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| 1 | 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 |
| 2 | Mass-transport Deposits of the Upper Cretaceous Qingshankou Formation, Songliao Terrestrial Basin, Northeast China: Depositional Characteristics, Recognition Criteria and External Geometry显示文摘Extensive mass transport deposits(MTDs), which form a significant component of the stratigraphic record in ancient and modern deep water systems, mostly distributed in the continental margin of ocean basins worldwide. To date, no large-scale MTDs have been found in Chinese terrestrial basins. Based on integrated analysis of the seismic, drilling, core and logging data, this article report MTDs have been found in Songliao terrestrial basin(SLTB), Northeast China. During the depositional period of the Upper Cretaceous Qingshankou Formation, slope break of lacustrine basins was an ideal discharge place for gravity depositions. Regional sedimentary study of MTDs reveals that Cretaceous-age MTDs in SLTB were deposited in slope-break environments by slide, slump and debris flow, and MTDs were mixed with little turbidite simultaneously. Besides the massive aspect, key features of MTDs are the common presence of deformational structures or softsedimentary deformation, floating shale clasts, boudins, microfaults, distortion beddings, rotated sand debris. Detailed mapping of two three-dimensional(3-D) seismic surveys acquired in Yingtai(YT) and Haituozi(HTZ) areas reveals that MTDs are characterized by chaotic, mounded, and transparent seismic reflection. Growth fault, slope gully and geomorphology of the slope break greatly influenced the sedimentary process and external geometry of MTDs, and as a consequence, MTDs in SLTB exhibit classic fan-like geometry and some special(non-fan-like) external geometry. Furthermore, fanlike MTDs can be divided into three subcategories, including isolated fan, mother-son fan and stacked fan. Non-fan-like MTDs can be divided into two subcategories, strip-like MTDs and faulted-pit MTDs. A new sedimentary model has been built for MTDs in SLTB. MTDs have become a new exploration and development target in the SLTB. | PAN Shuxin WEI Pingsheng WANG Tianqi LIU Caiyan CHEN Bintao LIANG Sujuan | 2014 | Acta Geologica Sinica(English Edition)2014，88，1： | 9 |
| 3 | miR-7/TGF-β2 axis sustains acidic tumor microenvironment-induced lung cancer metastasis显示文摘Acidosis,regardless of hypoxia involvement,is recognized as a chronic and harsh tumor microenvironment(TME)that educates malignant cells to thrive and metastasize.Although overwhelming evidence supports an acidic environment as a driver or ubiquitous hallmark of cancer progression,the unrevealed core mechanisms underlying the direct effect of acidification on tumorigenesis have hindered the discovery of novel therapeutic targets and clinical therapy.Here,chemical-induced and transgenic mouse models for colon,liver and lung cancer were established,respectively.miR-7 and TGF-β2 expressions were examined in clinical tissues(n=184).RNA-seq,miRNA-seq,proteomics,biosynthesis analyses and functional studies were performed to validate the mechanisms involved in the acidic TME-induced lung cancer metastasis.Our data show that lung cancer is sensitive to the increased acidification of TME,and acidic TME-induced lung cancer metastasis via inhibition of miR-7-5 p.TGF-β2 is a direct target of miR-7-5 p.The reduced expression of miR-7-5 p subsequently increases the expression of TGF-β2 which enhances the metastatic potential of the lung cancer.Indeed,overexpression of miR-7-5 p reduces the acidic p H-enhanced lung cancer metastasis.Furthermore,the human lung tumor samples also show a reduced miR-7-5 p expression but an elevated level of activated TGF-β2;the expressions of both miR-7-5 p and TGF-β2 are correlated with patients’survival.We are the first to identify the role of the miR-7/TGF-β2 axis in acidic p H-enhanced lung cancer metastasis.Our study not only delineates how acidification directly affects tumorigenesis,but also suggests miR-7 is a novel reliable biomarker for acidic TME and a novel therapeutic target for non-small cell lung cancer(NSCLC)treatment.Our study opens an avenue to explore the p H-sensitive subcellular components as novel therapeutic targets for cancer treatment. | Tao Su Suchao Huang Yanmin Zhang Yajuan Guo Shuwei Zhang Jiaji Guan Mingjing Meng Linxin Liu Caiyan Wang Dihua Yu Hiu-Yee Kwan Zhiying Huang Qiuju Huang Elaine Lai-Han Leung Ming Hu Ying Wang Zhongqiu Liu Linlin Lu | 2022 | Acta Pharmaceutica Sinica B2022，12，2： | 2 |
| 4 | Overexpression of OsSPL9 enhances accumulation of Cu in rice grain and improves its digestibility and metabolism显示文摘Copper(Cu)is an essential trace mineral element for all forms of life,and is an important structural component and co-factor for a variety of metalloenzymes(Pen^a et al.,1999;Bertinato and L'Abbe,2004).In humans,Cu deficiency is not common because of the ubiquitous occurrence of Cu and ease of gastrointestinal absorption(Zidar et al.,1977;Uauy et al.,1998).However,because of the low Cu content in most sources of feed,the use of Cu as a growth promoter to maximize animal production has been well documented in animal feeding(Braude,1945;Lu et al.,2010).Pre- | Mingfeng Tang Chuanshe Zhou Lu Meng Donghai Mao Can Peng Yuxing Zhu Daoyou Huang Zhiliang Tan Caiyan Chen Chengbing Liu Dechun Zhang | 2016 | Journal of Genetics and Genomics2016，43，11： | 2 |
| 5 | The analysis of deregulated expression and methylation of the PER2 genes in gliomas显示文摘 | Wang Fan Xiaowei Chen Caiyan Li Yongluo Lvan Chen Pingfei Liu Zhijun Chen | 2014 | Journal of Cancer Research and Therapeutics2014，，3： | 1 |
| 6 | Transferring conjugated poly (γ-glutamic acid-maleimide-co-L-lactide)-1,2-dipalmitoylsn-glycero-3-phosphoethanolamine copolymer nanoparticles for targeting drug delivery显示文摘 | Caiyan Zhao Xiaoguang Liu Junxing Liu Zhiwei Yang Xianghui Rong Mingjun Li Xingjie Liang Yan Wu | 2014 | Colloids and Surfaces B: Biointerfaces2014，，： | 1 |
| 7 | Tanshinones suppress non-small cell lung cancer through up-regulating miR-137显示文摘大进步在肺癌症的治疗被取得了,尤其是在基于 PD-1 包括象那些那样的免疫疗法的治疗学的药的多样化。在这些之中,有许多反疾病分子,从中国传统的药提取,例如 artemisinin 和 tanshinones。Tanshinones,包括 Tanshinone 我(T1 ) , Tanshinone IIA (T2A ) ,并且 ? cryptotanshinone (CT ) ,是 Salia miltiorrhiza 的 liposoluble 成分,传统的植物,它有利药用的价值。特别兴趣中是 tanshinone 在肿瘤房间上有的细胞毒素的效果,它被认为首先通过 apoptosis 的正式就职和房间周期前进, angiogenesis,房间侵略,和转移的禁止发生。以前的研究显示了 tanshinones 的导致 apoptosis 效果可能有效地指向并且禁止人的肺癌症细胞的生长[1 ] 。因此,推测那 tanshinones 是合理的可以在非小的房间肺癌症(NSCLC ) 的治疗起一个重要作用。研究已经证明了 tanshinone 分子能在 vitro 禁止肺癌症细胞的生长[2 ] ,并且机制可能通过细胞周期前进和细胞 apoptosis 的正式就职的打断,导致 miR-137 的起来规定表示。 | Bingjie Zhang Zhongliang Ma Xue Li Caiyan Zhang Yang Shao Zhenguo Liu Yanli Li Youxin Jin | 2016 | Acta Biochimica et Biophysica Sinica2016，48，8： | 1 |
| 8 | Endogenous hydrogen peroxide is a key factor in the yeast extract-induced activation of biphenyl biosynthesis in cell cultures of Sorbus aucuparia显示文摘 | Xiaofang Qiu Caiyan Lei Lili Huang Xing Li He Hao Zhigao Du Hong Wang Hechun Ye Ludger Beerhues Benye Liu | 2012 | Planta2012，，1： | 1 |
| 9 | Anti-tumor pharmacology of natural products targeting mitosis显示文摘Cancer has been an insurmountable problem in the history of medical science.The uncontrollable proliferation of cancer cells is one of cancers main characteristics,which is closely associated with abn ormal mitosis.Targeting mitosis is an effective method for cancer treatment.This review summarizes several natural products with anti-tumor effects related to mitosis,focusing on targeting microtubulin,inducing DNA damage,and modulating mitosis-associated kinases.Furthermore,the main disadvantages of several typical compounds,including drug resistance,toxicity to non-tumor tissues,and poor aqueous solubility and pharmacokinetic properties,are also discussed,together with strategies to address them.Improved understanding of cancer cell mitosis and natural products may pave the way to drug development for the treatment of cancer. | Manru Huang Caiyan Liu Yingying Shao Shiyue Zhou Gaoyong Hu Shuangshuang Yin Weiling Pu Haiyang Yu | 2022 | Cancer Biology & Medicine2022，19，6： | 1 |
| 10 | The nuclear cytokine IL-37a controls lethal cytokine storms primarily via IL-1R8-independent transcriptional upregulation of PPARγ显示文摘Cytokine storms are crucial in the development of various inflammatory diseases,including sepsis and autoimmune disorders.The immunosuppressive cytokine INTERLEUKIN(IL)-37 consists of five isoforms(IL-37a-e).We identified IL-37a as a nuclear cytokine for the first time.Compared to IL-37b,IL-37a demonstrated greater efficacy in protecting against Toll-like receptor-induced cytokine hypersecretion and lethal endotoxic shock.The full-length(FL)form of IL-37a and the N-terminal fragment,which is processed by elastase,could translocate into cell nuclei through a distinctive nuclear localization sequence(NLS)/importin nuclear transport pathway.These forms exerted their regulatory effects independent of the IL-1R8 receptor by transcriptionally upregulating the nuclear receptor peroxisome proliferator-activated receptor(PPARγ).This process involved the recruitment of the H3K4 methyltransferase complex WDR5/MLL4/C/EBPβand H3K4me1/2 to the enhancer/promoter of Pparg.The receptor-independent regulatory pathway of the nuclear IL-37a–PPARγaxis and receptor-dependent signaling by secreted IL-37a maintain homeostasis and are potential therapeutic targets for various inflammatory diseases,including sepsis. | Rongfei Wei Xiao Han Mengyuan Li Yuan Ji Lianfeng Zhang Maria-Ioanna Christodoulou Najwa Jameel Hameed Aga Caiyan Zhang Ran Gao Jiangning Liu Jinrong Fu Guoping Lu Xiaojun Xiao Xiaoyu Liu Ping-Chang Yang Iain B.McInnes Ying Sun Peisong Gao Chuan Qin Shau-Ku Huang Yufeng Zhou Damo Xu | 2023 | Cellular & Molecular Immunology2023，20，12： | 0 |
| 11 | Linguistic Characteristics of Mandarin-Speaking Huntington’s Disease Patients显示文摘Objective Linguistic problem is common in Huntington’s disease(HD)patients.It has been studied before in native speakers of alphabetic languages,such as English.As a hieroglyphic language,Chinese differs from alphabetic languages in terms of phonology,morphology,semantics and syntax.We aimed to investigate the linguistic characteristics of manifest HD in native speakers of Mandarin.Meanwhile,we expected to explore the linguistic differences associated with cortical or subcortical pathology.Methods Five HD patients and five Alzheimer’s disease(AD)patients matched in age,gender,disease course and educational level were enrolled.All the participants were Mandarin native speakers.All finished history inquiry,physical examination,basic test,genetic test and neuropsychological assessment.Language evaluation was performed by Aphasia Battery of Chinese.Results HD patients had a mean disease course of 5.4±2.97(range,2-10)years.They showed a linguistic disorder close to transcortical motor aphasia.They exhibited prominent phonological impairment,as well as slight semantic and syntactic abnormality.Tonic errors were found in speech.Character structural errors and substitutions were detected in writing.In comparison,AD patients showed a more severe linguistic impairment,characterized by global aphasia with more semantic errors.Conclusion Mandarin-speaking HD patients have a transcortical motor aphasia-like disturbance with prominent phonological impairment,whereas AD patients have a more severe global aphasia with salient semantic impairment. | Liling Dong Caiyan Liu Chenhui Mao Shanshan Chu Jie Li Xinying Huang Jing Gao | 2020 | Chinese Medical Sciences Journal2020，35，3： | 0 |
| 12 | Combined Cycle Fatigue Testing with Ultrasonic FrequencyComponent of S350 Steel Welded Joint显示文摘A combined cycle fatigue (CCF) testing system with ultrasonic frequency component was developed toevaluate the CCF properties of S350 steel welded joints in this study. The fatigue testing results indicated that the S-Ncurves of CCF did not have fatigue limit, which agreed with those of pure high frequency fatigue of welded joints. TheS-N curves showed that the CCF strength of welded joints dropped greatly with the increasing interaction between highand low frequency fatigue loading. An approximation design method of CCF was presented using amplitude envelopeas the stress range. | Liu Yang Wang Dongpo Deng Caiyan Wu Liangchen Yin Danqing Gong Baoming | 2014 | Transactions of Tianjin University2014，20，6： | 0 |
| 13 | Sustainable electrochemical dearomatization for the synthesis of diverse 2,3-functionalized indolines显示文摘Herein,we achieved a green and efficient dearomatization for the synthesis of 2,3-functionalized polycyclic indolines in an electrochemical way.This avoiding of external oxidants and metals approach allowed various nucleophilic sources(Nu¼anilines,TMSN3 and ROH)to perform the products,representing an environmentally benign means.Additionally,the continuous flow electrosynthesis and synthetic transformations also reveal the strong practicality of electrochemistry in organic synthesis. | Jun Chen Rong Zhang Caiyan Ma Peng Zhang Yonghong Zhang Bin Wang Fei Xue Weiwei Jin Yu Xia Chenjiang Liu | 2024 | Green Synthesis and Catalysis2024，5，1： | 0 |
| 14 | IKKβ mediates homeostatic function in inflammation via competitively phosphorylating AMPK and IκBα显示文摘Inhibitor of nuclear factor kappa-B kinase subunit beta(IKKβ)is one of important kinases in inflammation to phosphorylate inhibitor of nuclear factor kappa-B(IκBα)and then activate nuclear factor kappa-B(NF-κB).Inhibition of IKKβhas been a therapeutic strategy for inflammatory and autoimmune diseases.Here we report that IKKβis constitutively activated in healthy donors and healthy Ikkβ^(C46A)(cysteine 46 mutated to alanine)knock-in mice although they possess intensive IKKβ-IκBα-NF-κB signaling activation.These indicate that IKKβactivation probably plays homeostatic role instead of causing inflammation.Compared to IkkβWTlittermates,lipopolysaccharides(LPS)could induce high mortality rate in Ikkβ^(C46A) mice which is correlated to breaking the homeostasis by intensively activating p-IκBα-NF-κB signaling and inhibiting phosphorylation of 5’adenosine monophosphate-activated protein kinase(p-AMPK)expression.We then demonstrated that IKKβkinase domain(KD)phosphorylates AMPKa1 via interacting with residues Thr183,Ser184,and Thr388,while IKKβhelix-loop-helix motifs is essential to phosphorylate IκBαaccording to the previous reports.Kinase assay further demonstrated that IKKβsimultaneously catalyzes phosphorylation of AMPK and IκBαto mediate homeostasis.Accordingly,activation of AMPK rather than inhibition of IKKβcould substantially rescue LPS-induced mortality in Ikkβ^(C46A) mice by rebuilding the homeostasis.We conclude that IKKβactivates AMPK to restrict inflammation and IKKβmediates homeostatic function in inflammation via competitively phosphorylating AMPK and IκBα. | Juan Liu Yuxin Zhuang Jianlin Wu Qiang Wu Meixian Liu Yue Zhao Zhongqiu Liu Caiyan Wang Linlin Lu Yingjiao Meng Kawai Lei Xiaojuan Li Qibiao Wu Elaine Lai-Han Leung Zhengyang Guo Liang Liu Ting Li | 2022 | Acta Pharmaceutica Sinica B2022，12，2： | 0 |
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