A new Al−4.87Mn−1.42Mg−0.63Sc−0.20Zr(wt.%)alloy was fabricated by selective laser melting(SLM)and its microstructure and mechanical properties before and after aging were investigated.The results show that at a laser ...A new Al−4.87Mn−1.42Mg−0.63Sc−0.20Zr(wt.%)alloy was fabricated by selective laser melting(SLM)and its microstructure and mechanical properties before and after aging were investigated.The results show that at a laser power input of 300 W,increasing laser scanning speeds from 700 to 1500 mm/s improves the mechanical properties.In the meantime,the lattice distortion values increase from 0.15%to 0.31%,showing an increasing solute supersaturation.At a laser scanning speed of 1500 mm/s,the yield strength,ultimate tensile strength and elongation of the as-SLM alloys are 356 MPa,412 MPa and 17.7%,respectively.After aging at 350°C for 8 h,these values increase to 527 MPa,554 MPa and 10.4%,respectively.The contributions to the yield strength increments from the secondary Al6(Fe,Mn)needle-like phase and re-precipitated L12 structured Al6(Sc,Zr,Ti)nano-particles during aging are 74 and 79 MPa,respectively.As the aging temperature increases to 450°C,the dominant precipitation strengthening is attributed to the secondary Al6(Sc,Zr,Ti)nano-particles.展开更多
Photodynamic therapy(PDT)has emerged as an efficient cancer treatment method with minimal invasiveness.However,the majority of current photosensitizers(PSs)display severe dark toxicity and low tumor specificity due to...Photodynamic therapy(PDT)has emerged as an efficient cancer treatment method with minimal invasiveness.However,the majority of current photosensitizers(PSs)display severe dark toxicity and low tumor specificity due to their"always-on"photoactivity in blood circulation.To address this concern,we herein report a series of acid-activatable PSs for ultrasensitive PDT of triple-negative breast tumors.These set of novel PSs are synthesized by covalently modifying tetrakis(4-carboxyphenyl)porphyrin(TCPP)with a variety of tertiary amines for acidity-activatable fluorescence imaging and reactive oxygen species(RoS)generation.The resultant TCPP derivatives are grafted with a poly(ethylene glycol)(PEG)chain via a matrix metalloproteinase-2(MMP-2)-liable peptide spacer and chelated with Mn^(2+)for magnetic resonance imaging(MRI)capability.The PEGylated TCPP derivatives are amphiphilic and self-assemble into micellar nanoparticles to elongate blood circulation and for tumor-specific PDT.We further demonstrate that the PEGylated TCPP nanoparticles could serve as a nanoplatform to deliver the anticancer drug doxorubicin(DOX)and perform fluorescence image-guided combinatorial PDT and chemotherapy,which efficiently suppress the growth of 4T1 breast tumors and lung metastases in a mouse model.These acid-activatable PS-incorporated nanoparticles might provide a versatile platform for precise PDT and combinatorial breast cancer therapy.展开更多
The metabolic process of chiral drugs plays a significant role in clinics and in research on drugs.Here,we experimentally demonstrate by all-optical means that the chiral molecules can be quickly discriminated and mon...The metabolic process of chiral drugs plays a significant role in clinics and in research on drugs.Here,we experimentally demonstrate by all-optical means that the chiral molecules can be quickly discriminated and monitored with the ultrahighorder modes excited in a metal cladding optofluidic chip,achieving over 5 times sensitivity with a low-dosage sample.We show that the varying concentration of the chiral drugs can be monitored both in cell and animal experiments,presenting a significant difference between chiral enantiomers at the optimal function time and the effect of the reaction.To our knowledge,this approach provides a new way to achieve important chiral discrimination for the pharmacokinetics and the pharmacodynamics and may present opportunities in indicating the health status of humans.展开更多
Glioblastoma(GBM) therapy is severely impaired by the blood-brain barrier(BBB) and invasive tumor growth in the central nervous system.To improve GBM therapy,we herein presented a dual-targeting nanotheranostic for se...Glioblastoma(GBM) therapy is severely impaired by the blood-brain barrier(BBB) and invasive tumor growth in the central nervous system.To improve GBM therapy,we herein presented a dual-targeting nanotheranostic for second near-infrared(NIR-Ⅱ) fluorescence imaging-guided photoimmunotherapy.Firstly,a NIR-Ⅱ fluorophore MRP bearing donor-acceptor-donor(D-A-D) backbone was synthesized.Then,the prodrug nanotheranostics were prepared by self-assembling MRP with a prodrug of JQ1(JPC) and T7 ligand-modified PEG5k-DSPE.T7 can cross the BBB for tumor-targeted delivery of JPC and MRP.JQ1 could be restored from JPC at the tumor site for suppressing interferon gamma-inducible programmed death ligand 1 expression in the tumor cells.MRP could generate NIR-Ⅱ fluorescence to navigate 808 nm laser,induce a photothermal effect to trigger in-situ antigen release at the tumor site,and ultimately elicit antitumor immunogenicity.Photo-immunotherapy with JPC and MRP dual-loaded nanoparticles remarkably inhibited GBM tumor growth in vivo.The dual-targeting nanotheranostic might represent a novel nanoplatform for precise photo-immunotherapy of GBM.展开更多
基金supported by the Science and Technology Innovation Program of Hunan Province,China(No.2023RC3055)the Natural Science Foundation of Hunan Province,China(Nos.2023JJ30671)+1 种基金the Natural Science Foundation of Changsha City,China(No.Kq2208264)the National Natural Science Foundation of China(No.51601229).
文摘A new Al−4.87Mn−1.42Mg−0.63Sc−0.20Zr(wt.%)alloy was fabricated by selective laser melting(SLM)and its microstructure and mechanical properties before and after aging were investigated.The results show that at a laser power input of 300 W,increasing laser scanning speeds from 700 to 1500 mm/s improves the mechanical properties.In the meantime,the lattice distortion values increase from 0.15%to 0.31%,showing an increasing solute supersaturation.At a laser scanning speed of 1500 mm/s,the yield strength,ultimate tensile strength and elongation of the as-SLM alloys are 356 MPa,412 MPa and 17.7%,respectively.After aging at 350°C for 8 h,these values increase to 527 MPa,554 MPa and 10.4%,respectively.The contributions to the yield strength increments from the secondary Al6(Fe,Mn)needle-like phase and re-precipitated L12 structured Al6(Sc,Zr,Ti)nano-particles during aging are 74 and 79 MPa,respectively.As the aging temperature increases to 450°C,the dominant precipitation strengthening is attributed to the secondary Al6(Sc,Zr,Ti)nano-particles.
基金the financial supports from the Natural Science Foundation of Hunan Province, China (Nos. 2020JJ4114, 2016JJ3151)the National Natural Science Foundation of China (No. 51601229)+2 种基金the Young Elite Scientist Sponsorship Program by CAST, China (No. 2015QNRC001)the Hunan Province Innovation Platform and Talent Plan Project, China (No. 2015RS4001)the Open-end Fund for the Valuable and Precision Instruments of Central South University, China (No. CSUZC201815)。
基金financially supported by the Natural Science Foundation of Hunan Province(Nos.2020JJ4114,2016JJ3151)the National Natural Science Foundation of China(No.51601229)+2 种基金the Young Elite Scientist Sponsorship Program by CAST(No.2015QNRC001)the Hunan Province Innovation Platform and Talent Plan Project,China(No.2015RS4001)the Open-End Fund for the Valuable and Precision Instruments of Central South University,China(No.CSUZC201815)。
文摘采用选择激光熔化(SLM)技术在不同工艺参数下制备Al-4.77Mn-1.37Mg-0.67Sc-0.25Zr合金(质量分数,%),通过拉伸试验和显微观察研究合金的组织和力学性能。结果表明:当能量密度为104~143 J/mm^(3)时,力学性能保持相对稳定;屈服强度为335~338 MPa,抗拉强度为397~400 MPa,伸长率均在11%以上。在此能量密度区间内,SLM合金缺陷和粗大金属间化合物较少,与此同时,有大量细小的Al Fe Mn Sc Zr相析出。当能量密度超过152 J/mm^(3)时,可以观察到一些孔洞和裂纹,且伸长率急剧下降。定量计算结果表明,该合金固溶强化、晶界强化和析出强化占比分别为44%、41%和15%。
基金financially supported by the Natural Science Foundation of Hunan Province,China(Nos.2020JJ4114,2016JJ3151)the National Natural Science Foundation of China(No.51601229)+2 种基金the Young Elite Scientist Sponsorship Program by CAST,China(No.2015QNRC001)the Hunan Province Innovation Platform and Talent Plan,China(No.2015RS4001)the Open-End Fund for the Valuable and Precision Instruments of Central South University,China(No.CSUZC201815)。
基金supported by the National Natural Science Foundation of China(Nos.82102915,22074043 and U22A20328)Lingang Laboratory(No.LG-QS-202206-04)+1 种基金China Postdoctoral Science Foundation(No.2021M700157)Shanghai Post-Doctoral Excellence Program(No.2021424).
文摘Photodynamic therapy(PDT)has emerged as an efficient cancer treatment method with minimal invasiveness.However,the majority of current photosensitizers(PSs)display severe dark toxicity and low tumor specificity due to their"always-on"photoactivity in blood circulation.To address this concern,we herein report a series of acid-activatable PSs for ultrasensitive PDT of triple-negative breast tumors.These set of novel PSs are synthesized by covalently modifying tetrakis(4-carboxyphenyl)porphyrin(TCPP)with a variety of tertiary amines for acidity-activatable fluorescence imaging and reactive oxygen species(RoS)generation.The resultant TCPP derivatives are grafted with a poly(ethylene glycol)(PEG)chain via a matrix metalloproteinase-2(MMP-2)-liable peptide spacer and chelated with Mn^(2+)for magnetic resonance imaging(MRI)capability.The PEGylated TCPP derivatives are amphiphilic and self-assemble into micellar nanoparticles to elongate blood circulation and for tumor-specific PDT.We further demonstrate that the PEGylated TCPP nanoparticles could serve as a nanoplatform to deliver the anticancer drug doxorubicin(DOX)and perform fluorescence image-guided combinatorial PDT and chemotherapy,which efficiently suppress the growth of 4T1 breast tumors and lung metastases in a mouse model.These acid-activatable PS-incorporated nanoparticles might provide a versatile platform for precise PDT and combinatorial breast cancer therapy.
基金supported by the National Natural Science Foundation of China(NSFC)(Nos.12104298 and 12192252)the Shanghai Municipal Science and Technology Major Project(No.2019SHZDZX01-06)the Natural Science Foundation of Shanghai(No.23ZR1428400)。
文摘The metabolic process of chiral drugs plays a significant role in clinics and in research on drugs.Here,we experimentally demonstrate by all-optical means that the chiral molecules can be quickly discriminated and monitored with the ultrahighorder modes excited in a metal cladding optofluidic chip,achieving over 5 times sensitivity with a low-dosage sample.We show that the varying concentration of the chiral drugs can be monitored both in cell and animal experiments,presenting a significant difference between chiral enantiomers at the optimal function time and the effect of the reaction.To our knowledge,this approach provides a new way to achieve important chiral discrimination for the pharmacokinetics and the pharmacodynamics and may present opportunities in indicating the health status of humans.
基金Financial supports from the National Natural Science Foundation of China (22074043, 22174047, 32050410287)Science and Technology Commission of Shanghai Municipality (20142202800, China)+1 种基金China Postdoctoral Science Foundation (2021M700157)Shanghai Post-Doctoral Excellence Program (2021424, China)
文摘Glioblastoma(GBM) therapy is severely impaired by the blood-brain barrier(BBB) and invasive tumor growth in the central nervous system.To improve GBM therapy,we herein presented a dual-targeting nanotheranostic for second near-infrared(NIR-Ⅱ) fluorescence imaging-guided photoimmunotherapy.Firstly,a NIR-Ⅱ fluorophore MRP bearing donor-acceptor-donor(D-A-D) backbone was synthesized.Then,the prodrug nanotheranostics were prepared by self-assembling MRP with a prodrug of JQ1(JPC) and T7 ligand-modified PEG5k-DSPE.T7 can cross the BBB for tumor-targeted delivery of JPC and MRP.JQ1 could be restored from JPC at the tumor site for suppressing interferon gamma-inducible programmed death ligand 1 expression in the tumor cells.MRP could generate NIR-Ⅱ fluorescence to navigate 808 nm laser,induce a photothermal effect to trigger in-situ antigen release at the tumor site,and ultimately elicit antitumor immunogenicity.Photo-immunotherapy with JPC and MRP dual-loaded nanoparticles remarkably inhibited GBM tumor growth in vivo.The dual-targeting nanotheranostic might represent a novel nanoplatform for precise photo-immunotherapy of GBM.
