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| 1 | Identification and expansion of cancer stem cells in tumor tissues and peripheral blood derived from gastric adenocarcinoma patients显示文摘胃的癌症是世界范围的第四很普通的癌症,与死亡的高率和低 5 年的幸存率。迄今为止,有为胃的癌症的有效治疗学的协议的缺乏。最近的研究建议癌症干细胞(CSC ) 为肿瘤开始,侵略,转移,和抵抗负责到 anticancer 治疗。因此,指向胃的 CSC 的治疗是吸引人的。然而,在人的胃的腺癌(GAC ) 的 CSC 没被描述。这里,我们从 GAC 病人在肿瘤纸巾和外部血识别 CSC。从肿瘤纸巾和病人的外部血被孤立的人的 GAC (GCSC ) 的 CSC 带了 CD44 和 CD54 表面标记,当注入了 immunodeficient 老鼠时,高度类似于原来的人的肿瘤的产生肿瘤,在 vitro 区分了进胃的上皮的房间,并且在 vivo 并且在 vitro 自我更新。我们的调查结果建议有效治疗学的协议必须指向 GCSC。从 GAC 病人的循环的 GCSC 的俘获也为为肿瘤转移潜在地负责的一张批评房间人口的鉴定显示出大潜力,并且为早诊断并且胃的癌症的纵的监视提供一个有效协议。 | Tie Chen Kun Yang Jianhua Yu Wentong Meng Dandan Yuan Feng Bi Fang Liu Jie Liu Bing Dai Xinzu Chen Fang Wang Fan Zeng Hong Xu Jiankun Hu Xianming Mo | 2012 | Cell Research2012，22，1： | 50 |
| 2 | Celastrol induces ferroptosis in activated HSCs to ameliorate hepatic fibrosis via targeting peroxiredoxins and HO-1显示文摘Ferroptosis is a form of regulated cell death, characterized by excessive membrane lipid peroxidation in an iron-and ROS-dependent manner. Celastrol, a natural bioactive triterpenoid extracted from Tripterygium wilfordii, shows effective anti-fibrotic and anti-inflammatory activities in multiple hepatic diseases. However, the exact molecular mechanisms of action and the direct protein targets of celastrol in the treatment of liver fibrosis remain largely elusive. Here, we discover that celastrol exerts anti-fibrotic effects via promoting the production of reactive oxygen species(ROS) and inducing ferroptosis in activated hepatic stellate cells(HSCs). By using activity-based protein profiling(ABPP) in combination with bio-orthogonal click chemistry reaction and cellular thermal shift assay(CETSA), we show that celastrol directly binds to peroxiredoxins(PRDXs), including PRDX1, PRDX2, PRDX4 and PRDX6,through the active cysteine sites, and inhibits their anti-oxidant activities. Celastrol also targets to heme oxygenase 1(HO-1) and upregulates its expression in activated-HSCs. Knockdown of PRDX1, PRDX2,PRDX4, PRDX6 or HO-1 in HSCs, to varying extent, elevated cellular ROS levels and induced ferroptosis. Taken together, our findings reveal the direct protein targets and molecular mechanisms via which celastrol ameliorates hepatic fibrosis, thus supporting the further development of celastrol as a promising therapeutic agent for liver fibrosis. | Piao Luo Dandan Liu Qian Zhang Fan Yang Yin-Kwan Wong Fei Xia Junzhe Zhang Jiayun Chen Ya Tian Chuanbin Yang Lingyun Dai Han-Ming Shen Jigang Wang | 2022 | Acta Pharmaceutica Sinica B2022，12，5： | 14 |
| 3 | Research status of biodegradable metals designed for oral and maxillofacial applications:A review显示文摘The oral and maxillofacial regions have complex anatomical structures and different tissue types,which have vital health and aesthetic functions.Biodegradable metals(BMs)is a promising bioactive materials to treat oral and maxillofacial diseases.This review summarizes the research status and future research directions of BMs for oral and maxillofacial applications.Mg-based BMs and Zn-based BMs for bone fracture fixation systems,and guided bone regeneration(GBR)membranes,are discussed in detail.Zn-based BMs with a moderate degradation rate and superior mechanical properties for GBR membranes show great potential for clinical translation.Fe-based BMs have a relatively low degradation rate and insoluble degradation products,which greatly limit their application and clinical translation.Furthermore,we proposed potential future research directions for BMs in the oral and maxillofacial regions,including 3D printed BM bone scaffolds,surface modification for BMs GBR membranes,and BMs containing hydrogels for cartilage regeneration,soft tissue regeneration,and nerve regeneration.Taken together,the progress made in the development of BMs in oral and maxillofacial regions has laid a foundation for further clinical translation. | Dandan Xia Fan Yang Yufeng Zheng Yunsong Liu Yongsheng Zhou | 2021 | Bioactive Materials2021，6，11： | 9 |
| 4 | CD4^(+)CD25^(+)but not CD4^(+)Foxp3^(+) T cells as a regulatory subset in primary biliary cirrhosis显示文摘Increasing evidence indicates a role for regulatory T cells(Tregs)in the immune response and in autoimmune diseases,but the role of Tregs and cytokines in autoimmune hepatic diseases remains largely unclear and controversial,especially in patients with primary biliary cirrhosis(PBC).This study was undertaken to investigate Tregs and different cytokines in the liver and peripheral blood of PBC patients.We found that these patients demonstrated a reduction of CD4^(+)CD25^(+) T cells but elevated CD4^(+)Foxp3^(+) T cells in peripheral blood mononuclear cells(PBMCs)and CD41 T cells.The percentage of CD4^(+)CD25^(+) T cells in PBMCs was negatively correlated with elevated plasma interferon(IFN)-c levels.A liver-specific analysis showed that the frequency of Foxp31 Tregs,transforming growth factor(TGF)-b1 and IFN-c were increased in PBC patients.Our findings suggest that an imbalance between CD4^(+)CD25^(+) Tregs and cytotoxic cytokines plays a crucial role in the pathogenesis of PBC while the role of Foxp3 needs further investigation. | Dandan Wang Huayong Zhang Jun Liang Zhifeng Gu Qiang Zhou Xiangshan Fan Yayi Hou Lingyun Sun | 2010 | Cellular & Molecular Immunology2010，7，6： | 9 |
| 5 | Pyrroloquinoline quinone regulates the redox status in vitro and in vivo of weaned pigs via the Nrf2/HO-1 pathway显示文摘Background:Oxidative stress is a main cause of piglet gut damage and diarrhea.Pyrroloquinoline quinone(PQQ),is a novel redox cofactor with antioxidant properties.However,the effect and mechanism that PQQ supplementation decreases oxidative injury in weaned pigs is not understood.Therefore,the aim of this study is to confirm the effect of PQQ on regulating redox status in weaned pigs and the mechanism for antioxidant function by porcine intestinal epithelial cell line(IPEC-J2)challenged with H_(2)O_(2).Results:Experiment 1,144 Duroc×Landrace×Yorkshire pigs(weaned at 28 d)were allocated to four groups:received a basal diet(control)and diets supplemented with 0.15%,0.30%and 0.45%PQQ,respectively.On d 28,growth performance,diarrhea incidence and redox factors were measured.Experiment 2,IPEC-J2 were treated with or without PQQ in the presence or absence of H_(2)O_(2)for indicated time points.Experiment 3,IPEC-J2 were transfected with or without Nrf2 siRNA,then treated according to Experiment 2.The cell viability,redox factors,protein of tight junctions and Nrf2 pathway were determined.In vivo,PQQ supplementation demonstrated dose-related improvements in average daily gain,and gain to feed ratio(Linear P<0.05).During d 0–28,compared to controls,0.45%PQQ supplementation for pigs decreased diarrhea incidence and MDA content in liver and jejunum,and increased concentration of SOD in liver;0.3%PQQ supplementation decreased ileal and liver MDA concentration;and 0.15%PQQ supplementation decreased ileal MDA concentration(P<0.05).In vitro,compared to cells cultured with H_(2)O_(2),pre-treatment with PQQ increased cell viability,tight junction proteins expression including ZO-1,ZO-2,Occludin and Claudin-1;and decreased ROS concentration and level of Caspase-3(P<0.05);as well as upregulated the ratio of Bcl-2 to Bax and protein expression of nuclear Nrf2,HO-1.Notably,Nrf2 knockdown by transfection with Nrf2 siRNA largely abrogated the positive effects of PQQ pretreatment on H_(2)O_(2)-induced intracellular changes.Conclusions:PQQ administration attenuated oxidative stress in weaned pigs which is associated with activation of Nrf2/HO-1 pathway. | Caiyun Huang Zijuan Fan Dandan Han Lee J.Johnston Xi Ma Fenglai Wang | 2021 | Journal of Animal Science and Biotechnology2021，12，4： | 4 |
| 6 | Effect of Shengmai Yin on the DNA methylation status of nasopharyngeal carcinoma cell and its radioresistant strains显示文摘Shengmai Yin(SMY)is a Chinese herbal decoction that effectively alleviates the side effects of radiotherapy in various cancers and helps achieve radiotherapy’s clinical efficacy.In this study,we explored the interaction mechanism among SMY,DNA methylation,and nasopharyngeal carcinoma(NPC).We identified differences in DNA methylation levels in NPC CNE-2 cells and its radioresistant cells(CNE-2R)using the methylated DNA immunoprecipitation array and found that CNE-2R cells showed genomewide changes in methylation status towards a state of hypomethylation.SMY may restore its original DNA methylation status,and thus,enhance radiosensitivity.Furthermore,we confirmed that the differential gene Tenascin-C(TNC)was overexpressed in CNE-2R cells and that SMY downregulated TNC expression.This downregulation of TNC inhibited NPC cell radiation resistance,migration,and invasion.Furthermore,we found that TNC was hypomethylated in CNE-2R cells and partially restored to a hypermethylated state after SMY intervention.DNA methyltransferases 3 a may be the key protein in DNA methylation of TNC. | Shiya Liu Zhiyuan Wang Daoqi Zhu Jiabin Yang Dandan Lou Ruijiao Gao Zetai Wang Aiwu Li Ying Lv Qin Fan | 2021 | Journal of Pharmaceutical Analysis2021，11，6： | 4 |
| 7 | Energy-level dependent H_2_O_2 production on metal-free,carbon-content tunable carbon nitride photocatalysts显示文摘Light-driven production of H_2O_2 from water and molecular oxygen could be a promising way for obtaining both solar fuels and fundamental chemicals. During that process, the H_2O_2 yield is strongly dependent on the reaction pathway associated with two-electron reduction of dioxygen by the photo-generated electrons. Herein, we synthesized a series of metal-free, carbon-content tunable carbon nitride photocatalysts(named C_3N_4-Carbon) by a facile hydrothermal reaction and subsequent thermal treatment at appropriate temperatures. The energy levels of the C_3N_4-Carbon catalysts vary with the carbon doping level, which is conveniently tuned by changing the initial glucose concentration during the hydrothermal reaction. The surface carbon species evolve with the carbon content and the nitrogen atoms in the structure of carbon nitride are partially substituted by foreign carbon atoms based on XPS measurements. The optimal catalyst leads to the highest H_2O_2 yield of 1271 μmol L^(-1) in an acidic aqueous solution(pH 3) after a reaction period of 4 h, twice higher than the pristine C_3N_4. In addition, the largest formation rate constant and the smallest decomposition rate constant of H_2O_2 are obtained on the optimal one according to the kinetics analyses. The decomposition tests of H_2O_2 indicate that the formation rate could be a dominant factor impacting the H_2O_2 yield. The conduction band position of the optimal catalyst is positively shifted to 0.06 V versus RHE, which is more favorable to the reduction of dioxygen to H_2O_2(O2/H_2O_2 at 0.69 V versus RHE). The positive shift of valence band also improves hole collection and leads to enhanced formation of H_2O_2. | Ruirui Wang Xin Zhang Fan Li Ding Cao Min Pu Dandan Han Junjiao Yang Xu Xiang | 2018 | Journal of Energy Chemistry2018，27，2： | 4 |
| 8 | Characterization of viromes within mosquito species in China显示文摘Mosquitoes are vectors of multiple disease-causing agents that cause worldwide outbreaks of serious infectious diseases in both humans and animals. These arboviral agents include Dengue virus (DENV), Zika virus (ZIKV), chikungunya virus, yellow fever virus, Japanese encephalitis virus (JEV),and Rift Valley fever virus. Thus, mosquitoes are key to the study of viral origin, spread, and the epidemic tendency of these infectious diseases (Hall and Macdonald, 2016). | Jiang Du Fan Li Yelin Han Shihong Fu Bo Liu Nan Shao Haoxiang Su Weijia Zhang Dandan Zheng Wenwen Lei Jie Dong Lilian Sun Ying He Jianmin Wang Fan Yang Huanyu Wang Guodong Liang Zhiqiang Wu Qi Jin | 2020 | Science China(Life Sciences)2020，63，7： | 2 |
| 9 | Reprogramming of phytopathogen transcriptome by a non-bactericidal pesticide residue alleviates its virulence in rice显示文摘Bacteria equipped with virulence systems based on highly bioactive small molecules can circumvent their host's defense mechanisms.Pathogens employing this strategy are currently threatening global rice production.In the present study,variations in the virulence of the highly destructive Barkholderiaplantarii were observed in different rice-producing regions.The environment-linked variation was not attributable to any known host-related or external factors.Co-occurrence analyses indicated a connection between reduced virulence and 5-Amino-l,3,4-thiadiazole-2-thiol(ATT),a non-bactericidal organic compound.ATT,which accumulates in rice plants during metabolization of specific agrochemicals,was found to reduce virulence factor secretion by B.plantarii up to 88.8%and inhibit pathogen virulence by hijacking an upstream signaling cascade.Detailed assessment of the newly discovered virulence inhibitor resulted in mechanistic insights into positive effects of ATT accumulation in plant tissues.Mechanisms of virulence alleviation were deciphered by integrating high-throughput data,gene knockout mutants,and molecular interaction assays.TroK,a histidine protein kinase in a two-component system that regulates virulence factor secretion,is likely the molecular target antagonized by ATT.Our findings provide novel insights into virulence modulation in an important plant-pathogen system that relies on the host's metabolic activity and subsequent signaling interference. | Haruna Matsumoto Yuan Qian Xiaoyan Fan Sunlu Chen Yanxia Nie Kun Qiao Dandan Xiang Xinzhong Zhang Meng Li Bo Guo Peilin Shen Qiangwei Wang Yunlong Yu Tomislav Cemava Mengcen Wang | 2022 | Fundamental Research2022，2，2： | 2 |
| 10 | Pomegranate-inspired porous SnSe/ZnSe@C anode:A stress-buffer nanostructure for fast and ultrastable sodium-ion storage显示文摘Tin selenide(SnSe)is considered as a potential anode for sodium-ion batteries(SIBs)owing to its high theoretical specific capacity.Unfortunately,it suffers from drastic volume expansion/contraction during sodium ions insertion/extraction,resulting in poor cycling stability.Herein,a pomegranate-inspired porous carbon shell wrapped heterogeneous SnSe/ZnSe composite(SnSe/ZnSe@C)is exquisitely designed and fabricated through electrostatic spraying followed by high-temperature selenization.The polyacrylonitrile-derived carbon shell acts as an adhesive to link the porous cubic SnSe/ZnSe and form highly interconnected microcircuits to improve the electron/ion transfer efficiency and inhibit the bulk volume change of internal metallic selenide nanoparticles and polyselenides dissolution during repeated cycling.Moreover,the abundant heterostructure interface of SnSe/ZnSe further significantly accelerates the electrons/ions transport.As a result,the as-prepared SnSe/ZnSe@C electrode exhibits a high specific capacity(508.3 m Ah g^(-1)at 0.05 A g^(-1)),excellent rate performance(177.8 m Ah g^(-1)at 10.0 A g^(-1)),and remarkable cycling stability(195.9 m Ah g^(-1)after 10,000 cycles at 5.0 A g^(-1)).Furthermore,in-situ Xray diffraction(XRD)/Raman,ex-situ transmission electron microscopy,and kinetic analysis clearly reveal a four-step electrochemical reaction process and battery-capacitor dual-mode sodium storage mechanism.This work provides a new perspective for developing commercial SIBs anode materials with high capacity and long lifespan. | Zhixin Liang Qinghua Li Wang Zhang Dandan Yu Wei Zhang Jiawei Wu Gaoyu Wang Wenbo Fan Junling Wang Shaoming Huang | 2022 | Journal of Energy Chemistry2022，，12： | 2 |
| 11 | Tripartite entangled state,tripartite entangled Wigner operator and their generalization to an n-mode case显示文摘For entangled three particles one should treat their wave function as a whole.There is no physical meaning talking about the wave function(or Wigner function) for any one of the tripartite,and therefore considering the entangled Wigner function(Wigner operator) is of necessity.In this paper,we introduce a pair of mutually conjugate tripartite entangled state representations for defining the Wigner operator of entangled tripartite.Its marginal distributions and the Wigner function of the three-mode squeezed vacuum state are presented.Deriving wave function from its corresponding tripartite entangled Wigner function is also discussed.Moreover,through establishing the n-mode entangled state representation,we introduce the n-mode entangled Wigner operator,which would be more generally useful in quantum physics. | L CuiHong GU DanDan FAN HongYi WANG YaWei | 2013 | Science China(Physics,Mechanics & Astronomy)2013，56，9： | 2 |
| 12 | Research Progress of Rice-Fish Integrated Farming显示文摘Rice-fish integrated farming( RFIF) can change the agricultural production pattern from mono-farming model to the co-farming model,and the stereoscopic and integrated farming system established by RFIF can change the flat production to the stereoscopic production. Therefore,RFIF is the important development direction for agriculture to change pattern and adjust structure. In order to further promote development of the research and application of RFIF,the general development situation of RFIF in China was reviewed; the effects of RFIF on increasing farmer' income and enhancing agricultural efficiency were clarified. The technologies matched with RFIF,such as rice paddy engineering technology,safe plant protection technology,security fertilization technology,fish disease prevention and control technology and water quality management technology,were summarized,and the supporting role of RFIF for agriculture was pointed out. In addition,the development prospect of RFIF was proposed,as well as the key research direction of RFIF. | Shunlong MENG Gengdong HU DANDan LI Liping QIU Chao SONG Limin FAN Yao ZHENG Wei WU Jiazhang CHEN Xuwen BING | 2018 | Agricultural Biotechnology2018，7，4： | 2 |
| 13 | Design and evaluation of a recombinant multi-epitope-based ELISA for the serological surveillance of HEV infection in northern China 显示文摘 | Gao Shenyang Li Dandan Fan Chen | 2011 | Arch Virol2011，，： | 1 |
| 14 | Photocrosslinkable Col/PCL/Mg composite membrane providing spatiotemporal maintenance and positive osteogenetic effects during guided bone regeneration显示文摘Guided bone regeneration membranes have been effectively applied in oral implantology to repair bone defects.However,typical resorbable membranes composed of collagen(Col)have insufficient mechanical properties and high degradation rate,while non-resorbable membranes need secondary surgery.Herein,we designed a photocrosslinkable collagen/polycaprolactone methacryloyl/magnesium(Col/PCLMA/Mg)composite membrane that provided spatiotemporal support effect after photocrosslinking.Magnesium particles were added to the PCLMA solution and Col/PCLMA and Col/PCLMA/Mg membranes were developed;Col membranes and PCL membranes were used as controls.After photocrosslinking,an interpenetrating polymer network was observed by scanning electron microscopy(SEM)in Col/PCL and Col/PCL/Mg membranes.The elastic modulus,swelling behavior,cytotoxicity,cell attachment,and cell proliferation of the membranes were evaluated.Degradation behavior in vivo and in vitro was monitored according to mass change and by SEM.The membranes were implanted into calvarial bone defects of rats for 8 weeks.The Col/PCL and Col/PCL/Mg membranes displayed much higher elastic modulus(p<0.05),and a lower swelling rate(p<0.05),than Col membranes,and there were no differences in cell biocompatibility among groups(p>0.05).The Col/PCL and Col/PCL/Mg membranes had lower degradation rates than the Col membranes,both in vivo and in vitro(p<0.05).The Col/PCL/Mg groups showed enhanced osteogenic capability compared with the Col groups at week 8(p<0.05).The Col/PCL/Mg composite membrane represents a new strategy to display space maintenance and enhance osteogenic potential,which meets clinical needs. | Feilong Wang Dandan Xia Siyi Wang Ranli Gu Fan Yang Xiao Zhao Xuenan Liu Yuan Zhu Hao Liu Yongxiang Xu Yunsong Liu Yongsheng Zhou | 2022 | Bioactive Materials2022，7，7： | 1 |
| 15 | Genome-wide association study of the backfat thickness trait in two pig populations显示文摘Backfat thickness is a good predictor of carcass lean content,an economically important trait,and a main breeding target in pig improvement.In this study,the candidate genes and genomic regions associated with the tenth rib backfat thickness trait were identified in two independent pig populations,using a genome-wide association study of porcine 60K SNP genotype data applying the compressed mixed linear model(CMLM)statistical method.For each population,30 most significant single-nucleotide polymorphisms(SNPs)were selected and SNP annotation implemented using Sus scrofa Build 10.2.In the first population,25 significant SNPs were distributed on seven chromosomes,and SNPs on SSC1 and SSC7 showed great significance for fat deposition.The most significant SNP(ALGA0006623)was located on SSC1,upstream of the MC4R gene.In the second population,27 significant SNPs were recognized by annotation,and 12 SNPs on SSC12 were related to fat deposition.Two haplotype blocks,M1GA0016251-MARC0075799 and ALGA0065251-MARC0014203-M1GA0016298-ALGA0065308,were detected in significant regions where the PIPNC1 and GH1 genes were identified as contributing to fat metabolism.The results indicated that genetic mechanism regulating backfat thickness is complex,and that genome-wide associations can be affected by populations with different genetic backgrounds. | Dandan ZHU Xiaolei LIU Rothschild MAX Zhiwu ZHANG Shuhong ZHAO Bin FAN | 2014 | Frontiers of Agricultural Science and Engineering2014，1，2： | 1 |
| 16 | Multidisciplinary Stepwise Management Strategy for Acute Superior Mesenteric Venous Thrombosis: An Intestinal Stroke Center Experience显示文摘 | Shuofei Yang Xinxin Fan Weiwei Ding Baochen Liu Jiaxiang Meng Dandan Xu Changsheng He Wenkui Yu Xingjiang Wu Jieshou Li | 2014 | Thrombosis Research2014，，： | 1 |
| 17 | Two-Dimensional Tunable and Temperature-Insensitive Lyot Filter for FM-to-AM Compensation显示文摘Utilizing polarization maintaining photonic crystal fiber(PM-PCF)with the low temperature coefficient of birefringence,a two-dimensional tunable and temperature-insensitive Lyot filter aiming to compensate the frequency modulation to amplitude modulation(FM-to-AM)conversion in high power laser facility is demonstrated.The Jones matrix is applied to analyze the relationship between optical characteristics of the filter and physical parameters(including amplitude ratio,phase delay,and susceptibility of the birefringence to temperature)of the polarization optical field.Both the transmission peak wavelength and extinction ratio of the spectral transmission are able to be changed simultaneously,hence,it shows more efficient FM-to-AM compensation ability.Besides,the transmission peak shift is about 18pm/°C with the PM-PCF configuration,which is about two orders of magnitude less than the normal polarization maintaining fiber(PMF)configuration.The demonstrated filter presents a practical application potential in large scale laser driven facility. | Mengqiu Fan Xiaocheng Tian Dandan Zhou Jiatian Wei Handing Xia Hongwei Lv Hao Zhao Dangpeng Xu Wanguo Zheng | 2021 | Photonic Sensors2021，11，3： | 1 |
| 18 | Low-temperature growth and optical properties of Ce-doped ZnO nanorods显示文摘 | Jinghai Yang Ming Gao Yongjun Zhang Lili Yang Jihui Lang Dandan Wang Huilian Liu Yanqing Liu Yaxin Wang Hougang Fan | 2008 | Applied Surface Science2008，255，： | 1 |
| 19 | PHF6 functions as a tumor suppressor by recruiting methyltransferase SUV39H1 to nucleolar region and offers a novel therapeutic target for PHF6-muntant leukemia显示文摘Mutations in the plant homeodomain-like finger protein 6(PHF6)gene are strongly associated with acute myeloid(AML)and T-cell acute lymphoblastic leukemia(T-ALL).In this study,we demonstrated that PHF6 can bind to H3K9me3 and H3K27me1 on the nucleolar chromatin and recruit histone methyltransferase SUV39H1 to the rDNA locus.The deletion of PHF6 caused a decrease in the recruitment of SUV39H1 to rDNA gene loci,resulting in a reduction in the level of H3K9me3 and the promotion of rDNA transcription.The knockdown of either SUV39H1 or PHF6 significantly attenuated the effects of increase in H3K9me3 and suppressed the transcription of rDNA induced by the overexpression of the other interacting partner,thereby establishing an interdependent relationship between PHF6 and SUV39H1 in their control of rRNA transcription.The PHF6 clinical mutants significantly impaired the ability to bind and recruit SUV39H1 to the rDNA loci,resulting in an increase in rDNA transcription activity,the proliferation of in vitro leukemia cells,and the growth of in vivo mouse xenografts.Importantly,significantly elevated levels of pre-rRNA were observed in clinical AML patients who possessed a mutated version of PHF6.The specific rDNA transcription inhibitor CX5461 significantly reduced the resistance of U937 AML cells deficient in PHF6 to cytarabine,the drug that is most commonly used to treat AML.Collectively,we revealed a novel molecular mechanism by which PHF6 recruits methyltransferase SUV39H1 to the nucleolar region in leukemia and provided a potential therapeutic target for PHF6-mutant leukemia. | Hsiang-i Tsai Yanping Wu Rui Huang Dandan Su Yingyi Wu Xiaoyan Liu Linglu Wang Zhanxue Xu Yuxin Pang Chong Sun Chao He Fan Shu Haitao Zhu Dongqing Wang Fang Cheng Laiqiang Huang Hongbo Chen | 2022 | Acta Pharmaceutica Sinica B2022，12，4： | 1 |
| 20 | Excessive branched-chain amino acid accumulation restricts mesenchymal stem cell-based therapy efficacy in myocardial infarction显示文摘Mesenchymal stem cells(MSCs)delivered into the post-ischemic heart milieu have a low survival and retention rate,thus restricting the cardioreparative efficacy of MSC-based therapy.Chronic ischemia results in metabolic reprogramming in the heart,but little is known about how these metabolic changes influence implanted MSCs.Here,we found that excessive branched-chain amino acid(BCAA)accumulation,a metabolic signature seen in the post-ischemic heart,was disadvantageous to the retention and cardioprotection of intramyocardially injected MSCs.Discovery-driven experiments revealed that BCAA at pathological levels sensitized MSCs to stress-induced cell death and premature senescence via accelerating the loss of histone 3 lysine 9 trimethylation(H3K9me3).A novel mTORC1/DUX4/KDM4E axis was identified as the cause of BCAA-induced H3K9me3 loss and adverse phenotype acquisition.Enhancing BCAA catabolic capability in MSCs via genetic/pharmacological approaches greatly improved their adaptation to the high BCAA milieu and strengthened their cardioprotective efficacy.We conclude that aberrant BCAA accumulation is detrimental to implanted MSCs via a previously unknown metabolite-signaling-epigenetic mechanism,emphasizing that the metabolic changes of the post-ischemic heart crucially influence the fate of implanted MSCs and their therapeutic benefits. | Fuyang Zhang Guangyu Hu Xiyao Chen Ling Zhang Lanyan Guo Congye Li Hang Zhao Zhe Cui Xiong Guo Fangfang Sun Dandan Song Wenjun Yan Yunlong Xia Shan Wang Miaomiao Fan Ling Tao | 2022 | Signal Transduction and Targeted Therapy2022，7，7： | 1 |
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