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应用DPRA替代方法评价3种香豆素类化合物的皮肤致敏性
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作者 张红菱 程琳 +3 位作者 王海燕 罗飞亚 张会亮 孙磊 《日用化学工业(中英文)》 CAS 北大核心 2024年第2期156-160,共5页
应用直接多肽反应试验(DPRA)方法,对化妆品植物提取物原料中存在的蛇床子素、滨蒿内酯、东莨菪内酯3种未知致敏性的香豆素类化合物进行评价。3种香豆素类化合物与半胱氨酸多肽和赖氨酸多肽模拟的皮肤蛋白共同孵育,使用高效液相色谱法检... 应用直接多肽反应试验(DPRA)方法,对化妆品植物提取物原料中存在的蛇床子素、滨蒿内酯、东莨菪内酯3种未知致敏性的香豆素类化合物进行评价。3种香豆素类化合物与半胱氨酸多肽和赖氨酸多肽模拟的皮肤蛋白共同孵育,使用高效液相色谱法检测3种化合物的多肽消耗率。在标准色谱条件下,蛇床子素和滨蒿内酯与两种多肽的反应体系峰型均正常,东莨菪内酯与赖氨酸反应体系峰型异常,以体积分数0.1%的甲酸水-乙腈流动相体系对标准流动相体系进行优化后检测。结果表明:蛇床子素与半胱氨酸反应体系在反应24 h前产生沉淀,致敏性结果为不确定;滨蒿内酯多肽消耗率均值为6.95%,判定致敏性为阳性,反应等级为弱反应;东莨菪内酯的半胱氨酸多肽消耗率为75.82%,优化色谱条件后的赖氨酸多肽消耗率为80.46%,判定致敏性为阳性,反应等级为中度反应。阳性和阴性对照化合物的结果均与小鼠淋巴结试验(LLNA)致敏性结果一致,实验结果可为3种香豆素类化合物的致敏性提供参考和依据。 展开更多
关键词 直接多肽反应试验 皮肤致敏性 高效液相色谱 香豆素
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Investigation on the fabrication of lightweight aggregate with acid-leaching tailings of vanadium-bearing stone coal minerals and red mud 被引量:6
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作者 Chunguang Song hongling zhang +4 位作者 Yuming Dong Lili Pei Honghui Liu Junsheng Jiang Hongbin Xu 《Chinese Journal of Chemical Engineering》 SCIE EI CAS CSCD 2021年第4期353-359,共7页
Proper treatment of acidleaching tailings(ALTs)of vanadiumbearing stone coal minerals is of great urgency.One approach is adding it into the raw materials during the preparation of lightweight aggregate(LWA).But clay ... Proper treatment of acidleaching tailings(ALTs)of vanadiumbearing stone coal minerals is of great urgency.One approach is adding it into the raw materials during the preparation of lightweight aggregate(LWA).But clay is always needed.In this paper,another solid waste,red mud,was mixed with ALTs as a source of flux components instead of clay.Evaluation of the physical characteristics,morphological structures,as well as crystal phases during the sintering process were investigated.When their mixtures with a proper ratio were sintered at 1080℃,a glassy phase with certain viscosity was formed,and the gases generated simultaneously were encapsulated by the melt.Finally,LWA with a onehour water absorption as low as 1.46%,a bulk density as low as 728.76 kgm 3 and a compressive strength as high as 10.77 MPa was fabricated. 展开更多
关键词 Acid-leaching tailings Red mud Waste treatment SINTERING Preparation Lightweight aggregate
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通过改变原子电负性调控异硫氰酸苯并恶唑荧光染料的激发态分子内质子转移过程和光物理性质
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作者 张洪苓 刘青桐 +2 位作者 王艺颖 唐喆 周潘旺 《Chinese Journal of Chemical Physics》 SCIE EI CAS CSCD 2022年第2期331-337,I0011-I0025,I0003,共23页
激发态分子内质子转移因其独特的光学性质而受到研究人员的青睐.然而,关于改变原子电负性对激发态分子内质子转移过程和光物理性质影响的系统研究相对较少.本文通过理论方法选择了一系列苯并噁唑异硫氰酸酯荧光染料(2-HOB、2-HSB和2-HSe... 激发态分子内质子转移因其独特的光学性质而受到研究人员的青睐.然而,关于改变原子电负性对激发态分子内质子转移过程和光物理性质影响的系统研究相对较少.本文通过理论方法选择了一系列苯并噁唑异硫氰酸酯荧光染料(2-HOB、2-HSB和2-HSeB),并通过改变氧族原子的电负性,系统地研究了激发态分子内质子转移过程和光物理性质.计算的键角、键长、能隙和红外光谱分析表明,3个分子的分子内氢键强度依次为2-HOB<2-HSB<2-HSeB.相应地,势能曲线的能垒大小为2-HOB>2-HSB>2-HSeB.此外,计算的电子光谱表明,随着原子电负性的降低,发射光谱发生红移.本工作将为基于激发态分子内质子转移性质的新型染料的合成和应用提供一定的理论指导. 展开更多
关键词 激发态分子内质子转移 光物理性质 能垒 电负性
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A multi-functional nanoplatform for efficacy tumor theranostic applications 被引量:3
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作者 Jinjin Shi hongling zhang +2 位作者 Zhaoyang Chen Lihua Xu Zhenzhong zhang 《Asian Journal of Pharmaceutical Sciences》 SCIE CAS 2017年第3期235-249,共15页
Nanomaterials with multiple functions have become more and more popular in the domain of cancer research. MoS2 has a great potential in photothermal therapy, X-ray/CT imaging and drug delivery. In this study, a water ... Nanomaterials with multiple functions have become more and more popular in the domain of cancer research. MoS2 has a great potential in photothermal therapy, X-ray/CT imaging and drug delivery. In this study, a water soluble MoS2 nanosystem(MoS2-PEG) was synthesized and explored in drug delivery, photothermal therapy(PTT) and X-ray imaging.Doxorubicin(DOX) was loaded onto MoS2-PEG with a high drug loading efficiency(~69%)and obtained a multifunctional drug delivery system(MoS2-PEG/DOX). As the drug delivery, MoS2-PEG/DOX could efficiently cross the cell membranes, and escape from the endosome via NIR light irradiation, lead to more apoptosis in MCF-7 cells, and afford higher antitumor efficacy without obvious toxic effects to normal organs owing to its prolonged blood circulation and 11.6-fold higher DTX uptake of tumor than DOX. Besides, MoS2-PEG/DOX not only served as a drug delivery system, but also as a powerful PTT agent for thermal ablation of tumor and a strong X-ray contrast agent for tumor diagnosis. In the in vitro and in vivo studies, MoS2-PEG/DOX exhibited excellent tumor-targeting efficacy, outstanding synergistic anti-cancer effect of photothermal and chemotherapy and X-ray imaging property,demonstrating that MoS2-PEG/DOX had a great potential for simultaneous diagnosis and photothermal-chemotherapy in cancer treatment. 展开更多
关键词 MULTIFUNCTIONAL drug delivery ENDOSOME ESCAPE TUMOR-TARGETING BIO-IMAGING THERANOSTIC
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Fabrication and application of hierarchical mesoporous MoO2/Mo2C/C microspheres 被引量:2
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作者 Xiaoyan Li Qinggui xiao +2 位作者 hongling zhang Hongbin Xu Yi zhang 《Journal of Energy Chemistry》 SCIE EI CAS CSCD 2018年第3期940-948,共9页
Hierarchical mesoporous MoO_2/Mo_2C/C microspheres,which are composed of primary nanoparticles with a size of about 30 nm,have been designed and synthesized through polymer regulation and subsequent carbonization proc... Hierarchical mesoporous MoO_2/Mo_2C/C microspheres,which are composed of primary nanoparticles with a size of about 30 nm,have been designed and synthesized through polymer regulation and subsequent carbonization processes.The as-synthesized microspheres were characterized by XRD,Raman,SEM,TEM,XPS measurements and so on.It was found that polyethylene glycol acted as a structure-directing agent,mild reducing agent and carbon source in the formation of these hierarchical mesoporous Mo O_2/Mo_2C/C microspheres.Moreover,the electrochemical property of the microspheres was also investigated in this work.Evaluated as an anode material for lithium ion batteries,the hierarchical mesoporous Mo O_2/Mo_2C/C electrode delivered the discharge specific capacities of 665 and 588 m Ah/g after 100 cycles at current densities of 100 and 200 m A/g,respectively.The satisfactory cycling performance and controllable process facilitate the practical applications of the hierarchical mesoporous Mo O_2/Mo_2C/C as a potential anode material in high-energy density lithium-ion batteries. 展开更多
关键词 制造 聚乙烯乙二醇 代理人 聚合物 XRD SEM TEM XPS
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Extracorporeal membrane oxygenation in adult patients with sepsis and septic shock: Why, how, when, and for whom
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作者 hongling zhang Youdong Xu +6 位作者 Xin Huang Shunyin Yang Ruiting Li Yongran Wu Xiaojing Zou Yuan Yu You Shang 《Journal of Intensive Medicine》 CSCD 2024年第1期62-72,共11页
Sepsis and septic shock remain the leading causes of death in intensive care units.Some patients with sepsis fail to respond to routine treatment and rapidly progress to refractory respiratory and circulatory failure,... Sepsis and septic shock remain the leading causes of death in intensive care units.Some patients with sepsis fail to respond to routine treatment and rapidly progress to refractory respiratory and circulatory failure,necessitating extracorporeal membrane oxygenation(ECMO).However,the role of ECMO in adult patients with sepsis has not been fully established.According to existing studies,ECMO may be a viable salvage therapy in carefully selected adult patients with sepsis.The choice of venovenous,venoarterial,or hybrid ECMO modes is primarily determined by the patient’s oxygenation and hemodynamics(distributive shock with preserved cardiac output,septic cardiomyopathy(left,right,or biventricular heart failure),or right ventricular failure caused by acute respiratory distress syndrome).Veno-venous ECMO can be used in patients with sepsis and severe acute respiratory distress syndrome when conventional mechanical ventilation fails,and early application of veno-arterial ECMO in patients with sepsis-induced refractory cardiogenic shock may be critical in improving their chances of survival.When ECMO is indicated,the choice of an appropriate mode and determination of the optimal timing of initiation and weaning are critical,particularly in an experienced ECMO center.Furthermore,some special issues,such as ECMO flow,anticoagulation,and antibiotic therapy,should be noted during the management of ECMO support. 展开更多
关键词 Extracorporeal membrane oxygenation SEPSIS Shock Acute respiratory distress syndrome(ARDS) Septic cardiomyopathy MOD
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内镜电凝止血与组织胶注射治疗上消化道溃疡伴出血的疗效观察
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作者 高显奎 赵太云 +7 位作者 陆兴俊 张洪领 房修罗 闫碧春 王胤 王永翠 刘苗苗 冉若男 《中华消化病与影像杂志(电子版)》 2023年第6期452-455,共4页
目的观察内镜电凝止血术与内镜组织胶注射术治疗对消化性溃疡伴出血患者的临床疗效。方法回顾性分析2021年1月至2023年1月亳州市人民医院收治的因消化性溃疡所致上消化道出血的86例患者的临床资料,根据治疗方案的不同,将患者分为对照组... 目的观察内镜电凝止血术与内镜组织胶注射术治疗对消化性溃疡伴出血患者的临床疗效。方法回顾性分析2021年1月至2023年1月亳州市人民医院收治的因消化性溃疡所致上消化道出血的86例患者的临床资料,根据治疗方案的不同,将患者分为对照组(内镜组织胶注射)46例和观察组(内镜电凝止血)40例。统计并比较两组患者的一般基线资料(年龄、性别、体重指数、病程、Forrest分级、溃疡类型、血红蛋白水平)、疗效、术中内镜下止血率、术后1周内再出血率和异位栓塞率、病情康复相关指标(呕血消失时间、住院时间、潜血转阴时间)及不良反应发生率。结果两组患者的一般基线资料比较差异无统计学意义(P>0.05)。观察组的治疗总有效率高于对照组(P<0.05)。观察组的术中内镜下止血率显著高于对照组(P<0.05),术后1周内再出血率显著低于对照组(P<0.05),两组术后1周内异位栓塞率比较差异无统计学意义(P>0.05)。观察组的病情康复相关指标显著优于对照组(P<0.001)。两组患者的不良反应总发生率差异无统计学意义(P>0.05)。结论内镜电凝止血术较内镜组织胶注射术对消化性溃疡伴出血患者具有更好的止血效果,不但可以减少患者术后的再出血率,还能加快患者的康复进程。 展开更多
关键词 消化性溃疡出血 内镜组织胶注射术 内镜电凝止血术 疗效
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底心正交和三方CrOOH热分解制备氧化铬绿的研究
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作者 穆攀攀 张红玲 +4 位作者 娄太平 周鹏 史海琴 陈林明 徐红彬 《过程工程学报》 CAS CSCD 北大核心 2023年第2期272-279,共8页
羟基氧化铬(CrOOH)热分解制备氧化铬绿颜料是铬酸盐氢还原法制备氧化铬绿清洁工艺的单元之一。研究表明,CrOOH的结构对其热分解所得氧化铬绿的色度有显著影响,但CrOOH晶体结构对所得氧化铬绿色度的影响尚未有系统研究报道。本工作通过... 羟基氧化铬(CrOOH)热分解制备氧化铬绿颜料是铬酸盐氢还原法制备氧化铬绿清洁工艺的单元之一。研究表明,CrOOH的结构对其热分解所得氧化铬绿的色度有显著影响,但CrOOH晶体结构对所得氧化铬绿色度的影响尚未有系统研究报道。本工作通过铬酸钠溶液氢还原制备得到了两种晶型的CrOOH并借助化学滴定、傅里叶变换红外光谱(FT-IR)、X射线衍射(XRD)、扫描电子显微镜(SEM)和热重-差示扫描量热分析(TG-DSC)对其组成、结构、形貌和热分解过程进行了研究。以两种不同晶型的CrOOH为原料调控制备得到了不同色度的氧化铬绿颜料,借助XRD和SEM对其物相和形貌进行了表征,并使用Datacolor110色度仪测定了其色度参数。结果表明,两种CrOOH的晶体结构分别为底心正交和三方,其形貌分别呈现片状和六方片状,组成可分别写作Cr_(2)O_(3)·1.49H2O和Cr_(2)O_(3)·1.12H2O。与三方CrOOH相比,底心正交的CrOOH热分解得到的氧化铬绿颗粒尺寸更小、大小更均匀、颜色更亮更黄。最终,以不同比例的底心正交和三方CrOOH为原料,调控制备得到了多种色调的氧化铬绿颜料。 展开更多
关键词 羟基氧化铬 热分解 氧化铬绿 晶型 色度
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Spatiotemporal transformable nano-assembly for on-demand drug delivery to enhance anti-tumor immunotherapy
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作者 Chenglin Liang Ge zhang +5 位作者 Linlin Guo Xinyi Ding Heng Yang hongling zhang Zhenzhong zhang Lin Hou 《Asian Journal of Pharmaceutical Sciences》 SCIE CAS 2024年第1期103-118,共16页
Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy,but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration.Herein,we designed a ca... Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy,but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration.Herein,we designed a cancer-associated fibroblasts(CAFs)triggered structure-transformable nano-assembly(HSD-P@V),which can directionally deliver valsartan(Val,CAFs regulator)and doxorubicin(DOX,senescence inducer)to the specific targets.In detail,DOX is conjugated with hyaluronic acid(HA)via diselenide bonds(Se-Se)to form HSD micelles,while CAFs-sensitive peptide is grafted onto the HSD to form a hydrophilic polymer,which is coated on Val nanocrystals(VNs)surface for improving the stability and achieving responsive release.Once arriving at tumor microenvironment and touching CAFs,HSD-P@V disintegrates into VNs and HSD micelles due to sensitive peptide detachment.VNs can degrade the extracellularmatrix,leading to the enhanced penetration of HSD.HSD targets tumor cells,releases DOX to induce senescence,and recruits effector immune cells.Furthermore,senescent cells are cleared by the recruited immune cells to finish the integrated anti-tumor therapy.In vitro and in vivo results show that the nanoassembly remarkably inhibits tumor growth as well as lungmetastasis,and extends tumorbearing mice survival.This work provides a promising paradigm of programmed delivering multi-site nanomedicine for cancer immunotherapy. 展开更多
关键词 Cells senescence Tumor stroma Structure transformable Programmed delivery Anti-tumor immunotherapy
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二次铝灰硫酸铵焙烧提铝过程氟的迁移规律 被引量:3
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作者 雷炳宏 刘宏辉 +4 位作者 张笛 董玉明 张红玲 娄太平 徐红彬 《过程工程学报》 CAS CSCD 北大核心 2022年第1期108-117,共10页
采用硫酸铵焙烧-水浸法回收二次铝灰中的铝是实现其无害化与资源化最重要的途径之一。二次铝灰的无害化与资源化利用要求尾渣氟的浸出毒性满足国标要求(无机氟化物质量浓度低于100 mg/L)。二次铝灰中氟的浸出毒性远高于100 mg/L,故需深... 采用硫酸铵焙烧-水浸法回收二次铝灰中的铝是实现其无害化与资源化最重要的途径之一。二次铝灰的无害化与资源化利用要求尾渣氟的浸出毒性满足国标要求(无机氟化物质量浓度低于100 mg/L)。二次铝灰中氟的浸出毒性远高于100 mg/L,故需深入研究二次铝灰硫酸铵焙烧-水浸提铝过程氟的迁移规律。借助复合氟离子电极、XRD、XPS、SEM和XRF研究了二次铝灰硫酸铵焙烧-水浸提铝过程氟的迁移转化行为。结果表明,延长焙烧时间、提高焙烧温度、增大硫酸铵配比可促进二次铝灰中的氟进入焙烧尾气;延长浸出时间、提高浸出温度、增大液固比有利于降低浸出渣中氟的含量和占比。在焙烧温度450℃、焙烧时间2 h、物料配比6:1、浸出温度85℃、浸出时间80 min、液固比6:1条件下,二次铝灰中43.85%的氟以气态形式进入尾气,23.92%的氟进入浸出液中,32.23%的氟以AlF_(3)和AlF_(3)·3H_(2)O形式残留在浸出渣中。焙烧尾气经脱氟、喷淋吸收,可转化为硫酸铵;浸出液脱氟后可制备聚合硫酸铝,用作水处理剂;浸出渣的浸出毒性符合国家标准,可用作建筑材料,从而实现二次铝灰的资源化与无害化处理。 展开更多
关键词 二次铝灰 硫酸铵 焙烧 迁移规律
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石煤钒矿酸浸尾渣高温焙烧制备陶粒过程元素硫释放规律
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作者 宋春光 张红玲 +4 位作者 董玉明 裴丽丽 刘宏辉 江军生 徐红彬 《过程工程学报》 CAS CSCD 北大核心 2021年第2期167-173,共7页
以石煤钒矿酸浸提钒过程产生的尾渣为原料制备陶粒是实现尾渣资源化的重要途径之一。作为陶粒最主要用途的轻集料对硫含量有严格限制(以SO3计,硫酸盐和硫化物含量≤1.0wt%)。尾渣含硫量通常远高于1.0wt%,故需深入研究尾渣制备陶粒过程... 以石煤钒矿酸浸提钒过程产生的尾渣为原料制备陶粒是实现尾渣资源化的重要途径之一。作为陶粒最主要用途的轻集料对硫含量有严格限制(以SO3计,硫酸盐和硫化物含量≤1.0wt%)。尾渣含硫量通常远高于1.0wt%,故需深入研究尾渣制备陶粒过程元素硫的释放规律。借助热重–红外联用分析了以尾渣为原料制备陶粒过程中的质量、热量变化以及气体释放规律,测试了不同温度焙烧所得样品的硫含量,表征了其物相,并结合热力学计算,讨论了尾渣中硫的释放机理。结果表明,随温度增加,尾渣中的含硫物质逐渐分解并释放出SO_(2)气体,样品的硫含量逐渐降低;1200℃下样品的硫含量可降低至0.44wt%,满足轻集料硫含量要求;尾渣中含有的SiO_(2),Fe_(2)O_(3),Al_(2)O_(3)等组分可促进硫的释放。 展开更多
关键词 酸浸尾渣 石煤钒矿 陶粒 轻集料
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饱和铬酸钠共存苛性碱中铬铁矿的氧化分解行为
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作者 李双 张红玲 +5 位作者 刘宏辉 高增礼 程西川 王明华 蔡再华 徐红彬 《过程工程学报》 CAS CSCD 北大核心 2022年第11期1538-1546,共9页
为考察铬铁矿苛性碱氧化浸出反应体系循环苛性碱溶液对铬铁矿氧化分解行为的影响,以90℃下饱和铬酸钠共存苛性碱(代替单一苛性碱溶液)作为反应介质,研究了苛性碱浓度、氧气分压、铬铁矿粉粒度、反应温度、反应时间等参数对铬铁矿氧化分... 为考察铬铁矿苛性碱氧化浸出反应体系循环苛性碱溶液对铬铁矿氧化分解行为的影响,以90℃下饱和铬酸钠共存苛性碱(代替单一苛性碱溶液)作为反应介质,研究了苛性碱浓度、氧气分压、铬铁矿粉粒度、反应温度、反应时间等参数对铬铁矿氧化分解过程的影响规律,分析了铬酸钠与苛性碱的分离效果以及铬酸钠与铝、硅杂质元素的分离效果。研究结果表明,铬铁矿氧化分解的较佳工艺条件为苛性碱浓度50wt%、氧气分压3.2 MPa、铬铁矿粒度小于48μm、反应温度250℃、反应时间240 min。在较优工艺条件下,铬铁矿中铬元素的浸出率达到95.24%;铬铁矿中浸出的铬有96.36%以铬酸钠晶体的形式在后续浸出渣溶解分离过程中进入溶晶液,而铬铁矿中浸出的铝、硅分别有84.92%和95.04%进入到浸出液中;同时,未参与反应的苛性碱有89.41%保留在浸出液中。与苛性碱单一反应介质氧化分解铬铁矿的过程相比,本工作采用的反应方式将从铬铁矿中浸出的主元素铬、杂质元素铝和硅,以及未参与反应的苛性碱分别调整到溶晶液和浸出液中,获得了较好的分离效果。 展开更多
关键词 铬铁矿 氧化分解 苛性碱循环 饱和铬酸钠 杂质分离
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In situ triggering antitumor efficacy of alcoholabuse drug disulfiram through Cu-based metalorganic framework nanoparticles 被引量:2
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作者 Lin Hou Yanlong Liu +5 位作者 Wei Liu Mervat Balash hongling zhang Yi zhang Huijuan zhang Zhenzhong zhang 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2021年第7期2016-2030,共15页
Although approved as an alcohol-abuse drug,disulfiram(DSF)exhibited potential anticancer activity when chelated with copper(Cu).However,the low level of intrinsic Cu,toxicity originated from exogenous Cu supplementati... Although approved as an alcohol-abuse drug,disulfiram(DSF)exhibited potential anticancer activity when chelated with copper(Cu).However,the low level of intrinsic Cu,toxicity originated from exogenous Cu supplementation,and poor stability of DSF in vivo severely limited its application in cancer treatment.Herein,we proposed an in situ DSF antitumor efficacy triggered system,taking advantages of Cu-based metal-organic framework(MOF).In detail,DSF was encapsulated into Cu-MOF nanoparticles(NPs)during its formation,and the obtained NPs were coated with hyaluronic acid to enhance the tumor targetability and biocompatibility.Notably,DSF loaded Cu-MOF NPs maintained stability and integrity without Cu;leakage in blood circulation,thus showing excellent biosafety.Once accumulating at tumor site,NPs were internalized into tumor cells via receptor-mediated endocytosis and released DSF and Cu;simultaneously in the hyaluronidase-enriched and acidic intracellular tumor microenvironment.This profile lead to in situ chelation reaction between DSF and Cu;,generating toxic DSF/Cu complex against tumor cells.Both in vitro and in vivo results demonstrated the programmed degradation and recombination property of Cu-based MOF NPs,which facilitated the tumor-specific chemotherapeutic effects of DSF.This system provided a promising strategy for the application of DSF in tumor therapy. 展开更多
关键词 DISULFIRAM Copper Metal-organic framework Hyaluronic acid Lysosomal escape DSF/Cu complex In situ Antitumor therapy
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Epigenetic integrity of paternal imprints enhances the developmental potential of androgenetic haploid embryonic stem cells 被引量:1
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作者 hongling zhang Yuanyuan Li +4 位作者 Yongjian Ma Chongping Lai Qian Yu Guangyong Shi Jinsong Li 《Protein & Cell》 SCIE CSCD 2022年第2期102-119,共18页
The use of two inhibitors of Mek1/2 and Gsk3β(2i)promotes the generation of mouse diploid and haploid embryonic stem cells(ESCs)from the inner cell mass of biparental and uniparental blastocysts,respectively.However,... The use of two inhibitors of Mek1/2 and Gsk3β(2i)promotes the generation of mouse diploid and haploid embryonic stem cells(ESCs)from the inner cell mass of biparental and uniparental blastocysts,respectively.However,a system enabling long-term maintenance of imprints in ESCs has proven challenging.Here,we report that the use of a two-step a2i(alternative two inhibitors of Src and Gsk3β,TSa2i)derivation/culture protocol results in the establishment of androgenetic haploid ESCs(AG-haESCs)with stable DNA methylation at paternal DMRs(differentially DNA methylated regions)up to passage 60 that can efficiently support generating mice upon oocyte injection.We also show coexistence of H3K9me3 marks and ZFP57 bindings with intact DMR methylations.Furthermore,we demonstrate that TSa2itreated AG-haESCs are a heterogeneous cell population regarding paternal DMR methylation.Strikingly,AGhaESCs with late passages display increased paternal-DMR methylations and improved developmental potential compared to early-passage cells,in part through the enhanced proliferation of H19-DMR hypermethylated cells.Together,we establish AG-haESCs that can longterm maintain paternal imprints. 展开更多
关键词 paternal imprints androgenetic haploid ESCs DMRs semi-cloned mice alternative 2i
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