_(15)-C NAs outperformed free ART and other NAs,suppressing 4T1 tumor growth via dual action:LONP1-directed mitochondrial proteostasis collapse and reactive oxygen species(ROS) amplification through Fe^(2+)-ART interactions.This study elucidated a novel anti-tumor mechanism of ART through the rational design of derivatives with spatially configured aliphatic chains,and developed reductionresponsive NAs to provide an advanced delivery strategy.展开更多
Virtual supply chain, as a modern collaborative mode of enterprises, is important to decrease the cost and improve the efficiency and the quality of supply chains, and to satisfy customers. Based on the analysis of th...Virtual supply chain, as a modern collaborative mode of enterprises, is important to decrease the cost and improve the efficiency and the quality of supply chains, and to satisfy customers. Based on the analysis of the conception and characteristics of the virtual supply chain, the architecture of virtual supply chain is built, and corresponding objects, tasks, information and technologies are described. Three operation modes-Order-driven, manufacturer-centered, and retailer-centered are researched. As a case, virtual supply chain is applied in the electronic commerce and networked customization system of ceramic products.展开更多
The surface chemical structure development in solution-cast styrene(S)/butadiene(B) block copolymer films as a function of solvent evaporation time was investigated using sum frequency generation vibrational spectrosc...The surface chemical structure development in solution-cast styrene(S)/butadiene(B) block copolymer films as a function of solvent evaporation time was investigated using sum frequency generation vibrational spectroscopy(SFG).The surface structure formation of the styrene(S)/butadien(B) block copolymer(30 wt% PS) films during the solution-to-film process was found to be controlled mainly by dynamic factors,such as the mobility of the PB block in solution.For SB diblock copolymers,a pure PB surface layer was formed only when the film was cast by dilute toluene solution.With increasing concentration of casting solution,PB and PS components were found to coexist on the film surface,and the morphology of the PB component on the film surface changed from cylindrical rods to spheres.For SBS triblock copolymers,a small amount of PS component existed on the surface even if the film was cast by 1.0 wt% toluene solution.In addition,PS components at the outermost layer of the film increased and the length of PB cylindrical rods on the surface decreased with increasing concentration of casting solution.展开更多
基金financially supported by the Liaoning Revitalization Talents Program (No.XLYC2403107)the Excellent Youth Science Foundation of Liaoning Province (No.2024JH3/10200046)the Basic Scientific Research Project of Liaoning Provincial Department of Education (No.LJ212410163015)。
文摘Despite demonstrating significant anti-tumor potential as an artemisinin derivative,artesunate faces delivery efficiency challenges due to low water solubility and insufficient targeting specificity.To improve the delivery efficiency,we engineered three artesunate(ART) derivatives,AC_(15)-L(linear),AC_(15)-B(branched),and AC_(15)-C(cyclic) with distinct aliphatic chain architectures.Unexpectedly,we observed that AC_(15)-C exhibited superior cytotoxicity against 4T1 breast cancer cells,and had the highest binding affinity for Lon protease 1(LONP1)(-72.6 kcal/mol).Subsequently,disulfide bond-containing lipid-PEG(DSPESS-PEG2K) modified chain architecture-engineered ART derivatives nanoassemblies(NAs) were developed to mitigate solubility-related limitations while enhancing targeting precision.Molecular docking and experimental validation demonstrated that ART derivatives inhibited LONP1 through hydrophobic interactions while preserved Fe^(2+)-mediated Fenton-like reaction activity.In vitro and in vivo evaluations demonstrated that AC_(15)-C NAs outperformed free ART and other NAs,suppressing 4T1 tumor growth via dual action:LONP1-directed mitochondrial proteostasis collapse and reactive oxygen species(ROS) amplification through Fe^(2+)-ART interactions.This study elucidated a novel anti-tumor mechanism of ART through the rational design of derivatives with spatially configured aliphatic chains,and developed reductionresponsive NAs to provide an advanced delivery strategy.
文摘Virtual supply chain, as a modern collaborative mode of enterprises, is important to decrease the cost and improve the efficiency and the quality of supply chains, and to satisfy customers. Based on the analysis of the conception and characteristics of the virtual supply chain, the architecture of virtual supply chain is built, and corresponding objects, tasks, information and technologies are described. Three operation modes-Order-driven, manufacturer-centered, and retailer-centered are researched. As a case, virtual supply chain is applied in the electronic commerce and networked customization system of ceramic products.
基金support from the National Natural Science Foundation of China (20874089)the Graduate Research Foundation of Zhejiang Province (YK2010056)
文摘The surface chemical structure development in solution-cast styrene(S)/butadiene(B) block copolymer films as a function of solvent evaporation time was investigated using sum frequency generation vibrational spectroscopy(SFG).The surface structure formation of the styrene(S)/butadien(B) block copolymer(30 wt% PS) films during the solution-to-film process was found to be controlled mainly by dynamic factors,such as the mobility of the PB block in solution.For SB diblock copolymers,a pure PB surface layer was formed only when the film was cast by dilute toluene solution.With increasing concentration of casting solution,PB and PS components were found to coexist on the film surface,and the morphology of the PB component on the film surface changed from cylindrical rods to spheres.For SBS triblock copolymers,a small amount of PS component existed on the surface even if the film was cast by 1.0 wt% toluene solution.In addition,PS components at the outermost layer of the film increased and the length of PB cylindrical rods on the surface decreased with increasing concentration of casting solution.
