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| 1 | Loss of stat3 function leads to spine malformation and immune disorder in zebrafish显示文摘STAT(Signal Transducers and Activators of Transcription) gene family members have been revealed to be involved in cell growth and differentiation in vertebrates. Despite their physiological importance,their functions are poorly studied at organ and systemic levels. In this study, we performed a genome-wide analysis using data from invertebrates to vertebrates to identify STAT genes and analyze their evolutionary history. Interestingly, the STAT gene family undergoes genome duplications during the evolutionary history with STAT3 homologues firstly appearing in the basal extant vertebrate, sea lamprey, suggesting its possible roles in spine formation. To investigate the functions of stat3 in fish species, TALEN technology was performed to generate mutant zebrafish lines. Stat3 mutant zebrafish showed no obvious defects at early developmental stage but displayed severe lateral and vertical curvature of the spine(scoliosis), spine fracture and the incomplete bone joints with narrower junction between vertebrae at early juvenile stage, as indicated by Alizarin red and Alcian blue staining,radiography and micro-computed tomography(Micro CT) analysis. Transcriptome analysis reveals dramatic alterations in a number of genes involved in immune and infection response, skeletal development and somatic growth, especially downregulated expression of collagen gene family, in the juvenile stat3 mutant zebrafish. Moreover, most of the collagen genes were detected to have abnormal expression pattern during the formation of spine deformities in stat3 mutants. Our data reveal that stat3 is specially expressed in vertebrates and required for normal spine development and immune function in zebrafish. | Shuting Xiong Junjie Wu Jing Jing Peipei Huang Zhi Li Jie Mei Jian-Fang Gui | 2017 | Science Bulletin2017，62，3： | 7 |
| 2 | Essential roles of stat5.1/stat5b in controlling fish somatic growth显示文摘Signal transducer and activator of transcription 5b(STAT5b) has been identified as a key downstream mediator of growth hormone(GH) signaling in somatic growth of mammalian. However, the corresponding homologue gene of Stat5b is unknown in fish species. In this study, we generated loss-offunction mutants in stat5.1 and stat5.2, two stat5 homologues existing in zebrafish. In stat5.1-deficient zebrafish, a significant reduction of body length and body weight was detected in the embryos/larvae and adults compared with the wild-type control fish, and sexual size dimorphism in adult zebrafish was also eliminated. However, the stat5.2-deficient zebrafish displayed a normal developmental phenotype during all lifespan. Chromatin immunoprecipitation combined with deep sequencing(Ch IP-seq) method was adopted to further investigate the potential transcriptional targets of Stat5 protein and cast much light upon the biological function of Stat5. We identified more than 800 genes as transcriptional targets of Stat5 during zebrafish embryogenesis. KEGG analysis indicated that the Stat5 target gene network is predominantly linked to the metabolic pathways, neuroactive ligand-receptor interaction and JAK-STAT signaling pathways. Further validation studies suggested that Stat5.1 protein could directly regulate the expression of gh1, and stat5.1-mutated zebrafish showed a reduction of gh1 mRNA level. In the present study, stat5.1 was revealed as the corresponding homologue gene of Stat5b in fish species. Additionally,we found a novel molecular interaction between Stat5.1/Stat5b and GH, and unraveled a positive feedback loop Stat5.1-GH-Stat5.1 which is necessary for somatic growth and body development in zebrafish. | Shuting Xiong Jie Mei Peipei Huang Jing Jing Zhi Li Jingliang Kang Jian-Fang Gui | 2017 | Journal of Genetics and Genomics2017，44，12： | 4 |
| 3 | A novel PDZ domain-containing gene is essential for male sex differentiation and maintenance in yellow catfish(Pelteobagrus fulvidraco)显示文摘The sex-determining genes are found to be variable among different fish species. Yellow catfish(Pelteobagrus fulvidraco) is an important aquaculture fish species in China with XX/XY sex-determining type. Recently, YY super-male yellow catfish has been successfully produced by combining hormonalinduced sex reversal method with sex chromosome-linked markers. Here, we identified a novel PDZ domain-containing gene in yellow catfish designated as pfpdz1, in whose intron the sex-linked marker was located. The coding sequence of pfpdz1 in Y chromosome was identical to that in X chromosome except a missense SNP(A/T) that changes an amino acid(E8V) in the N-terminal region. Pfpdz1 displayed male-specific expression during sex differentiation. Overexpression of pfpdz1 using additive transgenesis induces XX ovary to differentiate into testis-like tissue, while the targeted inactivation of pfpdz1 in Y chromosome using CRISPR/Cas9-mediated mutagenesis triggers ovarian differentiation. Furthermore,we demonstrated that pfpdz1 initiates testicular differentiation through upregulating expression of amh, dmrt1 and sox9a1, as well as downregulating expression of cyp19a1, foxl2 and wnt4. Our data provide functional evidence that pfpdz1 is significant for male differentiation and maintenance in yellow catfish. | Cheng Dan Qiaohong Lin Gaorui Gong Tianyi Yang Shuting Xiong Yang Xiong Peipei Huang Jian-Fang Gui Jie Mei | 2018 | Science Bulletin2018，63，21： | 4 |
| 4 | Exosomes secreted from cardiomyocytes suppress the sensitivity of tumor ferroptosis in ischemic heart failure显示文摘Heart failure(HF)patients in general have a higher risk of developing cancer.Several animal studies have indicated that cardiac remodeling and HF remarkably accelerate tumor progression,highlighting a cause-and-effect relationship between these two disease entities.Targeting ferroptosis,a prevailing form of non-apoptotic cell death,has been considered a promising therapeutic strategy for human cancers.Exosomes critically contribute to proximal and distant organ-organ communications and play crucial roles in regulating diseases in a paracrine manner.However,whether exosomes control the sensitivity of cancer to ferroptosis via regulating the cardiomyocyte-tumor cell crosstalk in ischemic HF has not yet been explored.Here,we demonstrate that myocardial infarction(MI)decreased the sensitivity of cancer cells to the canonical ferroptosis activator erastin or imidazole ketone erastin in a mouse model of xenograft tumor.Post-MI plasma exosomes potently blunted the sensitivity of tumor cells to ferroptosis inducers both in vitro in mouse Lewis lung carcinoma cell line LLC and osteosarcoma cell line K7M2 and in vivo with xenograft tumorigenesis model.The expression of miR-22-3p in cardiomyocytes and plasma-exosomes was significantly upregulated in the failing hearts of mice with chronic MI and of HF patients as well.Incubation of tumor cells with the exosomes isolated from post-MI mouse plasma or overexpression of miR-22-3p alone abrogated erastin-induced ferroptotic cell death in vitro.Cardiomyocyte-enriched miR-22-3p was packaged in exosomes and transferred into tumor cells.Inhibition of cardiomyocyte-specific miR-22-3p by AAV9 sponge increased the sensitivity of cancer cells to ferroptosis.ACSL4,a pro-ferroptotic gene,was experimentally established as a target of miR-22-3p in tumor cells.Taken together,our findings uncovered for the first time that MI suppresses erastin-induced ferroptosis through releasing miR-22-3p-enriched exosomes derived from cardiomyocytes.Therefore,targeting exosome-mediated cardiomyocyte/tumor pathological communication may offer a novel approach for the ferroptosis-based antitumor therapy. | Ye Yuan Zhongting Mei Zhezhe Qu Guanghui Li Shuting Yu Yingqi Liu Kuiwu Liu Zhihua Shen Jiaying Pu Yanquan Wang Changhao Wang Zhiyong Sun Qian Liu Xiaochen Pang Ao Wang Zijing Ren Tong Wang Ying Liu Jinhuan Hong Jiajie Xie Xin Li Zhonghua Wang Weijie Du Baofeng Yang | 2023 | Signal Transduction and Targeted Therapy2023，8，4： | 2 |
| 5 | Accumulation and risk assessment of heavy metals in dust in main living areas of Guiyang City, Southwest China显示文摘Guiyang is a famous tourist city located in southwestern China. In this study, dust from eleven residential areas, seven city squares, and nine schools was collected to measure the heavy metal levels and evaluate its risk. At each sampling site, 4–5 sub-samples were taken as a bulk sample. All samples were air-dried, ground, passed through a 0.105 mm nylon sieve, digested with HNO3-HClO4 to determine the concentrations of Cd, Cu, Ni, Pb and Zn by ICP-MS, and digested with 1:1 aqua regia to determine As by AFS. The results show that the concentrations of As, Cd, Cu, Ni, Pb and Zn in dust of Guiyang City follow normal distribution with means of 16.1, 1.54, 138, 47.7, 129 and 479 mg/kg, respectively. Levels of As, Cd, Cu, Ni, Pb and Zn exceed the background level of soil in Guizhou Province by 33%, 96%, 100%, 78%, 96%, and 100%, respectively. Cd, Cu, Pb and Zn are heavily accumulated in dust of living areas with accumulation factors of 4.10, 5.12, 4.12 and 5.51, respectively. City square possesses the highest geometric means of As, Cd, Cu, Pb, and Zn. The risks of heavy metal exposure to teenagers are not obvious and in an order of As>Pb>Cu>Ni>Zn(Cd). | LI Xiaoyan ZHANG Shuting YANG Mei | 2014 | Chinese Journal Of Geochemistry2014，33，3： | 1 |
| 6 | Effect of two typical focus positions on microstructure shape and morphology in femtosecond laser multi-pulse ablation of metals显示文摘 | Wenjun Wang Xuesong Mei Gedong Jiang Shuting Lei Chengjuan Yang | 2008 | Applied Surface Science2008，，： | 1 |
| 7 | Evaluation of antimicrobial and anticancer activities of three peptides identified from the skin secretion of Hylarana latouchii显示文摘The skins of frogs of the family Ranidae are particularly rich sources of biologically active peptides, among which antimicrobial peptides (AMPs) constitute the major portion. Some of these have attracted the interest of researchers because they possess both antimicrobial and anticancer activities. In this study, with ‘shotgun’ cloning & MS/MS fragmentation, three AMPs, homologues of family brevinin-1 (brevinin-1HL), & temporin (temporin-HLa and temporin-HLb), were discovered from the skin secretion of the broad-folded frog, Hylarana latouchii. They exhibited various degrees of antimicrobial & antibiofilm activities against test microorganisms & hemolysis on horse erythrocytes. It was found that they could induce bacteria death through disrupting cell membranes & binding to bacterial DNA. In addition, they also showed different potencies towards human cancer cell lines. The secondary structure & physicochemical properties of each peptide were investigated to preliminarily reveal their structure–activity relationships. Circular dichroism spectrometry showed that they all adopted a canonical α-helical conformation in membrane-mimetic solvents. Notably, the prepropeptide of brevinin-1HL from H. latouchii was highly identical to that of brevinin-1GHd from Hylarana guentheri, indicating a close relationship between these two species. Accordingly, this study provides candidates for the design of novel anti-infective & antineoplastic agents to fight multidrug-resistant bacteria & malignant tumors & also offers additional clues for the taxonomy of ranid frogs. | Yan Lin Tianxing Lin Ningna Cheng Shuting Wu Jiancai Huang Xiaoling Chen Tianbao Chen Mei Zhou Lei Wang Chris Shaw | 2021 | Acta Biochimica et Biophysica Sinica2021，53，11： | 0 |
| 8 | Mettl13 protects against cardiac contractile dysfunction by negatively regulating C-Cbl-mediated ubiquitination of SERCA2a in ischemic heart failure显示文摘Ischemic heart failure(HF)remains a leading cause of morbidity and mortality.Maintaining homeostasis of cardiac function and preventing cardiac remodeling deterioration are critical to halting HF progression.Methyltransferase-like protein 13(Mettl13)has been shown to regulate protein translation efficiency by acting as a protein lysine methyltransferase,but its role in cardiac pathology remains unexplored.This study aims to characterize the roles and mechanisms of Mettl13 in cardiac contractile function and HF.We found that Mettl13 was downregulated in the failing hearts of mice post-myocardial infarction(MI)and in a cellular model of oxidative stress.Cardiomyocyte-specific overexpression of Mettl13 mediated by AAV9-Mettl13 attenuated cardiac contractile dysfunction and fibrosis in response to MI,while silencing of Mettl13 impaired cardiac function in normal mice.Moreover,Mettl13 overexpression abrogated the reduction in cell shortening,Ca^(2+)transient amplitude and SERCA2a protein levels in the cardiomyocytes of adult mice with MI.Conversely,knockdown of Mettl13 impaired the contractility of cardiomyocytes,and decreased Ca^(2+)transient amplitude and SERCA2a protein expression in vivo and in vitro.Mechanistically,Mettl13 impaired the stability of c-Cbl by inducing lysine methylation of c-Cbl,which in turn inhibited ubiquitination-dependent degradation of SERCA2a.Furthermore,the inhibitory effects of knocking down Mettl13 on SERCA2a protein expression and Ca^(2+)transients were partially rescued by silencing c-Cbl in H_(2)O_(2)-treated cardiomyocytes.In conclusion,our study uncovers a novel mechanism that involves the Mettl13/c-Cbl/SERCA2a axis in regulating cardiac contractile function and remodeling,and identifies Mettl13 as a novel therapeutic target for ischemic HF. | Shuting Yu ZhiYong Sun Xiuzhu Wang Tiantian Ju Changhao Wang Yingqi Liu Zhezhe Qu KuiWu Liu Zhongting Mei Na Li Meixi Lu Fan Wu Min Huang Xiaochen Pang Yingqiong Jia Ying Li Yaozhi Zhang Shunkang Dou Jianhao Jiang Xin Li Baofeng Yang Weijie Du | 2023 | Science China(Life Sciences)2023，66，12： | 0 |
| 9 | Tuning Magnetic Relaxation in Square-Pyramidal Dysprosium Single-Molecule Magnets Using Apical Alkoxide Ligands显示文摘Eight square-pyramidal dysprosium complexes of the type[Dy(X)(DBP)_(2){TMG(H)}_(2)]were synthesized,where TMG(H)denotes 1,1,3,3-tetramethylguanidine,X denotes an alkoxide ligand or anionic guanidinate in the apical position,and DBP denotes 2,6-di-tert-butylphenoxide.These complexes,expressed as 5-Dy-X,are single-molecule magnets(SMMs)with properties dependent on the nature of the apical X ligand. | Zhenhua Zhu Yi-Quan Zhang Xiao-Lei Li Mei Guo Jingjing Lu Shuting Liu Richard A.Layfield Jinkui Tang | 2021 | CCS Chemistry2021，3，12： | 0 |
| 10 | Elp3 modulates neural crest and colorectal cancer migration requiring functional integrity of HAT and SAM domains显示文摘Cell migration is a finely tuned biological process that often involves epithelial-mesenchymal transition(EMT).EMT is typically characterized by the upregulation of mesenchymal markers such as Snail1.This process has been shown to be of critical importance to normal developmental processes,including neural crest migration and invasion.Interestingly,similar mechanisms are utilized in disease processes,such as tumor metastasis and migration.Notably,EMT and EMT-like processes confer tumor cells with the ability to migrate,invade,and adopt stem cell-like properties that largely account for immunosuppression and tumor recurrence.Therefore,identifying sensitive EMT markers may contribute to cancer prognosis and diagnosis in many facets.Previously,we showed that Elp3 plays an essential role during neural crest migration by stabilizing Snail1.In the current study,we further elucidate the molecular mechanism underlying colorectal cancer migration.We found that mElp3 exerted an identical function to xElp3 in modulating neural crest migration,and both HAT and SAM domains are imperative during this migratory process.Interestingly,overexpression of mElp3 in SW480 cells promoted cell migration and invasion,and we further showed that Elp3 stabilized Snail1 requiring integrity of both SAM and HAT domains.Our findings warrant further exploration of the specific target of Elp3 in cancer cells. | XIANGCAI YANG YA XU SHUTING MEI JIEJING LI | 2022 | BIOCELL2022，46，2： | 0 |
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