Mg-Gd-Y合金及其构件的组织与性能研究

目的针对VW103(Mg-10Gd-3Y)和VW63(Mg-6Gd-3Y)2种铸造镁合金,从材料微观结构入手,探讨分析2种合金力学性能差异性,获取了2种镁合金在工程应用中的铸造性能及其力学特性。方法采用热分析法和改进的裂纹环试样等方法,开展2种合金的凝固温度范围和铸造裂纹倾向研究。测量和分析其凝固温度范围、液态流动性、热态和冷态下的材料抗裂性能,获得Mg-Gd-Y稀土铸造镁合金的铸造特性;基于构件本体不同区域取样,获得Mg-Gd-Y合金在室温和150℃下的力学性能,并对整体铸件结构的承载能力和稳定性进行评估。结果在铸造性能方面,热态下脱模,VW103和VW632种合金均未出现开裂现象;冷态下脱模,VW103合金试样出现开裂。在力学性能方面,与VW103合金相比,VW63合金具有更好的综合力学性能,VW63合金铸件本体试样在高温(150℃)条件下拉伸性能均值为320 MPa,表现出优异的力学性能。结论VW63合金具有更好的力学性能和铸造性能,采用VW63合金、树脂砂反重力方法制备的整体铸件满足了结构承载能力需求,并且在测试过程中铸件位移(变形)与载荷和加载时间呈现出良好的线性关系,证实了VW63铸件的安全性与可靠性,可为VW63合金的后续应用提供参考。

Characterizing the tumor microenvironment at the single-cell level reveals a novel immune evasion mechanism in osteosarcoma

The immune microenvironment extensively participates in tumorigenesis as well as progression in osteosarcoma(OS).However,the landscape and dynamics of immune cells in OS are poorly characterized.By analyzing single-cell RNA sequencing(sc RNA-seq)data,which characterize the transcription state at single-cell resolution,we produced an atlas of the immune microenvironment in OS.The results suggested that a cluster of regulatory dendritic cells(DCs)might shape the immunosuppressive microenvironment in OS by recruiting regulatory T cells.We also found that major histocompatibility complex class I(MHC-I)molecules were downregulated in cancer cells.The findings indicated a reduction in tumor immunogenicity in OS,which can be a potential mechanism of tumor immune escape.Of note,CD24 was identified as a novel“don’t eat me”signal that contributed to the immune evasion of OS cells.Altogether,our findings provide insights into the immune landscape of OS,suggesting that myeloid-targeted immunotherapy could be a promising approach to treat OS.

Neuro-bone tissue engineering:emerging mechanisms,potential strategies,and current challenges

The skeleton is a highly innervated organ in which nerve fibers interact with various skeletal cells.Peripheral nerve endings release neurogenic factors and sense skeletal signals,which mediate bone metabolism and skeletal pain.In recent years,bone tissue engineering has increasingly focused on the effects of the nervous system on bone regeneration.Simultaneous regeneration of bone and nerves through the use of materials or by the enhancement of endogenous neurogenic repair signals has been proven to promote functional bone regeneration.Additionally,emerging information on the mechanisms of skeletal interoception and the central nervous system regulation of bone homeostasis provide an opportunity for advancing biomaterials.However,comprehensive reviews of this topic are lacking.Therefore,this review provides an overview of the relationship between nerves and bone regeneration,focusing on tissue engineering applications.We discuss novel regulatory mechanisms and explore innovative approaches based on nerve–bone interactions for bone regeneration.Finally,the challenges and future prospects of this field are briefly discussed.

临床试验用药品规范化管理的实践

为了更好地保障受试者的安全和临床试验的质量,根据我国《药物临床试验质量管理规范》(简称“GCP”),结合萍乡市人民医院(以下简称“我院”)临床试验用药品管理现状,我院探索建立了一套更加规范、科学的临床试验用药品管理模式,修订了药品管理制度、标准操作规程及预案,配备药品规范化管理设施设备,配备专人专职管理药品,并通过质量控制不断持续改进。实践证明依托GCP中心药房和专业科室小药库对试验用药品进行专人专职管理,可有效提升试验用药品的管理水平,因此建立临床试验用药品规范化管理模式是各临床试验机构发展的必然趋势。

ZM5镁合金阻燃与中间合金变质细化行为研究

采用光学显微镜等研究了Ca、Ce、Y阻燃元素,以及Al-8Ti-2C和Al-4C中间合金对ZM5合金显微组织及力学性能的影响。结果表明:复合添加阻燃元素比单独添加更有利于提高ZM5合金阻燃性能,复合添加0.5%Ce和0.5%Y时,合金燃点提高70℃;单独添加0.5%的Ca时,合金晶粒得到细化;同时添加0.5%的Ca和Al-4C中间合金时,ZM5合金抗拉强度、屈服强度和伸长率分别达到245 MPa、96 MPa和9.5%。

镁合金新材料及制备加工新技术发展与应用

镁合金是国际公认的最有潜力的轻量化材料之一,被誉为“21世纪绿色工程金属”,其突出的结构减重效果有望解决我国关键装备和重大工程中迫切的轻量化问题。本文综述了近年来镁合金新材料的发展、镁合金制备加工新技术进展以及镁合金的应用发展现状,对当前镁合金领域存在的缺点进行了总结,并对镁合金未来发展重点及主要任务进行了展望。

航空航天用高强度Mg-RE系合金的研究进展

近年来,镁稀土合金由于其高强度、低密度和高温性能良好等特点,在追求轻量化的航空航天产业当中受到越来越多的关注。总结当前主流的2系高强度Mg-RE合金(Mg-Gd和Mg-Y系合金)的性能特点、强化机制和研究进展,简要介绍其他Mg-RE合金的研究情况,最后回顾镁稀土合金在航空航天领域的应用。

Application of Finite Element Analysis for Investigation of Intervertebral Disc Degeneration:from Laboratory to Clinic

Due to the ethical concern and inability to detect inner stress distributions of intervertebral disc(IVD),traditional methods for investigation of intervertebral disc degeneration(IVDD)have significant limitations.Many researchers have demonstrated that finite element analysis(FEA)is an effective tool for the research of IVDD.However,the specific application of FEA for investigation of IVDD has not been systematically elucidated before.In the present review,we summarize the current finite element models(FEM)used for the investigation of IVDD,including the poroelastic non linear FEM,difTusive-reactive theory model and cell-activity coupled mechano-electrochemical theory model.We further elaborate the use of FEA for the research of IVDD pathogenesis especially for nutrition and biomechanics associated etiology,and the biological,biomechanical and clinical influences of IVDD.In addition,the application of FEA for evaluation and exploration of various treatments for IVDD is also elucidated.We conclude that FEA is an excellent technique for research of IVDD,which could be used to explore the etiology,biology and biomechanics of IVDD.In the future,FEA may help us to achieve the goal of individualized precision therapy.

Traumatic brain injury stimulates sympathetic tone-mediated bone marrow myelopoiesis to favor fracture healing

Traumatic brain injury(TBI)accelerates fracture healing,but the underlying mechanism remains largely unknown.Accumulating evidence indicates that the central nervous system(CNS)plays a pivotal role in regulating immune system and skeletal homeostasis.However,the impact of CNS injury on hematopoiesis commitment was overlooked.Here,we found that the dramatically elevated sympathetic tone accompanied with TBI-accelerated fracture healing;chemical sympathectomy blocks TBIinduced fracture healing.TBI-induced hypersensitivity of adrenergic signaling promotes the proliferation of bone marrow hematopoietic stem cells(HSCs)and swiftly skews HSCs toward anti-inflammation myeloid cells within 14 days,which favor fracture healing.Knockout ofβ3-orβ2-adrenergic receptor(AR)eliminate TBI-mediated anti-inflammation macrophage expansion and TBIaccelerated fracture healing.RNA sequencing of bone marrow cells revealed that Adrb2 and Adrb3 maintain proliferation and commitment of immune cells.Importantly,flow cytometry confirmed that deletion ofβ2-AR inhibits M2 polarization of macrophages at 7th day and 14th day;and TBI-induced HSCs proliferation was impaired inβ3-AR knockout mice.Moreover,β3-andβ2-AR agonists synergistically promote infiltration of M2 macrophages in callus and accelerate bone healing process.Thus,we conclude that TBI accelerates bone formation during early stage of fracture healing process by shaping the anti-inflammation environment in the bone marrow.These results implicate that the adrenergic signals could serve as potential targets for fracture management.

Infuence of urbanization on schistosomiasis infection risk in Anhui Province based on sixteen year’s longitudinal surveillance data:a spatio-temporal modelling study

Background Urbanization greatly afects the natural and social environment of human existence and may have a multifactoral impact on parasitic diseases.Schistosomiasis,a common parasitic disease transmitted by the snail Oncomelania hupensis,is mainly found in areas with population aggregations along rivers and lakes where snails live.Previous studies have suggested that factors related to urbanization may infuence the infection risk of schistosomiasis,but this association remains unclear.This study aimed to analyse the efect of urbanization on schistosomiasis infection risk from a spatial and temporal perspective in the endemic areas along the Yangtze River Basin in China.Methods County-level schistosomiasis surveillance data and natural environmental factor data covering the whole Anhui Province were collected.The urbanization level was characterized based on night-time light data from the Defense Meteorological Satellite Program Operational Linescan System(DMSP-OLS)and the National Polar-Orbiting Partnership’s Visible Infrared Imaging Radiometer Suite(NPP-VIIRS).The geographically and temporally weighted regression model(GTWR)was used to quantify the infuence of urbanization on schistosomiasis infection risk with the other potential risk factors controlled.The regression coefcient of urbanization was tested for signifcance(α=0.05),and the infuence of urbanization on schistosomiasis infection risk was analysed over time and across space based on signifcant regression coefcients.Variables studied included climate,soil,vegetation,hydrology and topography.Results The mean regression coefcient for urbanization(0.167)is second only to the leached soil area(0.300),which shows that the urbanization is the most important infuence factors for schistosomiasis infection risk besides leached soil area.The other important variables are distance to the nearest water source(0.165),mean minimum temperature(0.130),broadleaf forest area(0.105),amount of precipitation(0.073),surface temperature(0.066),soil bulk density(0.037)and grassland area(0.031).The infuence of urbanization on schistosomiasis infection risk showed a decreasing trend year by year.During the study period,the signifcant coefcient of urbanization level increased from−0.205 to−0.131.Conclusions The infuence of urbanization on schistosomiasis infection has spatio-temporal heterogeneous.The urbanization does reduce the risk of schistosomiasis infection to some extend,but the strength of this infuence decreases with increasing urbanization.Additionally,the efect of urbanization on schistosomiasis infection risk was greater than previous reported natural environmental factors.This study provides scientifc basis for understanding the infuence of urbanization on schistosomiasis,and also provides the feasible research methods for other similar studies to answer the issue about the impact of urbanization on disease risk.

Ferroptosis as a novel form of regulated cell death:Implications in the pathogenesis,oncometabolism and treatment of human cancer

The treatment of cancer mainly involves surgical excision supplemented by radiotherapy and chemotherapy.Chemotherapy drugs act by interfering with tumor growth and inducing the death of cancer cells.Anti-tumor drugs were developed to induce apoptosis,but some patient’s show apoptosis escape and chemotherapy resistance.Therefore,other forms of cell death that can overcome the resistance of tumor cells are important in the context of cancer treatment.Ferroptosis is a newly discovered iron-dependent,non-apoptotic type of cell death that is highly negatively correlated with cancer development.Ferroptosis is mainly caused by the abnormal increase in iron-dependent lipid reactive oxygen species and the imbalance of redox homeostasis.This review summarizes the progression and regulatory mechanism of ferroptosis in cancer and discusses its possible clinical applications in cancer diagnosis and treatment.

高Nb-TiAl合金的高温变形行为及其板材的性能

对高Nb-TiAl合金进行多步热压缩,研究其高温变形行为及其板材的性能。结果表明,热压缩变形后高Nb-TiAl合金的组织中等轴γ晶粒和α晶粒的增多、层片晶团的体积分数和尺寸降低,使其变形能力提高。根据这些结果确定了最优轧制工艺为应变速率低于0.5 s^(-1)、道次变形量前期应不高于25%、变形温度高于1150℃。选用上述工艺对其其进行5道次大变形量轧制,制备出表面质量良好、无缺陷的高Nb-TiAl合金板材,其尺寸为600 mm×85 mm×3 mm。这种板材具有双态组织,平均晶粒尺寸小于5μm,其室温屈服强度、抗拉强度和塑性分别为948 MPa、1084 MPa和0.94%,800℃下抗拉强度为758 MPa。

A semi-transparent selective undo algorithm for multi-user collaborative editors

Multi-user collaborative editors are useful computer-aided tools to support human-to-human collaboration.For multi-user collaborative editors,selective undo is an essential utility enabling users to undo any editing operations at any time.Collaborative editors usually adopt operational transformation(OT)to address concurrency and consistency issues.However,it is still a great challenge to design an efficient and correct OT algorithm capable of handling both normal do operations and user-initiated undo operations because these two kinds of operations can interfere with each other in various forms.In this paper,we propose a semi-transparent selective undo algorithm that handles both do and undo in a unified framework,which separates the processing part of do operations from the processing part of undo operations.Formal proofs are provided to prove the proposed algorithm under the well-established criteria.Theoretical analysis and experimental evaluation are conducted to show that the proposed algorithm outperforms the prior OT-based selective undo algorithms.

A core-shell composite pigment with rutile TiO_(2) intensification for UV inhibition

Organic pigments generlly have bright colors but poor ultraviolet(UV)resistance.To improve the UV for UVinhibition is proposed by afacile sol-gel method inthis work.Acore-shellstructure,witha homo resistance and extend the applications,a core-shell composite pigment with rutile Tio intensification geneous sol-gel TiO_(2) shell containing additional nanosized rutile TiO2 particles and with the pigment as the core,was established taking advantage of UV resistance of TiO2 and binding ability of sol-gel.While the sol-gel TiO2 shell alone has already shown obvious ultraviolet shielding effect,as tested over different sol-gel aging times and Tio2 loadings,the UV resistance of the fluorescent pigments was further enhanced by binding the nanosized rutile TiO2 in the sol-gel shell At a sol-gel TiO2 to rutile TiO2 ratio of 2:1,the UV exposure time is extended about eight times compared with that of the original pigment and twice as that of the modifed pigment with pure sol-gel TiO2 for the same color change.Therefore,the novel core-shell composite pigment intensified with nanosized rutile Tio2 particles is proved to be effcient in improving the uV resistance of organic pigments.

Soluble IL-2Rα correlates with imbalances of Th1/Th2 and Tc1/Tc2 cells in patients with acute brucellosis

Background Previous studies showed that soluble IL-2Rαis an important marker of cellular immune activation and might be a marker of treatment efficacy for children with brucellosis.However,data regarding adult patients with brucellosis were unknown.The aim of study was to explore the potential role of serum sIL-2Rαevaluating treatment responses in adult patients with brucellosis,and T cell immune status was also examined.Methods During January 2016–April 2017,30 patients with acute brucellosis from the Third People’s Hospital of Linfen in Shanxi Province and Beijing Di Tan Hospital,and 28 healthy controls were included in this study.Peripheral blood samples were collected before and after six weeks of antibiotic treatment.Serum sIL-2Rαlevels were measured by enzyme-linked immunosorbent assay,and the percentage of Th1,Th2,Tc1,Tc2,and Tregs was detected by flow cytometry after intracellular staining for cytokines(interferon-γand interleukin-4)and Foxp3 in T lymphocytes from peripheral blood.The obtained data were analyzed with Wilcoxon ranked sum tests for paired values,Mann-Whitney U-tests for comparisons between patients and healthy controls,and Spearman rank tests for correlation analyses.Results Serum sIL-2Rαlevels were significantly higher in patients than in controls(P=0.001).A significant decline was observed in patients after the cessation of treatment(P<0.001)and return to normal(P>0.05).Th1,Tc1,Th2,and Tc2 cell frequencies were higher in patients than in healthy subjects(P<0.05),while the Th1/Th2 and Tc1/Tc2 ratios were significantly lower(P=0.0305 and 0.0005,respectively)and returned to normal levels after treatment.In patients with acute brucellosis,serum sIL-2Rαlevels were negatively correlated with the Th1/Th2 ratio(r=−0.478,P=0.028),Tc1/Tc2 ratio(r=−0.677,P=0.001),and Tc1 percentage(r=−0.516,P=0.017).Serum sIL-2Rαand Tc2 percentages were positively correlated(r=0.442,P=0.045).Conclusions Based on the correlations with Th1/Th2 and Tc1/Tc2 ratios,serum sIL-2Rαlevels may reflect the immune response status.sIL-2Rαmay be a marker for therapeutic efficacy in acute brucellosis.

Decellularized Disc Hydrogels for hBMSCs tissue-specific differentiation and tissue regeneration

Tissue specificity,a key factor in the decellularized tissue matrix(DTM),has shown bioactive functionalities in tuning cell fate-e.g.,the differentiation of mesenchymal stem cells.Notably,cell fate is also determined by the living microenvironment,including material composition and spatial characteristics.Herein,two neighboring tissues within intervertebral discs,the nucleus pulposus(NP)and annulus fibrosus(AF),were carefully processed into DTM hydrogels(abbreviated DNP-G and DAF-G,respectively)to determine the tissue-specific effects on stem cell fate,such as specific components and different culturing methods,as well as in vivo regeneration.Distinct differences in their protein compositions were identified by proteomic analysis.Interestingly,the fate of human bone marrow mesenchymal stem cells(hBMSCs)also responds to both culturing methods and composition.Generally,hBMSCs cultured with DNP-G(3D)differentiated into NP-like cells,while hBMSCs cultured with DAF-G(2D)underwent AF-like differentiation,indicating a close correlation with the native microenvironments of NP and AF cells,respectively.Furthermore,we found that the integrin-mediated RhoA/LATS/YAP1 signaling pathway was activated in DAF-G(2D)-induced AF-specific differentiation.Additionally,the activation of YAP1 determined the tendency of NP-or AF-specific differentiation and played opposite regulatory effects.Finally,DNP-G and DAF-G specifically promoted tissue regeneration in NP degeneration and AF defect rat models,respectively.In conclusion,DNP-G and DAF-G can specifically determine the fate of stem cells through the integrin-mediated RhoA/LATS/YAP1 signaling pathway,and this tissue specificity is both compositional and spatial,supporting the utilization of tissue-specific DTM in advanced treatments of intervertebral disc degeneration.

Proper animal experimental designs for preclinical research of biomaterials for intervertebral disc regeneration

Low back pain is a vital musculoskeletal disease that impairs life quality,leads to disability and imposes heavy economic burden on the society,while it is greatly attributed to intervertebral disc degeneration(IDD).However,the existing treatments,such as medicines,chiropractic adjustments and surgery,cannot achieve ideal disc regeneration.Therefore,advanced bioactive therapies are implemented,including stem cells delivery,bioreagents administration,and implantation of biomaterials etc.Among these researches,few reported unsatisfying regenerative outcomes.However,these advanced therapies have barely achieved successful clinical translation.The main reason for the inconsistency between satisfying preclinical results and poor clinical translation may largely rely on the animal models that cannot actually simulate the human disc degeneration.The inappropriate animal model also leads to difficulties in comparing the efficacies among biomaterials in different reaches.Therefore,animal models that better simulate the clinical charateristics of human IDD should be acknowledged.In addition,in vivo regenerative outcomes should be carefully evaluated to obtain robust results.Nevertheless,many researches neglect certain critical characteristics,such as adhesive properties for biomaterials blocking annulus fibrosus defects and hyperalgesia that is closely related to the clinical manifestations,e.g,low back pain.Herein,in this review,we summarized the animal models established for IDD,and highlighted the proper models and parameters that may result in acknowledged IDD models.Then,we discussed the existing biomaterials for disc regeneration and the characteristics that should be considered for regenerating different parts of discs.Finally,well-established assays and parameters for in vivo disc regeneration are explored.

Corrigendum to‘Decellularized disc hydrogels for hBMSC tissue-specific differentiation and tissue regeneration’[Bioactive Materials 6(2021)3541-3556]

The authors regret missing out the below change in the acknowledgment section of the article.The original sentence reads as"This work was supported by the Major Research Plan of National Natural Science Foundation of China[No.91649204],the National Key Research and Development Program of China[2016YFC1100100],…"and the same has been corrected to"This work was supported by the National Key Research and Development Program of China[2016YFC1100100],the Major Research Plan of National Natural Science Foundation of China[No.91649204],…"and the same has been corrected to"This work was supported by the National Key Research and Development Program of China[2016YFC1100100],the Major Research Plan of National Natural Science Foundation of China[No.91649204],…".