Recent research progress in the mechanism and suppression of fusion welding-induced liquation cracking of nickel based superalloys

Nickel-based superalloys are extensively used in the crucial hot-section components of industrial gas turbines,aeronautics,and astronautics because of their excellent mechanical properties and corrosion resistance at high temperatures.Fusion welding serves as an effective means for joining and repairing these alloys;however,fusion welding-induced liquation cracking has been a challenging issue.This paper comprehensively reviewed recent liquation cracking,discussing the formation mechanisms,cracking criteria,and remedies.In recent investigations,regulating material composition,changing the preweld heat treatment of the base metal,optimizing the welding process parameters,and applying auxiliary control methods are effective strategies for mitigating cracks.To promote the application of nickel-based superalloys,further research on the combination impact of multiple elements on cracking prevention and specific quantitative criteria for liquation cracking is necessary.

Effect of icosahedral phase formation on the stress corrosion cracking(SCC)behaviors of the as-cast Mg-8%Li(in wt.%)based alloys

Through exploring the stress corrosion cracking(SCC)behaviors of the as-cast Mg-8%Li and Mg-8%Li-6%Zn-1.2%Y alloys in a 0.1 M NaCl solution,it revealed that the SCC susceptibility index(I_(SCC))of the Mg-8%Li alloy was 47%,whilst the I_(SCC)of the Mg-8%Li-6%Zn-1.2%Y alloy was 68%.Surface,cross-sectional and fractography observations indicated that for the Mg-8%Li alloy,theα-Mg/β-Li interfaces acted as the preferential crack initiation sites and propagation paths during the SCC process.With regard to the Mg-8%Li-6%Zn-1.2%Y alloy,the crack initiation sites included the I-phase and the interfaces of I-phase/β-Li andα-Mg/β-Li,and the preferential propagation paths were the I-phase/β-Li andα-Mg/β-Li interfaces.Moreover,the SCC of the two alloys was concerned with hydrogen embrittlement(HE)mechanism.

Exploring an eco-friendly approach to improve soil tensile behavior and cracking resistance

Soil tensile strength is a critical parameter governing the initiation and propagation of tensile cracking.This study proposes an eco-friendly approach to improve the tensile behavior and crack resistance of clayey soils.To validate the feasibility and efficacy of the proposed approach,direct tensile tests were employed to determine the tensile strength of the compacted soil with different W-OH treatment concentrations and water contents.Desiccation tests were also performed to evaluate the effectiveness of W-OH treatment in enhancing soil tensile cracking resistance.During this period,the effects of W-OH treatment concentration and water content on tensile properties,soil suction and microstructure were investigated.The tensile tests reveal that W-OH treatment has a significant impact on the tensile strength and failure mode of the soil,which not only effectively enhances the tensile strength and failure displacement,but also changes the brittle failure behavior into a more ductile quasi-brittle failure behavior.The suction measurements and mercury intrusion porosimetry(MIP)tests show that W-OH treatment can slightly reduce soil suction by affecting skeleton structure and increasing macropores.Combined with the microstructural analysis,it becomes evident that the significant improvement in soil tensile behavior through W-OH treatment is mainly attributed to the W-OH gel's ability to provide additional binding force for bridging and encapsulating the soil particles.Moreover,desiccation tests demonstrate that W-OH treatment can significantly reduce or even inhibit the formation of soil tensile cracking.With the increase of W-OH treatment concentration,the surface crack ratio and total crack length are significantly reduced.This study enhances a fundamental understanding of eco-polymer impacts on soil mechanical properties and provides valuable insight into their potential application for improving soil crack resistance.

Development and Catalytic Cracking Performance of Ultrastable Y Zeolite Rich in Secondary Pores

A novel ultra-stable zeolite, NSZ, rich in secondary pores was developed through the combination of gas-phase andmild hydrothermal methods. This zeolite was successfully tested in an industrial setting for the first time in the world. The porestructure characteristics of the NSZ zeolite prepared for industrial use were analyzed and characterized using BET. The resultsindicate a significant increase in the secondary pore volume of NSZ zeolite compared to the existing ultra-stable zeolite HSZ-5, which is produced through a conventional gas-phase method. The average secondary pore volume to total pore volume ratioin NSZ zeolite was found to be 58.96% higher. The catalytic cracking performance of NSZ zeolite was evaluated. The resultsshowed that the NSC-LTA catalyst, with NSZ as the active component, outperformed the HSC-LTA catalyst with HSZ-5 zeolitein terms of obtaining more high-value products (gasoline and liquefied petroleum gas) during the hydrogenated light cycle oilprocessing. Additionally, the NSC-LTA catalyst showed a significant improvement in coke selectivity.

Cracking on a nickel-based superalloy fabricated by direct energy deposition

Cracks have consistently been a significant challenge limiting the development of additive manufactured nickel-based superalloys.It is essential to investigate the location of cracks and their forming mechanism.This study extensively examines the impact of solidification process,microstructural evolution,and stress concentration on crack initiation during direct energy deposition(DED).The results emphasize that the crack formation is significantly related to large-angle grain boundaries,rapid cooling rates.Cracks caused by large-angle grain boundaries and a fast-cooling rate predominantly appear near the edge of the deposited samples.Liquation cracks are more likely to form near the top of the deposited sample,due to the presence ofγ/γ'eutectics.The secondary dendritic arm and the carbides in the interdendritic regions can obstruct liquid flow during the final stage of solidification,which results in the formation of solidification cracks and voids.This work paves the way to avoid cracks in nickel-based superalloys fabricated by DED,thereby enhancing the performance of superalloys.

HZSM-5 zeolites undergoing the high-temperature process for boosting the bimolecular reaction in n-heptane catalytic cracking

High-temperature treatment is key to the preparation of zeolite catalysts.Herein,the effects of hightemperature treatment on the property and performance of HZSM-5 zeolites were studied in this work.X-Ray diffraction,N2physisorption,27Al magic angle spinning nuclear magnetic resonance(MAS NMR),and temperature-programmed desorption of ammonia results indicated that the hightemperature treatment at 650℃ hardly affected the inherent crystal and texture of HZSM-5zeolites but facilitated the conversion of framework Al to extra-framework Al,reducing the acid site and enhancing the acid strength.Moreover,the high-temperature treatment improved the performance of HZSM-5 zeolites in n-heptane catalytic cracking,promoting the conversion and light olefins yield while inhibiting coke formation.Based on the kinetic and mechanism analysis,the improvement of HZSM-5 performance caused by high-temperature treatment has been attributed to the formation of extra-framework Al,which enhanced the acid strength,facilitated the bimolecular reaction,and promoted the entropy change to overcome a higher energy barrier in n-heptane catalytic cracking.

Brønsted-acid sites induced photocatalytic cracking of low-polarity polyethylene plastics

Polyolefins such as polyethylene(PE)are one of the largest-scale synthetic plastics and play a key role in modern society.However,polyethylene is extremely inert to chemical recycling owing to its lack of chemical functionality and low polarity,making it one of the most challenging environmental hazards globally.Herein,we developed a phosphorylated CeO_(2)catalyst by an organophosphate precursor and featured efficient photocatalysis of low-density polyethylene(LDPE)without the acid or alkaline pre-treatment.Compared to pristine CeO_(2),the surface phosphorylation allows to introduce Brønsted acid sites,which facilitate to form carbonium ions on LDPE via protonation.In addition,the suitable band structure of the phosphorylated CeO_(2)catalyst enables efficient photoabsorption and generates reactive oxygen species,leading to the C–C bond cleavage of LDPE.As a result,the phosphorylated CeO_(2)catalyst exhibited an outstanding carbon conversion rate of>94%after 48 h of photocatalysis under 50 mW/cm^(2)of simulated sunlight,with a high CO_(2)product selectivity of>99%.Furthermore,the PE microparticles with sizes larger than 10μm released from LDPE plastic wrap were directly and completely degraded by photocatalysis within 12 h,suggesting an attractive and environmentally benign strategy of utilizing solar energy-based photocatalysis for reducing potential hazards of LDPE plastic trashes.

A molecular insight into coke formation process of vacuum residue in thermal cracking reaction

Understanding the coking behaviors has been considered to be really essential for developing better vacuum residue processing technologies.A battery of thermal cracking tests of typical vacuum residue at 410℃ with various reaction time were performed to evaluate the coke formation process.The total yields of ideal components including naphtha,atmospheric gas oil(AGO)and vacuum gas oil(VGO)of thermal cracking reactions increased from 10.89%to 40.81%,and the conversion ratios increased from8.05%to 43.33%with increasing the reaction time from 10 to 70 min.The asphaltene content increased from 12.14%to a maximum of 22.39%and then decreased,and this maximum of asphaltene content occurred at the end of the coking induction period.The asphaltenes during the coking induction period,at the end and after coking induction period of those tested thermal cracking reactions were characterized to disclose the structure changing rules for coke formation process,and the coke formation pathways were discussed to reveal the coke formation process at molecular level.

Thermally-induced cracking behaviors of coal reservoirs subjected to cryogenic liquid nitrogen shock

The benefits of using cryogenic liquid nitrogen shock to enhance coal permeability have been confirmed from experimental perspectives.In this paper,we develop a fully coupled thermo-elastic model in combination with the strain-based isotropic damage theory to uncover the cooling-dominated cracking behaviors through three typical cases,i.e.coal reservoirs containing a wellbore,a primary fracture,and a natural fracture network,respectively.The progressive cracking processes,from thermal fracture initiation,propagation or cessation,deflection,bifurcation to multi-fracture interactions,can be well captured by the numerical model.It is observed that two hierarchical levels of thermal fractures are formed,in which the number of shorter thermal fractures consistently exceeds that of the longer ones.The effects of coal properties related to thermal stress levels and thermal diffusivity on the fracture morphology are quantified by the fracture fractal dimension and the statistical fracture number.The induced fracture morphology is most sensitive to changes in the elastic modulus and thermal expansion coefficient,both of which dominate the complexity of the fracture networks.Coal reservoir candidates with preferred thermal-mechanical properties are also recommended for improving the stimulation effect.Further findings are that there exists a critical injection temperature and a critical in-situ stress difference,above which no thermal fractures would be formed.Preexisting natural fractures with higher density and preferred orientations are also essential for the formation of complex fracture networks.The obtained results can provide some theoretical support for cryogenic fracturing design in coal reservoirs.

Preparation and Electrochemical Performance Study of Catalytic Cracking Oil Slurry-based Porous Carbon Materials

Catalytic cracking oil slurry is a by-product of catalytic cracking projects,and the efficient conversion and sustainable utilization of this material are issues of continuous concern in the petroleum refining industry.In this study,oxygen-enriched activated carbon is prepared using a one-step KOH activation method with catalytic cracking oil slurry as the raw material.The as-prepared oil slurry-based activated carbon exhibits a high specific surface area of 2102 m^(2)/g,welldefined micropores with an average diameter of 2 nm,and a rich oxygen doping content of 32.97%.The electrochemical performance of the nitrogen-doped porous carbon is tested in a three-electrode system using a 6 mol/L KOH solution as the electrolyte.It achieves a specific capacitance of up to 230 F/g at a current density of 1 A/g.Moreover,the capacitance retention rate exceeds 89%after 10000 charge and discharge cycles,demonstrating excellent cycle stability.This method not only improves the utilization efficiency of industrial fuel waste but also reduces the production cost of supercapacitor electrode materials,thereby providing a simple and effective strategy for the resource utilization of catalytic cracking oil slurries.

Microstructure control and hot cracking behavior of the new Ni-Co based superalloy prepared by electron beam smelting layered solidification technology

The prevention of hot cracking formation is of utmost importance in the production of the new Ni-Co based superalloys through the utilization of the electron beam smelting layered solidification technique(EBSL),as it ensures exceptional homogeneity and dependable consistency of the specimens.In contrast to previous studies that focused on minimizing the liquid film and solidification range,our methodology adopts a distinct approach.In this research,a novel methodology was employed to mitigate internal stresses through the implementation of equiaxed grain layers via an alternately reduced cooling method.This ultimately resulted in the elimination of hot cracking.To be more specific,the transition from a columnar to an equiaxed structure was observed during the layer-by-layer construction process in the fabrication of the new Ni-Co based superalloy in EBSL.The EBSL-Ni-Co superalloy,when subjected to the alternating reduction cooling method,exhibited an internal stress of 49 MPa.This value represents a significant reduction of 83.8%compared to the internal stress observed when employing the linear reduction cooling method.Additionally,the solvus temperature of theγ-γ’eutectic phases in EBSL-Ni-Co superalloys produced by the alternating reduction cooling method is significantly higher.Intriguingly,the Nth layer of the EBSL-Ni-Co based superalloys produced by EBSL simultaneously heats treated with the preceding layers.And the low melting point phase gradually dissolved back into the matrix.The implementation of an alternating reduced cooling method successfully mitigated the formation of the liquid film in theγ-γ’eutectic phase and the buildup of internal stresses in the EBSL-Ni-Co superalloy during its manufacturing process.These discoveries open up a novel preparation procedure pathway for the manufacture of crack-free superalloys with superior mechanical characteristics using EBSL.

Stress corrosion cracking behavior of buried oil and gas pipeline steel under the coexistence of magnetic field and sulfate-reducing bacteria

Magnetic field and microorganisms are important factors influencing the stress corrosion cracking(SCC)of buried oil and gas pipelines. Once SCC occurs in buried pipelines, it will cause serious hazards to the soil environment. The SCC behavior of X80 pipeline steel under the magnetic field and sulfate-reducing bacteria(SRB) environment was investigated by immersion tests, electrochemical tests, and slow strain rate tensile(SSRT) tests. The results showed that the corrosion and SCC sensitivity of X80 steel decreased with increasing the magnetic field strength in the sterile environment. The SCC sensitivity was higher in the biotic environment inoculated with SRB, but it also decreased with increasing magnetic field strength, which was due to the magnetic field reduces microbial activity and promotes the formation of dense film layer. This work provided theoretical guidance on the prevention of SCC in pipeline steel under magnetic field and SRB coexistence.

Simulation of Corrosion-Induced Cracking of Reinforced Concrete Based on Fracture Phase Field Method

Accurate simulation of the cracking process caused by rust expansion of reinforced concrete(RC)structures plays an intuitive role in revealing the corrosion-induced failure mechanism.Considering the quasi-brittle fracture of concrete,the fracture phase field driven by the compressive-shear term is constructed and added to the traditional brittle fracture phase field model.The rationality of the proposed model is verified by a mixed fracture example under a shear displacement load.Then,the extended fracture phase model is applied to simulate the corrosion-induced cracking process of RC.The cracking patterns caused by non-uniform corrosion expansion are discussed for RC specimens with homogeneous macroscopically or heterogeneous with different polygonal aggregate distributions at the mesoscopic scale.Then,the effects of the protective layer on the crack propagation trajectory and cracking resistance are investigated,illustrating that the cracking angle and cracking resistance increase with the increase of the protective layer thickness,consistent with the experimental observation.Finally,the corrosion-induced cracking process of concrete specimens with large and small spacing rebars is simulated,and the interaction of multiple corrosion cracking is easily influenced by the reinforcement spacing,which increases with the decrease of the steel bar interval.These conclusions play an important role in the design of engineering anti-corrosion measures.The fracture phase field model can provide strong support for the life assessment of RC structures.

Effect of Shrinkage Reducing Agent and Steel Fiber on the Fluidity and Cracking Performance of Ultra-High Performance Concrete

Due to the low water-cement ratio of ultra-high-performance concrete(UHPC),fluidity and shrinkage cracking are key aspects determining the performance and durability of this type of concrete.In this study,the effects of different types of cementitious materials,chemical shrinkage-reducing agents(SRA)and steel fiber(SF)were assessed.Compared with M2-UHPC and M3-UHPC,M1-UHPC was found to have better fluidity and shrinkage cracking performance.Moreover,different SRA incorporation methods,dosage and different SF types and aspect ratios were implemented.The incorporation of SRA and SF led to a decrease in the fluidity of UHPC.SRA internal content of 1%(NSRA-1%),SRA external content of 1%(WSRA-1%),STS-0.22 and STE-0.7 decreased the fluidity of UHPC by 3.3%,8.3%,9.2%and 25%,respectively.However,SRA and SF improved the UHPC shrinkage cracking performance.NSRA-1%and STE-0.7 reduced the shrinkage value of UHPC by 40%and 60%,respectively,and increased the crack resistance by 338%and 175%,respectively.In addition,the addition of SF was observed to make the microstructure of UHPC more compact,and the compressive strength and flexural strength of 28 d were increased by 26.9%and 19.9%,respectively.

Research Advances on Cyclohexane Catalytic Cracking

This article elaborates on the research achievements of domestic and foreign researchers in exploring the conversion pathways and reaction mechanisms of cyclohexane catalytic cracking in recent years.It analyzes the effects of different catalysts and process conditions on the conversion laws of cyclohexane,summarizes the conversion pathways of cyclohexane,and discusses the chemical mechanisms of several main reactions of cyclohexane in catalytic cracking,such as cracking,isomerization,hydrogen transfer,dehydrogenation,and alkylation;Several advanced characterization methods and common research methods were listed,and prospects for future development in this field were proposed based on existing research.

miRNA-223、miRNA-21及miRNA-27a与冠心病冠脉病变的关系

目的 探讨miRNA-223、miRNA-21及miRNA-27a与冠心病冠脉病变的关系。方法 选取2021年1月至2022年12月商丘市第一人民医院收治的CHD患者86例为观察组,选取70名同期院内健康体检者作为对照组。对比两组血清miRNA-223、miRNA-21、miRNA-27a水平;分析影响CHD冠脉病变的单因素,采用Logistic回归分析影响CHD冠脉病变的单因素、多因素;对比不同CHD冠脉病变类型的血清miRNA-223、miRNA-21、miRNA-27a水平;对比不同CHD冠脉病变支数的血清miRNA-223、miRNA-21、miRNA-27a水平。结果 观察组miRNA-223、miRNA-21、miRNA-27a表达水平比对照组高,差异有统计学意义(P<0.05);Logistic多因素分析显示,患有高血压、糖尿病以及miRNA-223>1.5、miRNA-21>6.0、miRNA-27a>5.5均是影响CHD冠脉病变的独立危险因素(P<0.05);miRNA-223、miRNA-21、miRNA-27a表达水平:急性心肌梗死>不稳定型心绞痛>稳定型心绞痛,差异有统计学意义(P<0.05);miRNA-223、miRNA-21、miRNA-27a表达水平:三支>双支>单支,差异有统计学意义(P<0.05)。结论 不同冠脉病变CHD患者miRNA-223、miRNA-21、miRNA-27a表达水平不同,提示以上指标对判断CHD患者冠脉病变类型具有一定的临床价值。

外周血EOS、IL-21、CCL4与慢性鼻-鼻窦炎伴鼻息肉患者术后复发的相关性

目的探究外周血嗜酸性粒细胞数(EOS)、白细胞介素-21(IL-21)、趋化因子4(CCL4)与慢性鼻-鼻窦炎伴鼻息肉(CRSwNP)患者术后复发的相关性。方法回顾性选取青岛市第八人民医院2020年1月至2022年6月收治的86例行慢性鼻-鼻窦炎伴鼻息肉切除术患者,收集所有患者的一般资料,对患者进行外周血EOS、IL-21、CCL4检测;并对患者进行随访1年,统计其复发情况,根据患者的术后复发情况将患者分为复发组(n=34)与正常组(n=52)。比较两组的临床资料和外周血EOS、IL-21、CCL4水平;采用Pearson相关性分析探讨外周血EOS、IL-21、CCL4与CRSwNP患者鼻窦CT Lund-Mackay评分的相关性;采用受试者工作特征(ROC)曲线评估CRSwNP患者术后复发的预测价值。结果随访期间共记录到术后复发患者34例,占比39.53%,未复发患者52例,占比60.47%。两组患者的嗜酸性粒细胞型鼻息肉例数、鼻窦CT Lund-Mackay评分、外周血EOS、IL-21、CCL4水平进行比较,差异有统计学意义(t=4.250、5.300、3.890、3.089、3.499,P<0.05)。多因素logistic回归分析结果显示外周血EOS、IL-21、CCL4水平均是CRSwNP患者术后复发的独立危险因素(P<0.05)。Pearson相关性分析结果显示,外周血EOS、IL-21、CCL4水平与CRSwNP患者鼻窦CT Lund-Mackay评分具有相关性(r=0.433、0.681、0.547,P<0.05)。ROC曲线结果显示,外周血EOS、IL-21、CCL4及三者联合对预测CRSwNP患者术后复发的AUC面积分别为:0.725、0.686、0.709、0.834,且联合预测的灵敏度和特异度最高,效果最好(P<0.05)。结论外周血EOS、IL-21、CCL4与CRSwNP患者病情程度具有相关性,通过外周血EOS、IL-21、CCL4预测慢性鼻-鼻窦炎伴鼻息肉患者术后复发具有一定的预测价值。

血清成纤维细胞生长因子21和脂肪酸结合蛋白4检测对急性ST段抬高型心肌梗死患者经皮冠状动脉介入治疗术后心力衰竭的预测价值

目的探究血清成纤维细胞生长因子21(FGF21)和脂肪酸结合蛋白4(FABP4)检测对急性ST段抬高型心肌梗死(STEMI)患者经皮冠状动脉介入治疗(PCI)术后心力衰竭的预测价值。方法选取2020年9月至2022年9月内蒙古医科大学附属医院接诊的113例STEMI患者为研究对象,依据PCI术后1年是否发生心力衰竭(心衰),将其分为心衰组(n=32)和非心衰组(n=81)。应用ELISA法测定血清FGF21、FABP4表达水平,比较两组血清FGF21、FABP4水平,多因素logistic回归分析影响STEMI患者PCI术后发生心力衰竭的相关因素,ROC曲线评估血清FGF21、FABP4水平对STEMI患者PCI术后心力衰竭发生的预测价值。结果心衰组心率次数、C反应蛋白(CRP)、心肌肌钙蛋白(cTnI)、N末端B型利钠肽原(BNP)、利尿剂使用比例均显著高于非心衰组,左心室射血分数(LVEF)显著低于非心衰组(P<0.05)。心衰组血清FGF21、FABP4表达水平均明显高于非心衰组[(228.37±33.07)ng/L比(185.68±25.52)ng/L、(34.26±5.51)ng/ml比(26.87±4.67)ng/ml,t=7.345、7.195,P<0.05]。血清FGF21(95%CI 1.371~8.191)、FABP4(95%CI 1.176~4.090)及发病到至导丝通过时间(95%CI 1.058~8.157)是影响STEMI患者PCI术后发生心力衰竭的危险因素(OR>1,P<0.05),LVEF(95%CI 0.473~0.913)是保护因素(OR<1,P<0.05)。血清FGF21、FABP4单独及二者联合预测STEMI患者PCI术后发生心力衰竭的曲线下面积(AUC)分别为0.828、0.856、0.934,二者联合优于单一(Z二者联合-FGF21=1.971、Z二者联合-FABP4=2.417,P=0.048、P=0.015)。结论STEMI患者PCI术后发生心力衰竭血清FGF21、FABP4水平均明显升高,二者联合对STEMI患者PCI术后发生心力衰竭的风险具有更高的预测价值。

miR-21调控TLK2表达对急性髓系白血病细胞增殖和凋亡的影响

目的:探讨mi R-21调控TLK2表达对急性髓系白血病(AML)细胞增殖和凋亡的影响。方法:选取2019年1月至2022年7月在新乡市中心医院收治的70例AML患者,同时选取30例缺铁性贫血患者作为对照组,使用Ficoll密度梯度离心法获取两组患者的骨髓单个核细胞。RT-q PCR测定各组骨髓单个核细胞中mi R-21、TLK2 m RNA的表达水平。使用脂质体转染技术将mimics-mi R-21、mimics-NC、inhibitor-mi R-21、inhibitor-NC及NC转染至HL-60细胞。采用CCK-8法测定各组HL-60转染细胞经阿糖胞苷处理后的活性。TUNEL法测定HL-60转染细胞凋亡率。RT-q PCR测定转染inhibitor-mi R-21后HL-60细胞TLK2 m RNA的表达。结果:AML患者骨髓单个核细胞中mi R-21、TLK2 m RNA的相对表达水平均明显高于对照组患者(均P<0.05)。HL-60细胞经阿糖胞苷处理后,inhibitor-mi R-21组和mimics-mi R-21组的细胞活性均随阿糖胞苷浓度升高显著下降(P<0.05),但在每个阿糖胞苷浓度点,inhibitor-mi R-21组的细胞活性均低于对照组(P<0.05),而mimics-mi R-21组的细胞活性均高于对照组(P<0.05)。inhibitor-mi R-21组的细胞凋亡率显著升高(P<0.05),而mimics-mi R-21组的细胞凋亡率显著降低(P<0.05)。HL-60细胞经inhibitor-mi R-21处理后,TLK2 m RNA的相对表达量明显下降(P<0.05)。结论:mi R-21在AML患者中呈高表达,可能通过抑制TLK2的表达来促使AML细胞凋亡。

IL-21和CCL19修饰可提高NKP30 CAR-T细胞对肺癌的杀伤效率并促进其肿瘤浸润

目的探讨细胞因子IL-21和趋化因子CCL19修饰的NKP30 CAR-T细胞是否增强对肺癌的杀伤和浸润作用。方法在NKP30 CAR基础上融合基因IL-21和CCL19构建IL-21-CCL19 NKP30 CAR;CAR-T细胞的培养使用CD3CD28单抗及细胞因子IL-2刺激;流式细胞术检测免疫细胞表型;迁移实验检测IL-21对免疫细胞的迁移作用;乳酸脱氢酶(LDH)及成球实验检测CAR-T细胞的杀伤及浸润能力;酶联免疫斑点技术(ELISPOT)检测IFN-γ的分泌数量;ELISA检测IL-21及CCL19的分泌情况;体内实验中,将肿瘤细胞显微注射到斑马鱼卵黄囊,构建斑马鱼移植瘤模型,24 h后将免疫细胞注射至同样部位,体式荧光显微镜拍摄荧光。结果NKP30配体(B7H6)在正常组织及血液细胞不表达,在肺癌细胞上高表达(90%以上)。IL-21-CCL19 NKP30 CAR-T细胞与NKP30 CAR-T细胞和常规T细胞相比,具有更强的增殖能力、迁移能力及中心记忆T细胞的形成(P<0.001),免疫抑制分子CTLA4与PD1显著降低(P<0.005),对肺癌细胞具有更强的杀伤能力(P<0.001),伴随IFN-γ数量明显增加(P<0.001)。IL-21-CCL19 CAR-T细胞杀伤肺癌细胞中产生大量细胞因子IL‑21(3152.33±526.74 pg/mL)和趋化因子CCL19(1853±211.95 pg/mL)。体内实验中,CAR-T细胞和普通T细胞比较,具有较强的杀伤能力和增殖能力,但2种CAR-T细胞无明显差异(P>0.05)。结论IL-21-CCL19 NKP30 CAR-T细胞更容易浸润到肿瘤内部,有效杀伤肿瘤细胞,同时产生更多的记忆T细胞。