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| 1 | BE-PLUS: a new base editing tool with broadened editing window and enhanced fidelity显示文摘基础编辑() ,包含 cytidine 脱氨基酶和催化地有缺点的 Cas9,广泛地被用来执行基础编辑。然而,狭窄的编辑窗口是限制它的实用程序。这里,我们开发了依照到由熔化 10 的 U (T) 范围(加) 的更大的 C 为招募 GCN4 肽拷贝到 nCas9 (D10A ) 的编程作为基础编辑命名的一种新编辑技术 scFv-APOBEC-UGI-GB1 到目标地点。新系统完成与一扇拓宽的窗户的基础编辑,导致一个增加的指向染色体的范围。有趣地,新系统很产出更少讨厌的 indels 和 non-C-to-T 变换。我们也通过站 codons (iSTOP ) 的正式就职越过整个染色体在基因混乱表明了它的潜在的使用。一起拿,加系统与编辑窗口和提高的忠实增加提供一个新编辑工具。 | Wen Jiang Songjie Feng Shisheng Huang Wenxia Yu Guanglei Li Guang Yang Yajing Liu Yu Zhang Lei Zhang Yu Hou Jia Chen Jieping Chen Xingxu Huang | 2018 | Cell Research2018,28,8: | 20 |
| 2 | Dapper1 promotes autophagy by enhancing the Beclinl -Vps34-Atg14L complex formation显示文摘 | Benvu Ma Weipeng Cao Wenxia Li Chan Gao Zhen Qi Yan Zhao Jun Du Hua Xue Junya Peng Jun Wen Hua Chen Yuanheng Ning Lei Huang Hong Zhang Xiang Gao Li Yu Ye-Guang Chen | 2014 | Cell Research2014,24,8: | 12 |
| 3 | In vivo evaluation of renal function using diffusion weighted imaging and diffusion tensor imaging in type 2 diabetics with normoalbuminuria versus microalbuminuria显示文摘这个工作试图估计散开的价值加权的成像(DWI ) 和在有希望地与 normoalbuminuria (NAU ) 对 microalbuminuria (MAU ) 在类型 2 糖尿病的病人检测早阶段的肾损害的散开张肌成像(DTI ) 。有正常的肾功能的 30 个 T2DM 病人的一个总数被招募并且分到 NAU 组(n = 14 ) 或 MAU 组(n = 16 ) 根据 8 h,一夜间尿的蛋白尿排泄率(AER ) 结果。健康检查接受者的一个当代的队作为控制被包括(n = 12 ) 。DWI 和 DTI 扫描用 SE 单个射击的 EPI,和明显的散开系数(模数转换器) 在双边的肾上被执行,肾的实质的部分 anisotropy (FA ) 从模数转换器和三个组的 FA 地图是坚定的。模数转换器和 FA 价值在三个组之中被比较。根据有 400 s/mm 的 b 价值的 DWI <啜class=“ a-plus-plus ”> MAU 和 NAU 组显著地显示出的 2 ,与健康控制相比降低了吝啬的模数转换器价值( P 3 公里<啜class=“ a-plus-plus ”> 2 /s]比的稍微低 NAU 组[( 2.31 b >水平枌?枌?? | Xiaoyan Chen Wenxia Xiao Xinchun Li Jianxun He Xiaochun Huang Yuyu Tan | 2014 | Frontiers of Medicine2014,8,4: | 10 |
| 4 | Oral bacteria colonize and compete with gut microbiota in gnotobiotic mice显示文摘The oral microbiota is associated with oral diseases and digestive systemic diseases.Nevertheless,the causal relationship between them has not been completely elucidated,and colonisation of the gut by oral bacteria is not clear due to the limitations of existing research models.The aim of this study was to develop a human oral microbiota-associated (HOMA) mouse model and to investigate the ecological invasion into the gut.By transplanting human saliva into germ-free (GF) mice,a HOMA mouse model was first constructed.16S rRNA gene sequencing was used to reveal the biogeography of oral bacteria along the cephalocaudal axis of the digestive tract.In the HOMA mice,84.78% of the detected genus-level taxa were specific to the donor.Principal component analysis (PCA) revealed that the donor oral microbiota clustered with those of the HOMA mice and were distinct from those of specific pathogen-free (SPF) mice.In HOMA mice,OTU counts decreased from the stomach and small intestine to the distal gut.The distal gut was dominated by Streptococcus,Veillonella,Haemophilus,Fusobacterium,Trichococcus and Actinomyces.HOMA mice and human microbiota-associated (HMA) mice along with the GF mice were then cohoused.Microbial communities of cohoused mice clustered together and were significantly separated from those of HOMA mice and HMA mice.The Source Tracker analysis and network analysis revealed more significant ecological invasion from oral bacteria in the small intestines,compared to the distal gut,of cohoused mice.In conclusion,a HOMA mouse model was successfully established.By overcoming the physical and microbial barrier,oral bacteria colonised the gut and profiled the gut microbiota,especially in the small intestine. | Bolei Li Yang Ge Lei Cheng Benhua Zeng Jinzhao Yu Xian Peng Jianhua Zhao Wenxia Li Biao Ren Mingyun Li Hong Wei Xuedong Zhou | 2019 | International Journal of Oral Science2019,11,3: | 7 |
| 5 | Multistage Deformation in the Northeastern Segment of the Jiangshao Fault (Suture) Belt: Constraints for the Relationship between the Yangtze Plate and the Cathaysia Old Land显示文摘Multistage deformation events have occurred in the northeastern Jiangshao Fault (Suture) Belt. The earliest two are ductile deformation events. The first is the ca. 820 Ma top-to-the-northwest ductile thrusting, which directly resulted from the collision between the Cathaysia Old Land and the Chencai Arc (?) during the Late Neoproterozoic, and the Jiangnan Orogenic Belt that formed as the ocean closed between the Yangtze Plate and the jointed Cathaysia Old Land and the Chencai Arc due to continuous compression. The second is the ductile left-lateral strike-slipping that occurred in the latest Early Paleozoic. Since the Jinning period, all deformation events represent the reactivation or inversion of intraplate structures due to the collisions between the North China and Yangtze plates during the Triassic and between the Philippine Sea and Eurasian plates during the Cenozoic. In the Triassic, brittle right-lateral strike-slipping and subsequent top-to-the south thrusting occurred along the whole northeastern Jiangshao Fault Zone because of the collision between the North China and Yangtze plates. In the Late Mesozoic, regional extension took place across southeastern China. In the Cenozoic, the collision between the Philippine Sea and Eurasian plates resulted in brittle thrusts along the whole Jiangnan Old land in the Miocene. The Jiangshao Fault Belt is a weak zone in the crust with long history, and its reactivation is one of important characteristics of the deformation in South China; however, late-stage deformation events did not occur beyond the Jiangnan Old Land and most of them are parallel to the strike of the Old Land, which is similar to the Cenozoic deformation in Central Asia. In addition, the Jiangnan old Land is not a collisional boundary between the Yangtze Plate and Cathaysia Old Land in the Triassic. | ZHANG Jin LI Jinyi XIAO Wenxia FENG Qianwen MA Zongjin | 2013 | Acta Geologica Sinica(English Edition)2013,87,4: | 7 |
| 6 | The FGOALS climate system model as a modeling tool for supporting climate sciences:An overview显示文摘Climate system models are useful tools for understanding the interactions among the components of the climate system and predicting/projecting future climate change. The development of climate models has been a central focus of the State Key Laboratory of Numerical Modeling for Atmospheric Sciences and Geophysical Fluid Dynamics, Institute of Atmospheric Physics, Chinese Academy of Sciences(LASG/IAP) since the establishment of the laboratory in 1985. In China, many pioneering component models and fully coupled models of the climate system have been developed by LASG/IAP. The fully coupled climate system developed in the recent decade is named FGOALS(Flexible Global Ocean-Atmosphere-Land System Model). In this paper, an application-oriented review of the LASG/IAP FGOALS model is presented. The improved model performances are demonstrated in the context of cloud-radiation processes, Asian monsoon, ENSO phenomena, Atlantic Meridional Overturning Circulation(AMOC) and sea ice. The FGOALS model has contributed to both CMIP5(Coupled Model Intercomparison Project-phase 5) and IPCC(Intergovernmental Panel on Climate Change) AR5(the Fifth Assessment Report). The release of FGOALS data has supported the publication of nearly 500 papers around the world. The results of FGOALS are cited ~106 times in the IPCC WG1(Working Group 1) AR5. In addition to the traditional long-term simulations and projections, near-term decadal climate prediction is a new set of CMIP experiment, progress of LAGS/IAP in the development of nearterm decadal prediction system is reviewed. The FGOALS model has supported many Chinese national-level research projects and contributed to the national climate change assessment report. The crucial role of FGOALS as a modeling tool for supporting climate sciences is highlighted by demonstrating the model's performances in the simulation of the evolution of Earth's climate from the past to the future. | TianJun Zhou Bin Wang YongQiang Yu YiMin Liu WeiPeng Zheng LiJuan Li Bo Wu PengFei Lin Zhun Guo WenMin Man Qing Bao AnMin Duan HaiLong Liu XiaoLong Chen Bian He JianDong Li LiWei Zou XiaoCong Wang LiXia Zhang Yong Sun WenXia Zhang | 2018 | Earth and Planetary Physics2018,2,4: | 6 |
| 7 | ILF3 is a substrate of SPOP for regulating serine biosynthesis in colorectal cancer显示文摘The Serine-Glycien-One-Carbon(SGOC)pathway is pivotal in multiple anabolic processes.Expression levels of SGOC genes are deregulated under tumoeigenic condltions,suggesting panicipation of oncogenes in deregulating the SGOC biosynthetic pathway.However,the underlying mechanism remains elusive.Here,we identifed that Interleukin enfiarccer-binding factor 3(ILF3)is overexpressed in primary CRC patient specimens and correlates with poor progroosis.ILF3 is critical in regulating the SGOC pathway by directly regulating the mRNA stability of SGOC genes,thereby increasing SGOC genes expression and facilitating tumor growth.Mehhanktic studies showed that the EGF-MIEK-ERK pathway nnediates ILF3 phosphorylation,which hin ders E3 ligase speckle-type POZ protein(SPOP)-mediated poly-ubiquitination and degradation of ILF3.Sign iftca ntly,combination of SGOC inhibitor and the anti-EGFR monoclonal antibody cetuximab can hinder the growth of patient-derived xenografts that sustain high ERK-ILF3 levels.Taken together,deregutation of ILF3 via the EGF-ERK signaling plays an important role in systemic serine metabolic reprogramming and confers a predilection toward CRC development.Our findings indicate that clinical evaluation of SCOC inhibitor is warranted for CRC patients with ILF3 overexpression. | Kai Li Jian-lin Wu Baifu Qin Zongmin Fan Qin Tang Weisi Lu Haipeng Zhang Fan Xing Manqi Meng Shaomin Zou Wenxia Wei Honglei Chen Jian Cai Huaiming Wang Hui Zhang Jiayue Cai Ling Fang Xiqing Bian Chuangqi Chen Ping Lan Bart Ghesquiere Lekun Fang Mong-Hong Lee | 2020 | Cell Research2020,30,2: | 6 |
| 8 | Expert consensus on regenerative endodontic procedures显示文摘Regenerative endodontic procedures(REPs)is a biologic-based treatment modality for immature permanent teeth diagnosed with pulp necrosis.The ultimate objective of REPs is to regenerate the pulp-dentin complex,extend the tooth longevity and restore the normal function.Scientific evidence has demonstrated the efficacy of REPs in promotion of root development through case reports,case series,cohort studies,and randomized controlled studies.However,variations in clinical protocols for REPs exist due to the empirical nature of the original protocols and rapid advancements in the research field of regenerative endodontics.The heterogeneity in protocols may cause confusion among dental practitioners,thus guidelines and considerations of REPs should be explicated.This expert consensus mainly discusses the biological foundation,the available clinical protocols and current status of REPs in treating immature teeth with pulp necrosis,as well as the main complications of this treatment,aiming at refining the clinical management of REPs in accordance with the progress of basic researches and clinical studies,suggesting REPs may become a more consistently evidence-based option in dental treatment. | Xi Wei Maobin Yang Lin Yue Dingming Huang Xuedong Zhou Xiaoyan Wang Qi Zhang Lihong Qiu Zhengwei Huang Hanguo Wang Liuyan Meng Hong Li Wenxia Chen Xiaoying Zou Junqi Ling | 2022 | International Journal of Oral Science2022,14,4: | 5 |
| 9 | Wind farm polymerization influences on security and economic operation in power system based on Copula function显示文摘Wind speed dependences on different areas in a wind farm have influences on security and economic operation in power system.In order to simulate the correlation of wind speed series between different positions,this paper applies Copula function and rank correlation matrix methods to measure the coherence of wind speed in a wind farm.The correlated wind sample space is established.According to active power output characteristics of wind turbines,the polymerization model in a wind farm can be achieved.Monte Carlo optimal power flow is applied to IEEE-30 and IEEE-300 bus systems based on the principle of energy saving dispatching.The study shows that the accuracy of outputs is improved,thus reducing the fluctuation ranges in unit generating costs and power flow in branches while considering wind speed polymerization.This approach provides a new method to improve the effectiveness of energy saving dispatching and system operation arrangement.Results have been tested to be effective. | Xiong PAN Zhuo LIU Wenxia LIU Yanqing LI | 2015 | Journal of Modern Power Systems and Clean Energy2015,3,3: | 4 |
| 10 | Fatigue crack propagation behavior of Ni-based superalloys after overloading at elevated temperatures显示文摘The fatigue crack propagation behavior of three superalloys subjected to a single overloading at elevated temperatures was investigated. The fatigue crack propagation rate FCPR versus stress intensity factor range data da/dN—ΔK were calculated using the two-point secant method. It was found that the crack growth rates of the investigated materials were retarded after overloading with an overload ratio R OL=1.6. The size of the plastic zone in the front of the crack tip and its relation to loading level were discussed. The overload retardation effects are attributed to crack closure. The fatigue damage in the plastic zone can also be a factor to explain the overload retardation. | Xinyue Huang Liang Wang Yunming Hu Guangping Guo David Salmon Ying Li Wenxia Zhao | 2016 | Progress in Natural Science:Materials International2016,26,2: | 4 |
| 11 | A photocleavable low molecular weight hydrogel for light-triggered drug delivery显示文摘A photocleavable low-molecular-weight hydrogelator (LMWG) was synthesized based on coumarin derivative.~1H NMR and UV spectroscopy study suggested that the gelator had good gelling ability, and the driving force for the gelation were hydrogen bonding and π-π stacking. This molecular hydrogel exhibited satisfied photocleavage at C-N bond in 7-amino coumarin with the light irradiation (365 nm,77.5 mW/cm^2). The promising photo-triggered drug release of antineoplastics cytarabine hydrochloride has been obtained, due to the photocleavage motived gel-sol transition. | Qihong Liu Hao Wang Guotao Li Miaochang Liu Jinchang Ding Xiaobo Huang Wenxia Gao Huayue Wu | 2019 | Chinese Chemical Letters2019,30,2: | 4 |
| 12 | Moisture-induced degradation of the narrow-band red-emitting SrLiAl3N4:Eu2+phosphor显示文摘The degradation of materials plays an important role in their application and service process. In this work, the moisture-induced degradation of SrLiAl3 N4:Eu2+(SLAN), a very promising narrow-band redemitting phosphor, was comprehensively investigated by treating it in two different moisture conditions in order to reveal the potential mechanism and optimize the luminescence properties. The degradation rate gradually slows down with the decreasing environmental humidity indicating that water plays a key role in the degradation. Moreover, we take the other option with 100% humidity at different temperatures for rapid degradation. In the rapid degradation, the luminescence of SLAN is quenched quickly and the phase and micro structure change obviously, with the phosphor being bleached. The host turns into NH_3, Al_2 O_3, Sr_3 Al_2(OH)_(12) and LiAl_2(OH)_7 finally. It is further confirmed that the rapid degradation occurs with the help of water and the phosphor is oxidized during this process. | Wenxia Li Zhen Song Dianpeng Cui Zhiguo Xia Quanlin Liu | 2018 | Journal of Rare Earths2018,36,4: | 4 |
| 13 | Response of grain size of Quaternary gravels to climate and tectonics in the northern Tibetan Plateau显示文摘The widely distributed thick gravel deposits along the rim of the Tibetan Plateau have been long thought to be the product of rapid tectonic uplift of the plateau. However, this has been challenged by recent works that suggest these thick gravels may be the result of climate change. In this paper we carried out a detailed field measurement of gravel grain sizes from the Jiuquan and Gobi Gravel Beds in the top of the Laojunmiao section in the Jiuxi Basin in the northern margin of Qilian Mts. (northern Tibetan Plateau). The results suggest that the grain sizes of the Jiuquan and Gobi Gravel Beds over the last 0.8 Ma are characterized by nine coarse-fine cycles having strong 100-ka and 41-ka periodicities that correlate well with the loess-paleosol monsoon record and isotopic global climatic record from deep sea sediments as well as by a long trend of coarsening in gravel grain size. The coarse gravel layers were formed during the warm-humid interglaciations while the fine layers correspond to the cold-dry glaciations. Because the paleoclimate in NW China began to get dramatically drier after the mid-Pleistocene, we think the persistent coarsening of gravel grain size was most probably caused by the rapid uplift of the northern Tibetan Plateau, and that the orbital scale cyclic variations in gravel grain size were driven by orbital forcing factors that were superimposed on the tectonically-forced long-term coarsening trend in gravel size. These findings also shed new light on the interaction results of climate and tectonics in relation to the uplift of the Tibetan Plateau. | FU KaiDao FANG XiaoMin GAO JunPing HAN WenXia LI LiLi | 2007 | Science China Earth Sciences2007,50,1: | 3 |
| 14 | Efficient base editing in G/C-rich regions to model androgen insensitivity syndrome显示文摘Dear Editor, Most disease-associated genomic mutations are base substitutions and approximately half of pathogenic human single nucleotide polymorphisms (SNPs)are related to C-to-T substitutions in the ClinVar database.Base editors (BEs),which combine Casg-DIOA nickase and APOBEC (apolipoprotein B mRNA editing enzyme,catalytic polypeptide-like)or AID (activation-induced deaminase)cytidine deaminase family members, have been successfully applied to mediate C-to-T conversion in vitro and in vivo, providing a powerful tool to model or repair diseaserelated human SNPs. | Jianan Li Zhen Liu Shisheng Huang Xiao Wang Guanglei Li Yuting Xu Wenxia Yu Shanshan Chen Yu Zhang Hanhui Ma Zunfu Ke Jia Chen Qiang Sun Xingxu Huang | 2019 | Cell Research2019,29,2: | 3 |
| 15 | 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 |
| 16 | Surface tension of liquid Au-Bi-Sn alloys显示文摘The surface tension of a promising lead-free solder Au-Bi-Sn alloys was investigated both by the sessile-drop method and calculation. Experimental measurements were carried out for two cross-sections with the constant gold to bismuth ration of 1:1 and 1:2. For all the investigated compositions, decrease of the surface tension is observed with increasing temperature. Meanwhile, the surface tension values were also calculated based on Butler's equation, with using the newest research on thermodynamics data of Au-Bi-Sn ternary system. Compared with the experimental results, a good agreement was obtained. | Guo, Zhongnan Li, Shan Mikula, Adolf Yuan, Wenxia | 2012 | Rare Metals2012,31,3: | 2 |
| 17 | Micro and nanolattice fabrication using projection micro litho stereo exposure additive manufacturing techniques and synchrotron X-ray 3D imaging-based defect characterization显示文摘Synchrotron radiation X-ray micro-computed tomography(SR-μCT)is a 3D imaging technique that is widely employed for the characterization of defects in advanced materials and structures.In this study,we characterize several typical defects in octettruss and re-entrant 3D lattice structures by using SR-μCT.The 3D micro-lattice structures are manufactured using projection micro litho stereo exposure(PμLSE)additive manufacturing technology.The as-fabricated 3D lattice samples are characterized using optical microscopy,and subsequently,by SR-μCT.Further more,a statistical analysis is performed to characterize the surface roughness and internal defects qualitatively,whereby the statistical geometrical parameters of struts along different directions and strut joints are analyzed and classified.Consequently,several typical defects are identified:(1)holes at the joints of the strut and irregular diameter deviations of the strut in the octet-truss lattice structure;(2)irregular diameter variations,bulges,dislocations,grooves,accumulations,and torsion in the re-entrant lattice structure.All of these defects are related to the building direction,the weight of the structure,bubbles,dust,and impurities during the PμLSE additive manufacturing process. | HU WenXia LIU LiWu WU WenWang XI Li LENG JinSong FANG DaiNing | 2020 | Science China(Technological Sciences)2020,63,4: | 2 |
| 18 | What triggered the Asian elephant’s northward migration across southwestern Yunnan?显示文摘The Asian elephant(Elephas maximus),an endangered species on the International Union for Conservation of Nature Red List,is the largest terrestrial animal living in Asia.They require a relatively large space to live in.In China,the wild Asian elephants exist only in XiShuangBanNa,Pu’Er,and LinCang of southern Yunnan Province,with 95%of the wild population residing in the XiShuangBanNa National Nature Reserve.In recent years,territorial conflicts have arisen between humans and elephants around the national nature reserve.A herd of wild Asian elephants roamed north,venturing over 500 km from the largest area of the reserve,MengYang(998 km^(2),600–1,500 m above sea level[ASL]in altitude),in March of 2020 to KunMing(the capital of Yunnan Province,ca.2000 m ASL in altitude)in early June 2021(Figure 1A).These elephants,traipsing north through fields,highways,villages,and towns,have stepped into the international spotlight,not only because such long-distance migration never happened in the past half a century but also because the United Nations Biodiversity Conference will be held in KunMing in the coming October.However,no one knows exactly why this has happened,as elephant migration,a complex ecological process,can be of varied duration,distance,timing,and driver. | Haijun Wang Puze Wang Xu Zhao Wenxia Zhang Jing Li Chi Xu Ping Xie | 2021 | The Innovation2021,2,3: | 2 |
| 19 | Effect of boron addition on the MoO_3/CeO_2–Al_2O_3 catalyst in the sulfur-resistant methanation显示文摘The effect of boron on the performance of MoO_3/CeO_2–Al_2O_3 catalysts, which were prepared with impregnation method, was investigated. The catalysts were characterized with N_2 adsorption–desorption, XRD, H_2-TPR, and NH_3-TPD, and were tested in sulfur-resistant methanation. The results indicated that the MoO_3/CeO_2–Al_2O_3 catalysts modified by boron showed higher catalytic performance in sulfur-resistant methanation. The CO conversion increased from 47% to 62% with 0.5 wt% boron content. When the content of boron was under 0.5 wt%, the results suggested there was an increase in the amorphous form of MoO_3 caused by the generation of weak and intermediate acid sites, which had weakened the interaction between the active components and supports. While, the catalyst added 2.0 wt% boron showed the strong acid sites and the largest crystalline size resulting in the uneven distribution of ceria. | Baowei Wang Wenxia Yu Weihan Wang Zhenhua Li Yan Xu Xinbin Ma | 2018 | Chinese Journal of Chemical Engineering2018,26,3: | 2 |
| 20 | EGFR TKIs impair lysosome-dependent degradation of SQSTM1 to compromise the effectiveness in lung cancer显示文摘Tyrosine kinase inhibitors for epidermal growth factor receptor(EGFR TKIs)greatly improved clinical outcomes of patients with non-small cell lung cancer(NSCLC).Unfortunately,primary and acquired resistance limits their clinical benefits.To overcome such resistance,new generations of EGFR TKIs have been developed by targeting newly identified mutations in EGFR.However,much less effort has been put into alternative strategies,such as targeting the intrinsic protective responses to EGFR TKIs.In this study,we found that EGFR TKIs,including gefitinib and AZD9291,impaired lysosome-dependent degradation of SQSTM1,thus compromising their anti-cancer efficiency.By accumulating in the lysosome lumen,gefitinib and AZD9291 attenuated lysosomal acidification and impaired autolysosomal degradation of SQSTM1 owing to their intrinsic alkalinity.As a result,SQSTM1 protein was stabilized in response to gefitinib and AZD9291 treatment and conferred EGFR TKI resistance.Depleting SQSTM1 significantly increased the sensitivity of NSCLC cells to gefitinib and AZD9291 both in vitro and in vivo.Furthermore,a chemically modified gefitinib analog lacking alkalinity displayed stronger inhibitory effects on NSCLC cells.Therefore,targeting accumulated SQSTM1 or chemically modified EGFR TKIs may represent new strategies to increase the effectiveness of EGFR targeted therapy. | Lixian Yang Shilong Ying Shiman Hu Xiangtong Zhao Muchun Li Miaoqin Chen Yiran Zhu Ping Song Liyuan Zhu Tingting Jiang Huimin An Neelum Aziz Yousafzai Wenxia Xu Zhiguo Zhang Xian Wang Lifeng Feng Hongchuan Jin | 2019 | Signal Transduction and Targeted Therapy2019,4,1: | 2 |