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| 1 | Oncogenic AURKA-enhanced N6-methyladenosine modification increases DROSHA mRNA stability to transactivate STC1 in breast cancer stem-like cells显示文摘RNase III DROSHA is upregulated in multiple cancers and contributes to tumor progression by hitherto unclear mechanisms.Here,we demonstrate that DROSHA interacts withβ-Catenin to transactivate STC1 in an RNA cleavage-independent manner,contributing to breast cancer stem-like cell(BCSC)properties.DROSHA mRNA stability is enhanced by N6-methyladenosine(m^(6)A)modification which is activated by AURKA in BCSCs.AURKA stabilizes METTL14 by inhibiting its ubiquitylation and degradation to promote DROSHA mRNA methylation.Moreover,binding of AURKA to DROSHA transcript further strengthens the binding of the m^(6)A reader IGF2BP2 to stabilize m^(6)A-modified DROSHA.In addition,wild-type DROSHA,but not an m^(6)A methylation-deficient mutant,enhances BCSC stemness maintenance,while inhibition of DROSHA m^(6)A modification attenuates BCSC traits.Our study unveils the AURKA-induced oncogenic m^(6)A modification as a key regulator of DROSHA in breast cancer and identifies a novel DROSHA transcriptional function in promoting the BCSC phenotype. | Fei Peng Jie Xu Bai Cui Qilan Liang Sai Zeng Bin He Hong Zou Manman Li Huan Zhao Yuting Meng Jin Chen Bing Liu Shasha Lv Peng Chu Fan An Zifeng Wang Junxiu Huang Yajing Zhan Yuwei Liao Jinxin Lu Lingzhi Xu Jin Zhang Zhaolin Su Zhiguang Li Fangjun Wang Eric W-FLam Quentin Liu | 2021 | Cell Research2021，31，3： | 9 |
| 2 | Study of establishing disease-syndrome combined with animal model for immune thrombocytopenic purpura without additional conditions显示文摘Objective:To explore the feasibility of establishing the disease-syndrome combined animal model for immune thrombocytopenic purpura(ITP)without additional conditions.Methods:Three batches of data related to the ITP model mice obtained by replication at different time were analyzed,and whether the APS-injected model mice replicated through the passive immune modeling method could simulate the pathogenesis and clinical characteristics of human ITP was evaluated according to the differentiation criteria for diseasesyndrome combined model.Results:The APS-injected replicated ITP model mice possessed the following traits:(1)Compared with the normal group,the platelet count was significantly decreased,and coagulation time was significantly increased in the model group(P<.01).(2)Compared with the normal group,the medullary thrombocytogenous megakaryocytes were significantly decreased(P<.05,.01,.001).(3)The APS-injected sites and other parts of the model mice had spontaneous hemorrhage.(4)Behavioral changing signs were observed 1 week after the modeling(i.e.low activity,delayed activity,poor appetite,skin petechia/hemorrhage and spontaneous hemorrhage at the injected sites or other parts),and were getting more and more severe.Conclusion:According to the syndrome differentiation criteria for disease-syndrome combined model of ITP,the APS-injected animal model of ITP replicated through the passive immune modeling method without additional conditions possesses the characteristics of disease-syndrome combined model.It provides an ideal tool for the development of traditional Chinese medicine pharmacology experiment. | Haiyan Lang Ming Guo Yuting Chu Wei Ma Yayue Zhang Ling Zhang Xinyi Chen | 2016 | Journal of Traditional Chinese Medical Sciences2016，3，3： | 2 |
| 3 | Investigation of hemostatic effect of Spleeninvigorating,Qi-replenishing and Bloodarresting Formula on simvastatin-induced zebrafish hemorrhage model显示文摘Blood-arresting Formula on simvastatin-induced zebrafish hemorrhage model compared with that of the Heat-clearing and Blood-cooling Formula.Methods:AB strain wild type zebrafish were treated with 0.5 mM simvastatin for 24 hours to establish the zebrafish hemorrhage model.Under strictly blind experimental conditions,the zebrafish were then treated with experimental agents in different concentration within the maximum non-lethal dose.The intervention effect of the Spleen-invigorating,Qi-replenishing and Blood-arresting Formula was comprehensively assessed by examining the main observational parameters such as the bleeding reduction rate and hemostatic rate while referring to the additional parameters such as blood flow,improvement rate of blood flow,velocity of movement,improvement rate of motion under spleen-qi deficiency.Results:Hemostatic effect:The bleeding rate and hemostatic rate in the zebrafish were respectively,30%,15%,45%,40%and 60%,80%,40%,47%when equal concentration of 500 mg/mL,1000 mg/mL were used.This showed that the experimental herbs B1 was superior to B2 in decreasing the bleeding rate and improving hemostatic effect in the zebrafish.Improvement of blood flow:With equal concentration,the experimental herb B1 was superior to B2 in increasing the blood flow and improvement rate of blood flow in hemorrhagic zebrafish.Promotion of the improvement of motion:With equal concentration of 500 mg/mL and 1000 mg/mL,the experimental herb B1 was superior to B2 in promoting the velocity of motion in the zebrafish and promoting the improvement rate of motion.Conclusion:The manifestations of simvastatin-induced zebrafish hemorrhage are basically similar to that of failure of the spleen to control blood in human beings.The Spleeninvigorating,Qi-replenishing and Blood-arresting Formula has good hemostatic effect on simvastatin-induced hemorrhage in the zebrafish.It also boasts the functions of improving blood flow and velocity of motion in the hemorrhagic zebrafish.Such a conclusion provides the experimental basis for the treatment of the syndrome of failure of the spleen to control blood by this formula. | Yuting Chu Ling Zhang Xiaoyu Zhu Yayue Zhang Bo Xia Li Hou Rushun Song Tiantian Li Chunqi Li Qing Dong a Xinyi Chen | 2016 | Journal of Traditional Chinese Medical Sciences2016，3，4： | 1 |
| 4 | Quadrupole-Linear Ion Trap Tandem Mass Spectrometry System for Clinical Biomarker Analysis显示文摘The accurate and efficient measurement of small molecule disease markers for clinical diagnosis is of great importance.In this study,a quadrupole-linear ion trap(Q-LIT)tandem mass spectrometer was designed and built in our laboratory.Target precursor ions were first selected in the quadrupole,and then injected,trapped,and fragmented simultaneously in the linear ion trap(LIT)to reduce the space charge effect,enrich the target product ions,and promote sensitivity.The targeted analytes were measured with selected reaction monitoring using a positive scan mode with electrospray ionization(ESI).Ions with a mass-to-charge ratio(m/z)ranging from 195 to 2022 were demonstrated.When scanning at 1218amu.s^(-1),unit resolution and an accuracy of higher than m/z 0.28 was obtained for m/z up to 2000.The dimensionless Mathieu parameter(q)value used in this study was 0.40 for collision-induced dissociation(CID),which was activated by resonance excitation.And an overall CID efficiency of 64%was achieved(activation time,50 ms).Guanidinoacetic acid(GAA)and creatine(CRE)were used as model compounds for small molecule clinical biomarkers.The limits of quantification were 1.0 and 0.2 nmol.L^(-1)for GAA and CRE,respectively.A total of 77 actual samples were successfully analyzed by the home-built ESI-Q-LIT tandem mass spectrometry system.The developed method can reduce matrix interference,minimize space charge effects,and avoid the chromatographic separation of complex samples to simplify the pretreatment process.This novel Q-LIT system is expected to be a good candidate for the determination of biomarkers in clinical diagnosis and therapeutics. | Xiang Fang Jie Xie Shiying Chu You Jiang Yuting An Chang Li Xiaoyun Gong Rui Zhai Zejian Huang Chunling Qiu Xinhua Dai | 2022 | Engineering2022，，9： | 1 |
| 5 | Computational Tools and Resources for CRISPR/Cas Genome Editing显示文摘The past decade has witnessed a rapid evolution in identifying more versatile clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein(Cas)nucleases and their functional variants,as well as in developing precise CRISPR/Cas-derived genome editors.The programmable and robust features of the genome editors provide an effective RNAguided platform for fundamental life science research and subsequent applications in diverse scenarios,including biomedical innovation and targeted crop improvement.One of the most essential principles is to guide alterations in genomic sequences or genes in the intended manner without undesired off-target impacts,which strongly depends on the efficiency and specificity of single guide RNA(sgRNA)-directed recognition of targeted DNA sequences.Recent advances in empirical scoring algorithms and machine learning models have facilitated sgRNA design and off-target prediction.In this review,we first briefly introduce the different features of CRISPR/Cas tools that should be taken into consideration to achieve specific purposes.Secondly,we focus on the computer-assisted tools and resources that are widely used in designing sgRNAs and analyzing CRISPR/Cas-induced on-and off-target mutations.Thirdly,we provide insights into the limitations of available computational tools that would help researchers of this field for further optimization.Lastly,we suggest a simple but effective workflow for choosing and applying web-based resources and tools for CRISPR/Cas genome editing. | Chao Li Wen Chu Rafaqat Ali Gill Shifei Sang Yuqin Shi Xuezhi Hu Yuting Yang Qamar U.Zaman Baohong Zhang | 2023 | Genomics, Proteomics & Bioinformatics2023，21，1： | 0 |
| 6 | CUL4B orchestrates mesenchymal stem cell commitment by epigenetically repressing KLF4 and C/EBPδ显示文摘Dysregulated lineage commitment of mesenchymal stem cells(MSCs)contributes to impaired bone formation and an imbalance between adipogenesis and osteogenesis during skeletal aging and osteoporosis.The intrinsic cellular mechanism that regulates MSC commitment remains unclear.Here,we identified Cullin 4B(CUL4B)as a critical regulator of MSC commitment.CUL4B is expressed in bone marrow MSCs(BMSCs)and downregulated with aging in mice and humans.Conditional knockout of Cul4b in MSCs resulted in impaired postnatal skeletal development with low bone mass and reduced bone formation.Moreover,depletion of CUL4B in MSCs aggravated bone loss and marrow adipose accumulation during natural aging or after ovariectomy.In addition,CUL4B deficiency in MSCs reduced bone strength.Mechanistically,CUL4B promoted osteogenesis and inhibited adipogenesis of MSCs by repressing KLF4 and C/EBPδexpression,respectively.The CUL4B complex directly bound to Klf4 and Cebpd and epigenetically repressed their transcription.Collectively,this study reveals CUL4B-mediated epigenetic regulation of the osteogenic or adipogenic commitment of MSCs,which has therapeutic implications in osteoporosis. | Ruiqi Yu Hong Han Shuxian Chu Yijun Ding Shiqi Jin Yufeng Wang Wei Jiang Yuting Liu Yongxin Zou Molin Wang Qiao Liu Gongping Sun Baichun Jiang Yaoqin Gong | 2023 | Bone Research2023，11，2： | 0 |
| 7 | Modelling the variation of demersal fi sh distribution in Yellow Sea under climate change显示文摘Climate change can aff ect fi sh individuals or schools,and consequently the fi sheries.Studying future changes of fi sh distribution and abundance helps the scientifi c management of fi sheries.The dynamic bioclimate envelope model(DBEM)was used to identify the“environmental preference profi les”of the studied species based on outputs from three Earth system models(ESMs).Changes in ocean conditions in climate change scenarios could be transformed by the model into those in relative abundance and distribution of species.Therefore,the distributional response of 17 demersal fi shes to climate change in the Yellow Sea could be projected from 1970 to 2060.Indices of latitudinal centroid(LC)and mean temperature of relative abundance(MTRA)were used to represent the results conducted by model.Results present that 17 demersal fi sh species in the Yellow Sea show a trend of anti-poleward shift under both low-emission scenario(RCP 2.6)and high-emission scenario(RCP 8.5)from 1970 to 2060,with the projected average LC in three ESMs shifting at a rate of-1.17±4.55 and-2.76±3.82 km/decade,respectively,which is contrary to the previous projecting studies of fi shes suggesting that fi shes tend to move toward higher latitudes under increased temperature scenarios.The Yellow Sea Cold Water Mass could be the major driver resulting in the shift,which shows a potential signifi cance to fi shery resources management and marine conservation,and provides a new perspective in fi sh migration under climate change. | Yugui ZHU Yuting LIN Jiansong CHU Bin KANG Gabriel REYGONDEAU Qianshuo ZHAO Zhixin ZHANG Yunfeng WANG William W.L.CHEUNG | 2022 | Journal of Oceanology and Limnology2022，40，4： | 0 |
| 8 | ICAM-1 depletion in the center of immunological synapses is important for calcium releasing in T-cells显示文摘T-cell activation requires the formation of the immunological sy napse(IS)bet ween a T-cll and anantigen-presenting cell(AP C)to control the development of the adaptive immune response.How-ever,calcium release,an initial signal of T-cell activation,has been found to occur before IS for-mation.The mechanism for triggering the calcium signaling and relationship bet ween calciumrelease and IS format ion remains unclear.Herein,using live-cell imaging,we found that int ercellularadhesion molecule 1(ICAM-1),an essential mdlecule for IS formation,accumulated and then wasdepleted at the center of the synapse before complete IS formation.During the proces of ICAM1depletion,calcium was released.if ICAM-1 failed to be depleted from the center of the synapse,thesustained calcium signaling could not be induced.Moreover,depletion of ICAM-1 in ISs preferen-tially ccurred with the contact of antigen-specific T-cels and dendritic clls(DCs).Blocking thebinding ofICA M-1 and lymphocy te finction-associated antigen 1(LFA-1),ICAM-1 failed to depleteat the center of the synapse,and calcium release in T-clls decreased.In studying the mechanism ofhow the depletion ofiCA M1 could influence calcium release in T-clls,we found that the movementof ICAM-1 was associat ed with the localization of LFA-1 in the IS,which afected the localization ofcalcium microdomains,ORAIl and mitochondria in IS.Therefore,the depletion of ICAM-1 in the center of the synapse is an important factor for an initial sust ained calcium release in T-cells. | Yuanzhen Suo Wei Lin Yuting Deng Zhichao Fan Lizeng Qin Guosheng Jiang Yiwei Chu Xunbin Wei | 2018 | Journal of Innovative Optical Health Sciences2018，，2： | 0 |
| 9 | Spatiotemporally-regulated multienzymatic polymerization endows hydrogel continuous gradient and spontaneous actuation显示文摘There are several natural materials which have evolved functional gradients,ingeniously attaining maximal efficacy from limited components.Herein,we utilized the spatiotemporal distribution of initiator acetylacetone to regulate the multienzyme polymerization and fabricate a chitosan-polymer hydrogel.The temporal priority order of acetylacetone was higher than phenolmodified chitosan by density functional theory calculation.The acetylacetone within the gelatin could gradually diffuse spatially into the chitosan hydrogel to fabricate the composite hydrogel with gradient network structure.The gradient hydrogel possessed a transferring topography from the two-dimensional pattern.A continuously decreased modulus along with acetylacetone diffusion was confirmed by atomic force microscope-based force mapping experiment.The water-retaining ability of various regions was confirmed by low-field nuclear magnetic resonance(NMR)and thermogravimetric analysis(TG)analysis,which led to the spontaneous actuation of gradient hydrogel with maximum 1821°/h curling speed and 227°curling angle.Consequently,the promising gradient hydrogels could be applied as intelligent actuators and flexible robots. | Saiji Shen Chu Wu Yinghui Shang Hongdou Shen Yue Liao Yuting Guo Min Hu Xia Wang Gang Li Qigang Wang | 2022 | Science China Chemistry2022，65，1： | 0 |
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