Arrhythmogenic right ventricular cardiomyopathy(ARVC)is a progressive disease characterized by adipose and fibrous replacement of the myocardium.While elevated testosterone levels have been implicated in the pathologi...Arrhythmogenic right ventricular cardiomyopathy(ARVC)is a progressive disease characterized by adipose and fibrous replacement of the myocardium.While elevated testosterone levels have been implicated in the pathological process of ARVC,its exact contribution to cardiac fibrosis in ARVC remains unclear.In this study,we analyzed the potential contribution of gender-based differences on the distribution of the low-voltage area in an ARVC cohort undergoing an electrophysiological study,which was indicated by feature selection.Additionally,we established engineered cardiac spheroid models in vitro using patient-specific induced pluripotent stem cell(iPSC)-derived cardiomyocytes(iPSC-CMs)and iPSC-derived cardiac fibroblasts(icFBs).We elucidated the pathogenicity of abnormal splicing in the plakophilin-2(PKP2)gene caused by an intronic mutation.Additionally,pathogenic validation of the desmoglein-2(DSG2)point mutation further confirms the reliability of the models.Moreover,testosterone exacerbated the DNA damage in the mutated cardiomyocytes and further activated myofibroblasts in a chain reaction.In conclusion,we designed and constructed an in vitro three-dimensionally-engineered cardiac spheroid model of ARVC based on clinical findings and provided direct evidence of the fibrotic role of testosterone in ARVC.展开更多
In the directed energy deposition(DED)process with high heat input,repeated heating and cooling cycles in the deposited layers have a signifcant efect on the microstructure.Because of the diferences in the cyclic numb...In the directed energy deposition(DED)process with high heat input,repeated heating and cooling cycles in the deposited layers have a signifcant efect on the microstructure.Because of the diferences in the cyclic numbers and peak temperatures from the lower layer to the upper layer,inhomogeneous microstructures are formed in the as-built components.In this work,a cyclic heat treatment(CHT)with gradual cooling was used to simulate the thermal process during the DED process of Ti-5Al-3Mo-3V-2Cr-2Zr-1Nb-1Fe(Ti5321)near-βTi alloy.The efect of CHT on the microstructural evolution,especially the spheroidization ofαphase,was investigated.As the CHT cycle increased,the volume fraction ofαphase gradually increased from 35.9%after 1 cycle to 60.9%after 100 cycles,and the length ofαphase frst increased and then gradually decreased,while the width ofαphase increased slowly.The aspect ratio ofαphase decreased from 9.90±3.39 after 1 cycle to 2.37±0.87 after 100 cycles,implying that CHT inducedαphase spheroidization.This phenomenon resulted from both the boundary splitting mechanism and the termination migration mechanism during CHT.The evolution of microstructure afects its mechanical properties.As the CHT cycles increased,the hardness increased overall,from 342.8±5.3 HV after 1 cycle to 400.3±3.4 HV after 100 cycles.This work provides a potential method to tailor the microstructure of near-βTi alloys by heat treatment alone,especially for non-deformable additively manufactured metal components.展开更多
Traditional heat treatment methods require a significant amount of time and energy to affect atomic diffusion and enhance the spheroidization process of carbides in bearing steel,while pulsed current can accelerate at...Traditional heat treatment methods require a significant amount of time and energy to affect atomic diffusion and enhance the spheroidization process of carbides in bearing steel,while pulsed current can accelerate atomic diffusion to achieve ultra-fast spheroidization of carbides.However,the understanding of the mechanism by which different pulse current parameters regulate the dissolution behavior of carbides requires a large amount of experimental data to support,which limits the application of pulse current technology in the field of heat treatment.Based on this,quantify the obtained pulse current processing data to create an important dataset that could be applied to machine learning.Through machine learning,the mechanism of mutual influence between carbide regulation and various factors was elucidated,and the optimal spheroidization process parameters were determined.Compared to the 20 h required for traditional heat treatment,the application of pulsed electric current technology achieved ultra-fast spheroidization of GCr15 bearing steel within 90 min.展开更多
Cellular spheroids,closely resembling native tissue microenvironments,have emerged as pivotal constructs in biomedicine as they can facilitate complex cell-cell and cell-matrix interactions.However,current methods for...Cellular spheroids,closely resembling native tissue microenvironments,have emerged as pivotal constructs in biomedicine as they can facilitate complex cell-cell and cell-matrix interactions.However,current methods for constructing spheroid assembloids with spatial arrangement or heterogeneous structures are limited,which has become a barrier for studying tissue engineering and in vitro disease modeling.Here,we demonstrate an acoustofluidic pick-and-place operation system capable of spatially assembling of spheroids into desired patterns in both two dimensional(2D)and three dimensional(3D)spaces.The underlying physical mechanism of the device is systematically studied to explain the interrelationship between trapping cell spheroids,acoustic streaming,and the acoustic radiation force(ARF)induced by the acoustically activated microneedle.We exploit these mechanisms to successfully transfer cellular spheroids into hydrogel solutions,enabling them to be precisely patterned and fused into assembloids of predefined shapes.Besides,we demonstrate arranging MC3T3-E1 cellular spheroids into a ring shape to fabricate the osteogenic tissues.Besides,a co-culture model involving tumor cells(MCF-7)and normal human dermal fibroblasts(NHDFs)is constructed to validate our method’s ability to reconstruct heterogeneous tumor model,revealing that the fibroblast spheroids promote tumor spheroid invasion.Our method holds significant potential prospects in regenerative medicine,disease model construction and drug screening.展开更多
AIM:To investigate the efficacy of Eleutherine bulbosa(Mill.)Urb.bulb extract(EBE)on the 3D human retinoblastoma cancer cells(WERI-Rb-1)spheroids and explore its apoptotic mechanism.METHODS:The 3D WERI-Rb-1 and human ...AIM:To investigate the efficacy of Eleutherine bulbosa(Mill.)Urb.bulb extract(EBE)on the 3D human retinoblastoma cancer cells(WERI-Rb-1)spheroids and explore its apoptotic mechanism.METHODS:The 3D WERI-Rb-1 and human retinal pigmented epithelium cells(ARPE-19)spheroids were developed using type 1 murine collagen that was excised from the rat tail tendon and cultured via hanging drop and embedded techniques.The cytotoxic activity was examined by Alamar blue assay meanwhile,the morphological characteristics were assessed by 4’,6-diamidino-2-phenylindole(DAPI)and scanning electron microscopy(SEM).The mRNA and protein expressions of apoptotic and antioxidant signal transduction pathways were explored to ascertain its molecular mechanisms.The statistical analysis was carried out using GraphPad Prism.RESULTS:The Alamar blue assay portrayed higher half maximal inhibitory concentration(IC50)values of EBE and cisplatin on 3D WERI-Rb-1 model as compared to the previous study on 2D model.The results of DAPI and SEM illustrated apoptotic features upon treatment with EBE and cisplatin in a dose-dependent manner on 3D WERI-Rb-1 model.The mRNA and protein levels of apoptotic and antioxidant-related pathways were significantly affected by EBE and cisplatin,respectively(P<0.05).The regulation of gene and protein expressions of 3D WERI-Rb-1 spheroids differed from the 2D study,suggesting that the tumor microenvironment of extracellular matrix(ECM)collagen matrix hindered the EBE treatment efficacy,leading to apoptotic evasion.CONCLUSION:A significant inhibition effect of EBE is observed on the 3D WERI-Rb-1 spheroids.The presence of ECM causes an increase in cytotoxic resistance upon treatment with EBE and cisplatin.展开更多
Xerostomia(dry mouth)is frequently experienced by patients treated with radiotherapy for head and neck cancers or with Sjögren’s syndrome,with no permanent cure existing for this debilitating condition.To this e...Xerostomia(dry mouth)is frequently experienced by patients treated with radiotherapy for head and neck cancers or with Sjögren’s syndrome,with no permanent cure existing for this debilitating condition.To this end,in vitro platforms are needed to test therapies directed at salivary(fluid-secreting)cells.However,since these are highly differentiated secretory cells,the maintenance of their differentiated state while expanding in numbers is challenging.In this study,the efficiency of three reversible thermo-ionically crosslinked gels:(1)alginate–gelatin(AG),(2)collagen-containing AG(AGC),and(3)hyaluronic acid-containing AG(AGHA),to recapitulate a native-like environment for human salivary gland(SG)cell expansion and 3D spheroid formation was compared.Although all gels were of mechanical properties comparable to human SG tissue(~11 kPa)and promoted the formation of 3D spheroids,AGHA gels produced larger(>100 cells/spheroid),viable(>93%),proliferative,and well-organized 3D SG spheroids while spatially and temporally maintaining the high expression of key SG proteins(aquaporin-5,NKCC1,ZO-1,α-amylase)for 14 days in culture.Moreover,the spheroids responded to agonist-induced stimulation by increasingα-amylase secretory granules.Here,we propose alternative lowcost,reproducible,and reversible AG-based 3D hydrogels that allow the facile and rapid retrieval of intact,highly viable 3D-SG spheroids.展开更多
3D （Three-dimensional） Caco-2 spheroids closely recapitulating in vivo physiological organization of intestinal epithelial cells, provide an excellent in vitro model system to study their pathophysiology and their r...3D （Three-dimensional） Caco-2 spheroids closely recapitulating in vivo physiological organization of intestinal epithelial cells, provide an excellent in vitro model system to study their pathophysiology and their response to stressful stimuli. The objective of this technical note is to provide optimized in vitro experimental protocols for culturing 3D Caco-2 spheroids and for analyzing their cell growth features. An optimized 3D Caco-2 spheroid culturing technique based on a new configuration of the culture medium is provided A methodological approach to determine the distribution of the cell cycle phases in disaggregated Caco-2 spheroids by using cytofluorimetric analysis is also described. The optimized culturing protocol favors 3D Caco-2 spheroid differentiation process, as evaluated by the number of well-differentiated spheroids with a single hollow lumen. The cytofluorimetric analysis allows rapid collection of cell cycle phase data from high numbers of spheroid samples, thus, permitting to estimate their growth dynamics in a relatively short time. The optimized technical approaches described here can be applied in systematic manner to a variety of research activities utilizing 3D Caco-2 spheroids. Ease of use, time and economic saving advantages deriving from these protocols further highlight their potential.展开更多
Abstract： The dynamic spheroidization kinetics behavior of Ti-6.5Al-2Zr-1Mo-1V alloy with a lamellar initial microstructure was studied by isothermal hot compression tests in the temperature range of 750-950℃ and st...Abstract： The dynamic spheroidization kinetics behavior of Ti-6.5Al-2Zr-1Mo-1V alloy with a lamellar initial microstructure was studied by isothermal hot compression tests in the temperature range of 750-950℃ and strain rates of 0.001-10 s^-1. The results show that the spheroidized fraction of alpha lamellae increases with the increase of temperature and the decrease of strain rate. The spheroidization kinetics curves predicted by JMAK equation agree well with experimental ones. The corresponding SEM and TEM observations indicate that the dynamic spheroidization process can be divided into two stages. The primary stage is boundary splitting formed by two competing mechanisms which are dynamic recrystallization and mechanical twin. In the second stage, the penetration of beta phase into the alpha/alpha grain boundaries is dominant, which is controlled in nature by diffusion of the chemical elements such as Al, Mo and V.展开更多
The influence of rare earth metals and heat treatment on the microstructure and performance of M42 steel has been investigated by means of an optical microscope OM scanning electron microscope SEM energy dispersive sp...The influence of rare earth metals and heat treatment on the microstructure and performance of M42 steel has been investigated by means of an optical microscope OM scanning electron microscope SEM energy dispersive spectroscopy EDS transmission electron microscope TEM electron back-scatter diffraction EBSD and X-ray diffraction XRD . The results show that M2 C is the prevailing type of eutectic carbides in M42 steel. After modification with rare earth metals M2 C eutectic carbides change from the ordered lamellar structure into a circular structure.Despite different morphologies the two carbides present the same characteristics of microstructure and growth orientation.Compared with lamellar carbides M2 C carbides with the circular structure are much easier to decompose and spheroidize after heating which remarkably refines the carbide dimensions.The refined carbides improve the supersaturation of alloying elements in martensite and increase the hardness of M42 steel by 1.5 HRC.展开更多
Spheroidizing annealing and torsion testing of 0.027 wt% carbon steel rod were conducted to evaluate spheroidization kinetic behavior at 943 K （670 ℃） under deformed and non-deformed states. Kinetic curves were als...Spheroidizing annealing and torsion testing of 0.027 wt% carbon steel rod were conducted to evaluate spheroidization kinetic behavior at 943 K （670 ℃） under deformed and non-deformed states. Kinetic curves were also predicted using the Johnson-Mehl-Avrami-Kolmogorov equation, and the results agree well with the experimental ones. After spheroidization was performed twice, the spherical cementite and precipitated carbides became smaller and the distribution was more uniform. Comparison of materials subjected to single and double spheroidizing annealing indicated a difference in grain size. Torsion performance was considerably improved under double spheroidization, especially the maximum torque with slight variations.展开更多
Surface modification may have important influences on the penetration behavior of nanoscale drug delivery system. In the present study, we mainly focused on whether cell targeting or cell penetration could affect pene...Surface modification may have important influences on the penetration behavior of nanoscale drug delivery system. In the present study, we mainly focused on whether cell targeting or cell penetration could affect penetration abilities of nanostructured lipid carriers（NLC）. Real--time penetration of folate--or cell penetrating peptide（CPP）-modified NLC was evaluated using a multicellular tumor spheroid（MTS） established by stacking culture method as an in vitro testing platform. The results suggested that CPP modification had a better penetration behavior both on penetration depth and intensity compared with folate-modified NLC at the early stage of penetration process.展开更多
For processing parts made from medium carbon steel, toughness and flexibility are of importance. There- fore, to achieve these properties, the cementite in the steels is spheroidized through heat treatment. Different ...For processing parts made from medium carbon steel, toughness and flexibility are of importance. There- fore, to achieve these properties, the cementite in the steels is spheroidized through heat treatment. Different parameters such as the time and temperature of spheroidizing and the initial microstructure of the steel affect the amount of spheroidized cementite. In the present work, the percent of contribution of two parameters, i.e. initial microstructure and spheroidizing time, to the percent of spheroidization in CK60 steel was investigated using Taguchi robust design. The initial microstructures consisted of martensite, coarse pearlite, fine pearlite and bainite and the chosen spheroidization times were 4, 8, 12, and 16h. Spheroidizing was done at the constant temperature 700℃. After spheroidizing was completed, the samples were prepared in order to observe their microstructure under an optical microscope and to determine the spheroidized percent using MIPTM （metallographic image processing） software. It was found that the spheroidizing time had the most influence （58.5 ~//0） on spheroidized percent and the initial microstructure only had a 31.1% contribution. Finally, the instantaneous growth rate of the carbide was also deduced.展开更多
AIM To develop a culture mode providingdurable biomaterials with high yields andactivities used in bioartificial liver.METHODS Hepatocytes were isolated from awhole pig liver by Seglen’s method of orthotopicperfusion...AIM To develop a culture mode providingdurable biomaterials with high yields andactivities used in bioartificial liver.METHODS Hepatocytes were isolated from awhole pig liver by Seglen’s method of orthotopicperfusion with collagenase.In culture onmicrocarriers,primary porcine hepatocyteswere inoculated at a concentration of 5×10~7/mLinto the static culture systems containing 2 g/LCytodex-3,then supplemented with 100 mL/Lfetal calf serum(FCS)or 100 mL/L porcineportal vein serum(PPVS)respectively.Inspheroidal aggregate culture hepatocytes wereinoculated into 100 mL siliconized flasks at aconcentration of 5.0×10~6/mL.RESULTS In culture on microcarriershepatocytes tended to aggregate on Cytodex-3obviously after being inoculated.Typical multi-cellular aggregated spheroids could be found inthe two systems 24 h-48 h after hepatocyteswere cultured.The morphological charact-eristics and synthetic functions were maintainedfor 5 wk in FCS culture system and 8 wk in PPVSculture system.In spheroidal aggregate cultureabout 80%-90% isolated hepatocytes becameaggregated spheroids 24h after cultured insuspension and mean diameter of the spheroidswas 100μm.The relationship among thehepatocytes resembled that in the liver in vivo.Synthetic functions of albumin and urea of the spheroids were twice those of hepatocytescultured on monolayers.CONCLUSION As high-yields and high-activitymodes of culture on microcarriers or inspheroidal aggregate culture with portal veinserum are promising to provide biomaterials forbioartificial liver(BAL)efficiently.展开更多
During the plasma spheroidization process powders undergo different changes in their microstructures and crystal phases. In this paper, simple calculation of heat transfer between the plasma and a suspended particle w...During the plasma spheroidization process powders undergo different changes in their microstructures and crystal phases. In this paper, simple calculation of heat transfer between the plasma and a suspended particle was performed based on three hypotheses for the purpose of guiding experiments. Experimental investigation of the crystal phases and microstructural changes during the plasma processing was made using silica, alumina and nickel powders as starting materials. It has been revealed from the experimental results that these materials undergo different changes in crystal phases and microstructures, and these changes are essentially determined by the structures, properties and aggregate states of the starting materials.展开更多
In isothermal spheroidizing process,the spheroidization and growth of the carbide formed in hot-deformed high-carbon chromium cast steel at high temperature were investigated.The results showed that the spheroidizing ...In isothermal spheroidizing process,the spheroidization and growth of the carbide formed in hot-deformed high-carbon chromium cast steel at high temperature were investigated.The results showed that the spheroidizing growth of carbide proceeds in such a way that the bigger carbide particles swallow the smaller ones,and the short rhabdoid carbides dissolve and are spheroidized by itself.When the samples were held at 720℃ for more than 3 h,the spheroidization is not obvious.The feature of the process is the size increment and the amount decrement of carbide particles.The empirical equation for growth rate of carbides was obtained.The volume fraction of carbides keeps constant.The growth process agrees well with Ostwald Ripening Law.展开更多
A new spheroidizing process of ultra-high carbon steel （UHCS） containing C 1.55%, Cr 1.45%, and Al 1.5% in mass percent has been proposed. The effect of processing parameters on the microstructure was analyzed. The ...A new spheroidizing process of ultra-high carbon steel （UHCS） containing C 1.55%, Cr 1.45%, and Al 1.5% in mass percent has been proposed. The effect of processing parameters on the microstructure was analyzed. The UHCS produced by this new process has a microstructure with recrystallized ferrite matrix and fine and uniform carbide particles. After this spheroidizing, the UHCS exhibits good mechanical properties at ambient temperature, for example σb= 1 100 MPa, σs =915 MPa, δ=8% and high ratio of σs/σb.展开更多
A micro-modeling method (MM) for the quantitative prediction of the shrinkage cavity formation in SGiron castings is proposed. The mathematical models describing the volume changes during the solidification ofspheroid...A micro-modeling method (MM) for the quantitative prediction of the shrinkage cavity formation in SGiron castings is proposed. The mathematical models describing the volume changes during the solidification ofspheroidal graphite cast iron are established based on the models of solidification kinetics. The shrinkage cavityformation of T-shaped SG iron castings is calculated with MM method. The calculated results are compared with theexperimental results. It is shown that the predicted size, shape and distribution of shrinkage cavity by MM methodare in good agreement with the measured results.展开更多
Amorphous spherical silica powders were prepared by inductively coupled thermal plasma treatment at a radio frequency of 36.2 MHz. The effects of the added content of hydrogen and nitrogen into argon(serving as the sh...Amorphous spherical silica powders were prepared by inductively coupled thermal plasma treatment at a radio frequency of 36.2 MHz. The effects of the added content of hydrogen and nitrogen into argon(serving as the sheath gas), as well as the carrier gas flow rate, on the spheroidization rate of silica powders, were investigated. The prepared silica powders before and after plasma treatment were examined by scanning electron microscopy, X-ray diffraction, and laser granulometric analysis. Results indicated that the average size of the silica particles increased, and the transformation of crystals into the amorphous state occurred after plasma treatment. Discharge image processing was employed to analyze the effect of the plasma temperature field on the spheroidization rate. The spheroidization rate of the silica powder increased with the increase of the hydrogen content in the sheath gas. On the other hand, the spheroidization rate of the silica power first increased and then decreased with the increase of the nitrogen content in the sheath gas. Moreover, the amorphous content increased with the increase of the spheroidization rate of the silica powder.展开更多
The effects of isothermal holding process on the microstructure evolution of semi-solid 7075 strength aluminum alloy produced by the recrystallisation and partial remelting(RAP) process were investigated. Tensile mech...The effects of isothermal holding process on the microstructure evolution of semi-solid 7075 strength aluminum alloy produced by the recrystallisation and partial remelting(RAP) process were investigated. Tensile mechanical properties of as-received and thixoformed alloys at room temperature were examined. The results show that the microstructure of as-received alloy exhibits remarkable orientation along the deformation direction.With the increase of isothermal holding time, the solid particle grain size continuously increases and the degree of spheroidization also improves. Coalescence mechanism is dominant when reheated at 595 °C and Ostwald ripening mechanism is dominant when reheated at 615 °C in the semi-solid state. A lower coarsening rate is observed for 615 °C(coarsening rate K = 391 μm3 s-1) compared with the coarsening rate for 595 °C(coarsening rate K = 501 μm3 s-1). The RAP 7075 aluminum alloy can be successfully thixoformed and the filling of components is good after thixoforming. The thixoformed components exhibit favorite mechanical properties.展开更多
The warm compression tests were performed on the eutectoid steel to investigate the evolution of cementite morphology. Several processing parameters, such as temperature, strain rate and reduction, were changed to ana...The warm compression tests were performed on the eutectoid steel to investigate the evolution of cementite morphology. Several processing parameters, such as temperature, strain rate and reduction, were changed to analyze the effect of each parameter on spheroidization of cementite. The results showed that the warm compression promoted the fragmentize and the spheroidization of lamellar cementites. When the specimen was compressed with reduction of 50% at 700 ℃ and in the strain rate of 0.01 s-1, the excellent spheroidized cementite was obtained. The mechanism of fragmentation and spheroidization of lamellar cementites during compression was discussed by using transmission electron microscope. The formation of spheroidized cementite was related to the time of compression process. The fragmentize of lamellar cementites was due to the extension of sub-grain boundary in the cementite. The spheroidization of cementite depended on the diffusion of carbon atoms at the tip of bended and breakup cementite.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82370322 to CC,82200352 to FZ,82300352 to YZ,22275034 to HX,and 82070343 to MLC)the Natural Science Foundation of Jiangsu Province of China(Nos.BK20220710 to FZ and BK20230733 to YZ)Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.JX13414086 to HYC).
文摘Arrhythmogenic right ventricular cardiomyopathy(ARVC)is a progressive disease characterized by adipose and fibrous replacement of the myocardium.While elevated testosterone levels have been implicated in the pathological process of ARVC,its exact contribution to cardiac fibrosis in ARVC remains unclear.In this study,we analyzed the potential contribution of gender-based differences on the distribution of the low-voltage area in an ARVC cohort undergoing an electrophysiological study,which was indicated by feature selection.Additionally,we established engineered cardiac spheroid models in vitro using patient-specific induced pluripotent stem cell(iPSC)-derived cardiomyocytes(iPSC-CMs)and iPSC-derived cardiac fibroblasts(icFBs).We elucidated the pathogenicity of abnormal splicing in the plakophilin-2(PKP2)gene caused by an intronic mutation.Additionally,pathogenic validation of the desmoglein-2(DSG2)point mutation further confirms the reliability of the models.Moreover,testosterone exacerbated the DNA damage in the mutated cardiomyocytes and further activated myofibroblasts in a chain reaction.In conclusion,we designed and constructed an in vitro three-dimensionally-engineered cardiac spheroid model of ARVC based on clinical findings and provided direct evidence of the fibrotic role of testosterone in ARVC.
基金sponsored by the National Natural Science Foundation of China(No.52271108)the Foundation of Xi’an Key Laboratory of High-Performance Titanium Alloy(No.NIN-HTL-2022-02)+2 种基金the Natural Science Foundation of Shanghai(No.21ZR1445100)the Shanghai Science and Technology Development Funds(No.22QB1406500)the ECU DVC Strategic Research Support Fund(No.23965).
文摘In the directed energy deposition(DED)process with high heat input,repeated heating and cooling cycles in the deposited layers have a signifcant efect on the microstructure.Because of the diferences in the cyclic numbers and peak temperatures from the lower layer to the upper layer,inhomogeneous microstructures are formed in the as-built components.In this work,a cyclic heat treatment(CHT)with gradual cooling was used to simulate the thermal process during the DED process of Ti-5Al-3Mo-3V-2Cr-2Zr-1Nb-1Fe(Ti5321)near-βTi alloy.The efect of CHT on the microstructural evolution,especially the spheroidization ofαphase,was investigated.As the CHT cycle increased,the volume fraction ofαphase gradually increased from 35.9%after 1 cycle to 60.9%after 100 cycles,and the length ofαphase frst increased and then gradually decreased,while the width ofαphase increased slowly.The aspect ratio ofαphase decreased from 9.90±3.39 after 1 cycle to 2.37±0.87 after 100 cycles,implying that CHT inducedαphase spheroidization.This phenomenon resulted from both the boundary splitting mechanism and the termination migration mechanism during CHT.The evolution of microstructure afects its mechanical properties.As the CHT cycles increased,the hardness increased overall,from 342.8±5.3 HV after 1 cycle to 400.3±3.4 HV after 100 cycles.This work provides a potential method to tailor the microstructure of near-βTi alloys by heat treatment alone,especially for non-deformable additively manufactured metal components.
基金supported by the National Key R&D Program of China(2020YFA0714900,2023YFB3709903)the National Natural Science Foundation of China(U21B2082,52474410)+6 种基金the Key R&D Program of Shandong Province,China(2023CXGC010406)the Scientific Research Special Project for First-Class Disciplines in Inner Mongolia Autonomous Region(YLXKZX-NKD-001)the International Science and Technology Cooperation Project of Higher Education Institutions in Inner Mongolia Autonomous Region(GHXM-002)the Natural Science Foundation of Inner Mongolia Autonomous Region of China(2024ZD06)the Technology Support Project for the Construction of Major Innovation Platforms in Inner Mongolia Autonomous Region(XM2024XTGXQ16)the Beijing Municipal Natural Science Foundation(2222065)the Fundamental Research Funds for the Central Universities(FRF-TP-22-02C2).
文摘Traditional heat treatment methods require a significant amount of time and energy to affect atomic diffusion and enhance the spheroidization process of carbides in bearing steel,while pulsed current can accelerate atomic diffusion to achieve ultra-fast spheroidization of carbides.However,the understanding of the mechanism by which different pulse current parameters regulate the dissolution behavior of carbides requires a large amount of experimental data to support,which limits the application of pulse current technology in the field of heat treatment.Based on this,quantify the obtained pulse current processing data to create an important dataset that could be applied to machine learning.Through machine learning,the mechanism of mutual influence between carbide regulation and various factors was elucidated,and the optimal spheroidization process parameters were determined.Compared to the 20 h required for traditional heat treatment,the application of pulsed electric current technology achieved ultra-fast spheroidization of GCr15 bearing steel within 90 min.
基金supported by National Natural Science Foundation of China(Grant No.12032015,12121002,and 12402062)Natural Science Foundation of Shanghai(Grant No.24ZR1434900)+4 种基金The Innovation Program of Shanghai Municipal Education Commission(Grant No.2019-01-07-00-02-E00030)Shanghai Pilot Program for Basic Research—Shanghai Jiao Tong University(Grant No.21TQ1400203)the Open Research Project Programme of the Science and Technology Development Fund(Grant No.006/2022/ALC)the Macao Centre for Research and Development in Advanced Materials(University of Macao)(Grant.No.MCRDAM-IAPME(UM)-2022-2024/ORP/002/2023)the Science and Technology Commission of Shanghai Municipality(Grant No.20DZ2220400).
文摘Cellular spheroids,closely resembling native tissue microenvironments,have emerged as pivotal constructs in biomedicine as they can facilitate complex cell-cell and cell-matrix interactions.However,current methods for constructing spheroid assembloids with spatial arrangement or heterogeneous structures are limited,which has become a barrier for studying tissue engineering and in vitro disease modeling.Here,we demonstrate an acoustofluidic pick-and-place operation system capable of spatially assembling of spheroids into desired patterns in both two dimensional(2D)and three dimensional(3D)spaces.The underlying physical mechanism of the device is systematically studied to explain the interrelationship between trapping cell spheroids,acoustic streaming,and the acoustic radiation force(ARF)induced by the acoustically activated microneedle.We exploit these mechanisms to successfully transfer cellular spheroids into hydrogel solutions,enabling them to be precisely patterned and fused into assembloids of predefined shapes.Besides,we demonstrate arranging MC3T3-E1 cellular spheroids into a ring shape to fabricate the osteogenic tissues.Besides,a co-culture model involving tumor cells(MCF-7)and normal human dermal fibroblasts(NHDFs)is constructed to validate our method’s ability to reconstruct heterogeneous tumor model,revealing that the fibroblast spheroids promote tumor spheroid invasion.Our method holds significant potential prospects in regenerative medicine,disease model construction and drug screening.
基金Supported by Universiti Putra Malaysia,Serdang,Selangor,Malaysia(UPM/700-2/1/GPB/2017/9549900).
文摘AIM:To investigate the efficacy of Eleutherine bulbosa(Mill.)Urb.bulb extract(EBE)on the 3D human retinoblastoma cancer cells(WERI-Rb-1)spheroids and explore its apoptotic mechanism.METHODS:The 3D WERI-Rb-1 and human retinal pigmented epithelium cells(ARPE-19)spheroids were developed using type 1 murine collagen that was excised from the rat tail tendon and cultured via hanging drop and embedded techniques.The cytotoxic activity was examined by Alamar blue assay meanwhile,the morphological characteristics were assessed by 4’,6-diamidino-2-phenylindole(DAPI)and scanning electron microscopy(SEM).The mRNA and protein expressions of apoptotic and antioxidant signal transduction pathways were explored to ascertain its molecular mechanisms.The statistical analysis was carried out using GraphPad Prism.RESULTS:The Alamar blue assay portrayed higher half maximal inhibitory concentration(IC50)values of EBE and cisplatin on 3D WERI-Rb-1 model as compared to the previous study on 2D model.The results of DAPI and SEM illustrated apoptotic features upon treatment with EBE and cisplatin in a dose-dependent manner on 3D WERI-Rb-1 model.The mRNA and protein levels of apoptotic and antioxidant-related pathways were significantly affected by EBE and cisplatin,respectively(P<0.05).The regulation of gene and protein expressions of 3D WERI-Rb-1 spheroids differed from the 2D study,suggesting that the tumor microenvironment of extracellular matrix(ECM)collagen matrix hindered the EBE treatment efficacy,leading to apoptotic evasion.CONCLUSION:A significant inhibition effect of EBE is observed on the 3D WERI-Rb-1 spheroids.The presence of ECM causes an increase in cytotoxic resistance upon treatment with EBE and cisplatin.
基金support from Fonds de Recherche du Québec Santé(FRQS,grant no.281271)support from FRQS doctoral award #304367funding from CFI,Rheolution Inc.,and Investissement Québec.
文摘Xerostomia(dry mouth)is frequently experienced by patients treated with radiotherapy for head and neck cancers or with Sjögren’s syndrome,with no permanent cure existing for this debilitating condition.To this end,in vitro platforms are needed to test therapies directed at salivary(fluid-secreting)cells.However,since these are highly differentiated secretory cells,the maintenance of their differentiated state while expanding in numbers is challenging.In this study,the efficiency of three reversible thermo-ionically crosslinked gels:(1)alginate–gelatin(AG),(2)collagen-containing AG(AGC),and(3)hyaluronic acid-containing AG(AGHA),to recapitulate a native-like environment for human salivary gland(SG)cell expansion and 3D spheroid formation was compared.Although all gels were of mechanical properties comparable to human SG tissue(~11 kPa)and promoted the formation of 3D spheroids,AGHA gels produced larger(>100 cells/spheroid),viable(>93%),proliferative,and well-organized 3D SG spheroids while spatially and temporally maintaining the high expression of key SG proteins(aquaporin-5,NKCC1,ZO-1,α-amylase)for 14 days in culture.Moreover,the spheroids responded to agonist-induced stimulation by increasingα-amylase secretory granules.Here,we propose alternative lowcost,reproducible,and reversible AG-based 3D hydrogels that allow the facile and rapid retrieval of intact,highly viable 3D-SG spheroids.
文摘3D （Three-dimensional） Caco-2 spheroids closely recapitulating in vivo physiological organization of intestinal epithelial cells, provide an excellent in vitro model system to study their pathophysiology and their response to stressful stimuli. The objective of this technical note is to provide optimized in vitro experimental protocols for culturing 3D Caco-2 spheroids and for analyzing their cell growth features. An optimized 3D Caco-2 spheroid culturing technique based on a new configuration of the culture medium is provided A methodological approach to determine the distribution of the cell cycle phases in disaggregated Caco-2 spheroids by using cytofluorimetric analysis is also described. The optimized culturing protocol favors 3D Caco-2 spheroid differentiation process, as evaluated by the number of well-differentiated spheroids with a single hollow lumen. The cytofluorimetric analysis allows rapid collection of cell cycle phase data from high numbers of spheroid samples, thus, permitting to estimate their growth dynamics in a relatively short time. The optimized technical approaches described here can be applied in systematic manner to a variety of research activities utilizing 3D Caco-2 spheroids. Ease of use, time and economic saving advantages deriving from these protocols further highlight their potential.
基金Project(2014ZE56015)supported by Aeronautical Science Foundation of ChinaProject(51261020)supported by the National Natural Science Foundation of ChinaProject(Zk201001004)supported by the Open Fund of the Aeronautical Science and Technology Key Laboratory of Aeronautical Material Hot Processing Technology,China
文摘Abstract： The dynamic spheroidization kinetics behavior of Ti-6.5Al-2Zr-1Mo-1V alloy with a lamellar initial microstructure was studied by isothermal hot compression tests in the temperature range of 750-950℃ and strain rates of 0.001-10 s^-1. The results show that the spheroidized fraction of alpha lamellae increases with the increase of temperature and the decrease of strain rate. The spheroidization kinetics curves predicted by JMAK equation agree well with experimental ones. The corresponding SEM and TEM observations indicate that the dynamic spheroidization process can be divided into two stages. The primary stage is boundary splitting formed by two competing mechanisms which are dynamic recrystallization and mechanical twin. In the second stage, the penetration of beta phase into the alpha/alpha grain boundaries is dominant, which is controlled in nature by diffusion of the chemical elements such as Al, Mo and V.
基金The National Natural Science Foundation of China(No.51301038,51201031,51371050)the Industry-AcademiaResearch Cooperative Innovation Fund of Jiangsu Province(No.BY2014127-03)+1 种基金the Natural Science Foundation of Jiangsu Province(No.BK20141306)the Scientific and Technological Innovation Fund of Danyang(No.SY201305)
文摘The influence of rare earth metals and heat treatment on the microstructure and performance of M42 steel has been investigated by means of an optical microscope OM scanning electron microscope SEM energy dispersive spectroscopy EDS transmission electron microscope TEM electron back-scatter diffraction EBSD and X-ray diffraction XRD . The results show that M2 C is the prevailing type of eutectic carbides in M42 steel. After modification with rare earth metals M2 C eutectic carbides change from the ordered lamellar structure into a circular structure.Despite different morphologies the two carbides present the same characteristics of microstructure and growth orientation.Compared with lamellar carbides M2 C carbides with the circular structure are much easier to decompose and spheroidize after heating which remarkably refines the carbide dimensions.The refined carbides improve the supersaturation of alloying elements in martensite and increase the hardness of M42 steel by 1.5 HRC.
基金This work was supported by the National Natural Science Foundation of China （Grant No. 51271035）.
文摘Spheroidizing annealing and torsion testing of 0.027 wt% carbon steel rod were conducted to evaluate spheroidization kinetic behavior at 943 K （670 ℃） under deformed and non-deformed states. Kinetic curves were also predicted using the Johnson-Mehl-Avrami-Kolmogorov equation, and the results agree well with the experimental ones. After spheroidization was performed twice, the spherical cementite and precipitated carbides became smaller and the distribution was more uniform. Comparison of materials subjected to single and double spheroidizing annealing indicated a difference in grain size. Torsion performance was considerably improved under double spheroidization, especially the maximum torque with slight variations.
基金National key Basic Research Program(Grant No.2013CB932501)National Natural Science Foundation of China(Grant No.81273454 and 81473156)+1 种基金Beijing National Science Foundation(Grant No.7132113)Doctoral Foundation of the Ministry of Education(Grant No.20130001110055)
文摘Surface modification may have important influences on the penetration behavior of nanoscale drug delivery system. In the present study, we mainly focused on whether cell targeting or cell penetration could affect penetration abilities of nanostructured lipid carriers（NLC）. Real--time penetration of folate--or cell penetrating peptide（CPP）-modified NLC was evaluated using a multicellular tumor spheroid（MTS） established by stacking culture method as an in vitro testing platform. The results suggested that CPP modification had a better penetration behavior both on penetration depth and intensity compared with folate-modified NLC at the early stage of penetration process.
文摘For processing parts made from medium carbon steel, toughness and flexibility are of importance. There- fore, to achieve these properties, the cementite in the steels is spheroidized through heat treatment. Different parameters such as the time and temperature of spheroidizing and the initial microstructure of the steel affect the amount of spheroidized cementite. In the present work, the percent of contribution of two parameters, i.e. initial microstructure and spheroidizing time, to the percent of spheroidization in CK60 steel was investigated using Taguchi robust design. The initial microstructures consisted of martensite, coarse pearlite, fine pearlite and bainite and the chosen spheroidization times were 4, 8, 12, and 16h. Spheroidizing was done at the constant temperature 700℃. After spheroidizing was completed, the samples were prepared in order to observe their microstructure under an optical microscope and to determine the spheroidized percent using MIPTM （metallographic image processing） software. It was found that the spheroidizing time had the most influence （58.5 ~//0） on spheroidized percent and the initial microstructure only had a 31.1% contribution. Finally, the instantaneous growth rate of the carbide was also deduced.
基金the National Natural Science Foundation of China,No.39570212
文摘AIM To develop a culture mode providingdurable biomaterials with high yields andactivities used in bioartificial liver.METHODS Hepatocytes were isolated from awhole pig liver by Seglen’s method of orthotopicperfusion with collagenase.In culture onmicrocarriers,primary porcine hepatocyteswere inoculated at a concentration of 5×10~7/mLinto the static culture systems containing 2 g/LCytodex-3,then supplemented with 100 mL/Lfetal calf serum(FCS)or 100 mL/L porcineportal vein serum(PPVS)respectively.Inspheroidal aggregate culture hepatocytes wereinoculated into 100 mL siliconized flasks at aconcentration of 5.0×10~6/mL.RESULTS In culture on microcarriershepatocytes tended to aggregate on Cytodex-3obviously after being inoculated.Typical multi-cellular aggregated spheroids could be found inthe two systems 24 h-48 h after hepatocyteswere cultured.The morphological charact-eristics and synthetic functions were maintainedfor 5 wk in FCS culture system and 8 wk in PPVSculture system.In spheroidal aggregate cultureabout 80%-90% isolated hepatocytes becameaggregated spheroids 24h after cultured insuspension and mean diameter of the spheroidswas 100μm.The relationship among thehepatocytes resembled that in the liver in vivo.Synthetic functions of albumin and urea of the spheroids were twice those of hepatocytescultured on monolayers.CONCLUSION As high-yields and high-activitymodes of culture on microcarriers or inspheroidal aggregate culture with portal veinserum are promising to provide biomaterials forbioartificial liver(BAL)efficiently.
基金supported by National Natural Science Foundation of China (No.50574083)
文摘During the plasma spheroidization process powders undergo different changes in their microstructures and crystal phases. In this paper, simple calculation of heat transfer between the plasma and a suspended particle was performed based on three hypotheses for the purpose of guiding experiments. Experimental investigation of the crystal phases and microstructural changes during the plasma processing was made using silica, alumina and nickel powders as starting materials. It has been revealed from the experimental results that these materials undergo different changes in crystal phases and microstructures, and these changes are essentially determined by the structures, properties and aggregate states of the starting materials.
基金Item Sponsored by Guiding Programme of Science and Technology Research of Hebei of China(94122123)
文摘In isothermal spheroidizing process,the spheroidization and growth of the carbide formed in hot-deformed high-carbon chromium cast steel at high temperature were investigated.The results showed that the spheroidizing growth of carbide proceeds in such a way that the bigger carbide particles swallow the smaller ones,and the short rhabdoid carbides dissolve and are spheroidized by itself.When the samples were held at 720℃ for more than 3 h,the spheroidization is not obvious.The feature of the process is the size increment and the amount decrement of carbide particles.The empirical equation for growth rate of carbides was obtained.The volume fraction of carbides keeps constant.The growth process agrees well with Ostwald Ripening Law.
基金Item Sponsored by Provincial Natural Science Foundation of Hebei Province of China (500023)
文摘A new spheroidizing process of ultra-high carbon steel （UHCS） containing C 1.55%, Cr 1.45%, and Al 1.5% in mass percent has been proposed. The effect of processing parameters on the microstructure was analyzed. The UHCS produced by this new process has a microstructure with recrystallized ferrite matrix and fine and uniform carbide particles. After this spheroidizing, the UHCS exhibits good mechanical properties at ambient temperature, for example σb= 1 100 MPa, σs =915 MPa, δ=8% and high ratio of σs/σb.
文摘A micro-modeling method (MM) for the quantitative prediction of the shrinkage cavity formation in SGiron castings is proposed. The mathematical models describing the volume changes during the solidification ofspheroidal graphite cast iron are established based on the models of solidification kinetics. The shrinkage cavityformation of T-shaped SG iron castings is calculated with MM method. The calculated results are compared with theexperimental results. It is shown that the predicted size, shape and distribution of shrinkage cavity by MM methodare in good agreement with the measured results.
基金financially supported by the National Natural Science Foundation of China (Nos. 21377133, 11535003, and 11405221)
文摘Amorphous spherical silica powders were prepared by inductively coupled thermal plasma treatment at a radio frequency of 36.2 MHz. The effects of the added content of hydrogen and nitrogen into argon(serving as the sheath gas), as well as the carrier gas flow rate, on the spheroidization rate of silica powders, were investigated. The prepared silica powders before and after plasma treatment were examined by scanning electron microscopy, X-ray diffraction, and laser granulometric analysis. Results indicated that the average size of the silica particles increased, and the transformation of crystals into the amorphous state occurred after plasma treatment. Discharge image processing was employed to analyze the effect of the plasma temperature field on the spheroidization rate. The spheroidization rate of the silica powder increased with the increase of the hydrogen content in the sheath gas. On the other hand, the spheroidization rate of the silica power first increased and then decreased with the increase of the nitrogen content in the sheath gas. Moreover, the amorphous content increased with the increase of the spheroidization rate of the silica powder.
基金financially supported by the National Natural Science Foundation of China(No.E050802)
文摘The effects of isothermal holding process on the microstructure evolution of semi-solid 7075 strength aluminum alloy produced by the recrystallisation and partial remelting(RAP) process were investigated. Tensile mechanical properties of as-received and thixoformed alloys at room temperature were examined. The results show that the microstructure of as-received alloy exhibits remarkable orientation along the deformation direction.With the increase of isothermal holding time, the solid particle grain size continuously increases and the degree of spheroidization also improves. Coalescence mechanism is dominant when reheated at 595 °C and Ostwald ripening mechanism is dominant when reheated at 615 °C in the semi-solid state. A lower coarsening rate is observed for 615 °C(coarsening rate K = 391 μm3 s-1) compared with the coarsening rate for 595 °C(coarsening rate K = 501 μm3 s-1). The RAP 7075 aluminum alloy can be successfully thixoformed and the filling of components is good after thixoforming. The thixoformed components exhibit favorite mechanical properties.
基金Item Sponsored by National Natural Science Foundation of China(50271060)Natural Science Foundation of Hebei Province of China(503291)
文摘The warm compression tests were performed on the eutectoid steel to investigate the evolution of cementite morphology. Several processing parameters, such as temperature, strain rate and reduction, were changed to analyze the effect of each parameter on spheroidization of cementite. The results showed that the warm compression promoted the fragmentize and the spheroidization of lamellar cementites. When the specimen was compressed with reduction of 50% at 700 ℃ and in the strain rate of 0.01 s-1, the excellent spheroidized cementite was obtained. The mechanism of fragmentation and spheroidization of lamellar cementites during compression was discussed by using transmission electron microscope. The formation of spheroidized cementite was related to the time of compression process. The fragmentize of lamellar cementites was due to the extension of sub-grain boundary in the cementite. The spheroidization of cementite depended on the diffusion of carbon atoms at the tip of bended and breakup cementite.
