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| 1 | Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion显示文摘The recent outbreak of coronavirus disease(COVID-19)caused by SARS-CoV-2 infection in Wuhan,China has posed a serious threat to global public health.To develop specific anti-coronavirus therapeutics and prophylactics,the molecular mechanism that underlies viral infection must first be defined.Therefore,we herein established a SARS-CoV-2 spike(S)protein-mediated cell-cell fusion assay and found that SARS-CoV-2 showed a superior plasma membrane fusion capacity compared to that of SARS-CoV.We solved the X-ray crystal structure of six-helical bundle(6-HB)core of the HR1 and HR2 domains in the SARS-CoV-2 S protein S2 subunit revealing that several mutated amino acid residues in the HR1 domain may be associated with enhanced interactions with the HR2 domain.We previously developed a pan-coronavirus fusion inhibitor,EK1,which targeted the HR!domain and could inhibit infection by divergent human coronaviruses tested,including SARS-CoV and MERS-CoV.Here we generated a series of lipopeptides derived from EK1 and found that EK1C4 was the most potent fusion inhibitor against SARS-CoV-2 S protein-mediated membrane fusion and pseudovirus infection with IC50s of 1.3 and 15.8 nM,about 241-and 149-fold more potent than the original EK1 peptide,respectively.EK1C4 was also highly effective against membrane fusion and infection of other human coronavirus pseudoviruses tested,including SARS-CoV and MERS-CoV,as well as SARSr-CoVs,and potently inhibited the replication of 5 live human coronaviruses examined,including SARS-CoV-2.Intranasal application of EK1C4 before or after challenge with HCoV-OC43 protected mice from infection,suggesting that EK1C4 could be used for prevention and treatment of infection by the currently circulating SARS-CoV-2 and other emerging SARSr-CoVs. | Shuai Xia Meiqin Liu Chao Wang Wei Xu Qiaoshuai Lan Siliang Feng Feifei Qi Linlin Bao Lanying Du Shuwen Liu Chuan Qin Fei Sun Zhengli Shi Yun Zhu Shibo Jiang Lu Lu | 2020 | Cell Research2020，30，4： | 81 |
| 2 | H7N9 virulent mutants detected in chickens in China pose an increased threat to humans显示文摘 | Jianzhong Shi Guohua Deng Huihui Kong Chunyang Gu Shujie Ma Xin Yin Xianying Zeng Pengfei Cui Yan Chen Huanliang Yang Xiaopeng Wan Xiurong Wang Liling Liu Pucheng Chen Yongping Jiang Jinxiong Liu Yuntao Guan Yasuo Suzuki Mei Li Zhiyuan Qu Lizheng Guan Jinkai Zang Wenli Gu Shuyu Han Yangming Song Yuzhen Hu Zeng Wang Linlin Gu Wenyu Yang Libin Liang Hongmei Bao Guobin Tian Yanbing Li Chuanling Qiao Li Jiang Chengjun Li Zhigao Bu Hualan Chen | 2017 | Cell Research2017，27，12： | 70 |
| 3 | Phosphorylcholine polymer nanocapsules prolong the circulation time and reduce the immunogenicity of therapeutic proteins显示文摘蛋白质治疗,治疗学的蛋白质在那里被交付对待混乱,为治疗疾病被认为最安全、很直接的途径。然而,它的应用被有效策略的少量高度为在他们的管理以后在 vivo 交付蛋白质和治疗学的蛋白质的快速的清理限制。这里,我们表明能显著地延长治疗学的蛋白质的发行量时间以及最小化他们的 immunogenicity 的新奇策略。这被与抵抗蛋白质吸附的 crosslinked phosphorylcholine 聚合物的薄层包含单个蛋白质分子完成。通过广泛的细胞的研究,我们证明 crosslinked phosphorylcholine 聚合物壳有效地阻止包含的蛋白质是由巨噬细胞的 phagocytosed,它在 vivo 在 nanoparticles 的清理起一个必要作用。而且,聚合物壳阻止包含的蛋白质被有免疫力的房间识别。作为结果,对治疗学的蛋白质的有免疫力的回答有效地被压制。这个工作描述一个可行方法延长循环时间并且减少治疗学的蛋白质的 immunogenicity,它可以在多样的疾病的治疗支持新奇蛋白质治疗的发展和申请。 | Sheng Liang Yang Liu Xin Jin Gan Liu Jing Wen Linlin Zhang Jie Li Xubo Yuan Irvin S.Y. Chen Wei Chen Hui Wang Linqi Shi Xinyuan Zhu Yunfeng Lu | 2016 | Nano Research2016，9，4： | 11 |
| 4 | Carboniferous Alaskan-type complex along the Sino–Mongolian boundary,southern margin of the Central Asian Orogenic Belt显示文摘We present zircon ages and geochemical data for the Hongshishan Carboniferous Alaskan-type mafic–ultramafic complex exposed in the Beishan area along the Sino–Mongolian boundary, southern margin of the Central Asian Orogenic Belt. This complex mainly consists of dunite,harzburgite, lherzolite, wehrlite, and gabbro, which intrudes Early Carboniferous volcanic rocks and reveals a zoned structure. Zircons of a gabbro sample yielded a 206Pb/238 U age of 357 ± 4 Ma, reflecting the time of Early Carboniferous magmatism. Zircon ages were also obtained for an andesite(322 ± 3 Ma) and a basaltic andesite(304 ± 2 Ma).High initial Nd isotope whole-rock values suggest that the Hongshishan gabbro [e_(Nd(t))= +9.6-+10.2] and basalt[eNd(t)= +10.0-+10.8] were derived from a depleted mantle source. Slightly lower eNd(t)values for the ultramafic rocks [eNd(t)= +8.5-+8.7] suggest some interaction of the parental magma with the continental crust. In contrast, the Late Carboniferous Quershan samples in this area represent subduction-related arc volcanic rocks with Adakite-like compositions. The early Carboniferous Hongshishan Alaskan-type complex was interpreted to represent the remnants of a magma chamber that crystallized at the base of a mature island arc, whereas the Quershan island arc volcanic rockssuggest the resurrection of the subduction process after arccontinent collision and uplift of the roots of the arc. | Yuruo Shi Linlin Li Alfred Kroner Jing Ding Wei Zhang Zengbao Huang Ping Jian | 2017 | Acta Geochimica2017，36，2： | 6 |
| 5 | First demonstration of 1.3μm quarter-wavelength shift distributed feedback(DFB) semiconductor laser based on conventional photolithography显示文摘A 1.3 μm distributed feedback(DFB) semiconductor laser with equivalent λ/4 phase shift based on reconstruction equivalent chirp(REC) technique is numerically studied and experimentally demonstrated.The simulation results show that the 1.3 μm DFB laser with equivalent λ/4 phase shift based on the REC technique performs the same as that of actual λ/4 phase shift DFB laser,with nearly the same P-I curves,the internal power distributions and the output ASE spectra.Compared with the traditional λ/4 phase shift DFB laser,the REC based laser only changes the sampling structures with the uniform seed waveguide grating instead of the actual grating structures.As a result,the fabrication of such laser will be very easy.In this paper,we successfully fabricated the 1.3 μm DFB laser based on the REC technique for the first time to the best of our knowledge. | LU LinLin SHI YueChun CHEN XiangFei | 2013 | Chinese Science Bulletin2013，58，7： | 6 |
| 6 | Quantification of microcystin-producing and non-microcystin producing Microcystis populations during the 2009 and 2010 blooms in Lake Taihu using quantitative real-time PCR显示文摘Lake Taihu,a large,shallow hypertrophic freshwater lake in eastern China,has experienced lake-wide toxic cyanobacterial blooms annually during summer season in the past decades.Spatial changes in the abundance of hepatotoxin microcystin-producing and nonmicrocystin producing Microcystis populations were investigated in the lake in August of 2009 and 2010.To monitor the densities of the total Microcystis population and the potential microcystin-producing subpopulation,we used a quantitative real-time PCR assay targeting the phycocyanin intergenic spacer(PC-IGS) and the microcystin synthetase gene(mcyD),respectively.On the basis of quantification by real-time PCR analysis,the abundance of potential toxic Microcystis genotypes and the ratio of the mcyD subpopulation to the total Microcystis varied significantly,from 4.08×104 to 5.22×107 copies/mL,from 5.7% to 65.8%,respectively.Correlation analysis showed a strong positive relationship between chlorophyll-a,toxic Microcystis and total Microcystis;the abundance of toxic Microcystis correlated positively with total phosphorus and ortho-phosphate concentrations,but negatively with TN:TP ratio and nitrate concentrations.Meanwhile the proportion of potential toxic genotypes within Microcystis population showed positive correlation with total phosphorus and ortho-phosphate concentrations.Our data suggest that increased phosphorus loading may be a significant factor promoting the occurrence of toxic Microcystis bloom in Lake Taihu. | Daming Li Fanxiang Kong Xiaoli Shi Linlin Ye Yang Yu Zhen Yang | 2012 | Journal of Environmental Sciences2012，24，2： | 5 |
| 7 | Extreme Pressure Equipments显示文摘Pressure equipments in the process industries and the newly developing industries usually have extreme sizes and/or are subjected to extreme operating conditions such as high pressure,blast loading,cryogenic temperature,elevated temperature,complex corrosion,and so on.In order to understand,research and develop these equipments systematically,a concept of extreme pressure equipments(EPEs) is proposed.The applications and demands of EPEs in petrochemical industry,coal chemical industry,advanced energy,military,space technology,and environment protection are introduced.Basic scientific problems in material,design,inspection, and safety related to EPEs are discussed.Then,take chemical composition,manufacturing process,service duration,and operating conditions for example,main factors which affect material properties of EPEs are analyzed.New design concepts including design based on life cycle,dynamic design and light-weight design are introduced.EPEs with higher efficiency,lower cost and safer performance are in urgent demand in national major projects including ten million ton oil refinery,one million ton ethylene,liquefied natural gas transportation,and nuclear power plant.Thus,further research should be conducted on information acquisition, multi-mechanism damage coupling model,damage inspection,life prediction,online safety monitoring,maintenance strategy,safety pre-warning system,and emergency system. | ZHENG Jinyang WU Linlin SHI Jianfeng | 2011 | Chinese Journal of Mechanical Engineering2011，24，2： | 4 |
| 8 | Organ donation in China:the major progress and the continuing problem显示文摘China has banned harvesting organs from executed prisoners since January 1st,2015[1],making voluntary donation the only legitimate venue for organ transplant.It is a critical move to settle all the controversies about China’s organ transplant process by making a loud and strong statement worldwide that the Chinese government respects human rights and is streamlining its organ transplant process to conform | Ni An Yuanyuan Shi Yabo Jiang Linlin Zhao | 2016 | The Journal of Biomedical Research2016，30，2： | 4 |
| 9 | Experimental demonstration of the three-phase-shifted DFB semiconductor laser with buried heterostructure using common holographic exposure显示文摘In this article,we report the first experimental demonstration of the three-phase-shifted(3PS)DFB semiconductor laser with buried heterostructure based on the Reconstruction-Equivalent-Chirp(REC)technique.The simulation results show that the performances of the equivalent 3PS DFB semiconductor laser are nearly the same as those of the true 3PS laser.Compared with the quarter-wave-phase shift(QWS)DFB semiconductor laser,the 3PS DFB semiconductor laser shows better single-longitude-mode(SLM)property even at high injection current with high temperature.However,it only changes theμm-level sampling structures but the seed grating is uniform using the REC technique.Therefore,its fabrication cost is low. | LU LinLin CAO BaoLi ZHANG LiBo TANG Song LI LianYan LI SiMin SHI YueChun CHEN XiangFei | 2014 | Science China(Technological Sciences)2014，57，11： | 4 |
| 10 | Can Ecological Product Win Consumers in China? A Study on the Effect of Product Attributes and Consumers' Face Consciousness on Ecological Product Preference显示文摘 | Zhuomin Shi Linlin Wen Wanyi Zheng | 2014 | Frontiers of Business Research in China2014，8，2： | 3 |
| 11 | SARS-CoV-2 infection aggravates chronic comorbidities of cardiovascular diseases and diabetes in mice显示文摘Background:Cardiovascular diseases(CVDs)and diabetes mellitus(DM)are top two chronic comorbidities that increase the severity and mortality of COVID-19.However,how SARS-CoV-2 alters the progression of chronic diseases remain unclear.Methods:We used adenovirus to deliver h-ACE2 to lung to enable SARS-CoV-2 infection in mice.SARS-CoV-2’s impacts on pathogenesis of chronic diseases were studied through histopathological,virologic and molecular biology analysis.Results:Pre-existing CVDs resulted in viral invasion,ROS elevation and activation of apoptosis pathways contribute myocardial injury during SARS-CoV-2 infection.Viral infection increased fasting blood glucose and reduced insulin response in DM model.Bone mineral density decreased shortly after infection,which associated with impaired PI3K/AKT/mTOR signaling.Conclusion:We established mouse models mimicked the complex pathological symptoms of COVID-19 patients with chronic diseases.Pre-existing diseases could impair the inflammatory responses to SARS-CoV-2 infection,which further aggravated the pre-existing diseases.This work provided valuable information to better understand the interplay between the primary diseases and SARS-CoV-2 infection. | Yuanwu Ma Dan Lu Linlin Bao Yajin Qu Jiangning Liu Xiaolong Qi Lei Yu Xu Zhang Feifei Qi Qi Lv Yunpeng Liu Xudong Shi Caixian Sun Jing Li Jie Wang Yunlin Han Kai Gao Wei Dong Ning Liu Shan Gao Jing Xue Qiang Wei Sidan Pan Hong Gao Lianfeng Zhang Chuan Qin | 2021 | Animal Models and Experimental Medicine2021，4，1： | 3 |
| 12 | Seismic behavior of breakwaters on complex ground by numerical tests:Liquefaction and post liquefaction ground settlements显示文摘A large number of breakwaters have been constructed along coasts to protect humans and infrastructures from tsunamis.There is a risk that foundation soils of these structures may liquefy,or partially liquefy during the earthquake preceding a tsunami,which would greatly reduce the structures’capacity to resist the tsunami.It is necessary to consider not only the soil’s liquefaction behavior due to earthquake motions but also its post-liquefaction behavior because this behavior will affect the breakwater’s capacity to resist an incoming tsunami.In this study,numerical tests based on a sophisticated constitutive model and a soil-water coupled finite element method are used to predict the mechanical behavior of breakwaters and the surrounding soils.Two real breakwaters subjected to two different seismic excitations are examined through numerical simulation.The simulation results show that,earthquakes affect not only the immediate behavior of breakwaters and the surrounding soils but also their long-term settlements due to post-earthquake consolidation.A soil profile with thick clayey layers beneath liquefied soil is more vulnerable to tsunami than a soil profile with only sandy layers.Therefore,quantitatively evaluating the seismic behavior of breakwaters and surrounding soils is important for the design of breakwater structures to resist tsunamis. | Gu Linlin Zhang Feng Bao Xiaohua Shi Zhenming Ye Guanlin Ling Xianzhang | 2018 | Earthquake Engineering and Engineering Vibration2018，17，2： | 3 |
| 13 | In-Situ SHRIMP U-Pb Dating of Xenotime Outgrowth on Detrital Zircon Grains from the Changzhougou Formation of the Ming Tomb District, Beijing显示文摘SHRIMP U-Pb dating of diagenetic xenotime from sedimentary rocks has provided age constraints for sedimentary diagenesis(Mc Naughton et al.,1999;Fletcher et al.,2000;England et al.,2001;Rasmussen et al.,2004;Vallini et al.,2007).Xenotime(YPO4)may grow during early diagenesis,typically being present as a trace constituent in siliciclastic sedimentary rocks(Rasmussen,2005),in the form of syntaxial outgrowths on detrital zircon grains.Diagenetic xenotime occurs in | SHI Yuruo Kennedy ALLEN Aleinikoff JOHN SONG Tianrui LI Linlin SUN Huiyi | 2015 | Acta Geologica Sinica(English Edition)2015，89，1： | 3 |
| 14 | A solvothermal pre-oxidation strategy converting pitch from soft carbon to hard carbon for enhanced sodium storage显示文摘Due to its low cost and easy availability, the pitch is considered a promising precursor for soft carbon anodes. However, pitch-derived soft carbon shows a high graphitization degree and small interlayer spacing, resulting in its much lower sodium storage performance than hard carbon. We propose a novel preoxidation strategy to introduce additional oxygen atoms into the low-cost soft carbon precursor pitch to fabricate a defect-rich and large-interlayer spacing hard carbon anode(HPP-1100). Compared with the direct pyrolysis of pitch carbon, the sodium storage capacity of HPP-1100 is significantly improved from 120.3 m Ah/g to 306.7 m Ah/g, with an excellent rate and cycling capability(116.5 m Ah/g at 10 C). Moreover, when assorted with an O_(3)-Na(NiFeMn)1/3O_(2)cathode, the full cell delivers a high reversible capacity of 274.0 m Ah/g at 0.1 C with superb cycle life. This work provides a new solution for realizing the application of low-cost pitch anodes in Na-ion batteries. | Jing Wang Lei Yan Binhua Liu Qingjuan Ren Linlin Fan Zhiqiang Shi Qingyin Zhang | 2023 | Chinese Chemical Letters2023，34，4： | 3 |
| 15 | Monochromatic green light stimulation during incubation shortened the hatching time via pineal function in White Leghorn eggs显示文摘Background:Effect of monochromatic green light illumination on embryo development has been reported in chickens.The avian pineal gland is an important photo-endocrine organ formed by a mediodorsal protrusion during embryonic development.However,the involvement of pineal gland in the light transduction process remains to be elucidated.In the present study,we investigated the influence of monochromatic green light on hatching time and explored the possible mechanism via pineal function.Results:A total of 600 eggs of White Leghorn(Shaver strain)were incubated under photoperiods of either 12 h of light and 12 h of darkness using monochromatic green light(12L:12D group)or 24 h of darkness(0L:24D group)for 18 d.Compared to 0L:24D group,the green light stimulation shortened the hatching time without extending the hatch window or impairing hatchability.The liver of embryos incubated in the 12L:12D light condition was heavier than those of the 0L:24D group on d 21 post incubation which may be linked to the observed increase in the serum concentration of insulin-like growth factor 1(IGF-1);primary secretion of the liver.Histological structure analysis of pineal gland demonstrated that the light stimulation increased follicle area,wall thickness and lumen area on d 10 and d 12 post incubation.Rhythmic function analysis demonstrated that three clock related genes(brain and muscle ARNT-like-1,BMAL1;circadian locomotor output cycles kaput,CLOCK;and cryptochrome-1,CRY1)and a melatonin rate-limiting enzyme related gene(arylalkylamine N-acetyltransferase,AANAT)were rhythmically expressed in the pineal gland of the 12L:12D group,but not in the 0L:24D group.Simultaneously,the light stimulation also increased the concentration of melatonin(MT),which was linked to hepatocyte proliferation and IGF-1 secretion in previous studies.Conclusions:The 12L:12D monochromatic green light stimulation during incubation shortened hatching time without impairing hatching performance.Pineal gland’s early histological development and maturation of its rhythmic function were accelerated by the light stimulation.It may be the key organ in the photo-endocrine axis that regulates embryo development,and the potential mechanism could be through enhanced secretion of MT in the 12L:12D group which promotes the secretion of IGF-1. | Panlin Wang Yanyan Sun Yunlei Li Jing Fan Yunhe Zong Adamu Mani Isa Lei Shi Yuanmei Wang Aixin Ni Pingzhuang Ge Linlin Jiang Shixiong Bian Hui Ma Zhengdong Yuan Xiaolin Liu Jilan Chen | 2021 | Journal of Animal Science and Biotechnology2021，12，3： | 3 |
| 16 | Phase group synchronization between any signals and its physical characteristics显示文摘The phase group synchronization between any signals is further revealed,which is based on proposing the new concepts of the greatest common factor frequency,the least common multiple period,quantized phase shift resolution,equivalent phase comparison frequency and so on.Then the problem of phase comparison and processing between different frequency signals is solved and shown in detail.Using the basic principle and the variation law of group phase difference,the frequency stability better than 10-14/s can be easily obtained in the time&frequency measurement and control domain,and experimental results also show the phase relations between atomic energy level transition signal and the locked crystal oscillator signal in an active hydrogen atomic clock are strict phase group synchronization,and locked precision with 10-13/s can be reached based on phase group synchronization.The phase group synchronization can provide technical support to frequency linking among radio frequency,microwave and light frequency. | DU BaoQiang SHI LinLin CHEN YaoMing DONG ShaoFeng YANG ZhiGang CAO LingZhi GUO ShuTing | 2014 | Science China(Physics,Mechanics & Astronomy)2014，57，4： | 2 |
| 17 | Effect of formulation variables on in vitro release of a water-soluble drug from chitosanesodium alginate matrix tablets显示文摘The objective of this study is to investigate the feasibility of using chitosanesodium alginate(CSeSA)based matrix tablets for extended-release of highly water-soluble drugs by changing formulation variables.Using trimetazidine hydrochloride(TH)as a water-soluble model drug,influence of dissolution medium,the amount of CSeSA,the CS:SA ratio,the type of SA,the type and amount of diluents,on in vitro drug release from CSeSA based matrix tablets were studied.Drug release kinetics and release mechanisms were elucidated.In vitro release experiments were conducted in simulated gastric fluid(SGF)followed by simulated intestinal fluid(SIF).Drug release rate decreased with the increase of CSeSA amount.CS:SA ratio had only slight effect on drug release and no influence of SA type on drug release was found.On the other hand,a large amount of water-soluble diluents could modify drug release profiles.It was found that drug release kinetics showed the best fit to Higuchi equation with Fickian diffusion as the main release mechanism.In conclusion,this study demonstrated that it is possible to design extended-release tablets of watersoluble drugs using CSeSA as the matrix by optimizing formulation components,and provide better understanding about drug release from CSeSA matrix tablets. | Liang Li Jinfeng Li Shanshan Si Linlin Wang Chenjun Shi Yujiao Sun Zhenglin Liang Shirui Mao | 2015 | Asian Journal of Pharmaceutical Sciences2015，10，4： | 2 |
| 18 | Experimental demonstration of λ/8 DFB semiconductor laser array for 1.3 μm CWDM system显示文摘In this article,we report the first experimental demonstration of an eight-wavelength λ/8 phased-shifted laser array based on the REC technique in the 1.3 μm wavelength domain.Measurement results exhibit good linearity of lasing wavelength with+/-0.35 nm wavelength residual.The SLM property was ensured with SMSRs all larger than 38 dB.Moreover,the directmodulation performance was also tested.The experimental results show that the modulation bandwidth can reach up to 13GHz even at the small injection current of 40 mA and the measured spurious-free dynamic range(SFDR)is up to 87 dB/Hz2/3,which shows good linearity.These measurements show that REC-based λ/8 phased-shifted laser array has good modulation performance and it may find potential application in actual fiber-optic systems. | LU LinLin HUANG Long SHI YueChun GUO RenJia LIU Rui LI LianYan LI SiMin CHEN XiangFei | 2014 | Science China(Technological Sciences)2014，57，9： | 2 |
| 19 | Effects of deltamethrin on the activation or expression of Nrf2 and on the GCS-HS protein level in primary astrocytes with laser scanning confocal microscope显示文摘Objective: To examine the effects of deltamethrin(DM) and tBHQ on the activation of Nrf2 and expression of GCS-HS in primary astrocytes. Methods: Rat primary astrocytes were treated with DM (10 μmol/L) and tBHQ (40 μmol/L), for 1 and 6 h respectively. Results: Analysis using immunofluorescent confocal microscopy revealed that tBHQ treatment led to a dramatic increase in the level of Nrf2. The ratio of cytoplasmic Nrf2 protein to nuclear Nrf2 protein was markedly reduced in astrocytes by either tBHQ or DM treatment. The level of Nrf2 was reduced by combined tBHQ with DM treatment for 1 h, but treatment the ratio of cytoplasmic Nrf2 protein to nuclear Nrf2 protein was increased compared with that of the tBHQ only. The expression of GCS-HS in astrocytes was not altered by DM or tBHQ or both in astrocytes. Conclusion: These findings demonstrated for the first time that Nrf2 was activated by pesticides and antioxidants in astrocytes, implicating a role of Nrf2 in response to pesticide neurotoxicity ingla. | Huangyuan Li Nian Shi Yufang Zhong Linlin Liu | 2006 | Journal of Nanjing Medical University2006，20，1： | 2 |
| 20 | A nanomedicine approach enables co-delivery of cyclosporin A and gefitinib to potentiate the therapeutic efficacy in drug-resistant lung cancer显示文摘Drug resistance,accounting for therapeutic failure in the clinic,remains a major challenge to effectively manage cancer.Cyclosporin A(CsA)can reverse multidrug resistance(MDR),especially resistance to epidermal growth factor receptor tyrosine kinase inhibitors.However,the application of both drugs in cancer therapies is hampered by their poor aqueous solubility and low bioavailability due to oral administration.CsA augments the potency of gefitinib(Gef)in both Gef-sensitive and Gef-resistant cell lines.Here,we show that the simultaneous encapsulation of CsA and Gef within polyethylene glycol-block-poly(D,L-lactic acid)(PEG-PLA)produced a stable and systemically injectable nanomedicine,which exhibited a sub-50-nm diameter and spherical structures.Impressively,the co-delivery of therapeutics via single nanoparticles(NPs)outperformed the oral administration of the free drug combination at suppressing tumor growth.Furthermore,in vivo results indicated that CsA formulated in NPs sensitized Gef-resistant cells and Gefresistant tumors to Gef treatment by inactivating the STAT3/Bcl-2 signaling pathway.Collectively,our nanomedicine approach not only provides an alternative administration route for the drugs of choice but also effectively reverses MDR,facilitating the development of effective therapeutic modalities for cancer. | Weidong Han Linlin Shi Lulu Ren Liqian Zhou Tongyu Li Yiting Qiao Hangxiang Wang | 2018 | Signal Transduction and Targeted Therapy2018，3，1： | 2 |
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