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
The spheroidization of the Widmanstätten structure through thermo-mechanical processes,leading to the formation of fine recrystallized and sub-grain structures,is crucial for achieving a balance between strength ...The spheroidization of the Widmanstätten structure through thermo-mechanical processes,leading to the formation of fine recrystallized and sub-grain structures,is crucial for achieving a balance between strength and plasticity.This study systematically examined the spheroidization mechanism of the Widmanstätten structure in Ti-25Zr-4Al-1.5Mn(wt.%,TiZrAlMn)alloy under varying rolling temperatures and its influence on microstructure and mechanical properties.After rolling at 900℃,the specimen exhibited a mixed morphology of Widmanstätten and Basket-weave structures,with a high yield strength of approximately 1038 MPa but low plasticity(∼5.2%).While the rolling temperature was reduced to 850℃,the specimen exhibited refined prior-β grains,discontinuous grain boundaries and a small amount of equiaxed α grains,which collectively enhanced plasticity(∼12.4%)while preserving yield strength.As the rolling temperature further decreased,the dynamic recrystallization mechanism shifted from the discontinuous dynamic recrystallization(DDRX)to continuous dynamic recrystallization(CDRX).Specimens rolled at 800℃ and 750℃ showed excellent strength-plasticity synergy,with yield strengths of 1070 MPa and 1110 MPa,respectively,and total elongations of 15%and 18%,respectively.The enhanced yield strength is attributed to both fine-grain and sub-grain strengthening.Furthermore,the lower degree of recrystallization in the 750-AC specimen preserved a relatively high dislocation density,offering additional strengthening.The favorable plasticity results from a combination of equiaxedαgrains,“soft”barrier sub-grains,and a small number of twins.Additionally,the 750-AC specimen retained 6.4%of the fine β grains and the weak basal texture.These characteristics contribute to the enhanced plasticity.Therefore,750℃is the optimal rolling temperature for achieving the best strength-plasticity synergy in the hot-rolled TiZrAlMn alloy.These findings demonstrate that selecting the appropriate temperature during thermomechanical processing to optimize recrystallized grains and sub-grain content ensures excellent plasticity at high yield strength.This offers valuable guidance for developing near-α Ti alloys with superior mechanical properties.展开更多
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
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
Eutectic high-entropy alloys(EHEAs),as a classification of high-entropy alloys(HEAs),have received worldwide interest due to superior fluidity and attractive properties.However,other than the FCC+B2 EHEA system,most o...Eutectic high-entropy alloys(EHEAs),as a classification of high-entropy alloys(HEAs),have received worldwide interest due to superior fluidity and attractive properties.However,other than the FCC+B2 EHEA system,most other reported EHEA systems show inherent brittleness during tensile loading at room temperature,which limits their advanced engineering application.In this work,a novel spheroidization+recrystallization(SR)strategy for synergistic strengthening and plasticizing of the brit-tle CoCrFeNi_(2)(V_(6)B_(3)Si)_(0.149)was proposed.The superior combination of strength and ductility was achieved by tailoring spherical M3 B2+recrystallized FCC duplex phases.Based on this strategy,the yield strength and elongation were improved from 565±15 MPa and 2.3%±0.3%to 841±24-1278±20 MPa and 14.7%±0.5%-22.5%±1.2%,with an increase of 48%-126%and 539%-878%,respectively.The synergistic increment in the strength and ductility of SR-FCC+M_(3)B_(2)EHEAs exceeds all reported fur-ther strengthened FCC+B2 EHEAs.Meanwhile,such simple thermo-mechanical processing is suitable for large-scale industrial production.The high strength results from the back stress provided by the dual heterogeneity of FCC grain sizes and soft FCC/hard M_(3)B_(2).The good ductility is attributed to the dislo-cation movement path released by spheroidized M3 B2 and a more uniform stress distribution caused by the recrystallized FCC.This work provides a new strategy for synergistic strengthening and plasticizing of the brittle EHEAs to meet industrial reliability requirements.展开更多
Delayed and nonhealing of diabetic wounds imposes substantial economic burdens and physical pain on patients.Mesenchymal stem cells(MSCs)promote diabetic wound healing.Particularly when MSCs aggregate into multicellul...Delayed and nonhealing of diabetic wounds imposes substantial economic burdens and physical pain on patients.Mesenchymal stem cells(MSCs)promote diabetic wound healing.Particularly when MSCs aggregate into multicellular spheroids,their therapeutic effect is enhanced.However,traditional culture platforms are inadequate for the efficient preparation and delivery of MSC spheroids,resulting in inefficiencies and inconveniences in MSC spheroid therapy.In this study,a three-dimensional porous nanofibrous dressing(NFD)is prepared using a combination of electrospinning and homogeneous freeze-drying.Using thermal crosslinking,the NFD not only achieves satisfactory elasticity but also maintains notable cytocompatibility.Through the design of its structure and chemical composition,the NFD allows MSCs to spontaneously form MSC spheroids with controllable sizes,serving as MSC spheroid delivery systems for diabetic wound sites.Most importantly,MSC spheroids cultured on the NFD exhibit improved secretion of vascular endothelial growth factor,basic fibroblast growth factor,and hepatocyte growth factor,thereby accelerating diabetic wound healing.The NFD provides a competitive strategy for MSC spheroid formation and delivery to promote diabetic wound healing.展开更多
Tissue engineering has been striving toward designing and producing natural and functional human tissues.Cells are the fundamental building blocks of tissues.Compared with traditional two-dimensional cultured cells,ce...Tissue engineering has been striving toward designing and producing natural and functional human tissues.Cells are the fundamental building blocks of tissues.Compared with traditional two-dimensional cultured cells,cell spheres are threedimensional(3D)structures that can naturally form complex cell–cell and cell–matrix interactions.This structure is close to the natural environment of cells in living organisms.In addition to being used in disease modeling and drug screening,spheroids have significant potential in tissue regeneration.The 3D bioprinting is an advanced biofabrication technique.It accurately deposits bioinks into predesigned 3D shapes to create complex tissue structures.Although 3D bioprinting is efficient,the time required for cells to develop into complex tissue structures can be lengthy.The 3D bioprinting of spheroids significantly reduces the time required for their development into large tissues/organs during later cultivation stages by printing them with high cell density.Combining spheroid fabrication and bioprinting technology should provide a new solution to many problems in regenerative medicine.This paper systematically elaborates and analyzes the spheroid fabrication methods and 3D bioprinting strategies by introducing spheroids as building blocks.Finally,we present the primary challenges faced by spheroid fabrication and 3D bioprinting with future requirements and some recommendations.展开更多
Cancer cell spheroids(CCS) are a valuable three-dimensional cell model in cancer studies because they could replicate numerous characteristics of solid tumors. Increasing researches have used matrix-assisted laser des...Cancer cell spheroids(CCS) are a valuable three-dimensional cell model in cancer studies because they could replicate numerous characteristics of solid tumors. Increasing researches have used matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDI-MSI) to investigate the spatial distribution of endogenous compounds(e.g., lipids) in CCS. However, only limited lipid species can be detected owing to a low ion yield by using MALDI. Besides, it is still challenging to fully characterize the structural diversity of lipids due to the existence of isomeric/isobaric species. Here, we carried out the initial application of MALDI coupled with laser-postionization(MALDI-2) and trapped ion mobility spectrometry(TIMS) imaging in HCT116 colon CCS to address these challenges. We demonstrated that MALDI-2 is capable of detecting more number and classes of lipids in HCT116 colon CCS with higher signal intensities than MALDI. TIMS could successfully separate numerous isobaric/isomeric species of lipids in CCS. Interestingly, we found that some isomeric/isobaric species have totally different spatial distributions in colon CCS. Further MS/MS imaging analysis was employed to determine the compositions of fatty acid chains for isomeric species by examining disparities in signal intensities and spatial distributions of product ions. This work stresses the robust ability of TIMS and MALDI-2 imaging in analyzing endogenous lipids in CCS, which could potentially become powerful tools for future cancer studies.展开更多
Multilayer paper-based cell culture,as an in vitro three-dimensional(3D)cell culture method,has been frequently used to research drug bioavailability,therapeutic efficacy,and dose-limiting toxicity in malignant tumors...Multilayer paper-based cell culture,as an in vitro three-dimensional(3D)cell culture method,has been frequently used to research drug bioavailability,therapeutic efficacy,and dose-limiting toxicity in malignant tumors.This paper proposes a heterogenous multilayer paper stacking co-culture system to establish a model of natural killer(NK)cells moving through the endothelium layer and attacking tumor spheroids.This system consists of three layers:a bottom tumor-spheroid layer,a middle invasion layer,and a top endothelium layer.NK-92 cells were placed in the supernatant on top of the three layers.After two days of co-culture,the attack of tumor spheroids by NK cells was observed.We additionally examined the infiltration of NK-92 cells within the tumor spheroids at different Z-axis depths using a confocal microscope,and the results suggested that the system successfully realizes NK cells traveling cross the endothelium layer to form tumor-infiltrating NK cells(TINKs).The potential application of multilayer paper for co-culture models involving cancer cells and immune cells holds great promise for exploring the interaction dynamics of these two cell types.展开更多
Laser three-dimensional(3D)printing offers significant advantages in integrating the shape and function of regen-erative tissues through biomimetic manufacturing.However,its effectiveness is limited by the lack of spe...Laser three-dimensional(3D)printing offers significant advantages in integrating the shape and function of regen-erative tissues through biomimetic manufacturing.However,its effectiveness is limited by the lack of specialized biopolymer powders-while solvent methods that use residual solvents produce powders with poor biocompati-bility,mechanical methods result in irregularly shaped crystals.In this study,a biopolymer powder spheroidiza-tion and shaping technology,which utilizes the evolution of irregular powders into spheres with minimal surface free energy in the molten state,is proposed based on the thermodynamic principle of minimum energy.Initially,the motion trajectory and temperature field of the poly(L-lactic acid)(PLLA)powder during spheroidization were quantitatively assessed and optimized using Stokes’law and Fourier’s principle.Subsequently,the cohesive forces and aggregation kinetics of the polymer chains were calculated using molecular dynamics.Finally,based on these calculations,a phase-field model was constructed to simulate the evolution of the spheroidization rate and deduce the optimal parameters for the process.This precise approach enhances PLLA spheroidization control for laser 3D printing,improves part densification and surface quality,and offers a clean and efficient path for preparing high-quality PLLA spheroidized powder for laser 3D printing.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
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financially supported by the National Natural Science Foundation of China(Nos.52125405,52127808,52071278,U22A20108 and 52471148)the Science Research Project of Hebei Education Department(No.KJZX202201)+2 种基金Natural Science Foundation of Hebei Province(No.242Q9906Z/E2021402002)Basic Research Project of Shijiazhuang City for Universities in Hebei Province(No.241791027A)the Hebei Provincial Department of Education Funding Project for Cultivating Innovative Ability of Graduate Students(Grant no.CXZZBS2025057/CXZZBS2025056).
文摘The spheroidization of the Widmanstätten structure through thermo-mechanical processes,leading to the formation of fine recrystallized and sub-grain structures,is crucial for achieving a balance between strength and plasticity.This study systematically examined the spheroidization mechanism of the Widmanstätten structure in Ti-25Zr-4Al-1.5Mn(wt.%,TiZrAlMn)alloy under varying rolling temperatures and its influence on microstructure and mechanical properties.After rolling at 900℃,the specimen exhibited a mixed morphology of Widmanstätten and Basket-weave structures,with a high yield strength of approximately 1038 MPa but low plasticity(∼5.2%).While the rolling temperature was reduced to 850℃,the specimen exhibited refined prior-β grains,discontinuous grain boundaries and a small amount of equiaxed α grains,which collectively enhanced plasticity(∼12.4%)while preserving yield strength.As the rolling temperature further decreased,the dynamic recrystallization mechanism shifted from the discontinuous dynamic recrystallization(DDRX)to continuous dynamic recrystallization(CDRX).Specimens rolled at 800℃ and 750℃ showed excellent strength-plasticity synergy,with yield strengths of 1070 MPa and 1110 MPa,respectively,and total elongations of 15%and 18%,respectively.The enhanced yield strength is attributed to both fine-grain and sub-grain strengthening.Furthermore,the lower degree of recrystallization in the 750-AC specimen preserved a relatively high dislocation density,offering additional strengthening.The favorable plasticity results from a combination of equiaxedαgrains,“soft”barrier sub-grains,and a small number of twins.Additionally,the 750-AC specimen retained 6.4%of the fine β grains and the weak basal texture.These characteristics contribute to the enhanced plasticity.Therefore,750℃is the optimal rolling temperature for achieving the best strength-plasticity synergy in the hot-rolled TiZrAlMn alloy.These findings demonstrate that selecting the appropriate temperature during thermomechanical processing to optimize recrystallized grains and sub-grain content ensures excellent plasticity at high yield strength.This offers valuable guidance for developing near-α Ti alloys with superior mechanical properties.
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.
基金This work was supported by the National Key Research and De-velopment Program of China(No.2018YFA0702901)National Nat-ural Science Foundation of China(No.U20A20278)Liao Ning Revitalization Talents Program(No.XLYC1807047).
文摘Eutectic high-entropy alloys(EHEAs),as a classification of high-entropy alloys(HEAs),have received worldwide interest due to superior fluidity and attractive properties.However,other than the FCC+B2 EHEA system,most other reported EHEA systems show inherent brittleness during tensile loading at room temperature,which limits their advanced engineering application.In this work,a novel spheroidization+recrystallization(SR)strategy for synergistic strengthening and plasticizing of the brit-tle CoCrFeNi_(2)(V_(6)B_(3)Si)_(0.149)was proposed.The superior combination of strength and ductility was achieved by tailoring spherical M3 B2+recrystallized FCC duplex phases.Based on this strategy,the yield strength and elongation were improved from 565±15 MPa and 2.3%±0.3%to 841±24-1278±20 MPa and 14.7%±0.5%-22.5%±1.2%,with an increase of 48%-126%and 539%-878%,respectively.The synergistic increment in the strength and ductility of SR-FCC+M_(3)B_(2)EHEAs exceeds all reported fur-ther strengthened FCC+B2 EHEAs.Meanwhile,such simple thermo-mechanical processing is suitable for large-scale industrial production.The high strength results from the back stress provided by the dual heterogeneity of FCC grain sizes and soft FCC/hard M_(3)B_(2).The good ductility is attributed to the dislo-cation movement path released by spheroidized M3 B2 and a more uniform stress distribution caused by the recrystallized FCC.This work provides a new strategy for synergistic strengthening and plasticizing of the brittle EHEAs to meet industrial reliability requirements.
基金supported by Fundamental Research Program of Shanxi Province(202203021222199)the Taiyuan University of Science and Technology Scientific Research Initial Funding(20222090)the National Natural Science Foundation of China(21975019).
文摘Delayed and nonhealing of diabetic wounds imposes substantial economic burdens and physical pain on patients.Mesenchymal stem cells(MSCs)promote diabetic wound healing.Particularly when MSCs aggregate into multicellular spheroids,their therapeutic effect is enhanced.However,traditional culture platforms are inadequate for the efficient preparation and delivery of MSC spheroids,resulting in inefficiencies and inconveniences in MSC spheroid therapy.In this study,a three-dimensional porous nanofibrous dressing(NFD)is prepared using a combination of electrospinning and homogeneous freeze-drying.Using thermal crosslinking,the NFD not only achieves satisfactory elasticity but also maintains notable cytocompatibility.Through the design of its structure and chemical composition,the NFD allows MSCs to spontaneously form MSC spheroids with controllable sizes,serving as MSC spheroid delivery systems for diabetic wound sites.Most importantly,MSC spheroids cultured on the NFD exhibit improved secretion of vascular endothelial growth factor,basic fibroblast growth factor,and hepatocyte growth factor,thereby accelerating diabetic wound healing.The NFD provides a competitive strategy for MSC spheroid formation and delivery to promote diabetic wound healing.
基金supported by the National Natural Science Foundation of China(Nos.61973206,61703265,61803250,and 61933008)the Shanghai Science and Technology Committee Rising-Star Program(No.19QA1403700)the National Center for Translational Medicine(Shanghai)SHU Branch.
文摘Tissue engineering has been striving toward designing and producing natural and functional human tissues.Cells are the fundamental building blocks of tissues.Compared with traditional two-dimensional cultured cells,cell spheres are threedimensional(3D)structures that can naturally form complex cell–cell and cell–matrix interactions.This structure is close to the natural environment of cells in living organisms.In addition to being used in disease modeling and drug screening,spheroids have significant potential in tissue regeneration.The 3D bioprinting is an advanced biofabrication technique.It accurately deposits bioinks into predesigned 3D shapes to create complex tissue structures.Although 3D bioprinting is efficient,the time required for cells to develop into complex tissue structures can be lengthy.The 3D bioprinting of spheroids significantly reduces the time required for their development into large tissues/organs during later cultivation stages by printing them with high cell density.Combining spheroid fabrication and bioprinting technology should provide a new solution to many problems in regenerative medicine.This paper systematically elaborates and analyzes the spheroid fabrication methods and 3D bioprinting strategies by introducing spheroids as building blocks.Finally,we present the primary challenges faced by spheroid fabrication and 3D bioprinting with future requirements and some recommendations.
基金supported by the National Natural Science Foundation of China (Nos.22036001, 22276034 and 22106130)。
文摘Cancer cell spheroids(CCS) are a valuable three-dimensional cell model in cancer studies because they could replicate numerous characteristics of solid tumors. Increasing researches have used matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDI-MSI) to investigate the spatial distribution of endogenous compounds(e.g., lipids) in CCS. However, only limited lipid species can be detected owing to a low ion yield by using MALDI. Besides, it is still challenging to fully characterize the structural diversity of lipids due to the existence of isomeric/isobaric species. Here, we carried out the initial application of MALDI coupled with laser-postionization(MALDI-2) and trapped ion mobility spectrometry(TIMS) imaging in HCT116 colon CCS to address these challenges. We demonstrated that MALDI-2 is capable of detecting more number and classes of lipids in HCT116 colon CCS with higher signal intensities than MALDI. TIMS could successfully separate numerous isobaric/isomeric species of lipids in CCS. Interestingly, we found that some isomeric/isobaric species have totally different spatial distributions in colon CCS. Further MS/MS imaging analysis was employed to determine the compositions of fatty acid chains for isomeric species by examining disparities in signal intensities and spatial distributions of product ions. This work stresses the robust ability of TIMS and MALDI-2 imaging in analyzing endogenous lipids in CCS, which could potentially become powerful tools for future cancer studies.
基金supported by the National Natural Science Foundation of China(No.32171401)the Natural Science Foundation of Chongqing(Nos.CSTB2022NSCQ-MSX0808 and cstc2021jcyj-bsh0239)the Innovation Platform for Academicians of Hainan Province(No.YSPTZX202126),China。
文摘Multilayer paper-based cell culture,as an in vitro three-dimensional(3D)cell culture method,has been frequently used to research drug bioavailability,therapeutic efficacy,and dose-limiting toxicity in malignant tumors.This paper proposes a heterogenous multilayer paper stacking co-culture system to establish a model of natural killer(NK)cells moving through the endothelium layer and attacking tumor spheroids.This system consists of three layers:a bottom tumor-spheroid layer,a middle invasion layer,and a top endothelium layer.NK-92 cells were placed in the supernatant on top of the three layers.After two days of co-culture,the attack of tumor spheroids by NK cells was observed.We additionally examined the infiltration of NK-92 cells within the tumor spheroids at different Z-axis depths using a confocal microscope,and the results suggested that the system successfully realizes NK cells traveling cross the endothelium layer to form tumor-infiltrating NK cells(TINKs).The potential application of multilayer paper for co-culture models involving cancer cells and immune cells holds great promise for exploring the interaction dynamics of these two cell types.
基金supported by National Key Research and Development Program of China(Grant No.2023YFB4605800)Natural Science Foundation of China(Grant Nos.51935014,52365046,52105352,82072084)+1 种基金JiangXi Provincial Natural Science Foundation of China(Grant No.20224ACB204013)Schig-Qinling Program(Grant No.2022360702014891).
文摘Laser three-dimensional(3D)printing offers significant advantages in integrating the shape and function of regen-erative tissues through biomimetic manufacturing.However,its effectiveness is limited by the lack of specialized biopolymer powders-while solvent methods that use residual solvents produce powders with poor biocompati-bility,mechanical methods result in irregularly shaped crystals.In this study,a biopolymer powder spheroidiza-tion and shaping technology,which utilizes the evolution of irregular powders into spheres with minimal surface free energy in the molten state,is proposed based on the thermodynamic principle of minimum energy.Initially,the motion trajectory and temperature field of the poly(L-lactic acid)(PLLA)powder during spheroidization were quantitatively assessed and optimized using Stokes’law and Fourier’s principle.Subsequently,the cohesive forces and aggregation kinetics of the polymer chains were calculated using molecular dynamics.Finally,based on these calculations,a phase-field model was constructed to simulate the evolution of the spheroidization rate and deduce the optimal parameters for the process.This precise approach enhances PLLA spheroidization control for laser 3D printing,improves part densification and surface quality,and offers a clean and efficient path for preparing high-quality PLLA spheroidized powder for laser 3D printing.
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.
