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| 1 | Propofol differentially induces unconsciousness and respiratory depression through distinct interactions between GABAa receptor and GABAergic neuron in corresponding nuclei显示文摘Propofol is the most commonly used intravenous anesthetic worldwide.It can induce loss of consciousness prior to the occurrence of severe respiratory suppression,which is also a pharmacodynamic feature of all general anesthetics.However,the neural mechanisms underlying this natural phenomenon are controversial and highly related to patient safety.In the present study,we demonstrated that the pharmacodynamic effects of propofol(50 and 100 μM)on suppression of consciousness-related excitatory postsynaptic currents in the medial prefrontal cortex(mPFC)and centromedian nucleus of the thalamus(CMT)were lower than those in the kernel respiratory rhythmogenesis nucleus pre-Botzinger complex(PrBo).Furthermore,we unexpectedly found that the GABAa receptor β3 subunit is the key target for propofol's action and that it is mutually and exclusively expressed in GABAergic neurons.It is also more abundant in the mPFC and CMT,but mainly co-localized with GABAergic neurons in the PrBo.As a result,the differentiated expression pattern should mediate more neuron suppression through the activation of GABAergic neurons in the mPFC and CMT at low doses of propofol(50 μM).However,PrBo GABAergic neurons were only activated by propofol at a high dose(100 μM).These results highlight the detailed pharmacodynamic effects of propofol on consciousness-related and respiration-related nuclei and provide the distinct interaction mechanism between the β3 subunit and GABAergic neurons in mediating the suppression of consciousness compared to the inhibition of respiration. | Junli Jiang Yingfu Jiao Po Gao Wen Yin Wei Zhou Yunchun Zhang Yanjun Liu Daxiang Wen Yuan Wang Liang Zhou Tian Yu Weifeng Yu | 2021 | Acta Biochimica et Biophysica Sinica2021，53，8： | 11 |
| 2 | Twa1/Gid8 is a β-catenin nuclear retention factor in Wnt signaling and colorectal tumorigenesis显示文摘 | Yi Lu Shanshan Xie Wen Zhang Cheng Zhang Cheng Gao Qiang Sun Yuqi Cai Zhangqi Xu Min Xiao Yanjun Xu Xiao Huang Ximei Wu Wei Liu Fudi Wang Yibin Kang Tianhua Zhou | 2017 | Cell Research2017，27，12： | 9 |
| 3 | Toripalimab plus chemotherapy as second-line treatment in previously EGFR-TKI treated patients with EGFR-mutant-advanced NSCLC:a multicenter phase-II trial显示文摘This multicenter phase-II trial aimed to investigate the efficacy,safety,and predictive biomarkers of toripalimab plus chemotherapy as second-line treatment in patients with EGFR-mutant-advanced NSCLC.Patients who failed from first-line EGFR-TKIs and did not harbor T790M mutation were enrolled.Toripalimab plus carboplatin and pemetrexed were administrated every three weeks for up to six cycles,followed by the maintenance of toripalimab and pemetrexed.The primary endpoint was objective-response rate(ORR).Integrated biomarker analysis of PD-L1 expression,tumor mutational burden(TMB),CD8+tumor-infiltrating lymphocyte(TIL)density,whole-exome,and transcriptome sequencing on tumor biopsies were also conducted.Forty patients were enrolled with an overall ORR of 50.0%and disease-control rate(DCR)of 87.5%.The median progression free survival(PFS)and overall survival were 7.0 and 23.5 months,respectively.The most common treatment-related adverse effects were leukopenia,neutropenia,anemia,ALT/AST elevation,and nausea.Biomarker analysis showed that none of PD-L1 expression,TMB level,and CD8+TIL density could serve as a predictive biomarker.Integrated analysis of whole-exome and transcriptome sequencing data revealed that patients with DSPP mutation had a decreased M2 macrophage infiltration and associated with longer PFS than those of wild type.Toripalimab plus chemotherapy showed a promising anti-tumor activity with acceptable safety profiles as the second-line setting in patients with EGFR-mutant NSCLC.DSPP mutation might serve as a potential biomarker for this combination.A phase-III trial to compare toripalimab versus placebo in combination with chemotherapy in this setting is ongoing(NCT03924050). | Tao Jiang Pingyang Wang Jie Zhang Yanqiu Zhao Jianying Zhou Yun Fan Yongqian Shu Xiaoqing Liu Helong Zhang Jianxing He Guanghui Gao Xiaoqian Mu Zhang Bao Yanjun Xu Renhua Guo Hong Wang Lin Deng Ningqiang Ma Yalei Zhang Hui Feng Sheng Yao Jiarui Wu Luonan Chen Caicun Zhou Shengxiang Ren | 2021 | Signal Transduction and Targeted Therapy2021，6，11： | 8 |
| 4 | Mechanism for suspension magnetization roasting of iron ore using straw-type biomass reductant显示文摘As an alternative reductant for fossil fuel in the future,straw-type biomass contributes to emission reduction and green utilization in the suspension roasting process.In this study,the influences of the roasting time,roasting temperature and dose of straw-type biomass after suspension magnetization roasting(SMR) and separation were investigated.The optimal conditions were determined to be a roasting time of 7.5 min with a straw-type biomass dose of 20 wt% and a roasting temperature of 800℃ in which an iron grade of 71.07% and recovery of 94.17% were obtained for the iron concentrate.The maximum saturation magnetization under optimal conditions was 35.05 A·m^(2)·g^(-1),and the gaseous regulation of the biomass revealed that cumulative reducing gas volume was 293.93 mL at the optimal roasting time of450 s.The transformation of hematite to magnetite was detected by X-ray diffraction(XRD).During microstructure evolution,the outer layer consisting of fissures and tiny holes continuously deepened toward the core. | Yue Cao Yongsheng Sun Peng Gao Yuexin Han Yanjun Li | 2021 | International Journal of Mining Science and Technology2021，31，6： | 8 |
| 5 | Immobilization of Papain in Biosilica Matrix and Its Catalytic Property显示文摘一个新奇方法通过 papain 导致的一个 biomimetic silicification 过程为 papain 固定被开发。由在一个硅石先锋答案孵化 papain, papain 硅石合成很快形成了, papain 被包含。封装效率和恢复活动分别地是 82.60% 和 83.09% 。与面对另外的猛抛硅石的种类在 biosilica 矩阵使不能调动的酶和 biomolecules 相比,这个 papain 封装过程,一条 biomimetic 途径,由它在温和条件(在中立附近的 pH 和周围的温度) 下面的 autosilification 活动的认识到的高封装效率。而且,包含的 papain 展览提高了热, pH,再循环并且存储稳定性。运动分析证明 biomimetic 硅石矩阵显著地没妨碍底层的集体运输或产品的版本。 | ZHOU Liya WANG Cui JIANG Yanjun GAO Jing | 2013 | Chinese Journal of Chemical Engineering2013，21，6： | 8 |
| 6 | Application of Avaatech X-ray fluorescence core-scanning in Sr/Ca analysis of speleothems显示文摘Application of X-ray fluorescence core-scanning(XRF-CS) on both marine and lake sediments has achieved remarkable results. However, its application has not been widely extended to the research on speleothems. In this study, we measure the Sr abundance and the Sr/Ca ratios of three stalagmites(two aragonite stalagmites, one calcite stalagmite) using the state-of-the-art fourth-generation Avaatech high-resolution XRF core scanner. Through comparisons among different scan paths and among different scan resolutions, as well as comparisons with inductively coupled plasma optical emission spectrometer(ICP-OES), Itrax XRF, and Artax XRF results, we confirm that the Avaatech XRF core scanner could precisely, quickly, and nondestructively analyze the high-resolution Sr abundance of speleothems. Furthermore, we combine the stalagmite δ^(18)O records to explore the paleoclimatic significance of the measured stalagmite Sr/Ca. | Dong LI Liangcheng TAN Fei GUO Yanjun CAI Youbin SUN Gang XUE Xing CHENG Hong YAN Hai CHENG R.Lawrence EDWARDS Yongli GAO Jessica KELLEY | 2019 | Science China Earth Sciences2019，62，6： | 7 |
| 7 | Enzyme@silica nanoflower@metal-organic framework hybrids: A novel type of integrated nanobiocatalysts with improved stability显示文摘一个新奇综合 nanobiocatalyst 系统基于 enzyme@silica,有改进稳定性的 nanoflower@metal 器官的框架(enzyme@SNF@ZIF-8 ) 结构第一次被制作。这个系统的通用性作为模型酶用青霉素 G acylase (针网阵列) 和过氧化氢酶(猫) 被验证。多微孔的 ZIF-8 层能被改变 ZIF-8 涂层周期的数字控制,它与不同 ZIF-8 层厚度生产 PGA@SNF@ZIF-8 nanobiocatalysts。在第二个 ZIF-8 涂层周期以后, PGA@SNF@ZIF-8 (2 ) 结构与一同类并且 well-intergrown ZIF-8 层被形成,它拥有优秀机械、化学的稳定性。而且, PGA@SNF@ZIF-8 (2 ) 表演与在硅石 nanoflowers (PGA@SNF ) 上使不能调动的免费针网阵列和针网阵列相比改进了 thermal/storage 稳定性和可重用性。获得的基于猫的 nanobiocatalysts (CAT@SNF@ZIF-8 (2 )) 也显示出优秀催化性能。 | Yingjie Du Jing Gao Huajiao Liu Liya Zhou Ying He Zhihong Huang Yanjun Jiang | 2018 | Nano Research2018，11，8： | 5 |
| 8 | Preparation of cross-linked enzyme aggregates of nitrile hydratase ES-NHT-118 from E.coli by macromolecular cross-linking agent显示文摘Cross-linked enzyme aggregates(CLEAs) of nitrile hydratase(NHase) ES-NHT-118 from Escherichia coli were prepared by using ammonium sulfate as precipitating agent followed by cross-linking with dextran polyaldehyde for the first time. In this process, egg white was added as protein feeder for facilitating the formation of CLEAs. The optimal conditions of the immobilization process were determined. Michaelis constants(Km) of free NHase and NHase CLEAs were also determined. The NHase CLEAs exhibited increased stability at varied pH and temperature conditions compared to its free counterpart. When exposed to high concentrations of acrylamide, NHase CLEAs also exhibited effective catalytic activity. | Liya Zhou Haixia Mou Jing Gao Li Ma Ying He Yanjun Jiang | 2017 | Chinese Journal of Chemical Engineering2017，25，4： | 5 |
| 9 | A Virulent PEDV Strain FJzz1 with Genomic Mutations and Deletions at the High Passage Level Was Attenuated in Piglets via Serial Passage In Vitro显示文摘Highly virulent porcine epidemic diarrhea virus(PEDV)strains re-emerged and circulated in China at the end of 2010,causing significant economic losses in the pork industry worldwide.To understand the genetic dynamics of PEDV during its passage in vitro,the PEDV G2 strain FJzzl was serially propagated in Vero cells for up to 200 passages.The susceptibility and adaptability of the FJzzl strain increased gradually as it was serially passaged in vitro.Sequence analysis revealed that amino acid(aa)changes were mainly concentrated in the S glycoprotein,which accounted for 72.22%-85.71%of all aa changes.A continuous aa deletion(^(55)I^(56)G^(57)E→^(55)K^(56)Δ^(57)Δ)occurred in the N-terminal domain of S1(Sl-NTD).To examine how the aa changes affected its virulence,FJzzl-F20 and FJzzl-F200 were selected to simultaneously evaluate their pathogenicity in suckling piglets.All the piglets in the FJzzl-F20-infected group showed typical diarrhea at 24 h postinfection,and the piglets died successively by 48 h postinfection.However,the clinical signs of the piglets in the FJzzl-F200-infected group were significantly weaker,and no deaths occurred.The FJzzl-F200-infected group also showed a lower level of fecal viral shedding and lower viral loads in the intestinal tissues,and no obvious histopathological lesions.TypeⅠandⅢinterferon were induced in the FJzzl-F200 infection group,together with pro-inflammatory cytokines,such as TNF-α,IL-1βand IL-8.These results indicate that the identified genetic changes may contribute to the attenuation of FJzzl strain,and the attenuated FJzzl-F200 may have the potential for developing PEDV live-attenuated vaccines. | Pengfei Chen Xiongwei Zhao Shuting Zhou Tianxing Zhou Xiangmei Tan Xia Wu Wu Tong Fei Gao Lingxue Yu Yifeng Jiang Hai Yu Zhibiao Yang Guangzhi Tong Yanjun Zhou | 2021 | Virologica Sinica2021，36，5： | 4 |
| 10 | Activation of anterior thalamic reticular nucleus GABAergic neurons promotes arousal from propofol anesthesia in mice显示文摘Propofol is widely used for the induction and maintenance of anesthesia,which causes a rapid loss of consciousness.However,the mechanisms underlying the hypnosis effect of propofol are still not fully understood.The thalamic reticular nucleus(TRN)is crucial for regulating wakefulness,sleep rhythm generation,and sleep stability,while the role of TRN in the process of propofol-induced anesthesia is still unknown.Here,we investigated the function of the anterior TRN in propofol general anesthesia.Our results demonstrated that the neural activity of anterior TRN is suppressed during propofol anesthesia,whereas it is robustly activated from anesthesia by recording the calcium signals using fiber photometry technology.The results showed that the activation of anterior TRN neurons by chemogenetic and optogenetic methods shortens the emergency time without changing the induction time.Conversely,chemogenetic or optogenetic inhibition of the TRN neurons leads to a delay in the recovery time.Our study showed that anterior TRN is crucial for behavioral arousal without affecting the induction time of propofol anesthesia. | Yanjun Liu Bing Chen Yirong Cai Yuan Han Ying Xia Nanqi Li Bingqian Fan Tianjie Yuan Junli Jiang Po Gao Weifeng Yu Yingfu Jiao Wenxian Li | 2021 | Acta Biochimica et Biophysica Sinica2021，53，7： | 3 |
| 11 | Casein kinase Ⅱ interacts with prion protein in vitro and forms complex with native prion protein in vivo显示文摘最必要、关键的步在能递送的海绵状的 encephalopathy 的致病期间是到病理学的 isoform 的细胞的 prion 蛋白质的 conformational 变化。酷蛋白 kinase II (CK2 ) 是一无所不在地表示了并且 evolutionarily 保存了为生存能力是必要的多种的蛋白质 kinase。探索在 CK2 和 prion 蛋白质(PrP ) 之间的可能的分子的相互作用,人的 CK2α 和 CK2β 的全身的序列互补 DNA 作为模板从房间线 SH-SY5Y 用彻底的送信人 RNA 与反向的抄写聚合酶链反应被放大;然后,熔化蛋白质 histidine-CK2α 和谷胱甘肽 S-transferase-histidine-CK2β 在 Escherichia 关口 i 被表示。在 CK2 和 PrP 之间的相互作用与 co-immunoprecipitation 和下拉试金被评估。结果证明 recombinant PrP 与 CK2α ,然而并非与 CK2β 明确地跳了。在仓鼠大脑的本国的 CK2 和 PrP 与对方一起交往了,形成蛋白质建筑群。从正常大脑的 PrP (diglycosylated, monoglycosylated 和 unglycosylated PrP ) 的三种不同 glycosylated 形式与 CK2α 子单元交往了,尽管 unglycosylated PrP 似乎与 CK2α 子单元有一个更强壮的有约束力的能力。负责与 CK2α 交往的领域在 PrP 的 C 终端片断被定位(残余 91 231 ) 。这研究为在 PrP 和 CK2α 之间的分子的相互作用建议了可靠试验性的数据(两个在 recombinant 和本国的范畴) ,为进一步估计 PrP-CK2 相互作用的潜在的生物意义的科学线索,和在 prion 疾病的致病的 CK2 的可能的角色。 | Jianming Chen Chen Gao Qi Shi Guirong Wang Yanjun Lei Bing Shan Baoyun Zhang Chenfang Dong SongShi Xin Wang Chan Tian Jun Han Xiaoping Dong | 2008 | Acta Biochimica et Biophysica Sinica2008，40，12： | 3 |
| 12 | Scattered Rural Settlements and Development of Mountainous Regions in Western Sichuan,China显示文摘Making rural settlements of Mountainous Regions in Western Sichuan as the study objects and using symbolic statistical methods,then combining the case study of Daofu County,the paper analyzes the negative impact of the scattered rural settlements on infrastructure construction,farm-ers' income increase and mountain ecological reconstruction in mountainous regions of western Sichuan. The results indicate that economic density is posi-tively related to both rural settlements density(R2=0.73) and rural population density(R2=0.77) ,and it is the same for relationship between towns density and rural settlements density(R2=0.88) and between towns density and eco-nomic density(R2=0.71) ,and the scattered distribution pattern of the rural settlements and shortage of economic centers is a major factor to the lagged socioeconomic development. On the eco-economic zoning to Daofu County,the paper indicates the spatial distribution model and the industrial develop-ment model of the rural settlements need to be changed,and rural population should be concentrated in larger rural settlements with development of off-farm industries while infrastructure construction is to reinforced. | GAO Yanjun CHEN Guojie SHEN Maoying | 2007 | Wuhan University Journal of Natural Sciences2007，12，4： | 3 |
| 13 | Hippocampus is more vulnerable to neural damages induced by repeated sevoflurane exposure in the second trimester than other brain areas显示文摘During the rapidly developing and sensitive period of the central nervous system (CNS), a harmful stimulus may have serious consequences. The effect of anesthetic exposure on the development of the offspring’s CNS during pregnancy is still unclear and has been widely concerned. In the present study, we compared the susceptibility of the hippocampus with those of other brain regions in offsprings when the mother mice were exposed to repeated sevoflurane. We found that other than affecting motor sensation, emotion, or social behavior of offspring mice, repeated sevoflurane exposure induced significant memory deficiency. Compared with other brain regions, the hippocampus, which is the key component of the brain serving for learning and memory, was more vulnerable to repeated sevoflurane exposure. We also found that repeated sevoflurane exposure to mother mice could inhibit the axon development of hippocampal neurons. We also predicted that N6-methyladenosine modification of mRNA might play an essential role in the vulnerability of the hippocampus to sevoflurane, while the underlying cellular mechanism needs to be explored in the future. Our study may provide a new perspective for studying the mechanism of hippocampus-specific injury induced by sevoflurane exposure. | Bing Chen Yanjun Liu Yirong Cai Dan Tang Saihong Xu Po Gao Weifeng Yu Yingfu Jiao Wenxian Li | 2020 | Acta Biochimica et Biophysica Sinica2020，52，8： | 3 |
| 14 | Phase Ⅲ Clinical Trials of the Cell Differentiation Agent-2 (CDA-2): Therapeutic Efficacy on Breast Cancer, Non-Small Cell Lung Cancer and Primary Hepatoma显示文摘 | Fengyi Feng Qing Lu Changquan Ling Yang Zhang Fengzhan Qin Huaqing Wang Wenxia Huang Shunchang Jiao Qiang Chen Mingzhong Li Yunzhong Zhu Meizhen Zhou Jun Ren Yetao Gao Jingpo Zhao Rongsheng Zheng Wenhua Zhao Zhiqiang Meng Fang Li Qizhong Zhang Dongli Zhao Liyan Xu Yongqiang Zhang Yanjun Zhang Zhenjiu Wang Shuonqi Liu Ming C. Liau | 2005 | Chinese Journal of Clinical Oncology2005，2，4： | 3 |
| 15 | Improving the Weld Formation and Mechanical Properties of the AA-5A06 Friction Pull Plug Welds by Axial Force Control显示文摘In the present study, the weld formation and mechanical properties of the AA-5A06 friction pull plug welded(FPPW) joints were improved by controlling the axial force history. Several defect-free FPPW joints were made successfully by using the welding parameters of 15–20 k N/s axial loading rate, 20–30 k N axial welding force and 6–7 mm axial feeding displacement. The results indicated that using higher axial loading rate and axial welding force produced more stable heat generation and shorter frictional heating time between the frictional interface. In this case, the plastic flow of the materials around the hole could be further improved since the axial feeding displacement of the plug was increased. The maximum ultimate tensile strength(UTS) and elongation of the FPPW 5A06 joints were 314 MPa and 4.8%, respectively. The thermal mechanically affect zone(TMAZ) had the lowest hardness value throughout the joint and was found as the fracture location to all the tensile samples. The softening of TMAZ was mainly caused by the weakening of the cold work hardening and the coarsening of grains. | Jinyong Gao Lijun Yang Lei Cui Peng Lu Jun Yang Yanjun Gao | 2020 | Acta Metallurgica Sinica(English Letters)2020，33，6： | 3 |
| 16 | An Effective Asphalt UV Blocking Material Based on Host-Guest Schiff Base/Layered Double Hydroxides显示文摘 | Chunhui Xia Rui Gao Kaitao Li Yang Yang Yanjun Lin Dongpeng Yan | 2017 | Chinese Journal of Chemistry2017，35，11： | 3 |
| 17 | Prediction of major adverse cardiac events is the first critical task in the management of immune checkpoint inhibitor-associated myocarditis显示文摘Dear Editor,The application of immune checkpoint inhibitors(ICIs),anti-tumor immunotherapy unleashing the host immune system to eradicate tumor cells,has revolutionized the treatment of various advanced cancers and showed remarkable anti-tumor effects[1].However,emphasis must be placed on fatal immune-related adverse events(irAEs),especially some fulminant irAEs like ICI-related cardiovascular AEs[2,3].However,due to the low rate of cardiovascular AEs,little is known about the effective methods for evaluating the risk of catastrophic cardiac events in ICI-associated myocarditis and its management[4,5]. | Yan Xu Yanjun Song Xiaoyan Liu Yuequan Shi Yingxian Liu Hao Qian Xiaoxing Gao Minjiang Chen Ruili Pan Jing Zhao Wei Zhong Wei Wu Mengzhao Wang | 2022 | Cancer Communications2022，42，9： | 3 |
| 18 | PrP mutants with different numbers of octarepeat sequences are more susceptible to the oxidative stress显示文摘One of the physiological functions of cellular prion protein(PrP C )is believed to work as a cellular resistance to oxidative stress,in which the octarepeats region within PrP plays an important role.However,the detailed mechanism is less clear.In this study,the expressing plasmids of wild-type PrP (PrP-PG5)and various PrP mutants containing 0(PrP-PG0),9(PrP-PG9)and 12(PrP-PG12)octarepeats were generated and PrP proteins were expressed both in E.coli and in mammalian cells.Protein aggregation and formation of carbonyl groups were clearly seen in the recombinant PrPs expressed from E.coli after treatment of H2O2.MTT and trypan blue staining assays revealed that the cells expressing the mutated PrPs within octarepeats are less viable than the cells expressing wild-type PrP.Statistically significant high levels of intracellular free radicals and low levels of glutathione peroxidase were observed in the cells transfected with plasmids containing deleted or inserted octarepeats.Remarkably more productions of carbonyl groups were detected in the cells expressing PrPs with deleted and inserted octarepeats after exposing to H2O2.Furthermore,cells expressing wild-type PrP showed stronger resistant activity to the challenge of H2O2 at certain extent than the mutated PrPs and mock. These data provided the evidences that the octarepeats number within PrP is critical for maintaining its activity of antioxidation.Loss of its protective function against oxidative stress may be one of the possible pathways for the mutated PrPs to involve in the pathogenesis of familial Creutzfeldt-Jacob diseases. | AN Run1 ,2,DONG ChenFang 2,LEI YanJun 1,2,HAN Lu 2,LI Ping 2,CHEN JianMing 2,WANG GuiRong 2, SHI Qi 2 ,GAO Chen 2 ,JIANG HuiYing 2 ,ZHOU Wei 2 ,HAN Jun 2 ,CHU YongLie 1 ,DONG XiaoPing 2 1School of Medicine,Xi’an JiaoTong University,Xi’an 710061,China 2State Key Laboratory for Infectious Disease Prevention and Control,National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention,YingXin Rd 100,Beijing 100052,China | 2008 | Science China(Life Sciences)2008，51，7： | 3 |
| 19 | Doppel-induced cytotoxicity in human neuronal SH-SY5Y cells is antagonized by the prion protein显示文摘Doppel (Dpl ) 由于结构、生物化学的类似是象蛋白质一样的 prion (PrP ) ;然而, Dpl 和 PrP 的自然功能仍然保持不清楚。在这研究,编码 Dpl 蛋白质的一个 531-bp 人 PRND 基因序列从人的外部血白细胞被放大。全身、各种各样的截断的人的 Dpl 和 PrP 蛋白质从 Escherichia 被表示并且净化 coli。全身的 Dpl 的补充导致了显著 cytotoxicity,和负责的区域到人的 neuroblastoma 房间 SH-SY5Y 上因为它的 cytotoxicity 在 Dpl 的中间的片断被印射[氨基酸(aa ) 81122 ] 。有趣地,导致 Dpl 的 cytotoxicity 被全身的野类型的 PrP 的存在反对。PrP 异种的碎片上的分析证明 N 终端碎裂(aa 2390 ) PrP 为保护的活动负责。有 Dpl 在 SH-SY5Y 房间上导致了象 Dpl 一样 cytotoxicity 的类似的第二等的结构的截断的 PrP (PrP32121 ) 。而且,铜离子的绑定能在导致 Dpl 的 cytotoxicity 上提高 PrP 的反对效果。Apoptosis 试金表明 Dpl 导致的 cytotoxicity 通过 apoptotic 机制发生了。这些结果建议 Dpl 的功能对 PrP 而非 synergistic 对抗。 | Ping Li Chenfang Dong Yanjun Lei Bing Shan Xinli Xiao Huiying Jiang Xin Wang Chen Gao Qi Shi Kun Xu Chan Tian Jun Han Xiaoping Dong | 2009 | Acta Biochimica et Biophysica Sinica2009，41，1： | 3 |
| 20 | Self-immolative micellar drug delivery:The linker matters显示文摘Redox-responsive polymer-drug conjugate micelles are excellent nanoscale vehicles for self-immolative intracellular drug delivery.To covalently connect the polymer and drug,disulfide-bearing linkers,such as 3,3'-dithiodipropionic acid (DDPA) and 4,4'-dithiodibutyric add (DDBA),are used.In this paper,we report the influence of linker length on the therapeutic outcome of redox-sensitive conjugate micelles.Curcumin was selected as the model drug and it was conjugated to a multivalent methoxy poly(ethylene glycol)-polylysine copolymer with DDPA or DDBA as the linker.The obtained two polymer-curcumin conjugates were amphiphilic and could self-assemble into micelles that have a hydrodynamic diameter less than 100 nm.The loading of curcumin in both micelles was above 20% (w/w).Irrespective of the linker type,micelle disassembly was observed due to the collapse of the disulfide bond in a reducing environment.However,the rate of curcumin release was much faster with the DDBA linker than with the DDPA linker as the side product was a 5-membered ring with a low ring strain.The linker length-induced variation of curcumin release kinetics caused a significant difference in the intracellular drug concentration and a higher cytotoxicity was witnessed in three model cell lines (HeLa,PC3,and 4T1) for the micelles with a DDBA linker compared to those containing a DDPA linker.As expected,this phenomenon was also observed in HeLa tumor-bearing nude mice in vivo.The current work highlights the significance of linker length in engineering redox-responsive on-demand delivery systems. | Xuan Meng Min Gao Jian Deng Di Lu Aiping Fan Dan Ding Deling Kong Zheng Wang Yanjun Zhao | 2018 | Nano Research2018，11，12： | 2 |
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