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
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
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
The low-strength and high-brittleness of AZ91 cast magnesium alloy mainly result from the coarse divorced eutectic phase. To solve these problems, the annealing treatment of AZ91 cast magnesium alloy was carried out a...The low-strength and high-brittleness of AZ91 cast magnesium alloy mainly result from the coarse divorced eutectic phase. To solve these problems, the annealing treatment of AZ91 cast magnesium alloy was carried out at 415 ℃ and held for 24 h in this study and the alloy was then slowly cooled to room temperature in furnace. The microstructures of the alloy were observed using a metallographic microscope, a transmission electron microscopy and an emission scanning electron microscopy, respectively. The phase analysis was performed using the X-ray diffraction, and the tensile test of the specimen at ambient temperature was performed on a material test machine. The results indicate that the coarse divorced eutectic phase dissolves into the Mg matrix during the isothermal process, and the lamellarβ-Mg17AI12 phase precipitates from the magnesium solid solution with a type of pearlite precipitation during furnace cooling. Consequently, the spheroidizing treatment was carried out at 320℃ for 20 h following the annealing process and the lamellar β-Mg17A12 phase was spheroidized. Compared with the as-cast alloy, the strength and ductility of the AZ91 magnesium alloy are increased obviously after annealing treatment; the yield strength and tensile strength are increased to 137.8 MPa and 240.4 MPa from 102.9 MPa and 199.3 MPa, respectively; and the elongation is improved to 6.12% from 4.35%. After being spheroidized, the strength and hardness decrease a little, but the ductility is elevated to 7.23%. The nucleation, growth and spheroidizing mechanism of the lamellarβ-Mg12TAI12 phase were also discussed.展开更多
The influences of Ce, K and Na on the structures and properties of Fe-W-C alloy were investigated, and the idea estimating spheroidizing effect of carbides using circular degree(C.D) was put forward. The result shows ...The influences of Ce, K and Na on the structures and properties of Fe-W-C alloy were investigated, and the idea estimating spheroidizing effect of carbides using circular degree(C.D) was put forward. The result shows that eutectic carbide turns into sphericity from network after modification, carbide is refined and uniformly distributed and C.D of eutectic carbide increases. The mechanism of carbide spheroidizing was analyzed. The impact toughness and abrasion resistance of Fe-W-C obviously improve with the rise of C.D of carbides. The service life of modified Fe-W-C roll is 30% higher than that of high chromium cast iron roll, while its production cost is reduced by 30%.展开更多
The spheroidizing mechanism of W-phase in the Mg–Zn–Y–Mn–（B） alloys during solid-solution treatment was investigated by using kinetic methodologies. The microstructure and mechanical properties of heat-treated ...The spheroidizing mechanism of W-phase in the Mg–Zn–Y–Mn–（B） alloys during solid-solution treatment was investigated by using kinetic methodologies. The microstructure and mechanical properties of heat-treated Mg_（94）Zn_（2.5）-Y_（2.5）Mn_1 alloy containing 0.003 wt% B were compared with heat-treated Mg_（94）Zn_（2.5）-Y_（2.5）Mn_1 alloy. The heat-treated Mg_（94）Zn_（2.5）-Y_（2.5）Mn_1 alloy with 0.003 wt% B contained fine and uniform W-phase particles, which exhibited optimal mechanical performance. The ultimate tensile strength, yield strength and elongation were 287.7, 125.5 MPa and 21.1%,respectively.展开更多
Bond-length-difference (BLD) analysis results show that austenrte and cementite containing Mg, Zr. S have very different valence electron structures from Fe -C austenite and cementite. We find that this difference is ...Bond-length-difference (BLD) analysis results show that austenrte and cementite containing Mg, Zr. S have very different valence electron structures from Fe -C austenite and cementite. We find that this difference is the tie of absorption hypothesis, surface tension hypothesis, undercooling hypothesis in graphite spheroidizing theory. By using "the model of valence electron theory of drag-like effect" in our previous paper in crystallization theory, the spheroidizing effect of Mg and Zr and the anti-spheroidizing effect of S can be explained with the valence electron structure data of phases. Therefore, electron theory of graphite spheroidizing can be advanced.展开更多
Liposarcoma is one of the most common soft tissue sarcomas,however,its occurrence rate is still rare compared to other cancers.Due to its rarity,in vitro experiments are an essential approach to elucidate liposarcoma ...Liposarcoma is one of the most common soft tissue sarcomas,however,its occurrence rate is still rare compared to other cancers.Due to its rarity,in vitro experiments are an essential approach to elucidate liposarcoma pathobiology.Conventional cell culture-based research(2D cell culture)is still playing a pivotal role,while several shortcomings have been recently under discussion.In vivo,mouse models are usually adopted for pre-clinical analyses with expectations to overcome the issues of 2D cell culture.However,they do not fully recapitulate human dedifferentiated liposarcoma(DDLPS)characteristics.Therefore,three-dimensional(3D)culture systems have been the recent research focus in the cell biology field with the expectation to overcome at the same time the disadvantages of 2D cell culture and in vivo animal models and fill in the gap between them.Given the liposarcoma rarity,we believe that 3D cell culture techniques,including 3D cell cultures/co-cultures,and Patient-Derived tumor Organoids(PDOs),represent a promising approach to facilitate liposarcoma investigation and elucidate its molecular mechanisms and effective therapy development.In this review,we first provide a general overview of 3D cell cultures compared to 2D cell cultures.We then focus on one of the recent 3D cell culture applications,Patient-Derived Organoids(PDOs),summarizing and discussing several PDO methodologies.Finally,we discuss the current and future applications of PDOs to sarcoma,particularly in the field of liposarcoma.展开更多
BACKGROUND Glioblastoma multiforme(GBM)is the most aggressive and prevalent primary malignant brain tumor in adults,marked by poor prognosis and high invasiveness.Traditional GBM invasion assays,such as those involvin...BACKGROUND Glioblastoma multiforme(GBM)is the most aggressive and prevalent primary malignant brain tumor in adults,marked by poor prognosis and high invasiveness.Traditional GBM invasion assays,such as those involving mouse brain xenografts,are often time-consuming and limited in efficiency.In this context,stem cell-derived neural organoids(NOs)have emerged as advanced,threedimensional,human-relevant platforms that mimic the cellular architecture and microenvironment of the human brain.These models provide novel opportunities to investigate glioblastoma stem cell invasion,a critical driver of tumor progression and therapeutic resistance.AIM To evaluate studies using stem cell-derived NOs to model glioblastoma migration/invasion,focusing on methodologies,applications and therapeutic implications.METHODS We conducted a systematic review following PRISMA guidelines,searching PubMed and Scopus for studies published between March 2019 and March 2025 that investigated NOs in the context of glioblastoma invasion/migration.After screening 377 articles based on predefined inclusion and exclusion criteria,10 original research articles were selected for analysis.Extracted data were categorized into four analytical domains:(1)Tumor model formation;(2)NO characteristics;(3)NO differentiation protocols;and(4)Invasion/migration assessment methodologies.RESULTS The included studies exhibit significant methodological heterogeneity GBM model development,particularly regarding model type,cell source and culture conditions.Most studies(70%)used suspension cell models,while 30%employed spheroids,with most research focusing on patient-derived glioblastoma stem cells.NOs were predominantly generated from human induced pluripotent stem cells using both guided and unguided differentiation protocols.Confocal fluorescence microscopy was the primary method used for assessing invasion,revealing invasion depths of up to 300μm.Organoid maturity and co-culture duration influenced results,while key factors for model optimization included tumor cell density,organoid age and extracellular matrix composition.Some studies also tested therapeutic strategies such as Zika virus and microRNA modulation.Collectively,findings support the utility of NOs as effective tools for studying GBM behavior and therapeutic responses in a humanized three-dimensional context.CONCLUSION Human NOs represent promising platforms for modeling glioblastoma invasion in a humanized three-dimensional environment.However,a limited number of studies and methodological heterogeneity hinder reproducibility.Protocol standardization is essential to enhance the translational application of these models.展开更多
For a long time,the conventional superplastic forming temperature for Ti alloys is generally too high(~900-920℃),which leads to too long production cycles,heavy surface oxidation,and property reduction.In this study,...For a long time,the conventional superplastic forming temperature for Ti alloys is generally too high(~900-920℃),which leads to too long production cycles,heavy surface oxidation,and property reduction.In this study,an ultrafine bimodal microstructure,consisting of ultrafine equiaxed microstructure(0.66μm)and 43.3%lamellar microstructure,was achieved in the Ti-6Al-4V alloy by friction stir processing(FSP).The low-temperature superplastic behavior and deformation mechanism of the FSP Ti-6Al-4V alloy were investigated at temperatures of 550-675℃and strain rates ranging from 1×10^(−4)to 3×10^(−3)s^(−1).The FSP alloy exhibited superplastic elongations of>200%at the temperature range from 550 to 650℃,and an optimal superplastic elongation of 611%was achieved at 625℃and 1×10^(−4)s^(−1).This is the first time to report the low-temperature superplasticity of the bimodal microstructure in Ti alloys.Grain boundary sliding was identified as the dominant deformation mechanism,which was effectively accommodated by the comprehensive effect of dislocation-inducedβphase precipitation and dynamic spheroidization of the lamellar structure.This study provides a novel insight into the low-temperature superplastic deformation behavior of the bimodal microstructure.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
Background: Despite considerable advancements in identifying factors contributing to the development of hepatocellular carcinoma(HCC), the pathogenesis of HCC remains unclear. In many cases, HCC is a consequence of pr...Background: Despite considerable advancements in identifying factors contributing to the development of hepatocellular carcinoma(HCC), the pathogenesis of HCC remains unclear. In many cases, HCC is a consequence of prolonged liver fibrosis, resulting in the formation of an intricate premalignant microenvironment. The accumulation of extracellular matrix(ECM) is a hallmark of premalignant microenvironment. Given the critical role of different matrix components in regulating cell phenotype and function, this study aimed to elucidate the interplay between the fibrotic matrix and malignant features in HCC. Methods: Liver tissues from both control(normal) and carbon tetrachloride(CCl_(4))-induced fibrotic rats were decellularized using sodium dodecyl sulfate(SDS) and Triton X-100. The resulting hydrogel from decellularized ECM was processed into micro-particles via the water-in-oil emulsion method. Microparticles were subsequently incorporated into three-dimensional liver biomimetic micro-tissues(MTs) comprising Huh-7 cells, human umbilical vein endothelial cells(HUVECs), and LX-2 cells. The MTs were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium(MTS) assay at day 11, immunofluorescence staining, immunoblotting, and spheroid migration assay at day 14 after co-culture. Results: Fibrotic matrix from CCl4-treated rat livers significantly enhanced the growth rate of the MTs and their expression of CCND1 as compared to the normal one. Fibrotic matrix, also induced the expression of epithelial-to-mesenchymal transition(EMT)-associated genes such as TWIST1, ACTA2, MMP9, CDH2, and VIMENTIN in the MTs as compared to the normal matrix. Conversely, the expression of CDH1 and hepatic maturation genes HNF4A, ALB, CYP3A4 was decreased in the MTs when the fibrotic matrix was used. Furthermore, the fibrotic matrix increased the migration of the MTs and their secretion of alpha-fetoprotein. Conclusions: Our findings suggest a regulatory role for the fibrotic matrix in promoting cancerous phenotype, which could potentially accelerate the progression of malignancy in the liver.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
Degenerative spine pathologies,including intervertebral disc(IVD)degeneration,present a significant healthcare challenge due to their association with chronic pain and disability.This study explores an innovative appr...Degenerative spine pathologies,including intervertebral disc(IVD)degeneration,present a significant healthcare challenge due to their association with chronic pain and disability.This study explores an innovative approach to IVD regeneration utilizing 3D bioprinting technology,specifically visible light-based digital light processing,to fabricate tissue scaffolds that closely mimic the native architecture of the IVD.Utilizing a hybrid bioink composed of gelatin methacrylate(GelMA)and poly(ethylene glycol)diacrylate(PEGDA)at a 10%concentration,we achieved enhanced printing fidelity and mechanical properties suitable for load-bearing applications such as the IVD.Preconditioning rat bone marrow-derived mesenchymal stem cell spheroids with chondrogenic media before incorporating them into the GelMA-PEGDA scaffold further promoted the regenerative capabilities of this system.Our findings demonstrate that this bioprinted scaffold not only supports cell viability and integration but also contributes to the restoration of disc height in a rat caudal disc model without inducing adverse inflammatory responses.The study underscores the potential of combining advanced bioprinting techniques and cell preconditioning strategies to develop effective treatments for IVD degeneration and other musculoskeletal disorders,highlighting the need for further research into the dynamic interplay between cellular migration and the hydrogel matrix.展开更多
The commercial ZK 60 magnesium alloy with extruded state experienced aging heat treatment(T 6)was dynamically loaded at strain rate of 3000 s−1 by means of the split Hopkinson pressure bar(SHPB)in this paper.Transmiss...The commercial ZK 60 magnesium alloy with extruded state experienced aging heat treatment(T 6)was dynamically loaded at strain rate of 3000 s−1 by means of the split Hopkinson pressure bar(SHPB)in this paper.Transmission electron microscopy(TEM)observations showed that the precipitatedβ′_(1) phases partially dissolved(spheroidized)with blurred interfaces within 160μs at 3000 s^(−1).The average length and diameter of the rod-shapedβ′_(1) phase particles were 48.5 and 9.8 nm after the T 6 heat treatment;while the average diameter of the sphericalβ′_(1) phases changed to 8.8 nm after loading.The deformedβ′_(1) phase generated larger lattice distortion energy than Mg matrix under high strain rate loading.Therefore,the difference of free energy(the driving force of dissolution)between theβ′_(1) phase and the matrix increased,making the instantaneous dissolution of theβ′_(1) phase thermodynamically feasible.The dissolution(spheroidization)of theβ′_(1) phase particles was kinetically promoted because the diffusion rate of the solute Zn atoms was accelerated by combined actions of adiabatic temperature rise,high density of dislocations(vacancies)and high deviatoric stresses during high strain rate loading.The increase in hardness of ZK 60-T 6 alloy could be attributed to solid solution strengthening,dislocation strengthening and second phase particle strengthening.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
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.
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.
基金supported by the National Science&Technology Pillar Program of China(Grant No.2006BAE04B05-1)the Natural Science Foundation of Shanxi Province(Grant No.2012JQ6020)the Doctor Foundation of Xian University of Science & Technology of China(2011QDJ017)
文摘The low-strength and high-brittleness of AZ91 cast magnesium alloy mainly result from the coarse divorced eutectic phase. To solve these problems, the annealing treatment of AZ91 cast magnesium alloy was carried out at 415 ℃ and held for 24 h in this study and the alloy was then slowly cooled to room temperature in furnace. The microstructures of the alloy were observed using a metallographic microscope, a transmission electron microscopy and an emission scanning electron microscopy, respectively. The phase analysis was performed using the X-ray diffraction, and the tensile test of the specimen at ambient temperature was performed on a material test machine. The results indicate that the coarse divorced eutectic phase dissolves into the Mg matrix during the isothermal process, and the lamellarβ-Mg17AI12 phase precipitates from the magnesium solid solution with a type of pearlite precipitation during furnace cooling. Consequently, the spheroidizing treatment was carried out at 320℃ for 20 h following the annealing process and the lamellar β-Mg17A12 phase was spheroidized. Compared with the as-cast alloy, the strength and ductility of the AZ91 magnesium alloy are increased obviously after annealing treatment; the yield strength and tensile strength are increased to 137.8 MPa and 240.4 MPa from 102.9 MPa and 199.3 MPa, respectively; and the elongation is improved to 6.12% from 4.35%. After being spheroidized, the strength and hardness decrease a little, but the ductility is elevated to 7.23%. The nucleation, growth and spheroidizing mechanism of the lamellarβ-Mg12TAI12 phase were also discussed.
文摘The influences of Ce, K and Na on the structures and properties of Fe-W-C alloy were investigated, and the idea estimating spheroidizing effect of carbides using circular degree(C.D) was put forward. The result shows that eutectic carbide turns into sphericity from network after modification, carbide is refined and uniformly distributed and C.D of eutectic carbide increases. The mechanism of carbide spheroidizing was analyzed. The impact toughness and abrasion resistance of Fe-W-C obviously improve with the rise of C.D of carbides. The service life of modified Fe-W-C roll is 30% higher than that of high chromium cast iron roll, while its production cost is reduced by 30%.
基金support from the National Natural Science Foundation of China(Nos.51474153 and 51574175)Ph.D.Programs Foundation of Ministry of Education of the People’s Republic of China(No.20111402110004)Natural Science Foundation of Shanxi Province(Nos.2009011028-3 and 2012011022-1)
文摘The spheroidizing mechanism of W-phase in the Mg–Zn–Y–Mn–（B） alloys during solid-solution treatment was investigated by using kinetic methodologies. The microstructure and mechanical properties of heat-treated Mg_（94）Zn_（2.5）-Y_（2.5）Mn_1 alloy containing 0.003 wt% B were compared with heat-treated Mg_（94）Zn_（2.5）-Y_（2.5）Mn_1 alloy. The heat-treated Mg_（94）Zn_（2.5）-Y_（2.5）Mn_1 alloy with 0.003 wt% B contained fine and uniform W-phase particles, which exhibited optimal mechanical performance. The ultimate tensile strength, yield strength and elongation were 287.7, 125.5 MPa and 21.1%,respectively.
文摘Bond-length-difference (BLD) analysis results show that austenrte and cementite containing Mg, Zr. S have very different valence electron structures from Fe -C austenite and cementite. We find that this difference is the tie of absorption hypothesis, surface tension hypothesis, undercooling hypothesis in graphite spheroidizing theory. By using "the model of valence electron theory of drag-like effect" in our previous paper in crystallization theory, the spheroidizing effect of Mg and Zr and the anti-spheroidizing effect of S can be explained with the valence electron structure data of phases. Therefore, electron theory of graphite spheroidizing can be advanced.
文摘Liposarcoma is one of the most common soft tissue sarcomas,however,its occurrence rate is still rare compared to other cancers.Due to its rarity,in vitro experiments are an essential approach to elucidate liposarcoma pathobiology.Conventional cell culture-based research(2D cell culture)is still playing a pivotal role,while several shortcomings have been recently under discussion.In vivo,mouse models are usually adopted for pre-clinical analyses with expectations to overcome the issues of 2D cell culture.However,they do not fully recapitulate human dedifferentiated liposarcoma(DDLPS)characteristics.Therefore,three-dimensional(3D)culture systems have been the recent research focus in the cell biology field with the expectation to overcome at the same time the disadvantages of 2D cell culture and in vivo animal models and fill in the gap between them.Given the liposarcoma rarity,we believe that 3D cell culture techniques,including 3D cell cultures/co-cultures,and Patient-Derived tumor Organoids(PDOs),represent a promising approach to facilitate liposarcoma investigation and elucidate its molecular mechanisms and effective therapy development.In this review,we first provide a general overview of 3D cell cultures compared to 2D cell cultures.We then focus on one of the recent 3D cell culture applications,Patient-Derived Organoids(PDOs),summarizing and discussing several PDO methodologies.Finally,we discuss the current and future applications of PDOs to sarcoma,particularly in the field of liposarcoma.
基金Supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico,No.307318/2023-0 and No.102035/2024-5Fundação de AmparoàPesquisa do Estado de São Paulo,No.2023/10843-7 and No 2019/21070-3Nanotechnology National Laboratory System 2.0,Ministry of Science,Technology,Innovation and Communication,No.442539/2019-3.
文摘BACKGROUND Glioblastoma multiforme(GBM)is the most aggressive and prevalent primary malignant brain tumor in adults,marked by poor prognosis and high invasiveness.Traditional GBM invasion assays,such as those involving mouse brain xenografts,are often time-consuming and limited in efficiency.In this context,stem cell-derived neural organoids(NOs)have emerged as advanced,threedimensional,human-relevant platforms that mimic the cellular architecture and microenvironment of the human brain.These models provide novel opportunities to investigate glioblastoma stem cell invasion,a critical driver of tumor progression and therapeutic resistance.AIM To evaluate studies using stem cell-derived NOs to model glioblastoma migration/invasion,focusing on methodologies,applications and therapeutic implications.METHODS We conducted a systematic review following PRISMA guidelines,searching PubMed and Scopus for studies published between March 2019 and March 2025 that investigated NOs in the context of glioblastoma invasion/migration.After screening 377 articles based on predefined inclusion and exclusion criteria,10 original research articles were selected for analysis.Extracted data were categorized into four analytical domains:(1)Tumor model formation;(2)NO characteristics;(3)NO differentiation protocols;and(4)Invasion/migration assessment methodologies.RESULTS The included studies exhibit significant methodological heterogeneity GBM model development,particularly regarding model type,cell source and culture conditions.Most studies(70%)used suspension cell models,while 30%employed spheroids,with most research focusing on patient-derived glioblastoma stem cells.NOs were predominantly generated from human induced pluripotent stem cells using both guided and unguided differentiation protocols.Confocal fluorescence microscopy was the primary method used for assessing invasion,revealing invasion depths of up to 300μm.Organoid maturity and co-culture duration influenced results,while key factors for model optimization included tumor cell density,organoid age and extracellular matrix composition.Some studies also tested therapeutic strategies such as Zika virus and microRNA modulation.Collectively,findings support the utility of NOs as effective tools for studying GBM behavior and therapeutic responses in a humanized three-dimensional context.CONCLUSION Human NOs represent promising platforms for modeling glioblastoma invasion in a humanized three-dimensional environment.However,a limited number of studies and methodological heterogeneity hinder reproducibility.Protocol standardization is essential to enhance the translational application of these models.
基金supported by the funding from the Shi Changxu Innovation Center for Advanced Materials(No.SCXKFJJ202210)the National Natural Science Foundation of China(No.52271043)+2 种基金the Youth Innovation Promotion Association of the Chinese Academy of Sciences(No.2021193)the Liaoning Province Excellent Youth Foundation(No.2024JH3/10200021)the Liaoning Revitalization Talents Program(No.XLYC2403094).
文摘For a long time,the conventional superplastic forming temperature for Ti alloys is generally too high(~900-920℃),which leads to too long production cycles,heavy surface oxidation,and property reduction.In this study,an ultrafine bimodal microstructure,consisting of ultrafine equiaxed microstructure(0.66μm)and 43.3%lamellar microstructure,was achieved in the Ti-6Al-4V alloy by friction stir processing(FSP).The low-temperature superplastic behavior and deformation mechanism of the FSP Ti-6Al-4V alloy were investigated at temperatures of 550-675℃and strain rates ranging from 1×10^(−4)to 3×10^(−3)s^(−1).The FSP alloy exhibited superplastic elongations of>200%at the temperature range from 550 to 650℃,and an optimal superplastic elongation of 611%was achieved at 625℃and 1×10^(−4)s^(−1).This is the first time to report the low-temperature superplasticity of the bimodal microstructure in Ti alloys.Grain boundary sliding was identified as the dominant deformation mechanism,which was effectively accommodated by the comprehensive effect of dislocation-inducedβphase precipitation and dynamic spheroidization of the lamellar structure.This study provides a novel insight into the low-temperature superplastic deformation behavior of the bimodal microstructure.
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 grants from Royan In-stitute(grant No.400000200)Bahar Tashkhis Teb Co.(BTT,9703,9809,and 9903)。
文摘Background: Despite considerable advancements in identifying factors contributing to the development of hepatocellular carcinoma(HCC), the pathogenesis of HCC remains unclear. In many cases, HCC is a consequence of prolonged liver fibrosis, resulting in the formation of an intricate premalignant microenvironment. The accumulation of extracellular matrix(ECM) is a hallmark of premalignant microenvironment. Given the critical role of different matrix components in regulating cell phenotype and function, this study aimed to elucidate the interplay between the fibrotic matrix and malignant features in HCC. Methods: Liver tissues from both control(normal) and carbon tetrachloride(CCl_(4))-induced fibrotic rats were decellularized using sodium dodecyl sulfate(SDS) and Triton X-100. The resulting hydrogel from decellularized ECM was processed into micro-particles via the water-in-oil emulsion method. Microparticles were subsequently incorporated into three-dimensional liver biomimetic micro-tissues(MTs) comprising Huh-7 cells, human umbilical vein endothelial cells(HUVECs), and LX-2 cells. The MTs were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium(MTS) assay at day 11, immunofluorescence staining, immunoblotting, and spheroid migration assay at day 14 after co-culture. Results: Fibrotic matrix from CCl4-treated rat livers significantly enhanced the growth rate of the MTs and their expression of CCND1 as compared to the normal one. Fibrotic matrix, also induced the expression of epithelial-to-mesenchymal transition(EMT)-associated genes such as TWIST1, ACTA2, MMP9, CDH2, and VIMENTIN in the MTs as compared to the normal matrix. Conversely, the expression of CDH1 and hepatic maturation genes HNF4A, ALB, CYP3A4 was decreased in the MTs when the fibrotic matrix was used. Furthermore, the fibrotic matrix increased the migration of the MTs and their secretion of alpha-fetoprotein. Conclusions: Our findings suggest a regulatory role for the fibrotic matrix in promoting cancerous phenotype, which could potentially accelerate the progression of malignancy in the liver.
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supported by NIH Grant(T32GM065841),Mayo Foundation for Education and Research.
文摘Degenerative spine pathologies,including intervertebral disc(IVD)degeneration,present a significant healthcare challenge due to their association with chronic pain and disability.This study explores an innovative approach to IVD regeneration utilizing 3D bioprinting technology,specifically visible light-based digital light processing,to fabricate tissue scaffolds that closely mimic the native architecture of the IVD.Utilizing a hybrid bioink composed of gelatin methacrylate(GelMA)and poly(ethylene glycol)diacrylate(PEGDA)at a 10%concentration,we achieved enhanced printing fidelity and mechanical properties suitable for load-bearing applications such as the IVD.Preconditioning rat bone marrow-derived mesenchymal stem cell spheroids with chondrogenic media before incorporating them into the GelMA-PEGDA scaffold further promoted the regenerative capabilities of this system.Our findings demonstrate that this bioprinted scaffold not only supports cell viability and integration but also contributes to the restoration of disc height in a rat caudal disc model without inducing adverse inflammatory responses.The study underscores the potential of combining advanced bioprinting techniques and cell preconditioning strategies to develop effective treatments for IVD degeneration and other musculoskeletal disorders,highlighting the need for further research into the dynamic interplay between cellular migration and the hydrogel matrix.
基金Projects(51871243,51574290)supported by the National Natural Science Foundation of ChinaProject(ASSIKFJJ202304001)supported by the Open Fund of the National Key Laboratory of Strength and Structural Integrity,China+3 种基金Project(HT-CSNS-DG-CD-0092/2021)supported by the Guangdong-Hong Kong-Macao Joint Laboratory for Neutron Scattering Science and Technology,ChinaProject(2022KF-08)supported by the Hubei Longzhong Laboratory,ChinaProject(22kfgk06)supported by the Shock and Vibration of Engineering Materials and Structures Key Laboratory of Sichuan Province,ChinaProject(PBSKL2022C01)supported by the State Key Laboratory of Precision Blasting and Hubei Key Laboratory of Blasting Engineering,China。
文摘The commercial ZK 60 magnesium alloy with extruded state experienced aging heat treatment(T 6)was dynamically loaded at strain rate of 3000 s−1 by means of the split Hopkinson pressure bar(SHPB)in this paper.Transmission electron microscopy(TEM)observations showed that the precipitatedβ′_(1) phases partially dissolved(spheroidized)with blurred interfaces within 160μs at 3000 s^(−1).The average length and diameter of the rod-shapedβ′_(1) phase particles were 48.5 and 9.8 nm after the T 6 heat treatment;while the average diameter of the sphericalβ′_(1) phases changed to 8.8 nm after loading.The deformedβ′_(1) phase generated larger lattice distortion energy than Mg matrix under high strain rate loading.Therefore,the difference of free energy(the driving force of dissolution)between theβ′_(1) phase and the matrix increased,making the instantaneous dissolution of theβ′_(1) phase thermodynamically feasible.The dissolution(spheroidization)of theβ′_(1) phase particles was kinetically promoted because the diffusion rate of the solute Zn atoms was accelerated by combined actions of adiabatic temperature rise,high density of dislocations(vacancies)and high deviatoric stresses during high strain rate loading.The increase in hardness of ZK 60-T 6 alloy could be attributed to solid solution strengthening,dislocation strengthening and second phase particle strengthening.
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.
