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| 1 | Cell membrane-based nanoparticles: a new biomimetic platform for tumor diagnosis and treatment显示文摘Taking inspiration from nature, the biomimetic concept has been integrated into drug delivery systems in cancer therapy. Disguised with cell membranes, the nanoparticles can acquire various functions of natural cells. The cell membrane-coating technology has pushed the limits of common nano-systems(fast elimination in circulation) to more effectively navigate within the body. Moreover, because of the various functional molecules on the surface, cell membrane-based nanoparticles(CMBNPs) are capable of interacting with the complex biological microenvironment of the tumor. Various sources of cell membranes have been explored to camouflage CMBNPs and different tumor-targeting strategies have been developed to enhance the anti-tumor drug delivery therapy. In this review article we highlight the most recent advances in CMBNP-based cancer targeting systems and address the challenges and opportunities in this field. | Ruixiang Li Yuwei He Shuya Zhang Jing Qin Jianxin Wang | 2018 | Acta Pharmaceutica Sinica B2018，8，1： | 36 |
| 2 | Minimal invasive microscopic tooth preparation in esthetic restoration: a specialist consensus显示文摘By removing a part of the structure,the tooth preparation provides restorative space,bonding surface,and finish line for various restorations on abutment.Preparation technique plays critical role in achieving the optimal result of tooth preparation.With successful application of microscope in endodontics for>30 years,there is a full expectation of microscopic dentistry.However,as relatively little progress has been made in the application of microscopic dentistry in prosthodontics,the following assumptions have been proposed:Is it suitable to choose the tooth preparation technique under the naked eye in the microscopic vision?Is there a more accurate preparation technology intended for the microscope?To obtain long-term stable therapeutic effects,is it much easier to achieve maximum tooth preservation and retinal protection and maintain periodontal tissue and oral function health under microscopic vision?Whether the microscopic prosthodontics is a gimmick or a breakthrough in obtaining an ideal tooth preparation should be resolved in microscopic tooth preparation.This article attempts to illustrate the concept,core elements,and indications of microscopic minimally invasive tooth preparation,physiological basis of dental pulp,periodontium and functions involved in tool preparation,position ergonomics and visual basis for dentists,comparison of tooth preparation by naked eyes and a microscope,and comparison of different designs of microscopic minimally invasive tooth preparation techniques.Furthermore,a clinical protocol for microscopic minimally invasive tooth preparation based on target restorative space guide plate has been put forward and new insights on the quantity and shape of microscopic minimally invasive tooth preparation has been provided. | Haiyang Yu Yuwei Zhao Junying Li Tian Luo Jing Gao Hongchen Liu Weicai Liu Feng Liu Ke Zhao Fei Liu Chufan Ma Juergen MSetz Shanshan Liang Lin Fan Shanshan Gao Zhuoli Zhu Jiefei Shen Jian Wang Zhimin Zhu Xuedong Zhou | 2019 | International Journal of Oral Science2019，11，4： | 25 |
| 3 | Potential influence of water level changes on energy flows in a lake food web显示文摘Large seasonal water-level fluctuations may influence isotopic signatures of primary producers and the types and amounts of these potential food sources accessible to aquatic fauna of Poyang Lake,the largest freshwater lake in China.In this study,the isotopic signatures of primary producers and consumers were determined,stable carbon and nitrogen isotope analysis and mixing models were combined to investigate the influence of water levels on the diet and isotopic composition of Poyang Lake fish and invertebrates.Five potential food sources (seston,benthic organic matter,aquatic macrophytes,attached algae,and terrestrial plants),4 species of invertebrates,and 10 species of fish were collected from the lake area during dry and wet seasons between January 2009 and April 2010.The δ 13C values of invertebrates and most fish were within the range of δ 13C values of the potential food sources for both seasons.The δ 13C values of invertebrates and most fish were lower in the dry season than in the wet season,whereas the δ 15N values exhibited different patterns for different species.Mixing models indicated that the most important food sources for common lake fauna were seston in the dry season and aquatic macrophytes and terrestrial plants in the wet season.The fauna were more omnivorous in the wet season than in the dry season.The food web dynamics of Poyang Lake are strongly influenced by changes in the abundance and accessibility of different basal food sources that occur because of seasonal flood pulses.The trophic links within the aquatic communities of Poyang Lake are modified by water-level fluctuations. | WANG YuYu YU XiuBo LI WenHua XU Jun CHEN YuWei FAN Na | 2011 | Chinese Science Bulletin2011，56，26： | 11 |
| 4 | Identification and primary genetic analysis of Arabidopsis stomatal mutants in response to multiple stresses显示文摘In response to variable environmental conditions, guard cells located in the leaf epidermis can integrate and cope with a multitude of complicated stimuli, thereby making stomata in an appro- priate state. However, many signaling components in guard cell signaling remain elusive. In our laboratory, a tool for non-invasive remote infrared thermal images was used to screen an ethyl methane sulfonate-mutagenized population for Arabidopsis stomatal response mutants under multiple stresses (ABA, H2O2, CO2, etc.). More than forty 'hot' or 'cold' mutants were isolated (above or below 0.5℃ in con- trast to normal plantlets). Identification and primary genetic analysis of these mutants show that they are monogenic recessive mutations and there exist distinct difference in stomata apertures compared to wild type. These mutants in response to various environmental stresses and hormones were comprehen- sively investigated, which enables us to further un- derstand the cross-talk in different signal transduction pathways. | SONG Yuwei KANG Yanli LIU Hao ZHAO Xiaoliang WANG Pengtao AN Guoyong ZHOU Yun MIAO Chen SONG Chunpeng | 2006 | Chinese Science Bulletin2006，51，21： | 11 |
| 5 | Extraction of Lithium from Salt Lake Brine with Triisobutyl Phosphate in Ionic Liquid and Kerosene显示文摘 | GAO Daolin YU Xiaoping GUO Yafei WANG Shiqiang LIU Mingming DENG Tianlong CHEN Yuwei BELZILE Nelson | 2015 | Chemical Research in Chinese Universities2015，31，4： | 10 |
| 6 | Synthesis of condensed polynuclear aromatic resin from furfural extract oil of reduced-pressure route Ⅱ显示文摘As an industrial byproduct of oil refining,furfural extract oil from reduced-pressure route Ⅱ with high aromatic content was used to prepare heat-resistant condensed polynuclear aromatic(COPNA) resin for the first time.The basic properties of furfural extract oil and the resultant COPNA resin were characterized by infrared spectroscopy(FT-IR),nuclear magnetic resonance spectroscopy(1H-NMR),thermogravimetric analysis(TGA) and elemental analysis(EA).The result showed that heat treated furfural extract oil was successfully used for the synthesis of heat-resistant COPNA resin.The average structural parameters of raw materials and prepared resin were calculated by the improved Brown-Ladner method,and the averaged molecular structure of the resin was obtained.The reaction mechanism for the synthesis of COPNA resin was suggested as an acid-catalyzed positive ion type polymerization. | Wu Mingbo Jiang Wei Wang Yuwei Li Shibin Zheng Jingtang | 2013 | Petroleum Science2013，10，4： | 10 |
| 7 | Oncogenic AURKA-enhanced N6-methyladenosine modification increases DROSHA mRNA stability to transactivate STC1 in breast cancer stem-like cells显示文摘RNase III DROSHA is upregulated in multiple cancers and contributes to tumor progression by hitherto unclear mechanisms.Here,we demonstrate that DROSHA interacts withβ-Catenin to transactivate STC1 in an RNA cleavage-independent manner,contributing to breast cancer stem-like cell(BCSC)properties.DROSHA mRNA stability is enhanced by N6-methyladenosine(m^(6)A)modification which is activated by AURKA in BCSCs.AURKA stabilizes METTL14 by inhibiting its ubiquitylation and degradation to promote DROSHA mRNA methylation.Moreover,binding of AURKA to DROSHA transcript further strengthens the binding of the m^(6)A reader IGF2BP2 to stabilize m^(6)A-modified DROSHA.In addition,wild-type DROSHA,but not an m^(6)A methylation-deficient mutant,enhances BCSC stemness maintenance,while inhibition of DROSHA m^(6)A modification attenuates BCSC traits.Our study unveils the AURKA-induced oncogenic m^(6)A modification as a key regulator of DROSHA in breast cancer and identifies a novel DROSHA transcriptional function in promoting the BCSC phenotype. | Fei Peng Jie Xu Bai Cui Qilan Liang Sai Zeng Bin He Hong Zou Manman Li Huan Zhao Yuting Meng Jin Chen Bing Liu Shasha Lv Peng Chu Fan An Zifeng Wang Junxiu Huang Yajing Zhan Yuwei Liao Jinxin Lu Lingzhi Xu Jin Zhang Zhaolin Su Zhiguang Li Fangjun Wang Eric W-FLam Quentin Liu | 2021 | Cell Research2021，31，3： | 9 |
| 8 | Epidemiological and etiological investigation of dengue fever in the Fujian province of China during 2004–2014显示文摘Dengue fever(DF) is a vector-borne disease and a tremendous socioeconomic burden on tropical and subtropical countries worldwide. To explore the characteristics of DF epidemic in the Fujian province, information of DF cases in Fujian during 2004–2014 was collected and analyzed. The complete E genes of 48 viral isolates were amplified and sequenced for phylogenetic analysis. A total of 733 cases was reported, of which 612(83.5%) occurred during the peak period from August to October. Additionally, 76%(190/250) of imported cases originated from Southeast Asia countries, by the epidemiological investigation. Phylogenetic analysis of the 48 viral isolates revealed that three genotypes(I, IV, V) of DENV1, and one genotype each of DENV2(cosmopolitan) and DENV3(I) circulated in Fujian during 2004–2014. Similar to the results of the epidemiological investigations, the source of most of the viral isolates, including imported and indigenous cases, may be Southeast Asia countries; however, importation from adjacent provinces was also observed in recent years. Overall, DF is considered an imported epidemic disease in Fujian. Increasing diversity of the viral source and geographic expansion of the area affected by DF in recent years highlights the necessity for strengthening surveillance of the DF epidemic and developing strategies for DF prevention and control in Fujian. | Jinzhang Wang Hongbing Chen Meng Huang Yongjun Zhang Jianfeng Xie Yansheng Yan Kuicheng Zheng Yuwei Weng | 2017 | Science China(Life Sciences)2017，60，1： | 9 |
| 9 | Drug targeting through platelet membrane-coated nanoparticles for the treatment of rheumatoid arthritis显示文摘The effective drug treatment of rheumatoid arthritis (RA) is hindered by poordelivery efficiency to the diseased site and the serious side effects caused bywide-spread drug distribution. Traditional drug-targeting strategies, such asligand modification, are complex, laborious, and inefficient. Inspired by theintrinsic relationship between platelets and RA, platelet-mimetic nanoparticles(PNPs) were developed for targeted drug delivery in RA. Through plateletreceptor-mediated adhesion, an intact platelet membrane was coated onto poly(lactic-co-glycolic add) nanopartides, endowing the resulting PNPs with variousfunctional receptors. By coating with platelet membranes, the nanoparticleswere stabilized and had a better circulation profile, providing a benefit forpassive targeting. In vitro binding of PNPs to inflamed endothelium, and in vivoaccumulation in joints of a collagen-induced arthritis (CIA) mouse model of RAwere significantly improved via P-selectin and GVPI recognition, indicating thatthe PNPs could effectively target to RA tissues through multiple mechanisms,similar to natural platelets. Moreover, FK506, a model drug, was loaded into thePNPs and used to treat RA. Pharmacodynamic studies demonstrated that theFK506-PNPs had a notable anti-arthritic effect in CIA mice. This study provides anew biomimetic targeting strategy with great potential for the treatment of RA. | Yuwei He Ruixiang Li Jianming Liang Ying Zhu Shuya Zhang Zicong Zheng Jing Qin Zhiqing Pang Jianxin Wang | 2018 | Nano Research2018，11，11： | 9 |
| 10 | Immunopotentiator Thymosin Alpha-1 Promotes Neurogenesis and Cognition in the Developing Mouse via a Systemic Th1 Bias显示文摘In early life, the immune system plays an essential role in brain development. In our study, the immunopotentiator thymosin alpha-1(Ta1) was peripherally administered to neonatal mice to explore whether the peripheral immunopotentiator affects neurodevelopment and cognition, and to further investigate the relevant mechanism. Compared with the control group, the Ta1 mice displayed better cognitive abilities in early life. The numbers of 5-bromodeoxyuridine(Brd U)+, nestin+,T-box transcription factor 2(Tbr2)+, Brd U+/doublecortin(DCX)+, Brd U+/ionized calcium-binding adaptor molecule 1(Iba1)+, and Brd U+/neuronal nuclei(Neu N)+ cells in the hippocampus were increased in the Ta1 group,accompanied by increased interleukin-4(IL-4), interferon-gamma, brain-derived neurotrophic factor, nerve growth factor, and insulin-like growth factor-1 as well as decreased IL-6 and tumor necrosis factor-a. Furthermore, the Ta1-group showed a Th1-polarized immune response, and the neurotrophic factors were positively associated with the Th1/Th2 ratio. More importantly, administration of Ta1 blocked lipopolysaccharide-induced impairment of hippocampal neurogenesis in early life. These findings suggest that peripheral Ta1 contributes to neurogenesis and cognition probably through a systemic Th1 bias, as well as neuroprotection against LPS infection by Ta1. | Ge Wang Fen He Yunlong Xu Yuwei Zhang Xiao Wang Chunhua Zhou Yihong Huang Juntao Zou | 2017 | Neuroscience Bulletin2017，33，6： | 8 |
| 11 | MIKC^(C)-type MADS-box genes in Rosa chinensis: the remarkable expansion of ABCDE model genes and their roles in floral organogenesis显示文摘MIKC^(C)-type MADS-box(MIKC^(C))genes encode transcription factors that have crucial roles in controlling floral organogenesis and flowering time in plants.Although this gene family has been well characterized in many plant species,its evolutionary and comprehensive functional analysis in rose is lacking.In this study,58 non-redundant MIKC^(C)uni-transcripts were extensively identified from rose transcriptomes.Phylogenetic analysis placed these genes into 12 clades with their Arabidopsis and strawberry counterparts,and revealed that ABCDE model(including AP1/FUL,AP3/PI,AG,and SEP clades),and SOC1 and AGL6 clade genes have remarkably expanded in Rosa chinensis,whereas genes from the FLC and AGL17 clades were undetectable.Sequence alignments suggest that the AP3/PI clade may contribute to more specific functions in rose due to a high variation of amino acid residues within its MADS-box domains.A comparative analysis of gene expression in specific floral organ differentiation stages and floral organs between R.chinensis cv.Old Blush and the closely related mutant genotype R.chinensis cv.Viridiflora(floral organs mutated into leaf-like structures)further revealed the roles of ABCDE model genes during floral organogenesis in rose.Analysis of co-expression networks provided an overview of the regulatory mechanisms of rose MIKC^(C)genes and shed light on both the prominent roles of AP3/PI clade genes in floral organogenesis and the roles of RcAGL19,RcAGL24,and RcSOC1 in regulating floral transition in rose.Our analyses provide an overall insight of MIKC^(C)genes in rose and their potential roles in floral organogenesis. | Jinyi Liu Xiaodong Fu Yuwei Dong Jun Lu Min Ren Ningning Zhou Changquan Wang | 2018 | Horticulture Research2018，5，1： | 7 |
| 12 | Aerosol size distributions during haze episodes in winter in Jinan, China显示文摘 | Yuwei Sun Xuehua Zhou Wenxing Wang | 2016 | Particuology2016，14，5： | 7 |
| 13 | Synthesis and Characterization of Condensed Polynuclear Aromatic Resin Derived from Ethylene Tar显示文摘As a kind of low-cost and readily available industrial byproduct, ethylene tar (ET) was for the first time utilized for the preparation of heat-resistant condensed polynuclear aromatic resin (COPNAR). The basic properties of ET and the resulted COPNAR were characterized by FT-IR, 1H-NMR, TGA and elemental analysis. The test results showed that ET with high aromatic content (>50%) was suitable for the synthesis of COPNAR with superior heat resistance. The average molecular structure of ET was obtained by means of the improved Brown-Ladner method, and the reaction mechanism was considered as an acid-catalyzed positive ion-typed polymerization. Our findings have provided a new route to develop ET into technology-added heat-resistant resins. | Wu Mingbo Shi Yangyang Li Shibin Wang Yuwei Tan Minghui Wang Ding Zheng Jingtang Tsubaki Noritatsu | 2012 | China Petroleum Processing & Petrochemical Technology2012，14，4： | 7 |
| 14 | Cryo-EM structure and biochemical analysis reveal the basis of the functional difference between human PI3KC3-C1 and-C2显示文摘Phosphatidylinositol 3 磷酸盐(PI3P ) 在小囊的 trafficking,细胞器生物的续生说和 autophagy 起必要作用。二班 III phosphatidylinositol 3-kinase (PI3KC3 ) 建筑群在哺乳动物, ATG14L 建筑群(PI3KC3-C1 ) 和 UVRAG 建筑群(PI3KC3-C2 ) 被识别了。PI3KC3-C1 为 autophagosome 生物的续生说是关键的,并且 PI3KC3-C2 涉及各种各样的膜 trafficking 事件。这里,我们在亚纳米分辨率报导人的 PI3KC3-C1 和 PI3KC3-C2 的 cryo 他们结构。二结构与不同特征分享普通塑造 L 的全面体系结构。他们检查直接表明 PI3KC3-C1 在类脂化合物单层上站起来,与 ATG14L 蝙蝠领域和 VPS34 C 终端领域(CTD ) 联系膜。生物化学的解剖显示 ATG14L 蝙蝠领域负责膜抛锚,而 VPS34 的 CTD 决定取向。而且, PI3KC3-C2 比 PI3KC3-C1 更微弱地绑在包含 PI liposomes 和净化的 endoplasmic 蜂窝胃(嗯) 泡,被 ATG14L 明确地决定的一个性质打领域。在里面 vivo 嗯本地化分析显示蝙蝠领域被要求为嗯 PI3KC3 的本地化。我们建议不同类脂化合物绑定能力是在 autophagy 区分 PI3KC3-C1 和 PI3KC3-C2 的函数的关键因素。 | Meisheng Ma Jun-Jie Liu Nan Li Yuwei Huang Na Ta Yang Chen Hua Fu Ming-Da Ye Yuehe Ding Weijiao Huang Jia Wang Meng-Qiu Dong Li Yu Hong-Wei Wang | 2017 | Cell Research2017，27，8： | 7 |
| 15 | Diterpenoid UDP-Glycosyltransferases from Chinese Sweet Tea and Ashitaba Complete the Biosynthesis of Rubusoside显示文摘 | Yuwei Sun Zhuo Chen Jianxu Li Jianhua Li Huajun LV Jingya Yang Weiwei Li Dingan Xie Zhiqiang Xiong Peng Zhang Yong Wang | 2018 | Molecular Plant2018，11，10： | 7 |
| 16 | Radiomic analysis of pulmonary ground-glass opacity nodules for distinction of preinvasive lesions, invasive pulmonary adenocarcinoma and minimally invasive adenocarcinoma based on quantitative texture analysis of CT显示文摘Objective: To identify the differences among preinvasive lesions, minimally invasive adenocarcinomas(MIAs)and invasive pulmonary adenocarcinomas(IPAs) based on radiomic feature analysis with computed tomography(CT).Methods: A total of 109 patients with ground-glass opacity lesions(GGOs) in the lungs determined by CT examinations were enrolled, all of whom had received a pathologic diagnosis. After the manual delineation and segmentation of the GGOs as regions of interest(ROIs), the patients were subdivided into three groups based on pathologic analyses: the preinvasive lesions(including atypical adenomatous hyperplasia and adenocarcinoma in situ) subgroup, the MIA subgroup and the IPA subgroup. Next, we obtained the texture features of the GGOs. The data analysis was aimed at finding both the differences between each pair of the groups and predictors to distinguish any two pathologic subtypes using logistic regression. Finally, a receiver operating characteristic(ROC) curve was applied to accurately evaluate the performances of the regression models.Results: We found that the voxel count feature(P<0.001) could be used as a predictor for distinguishing IPAs from preinvasive lesions. However, the surface area feature(P=0.040) and the extruded surface area feature(P=0.013) could be predictors of IPAs compared with MIAs. In addition, the correlation feature(P=0.046) could distinguish preinvasive lesions from MIAs better.Conclusions: Preinvasive lesions, MIAs and IPAs can be discriminated based on texture features within CT images, although the three diseases could all appear as GGOs on CT images. The diagnoses of these three diseases are very important for clinical surgery. | Wei Li Xuexiang Wang Yuwei Zhang Xubin Li Qian Li Zhaoxiang Ye | 2018 | Chinese Journal of Cancer Research2018，30，4： | 6 |
| 17 | Recombinant vaccine containing an RBD-Fc fusion induced protection against SARS-CoV-2 in nonhuman primates and mice显示文摘The novel coronavirus SARS-CoV-2 has infected more than 104 million individuals and resulted in more than 2.2 million deaths worldwide as of February 7,2021(http://gffzze7c39cdc9e894ca6s55kku6nbbbo96qu9.ffgz.tsg.suse.edu.cn).The COVID-19 pandemic highlights the need for safe and effective vaccines against SARS-CoV-2 infection. | Shihui Sun Lei He Zhongpeng Zhao Hongjing Gu Xin Fang Tiecheng Wang Xiaolan Yang Shaolong Chen Yongqiang Deng Jiangfan Li Jian Zhao Liang Li Xinwang Li Peng He Ge Li Hao Li Yuee Zhao Chunrun Gao Xiaoling Lang Xin Wang Guoqiang Fei Yan Li Shusheng Geng Yuwei Gao Wenjin Wei Zhongyu Hu Gencheng Han Yansong Sun | 2021 | Cellular & Molecular Immunology2021，18，4： | 5 |
| 18 | Improvements of heat resistance and adhesive property of condensed poly-nuclear aromatic resin via epoxy resin modification显示文摘A bisphenol epoxy resin was used as modifier to increase the heat resistance of condensed poly-nuclear aromatic(COPNA) resin. The basic properties of COPNA resin and modified resin were characterized by Fourier transform infrared spectroscopy(FT-IR), nuclear magnetic resonance spectroscopy(1H-NMR), vapor pressure osmometry(VPO) and elemental analysis(EA). Average structural parameters of resins were calculated by the improved Brown-Ladner method, and heat resistance of resins was tested by thermogravimetric analysis(TGA). The chemical structure, mechanical properties and heat resistivity of the resin/graphite composites prepared with different resins were compared. The results show that the adhesive property and heat resistance of COPNA resin can be remarkably improved by addition of 5 wt.% epoxy resin. The reason is that the reactions between epoxy groups of epoxy resin and hydroxyl groups of COPNA resin improve the heat resistance and adhesive property of COPNA resin. Electric motor brushes with good mechanical properties and low electrical resistivity were successfully prepared by using the modified resin as binder. | Wu Mingbo Wang Yuwei Jiang Wei Li Shibin Sun Qiqian Zheng Jingtang Qiu Jieshan | 2014 | Petroleum Science2014，11，4： | 5 |
| 19 | Image matching algorithm based on SIFT using color and exposure information显示文摘Image matching based on scale invariant feature transform(SIFT) is one of the most popular image matching algorithms, which exhibits high robustness and accuracy. Grayscale images rather than color images are generally used to get SIFT descriptors in order to reduce the complexity. The regions which have a similar grayscale level but different hues tend to produce wrong matching results in this case. Therefore, the loss of color information may result in decreasing of matching ratio. An image matching algorithm based on SIFT is proposed, which adds a color offset and an exposure offset when converting color images to grayscale images in order to enhance the matching ratio. Experimental results show that the proposed algorithm can effectively differentiate the regions with different colors but the similar grayscale level, and increase the matching ratio of image matching based on SIFT. Furthermore, it does not introduce much complexity than the traditional SIFT. | Yan Zhao Yuwei Zhai Eric Dubois Shigang Wang | 2016 | Journal of Systems Engineering and Electronics2016，27，3： | 5 |
| 20 | Structural insights into a high fidelity variant of SpCas9显示文摘The RNA-guided endonucleases of the CRISPR-Cas9 system, including the most w泊ely used Cas9 from Streptococcus pyogenes (SpCas9)z are becoming a robust genome editing tool in model organisms and hold immense promise for therapeutic applications. Many strategies have bee n employed to overcome the limitati ons caused by SpCas9zs off-target effects and its strin gent requirement for the protospacer adjacent motif (PAM) sequenee. However, the structural mechanisms underlying these strategies remain undefined. Here, we present crystal structure of a SpCas9 variant, xCas9 3.7 that has broad PAM compatibility and high DNA targeting specificity, in complex with a single-guide RNA and its double-stranded DNA targets. Structural comparison revealed that salt bridge-stabilized R1335 is critical for the stringent selection of PAM sequence by SpCas9. Unrestricted rotamerization of this residue by the E1219V mutation in xCas9 3.7 lessens the stringency for PAM recognition and allows SpCas9 to recognize multiple PAM sequences as further supported by biochemical data. Compared to those in wild-type (WT) SpCas9, REC2 and REC3 domains in xCas9 3.7 un dergo striki ng conformati onal changes, leadi ng to reduced con tact with DNA substrate. SpCas9 mutants en gineered to display less interaction with DNA and have conformationally more flexible REC2 and REC3 domains display enhanced specificity for DNA substrates in both biochemical and cellular assays. Taken together, our findings reveal the structural mechanisms underlying the broadened PAM compatibility and high DNA fidelity of xCas9 3.7, which can assist rational engineering of more efficient SpCas9 variants and probably other Cas9 orthologs. | Minghui Guo Kuan Ren Yuwei Zhu Ziyun Tang Yuhang Wang Bailing Zhang Zhiwei Huang | 2019 | Cell Research2019，29，3： | 5 |
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