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Impaired reproduction in transgenic mice overexpressing γ-aminobutyric acid transporter Ⅰ (GAT1.

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Cell Research 2004年第1期14卷 54-59页

作者： Jia Hua HU~(1,*), Jin Fu ZHANG~(2,*), Ying Hua MA~1, Jie JIANG~1, Na YANG~1, Xin Bo li~3, Zhi Guang yu CHI~4, Jian FEI~(1,5,**), li He GUO~(1,**) ~1Laboratory of Molecular Cell Biology, institute of Biochemistry and Cell Biology, shanghai institutes for Biological Sciences, Chinese Academy of Sciences, shanghai 200031, china. ~2Department of Urology, Tongji Hospital, Tongji University, 389 Xincun Road, shanghai 200065, china. ~3New Drug R & D Center, North china Pharmaceutical Group Corporation, 388 Heping East Road, Shijia Zhuang 050015, Hebei, china. ~4School of life sciences, fudan University, 220 Handan Road, shanghai 2.0433, china. ~5shanghai Research Center for Biomodel Organism, shanghai 201203, china. Laboratory of Molecular Cell Biology Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 China.

It is well documented that γ-aminobutyric acid (GABA) system existed in reproductive organs. Recent researches showed that GABA_A and GABA_B receptors were present in testis and sperm, and might mediate the acrosome reaction induced by GABA and progesterone. GABA transporter Ⅰ (GAT1. also existed in testis and sperm, but its physiological function was unknown. In the present study, we used GAT1.overexpressing mice to explore GAT1.function in male reproductive system. We found that the expression level of GAT1.continuously increased in wild-type mouse testis from 1.month to 2 months after birth. GAT1.overexpression in mouse affected testis development, which embodied reduced testis mass and slowed spermatogenesis in transgenic mice. Moreover, transgenic mice showed increase of the percentage of broken sperm. The further study revealed that the reproductive capacity was impaired in GAT1.overexpressing mice. In addition, testosterone level was significantly low in transgenic mice compared with that in wi

关键词： GABA GAT1 testes sperm reproduction transgenic.

Cloning,Structural Organization and Chromosomal Mapping of Rat Costimulatory Molecule 4-1.BL

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Acta Biochimica et Biophysica Sinica 2005年第10期37卷 694-701页

作者： Qiu-Ming DONG~1.li-Jie MA~2 Guang-Bo ZHANG~1.Ya-Fang WU~3 Jia-Yao SHEN~1.Ying CHEN~1.Yong-Jing CHEN~1.Xiang-Ke PU~1.Sai-yu HANG~1.Xue-Guang ZHANG~(1.) 1.Biotechnology {1.,Soochow University,Suzhou 21.007,china 2 Genetics {1.,fudan University,shanghai 2.0433,china 3 First Affiliated Hospital of Soochow University,Suzhou 21.006,china Biotechnologyinstitute SoochowUniversitySuzhou215007China

4-1.BL (TNFSF9) is a member of the tumor necrosis factor (TNF) ligand superfamily,whichis expressed on some activated antigen presenting cells and B *** isolated a rat cDNA clone encodingthe rat homologue of the human 4-1.BL (GenBank accession ***259541..The deduced rat 4-IBBLprotein,consisting of 308 amino acids with a molecular weight of 33,469 Da,was a typical type Ⅱtransmembrane glycoprotein,the same as human and routine 4-IBBL.“SDAA” in the cytoplasmic domain ofrat 4-1.BL was deduced to act as the phosphorylation site for casein kinase Ⅰ(“SXXS” motif),which ispresent in the cytoplasmic domains of human and murine 4-1.BL,and all other TNF ligand family membersknown to utilize reverse *** two introns of 4-1.BL were also cloned (GenBank accession ***332409).Rat 4-IBBL is much more homologous with murine 4-1.BL than with human 4-1.BL,in bothnucleotide and amino acid *** 4-1.BL was expressed in all tested tissues:brain,lung,colon,liver,thymus,testicle,kidney,adrenal,stomach,spleen and *** chromosomal location of rat 4-1.BL wasfirst identified by bioinformatics,then by fluorescence in situ hybridization at 9q1.(GenBank accessionUni Gene ***.46783).Rat,murine and human 4-1.BL genes are evolved from a common *** and characterization of the rat counterpart of human 4-1.BL will facilitate studies of the biologicalfunction of this molecule.

关键词： TNF superfamily rat 4-1.BL cloning mapping

The genetic load for hereditary hearing impairment in Chinese population and its clinical implication

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Journal of Otology 2009年第2期4卷 98-105页

作者： WANG Qiu-ju 1,2, RAO Shao-qi 1, 3, GUO yu-fen 4, li Qing-zhong 5, ZHAO Hui 1, ZHAO li-dong 1, yuAN Hu 1, ZONG liang 1, liU Qiong 1, ZHAO Ya-li 6, WANG Da-yong 1, HAN Ming-kun 1, JI yu-bin 1, li Jian-qiang 1, LAN Lan 1, YANG Wei-yan 1, SHEN Yan 2,6, HAN Dong-yi 1 1 Department of Otorhinolaryngology-Head and Neck Surgery, and institute of Otolaryngology, Chinese People’s liberation Army General Hospital, Beijing, 100853 china 2 Chinese National Human Genome Center, Beijing, 100176 china 3 Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-Sen University, Guangzhou, 510080, china 4 Department of Otorhinolaryngology, Head and Neck Surgery, Second Hospital of Lanzhou University, Lanzhou 730030, china 5 Department of Otolaryngology, EYE & ENT hospital of fudan University, shanghai, 200031,china 6 institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005 china Department of Otorhinolaryngology–Head and Neck Surgery and Institute of Otolaryngology Chinese People’s Liberation Army General Hospital Beijing 100853 China Chinese National Human Genome Center Beijing 100176 China Department of Medical Statistics and Epidemiology School of Public Health Sun Yat–Sen University Guangzhou 510080 China Department of Otorhinolaryngology Head and Neck Surgery Second Hospital of Lanzhou UniversityLanzhou 730030 China Department of Otolaryngology EYE & ENT hospital of Fudan University Shanghai 200031China institute of Basic Medical Sciences Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100005 China

Objective To understand the genetic load in the Chinese population for improvement in diagnosis, prevention and rehabilitation of deafness. Methods DNA samples, immortalized cell lines as well as detailed clinical and audiometric data were collected through a national genetic resources collecting network. Two conventional genetic approaches were used in the studies. linkage analysis in X chromosome and autosomes with microsatellite markers were performed in large families for gene mapping and positional cloning of novel genes. Candidate gene approach was used for screening the mtDNA 1.SrRNA, GJB2.and SLC26A4 mutations in population -based samples. Results A total of 2,572 Chinese hearing loss families or sporadic cases were characterized in the reported studies, including seven X-linked, one Y-linked, 28 large and multiplex autosomal dominant hearing loss families, 607 simplex autosomal recessive hereditary hearing loss families, 1.0 mitochondrial inheritance families, 1.7 GJB2 induced hearing loss cases, 230 cases with enlarged vestibular aqueduct (EVA) syndrome, 1.9 sporadic cases with auditory neuropathy, and 1.283 sporadic sensorineural hearing loss cases. Through linkage analysis or sequence analysis, two X-linked families were found transmitting two novel mutations in the POU3F4 gene, while another X -linked family was mapped onto a novel locus, nominated as AUNX1.(auditory neuropathy, X-linked locus 1.. The only Y-linked family was mapped onto the DFNY1.locus(Y-linked locus 1. DFNY1.. Eight of the 28 autosomal dominant families were linked to various autosomal loci. In population genetics studies, 2,567 familial cases and sporadic patients were subjected to mutation screening for three common hearing loss genes: mtDNA 1.S rRNA 1.55G, GJB2.and SLC26A4. The auditory neuropathy cases in our samples were screened for OTOF gene mutations. Conclusions These data show that the Chinese population has a genetic load on hereditary hearing loss. Establishing personalize

关键词： Hereditary hea ring loss linkage analysis DFNY1 AUNX1 auditory neuropathy enlarged vestibular aqueduct senserineural hearing loss genetic epidemiology

Cycloastragenol induces apoptosis and protective autophagy through AMPK/ULK1.mTOR axis in human non-small cell lung cancer cell lines

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Journal of Integrative Medicine 2024年第4期22卷 503-514页

作者： li-hua Zhu yu-pei liang lian Yang Feng Zhu li-jun Jia He-gen li Department of Oncology Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China Cancer institute of Traditional Chinese Medicine Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China Department of Laboratory Medicine Huadong HospitalFudan UniversityShanghai 200237China

Objective:Studies have demonstrated that cycloastragenol induces antitumor effects in prostate,colorectal and gastric cancers;however,its efficacy for inhibiting the proliferation of lung cancer cells is largely *** study explores the efficacy of cycloastragenol for inhibiting non-small cell lung cancer(NSCLC)and elucidates the underlying molecular ***:The effects of cycloastragenol on lung cancer cell proliferation were assessed using an adenosine triphosphate monitoring system based on firefly luciferase and clonogenic formation ***-induced apoptosis in lung cancer cells was evaluated using dual staining flow cytometry with an annexin V-fluorescein isothiocyanate/propidium iodide *** elucidate the role of cycloastragenol in the induction of apoptosis,apoptosis-related proteins were examined using Western *** and Western blotting were used to determine whether cycloastragenol could induce autophagy in lung cancer *** techniques,including small interfering RNA technology,were used to investigate the underlying *** effects against lung cancer and biosafety of cycloastragenol were evaluated using a mouse subcutaneous tumor ***:Cycloastragenol triggered both autophagy and ***,cycloastragenol promoted apoptosis by facilitating the accumulation of phorbol-1.-myristate-1.-acetate-induced protein 1.NOXA),a critical apoptosis-related ***,cycloastragenol induced a protective autophagy response through modulation of the adenosine 5'-monophosphate-activated protein kinase(AMPK)/unc-51.like autophagy-activating kinase(ULK1./mammalian target of rapamycin(mTOR)***:Our study sheds new light on the antitumor efficacy and mechanism of action of cycloastragenol in *** insight provides a scientific basis for exploring combination therapies that use cycloastragenol and inhibiting the AMPK/ULK1.mTOR pathway as a promising approach to

关键词： Non-small cell lung cancer Cycloastragenol Autophagy Apoptosis

母-胎免疫识别低下型反复自然流产配偶淋巴细胞免疫疗法的改进

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上海免疫学杂志 2003年第6期23卷 393-395页

作者：李大金余江朱影王明雁孟毅复旦大学附属妇产科研究所生殖免疫实验室上海200011 南京军区福州总医院妇产科福州350025

比较配偶淋巴细胞诱生后与非诱生免疫疗法 ,对于母胎免疫识别低下型反复自然流产 (RSA )的临床疗效 ,并分析其疗效机制。 1.4例母胎免疫识别低下型RSA患者随机分成 2组 ,分别采用经体外诱生的或未经体外诱生的配偶淋巴细胞对其进行... 详细信息

比较配偶淋巴细胞诱生后与非诱生免疫疗法 ,对于母胎免疫识别低下型反复自然流产 (RSA )的临床疗效 ,并分析其疗效机制。 1.4例母胎免疫识别低下型RSA患者随机分成 2组 ,分别采用经体外诱生的或未经体外诱生的配偶淋巴细胞对其进行皮内多点注射免疫治疗。分别观察随后的妊娠结局、封闭抗体水平。经配偶淋巴细胞免疫后 ,体外诱生的淋巴细胞免疫组妊娠成功率为 90 0 % ;未经体外诱生的淋巴细胞免疫组妊娠成功率为 84 8%。对于封闭抗体各项指标分析结果显示 ,配偶淋巴细胞皮内免疫能有效促进RSA患者封闭抗体及其抗独特型抗体水平的升高 ;经体外诱生的配偶淋巴细胞免疫疗法能显著提高RSA患者外周血抗CD3 BE的水平。配偶淋巴细胞皮内免疫疗法通过刺激封闭抗体的产生 ,改善随后的妊娠预后 ,配偶淋巴细胞经体外诱生后作为免疫原 ,通过升高抗CD3封闭抗体水平 ,有助于改善妊娠预后。

关键词：反复自然流产配偶淋巴细胞免疫疗法体外诱生封闭抗体封闭抗体抗独特型抗体妊娠结局

Screening of GJB2 mutations in Chinese population

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Journal of Otology 2007年第1期2卷 18-22页

作者： HAN Ming-kun1. HAN Dong-yi1. GUO yu-fen2, li Qing-zhong3, ZHAO Ya-li1. 4, RAO Shao-qi1. 5, 6, yuAN Hu1. ZONG liang1. GUAN Jing2, XU Bai-cheng2, WANG Da-yong1. LAN lan1. WANG Qiu-ju1. 7 1.Department of Otorhinolaryngology/ Head and Neck Surgery, and institute of Otolaryngology, china People liberation Army General Hospital, Beijing, china 2 Department of Otorhinolaryngology/ Head and Neck Surgery, the Second Affiliated Hospital of LanZhou University, Lanzhou, china 3 Deparment of Otlolaryngology, Eye and ENT Hospital of fudan University, shanghai, china 4 Department of Biochemistry and Molecular Biology, institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, china 5 Departments of Cardiovascular Medicine and Molecular Cardiology, the Cleveland Clinic Foundation, Cleveland, Ohio, USA 6 Department of Bioinformatics, Harbin Medical University, Harbin, china 7 china National Human Genome Center, Beijing, china Department of Otorhinolaryngology/ Head and Neck Surgery and Institute of Otolaryngology China People Liberation Army General Hospital Beijing China Department of Otorhinolaryngology/ Head and Neck Surgery the Second Affiliated Hospital of LanZhou University Lanzhou China Deparment of Otlolaryngology Eye and ENT Hospital of Fudan University Shanghai China Department of Biochemistry and Molecular Biology Institute of Basic Medical Sciences Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China Departments of Cardiovascular Medicine and Molecular Cardiology the Cleveland Clinic Foundation Cleveland Ohio USA Department of Bioinformatics Harbin Medical University Harbin China china National Human Genome Center Beijing China

The GJB2 gene(connexin 26) has been shown to be responsible for DFNB1.and DFNA3. We screened the GJB2 gene in 488 patients with prelingual deafness(Group 1., 1.4 with postlingual deafness(Group 2), and 1.7 normal hearing subjects(Group 3). We found that, in Group 1. 65 patients(1..32%) were homozygotes or compound heterozygotes and 51.patients (1..45%) carried a single pathogenic mutation. The 235delC mutation was the most frequent mutation, accounting for 73.22% of the known pathogenic alleles in Group 1. No homozygotes or compound heterozygotes were detected in Group 2 or Group 3. Some postlingual deaf patients (2.42%) and normal hearing subjects(4.27%) were 235delC carriers. Our preliminary data indicate that 235delC, the most frequent mutation identified in this study, is a major cause for prelingual deafness.

关键词： prelingual deafness postlingual deafness, GJB2 235delC Chinese

Small but mighty:Empowering sodium/potassium-ion battery performance with S-doped SnO_(2) quantum dots embedded in N,S codoped carbon fiber network

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Carbon Energy 2024年第5期6卷 186-200页

作者： Shengnan He Hui Wu Shuang li Ke liu Yaxiong Yang Hongge Pan Xuebin yu institute of Science and Technology for New Energy Xi'an Technological UniversityXi'anChina Department of Materials Science Fudan UniversityShanghaiChina Wanxiang A1.3 Systems Corporation HangzhouChina School of Material Science and Engineering Shanghai UniversityShanghaiChina

SnO_(2) has been extensively investigated as an anode material for sodium-ion batteries(SIBs)and potassium-ion batteries(PIBs)due to its high Na/K storage capacity,high abundance,and low ***,the sluggish reaction kinetics,low electronic conductivity,and large volume changes during charge and discharge hinder the practical applications of SnO_(2)-based electrodes for SIBs and *** rational structures with fast charge/ion transfer and robust stability is important to overcoming these ***,S-doped SnO_(2)(S-SnO_(2))quantum dots(QDs)(≈3 nm)encapsulated in an N,S codoped carbon fiber networks(S-SnO_(2)-CFN)are rationally fabricated using a sequential freeze-drying,calcination,and S-doping *** analysis and density functional theory calculations reveal that the integration of S-SnO_(2) QDs with N,S codoped carbon fiber network remarkably decreases the adsorption energies of Na/K atoms in the interlayer of SnO_(2)-CFN,and the S doping can increase the conductivity of SnO_(2),thereby enhancing the ion transfer *** synergistic interaction between S-SnO_(2) QDs and N,S codoped carbon fiber network results in a composite with fast Na+/K+storage and extraordinary long-term ***,the S-SnO_(2)-CFN delivers high rate capacities of 1.1.0 mAh g^(−1. at 20 A g^(−1. in SIBs and 1.2.8 mAh g^(−1. at 1. A g^(−1. in ***,it delivers ultra-stable sodium storage up to 1.,000 cycles at 5 A g^(−1. and potassium storage up to 5000 cycles at 2 A g^(−1..This study provides insights into constructing metal oxide-based carbon fiber network structures for high-performance electrochemical energy storage and conversion devices.

关键词： carbon fiber network heteroatom doping potassium-ion battery sodium-ion battery S-SnO_(2)quantum dot

Cloning, expression and characterization of human tissue-specific DNA polymerase λ2

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Science china(life Sciences) 2007年第4期50卷 457-465页

作者： GU Fu1. YOU Chun1. liU JianPing1. CHEN Ao1.,yu Yao1. WANG Xiang1. WAN DaFang2, GU JianRen2, yuAN HanYing1. li yuYang1.& Lü Hong1.1.State Key Laboratory of Genetic Engineering, institute of Genetics, School of life Sciences, fudan University, shanghai 2.0433, china 2 State Key Laboratory of Oncogenes and Related Genes, shanghai Cancer institute, shanghai 200032, china Present address: Food Inspection and Supervision institute of Shanxi Province, No. 222 Changzhi Road, Taiyuan 03001., china 1. State Key Laboratory of Genetic Engineering Institute of Genetics School of Life Sciences Fudan University Shanghai 200433 China 2. State Key Laboratory of Oncogenes and Related Genes Shanghai Cancer Institute Shanghai 200032 China

DNA polymerase (POL) λ plays an important role during DNA repair and DNA nonhomologous recom-bination processes. A novel POL λ variant was cloned from a human liver cDNA library and named POL λ2 (GenBank Accession No. AY302442). POL λ2 has 2206 base pairs in length with an open reading frame of 1.52 base pairs encoding a 482-amino-acids protein. Bioinformatics analysis reveals that POL λ2 spans 7.9 kb on human chromosome 1.q24 and is composed of 8 exons and 7 introns. It has the specific domain of DNA polymerase X family-POL Xc at the C-terminus and BRCT domain at the N-terminus. POL λ2 was localized predominantly in nucleus in transfected L0-2 cells. It was expressed abundantly in liver and testis, weakly in ovary, and undetectably in other tested human tissues. In comparison with the expression ratio between POL λ and POL λ2 in normal liver tissues and hepato-cellular carcinoma (HCC) adjacent tissues, the ratio was aberrant in 80% of those 1. HCC specimens examined due to the up-regulated expression of POL λ. This abnormality might be involved in hepato-carcinogenesis. The recombinant POL λ2 with His-tag was expressed as a soluble active protein in E. coli BL21.(DE3)CONDON Plus and purified by Ni-NTA resin and then desalted by Superdex-75 chro-matography in an FPLC system. The analysis using isotope α-32P-dCTP incorporation in vitro showed that the purified recombinant POL λ2 exhibited DNA polymerase activity.

关键词： POL λ2 gene cloning expression purification DNA polymerase activity hepatocellular carcinoma

Angiotensin AT1.receptor activation mediates high glucose-induced epithelial-mesenchymal transition in renal proximal tubular cells

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Angiotensin AT1 receptor activation mediates high glucose-in...