The high therapeutic resistance of tumor is the primary cause behind tumor recurrence and incurability.In recent years,scientists have devoted themselves to find a variety of treatments to solve this problem.Herein,we...The high therapeutic resistance of tumor is the primary cause behind tumor recurrence and incurability.In recent years,scientists have devoted themselves to find a variety of treatments to solve this problem.Herein,we propose a multi-hit strategy that is based on the biodegradable hollow mesoporous Prussian blue(HMPB)-based nanosystem for tumor-specific therapy that encapsulated the critical heat shock protein 90(HSP90)inhibitor 17-dimethylamino-ethylamino-17-demethoxydeldanamycin(17-DMAG).The nanosystem was further modified using thermotropic phase transition material star-PEG-PCL(sPP)and hyaluronic acid(HA),which offers near infrared light(NIR)responsive release characteristic,as well as enhanced tumor cell endocytosis.Upon cell internalization of 17-DMAG-HMPB@sPP@HA and under 808 nm laser irradiation,photothermal-conversion effect of HMPB directly kills cells using hyperthermia,which further causes phase transition of sPP to trigger release of 17-DMAG,inhibits HSP90 activity and blocks multiple signaling pathways,including cell cycle,Akt and HIF pathways.Additionally,the down-regulation of GPX4 protein expression by 17-DMAG and the release of ferric and ferrous ions from gradual degradation of HMPB in the endogenous mild acidic microenvironment in tumors promoted the occurrence of ferroptosis.Importantly,the antitumor effect of 17-DMAG and ferroptosis damage were amplified using photothermal effect of HMPB by accelerating release of ferric and ferrous ions,and reducing HSP90 expression in cells,which induced powerful antitumor effect in vitro and in vivo.This multi-hit therapeutic nanosystem helps provide a novel perspective for solving the predicament of cancer treatment,as well as a promising strategy for design of a novel cancer treatment nanoplatform.展开更多
The ballistic resistance and failure pattern of a bi-layer alumina 99.5%-aluminium alloy 1100-H12 target against steel 4340 ogival nosed projectile has been explored in the present experimental cum numerical study.In ...The ballistic resistance and failure pattern of a bi-layer alumina 99.5%-aluminium alloy 1100-H12 target against steel 4340 ogival nosed projectile has been explored in the present experimental cum numerical study.In the experimental investigation,damage induced in the ceramic layer has been quantified in terms of number of cracks developed and failure zone dimensions.The resultant damage in the backing layer has been studied with variation in the bulge and perforation hole in the backing layer with the varying incidence velocity.The discussion of the experimental results has been further followed by three dimensional finite element computations using ABAQUS/Explicit finite code to investigate the behaviour of different types of bi-layer targets under multi-hit projectile impact.The JH-2 constitutive model has been used to reproduce the behaviour of alumina 99.5%and JC constitutive model has been used for steel 4340 and aluminium alloy 1100-H12.The total energy dissipation has been noted to be of lesser magnitude in case of sub-sequential impact in comparison to simultaneous impact of two projectiles.The distance between the impact points of two projectiles also effected the ballistic resistance of bi-layer target.The ballistic resistance of single tile ceramic front layer and four tile ceramic of equivalent area found to be dependent upon the boundary conditions provided to the target.展开更多
针对多批次试验中由技术状态改进所带来的异总体统计问题,研究了顺序约束条件下的命中概率指标统计评定方法。首先在X-Y向不相关情况下,将命中概率指标归结为X向和Y向的准确度和密集度参数的估计。然后根据多批次试验规律,建立各个参数...针对多批次试验中由技术状态改进所带来的异总体统计问题,研究了顺序约束条件下的命中概率指标统计评定方法。首先在X-Y向不相关情况下,将命中概率指标归结为X向和Y向的准确度和密集度参数的估计。然后根据多批次试验规律,建立各个参数之间的顺序约束关系,基于Bayes方法获得验后分布密度核函数,并采用MCMC(Markov Chain Monte Carlo)方法获得各参数的验后抽样分布,进而获得命中概率指标的抽样分布,以此计算命中概率的期望和置信限。此外,针对运动目标或末端机动的情况,分析了X-Y向相关情况下的命中概率指标计算方法。通过正交变换实现去相关处理,并在命中概率计算中引入旋转角度参数,从而解决运动目标情况下的多批次命中概率计算。最后,通过实例进行了验证,所得命中概率值优于传统方法所获得的统计结果,表明该方法对多批次试验具有良好的适应性和工程推广价值。展开更多
Ceramics constitute an integral part of highly efficient armours due to their low density, high hardness, strength and stiffness. However, they lack toughness and multi-hit capability. Therefore, zirconia toughened al...Ceramics constitute an integral part of highly efficient armours due to their low density, high hardness, strength and stiffness. However, they lack toughness and multi-hit capability. Therefore, zirconia toughened alumina is investigated. The hardness is evaluated using Vickers, Knoop and instrumented indentations, while the fracture toughness is evaluated using the indentation technique and Charpy tests. The strength is evaluated using ring-on-ring, four point bend and drop weight tests. The Young’s modulus is evaluated using the unloading instrumented indentation curves. Microstructure, porosity and density are characterised using ultrasonic scanning, Archimedes principle, optical and scanning electron microscopy. Results show an indentation size effect on all mechanical properties. A substantial improvement in toughness is achieved through retardation of crack initiation by tetragonal-to-monoclinic phase transformation in zirconia particles, crack deviation thanks to appropriate grain structure, as well as energy absorption by densification due to remaining porosity. This improved toughness is expected to promote multi-hit capability.展开更多
基金This work was supported by:National Natural Science Foundation of China(Grant No:81503020)Natural Science Foundation of Liaoning Province(Grant No:2019-ZD-0459,2020-MS-196)and the Basic Research Project of Liaoning Provincial Department of Education(Grant No:2019LJC04).
文摘The high therapeutic resistance of tumor is the primary cause behind tumor recurrence and incurability.In recent years,scientists have devoted themselves to find a variety of treatments to solve this problem.Herein,we propose a multi-hit strategy that is based on the biodegradable hollow mesoporous Prussian blue(HMPB)-based nanosystem for tumor-specific therapy that encapsulated the critical heat shock protein 90(HSP90)inhibitor 17-dimethylamino-ethylamino-17-demethoxydeldanamycin(17-DMAG).The nanosystem was further modified using thermotropic phase transition material star-PEG-PCL(sPP)and hyaluronic acid(HA),which offers near infrared light(NIR)responsive release characteristic,as well as enhanced tumor cell endocytosis.Upon cell internalization of 17-DMAG-HMPB@sPP@HA and under 808 nm laser irradiation,photothermal-conversion effect of HMPB directly kills cells using hyperthermia,which further causes phase transition of sPP to trigger release of 17-DMAG,inhibits HSP90 activity and blocks multiple signaling pathways,including cell cycle,Akt and HIF pathways.Additionally,the down-regulation of GPX4 protein expression by 17-DMAG and the release of ferric and ferrous ions from gradual degradation of HMPB in the endogenous mild acidic microenvironment in tumors promoted the occurrence of ferroptosis.Importantly,the antitumor effect of 17-DMAG and ferroptosis damage were amplified using photothermal effect of HMPB by accelerating release of ferric and ferrous ions,and reducing HSP90 expression in cells,which induced powerful antitumor effect in vitro and in vivo.This multi-hit therapeutic nanosystem helps provide a novel perspective for solving the predicament of cancer treatment,as well as a promising strategy for design of a novel cancer treatment nanoplatform.
文摘The ballistic resistance and failure pattern of a bi-layer alumina 99.5%-aluminium alloy 1100-H12 target against steel 4340 ogival nosed projectile has been explored in the present experimental cum numerical study.In the experimental investigation,damage induced in the ceramic layer has been quantified in terms of number of cracks developed and failure zone dimensions.The resultant damage in the backing layer has been studied with variation in the bulge and perforation hole in the backing layer with the varying incidence velocity.The discussion of the experimental results has been further followed by three dimensional finite element computations using ABAQUS/Explicit finite code to investigate the behaviour of different types of bi-layer targets under multi-hit projectile impact.The JH-2 constitutive model has been used to reproduce the behaviour of alumina 99.5%and JC constitutive model has been used for steel 4340 and aluminium alloy 1100-H12.The total energy dissipation has been noted to be of lesser magnitude in case of sub-sequential impact in comparison to simultaneous impact of two projectiles.The distance between the impact points of two projectiles also effected the ballistic resistance of bi-layer target.The ballistic resistance of single tile ceramic front layer and four tile ceramic of equivalent area found to be dependent upon the boundary conditions provided to the target.
文摘针对多批次试验中由技术状态改进所带来的异总体统计问题,研究了顺序约束条件下的命中概率指标统计评定方法。首先在X-Y向不相关情况下,将命中概率指标归结为X向和Y向的准确度和密集度参数的估计。然后根据多批次试验规律,建立各个参数之间的顺序约束关系,基于Bayes方法获得验后分布密度核函数,并采用MCMC(Markov Chain Monte Carlo)方法获得各参数的验后抽样分布,进而获得命中概率指标的抽样分布,以此计算命中概率的期望和置信限。此外,针对运动目标或末端机动的情况,分析了X-Y向相关情况下的命中概率指标计算方法。通过正交变换实现去相关处理,并在命中概率计算中引入旋转角度参数,从而解决运动目标情况下的多批次命中概率计算。最后,通过实例进行了验证,所得命中概率值优于传统方法所获得的统计结果,表明该方法对多批次试验具有良好的适应性和工程推广价值。
文摘Ceramics constitute an integral part of highly efficient armours due to their low density, high hardness, strength and stiffness. However, they lack toughness and multi-hit capability. Therefore, zirconia toughened alumina is investigated. The hardness is evaluated using Vickers, Knoop and instrumented indentations, while the fracture toughness is evaluated using the indentation technique and Charpy tests. The strength is evaluated using ring-on-ring, four point bend and drop weight tests. The Young’s modulus is evaluated using the unloading instrumented indentation curves. Microstructure, porosity and density are characterised using ultrasonic scanning, Archimedes principle, optical and scanning electron microscopy. Results show an indentation size effect on all mechanical properties. A substantial improvement in toughness is achieved through retardation of crack initiation by tetragonal-to-monoclinic phase transformation in zirconia particles, crack deviation thanks to appropriate grain structure, as well as energy absorption by densification due to remaining porosity. This improved toughness is expected to promote multi-hit capability.
