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| 1 | Eleven COVID-19 Outbreaks with Local Transmissions Caused by the Imported SARS-CoV-2 Delta VOC-China,July-August,2021显示文摘Starting from December 2019,Wuhan,China,encountered the first outbreak of coronavirus disease 2019(COVID-19)(1-2).The epidemic was successfully suppressed by strict containment so that the number of infected people was reduced to 0 on April 8,2020(3–4).After that,China experienced roughly 3 dozen outbreaks with local transmission caused by imported severe acute respiratory syndrome coronavirus 2(SARS-CoV-2). | Lei Zhou Kai Nie Hongting Zhao Xiang Zhao Bixiong Ye Ji Wang Cao Chen Hong Wang Jiangli Di Jinsong Li Chao Li Zhixiao Chen Ruiqi Ren Peihua Niu Hui Chen Tao Chen Yali Wang Lili Li Bingxue Han Ruhan A Si Chen Dan Li Dan Li Chunxia Jin Xin Zhang Jiangmei Liu Chunyu Xu Yecheng Yao Yenan Feng Zhili Li Bike Zhang Yang Song Peter Hao Yanping Zhang Hao Li Qun Li George F.Gao Guoqing Shi Wenbo Xu | 2021 | China CDC weekly2021，3，41： | 13 |
| 2 | New innovations in pavement materials and engineering:A review on pavement engineering research 2021显示文摘Sustainable and resilient pavement infrastructure is critical for current economic and environmental challenges.In the past 10 years,the pavement infrastructure strongly supports the rapid development of the global social economy.New theories,new methods,new technologies and new materials related to pavement engineering are emerging.Deterioration of pavement infrastructure is a typical multi-physics problem.Because of actual coupled behaviors of traffic and environmental conditions,predictions of pavement service life become more and more complicated and require a deep knowledge of pavement material analysis.In order to summarize the current and determine the future research of pavement engineering,Journal of Traffic and Transportation Engineering(English Edition)has launched a review paper on the topic of'New innovations in pavement materials and engineering:A review on pavement engineering research 2021'.Based on the joint-effort of 43 scholars from 24 well-known universities in highway engineering,this review paper systematically analyzes the research status and future development direction of 5 major fields of pavement engineering in the world.The content includes asphalt binder performance and modeling,mixture performance and modeling of pavement materials,multi-scale mechanics,green and sustainable pavement,and intelligent pavement.Overall,this review paper is able to provide references and insights for researchers and engineers in the field of pavement engineering. | JTTE Editorial Office Jiaqi Chen Hancheng Dan Yongjie Ding Yangming Gao Meng Guo Shuaicheng Guo Bingye Han Bin Hong Yue Hou Chichun Hu Jing Hu Ju Huyan Jiwang Jiang Wei Jiang Cheng Li Pengfei Liu Yu Liu Zhuangzhuang Liu Guoyang Lu Jian Ouyang Xin Qu Dongya Ren Chao Wang Chaohui Wang Dawei Wang Di Wang Hainian Wang Haopeng Wang Yue Xiao Chao Xing Huining Xu Yu Yan Xu Yang Lingyun You Zhanping You Bin Yu Huayang Yu Huanan Yu Henglong Zhang Jizhe Zhang Changhong Zhou Changjun Zhou Xingyi Zhu | 2021 | Journal of Traffic and Transportation Engineering(English Edition)2021，8，6： | 7 |
| 3 | Dark matter direct search sensitivity of the PandaX-4T experiment显示文摘The Panda X-4T experiment, a 4-ton scale dark matter direct detection experiment, is being planned at the China Jinping Underground Laboratory. In this paper we present a simulation study of the expected background in this experiment. In a 2.8-ton fiducial mass and the signal region between 1-10 keV electron equivalent energy, the total electron recoil background is found to be 4.9 × 10^(-5) kg^(-1) d^(-1) keV^(-1). The nuclear recoil background in the same region is 2.8 × 10^(-7) kg^(-1) d^(-1) keV^(-1). With an exposure of 5.6 ton-years, the sensitivity of Panda X-4 T could reach a minimum spin-independent dark matter-nucleon cross section of 6 × 10^(-48) cm^2 at a dark matter mass of 40 Ge V/c^2. | HongGuang Zhang Abdusalam Abdukerim Wei Chen Xun Chen YunHua Chen XiangYi Cui BinBin Dong DeQing Fang ChangBo Fu Karl Giboni Franco Giuliani LinHui Gu XuYuan Guo ZhiFan Guo Ke Han ChangDa He ShengMing He Di Huang XingTao Huang Zhou Huang Peng Ji XiangDong Ji YongLin Ju ShaoLi Li Yao Li Heng Lin HuaXuan Liu JiangLai Liu YuGang Ma YaJun Mao KaiXiang Ni JinHua Ning XiangXiang Ren Fang Shi AnDi Tan AnQing Wang Cheng Wang HongWei Wang Meng Wang QiuHong Wang SiGuang Wang XiuLi Wang XuMing Wang Zhou Wang MengMeng Wu ShiYong Wu JingKai Xia MengJiao Xiao PengWei Xie BinBin Yan JiJun Yang Yong Yang ChunXu Yu JuMin Yuan JianFeng Yue Dan Zhang Tao Zhang Li Zhao QiBin Zheng JiFang Zhou Ning Zhou XiaoPeng Zhou | 2019 | Science China(Physics,Mechanics & Astronomy)2019，62，3： | 6 |
| 4 | Integrated genomic analysis identifies deregulated JAK/STAT-MYC-biosynthesis axis in aggressive NK-cell leukemia显示文摘好攻击的 NK 房间白血病(ANKL ) 是在从亚洲的人之中是更流行的 NK 房间瘤的一种稀罕形式并且中央并且南美洲。病人们通常在天以内死到月,甚至在收到迅速的治疗学的管理以后。这里,我们由集成整个染色体执行了 ANKL 的第一全面研究, transcriptome 并且定序指向,象功能的试金一样的 cytokine 数组。在 JAK-STAT 小径的变化在 48% 被识别(14/29 ) ANKL 病人,当细胞外的 STAT3 激发器 IL10 被 56 褶层的一般水准提高时(P < 0.0001 ) 在检查的所有病人的血浆。另外的经常变异的基因包括的 TP53 (34%) , TET2 (28%) , CREBBP (21%) 和 MLL2 (21%) 。耐心的 NK 白血病房间在多重新陈代谢的小径显示出 STAT3 phosphorylation, MYC 表示和 transcriptional 活动的突出的激活。机能上地, STAT3 激活和 MYC 表示为 ANKL 房间的增长和幸存是批评的。发信号的 STAT 调整了发信号的 MYC 抄写节目,和两 STAT, MYC 抄写被要求维持核苷酸合成和 glycolysis 的激活。一起, JAK-STAT 小径在 ANKL 为 genomic 改变和 IL10 刺激代表一个主要目标。这最新发现的 JAK/STAT-MYC-biosynthesis 轴可以在对待白血病的这种子类型为新奇治疗学的策略的发展提供机会。 | Liang Huang Dan Liu Na Wang Shaoping Ling Yuting Tang Jun Wu Lingtong Hao Hui Luo Xuelian Hu Lingshuang Sheng Lijun Zhu Di Wang Yi Luo Zhen Shang Min Xiao Xia Mao Kuangguo Zhou Lihua Cao Lili Dong Xinchang Zheng Pinpin Sui Jianlin He Shanlan Mo Jin Yan Qilin Ao Lugui Qiu Hongsheng Zhou Qifa Liu Hongyu Zhang Jianyong Li Jie Jin Li Fu Weili Zhao Jieping Chen Xin Du Guoliang Qing Hudan Liu Xin Liu Gang Huang Ding Ma Jianfeng Zhou Qian-fei Wang | 2018 | Cell Research2018，28，2： | 5 |
| 5 | CHIP regulates bone mass by targeting multiple TRAF family members in bone marrow stromal cells显示文摘Carboxyl terminus of Hsp70-interacting protein(CHIP or STUB1) is an E3 ligase and regulates the stability of several proteins which are involved in different cellular functions. Our previous studies demonstrated that Chip deficient mice display bone loss phenotype due to increased osteoclast formation through enhancing TRAF6 activity in osteoclasts. In this study we provide novel evidence about the function of CHIP. We found that osteoblast differentiation and bone formation were also decreased in Chip KO mice. In bone marrow stromal(BMS) cells derived from Chip^(-/-) mice, expression of a panel of osteoblast marker genes was significantly decreased. ALP activity and mineralized bone matrix formation were also reduced in Chip-deficient BMS cells. We also found that in addition to the regulation of TRAF6, CHIP also inhibits TNFα-induced NF-κB signaling through promoting TRAF2 and TRAF5 degradation. Specific deletion of Chip in BMS cells downregulated expression of osteoblast marker genes which could be reversed by the addition of NF-κB inhibitor. These results demonstrate that the osteopenic phenotype observed in Chip^(-/-) mice was due to the combination of increased osteoclast formation and decreased osteoblast differentiation. Taken together, our findings indicate a significant role of CHIP in bone remodeling. | Tingyu Wang Shan Li Dan Yi Guang-Qian Zhou Zhijie Chang Peter X.Ma Guozhi Xiao Di Chen | 2018 | Bone Research2018，6，2： | 5 |
| 6 | Norovirus Infection and Histo-blood Group Antigens in Children Hospitalized with Diarrhea in Lulong and Chenzhou in China显示文摘Norovirus(No V)is a pathogen that commonly causes viral diarrhea in children.Studies indicate that No V recognizes human histo-blood group antigens(HBGAs)as cell attachment factors.In order to explore the correlation between of No V infection and HBGAs,a cross-sectional study was conducted in children less than five years old who were hospitalized with diarrhea in two areas of China between November 2014 and February 2015. | SUN Xiao Man YAN Xiao Feng HE Zhi Gang Li Jing Xin GUO Ni Jun XU Zi Qian JIN Miao LI Dan Di ZHOU Yong Kang XIE Guang Cheng Pang Li Li ZHANG Qing LIU Na DUAN Zhao Jun | 2016 | Biomedical and Environmental Sciences2016，29，4： | 3 |
| 7 | Divergent Primary Immune Responses Induced by Human Immunodeficiency Virus-1 gp120 and Hepatitis B Surface Antigen Determine Antibody Recall Responses显示文摘The development of a vaccine based on human immunodeficiency virus type 1(HIV-1) envelope glycoprotein(Env) that elicits potent protective antibodies against infection has been challenging. Recently, we compared the antibody production patterns of HIV-1 Env gp120 and hepatitis B virus surface antigen(HBsAg) to provide insights into how we may improve the protective efficacy of Env-based immunogens. Our previous study showed that HIV Env and HBsAg display different mechanisms of antibody elicitation and that T cells facilitate the responses to repeated immunizations. Here, to elucidate the detailed roles of primary immunization in immune memory response formation and antibody production, we immunized C57BL/6 mice with each antigen and evaluated the development of T follicular helper(Tfh) cells, germinal centers,and the memory responses involved in prime and boost immunizations. We found that after prime immunization, compared with HBsAg, gp120 induced higher frequencies of Tfh cells and programmed death(PD)-1^+T cells, greater major histocompatibility complex II expression on B cells, comparable activated B cells, but weaker germinal center(GC)reactions and memory B cell responses in the draining lymph nodes, accompanied by slower antibody recall responses and poor immune memory responses. The above results suggested that more PD-1^+T cells arising in primary immunization may serve as major contributors to the slow antibody recall response elicited by HIV-1 Env. | Li Yuan Wen-Jiang Chen Jia-Ye Wang Yan Li Dan Tian Ming-Xia Wang Hao-Tong Yu Ying-Chu Xu Di Li Min Zhuang Hong Ling | 2018 | Virologica Sinica2018，33，6： | 2 |
| 8 | Preparation and Characterization of Biodegradable Polylactide(PLA) Microspheres Encapsulating Ginsenoside Rg3显示文摘In this study, the process of a biodegradable polylactide(PLA) microsphere encapsulating ginsenoside Rg3 was first studied by the emulsion solvent evaporation method, for enhancing solubility and stability of ginsenoside Rg3. Alabum was also first used as a modifier in this method. The mean diameter of the prepared PLA microspheres containing Rg3 was 40 μm. Ginsenoside Rg3 released from the microspheres was studied by HPLC and detected by UV. It was found that the drug release curve fitted the Model Heller-Baker best. | LIU Cheng-bai ZHANG Di LI De-guan JIANG Dan CHEN Xia | 2008 | Chemical Research in Chinese Universities2008，24，5： | 2 |
| 9 | Nociceptive behavioural assessments in mouse models of temporomandibular joint disorders显示文摘Orofacial pain or tenderness is a primary symptom associated with temporomandibular joint(TMJ)disorders(TMDs).To understand the pathological mechanisms underlying TMDs,several mouse models have been developed,including mechanical stimulus-induced TMD and genetic mouse models.However,a lack of feasible approaches for assessing TMD-related nociceptive behaviours in the orofacial region of mice has hindered the in-depth study of TMD-associated mechanisms.This study aimed to explore modifications of three existing methods to analyse nociceptive behaviours using two TMD mouse models:(1)mechanical allodynia was tested using von Frey filaments in the mouse TMJ region by placing mice in specially designed chambers;(2)bite force was measured using the Economical Load and Force(ELF)system;and(3)spontaneous feeding behaviour tests,including eating duration and frequency,were analysed using the Laboratory Animal Behaviour Observation Registration and Analysis System(LABORAS).We successfully assessed changes in nociceptive behaviours in two TMD mouse models,a unilateral anterior crossbite(UAC)-induced TMD mouse model and aβ-catenin conditional activation mouse model.We found that the UAC model andβ-catenin conditional activation mouse model were significantly associated with signs of increased mechanical allodynia,lower bite force,and decreased spontaneous feeding behaviour,indicating manifestations of TMD.These behavioural changes were consistent with the cartilage degradation phenotype observed in these mouse models.Our studies have shown reliable methods to analyse nociceptive behaviours in mice and may indicate that these methods are valid to assess signs of TMD in mice. | Jun Li Kaige Ma Dan Yi Chun-do Oh Di Chen | 2020 | International Journal of Oral Science2020，12，3： | 2 |
| 10 | UVB suppresses PTEN expression by upregulating miR-141 in HaCaT cells显示文摘MicroRNAs (miRNAs) are 21 to 24 nucleotide,non-coding RNA molecules that post-transcriptionally regulate the expression of target genes.Ultraviolet B (UVB) radiation has been shown to inhibit phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression in HaCaT cells through an unknown mechanism.In this study,we investigated whether miR-141 can regulate UVB exposure-mediated inhibition of PTEN expression.Real-time RT-PCR,annexin V/fluorescein isothiocyanate staining,Western blotting and anti-miRNA oligonucleotide transfection were employed in this study.We found that upregulation of miR-141 expression after UVB irradiation was inversely correlated with PTEN expression levels in HaCaT cells.Furthermore,miR-141 expression increased apoptosis,while anti-miR-141 partly restored PTEN expression and reversed the pro-apoptosis effect of UVB.UVB suppresses the expression of PTEN by upregulating miR-141 in HaCaT cells.Therefore,miR-141 is a potential gene therapy target for UVB-induced photodamage. | Wei Li Wu Di Lijuan Hua Bingrong Zhou ze Guo Dan Luo | 2011 | The Journal of Biomedical Research2011，25，2： | 2 |
| 11 | Antibody-drug conjugates in HER2-positive breast cancer显示文摘Antibody-drug conjugates(ADCs)combine the high specificity of monoclonal antibodies with the high anti-tumor activity of small molecular cytotoxic payloads.The anti-tumor activity of ADCs is mainly achieved by the direct blocking of the receptor by monoclonal antibodies,direct action and bystander effect of cytotoxic drugs,and antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity.ADCs have been used in adjuvant therapy and rescue treatment of human epidermal receptor 2(HER2)-positive breast cancer,greatly improving the prognosis of breast cancer patients.Several ongoing clinical trials of ADC for breast cancer and other solid tumors proved the potential of ADCs will provide more promising treatment options for patients with malignant tumors.This review introduces the mechanism and latest clinical progress of ADC drugs approved for HER2-positive breast cancer to guide clinical practice and conduct research. | Lixi Li Di Zhang Binliang Liu Dan Lv Jingtong Zhai Xiuwen Guan Zongbi Yi Fei Ma | 2022 | Chinese Medical Journal2022，，3： | 2 |
| 12 | Estrogen-dependent depressor response of melatonin via baroreflex afferent function and intensification of PKC-mediated Nav1.9 activation显示文摘Recent studies suggest that melatonin(Mel)plays an important role in the regulation of blood pressure(BP)via the aortic baroreflex pathway.In this study,we investigated the interaction between the baroreflex afferent pathway and Mel-mediated BP regulation in rats under physiological and hypertensive conditions.Mel(0.1,0.3,and 1.0 mg/mL)was microinjected into the nodose ganglia(NG)of rats.We showed that Mel-induced reduction of mean arterial pressure in female rats was significantly greater than that in male and in ovariectomized rats under physiological condition.Consistently,the expression of Mel receptors(MTNRs)in the NG of female rats was significantly higher than that of males.In L-NAME-induced hypertensive and spontaneously hypertensive rat models,MTNRs were upregulated in males but downregulated in female models.Interestingly,Mel-induced BP reduction was found in male hypertensive models.In whole-cell recording from identified baroreceptor neurons(BRNs)in female rats,we found that Mel(0.1μM)significantly increased the excitability of a female-specific subpopulation of Ah-type BRNs by increasing the Nav1.9 current density via a PKC-mediated pathway.Similar results were observed in baroreceptive neurons of the nucleus tractus solitarius,showing the facilitation of spontaneous and evoked excitatory post-synaptic currents in Ah-type neurons.Collectively,this study reveals the estrogen-dependent effect of Mel/MTNRs under physiological and hypertensive conditions is mainly mediated by Ah-type BRNs,which may provide new theoretical basis and strategies for the gender-specific anti-hypertensive treatment in clinical practice. | Di Wu Dan Zhao Di Huang Xun Sun Ke-xin Li Yan Feng Qiu-xin Yan Xin-yu Li Chang-peng Cui Hu-die Li Bai-yan Li | 2022 | Acta Pharmacologica Sinica2022，43，9： | 1 |
| 13 | Opportunities to search for extraterrestrial intelligence with the FAST显示文摘The discovery of ubiquitous habitable extrasolar planets,combined with revolutionary advances in instrumentation and observational capabilities,has ushered in a renaissance in the search for extraterrestrial intelligence(SETI).Large scale SETI activities are now underway at numerous international facilities.The Five-hundred-meter Aperture Spherical radio Telescope(FAST)is the largest single-aperture radio telescope in the world,and is well positioned to conduct sensitive searches for radio emission indicative of exo-intelligence.SETI is one of the five key science goals specified in the original FAST project plan.A collaboration with the Breakthrough Listen Initiative was initiated in 2016 with a joint statement signed both by Dr.Jun Yan,the then director of National Astronomical Observatories,Chinese Academy of Sciences(NAOC),and Dr.Peter Worden,Chairman of the Breakthrough Prize Foundation.In this paper,we highlight some of the unique features of FAST that will allow for novel SETI observations.We identify and describe three different signal types indicative of a technological source,namely,narrow band,wide-band artificially dispersed and modulated signals.Here,we propose observations with FAST to achieve sensitivities never before explored.For nearby exoplanets,such as TESS targets,FAST will be sensitive to an EIRP of 1.9×1011 W,well within the reach of current human technology.For the Andromeda Galaxy,FAST will be able to detect any Kardashev type II or more advanced civilization there. | Di Li Vishal Gajjar Pei Wang Andrew Siemion Zhi-Song Zhang Hai-Yan Zhang You-Ling Yue Yan Zhu Cheng-Jin Jin Shi-Yu Li Sabrina Berger Bryan Brzycki Jeff Cobb Steve Croft Daniel Czech David DeBoer Julia DeMarines Jamie Drew J.Emilio Enriquez Nectaria Gizani Eric J.Korpela Howard Isaacson Matthew Lebofsky Brian Lacki David H.E.MacMahon Morgan Nanez Chen-Hui Niu Xin Pei Danny C.Price Dan Werthimer Pete Worden Yunfan Gerry Zhang Tong-Jie Zhang FAST Collaboration | 2020 | Research in Astronomy and Astrophysics2020，20，5： | 1 |
| 14 | Detection of viral antigens in renal tissue of glomerulonephritis patients without serological evidence of hepatitis B virus and hepatitis C virus infection显示文摘 | Dan Kong Di Wu Tianzhen Wang Tianzhu Li Shengjie Xu Fulai Chen Xiaoming Jin Ge Lou | 2013 | International Journal of Infectious Diseases2013，，7： | 1 |
| 15 | Soybean isoflavone ameliorates β‐amyloid 1‐42‐induced learning and memory deficit in rats by protecting synaptic structure and function显示文摘 | Juan Ding Yuan‐Di Xi Dan‐Di Zhang Xia Zhao Jin‐Meng Liu Chao‐Qun Li Jing Han Rong Xiao | 2013 | Synapse2013，，12： | 1 |
| 16 | The involvement of sortase A in high virulence of STSS-causing Streptococcus suis serotype 2显示文摘 | Changjun Wang Ming Li Youjun Feng Feng Zheng Yaqing Dong Xiuzhen Pan Gong Cheng Ruiping Dong Dan Hu Xiaodan Feng Junchao Ge Di Liu Jing Wang Min Cao Fuquan Hu Jiaqi Tang | 2008 | Archives of Microbiology2008，，1： | 1 |
| 17 | Detection of viral antigens in renal tissue of glomerulonephritis patients without serological evidence of hepatitis B virus and hepatitis C virus infection显示文摘 | Dan Kong Di Wu Tianzhen Wang Tianzhu Li Shengjie Xu Fulai Chen Xiaoming Jin Ge Lou | 2013 | International Journal of Infectious Diseases2013，，7： | 1 |
| 18 | Gene Knockdown in Human Rhinovirus 1B Using 2′-OMe-modified si RNAs Results in the Reactivation of the Interferon Response显示文摘学习是调查 2-O-methylated (2-OMe ) 的击倒的效率的这的目的在人的鼻病毒 1B (HRV1B ) 上修改了小介入的 RNA (siRNAs ) 复制和干扰素反应。因此, 24 2-OMe-modified siRNAs 被设计指向 HRV1B。HRV1B 的 RNA 层次,像使用费的受体 3,黑瘤联系区别的基因 5, retinoic 酸可诱导的基因 -- 我,和干扰素在感染 HRV1B 的 HeLa 和 BEAS-2B 被决定有 2-OMe-modified siRNAs 的上皮的房间 transfected。结果表明所有 2-OMe-modified siRNAs 防碍 HRV1B 的复制在一房间特定并且 transfection 效率依赖者举止。像使用费的受体的病毒的激活 3,黑瘤联系区别的基因 5, retinoic 酸可诱导的基因 -- 我,和干扰素反应被检测。在结论,在这研究使用的 2-OMe-modified siRNAs 能防碍 HRV1B 复制,可能导致干扰素反应的复活。 | XIE Guang Cheng ZHANG Qing PANG Li Li LI Dan Di JIN Miao LI Hui Ying XU Zi Qian KONG Xiang Yu WANG Hong LU Shan DUAN Zhao Jun | 2016 | Biomedical and Environmental Sciences2016，29，2： | 1 |
| 19 | An improved evaluation of the neutron background in the PandaX-Ⅱ experiment显示文摘In dark matter direct detection experiments,neutron is a serious source of background,which can mimic the dark matter-nucleus scattering signals.In this paper,we present an improved evaluation of the neutron background in the PandaX-II dark matter experiment by a novel approach.Instead of fully relying on the Monte Carlo simulation,the overall neutron background is determined from the neutron-induced high energy signals in the data.In addition,the probability of producing a dark-matter-like background per neutron is evaluated with a complete Monte Carlo generator,where the correlated emission of neutron(s)andγ(s)in the(α,n)reactions and spontaneous fissions is taken into consideration.With this method,the neutron backgrounds in the Run 9(26-ton-day)and Run 10(28-ton-day)data sets of PandaX-II are estimated to be(0.66±0.24)and(0.47±0.25)events,respectively. | QiuHong Wang Abdusalam Abdukerim Wei Chen Xun Chen YunHua Chen XiangYi Cui YingJie Fan DeQing Fang ChangBo Fu LiSheng Geng Karl Giboni Franco Giuliani LinHui Gu XuYuan Guo Ke Han ChangDa He Di Huang Yan Huang YanLin Huang Zhou Huang Peng Ji XiangDong Ji YongLin Ju YiHui Lai Kun Liang HuaXuan Liu JiangLai Liu WenBo Ma YuGang Ma YaJun Mao Yue Meng Parinya Namwongsa KaiXiang Ni JinHua Ning XuYang Ning XiangXiang Ren ChangSong Shang Lin Si AnDi Tan AnQing Wang HongWei Wang Meng Wang SiGuang Wang XiuLi Wang Zhou Wang MengMeng Wu ShiYong Wu JingKai Xia MengJiao Xiao PengWei Xie BinBin Yan JiJun Yang Yong Yang ChunXu Yu Jumin Yuan Dan Zhang HongGuang Zhang Tao Zhang Li Zhao QiBin Zheng JiFang Zhou Ning Zhou XiaoPeng Zhou | 2020 | Science China(Physics,Mechanics & Astronomy)2020，63，3： | 0 |
| 20 | Identification and characterization of isocitrate dehydrogenase 1(IDH1)as a functional target of marine natural product grincamycin B显示文摘Grincamycins(GCNs)are a class of angucycline glycosides isolated from actinomycete Streptomyces strains that have potent antitumor activities,but their antitumor mechanisms remain unknown.In this study,we tried to identify the cellular target of grincamycin B(GCN B),one of most dominant and active secondary metabolites,using a combined strategy.We showed that GCN B-selective-induced apoptosis of human acute promyelocytic leukemia(APL)cell line NB4 through increase of ER stress and intracellular reactive oxygen species(ROS)accumulation.Using a strategy of combining phenotype,transcriptomics and protein microarray approaches,we identified that isocitrate dehydrogenase 1(IDH1)was the putative target of GCN B,and confirmed that GCNs were a subset of selective inhibitors targeting both wild-type and mutant IDH1 in vitro.It is well-known that IDH1 converts isocitrate to 2-oxoglutarate(2-OG),maintaining intracellular 2-OG homeostasis.IDH1 and its mutant as the target of GCN B were validated in NB4 cells and zebrafish model.Knockdown of IDH1 in NB4 cells caused the similar phenotype as GCN B treatment,and supplementation of N-acetylcysteine partially rescued the apoptosis caused by IDH1 interference in NB4 cells.In zebrafish model,GCN B effectively restored myeloid abnormality caused by overexpression of mutant IDH1(R132C).Taken together,we demonstrate that IDH1 is one of the antitumor targets of GCNs,suggesting wild-type IDH1 may be a potential target for hematological malignancies intervention in the future. | Zheng Wang Zeng-xia Li Wen-cao Zhao Hong-bo Huang Jia-qi Wang Hao Zhang Jun-yan Lu Rui-na Wang Wei Li Zhao Cheng Wen-long Xu Di Zhu Li-sha Zhou Wei Jiang Long Yu Jun-yan Liu Cheng Luo Heng Zhu Dan Ye Wei-jun Pan Jian-hua Ju Yong-jun Dang | 2021 | Acta Pharmacologica Sinica2021，42，5： | 0 |
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