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| 1 | PD-L1 is a direct target of cancer-FOXP3 in pancreatic ductal adenocarcinoma(PDAC),and combined immunotherapy with antibodies against PD-L1 and CCL5 is effective in the treatment of PDAC显示文摘High expression of PD-L1 marks the poor prognosis of pancreatic ductal adenocarcinomas(PDAC).However,the regulatory mechanism of PD-L1 remains elusive.We recently reported that cancer Forkhead box protein 3(Cancer-FOXP3 or C-FOXP3)promoted immune evasion of PDAC by recruiting Treg cells into PDAC via upregulation of CCL5.In this study,we confirmed that PD-L1 was overexpressed in PDAC samples from two independent cohorts of patients with radical resection.Moreover,C-FOXP3 was colocalized and correlated with the expression of PD-L1 in tumor cells at the mRNA and protein levels,and this finding was confirmed by the The Cancer Genome Atlas(TCGA)database.Chromatin immunoprecipitation(ChIP)revealed that C-FOXP3 directly bound to the promoter region of PD-L1 in pancreatic cancer cells.Furthermore,overexpression of C-FOXP3 activated the luciferase reporter gene under the control of the PD-L1 promoter.However,mutation of the binding motif-a completely reversed the luciferase activity.In addition,C-FOXP3-induced upregulation of PD-L1 effectively inhibited the activity of CD8+T cells.Based on our recent finding that the CCL-5 antibody achieved a better response to PDAC models with high C-FOXP3 levels,we further demonstrated that the PD-L1 antibody strengthened the antitumor effect of CCL-5 blockade in xenograft and orthotopic mouse models with high C-FOXP3 levels.In conclusion,C-FOXP3 directly activates PD-L1 and represents a core transcription factor that mediates the immune escape of PDAC.Combined blockade of PD-L1 and CCL-5 may provide an effective therapy for patients with PDAC that have high C-FOXP3 levels. | Xiuchao Wang Xin Li Xunbin Wei Haiping Jiang Chungen Lan Shengyu Yang Han Wang Yanhui Yang Caijuan Tian Zanmei Xu Jiangyan Zhang Jihui Hao He Ren | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 11 |
| 2 | Enhanced hyperplasia in muscles of transgenic zebrafish expressing Follistatin1显示文摘Myostatin is a member of the transforming growth factor-β(TGF-β) super-family and functions as a negative regulator of muscle growth.Binding of the specific receptor,Activin receptor IIB(Act RIIB),with myostatin or other related TGF-β members,could be inhibited by the activin-binding protein follistatin(Fst) in mammals.Overexpressing Fst in mouse skeletal muscle leads to muscle hypertrophy and hyperplasia.To determine if Fst has similar roles in fish,we generated transgenic zebrafish expressing high levels of zebrafish Fst1 using the promoter of the zebrafish skeletal muscle-specific gene,myosin,light polypeptide 2,skeletal muscle(Mylz2).Independent transgenic zebrafish lines exhibited elevated expression levels of myogenic regulatory genes MyoD and Pax7 in muscle cells.Adult Fst1 overexpressing transgenic zebrafish exhibited a slight body weight increase.The high level of Fst1 expression dramatically increased myofiber numbers in skeletal muscle,without significantly changing the fiber size.Our findings suggest that Fst1 overexpression can promote zebrafish muscle growth by enhancing myofiber hyperplasia. | LI Xi NIE Fen YIN Zhan HE JiangYan | 2011 | Science China(Life Sciences)2011，54，2： | 8 |
| 3 | Successful Production of an All-Female Common Carp (Cyprinus carpio L.) Population Using cyp17a1-Deficient Neomale Carp显示文摘Due to sexual dimorphism in the growth of certain cultured fish species,the production of monosex fishes is desirable for the aquaculture industry.Nowadays,the most widely practiced technique available for the mass production of monosex fish populations is sex steroid-induced sex reversal.Here,a novel strategy for the successful production of all-female(AF)common carp(Cyprinus carpio L.),to take advantage of the sexual dimorphism in growth documented in this species,has been developed using genetic engineering via single gene-targeting manipulation without any exogenous hormone treatments.Male and female heterozygous cyp17a1-deficient common carp were first obtained using the clustered regularly interspaced short palindromic repeats/CRISPR-associated endonuclease 9(CRISPR/Cas9)technique.An all-male phenotype for homozygous cyp17a1-deficient carp,regardless of the individuals’sexdetermination genotypes(XY or XX),has been observed.A male-specific DNA marker newly identified in our laboratory was used to screen the neomale carp population with the XX genotype from the cyp17a1-deficient carp.These neomale carp develop a normal testis structure with normal spermatogenesis and sperm capacity.The neomale common carp were then mated with wild-type(WT)females(cyp17a1^(+/+)XX genotype)using artificial fertilization.All the AF offspring sample fish from the neomale-WT female mating were confirmed as having the cyp17a^(1+/-)XX genotype,and normal development of gonads to ovaries was observed in 100.00%of this group at eight months post-fertilization(mpf).A total of 1000 carp fingerlings,500 from the WT male and female and 500 from the neomale and WT female mating,were mixed and reared in the same pond.The average body weight of cyp17a1^(+/-)XX females was higher by 6.60%(8 mpf)and 32.66%(12 mpf)than that of the control common carp.Our study demonstrates the first successful production of a monosex teleost population with the advantages of sexual dimorphism in growth using genetic manipulation targeting a single locus. | Gang Zhai Tingting Shu Kuangxin Chen Qiyong Lou Jingyi Jia Jianfei Huang Chuang Shi Xia Jin Jiangyan He Donghuo Jiang Xueqiao Qian Wei Hu Zhan Yin | 2022 | Engineering2022，8，1： | 7 |
| 4 | Androgen signaling regulates the transcription of anti-Müllerian hormone via synergy with SRY-related protein SOX9A显示文摘Anti-Müllerian hormone(amh) is one of the earliest functional genes expressed during testicular differentiation. It has been suggested that androgen signaling regulates critical genes for the differentiation and development of the testis. To elucidate the exact regulatory mechanisms involved in amh transcription mediated by androgen signaling, androgen signaling was manipulated in zebrafish by cytochrome P45017a1(cyp17a1) knockout and Flutamide treatment. In cyp17a1-deficient and Flutamide-treated testes,up-regulated sry-box9a(sox9a) and down-regulated amh were observed. Moreover, a physical association of the zebrafish androgen receptor(AR) and SOX9 A was found. The interaction between AR and SOX9 A was mediated via the DNA binding domain(DBD) of AR and the transactivation domain(TA) of SOX9 A,and was further enhanced by 5-alpha dihydrotestosterone(DHT), one of the most potent androgens.Intriguingly, together with SOX9 A, androgen signaling synergistically promoted amh transcription,mainly through the proximal 1 kb of the amh promoter region. Taken together, our data demonstrate a critical mechanism underlying the direct synergy of androgen signaling and SOX9 A in the regulation of amh transcription. | Gang Zhai Tingting Shu Yuguo Xia Xia Jin Jiangyan He Zhan Yin | 2017 | Science Bulletin2017，62，3： | 7 |
| 5 | Human papillomavirus 16 physical status detection in preinvasive and invasive cervical carcinoma by multiplex real-time polymerase chain reaction显示文摘Objective: To explore an ideal approach for detecting the physical status of HPV-16 in clinic use and to investigate the integrated HPV-16 in CINs and cervical cancer. Methods: Multiplex real-time PCR method was established to quantify the copy numbers of E2 and E6 genes (E2/E6) for analysis of the physical status of HPV-16 DNA and this assay was compared to Southern blot analysis. HPV-16-containing paraffin-embedded tissues including 49 CINs and 51 cervical squamous cancers were detected using the method. Results: (1) The cutoff ratio of E2/E6 to distinguish pure episomal from mixed HPV-16, was 0.81 in the multiplex real-time PCR; (2) The agreement rate between multiplex real-time PCR and Southern blot was 81.5% (the Kappa statistic was 0.844, P<0.001); (3) HPV-16 DNA existed in an episomal form in 57.1% and mixed form in 42.9% of CIN I lesions; The concomitant form of HPV-16 (>70%) constituted the majority in CIN II and CIN III; HPV-16 DNA mostly integrated into the host chromosome (s) in squamous cervical cancers (68.6%); (4) The incidence of HPV-16 integration was increased with the degree of cervical lesions; (5) The frequency of pure integrated HPV-16 in stage II+III (88%) was signifi- cantly higher than that in stage I (33.3%). Conclusion: (1) Mutiplex real-time PCR provides a rapid, sensitive and reliable method for clinic detection of the physical state of HPV-16 DNA; (2) The integration of the HPV-16 DNA is a very early and important event in the progression from preinvasive to invasive cervical cancer; (3) The pure integrated status of HPV-16 in cervical cancer may be associated with poor prognosis of cervical cancer, but further study will be needed to prove its prog- nostic significance. | Ying Zheng Zhilan Peng Jiangyan Lou He Wang | 2007 | The Chinese-German Journal of Clinical Oncology2007，6，1： | 5 |
| 6 | Neuroendocrine regulation of somatic growth in fishes显示文摘Growth is a polygenic trait that is under the influence of multiple physiological pathways regulating energy metabolism and muscle growth.Among the possible growth-regulating pathways in vertebrates,components of the somatotropic axis are thought to have the greatest influence.There is growing body of literature focusing on the somatotropic axis and its role regulating growth in fish.This includes research into growth hormone,upstream hypothalamic hormones,insulin-like growth factors,and downstream signaling molecules.Many of these signals have both somatic effects stimulating the growth of tissues and metabolic effects that play a role in nutrient metabolism.Signals of other endocrine axes exhibit profound effects on the function of the somatotropic axis in vivo.In this review we highlight recent advances in our understanding of the teleost fish endocrine somatotropic axis,including emerging research using genetic modified models.These studies have revealed new aspects and challenges associated with regulation of the important steps of somatic growth. | DAI XiangYan ZHANG Wei ZHUO ZiJian HE JiangYan YIN Zhan | 2015 | Science China(Life Sciences)2015，58，2： | 5 |
| 7 | Fast skeletal muscle-specific expression of a zebra_fish myosin light chain 2 gene and characterization of its promoter by direct Injection into skeletal muscle 显示文摘 | XU YANFEI HE JIANGYAN TIAN HOLIAN | 1999 | DNA and cell biology1999，，18： | 1 |
| 8 | Hyperandrogenism in POMCa-deficient zebrafish enhances somatic growth without increasing adiposity显示文摘The endocrine regulatory roles of the hypothalamic-pituitary-adrenocortical axis on anxiety-like behavior and metabolic status have been found throughout animal taxa.However,the precise effects of the balancing adrenal corticosteroid biosynthesis under the influence of adrenocorticotrophic hormone(ACTH),a pro-opiomelanocortin(POMC)-derived peptide,on animal energy expenditure and somatic growth remain unknown.POMC has also been identified as one of the candidate loci for polycystic ovary syndrome,which features hyperandrogenism and some prevalence of obesity in patients.Here we show that zebrafish lacking functional POMCa exhibit similar phenotypes of stress response and body weight gain but not obesity as observed in mammalian models.In contrast with the impaired anorexigenic signaling cascade of melanocyte-stimulating hormones and leptin,which are responsible for their obesity-prone weight gain observed in various pome mutant mammals,analyses with our pomca mutant series indicate that ACTH is the key regulator for the phenotype with enhanced somatic growth without obesity in pomca-deficient zebrafish.Hypocortisolism associated with hyperandrogenism has been observed in the pomca-deficient zebrafish,with enhanced activation of mammalian target of rapamycin complex 1;reutilization of amino acids and fatty acid^-oxidation are observed in the muscle tissue of the pomca-deficient fish.After reducing hyperandrogenism by crossing our pomca mutant fish with a cy p l 7a 1-deficient background,the phenotype of enhanced somatic growth in pomca-deficient fish was no longer observed.Thus,our work also demonstrated that the role of POMCa in stress response seems to be conserved in vertebrates,whereas its effect on adipostasis is unique to teleosts. | Chuang Shi Yao Lu Gang Zhai Jianfei Huang Guohui Shang Qiyong Lou Dongliang Li Xia Jin Jiangyan He Zhenyu Du Jianfang Gui Zhan Yin | 2020 | Journal of Molecular Cell Biology2020，12，4： | 1 |
| 9 | Supplementing Qi and activating blood circulation method to treat vertebrobasilar dolichoectasia with posterior circulatory watershed infarction:a case report of two patients显示文摘Vertebrobasilar dolichoectasia(VBD),a rare posterior circulation vascular variant disease,is an important risk factor for many acute cerebrovascular diseases.An insufficient understanding of VBD often leads to misdiagnose.Two cases of VBD that were initially diagnosed as posterior circulation watershed infarction are reported here.Absence of common causes of stroke including hypoperfusion,blood system diseases,carotid and aortic dissection,and eosinophil elevation,the symptoms of the 2 patients met the diagnostic criteria of VBD.Both patients displayed symptoms that were in line with the Traditional Chinese Medicine(TCM)syndrome pattern of'Qi deficiency and blood stasis'.Accordingly,they were comprehensively treated with Supplementing Qi and activating blood circulation method.The clinical manifestations of the 2 patients were remarkably improved and no recurrence of watershed infarction was found in a 1-year follow-up.A detailed medical history and laboratory examination are capable of improving diagnostic accuracy of VBD.TCM treatment based on syndrome identification might be a promising candidate for VBD management. | LI He SU Wenquan LI Shanshan JI Hanrui CHENG Jiangyan CUI Fangyuan TANG Lu ZHOU Li GAO Ying DONG Xinglu | 2023 | Journal of Traditional Chinese Medicine2023，43，4： | 0 |
| 10 | LRH-1 senses signaling from phosphatidylcholine to regulate the expansion growth of digestive organs via synergy with Wnt/β-catenin signaling in zebrafish显示文摘Liver receptor homolog-1(LRH-1)is an orphan nuclear receptor that is critical for the growth and proliferation of cancer cells and other biological processes,including lipid transportation and metabolism,sexual determination and steroidogenesis.However,because homozygous lrh-1^(-/-) mice die in utero,the regulatory mechanisms involved in embryonic development mediated by this receptor are poorly understood.In the present study,we performed transcription activator-like effector nuclease(TALEN)-mediated loss-of-function assays,taking advantage of zebrafish external fertilization,to investigate the function of lrh-1.The digestive organs were affected by lrh-1 depletion as a result of cellcycle arrest(at the checkpoint of G1 to S phase),but not cell apoptosis.Biochemical analysis revealed that LRH-1 augments the transcriptional activity of b-catenin 1 and 2 via physical interactions.Screening the specific ligand(s)sensed by LRH-1 during organogenesis revealed that phosphatidylcholine(PC),a potential ligand,is the upstream target of LRH-1 during endoderm development.These data provide evidence for the crosstalk between the PC/LRH-1 and Wnt/β-catenin signaling pathways during the expansion growth of endoderm organs. | Gang Zhai Jia Song Tingting Shu Junjun Yan Xia Jin Jiangyan He Zhan Yin | 2017 | Journal of Genetics and Genomics2017，44，6： | 0 |
| 11 | 1α,25(OH)2D3对斑马鱼脂肪组织中脂肪酸氧化的促进显示文摘文章简介1α,25(OH)2D3被认为是哺乳类动物的矿物质代谢的重要调控激素,但其在动物脂肪组织代谢中的精确机制却不够清晰。肝细胞微小体中的细胞色素P450酶2R1(CYP2R1)是活化维生素D3的第一步,即25位的羟基化的羟基化酶,此功能在脊椎动物中是保守。 | Xuyan Peng Guohui Shang Wenqing Wang Xiaowen Chen Qiyong Lou Gang Zhai Dongliang Li Zhenyu Du Yali Ye Xia Jin Jiangyan He Yi Zhang 殷战 | 2018 | 科学新闻2018，0，4： | 0 |
| 12 | A color-based FHGC approach facilities DNA-based clinical molecular diagnostics显示文摘The flow-through hybridization and gene chip(FHGC)was developed to used in clinical molecular diagnostics for thalassemia,human papillomavirus(HPV),and other dis-eases.FHGC could improve hybridization efficiency and reduce hands-on time,thus improving precision,repro-ducibility,and traceability.Multiple genotypes can be detected simultaneously without incurring high costs.^(1)During the experiment,the polymerase chain reaction(PCR)product or buffer forced through the membrane matrix,PCR products are apprehended by a probe attached to the membrane. | Ruyi Zhang Dongyang Deng Min Ren Jiangyan He Fang Chen Shujuan Yan | 2023 | Genes & Diseases2023，10，4： | 0 |
| 13 | Genomic polymorphisms at the crhr2 locus improve feed conversion efficiency through alleviation of hypothalamus-pituitary-interrenal axis activity in gibel carp(Carassius gibelio)显示文摘Improvement in fish feed conversion efficiency(FCE)is beneficial for sustaining global food fish supplies.Here,we show that a set of polymorphisms at locus of the corticotropin releasing hormone receptor 2(crhr2),which is involved in hypothalamuspituitary-interrenal(HPI)axis signaling,is associated with improved FCE in farmed allogynogenetic gibel carp strain CAS Ⅲ compared with that in the wild gibel carp strain Dongting(DT).This set of polymorphisms downregulates the expression levels of crhr2 mRNA in the brain and pituitary tissues in gibel carp strain CAS Ⅲ compared with those in strain DT.Furthermore,compromised HPI axis signaling is observed in gibel carp strain CAS Ⅲ,such as decreased α-melanocyte stimulating hormone protein levels,plasma cortisol content,and stress responses.Moreover,enhanced activation of protein kinase B/mammalian target of rapamycin complex 1 signaling observed in the muscle tissue of strain CAS Ⅲ in comparison to that in strain DT indicated elevated anabolic metabolism in strain CAS Ⅲ.Thus,these studies demonstrate that the genetic markers associated with compromised HPI axis signaling,such as crhr2,are potentially useful for genetic selection toward improvement in farmed fish growth and FCE,which would reduce fishmeal consumption and thereby indirectly facilitate sustainable fisheries. | Chuang Shi Qiyong Lou Beide Fu Junyan Jin Jianfei Huang Yao Lu Xia Jin Jiangyan He Gang Zhai Shouqi Xie Jingou Tong Jianfang Gui Zhan Yin | 2022 | Science China(Life Sciences)2022，65，1： | 0 |
| 14 | Viscosity Approximation Methods for Common Fixed Points of a Finite Family of Quasi-Nonexpansive Mappings in Real Hilbert Spaces显示文摘In this paper, we present two parallel algorithms to compute common fixed points of a finite family of quasi-nonexpansive mappings in real Hilbert spaces, which improve and generalize some known results in this direction. | Jiangyan HE Haiyun ZHOU Xiaoyan HUO | 2016 | Journal of Mathematical Research with Applications2016，36，3： | 0 |
| 15 | Nickel-catalyzed asymmetric arylative cyclization of N-alkynones:Efficient access to 1,2,3,6-tetrahydropyridines with a tertiary alcohol显示文摘Nickel/(S)-t-Bu-PHOX complex catalyzed asymmetric arylative cyclization of N-alkynones has been achieved, delivering 1,2,3,6-tetrahydropyridines containing a chiral tertiary alcohol in high yields and excellent enantioselectivities, which provides efficient access to chiral tetrahydropyridine and piperidine analogues. | Jiangyan Tian Wendian Li Ruihao Li Lin He Hui Lv | 2021 | Chinese Chemical Letters2021，32，12： | 0 |
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