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| 1 | The TWIST/Mi2/NuRD protein complex and its essential role in cancer metastasis显示文摘上皮间充质的转变(EMT ) 把上皮的肿瘤房间变换成侵略、变形的癌症房间,导致在癌症病人的死亡。尽管扭曲为胸和另外的癌症是 EMT 和转移的一个主人管理者,为调停扭曲的基因抄写负责的机制仍然保持未知。在这研究, TWIST 蛋白质建筑群的纯化和描述表明那扭曲与改变的 Mi2/nucleosome 和 deacetylase (Mi2/NuRD ) 的几个部件交往建筑群, MTA2, RbAp46, Mi2 和 HDAC2,和成员他们到为 transcriptional 压抑的 E-cadherin 倡导者的近似区域。从取决于的房间线高效地为转移扭曲的癌症的这些扭曲建筑群部件的弄空在老鼠在文化和肺转移压制房间移植和侵略。这些调查结果不仅提供在扭曲和 Mi2/NuRD 建筑群之间的新奇机械学、功能的连接而且为在癌症复杂的 Mi2/NuRD 的部件建立新必要角色转移。 | Junjiang Fu Li Qin Tao He Jun Qin Jun Hong Jiemin Wong Lan Liao Jianming XU | 2011 | Cell Research2011，21，2： | 51 |
| 2 | Extract of Naotaifang, a compound Chinese herbal medicine, protects neuron ferroptosis induced by acute cerebral ischemia in rats显示文摘Objective:Our previous research showed that Naotaifang(a compound traditional Chinese herbal medicine)extract(NTE)has clinically beneficial effects on neurological improvement of patients with acute cerebral ischemia.In this study,we investigated whether NTE protected acute brain injury in rats and whether its effects on ferroptosis could be linked to the dysfunction of glutathione peroxidase 4(GPX4)and iron metabolism.Methods:We established an acute brain injury model of middle cerebral artery occlusion(MCAO)in rats,in which we could observe the accumulation of iron in neurons,as detected by Perl’s staining.Using assay kits,we measured expression levels of ferroptosis biomarkers,such as iron,glutathione(GSH),reactive oxygen species(ROS)and malonaldehyde(MDA);further the expression levels of transferrin receptor1(TFR1),divalent metal transporter 1(DMT1),solute carrier family 7 member 11(SLC7 A11)and GPX4 were determined using immunohistochemical analysis,real-time quantitative polymerase chain reaction and Western blot assays.Results:We found that treatment with NTE reduced the expression levels of TFR1 and DMT1,reduced ROS,MDA and iron accumulation and reduced neurobehavioral scores,relative to untreated MCAO rats.Treatment with NTE increased the expression levels of SLC7 A11,GPX4 and GSH,and the number of Nissl bodies in the MCAO rats.Conclusion:Taken together,our data suggest that acute cerebral ischemia induces neuronal ferroptosis and the effects of treating MCAO rats with NTE involved inhibition of ferroptosis through the TFR1/DMT1 and SCL7 A11/GPX4 pathways. | Bin Lan Jin-wen Ge Shao-wu Cheng Xi-long Zheng Jun Liao Chao He Zheng-qing Rao Guo-zuo Wang | 2020 | Journal of Integrative Medicine2020，18，4： | 37 |
| 3 | Expenditure and financial burden for the diagnosis and treatment of colorectal cancer in China:a hospital.based,multicenter,cross-sectional survey显示文摘Background: The increasing prevalence of colorectal cancer(CRC) in China and the paucity of information about relevant expenditure highlight the necessity of better understanding the financial burden and effect of CRC diagnosis and treatment. We performed a survey to quantify the direct medical and non-medical expenditure as well as the resulting financial burden of CRC patients in China.Methods: We conducted a multicenter, cross-sectional survey in 37 tertiary hospitals in 13 provinces across China between 2012 and 2014. Each enrolled patient was interviewed using a structured questionnaire. All expenditure data were inflated to the 2014 Chinese Yuan(CNY; 1 CNY = 0.163 USD). We quantified the overall expenditure and financial burden and by subgroup(hospital type, age at diagnosis, sex, education, occupation, insurance type, household income, clinical stage, pathologic type, and therapeutic regimen). We then performed generalized linear modeling to determine the factors associated with overall expenditure.Results: A total of 2356 patients with a mean age of 57.4 years were included, 57.1 % of whom were men; 13.9% of patients had stage I cancer; and the average previous-year household income was 54,525 CNY.The overall average direct expenditure per patient was estimated to be 67,408 CNY, and the expenditures for stage Ⅰ, Ⅱ, Ⅲ, and Ⅳ disease were 56,099 CNY, 59,952 CNY, 67,292 CNY, and 82,729 CNY, respectively. Non-medical expenditure accounted for 8.3%of the overall expenditure. The 1-year out-of-pocket expenditure of a newly diagnosed patient was 32,649 CNY, which accounted for 59.9% of their previous-year household income and caused 75.0% of families to suffer an unmanageable financial burden. Univariate analysis showed that financial burden and overall expenditure differed in almost all subgroups(P < 0.05), except for sex. Multivariate analysis showed that patients who were treated in specialized hospitals and those who were diagnosed with adenocarcinoma or diagnosed at a later stage were likely to spend more,whereas those with a lower household income and those who underwent surgery spent less(all P < 0.05).Conclusions: For patients in China, direct expenditure for the diagnosis and treatment of CRC seemed catastrophic,and non-medical expenditure was non-ignorable. The financial burden varied among subgroups, especially among patients with different clinical stages of disease, which suggests that, in China, CRC screening might be cost-effective. | Hui-Yao Huang Ju-Fang Shi Lan-Wei Guo Ya-Na Bai Xian-Zhen Liao Guo-iangLiu A-Yan Mao Jian-Song Ren Xiao-Jie Sun Xin-Yu Zhu Le Wang Bing-Bing Song Ling-Bin Du Lin Zhu Ji-Yong Gong Qi Zhou Yu-Qin Liu Rong Cao Ling Mai Li Lan Xiao-Hua Sun Ying Ren Jin-Yi Zhou Yuan-Zheng Wang Xiao Qi Pei-An Lou Dian Shi Ni Li Kai Zhang Jie He Min Dai | 2017 | Chinese Journal of Cancer2017，36，8： | 25 |
| 4 | Shenmai injection enhances the cytotoxicity of chemotherapeutic drugs against colorectal cancers via improving their subcellular distribution显示文摘Shenmai 注射(SMI ) 是中国保护专利的注射,它主要用红人参和根值 Ophiopogonis 做的并且广泛地使用了由增加 Qi 和有营养的殷治疗冠的心疾病和肿瘤。在这研究,我们检验了 SMI 是否能在 vivo 并且在 vitro 在 colorectal 癌症在 adriamycin (ADR ) 和 paclitaxel (PTX ) 的 cytoxicity 上生产直接合作的效果,并且探索了内在的 pharmacokinetic 机制。有 LoVo 结肠癌异种皮移植的 BALB/c 裸体老鼠 intraperitoneally 与 ADR 被注射(2 mg 踘? 郱?? 耰? 耰? | Wen-yue LIU Jing-wei ZHANG Xue-quanYAO Chao JIANG Ji-chao HE Pin NI Jia-li LIU Qian-ying CHEN Qing-ran LI Xiao-jie ZANG Lan YAO Ya-zhong LIU Mu-lan WANG Pei-qiang SHEN Guang-ji WANG Fang ZHOU | 2017 | Acta Pharmacologica Sinica2017，38，2： | 24 |
| 5 | Individualized prediction of perineural invasion in colorectal cancer: development and validation of a radiomics prediction model显示文摘Objective: To develop and validate a radiomics prediction model for individualized prediction of perineural invasion(PNI) in colorectal cancer(CRC).Methods: After computed tomography(CT) radiomics features extraction, a radiomics signature was constructed in derivation cohort(346 CRC patients). A prediction model was developed to integrate the radiomics signature and clinical candidate predictors [age, sex, tumor location, and carcinoembryonic antigen(CEA) level]. Apparent prediction performance was assessed. After internal validation, independent temporal validation(separate from the cohort used to build the model) was then conducted in 217 CRC patients. The final model was converted to an easy-to-use nomogram.Results: The developed radiomics nomogram that integrated the radiomics signature and CEA level showed good calibration and discrimination performance [Harrell's concordance index(c-index): 0.817; 95% confidence interval(95% CI): 0.811–0.823]. Application of the nomogram in validation cohort gave a comparable calibration and discrimination(c-index: 0.803; 95% CI: 0.794–0.812).Conclusions: Integrating the radiomics signature and CEA level into a radiomics prediction model enables easy and effective risk assessment of PNI in CRC. This stratification of patients according to their PNI status may provide a basis for individualized auxiliary treatment. | Yanqi Huang Lan He Di Dong Caiyun Yang Cuishan Liang Xin Chen Zelan Ma Xiaomei Huang Su Yao Changhong Liang Jie Tian Zaiyi Liu | 2018 | Chinese Journal of Cancer Research2018，30，1： | 23 |
| 6 | Effects of short-acting β-adrenergic blocker on B-type natriuretic peptide at early stage of postresuscitation in rabbits显示文摘 | LI Xiang LI Pei-jie HE Yun-fen ZENG Hong LI Zi-li ZHANG Zheng-yi CAO Wen YANG Lan | 2006 | Chinese Medical Journal2006，，10： | 21 |
| 7 | Effects of Short-Term Forest Bathing on Human Health in a Broad-Leaved Evergreen Forest in Zhejiang Province,China显示文摘Objective To investigate the effects of short-term forest bathing on human health.Methods Twenty healthy male university students participated as subjects and were randomly divided into two groups of 10.One group was sent on a two-night trip to a broad-leaved evergreen forest,and the other was sent to a city area.Serum cytokine levels reflecting inflammatory and stress response,indicators reflecting oxidative stress,the distribution of leukocyte subsets,and plasma endothelin-1 (ET-1) concentrations were measured before and after the experiment to evaluate the positive health effects of forest environments.A profile of mood states (POMS) evaluation was used to assess changes in mood states.Results No significant differences in the baseline values of the indicators were observed between the two groups before the experiment.Subjects exposed to the forest environment showed reduced oxidative stress and pro-inflammatory level,as evidenced by decreased malondialdehyde,interleukin-6,and tumor necrosis factor α levels compared with the urban group.Serum cortisol levels were also lower than in the urban group.Notably,the concentration of plasma ET-1 was much lower in subjects exposed to the forest environment.The POMS evaluation showed that after exposure to the forest environment,subjects had lower scores in the negative subscales,and the score for vigor was increased.Conclusion Forest bathing is beneficial to human health,perhaps through preventive effects related to several pathological factors. | MAO Gen Xiang LAN Xiao Guang CAO Yong Bao CHEN Zhuo Mei HE Zhi Huat LV Yuan Dong WANG Ya Zhen HU Xi Lian WANG Guo Fu YAN Jing | 2012 | Biomedical and Environmental Sciences2012，25，3： | 20 |
| 8 | DNA methyltransferases and methyl-binding proteins of mammals显示文摘在哺乳动物, DNA methylation,从 S-adenosylmethionines 由甲基组的转移描绘了到一个底(主要指了 cytosine ) ,充当主要 epigenetic 修正。在到 DNA 序列安排的平行,到 DNA 序列的 methylation 的修正在生物功能和活动上有影响深远的影响因为它涉及控制基因抄写,调整染色质结构,支撑染色体稳定性并且正直,维持父母印和X染色体 inactivation ,象限制 transposable 元素一样压制相应再结合,在哪个期间 DNA methyltransferases ( DNMT )和甲基绑定蛋白质玩重要 rol 他们的离开正路能产生基因表示的 dysregulation,房间 maltransformation 等等。因此,获得蛋白质的这二种重要类型的好理解是必要的,它将帮助更好调查 epigenetic 机制并且基于它的可逆性根据我们的愿望操作修正。这里,我们简短在哺乳动物考察我们 DNMT 和甲基绑定蛋白质的当前的理解。 | Jie Lan Song Hua Xiaoning He Yong Zhang | 2010 | Acta Biochimica et Biophysica Sinica2010，42，4： | 20 |
| 9 | Diagnostic Values of Vascular Endothelial Growth Factor and Epidermal Growth Factor Receptor for Benign and Malignant Hydrothorax显示文摘 | Yan Gu Min Zhang Guo-Hua Li Jun-Zhen Gao Liping Guo Xiao-Juan Qiao Li-Hong Wang Lan He Mei-Ling Wang Li Yan Xiu-Hua Fu | 2015 | Chinese Medical Journal2015，，3： | 19 |
| 10 | Intra-herb pharmacokinetics interaction between quercetin and isorhamentin显示文摘瞄准:橡黄素和 isorhamnetin 是一些植物摘录的普通成分,例如银杏叶子的摘录和 Hippophae rhamnoides L 的全部的黄酮。在 isorhamnetin 和橡黄素之间的 intra 植物 pharmacokinetics 相互作用在现在的学习被调查。方法:人的 MDR1 cDNA transfected MDCKII 房间被用来验证 isorhamnein 是否与 P-gp 交往了。Caco-2 运输试金并且一使随机化,在老鼠的 3 方法转线路 pharmacokinetics 学习被用来调查 pharmacokinetics 相互作用。HPLC 被用来决定房间运输样品。橡黄素和 isorhamnetin 的全部的血浆集中被处理被液体层析双人脚踏车团 spectrometry (LC-MS/MS ) 与 β-glucuronidase 和 sulfatase 决定。结果:越过人的 MDR1 cDNA transfected MDCKII 房间, Caco-2 房间和野类型的 MDCKII 房间的 isorhamnetin 的渗透比率(吸收性的 permeability/secretive 渗透) 分别地是 0.25 ± 0 .02, 0.74 ± 0 .05,和 1.41 ± 0 .06。这结果在 isorhamnetin 的房间流出证明了 P-gp 的角色。当越过 Caco-2 房间单层与对方一起共同搬运时, isorhamnetin 和橡黄素的渗透比率到 4.3 和 2.2 次增加了。在到老鼠的与对方一起的 coadministration 以后, C 72 h , 和 isorhamnetin 和橡黄素的 AUC 0 ∞
显著地与单个管理相比增加了的最大 , AUC 0。结论:上述结果证明了 intra 植物是在橡黄素和 isorhamentin 之间的 pharmacokinetics 相互作用。而另外的药流出抽, P-gp 可能起一个重要作用,例如多药抵抗伙伴蛋白质 2 并且乳癌抵抗蛋白质,可能被包含。除药植物相互作用以外,因此, intra 植物相互作用可能与草药底的疗法的宽使用被带进看法。 | Ke LAN Jian-lin HE Yang TIAN Fei TAN Xue-hua JIANG Ling WANG Li-ming YE | 2008 | Acta Pharmacologica Sinica2008，29，11： | 16 |
| 11 | A human herpesvirus miRNA attenuates interferon signaling and contributes to maintenance of viral latency by targeting IKKε显示文摘类型我发信号的干扰素(IFN ) 是调停的主要反应抗病毒的天生的免疫。IFN 抄写依赖于抄写因素 IRF3/IRF7 和 NF-B 的激活。许多病毒的蛋白质作为能够防碍 IFN 发信号从主人便于避免被显示出天生的有免疫力的反应。这里,我们报导那病毒的 miRNA, miR-K12-11,由 Kaposi 的联系肉瘤的 herpesvirus (KSHV ) 编码了为 IFN 通过指向 I-kappa-B kinase epsilon (IKK ) 发信号和行为的调整是批评的。miR-K12-11 的宫外的表示导致了减少的 IKK 表示,当 miR-K12-11 的抑制被发现在感染 KSHV 的房间恢复 IKK 表示时。重要地, miR-K12-11 的表示稀释了由减少的调停 IKK 的 IRF3/IRF7 phosphorylation 并且由禁止刺激基因(ISG ) 的 IKK 依赖的 IFN 的激活发信号的 IFN,允许抗病毒的免疫的 miR-K12-11 抑制。我们的数据建议由 miR-K12-11 指向的 IKK 是 KSHV 利用调制在 KSHV 生命周期期间发信号的 IFN 的重要策略,特别在潜伏。我们也证明 IKK 能与 12-O-tetradecanoylphorbol 13 醋酸盐的处理 synergistically 提高 KSHV 复活。而且, miR-K12-11 的抑制提高了小囊的口炎病毒感染导致的 KSHV 复活。一起拿,我们的调查结果也建议 miR-K12-11 能由指向 IKK 贡献 KSHV 潜伏的维护。 | Deguang Liang Yuan Gao Xianzhi Lin Zhiheng He Qinglan Zhao Qiang Deng Ke Lan | 2011 | Cell Research2011，21，5： | 15 |
| 12 | Lycorine inhibits breast cancer growth and metastasis via inducing apoptosis and blocking Src/FAK-involved pathway显示文摘Breast cancer is the most commonly diagnosed cancer type worldwide among women and more than 90% of patients die from tumor metastasis. Lycorine, a natural alkaloid, has been widely reported possessing potential efficacy against cancer proliferation and metastasis. In our study, the anti-tumor potency on breast cancer was evaluated in vitro and in vivo for the first time. Our results indicated that lycorine inhibited breast cancer cells growth, migration and invasion as well as induced their apoptosis.In in vivo study, lycorine not only suppressed breast tumor growth in xenograft models and inhibited breast tumor metastasis in MDA-MB-231 tail vein model. More importantly, we found lycorine had less toxicity than first-line chemotherapy drug paclitaxel at the same effective dose in vivo. Furthermore, on mechanism, lycorine inhibited tumor cell migration and invasion via blocking the Src/FAK(focal adhesion kinase)-involved pathway. In conclusion, our study implied lycorine was a potential candidate for the treatment of breast cancer by inhibition of tumor growth and metastasis. | Xuexiang Ying Anling Huang Yajing Xing Liping Lan Zhengfang Yi Pingqing He | 2017 | Science China(Life Sciences)2017，60，4： | 15 |
| 13 | Household air pollution and lung cancer in China:a review of studies in Xuanwei显示文摘Over half of the world's population is exposed to household air pollution from the burning of solid fuels at home. Household air pollution from solid fuel use is a leading risk factor for global disease and remains a major public health problem, especially in low- and mid-income countries. This is a particularly serious problem in China, where many people in rural areas still use coal for household heating and cooking. This review focuses on several decades of research carried out in Xuanwei County, Yunnan Province, where household coal use is a major source of household air pollution and where studies have linked household air pollution exposure to high rates of lung cancer. We conducted a series of case-control and cohort studies in Xuanwei to characterize the lung cancer risk in this population and the factors associated with it. We found lung cancer risk to vary substantially between different coal types, with a higher risk associated with smoky(i.e., bituminous) coal use compared to smokeless(i.e., anthracite) coal use. The installation of a chimney in homes resulted in a substantial reduction in lung cancer incidence and mortality. Overall, our research underscores the need among existing coal users to improve ventilation, use the least toxic fuel, and eventually move toward the use of cleaner fuels, such as gas and electricity. | Wei Jie Seow Wei Hu Roel Vermeulen H.Dean Hosgood III George S.Downward Robert S.Chapman Xingzhou He Bryan A.Bassig Christopher Kim Cuiju Wen Nathaniel Rothman Qing Lan | 2014 | Chinese Journal of Cancer2014，33，10： | 15 |
| 14 | Tracing the first hematopoietic stem cell generation in human embryo by single-cell RNA sequencing显示文摘Tracing the emergence of the first hematopoietic stem cells(HSCs)in human embryos,particularly the scarce and transient precursors thereof,is so far challenging,largely due to the technical limitations and the material rarity.Here,using single-cell RNA sequencing,we constructed the first genome-scale gene expression landscape covering the entire course of endothelial-to-HSC transition during human embryogenesis.The transcriptomically defined HSC-primed hemogenic endothelial cells(HECs)were captured at Carnegie stage(CS)12-14 in an unbiased way,showing an unambiguous feature of arterial endothelial cells(ECs)with the up-regulation of RUNX1,MYB and ANGPTL Importantly,subcategorizing CD34+CD45-ECs into a CD44+population strikingly enriched HECs by over 10-fold.We further mapped the developmental path from arterial ECs via HSC-primed HECs to hematopoietic stem progenitor cells,and revealed a distinct expression pattern of genes that were transiently over-represented upon the hemogenic fate choice of arterial ECs#including EMCN,PROCR and RUNX1T1.We also uncovered another temporally and molecularly distinct intra-embryonic HEC population,which was detected mainly at earlier CS 10 and lacked the arterial feature.Finally,we revealed the cellular components of the putative aortic niche and potential cellular interactions acting on the HSCprimed HECs.The cellular and molecular programs that underlie the generation of the first HSCs from HECs in human embryos,together with the ability to distinguish the HSC-primed HECs from others,will shed light on the strategies for the production of clinically useful HSCs from pluripotent stem cells. | Yang Zeng Jian He Zhijie Bai Zongcheng Li Yandong Gong Chen Liu Yanli Ni Junjie Du Chunyu Ma Lihong Bian Yu Lan Bing Liu | 2019 | Cell Research2019，29，11： | 14 |
| 15 | Drug-resistant genes carried by Acinetobacter baumanii isolated from patients with lower respiratory tract infection显示文摘 | DAI Ning LI De-zhi CHEN Ji-chao CHEN Yu-sheng GENG Rong HU Ying-hui YANG Jing-ping DU Juan HU Cheng-ping ZHANG Wei LI Jia-shu YU Qin WAN Huan-ying MU Lan ZHONG Xiao-ning WEI Li-ping MA Jian-jun WANG Qiu-yue HU Ke TIAN Gui-zhen CAI Shao-xi WANG Rui-qin HE Bei WANG Si-qin WANG Zhan-wei ZHAO Su-rui GAO Zhan-cheng | 2010 | Chinese Medical Journal2010，，18： | 13 |
| 16 | Risk Factors for Lung Cancer in Non-smokers in Xuanwei County of China显示文摘Tobacco smoking and some types of occupational exposures have consistently been considered as important etiologic factors of lung cancer in industrial countrie.At the First World Conference of Lung Cancer(Wyndwer,1983),it was stressed that more attention should be paid to finding out the causes of lung cancer in non-smokers. In Xuanwei County,Yunnan Province,annual lung cancer death rate was 27.7per 100,000 in males,among China's highest,and 25.3per 100,000 in females,the China's highest.The remale's lung cancer death rate in Xuanwei County was even much higher than that of the same period in USA white women(ECACM,1979;Mulvihill,1976),Marked district variation in cancer mortality exists within xuanwei County.The county can be ivided into high-,medium-and low-mortality areas.Over90% of the population are farmers.The local residents traditionally burned three major kinds of fuels:“smoky” coal,“smokeless”coal and “wood”,for heating and cooking.The three lung cancer high mortality areas,including “Chengguan”,“Rongcheng”and “Laibin”communes,mainly burned the “smoky”!coal from Laibin smoky-coal mine.The fuel was burned in a shallow,unventiated fire pit in the floor of the dwelling.Fuel burning in shallow unventialated pits has resulted in high indoor air pollution levels.The concentrations of airborne particles(pm10) inside houses during smoky coal and wood combustion were very high.Indoor concentration of suspended particulates and dichloromethane extractable organics were 244.4mg/m^3 and 17.6mg/m^3 in burning of “smoky”coal;22.2mg/m^3,12.3mg/m^3 for burning wood;and 1.8mg/m^3,0.5mg/m^3 for burning of smokeless coals.Levels of individual polycyclic aromatic hydrocarbons.including benzo(a)pyrene,were generally highest during burning of smoky coal,intermediate in burning wood,and least in smokeless coal.Women did most household chores.which include starting fire and cooking.Less than 0.2% of females smoked tobacco.The population-based casecontrol study presented here is to evaluate the influence of factors on the occurrence of lung cancer in non-smoking women in Xuanwei County and to supplement the etiologic factors of lung cancer in Xuanwei County. | LAN QING, CHEN WEI, CHEN HONG, AND HE XING-ZHOUInstitute of Environmental Health and Engineering, Chinese Academy of Preventive Medicine 29 Nan Wei Road, Beijing 100050, China | 1993 | Biomedical and Environmental Sciences1993，6，2： | 13 |
| 17 | Improving Plant Genome Editing with High-Fidelity xCas9 and Non-canonical PAM-Targeting Cas9-NG显示文摘Two recently engineered SpCas9 variants, namely xCas9 and Cas9-NG, show promising potential in improving targeting specificity and broadening the targeting range. In this study, we evaluated these Cas9 variants in the model and crop plant, rice. We first tested xCas9-3.7, the most effective xCas9 variant in mammalian cells, for targeted mutagenesis at 16 possible NGN PAM (protospacer adjacent motif) combinations in duplicates. xCas9 exhibited nearly equivalent editing efficiency to wild-type Cas9 (Cas9-WT) at most canonical NGG PAM sites tested, whereas it showed limited activity at non-canonical NGH (H = A, C, T) PAM sites. High editing efficiency of xCas9 at NGG PAMs was further demonstrated with C to T base editing by both rAPOBECI and PmCDAI cytidine deaminases. With mismatched sgRNAs, we found that xCas9 had improved targeting specificity over the Cas9-WT. Furthermore, we tested two Cas9-NG variants, Cas9-NGv1 and Cas9-NG, for targeting NGN PAMs. Both Cas9-NG variants showed higher editing efficiency at most non-canonical NG PAM sites tested, and enabled much more efficient editing than xCas9 at AT-rich PAM sites such as GAT, GAA, and CAA. Nevertheless, we found that Cas9-NG variants showed significant reduced activity at the canonical NGG PAM sites. In stable transgenic rice lines, we demonstrated that Cas9-NG had much higher editing efficiency than Cas9-NGv1 and xCas9 at NG PAM sites. To expand the base-editing scope, we developed an efficient C to T base-editing system by making fusion of Cas9-NG nickase (D10A version), PmCDAI, and UGI. Taken together, our work benchmarked xCas9 as a high-fidelity nuclease for targeting canonical NGG PAMs and Cas9-NG as a preferred variant for targeting relaxed PAMs for plant genome editing. | Zhaohui Zhong Simon Sretenovic Qiurong Ren Lijia Yang Yu Bao Caiyan Qi Mingzhu Yuan Yao He Shishi Liu Xiaopei Liu Jiaheng Wang Lan Huang Yan Wang Dibin Baby David Wang Tao Zhang Yiping Qi Yong Zhang | 2019 | Molecular Plant2019，12，7： | 13 |
| 18 | PTEN and PDCD4 are Bona Fide Targets of microRNA-21 in Human Cholangiocarcinoma显示文摘Objective To investigate the expression profile of microRNA-21 in human cholangiocarcinoma tissues and to validate its bona fide targets in human cholangiocarcinoma cells. Methods The expression profile of microRNA-21 in human cholangiocarcinoma tissues and cholangiocarcinoma cell line, QBC939, was evaluated by using real-time PCR analysis. The bona fide targets of microRNA-21 were analyzed and confirmed by dual luciferase reporter gene assay and western blot, respectively. The expressional correlation of microRNA-21 and its targets was probed in human cholangiocarcinoma tissues by using real-time PCR, locked nucleic acid in situ hybridization (LNA-ISH), and immunohistochemistry analysis. Results Real-time PCR analysis revealed that microRNA-21 expression depicted a significant up-regulation in human cholangiocarcinoma tissues about 5.6-fold as compared to the matched normal bileduct tissues (P<0.05). The dual luciferase reporter gene assay revealed endogenous microRNA-21 in cholangiocarcinoma cell line, QBC939, inhibited the luciferase reporter activities of wild-type PTEN (P<0.01) and PDCD4 (P<0.05) and had no this effect on mutated PTEN and PDCD4. Moreover, loss of microRNA-21 function led to a significant increase of PTEN and PDCD4 protein levels in QBC939 cells. Elevated microRNA-21 levels were accompanied by marked reductions of PTEN and PDCD4 expression in the same cholangiocarcinoma tissue. Conclusion microRNA-21 expression is up-regulated in human cholangiocarcinoma and PTEN, PDCD4 are direct effectors of microRNA-21. | Chang-zheng Liu Wei Liu Yi Zheng Jin-mei Su Jing--jing Li Lan Yu Xiao-dong He Song-sen Chen | 2012 | Chinese Medical Sciences Journal2012，27，2： | 13 |
| 19 | Inactivation of mammalian target of rapamycin (mTOR) by rapamycin in a murine model of lipopolysaccharide-induced acute lung injury显示文摘背景 rapamycin (mTOR ) 的哺乳动物的目标小径,与各种各样的细胞的功能联系的一条关键细胞的发信号小径,在煽动性的过程有不同角色。在这研究, mTOR 禁止者 rapamycin (Rapa ) 被用来测试 mTOR 激活的抑制是否稀释导致的 lipopolysaccharide (LPS ) 在有 Rapa 或车辆的老鼠 pretreated intratracheally 被给 LPS 的鼠科的 model.Methods 的尖锐的肺损害(所有) 。本地房间数字和在 bronchoalveolar lavage 液体( BAL )在场的煽动性的 cytokines , wet-to-dry 重量比率,肺的组织病理学说,和幸存是 evaluated.Results S6 的 phosphorylation , mTOR 的一个主要下游的目标,让3褶层在 LPS 刺激以后在肺织物增加,但是增加被 Rapa 堵住。Rapa 减少了 TNF- 的层次(LPS 对 LPS + Rapa,(1672. | WANG Lan GUI Yao-song TIAN Xin-lun CAI Bai-qiang WANG De-tian ZHANG Dong ZHAO He XU Kai-feng | 2011 | Chinese Medical Journal2011，，19： | 12 |
| 20 | Efficacy and safety of icotinib in Chinese patients with advanced non-small cell lung cancer after failure of chemotherapy显示文摘 | Shao Lan Zhang Beibei He Chunxiao Lin Baochai Song Zhengbo Lou Guangyuan Yu Xinmin Zhang Yiping | 2014 | Chinese Medical Journal2014，，2： | 12 |
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