The growing interest in additive manufacturing of GH4169 alloy was accompanied by the demand on spherical GH4169 powders with high performance.The powder particles were treated by radio frequency plasma with the diffe...The growing interest in additive manufacturing of GH4169 alloy was accompanied by the demand on spherical GH4169 powders with high performance.The powder particles were treated by radio frequency plasma with the different feeding rates.The microstructure and morphology,the particle size distribution of as-treated powders were studied by scanning electron microscopy and laser particle size analysis.It was demonstrated that GH4169 powders with extremely fine followability were obtained by radio frequency plasma spheroidization technology.With the same plasma parameters,the spheroidization efficiency of the particles varied with the feeding rates.When the rate of the powder feeding rates was too small,the excessive absorption of the heating by the powders caused vaporization,then the collection decreased.When the feeding rates was too large,the powder particles were insufficiently absorbed,resulting in defects in the powders.The microstructure of the as-treated spherical particles was mainly cell crystals,columnar crystals,and even microcrystals.Under the suitable plasma parameters,the resulting powders haved a slightly increased average particle size,excellent spheroidization,surface smoothness,followability,and bulk ratio.展开更多
Objectives:Chondrosarcoma is the most common type of primary bone sarcoma in adults with a high risk of local recurrence and metastasis.Chondrosarcomas are largely resistant to chemotherapy and radiotherapy,meaning th...Objectives:Chondrosarcoma is the most common type of primary bone sarcoma in adults with a high risk of local recurrence and metastasis.Chondrosarcomas are largely resistant to chemotherapy and radiotherapy,meaning that surgery is the mainstay of treatment for most patients.Therefore,new therapeutic targets are required.Cluster of differentiation 44(CD44)is a transmembrane protein that has roles in cell proliferation,adhesion and migration and is shown to be overexpressed in several cancer types.Consequently,this work was undertaken to understand whether CD44 could be a potential therapeutic target in chondrosarcoma.Methods:In this study,tissue sections from chondrosarcoma patients were evaluated for CD44 expression using immunohistochemical analysis.The relationship between CD44 expression in the patient tissue and overall and event-free survival was investigated.Clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)gene editing was used to generate a CD44 knockout chondrosarcoma cell line which was used for a spheroid invasion assay to understand the role of CD44 in chondrosarcoma cell invasion.Results:Cox multivariate analysis of CD44 expression in chondrosarcoma patient tissue revealed that high CD44 expression was linked to decreased overall(p<0.01)and event-free survival(p<0.01).The observed invasion of CD44 knockout cells in the spheroid assay was less than that of the wild type cells(p<0.001).Conclusions:The increased expression of CD44 in intermediate and high grade chondrosarcomas,as well as reduced invasion of CD44 knockout cells suggests that CD44 plays an important role in chondrosarcoma progression and metastasis.These findings support further investigation of CD44 as an imaging and/or therapeutic target for the management of chondrosarcoma.展开更多
Objective:Breast cancer remains one of the most prevalent malignancies among women worldwide,and despite advances in therapy and treatment options,tumour relapse and metastasis remain major clinical challenges,largely...Objective:Breast cancer remains one of the most prevalent malignancies among women worldwide,and despite advances in therapy and treatment options,tumour relapse and metastasis remain major clinical challenges,largely driven by the breast cancer stem cells(BCSCs)niche that resists conventional treatments and regenerates tumours.In breast cancer,where approximately 30%of patients who initially respond to treatment ultimately relapse and die of metastatic disease,targeting BCSCs is critical for improving patient outcomes.Cyclin-dependent kinase inhibitor 1A/p21(CDKN1A/p21)is a multifunctional protein that is known primarily for its role in regulating the cell cycle in response to DNA damage.However,in this study,we aimed to explore the role of CDKN1A/p21 in the survival and expansion of BCSCs.Methods:We used three-dimensional in vitro models to assess the influence of CDKN1A/p21 expression on the survival of BCSCs both under basal conditions and after oxidative damage.Spatial transcriptomics analysis and chromatin immunoprecipitation-quantitative PCR(qPCR)were used to investigate the role of CDKN1A/p21 in the regulation and control of BCSC gene expression signatures.Results:We demonstrated that alterations in CDKN1A/p21 expression affect the ability of breast cancer cells to grow and survive after oxidative damage.Mechanistically,we found that CDKN1A/p21 directly binds to the promoter and regulates the expression of CD44,SPP1,and TMSB10,a combination gene signature that is associated with a greater probability of recurrence and metastasis in breast cancer patients.Conclusions:We propose that changes in gene regulation mediated by CDKN1A/p21 possibly contribute to cancer stem cell survival after oxidative damage,thus making CDKN1A/p21 a promising target for future drug discovery projects aimed at addressing the issue of therapeutic resistance and breast cancer metastasis.展开更多
Traditional heat treatment methods require a significant amount of time and energy to affect atomic diffusion and enhance the spheroidization process of carbides in bearing steel,while pulsed current can accelerate at...Traditional heat treatment methods require a significant amount of time and energy to affect atomic diffusion and enhance the spheroidization process of carbides in bearing steel,while pulsed current can accelerate atomic diffusion to achieve ultra-fast spheroidization of carbides.However,the understanding of the mechanism by which different pulse current parameters regulate the dissolution behavior of carbides requires a large amount of experimental data to support,which limits the application of pulse current technology in the field of heat treatment.Based on this,quantify the obtained pulse current processing data to create an important dataset that could be applied to machine learning.Through machine learning,the mechanism of mutual influence between carbide regulation and various factors was elucidated,and the optimal spheroidization process parameters were determined.Compared to the 20 h required for traditional heat treatment,the application of pulsed electric current technology achieved ultra-fast spheroidization of GCr15 bearing steel within 90 min.展开更多
Cellular spheroids,closely resembling native tissue microenvironments,have emerged as pivotal constructs in biomedicine as they can facilitate complex cell-cell and cell-matrix interactions.However,current methods for...Cellular spheroids,closely resembling native tissue microenvironments,have emerged as pivotal constructs in biomedicine as they can facilitate complex cell-cell and cell-matrix interactions.However,current methods for constructing spheroid assembloids with spatial arrangement or heterogeneous structures are limited,which has become a barrier for studying tissue engineering and in vitro disease modeling.Here,we demonstrate an acoustofluidic pick-and-place operation system capable of spatially assembling of spheroids into desired patterns in both two dimensional(2D)and three dimensional(3D)spaces.The underlying physical mechanism of the device is systematically studied to explain the interrelationship between trapping cell spheroids,acoustic streaming,and the acoustic radiation force(ARF)induced by the acoustically activated microneedle.We exploit these mechanisms to successfully transfer cellular spheroids into hydrogel solutions,enabling them to be precisely patterned and fused into assembloids of predefined shapes.Besides,we demonstrate arranging MC3T3-E1 cellular spheroids into a ring shape to fabricate the osteogenic tissues.Besides,a co-culture model involving tumor cells(MCF-7)and normal human dermal fibroblasts(NHDFs)is constructed to validate our method’s ability to reconstruct heterogeneous tumor model,revealing that the fibroblast spheroids promote tumor spheroid invasion.Our method holds significant potential prospects in regenerative medicine,disease model construction and drug screening.展开更多
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
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
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
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
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
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(CCl4)-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
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 1×10−4to 3×10−3s−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 1×10−4s−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
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
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
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
The influence of solution treatment on the microstructure and properties of Mg2Si/AZ91D composites fabricated from Mg-SiO2 system via in-situ processing method was investigated.The results show that coarse Chinese scr...The influence of solution treatment on the microstructure and properties of Mg2Si/AZ91D composites fabricated from Mg-SiO2 system via in-situ processing method was investigated.The results show that coarse Chinese script shape Mg2Si phases can be formed by adding SiO2 into AZ91D magnesium alloy with Si content up to 1.5% of the alloy melt.During solution treatment,the morphology and distribution of the coarse Chinese script shape Mg2Si phases are modified.Meanwhile,the β-Mg17Al12 phase is dissolved into the magnesium matrix.With increasing holding time,the coarse Mg2Si phases tend to dissolve,break and spheroidize.After solution treatment at 420 ℃ for 16 h,Mg2Si phases become the finest and relatively well-distributed phase.The tensile strength and elongation are increased by 14.9% and 38.9%,respectively.It is believed that the Mg2Si phases continuously dissolve and break,and finally the spheroidized Mg2Si particles are obtained due to the interface tension of Mg2Si/Mg interface.展开更多
The microstructure evolution and its effect on flow stress of TC17 alloy during deformation in the α+β two-phase region were investigated via microstructure characterization and isothermal compression tests. Results...The microstructure evolution and its effect on flow stress of TC17 alloy during deformation in the α+β two-phase region were investigated via microstructure characterization and isothermal compression tests. Results showed that the spheroidized rate of α phase at 820 and 850℃ slightly increased with increasing strain. With increasing deformation temperature, the spheroidized rate of α phase showed a slight increasing trend, but the volume fraction of α phase significantly decreased. The flow stress at 780 ℃ and 1 s^-1 decreased continuously and steady state condition was not achieved up to strain of 1.2 due to dislocation annihilation and α lamellae rotation. Under this condition, the dynamic spheroidization was retarded. At the deformation temperatures of 820 and 850℃, and a strain rate of 1 s^-1, a steady state flow stress was observed at strains above 0.8 due to the balance between work hardening and dynamic softening. The dynamic softening was attributed to the α lamellae rotation, dynamic recovery and a little spheroidization.展开更多
The improvement of hole-expansion properties for medium carbon steels by ultra fast cooling (UFC) after hot strip rolling was investigated.It was found that finely dispersed spherical cementite could be formed after...The improvement of hole-expansion properties for medium carbon steels by ultra fast cooling (UFC) after hot strip rolling was investigated.It was found that finely dispersed spherical cementite could be formed after ultra fast cooling , coiling and annealing treatment.Tensile strength of the steel after annealing was measured to be about 440MPa.During hole-expansion test , cracks were observed in the edge region around the punched hole because necking or cracking took place when tangential elongation exceeded the forming limit.Cracks were mainly formed by the coalescence of micro-voids.Fine and homogeneous microstructure comprised of ferrite and spheroidized cementite could increase elongation values of the tested sheets by suppressing the combination of the adjacent micro-voids , resulting in the improved hole-expansion property.展开更多
The spheroidization behavior of the dendritic b.c.c, phase dispersed in a bulk metallic glass (BMG) matrix was investigated through applying semi-solid isothermal processing and a subsequent rapid quenching procedur...The spheroidization behavior of the dendritic b.c.c, phase dispersed in a bulk metallic glass (BMG) matrix was investigated through applying semi-solid isothermal processing and a subsequent rapid quenching procedure to a Zr-basedβ-phase composite. The Zr-based composite with the composition of Z%62Ti138NbsoCuegNi5.6Be125 was prefabricated by a water-cooled copper mold-casting method and characterized by X-ray diffraction (XRD) and scanning electron microscope (SEM). The results show that the composite consists of a glassy matrix and uniformly distributed fine dendrites of theβ-Zr solid solution with the body-centered-cubic (b.c.c.) structure. Based on the differential scanning calorimeter (DSC) examination results, and in view of the b.c.c.β-Zr to h.c.p, α-Zr phase transition temperature, a semi-solid holding temperature of 900 ℃ was determined. After reheating the prefabricated composite to the semi-solid temperature, followed by an isothermal holding process at this temperature for 5 min, and then quenching the semi-solid mixture into iced-water; the two-phase microstructure composed of a BMG matrix and uniformly dispersed spherical b.c.c.β-Zr particles with a high degree of sphericity was achieved. The present spheroidization transition is a thermodynamically autonomic behavior, and essentially a diffusion process controlled by kinetic factors; and the formation of the BMG matrix should be attributed to the rapid quenching of the semi-solid mixture as well as the large glass-forming ability of the remaining melt in the semi-solid mixture.展开更多
基金supported financially by Yangjiang City Hardware Knives and Scissors and Nickel Alloy Industry Additive Manufacturing Technology Innovation Platform Construction(No.2015B020221002)Guangdong Province‘Sailing Plan’Introduces Special Funding for Innovation and Entrepreneurship Team(No.2015YT02G090)+1 种基金High-end Knives and Scissors Additive Manufacturing(3D Printing)of Engineering Technology Research Center in Guangdong Province(Grant No.509153168061)Initial Construction Subsidy for New Research and Development Institutions of Yangjiang City Hardware Knives and Scissors Industry and Technology Research(Grant No.611229498090)。
摘要The growing interest in additive manufacturing of GH4169 alloy was accompanied by the demand on spherical GH4169 powders with high performance.The powder particles were treated by radio frequency plasma with the different feeding rates.The microstructure and morphology,the particle size distribution of as-treated powders were studied by scanning electron microscopy and laser particle size analysis.It was demonstrated that GH4169 powders with extremely fine followability were obtained by radio frequency plasma spheroidization technology.With the same plasma parameters,the spheroidization efficiency of the particles varied with the feeding rates.When the rate of the powder feeding rates was too small,the excessive absorption of the heating by the powders caused vaporization,then the collection decreased.When the feeding rates was too large,the powder particles were insufficiently absorbed,resulting in defects in the powders.The microstructure of the as-treated spherical particles was mainly cell crystals,columnar crystals,and even microcrystals.Under the suitable plasma parameters,the resulting powders haved a slightly increased average particle size,excellent spheroidization,surface smoothness,followability,and bulk ratio.
基金funded by the Engineering and Physical Sciences Research Council,EP/T517914/1supported by a National Institute for Health and Care Research Academic Clinical Fellowship during this research.
摘要Objectives:Chondrosarcoma is the most common type of primary bone sarcoma in adults with a high risk of local recurrence and metastasis.Chondrosarcomas are largely resistant to chemotherapy and radiotherapy,meaning that surgery is the mainstay of treatment for most patients.Therefore,new therapeutic targets are required.Cluster of differentiation 44(CD44)is a transmembrane protein that has roles in cell proliferation,adhesion and migration and is shown to be overexpressed in several cancer types.Consequently,this work was undertaken to understand whether CD44 could be a potential therapeutic target in chondrosarcoma.Methods:In this study,tissue sections from chondrosarcoma patients were evaluated for CD44 expression using immunohistochemical analysis.The relationship between CD44 expression in the patient tissue and overall and event-free survival was investigated.Clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)gene editing was used to generate a CD44 knockout chondrosarcoma cell line which was used for a spheroid invasion assay to understand the role of CD44 in chondrosarcoma cell invasion.Results:Cox multivariate analysis of CD44 expression in chondrosarcoma patient tissue revealed that high CD44 expression was linked to decreased overall(p<0.01)and event-free survival(p<0.01).The observed invasion of CD44 knockout cells in the spheroid assay was less than that of the wild type cells(p<0.001).Conclusions:The increased expression of CD44 in intermediate and high grade chondrosarcomas,as well as reduced invasion of CD44 knockout cells suggests that CD44 plays an important role in chondrosarcoma progression and metastasis.These findings support further investigation of CD44 as an imaging and/or therapeutic target for the management of chondrosarcoma.
基金supported by the“Ramon y Cajal”Fellowship(RYC2021-030923-I)awarded to R.W.by the AIRC IG-2022 grant 27712 awarded to R.F.A.T.P was supported by AECC Summer Laboratory Practices 2024,PPLAB247653TOMA.
摘要Objective:Breast cancer remains one of the most prevalent malignancies among women worldwide,and despite advances in therapy and treatment options,tumour relapse and metastasis remain major clinical challenges,largely driven by the breast cancer stem cells(BCSCs)niche that resists conventional treatments and regenerates tumours.In breast cancer,where approximately 30%of patients who initially respond to treatment ultimately relapse and die of metastatic disease,targeting BCSCs is critical for improving patient outcomes.Cyclin-dependent kinase inhibitor 1A/p21(CDKN1A/p21)is a multifunctional protein that is known primarily for its role in regulating the cell cycle in response to DNA damage.However,in this study,we aimed to explore the role of CDKN1A/p21 in the survival and expansion of BCSCs.Methods:We used three-dimensional in vitro models to assess the influence of CDKN1A/p21 expression on the survival of BCSCs both under basal conditions and after oxidative damage.Spatial transcriptomics analysis and chromatin immunoprecipitation-quantitative PCR(qPCR)were used to investigate the role of CDKN1A/p21 in the regulation and control of BCSC gene expression signatures.Results:We demonstrated that alterations in CDKN1A/p21 expression affect the ability of breast cancer cells to grow and survive after oxidative damage.Mechanistically,we found that CDKN1A/p21 directly binds to the promoter and regulates the expression of CD44,SPP1,and TMSB10,a combination gene signature that is associated with a greater probability of recurrence and metastasis in breast cancer patients.Conclusions:We propose that changes in gene regulation mediated by CDKN1A/p21 possibly contribute to cancer stem cell survival after oxidative damage,thus making CDKN1A/p21 a promising target for future drug discovery projects aimed at addressing the issue of therapeutic resistance and breast cancer metastasis.
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).
摘要Traditional heat treatment methods require a significant amount of time and energy to affect atomic diffusion and enhance the spheroidization process of carbides in bearing steel,while pulsed current can accelerate atomic diffusion to achieve ultra-fast spheroidization of carbides.However,the understanding of the mechanism by which different pulse current parameters regulate the dissolution behavior of carbides requires a large amount of experimental data to support,which limits the application of pulse current technology in the field of heat treatment.Based on this,quantify the obtained pulse current processing data to create an important dataset that could be applied to machine learning.Through machine learning,the mechanism of mutual influence between carbide regulation and various factors was elucidated,and the optimal spheroidization process parameters were determined.Compared to the 20 h required for traditional heat treatment,the application of pulsed electric current technology achieved ultra-fast spheroidization of GCr15 bearing steel within 90 min.
基金supported by National Natural Science Foundation of China(Grant No.12032015,12121002,and 12402062)Natural Science Foundation of Shanghai(Grant No.24ZR1434900)+4 种基金The Innovation Program of Shanghai Municipal Education Commission(Grant No.2019-01-07-00-02-E00030)Shanghai Pilot Program for Basic Research—Shanghai Jiao Tong University(Grant No.21TQ1400203)the Open Research Project Programme of the Science and Technology Development Fund(Grant No.006/2022/ALC)the Macao Centre for Research and Development in Advanced Materials(University of Macao)(Grant.No.MCRDAM-IAPME(UM)-2022-2024/ORP/002/2023)the Science and Technology Commission of Shanghai Municipality(Grant No.20DZ2220400).
摘要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。
摘要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.
摘要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 NIH Grant(T32GM065841),Mayo Foundation for Education and Research.
摘要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.
摘要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Supported by Universiti Putra Malaysia,Serdang,Selangor,Malaysia(UPM/700-2/1/GPB/2017/9549900).
摘要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financially supported by grants from Royan In-stitute(grant No.400000200)Bahar Tashkhis Teb Co.(BTT,9703,9809,and 9903)。
摘要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(CCl4)-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 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).
摘要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 1×10−4to 3×10−3s−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 1×10−4s−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).
摘要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).
摘要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.
摘要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).
摘要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Project (BG2007030) supported by High-tech Research Program of Jiangsu Province, ChinaProject (07KJA43008) supported by the Natural Science Foundation of Jiangsu Province, ChinaProject (20070299004) supported by the Specialized Research Fund for the Doctoral Program of Higher Education of China
摘要The influence of solution treatment on the microstructure and properties of Mg2Si/AZ91D composites fabricated from Mg-SiO2 system via in-situ processing method was investigated.The results show that coarse Chinese script shape Mg2Si phases can be formed by adding SiO2 into AZ91D magnesium alloy with Si content up to 1.5% of the alloy melt.During solution treatment,the morphology and distribution of the coarse Chinese script shape Mg2Si phases are modified.Meanwhile,the β-Mg17Al12 phase is dissolved into the magnesium matrix.With increasing holding time,the coarse Mg2Si phases tend to dissolve,break and spheroidize.After solution treatment at 420 ℃ for 16 h,Mg2Si phases become the finest and relatively well-distributed phase.The tensile strength and elongation are increased by 14.9% and 38.9%,respectively.It is believed that the Mg2Si phases continuously dissolve and break,and finally the spheroidized Mg2Si particles are obtained due to the interface tension of Mg2Si/Mg interface.
基金Project(51575446)supported by the National Natural Science Foundation of ChinaProject(2017KJXX-27)supported by the Shaanxi Province Youth Science and Technology New Star Plan,ChinaProject(3102017AX003)supported by the Fundamental Research Funds for the Central Universities,China
摘要The microstructure evolution and its effect on flow stress of TC17 alloy during deformation in the α+β two-phase region were investigated via microstructure characterization and isothermal compression tests. Results showed that the spheroidized rate of α phase at 820 and 850℃ slightly increased with increasing strain. With increasing deformation temperature, the spheroidized rate of α phase showed a slight increasing trend, but the volume fraction of α phase significantly decreased. The flow stress at 780 ℃ and 1 s^-1 decreased continuously and steady state condition was not achieved up to strain of 1.2 due to dislocation annihilation and α lamellae rotation. Under this condition, the dynamic spheroidization was retarded. At the deformation temperatures of 820 and 850℃, and a strain rate of 1 s^-1, a steady state flow stress was observed at strains above 0.8 due to the balance between work hardening and dynamic softening. The dynamic softening was attributed to the α lamellae rotation, dynamic recovery and a little spheroidization.
基金Item Sponsored by National Natural Science Foundation of China ( 51004037 )Fundamental Research Funds for Central Universities of China ( N090307002 )
摘要The improvement of hole-expansion properties for medium carbon steels by ultra fast cooling (UFC) after hot strip rolling was investigated.It was found that finely dispersed spherical cementite could be formed after ultra fast cooling , coiling and annealing treatment.Tensile strength of the steel after annealing was measured to be about 440MPa.During hole-expansion test , cracks were observed in the edge region around the punched hole because necking or cracking took place when tangential elongation exceeded the forming limit.Cracks were mainly formed by the coalescence of micro-voids.Fine and homogeneous microstructure comprised of ferrite and spheroidized cementite could increase elongation values of the tested sheets by suppressing the combination of the adjacent micro-voids , resulting in the improved hole-expansion property.
基金supported by the Natural Science Research Projects of The Education Department of Henan Province,China(Grant No.2008A430010)the R&D start-up projects of high-level talents of North China University of Water Resources and Electric Power(Grant No.200709)
摘要The spheroidization behavior of the dendritic b.c.c, phase dispersed in a bulk metallic glass (BMG) matrix was investigated through applying semi-solid isothermal processing and a subsequent rapid quenching procedure to a Zr-basedβ-phase composite. The Zr-based composite with the composition of Z%62Ti138NbsoCuegNi5.6Be125 was prefabricated by a water-cooled copper mold-casting method and characterized by X-ray diffraction (XRD) and scanning electron microscope (SEM). The results show that the composite consists of a glassy matrix and uniformly distributed fine dendrites of theβ-Zr solid solution with the body-centered-cubic (b.c.c.) structure. Based on the differential scanning calorimeter (DSC) examination results, and in view of the b.c.c.β-Zr to h.c.p, α-Zr phase transition temperature, a semi-solid holding temperature of 900 ℃ was determined. After reheating the prefabricated composite to the semi-solid temperature, followed by an isothermal holding process at this temperature for 5 min, and then quenching the semi-solid mixture into iced-water; the two-phase microstructure composed of a BMG matrix and uniformly dispersed spherical b.c.c.β-Zr particles with a high degree of sphericity was achieved. The present spheroidization transition is a thermodynamically autonomic behavior, and essentially a diffusion process controlled by kinetic factors; and the formation of the BMG matrix should be attributed to the rapid quenching of the semi-solid mixture as well as the large glass-forming ability of the remaining melt in the semi-solid mixture.