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| 1 | Genome editing with RNA-guided Cas9 nuclease in Zebrafish embryos显示文摘有类型 II 的最近的进展定期聚类 interspaced 短 palindromic 重复(CRISPR ) 系统诺言染色体编辑的一条改进途径。然而,在模型有机体的这个系统的适用性和效率例如 zebrafish,几乎没被学习。这里,我们报导那指导 RNA 的 Cas9 核酸酶高效地便于染色体以一种简单、柔韧的方式在哺乳动物的房间和 zebrafish 胚胎编辑。当特定的 Cas/gRNA 被用来在 vivo 在 zebrafish 胚胎指向任何一个 etsrp, gata4 或 gata5 时,超过 35% 地点特定的体的变化被发现。Cas9/gRNA 高效地在结果导致了 etsrp 或 gata5 的 biallelic 变换体的房间,在 etsrp 在 fau 异种胚胎或贲门 bifida 显型 > tm236a 异种胚胎。最后,我们成功地完成了 Cas9/gRNA 系统在 zebrafish 胚胎导致的 mloxP 顺序的地点特定的插入。这些结果证明 Cas9/gRNA 系统有为 zebrafish 和另外的模型有机体成为一个简单、柔韧、有效的反向的基因工具的潜力。和另外的染色体工程技术, Cas9 系统为在生物学,农业,环境研究和药的应用是有希望的。 | Nannan Chang Changhong Sun Lu Gao Dan Zhu Xiufei Xu Xiaojun Zhu Jing-Wei Xiong Jianzhong Jeff Xi | 2013 | Cell Research2013，23，4： | 155 |
| 2 | Correction of β-thalassemia mutant by base editor in human embryos显示文摘 | Puping Liang Chenhui Ding Hongwei Sun Xiaowei Xie Yanwen Xu Xiya Zhang Ying Sun Yuanyan Xiong Wenbin Ma Yongxiang Liu Yali Wang Jianpei Fang Dan Liu Zhou Songyang Canquan Zhou Junjiu Huang | 2017 | Protein & Cell2017，8，11： | 34 |
| 3 | Biodegradation of benzo[a]pyrene in soil by Mucor sp.SF06 and Bacillus sp.SB02 co-immobilized on vermiculite显示文摘Two indigenous microorganisms, Bacillus sp. SB02 and Mucor sp. SF06, capable of degrading polycyclic aromatic hydrocarbons (PAHs) were co-immobilized on vermiculite by physical adsorption and used to degrade benzo[a] pyrene (BaP). The characteristics of BaP degradation by both free and co-immobilized microorganism were then investigated and compared. The removal rate using the immobilized bacterial-fungal mixed consortium was higher than that of the freely mobile mixed consortium. 95.3% of BaP was degraded using the co-immobilized system within 42 d, which was remarkably higher than the removal rate of that by the free strains. The optimal amount of inoculated co-immobilized system for BaP degradation was 2%. The immobilized bacterial-fungal mixed consortium also showed better water stability than the free strains. Kinetics of BaP biodegradation by co-immobilized SF06 and SB02 were also studied. The results demonstrated that BaP degradation could be well described by a zero-order reaction rate equation when the initial BaP concentration was in the range of 10—200 mg/kg. The scanning electronic microscope (SEM) analysis showed that the co-immobilized microstructure was suitable for the growth of SF06 and SB02. The mass transmission process of co-immobilized system in soil is discussed. The results demonstrate the potential for employing the bacterial-fungal mixed consortium, co-immobilized on vermiculite, for in situ bioremediation of BaP. | SU Dan LI Pei-jun FRANK Stagnitti XIONG Xian-zhe | 2006 | Journal of Environmental Sciences2006，18，6： | 29 |
| 4 | One-step generation of complete gene knockout mice and monkeys by CRISPR/Cas9-mediated gene editing with multiple sgRNAs显示文摘CRISPR/Cas9 系统是一个有效编辑基因的方法,但是编辑基因的动物的多数显示出 mosaicism,与编辑仅仅在房间的部分发生。这里,我们证明那单个基因或多重基因能被 Cas9 mRNA 和多重邻近的单个指南的 RNA 的 zygotic 注射完全在老鼠和猴子胚胎击倒(spaced 10-200 bp 分开) 指向仅仅一把单个钥匙每基因的 exon。个别地在 Y 染色体上跟随八基因的指向的删除的 F0 老鼠的 Phenotypic 分析在产生猛烈老鼠表明了这条途径的坚韧性。重要地,这条途径在高效率交付完全的基因大美人(Arntl 上的 100% 并且 91% 在 Prrt2 上) 在猴子胚胎。最后,我们能在一个单个步骤产生一只完全的 Prrt2 猛烈猴子,表明在很快建立编辑基因的猴子模型的这条途径的实用性。 | Erwei Zuo Yi-Jun Cai Kui Li Yu Wei Bang-An Wang Yidi Sun Zhen Liu Jiwei Liu Xinde Hu Wei Wei Xiaona Huo Linyu Shi Cheng Tang Dan Liang Yan Wang Yan-Hong Nie Chen-Chen Zhang Xuan Yao Xing Wang Changyang Zhou Wenqin Ying Qifang Wang Ren-Chao Chen Qi Shen Guo-Liang Xu Jinsong Li Qiang Sun Zhi-Qi Xiong Hui Yang | 2017 | Cell Research2017，27，7： | 21 |
| 5 | Effective gene editing by high-fidelity base editor 2 in mouse zygotes显示文摘通过相应再结合的指向的点 mutagenesis 广泛地在基因研究被使用了并且为在病人修理引起疾病的变化保持可观的诺言。然而,象 mosaicism 那样的问题和低 mutagenesis 效率继续提出挑战到如此的途径的临床的申请。最近,一个基础编辑器() 在 cytidine (C) 脱氨基酶上造的系统和 CRISPR/Cas9 技术在植物,酵母,和人的房间为指向的点 mutagenesis 作为一个其他的方法被开发。然而,基础编辑器高效地在 deamination 窗口中把 C 变换成 thymidine (T) 是否指向了在鼠标胚胎的基础编辑,仍然保持不清楚是可行的。在这份报告,我们产生了基础编辑的一个修改高保真版本 2 (HF2-BE2 ) ,并且调查了它在老鼠胚胎编辑功效的底。我们发现 HF2-BE2 能高效地把 C 变换成 T,与直到在老鼠胚胎的 100% biallelic 变化效率。不同于 BE3, HF2-BE2 能在目标和非目标海滨上把 C 变换成 T,扩展基础编辑器的编辑范围。令人惊讶地,我们发现 HF2-BE2 能也使脱去氨基对 gRNA 有约束力的区域近似的 C。一起拿,我们的工作表明由基础编辑,和下划线在鼠标产生点变化的可行性小心地优化编辑系统以便消除近似地点的 deamination 的底的需要。 | Puping Liang Hongwei Sun Ying Sun Xiya Zhang Xiaowei Xie Jinran Zhang zhen Zhang Yuxi Chen Chenhui Ding Yuanyan Xiong Wenbin Ma Dan Liu Junjiu Huang Zhou Songyang | 2017 | Protein & Cell2017，8，8： | 17 |
| 6 | 5-Hydroxymethylcytosine signatures in cell-free DNA provide information about tumor types and stages显示文摘5-Hydroxymethylcytosine (5hmC ) 是被连接了到基因规定和癌症致病的重要哺乳动物的 DNA epigenetic 修正。这里,我们用定序途径的一枝敏感化学基于标签的低输入的猎枪在传播没有房间的 DNA (cfDNA ) 探索了 5hmC 的诊断潜力。我们从七种不同癌症类型的 49 个病人定序没有房间的 5hmC 并且发现了能被用来与高精确性预言癌症类型和阶段的不同特征。明确地,我们发现肺癌症在 cfDNA 导致 5hmC 的进步全球损失,而 hepatocellular 癌和胰腺的癌症在没有房间的 hydroxymethylome 导致疾病特定的变化。我们的 proof-of-principle 结果建议没有房间的 5hmC 签名可以潜在地被使用不仅识别癌症类型而且在一些癌症追踪肿瘤舞台。 | Chun-Xiao Song Senlin Yin Li Ma Amanda Wheeler Yu Chen Yan Zhang Bin Liu Junjie Xiong Weihan Zhang Jiankun Hu Zongguang Zhou Biao Dong Zhiqi Tian Stefanie S Jeffrey Mei-Sze Chua Samuel So Weimin Li Yuquan Wei Jiajie Diao Dan Xie Stephen R Quake | 2017 | Cell Research2017，27，10： | 17 |
| 7 | PRRT2 deficiency induces paroxysmal kinesigenic dyskinesia by regulating synaptic transmission in cerebellum显示文摘在充满脯氨酸的 transmembrane 蛋白质的变化(PRRT2 ) 2 与发作性的 kinesigenic 运动障碍(PKD ) 和几另外的发作性的神经病学的疾病被联系,但是 PRRT2 功能和病原的机制仍然保持大部分阴暗。这里,我们证明 PRRT2 是与 SNARE 建筑群和 downregulates 的部件交往的 presynaptic 蛋白质它的形成。Loss-of-function 变异的老鼠显示出显型由小脑的概括发作,过高热,或 optogenetic 刺激触发了的象 PKD 一样。有在小脑的小粒房间(GC ) 的特定的 PRRT2 删除的变异的老鼠概括在 Prrt2 空的老鼠看见的行为的显型。而且,记录在显示出的小脑的片做了在短暂举起的 GC 结果的刺激由 Purkinje 房间开火的抑制跟随了的那 optogenetic。在 PKD 处理使用的 anticonvulsant 药 carbamazepine 也在变异的老鼠减轻了象 PKD 一样行为。一起,我们的调查结果作为 SNARE 建筑群的一个新奇管理者识别 PRRT2 并且提供位于 PRRT2 相关的行为下面的电路机制。 | Guo-He Tan Yuan-Yuan Liu Lu Wang Kui Li Ze-Qiang Zhang Hong-Fu Li Zhong-Fei Yang Yang Li Dan Li Ming-Yue Wu Chun-Lei Yu Juan-Juan Long Ren-Chao Chen Li-Xi Li Lu-Ping Yin Ji-Wei Liu Xue-Wen Cheng Qi Shen You-Sheng Shu Kenji Sakimura Lu-Jian Liao Zhi-Ying Wu Zhi-Qi Xiong | 2018 | Cell Research2018，28，1： | 14 |
| 8 | Identification of aberrant cell cycle regulation in Epstein-Barr virus-associated nasopharyngeal carcinoma by cDNA microarray and gene set enrichment analysis显示文摘 | Wenling Zhang Zhaoyang Zeng Yanhong Zhou Wei Xiong Songqing Fan Lan Xiao Donghai Huang Zheng Li Dan Li Minghua Wu Xiaoling Li Shourong Shen Rong Wang Li Cao Ke Tang Guiyuan Li | 2009 | Acta Biochimica et Biophysica Sinica2009，41，5： | 11 |
| 9 | The effects and regulatory mechanism of RIP3 on RGC-5 necroptosis following elevated hydrostatic pressure显示文摘Necroptosis 是在各种各样的疾病被含有的调整房间死亡的一种类型。交往受体的蛋白质 3 (RIP3 ) , RIP 家庭的一个成员,是 necroptotic 小径的一个重要调停人。在由 caspase-8 的 Asp328 的 RIP3 的劈开废除 RIP3 的 kinase 活动,它为 necroptosis 是批评的。而且, RIP3 是显著地 upregulated 在尖锐高 intra 眼睛的压力和氧葡萄糖剥夺的早阶段期间。在这研究, RIP3 的效果在提高的静水力学的压力(EHP ) 期间被调查, caspase-8 通过调整了 RIP3 劈开的可能的机制被探索。流动 cytometry 分析表明导致 EHP 的坏死的网膜的中心房间 5 的数字(RGC-5 ) 房间被减少在以后 RIP3 击倒。而且,在正常 RGC-5 房间的 malondialdehyde (MDA ) 层次和肝糖 phosphorylase (PYGL ) 活动比在在 EHP 以后的 RIP3 击倒的房间的那些高得多。导致 EHP 的 RGC-5 坏死显著地与 butylated hydroxyanisole (BHA ) 在处理以后被减少,反应的氧种类(ROS ) scavenger。MDA 层次和 PYGL 活动比在有在 EHP 以后的 caspase-8 抑制的房间的那些在正常 RGC-5 房间是更低的。西方的污点分析证明 RIP3 劈开产品是在有 caspase-8 抑制的房间的 upregulated。另外,流动 cytometry 分析表明导致 EHP 的坏死的 RGC-5 房间的数字在 caspase-8 抑制以后被增加。我们的结果建议 RGC-5 necroptosis 追随者 EHP 被 RIP3 通过 PYGL 活动和随后的 ROS 累积的正式就职调停。因此, caspase-8 可以经由 RIP3 劈开参予 RGC-5 necroptosis 的规定。 | Lei Shang Wei Ding Na Li Lvshuang Liao Dan Chen Jufang Huang Kun Xiong | 2017 | Acta Biochimica et Biophysica Sinica2017，49，2： | 9 |
| 10 | Photodegradation of 17α-ethynylestradiol in dissolved humic substances solution:Kinetics,mechanism and estrogenicity variation显示文摘17α-Ethynylestradiol(EE2) in natural waters may cause adverse effects on organisms due to its high estrogenic potency. Laboratory studies were performed to study the effects of a local humic acid(LHA), fulvic acid(LFA) and Aldrich humic acid(AHA) on the photochemical behavior and estrogenic potency of EE2. Here photolytic experiments demonstrated that pure aqueous EE2 could undergo direct and self-sensitized photodegradation at a global rate of 0.0068 hr^(-1).Photodegradation rate of EE2 in 5.0 mg/L dissolved humic substances(DHS) was determined to be 0.0274, 0.0296 and 0.0254 hr^(-1) for LHA, LFA and AHA, respectively. Reactive oxygen species(ROS) and triplet dissolved humic substances(~3DHS*) scavenging experiments indicated that the promotion effect of DHS on EE2 photodegradation was mainly aroused by the reactions of HOU(35%–50%),~1O_2(<10%) andDHS*(22%–34%). However, the photodegradation of EE2 could also be inhibited when DHS exceeded the threshold of 10 mg/L. Three hydroxylation products of EE2 were identified using GC–MS and their formation pathways were also proposed. In vitro estrogenicity tests showed that EE2 was transformed into chemicals without estrogenic potency. These findings could extend our knowledge on the photochemical behaviors of steroid estrogens in sunlit natural waters. | Dong Ren Bin Huang Dan Xiong Huan He Xiangqi Meng Xuejun Pan | 2017 | Journal of Environmental Sciences2017，29，4： | 9 |
| 11 | A deep learning-integrated micro-CT image analysis pipeline for quantifying rice lodging resistance-related traits显示文摘Lodging is a common problemin rice,reducing its yield andmechanical harvesting efficiency.Rice architecture is a key aspect of its domestication and a major factor that limits its high productivity.The ideal rice culm structure,includingmajor_axis_culm,minor axis_culm,andwall thickness_culm,is critical for improving lodging resistance.However,the traditionalmethod ofmeasuring rice culms is destructive,time consuming,and labor intensive.In this study,we used a high-throughput micro-CT-RGB imaging system and deep learning(SegNet)todevelopa high-throughputmicro-CTimageanalysis pipelinethatcanextract 24 riceculmmorphological traits and lodging resistance-related traits.When manual and automatic measurements were compared at themature stage,the mean absolute percentage errors for major_axis_culm,minor_axis_culm,andwall_thickness_culmin 104 indica rice accessionswere 6.03%,5.60%,and 9.85%,respectively,and the R^(2) valueswere 0.799,0.818,and 0.623.We also builtmodels of bending stress using culmtraits at the mature and tillering stages,and the R^(2) values were 0.722 and 0.544,respectively.The modeling results indicated that this method can quantify lodging resistance nondestructively,even at an early growth stage.In addition,we also evaluated the relationships of bending stress toshoot dryweight,culm density,and drought-related traits and found that plants with greater resistance to bending stress had slightly higher biomass,culm density,and culm area but poorer drought resistance.In conclusion,we developed a deep learning-integrated micro-CT image analysis pipeline to accurately quantify the phenotypic traits of rice culms in4.6 min per plant;this pipeline will assist in future high-throughput screening of large rice populations for lodging resistance. | Di Wu Dan Wu Hui Feng Lingfeng Duan Guoxing Dai Xiao Liu Kang Wang Peng Yang Guoxing Chen Alan P.Gay John H.Doonan Zhiyou Niu Lizhong Xiong Wanneng Yang | 2021 | Plant Communications2021，2，2： | 7 |
| 12 | Dynamic monitoring of the cytotoxic effects of protoberberine alkaloids from Rhizoma Coptidis on HepG2 cells using the xCELLigence system显示文摘AIM: To investigate the cytotoxic effects of the six protoberberine alkaloids(PAs) from Rhizoma Coptidis on HepG2 cells. METHOD: A systematic screening was conducted to investigate the dynamic response of HepG2 cells to the PAs using the impedance-based xCELLigence system. Cisplatin was selected as the positive control. The real time, concentration-response curves and the 50% inhibitory concentrations(IC50) were acquired to evaluate the anticancer activity of the PAs. RESULTS: All of the six PAs inhibited cell growth and induce death in HepG2 cells in a time- and concentration-dependent manner. The IC50 values of cisplatin, berberine, columbamine, coptisine, epiberberine, jatrorrhizine, and palmatine were 5.13, 42.33, 226.54, 36.90, 302.72, 383.54, and 456.96 μg·mL-1, respectively. The results obtained using the xCELLigence system corresponded well with those of the conventional methods. CONCLUSION: The xCELLigence system is a reliable and efficient tool for real-time screening of the cytotoxic effect of compounds in cell-based in vitro assays. Coptisine and berberine, with methylenedioxy group at C2 and C3 on the phenyl ring showed stronger effect.than the other four PAs. However, compared with cisplatin, the six PAs didn't show obvious cytotoxic effect on HepG2 cells.These results provided some useful data for the evaluation of the anticancer compounds, and the clinical application of traditional Chinese medicine. | ZHANG Le-Le MA Li-Na YAN Dan ZHANG Cong-En GAO Dan XIONG Yin SHENG Fei-Ya DONG Xiao-Ping XIAO Xiao-He | 2014 | Chinese Journal of Natural Medicines2014，12，6： | 6 |
| 13 | Influence of Danshen Injection on airway inflammation and CD4^+ CD25^+ regulatory T cells of asthmatic rats显示文摘Objective: To investigate the influence of Danshen Injection on airway inflammation and CD4+CD25+ regulatory T cells(CD4+CD25+ Tr) of asthmatic rats, and elucidate the possible mechanism of Danshen Injection in treatment of asthma. Methods: 30 Wister rats were randomly divided into control group, asthma group and Danshen Injection treated group. Bronchoalveolar lavage fluids(BALF) were collected, and cytology studies were conducted. Lung tissues were obtained and pathologic analyses were done with hematoxylin and eosin stain(HE). Flow cytometry was used to detect the CD4+CD25+ Tr ratio in peripheral blood mononuclear cells(PBMCs). Results: Total cell, the percentage of lymphocytes, neutrophils and eosinophils(Eos) in BALF of Danshen Injection-treated group were lower than that in asthma group(P ﹤ 0.05, P ﹤ 0.01). Compared with asthma group, less infiltration of inflammatory cells in lung tissues was observed in Danshen Injection-treated group. CD4+CD25+ Tr of asthma group was lower than that of control and Danshen Injection treated group (P ﹤ 0.05). Conclusion: Danshen Injection can suppress airway inflammation of asthmatic rats, probably by increasing the number of CD4+CD25+ Tr. | Keying Xue Yongming Zhou Shengdao Xiong Weining Xiong Dan Li | 2006 | Journal of Nanjing Medical University2006，20，5： | 6 |
| 14 | Tumor-derived neomorphic mutations in ASXL1 impairs the BAP1-ASXL1-FOXK1/K2 transcription network显示文摘Additional sex combs-like 1(ASXL1)interacts with BRCA1-associated protein 1(BAP1)deubiquitinase to oppose the polycomb repressive complex 1(PRC1)-mediated histone H2A ubiquitylation.Germline BAP1 mutations are found in a spectrum of human malignancies,while ASXL1 mutations recurrently occur in myeloid neoplasm and are associated with poor prognosis.Nearly all ASXL1 mutations are heterozygous frameshift or nonsense mutations in the middle or to a less extent the C-terminal region,resulting in the production of C-terminally truncated mutant ASXL1 proteins.How ASXL1 regulates specific target genes and how the C-terminal truncation of ASXL1 promotes leukemogen-esis are unclear.Here,we report that ASXL1 interacts with forkhead transcription factors FOXK1 and FOXK2 to regulate a subset of FOXK1/K2 target genes.We show that the C-terminally truncated mutant ASXL1 proteins are expressed at much higher levels than the wild-type protein in ASXL1 heterozygous leukemia cells,and lose the ability to interact with FOXK1/K2.Specific deletion of the mutant allele eliminates the expression of C-termi-nally truncated ASXL1 and increases the association of wild-type ASXL1 with BAP1,thereby restoring the expression of BAP1-ASXL1-FOXK1/K2 target genes,particularly those involved in glucose metabolism,oxygen sensing,and JAK-STAT3 signaling pathways.In addition to FOXK1/K2,we also identify other DNA-bind-ing transcription regulators including transcription factors(TFs)which interact with wild-type ASXL1,but not C-terminally truncated mutant.Our results suggest that ASXL1 mutations result in neomorphic alleles that contribute to leukemogenesis at least in part through dominantly inhibiting the wild-type ASXL1 from interacting with BAP1 and thereby impairing the function of ASXL1-BAP1-TF in regulating target genes and leukemia cell growth. | Yu-Kun Xia Yi-Rong Zeng Meng-Li Zhang Peng Liu Fang Liu Hao Zhang Chen-Xi He Yi-Ping Sun Jin-Ye Zhang Cheng Zhang Lei Song Chen Ding Yu-Jie Tang Zhen Yang Chen Yang Pu Wang Kun-Liang Guan Yue Xiong Dan Ye | 2021 | Protein & Cell2021，12，7： | 6 |
| 15 | Biopotency Assays:an Integrated Application to Quality Control of Chinese Materia Medica显示文摘The current quality control(QC) pattern for Chinese materia medica(CMM) lacks suitable methods and indicators to evaluate their safety and efficacy effectively, which impedes the smooth development of CMM. In this review, main problems of the current QC pattern for CMM, principally focused on the content determination of constituents,were summarized and the inspiration from the QC of biological products was introduced. With the aim at introducing a suitable tool to the QC of CMM, biopotency assay and its feasibility in the QC pattern for CMM were analyzed and confirmed by relevant researches with years of practice. From the applications of biopotency assays in the QC of CMM in the last 10 years, we propose that biopotency assays should be an integral part of the QC pattern for CMM, for these assays can make the QC indicators related to the clinical safety and efficacy, supplementing the existed QC system of CMM. | Yin Xiong Dan Yan Jia-bo Wang Xiao-he Xiao | 2014 | Chinese Herbal Medicines2014，6，4： | 6 |
| 16 | The mechanisms of IDH mutations in tumorigenesis显示文摘 | Dan Ye Yue Xiong Kun-Liang Guan | 2012 | Cell Research2012，22，7： | 5 |
| 17 | Model Predictive Control-Based Direct Torque Control for Matrix Converter-Fed Induction Motor with Reduced Torque Ripple显示文摘To reduce the torque ripple in motors resulting from the use of conventional direct torque control(DTC),a model predictive control(MPC)-based DTC strategy for a direct matrix converter-fed induction motor is proposed in this paper.Two new look-up tables are proposed,these are derived on the basis of the control of the electromagnetic torque and stator flux using all the feasible voltage vectors and their associated switching states.Finite control set model predictive control(FCS-MPC)has then been adopted to select the optimal switching state that minimizes the cost function related to the electromagnetic torque.Finally,the experimental results are shown to verify the reduced torque ripple performance of the proposed MPC-based DTC method. | Hanbing Dan Peng Zeng Wenjing Xiong Meng Wen Mei Su Marco Rivera | 2021 | CES Transactions on Electrical Machines and Systems2021，5，2： | 5 |
| 18 | RIP3/MLKL-mediated neuronal necroptosis induced by methamphetamine at 39℃显示文摘Methamphetamine is one of the most prevalent drugs abused in the world.Methamphetamine abusers usually present with hyperpyrexia (39℃),hallucination and other psychiatric symptoms.However,the detailed mechanism underlying its neurotoxic action remains elusive.This study investigated the effects of methamphetamine + 39℃ on primary cortical neurons from the cortex of embryonic Sprague-Dawley rats.Primary cortex neurons were exposed to 1 mM methamphetamine + 39℃.Propidium iodide staining and lactate dehydrogenase release detection showed that methamphetamine + 39℃ triggered obvious necrosis-like death in cultured primary cortical neurons,which could be partially inhibited by receptor-interacting protein-1 (RIP1) inhibitor Necrostatin-1 partially.Western blot assay results showed that there were increases in the expressions of receptor-interacting protein-3 (RIP3) and mixed lineage kinase domain-like protein (MLKL) in the primary cortical neurons treated with 1 mM methamphetamine + 39℃ for 3 hours.After pre-treatment with RIP3 inhibitor GSK’872,propidium iodide staining and lactate dehydrogenase release detection showed that neuronal necrosis rate was significantly decreased;RIP3 and MLKL protein expression significantly decreased.Immunohistochemistry staining results also showed that the expressions of RIP3 and MLKL were up-regulated in brain specimens from humans who had died of methamphetamine abuse.Taken together,the above results suggest that methamphetamine + 39℃ can induce RIP3/MLKL regulated necroptosis,thereby resulting in neurotoxicity.The study protocol was approved by the Medical Ethics Committee of the Third Xiangya Hospital of Central South University,China (approval numbers: 2017-S026 and 2017-S033) on March 7,2017. | Li-Min Guo Zhen Wang Shi-Ping Li Mi Wang Wei-Tao Yan Feng-Xia Liu Chu-Dong Wang Xu-Dong Zhang Dan Chen Jie Yan Kun Xiong | 2020 | Neural Regeneration Research2020，15，5： | 5 |
| 19 | Tau-Induced Ca^(2+)/Calmodulin-Dependent Protein Kinase-IV Activation Aggravates Nuclear Tau Hyperphosphorylation显示文摘Hyperphosphorylated tau is the major protein component of neurofibrillary tangles in the brains of patients with Alzheimer's disease(AD). However, the mechanism underlying tau hyperphosphorylation is not fully understood. Here, we demonstrated that exogenously expressed wild-type human tau40 was detectable in the phosphorylated form at multiple AD-associated sites in cytoplasmic and nuclear fractions from HEK293 cells.Among these sites, tau phosphorylated at Thr205 and Ser214 was almost exclusively found in the nuclear fraction at the conditions used in the present study. With the intracellular tau accumulation, the Ca^(2+)concentration was significantly increased in both cytoplasmic and nuclear fractions. Further studies using site-specific mutagenesis and pharmacological treatment demonstrated that phosphorylation of tau at Thr205 increased nuclear Ca^(2+)concentration with a simultaneous increase in the phosphorylation of Ca^(2+)/calmodulin-dependent protein kinase IV(Ca MKIV) at Ser196. On the other hand, phosphorylation of tau at Ser214 did not significantly change the nuclear Ca^(2+)/Ca MKIV signaling. Finally, expressing calmodulin-binding protein-4 that disrupts formation ofthe Ca^(2+)/calmodulin complex abolished the okadaic acidinduced tau hyperphosphorylation in the nuclear fraction.We conclude that the intracellular accumulation of phosphorylated tau, as detected in the brains of AD patients, can trigger nuclear Ca^(2+)/Ca MKIV signaling, which in turn aggravates tau hyperphosphorylation. Our findings provide new insights for tauopathies: hyperphosphorylation of intracellular tau and an increased Ca^(2+)concentration may induce a self-perpetuating harmful loop to promote neurodegeneration. | Yu-Ping Wei Jin-Wang Ye Xiong Wang Li-Ping Zhu Qing-Hua Hu Qun Wang Dan Ke Qing Tian Jian-Zhi Wang | 2018 | Neuroscience Bulletin2018，34，2： | 5 |
| 20 | A quality evaluation strategy for Rhizoma coptidis from a variety of different sources using chromatographic fingerprinting combined with biological fingerprinting显示文摘Most of herbal medicines of different sources are used for the same treatment goal in clinic despite their tremendous differences of the quality.Because the clinical efficacy is closely related to the quality of medicines,the implementation of an effective quality control(QC)process is vital.Chemical methods based on content determination and chromatographic fingerprints(CFs)have been recommended as powerful tools.In spite of advances in QC,it is still difficult to determine that which of the chemical compositions can best reflect the correlation with the desired biological activity.Herein,we have focused on the biological activities of multi-source herbal medicines to establish an analytical method.By looking for correlations between the biological activities and their chemical compositions,the method can identify reasonable chemical indicators or chemical methods with biological activity information.In this study,high-performance liquid chromatography(HPLC)and microcalorimetry are combined as a useful method for evaluating the quality of Rhizoma coptidis from different sources.The results of biological fingerprints(BFs)showed that the antibacterial activity sequence of R.coptidis of different sources was Coptis teeta Wall.(CT)>Coptis chinensis Franch.(CC)>Coptis deltoidea C.Y.Cheng et Hsiao(CD).The'spectrum-activity'relationships between CFs and BFs were investigated using the canonical correlation analysis(CCA).Compared with the CCA result of CFs and BFs,the canonical correlation coefficient r1and r2were 0.9974 and 0.9752,respectively.It revealed that there are a close correlation between the spectrum-activity relationships and several of the major anti-bacterial components in the CFs,including jatrorrhizine,coptisine,palmatine,and berberine.Of course,R.coptidis was only a representative of multisource medical plants.The result of the current study will provide an effective reference for evaluating the quality of multisource herbal medicines. | LI JunXian YAN Dan MA LiNa XIONG Yin YAN ChunXia LI BaoCai PENG Cheng XIAO XiaoHe | 2013 | Chinese Science Bulletin2013，58，33： | 5 |
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