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Acta Pharmacologica Sinica 2007年第4期28卷 584-590页

作者： Shi-lei CAO Qi-zhi ZHANG Xin-guo JIANG Department of Pharmaceutics,school of Pharmacy,fudan university,shanghai 200032,china Department of Pharmaceutics School of Pharmacy Fudan University Shanghai China

Aim:To develop a novel,in situ gel system for nasal delivery of scopolaminehydrobromide (SCOP) and study its efficacy on motion ***:SCOPin situ gels at 0.2%,0.5%,and 1.0% gellan gum concentration (w/v) were prepared,respectively,and characterized in terms of viscosity,in vitro release,and *** photon emission computing tomography technique was usedto evaluate the nasal residence time of gel containing ~99mTc *** antimotionsickness efficacy produced by the in situ gel formulation was investigated in ratsand compared with those achieved after subcutaneous and oral ***:The viscosity of the gellan gum formulations either in solution or in gelincreased with increasing concentrations of gellan *** release in vitro wasmoderate in artificial nasal *** micrographic results showed that in situ gelswere safe,without nasal *** comparison with phosphate buffer saline,a prolonged radioactivity of99mTc in the rabbit nasal cavity was observed afteradministration of the gellan gum *** SCOP in situ gel at a doseof 100 pg/kg decreased symptoms of motion sickness significantly in comparisonwith subcutaneous and oral administration (P<0.01).Conclusion:SCOP nasal insitu gel is a safe and promising therapeutic alternative to existing medications formotion sickness.

关键词： scopolamine gellan gum nasal delivery motion sickness residence time nasal ciliotoxicity

Identification and Characterization of a Rat Novel Gene RSEP4 Expressed Specifically in Central Nervous System

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Acta Biochimica et Biophysica Sinica 2004年第7期36卷 501-507页

作者： Xi-Dao WANG1,2, Ling-Wei KONG1, Zhi-Qin XIE1, Yu-Qiu ZHANG3, Zhi-Xin LIN2, Zhi-Qi ZHAO3,lei YU4, and Nai-He JING1* 1 Laboratory of Molecular Cell Biology, Laboratory of Stem Cell Biology, Institute of Biochemistry and Cell Biology, shanghai Institutes for Biological sciences, Chinese Academy of sciences, Graduate school of the Chinese Academy of sciences, shanghai 200031, china school of Life Science and Biotechnology, 2 shanghai Jiaotong university, shanghai 200030, china Institute of Neurobiology, fudan university, shanghai 200433, china 3 4 Department of Cell Biology, Neurobiology and Anatomy, College of Medicine, university of Cincinnati, Cincinnati, Ohio, USA Laboratory of Molecular Cell Biology Laboratory of Stem Cell Biology Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Graduate School of the Chinese Academy of SciencesShanghai 200031 China school of Life Science and Biotechnology Shanghai Jiaotong UniversityShanghai 200030 China Institute of Neurobiology Fudan UniversityShanghai 200433 China Department of Cell Biology Neurobiology and Anatomy College of Medicine University of CincinnatiCincinnati Ohio USA

The low-abundantly expressed genes composed the majorities of the mRNAs expressed in the central nervous system (CNS), and were thought to be important for the normal brain functions. Through differential screening a low-abundance cDNA sublibrary with mRNA from neuropathic pain of chronic constriction injury (CCI) model, we have identified a novel rat gene, rat spinal-cord expression protein 4 gene (RSEP4). The total length of RSEP4 cDNA is 2006 bp, with a 501 nucleotide open reading frame (ORF) that encodes a 167 amino acid polypeptide. Northern blot revealed that RSEP4 was expressed specifically in the CNS. In situ hybridization showed that the mRNA of RSEP4 was strongly expressed in the CA1, CA2, CA3 and DG regions of hippocampus, the Purkinje cells of cerebellum, and the small sensory neurons of dorsal horn and large motor neurons of ventral horn of spinal cord. Over-expression of RSEP4-EGFP fusion protein in the human embryonic kidney 293T cells showed that RSEP4 protein was mainly localized in the cell cytoplasm. These results suggest that RSEP4 may play some roles in the CNS.

关键词： central nervous system (CNS) rat Northern blot in situ hybridization

Selenopeptide nanomedicine ameliorates atherosclerosis by reducing monocyte adhesions and inflammations

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Nano Research 2024年第7期17卷 6332-6341页

作者： zhen Luo Yuxing Jiang Zimo Liu Lamei Guo Li Zhang Hongtao Rong Zhongyu Duan Hongwen Liang Aili Zhang lei Wang Yu Yi Hao Wang CAS Center for Excellence in Nanoscience CAS Key Laboratory for Biomedical Effects of Nanomaterials and NanosafetyNational Center for Nanoscience and Technology(NCNST)No.11 BeiyitiaoZhongguancunBeijing 100190China school of Chemical Engineering and Technology Hebei University of TechnologyTianjin 300130China Tianjin Medical university General Hospital Tianjin 300052China university of Chinese Academy of sciences Beijing 100049China school of Environmental Science and Safety Engineering Tianjin University of TechnologyTianjin 300384China College of Pharmacy Chongqing Medical UniversityChongqing 400016China school of Biomedical Engineering Shanghai Jiao Tong UniversityShanghai 200240China

Atherosclerosis is an inflammatory disease that may cause severe heart disease and *** pharmacotherapy for atherosclerosis shows limited *** the progression of atherosclerosis,monocyte adhesions and inflammatory macrophages play vital ***,precise regulations of inflammatory immune microenvironments in pathological tissues remain ***,we report an atherosclerotic plaque-targeted selenopeptide nanomedicine for inhibiting atherosclerosis progression by reducing monocyte adhesions and inflammation of *** targeted nanomedicine has 2.2-fold enhancement in atherosclerotic lesion *** oxidation-responsibility of selenopeptide enables eliminations of reactive oxygen species and specific release of anti-inflammatory drugs,thereby reducing inflammation responses of ***,we find the oxidative metabolite of selenopeptide,octadecyl selenite,can bind to P-selectin in a high affinity with a dissociation constant of 1.5μ*** in situ generated active seleno-species further inhibit monocyte adhesions for anti-inflammation in *** local regulations of monocyte adhesions and inflammations,the selenopeptide nanomedicine achieves 2.6-fold improvement in atherosclerotic plaque inhibition compared with simvastatin in the atherosclerosis mouse ***,the selenopeptide nanomedicine also displays excellent biological safety in both mice and rhesus *** study provides a safe and effective platform for regulating inflammatory immune microenvironments for inflammatory diseases such as atherosclerosis.

关键词： selenopeptide self-assembly atherosclerosis monocyte adhesion anti-inflammation

Preparation of tungsten-particle-reinforced Zr-based bulk metallic glass composites by two-step spark plasma sintering:microstructure evolution,densification mechanism and mechanical properties

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Rare Metals 2024年第4期43卷 1793-1808页

作者： Yun-Fei Ma Pan Gong Mao Zhang Hui-EHu zhen Peng Xiao Xu Xin Wang Mehdi Malekan Xue-Feng Tang lei Deng Jun-Song Jin Xin-Yun Wang State Key Laboratory of Materials Processing and Die and Mould Technology School of Materials Science and EngineeringHuazhong University of Science and TechnologyWuhan430074China Research Institute of Huazhong university of Science and Technology in Shenzhen Shenzhen518057China Department of Chemistry and Materials Naval University of EngineeringWuhan430032China school of Materials Science and Engineering Jiangsu UniversityZhenjiang212013China College of Machine Shanghai Dianji UniversityShanghai201306China school of Metallurgy and Materials Engineering College of EngineeringUniversity of TehranTehran 11155-4563Iran

A new two-step spark plasma sintering(TSS)process with low-temperature pre-sintering and high-temperature final sintering has been successfully applied to prepare the tungsten-particle(Wp)-reinforced bulk metallic glass composites(Wp/BMGCs).Compared to normal spark plasma sintering(NS),the densification rate and relative density of Wp/BMGCs can be improved by selecting TSS with appropriate sintering pressure in the low temperature pre-sintering ***,the compressive strength and plastic strain of 30%Wp/BMGCs prepared by TSS are both higher than those of the samples prepared by *** TSS process can significantly enhance the compressive strength of 30%Wp/BMGCs by 12%and remarkably increase the plastic strain by 50%,while the trend is completely opposite for 50%Wp/***-in situ experiments and finite element simulations reveal that uneven temperature distribution among particles during low-temperature pre-sintering causes local overheating at contact points between particles,accelerating formation of sintering neck between particles and plastic deformation of *** the volume fraction of Wp is low,TSS can improve the interface bonding between particles by increasing the number of sintering *** makes the fracture mode of Wp/BMGCs being predominantly transgranular ***,as the volume fraction of Wp increases,the adverse effects of Wp plastic deformation are becoming more and more *** aggregated Wp tends to form a solid"cage structure"that hinders the bonding between particles at the interface;correspondingly,the fracture behavior of Wp/BMGCs is mainly dominated by intergranular ***,reducing the sintering pressure during the low-temperature pre-sintering stage of TSS has been shown to effectively decrease plastic deformation in Wp,resulting in a higher degree of densification and better mechanical properties.

关键词： Bulk metallic glass composites Tungsten particle Two-step spark plasma sintering Densification mechanism Mechanical properties

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IL-12p40 is not required for islet allograft rejection

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Acta Pharmacologica Sinica 2006年第8期27卷 1065-1070页

作者： En-guang BI~(2,5) Wei SHI~(3,5) Jia ZOU~2 zhen-hua HAO~3 zhen-hu LI~2 Duan CAI~3 Hua-qun ZHANG~3 Bing SUN~(2,4,6) ~2Laboratory of Molecular Cell Biology shanghai Institutes for Biological sciences,Chinese Academy of sciences,Graduate school of the Chinese Academy of sciences,shanghai 200031,china ~3the Huashan Hospital of fudan university,shanghai 200040,china ~4E-institutes of shanghai Universities Immunology Division,shanghai 200025.china Laboratory of Molecular Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Graduate School of the Chinese Academy of Sciences Shanghai China the Huashan Hospital of fudan university Shanghai China E-institutes of shanghai Universities Immunology Division Shanghai China

Aim:To investigate whether IL-12p40 plays a crucial role in regulating islet al-lograft rejection in a streptozotocin(STZ)-induced diabetes mouse ***:C57BL/6 and IL-12p40 gene knockout mice were selected as recipient mice,towhich the diabetes was induced with a treatment of STZ(150-200 mg/kg)by asingle ip ***/c mice were selected as donor mice and islet cells wereisolated from the *** 500 islets were transplanted into recipient mice be-neath the capsule of the left *** the islet transplantation the glu-cose from the mice sera was monitored and the rejection rate of islets was ***:STZ could induce diabetes in the recipient mice within 1 *** of allograft islets,the increased glucose in wild-type(WT)micereturned to normal level and was maintained for 10 ***,the rejectionrate of islet allograft between IL-12p40-deficient mice and WT mice was ***:The results suggested that,although islet allograft rejection is be-lieved to be Th1-cell predominant,the Th1 response inducer,IL-12 and IL-23 arenot essential to induce islet allograft rejection.

关键词： Th1 cells Th2 cells islets of Langerhans transplantation homologous transplantation IL-12p40-deficient mice

Stereoselectivity in metabolic 3-reduction of tibolone in healthy Chinese female volunteers

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Acta Pharmacologica Sinica 2005年第12期26卷 1527-1530页

作者： Ming ZUO~1 Ming-jie GAO zhen LIU lei CAI Geng-li DUAN~2 Department of Pharmaceutical Analysis,school of Pharmacy,fudan university,shanghai 200032,china Laboratory for Chemical Defense and Microscale Analysis,Zhijiang 443200,china. Department of Pharmaceutical Analysis School of Pharmacy Fudan University Shanghai China

Aim:To investigate the stereoselectivity in human metabolic 3-reduction ***:Twenty healthy Chinese female volunteers were given a singleoral dose of tibolone(2.5 mg),and serial blood samples were collected *** plasma concentrations of the two pharmacologically active 3-hydroxyl metabolites of tibolone,3α-hydroxyl-7-methyl-norethynodrel(3α-HMN)and 3β-hydroxyl-7-methyl-norethynodrel(3β-HMN)in plasma were determinedby using a validated liquid chromatography-mass spectrometry(LC-MS)***:The apparent elimination half-life(Tw)of 3α-HMN was 1.43±0.52 h,andthat of 3β-HMN was 1.53±0.60 *** plasma concentrations(Cmax)werefound to be 8.75±4.36 μg/L for 3α-HMN and 3.59+ 1.81 μg/L for 3β-*** the plasma concentration versus time curve(AUC0-t)were 26.30±12.14 μg.h-1·L-1for 3α-HMN and 9.89±4.93 μg·h-1·L-1for 3β-***:Stereo-selective differences exist in the pharmacokinetics of tibolone metabolism inhumans.

关键词： tibolone metabolite pharmacokinetics stereoSelectivity

Advances in non-invasive imaging of proteinopathies in animal models of neurodegenerative diseases

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Neural Regeneration Research 2024年第10期19卷 2115-2116页

作者： lei Cao Bin Ji Ruiqing Ni Changes Technology Corporation Ltd. ShanghaiChina fudan university ShanghaiChina school of Pharmacy Fudan UniversityShanghaiChina Institute for Biomedical Engineering University of Zurich&ETH Zurich Institute for Regenerative MedicineUniversity of ZurichZurichSwitzerland

Neurodegenerative diseases,including Alzheimer's disease(AD),frontotemporal dementia,Parkinson's disease,and dementia with Lewy bodies,represent tremendous unmet clinical needs.A common feature of these diseases is the aberrant cerebral accumulation of pathological protein aggregates,affecting selectively vulnerable circuits in a disease-specific *** studies have established a relationship between abnormal aggregation and neuronal dysfunction or loss,suggesting multifactorial pathogenesis mechanisms in these neurodegenerative disorders.

关键词： diseases degenerative clinical

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Source localization in signed networks with effective distance

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Chinese Physics B 2024年第2期33卷 577-585页

作者：马志伟孙蕾丁智国黄宜真胡兆龙 Zhejiang Normal university School of Computer Science and TechnologyJinhua 321004China shanghai Business school School of Business and EconomicsShanghai 200235China Jinhua Polytechnic School of Information EngineeringJinhua 321016China

While progress has been made in information source localization,it has overlooked the prevalent friend and adversarial relationships in social *** paper addresses this gap by focusing on source localization in signed network *** the topological characteristics of signed networks and transforming the propagation probability into effective distance,we propose an optimization method for observer ***,by using the reverse propagation algorithm we present a method for information source localization in signed *** experimental results demonstrate that a higher proportion of positive edges within signed networks contributes to more favorable source localization,and the higher the ratio of propagation rates between positive and negative edges,the more accurate the source localization ***,this aligns with our observation that,in reality,the number of friends tends to be greater than the number of adversaries,and the likelihood of information propagation among friends is often higher than among *** addition,the source located at the periphery of the network is not easy to ***,our proposed observer selection method based on effective distance achieves higher operational efficiency and exhibits higher accuracy in information source localization,compared with three strategies for observer selection based on the classical full-order neighbor coverage.

关键词： complex networks signed networks source localization effective distance

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Association between the frontoparietal network,clinical symptoms and treatment response in individuals with untreated anorexia nervosa

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General Psychiatry 2024年第3期37卷 364-374页

作者： Qianqian He Hui zheng Jialin Zhang Ling Yue Qing Kang Cheng Lian lei Guo Yan Chen Yanran Hu Yuping Wang Sufang Peng zhen Wang Qiang Liu Jue Chen Department of Clinical Psychology Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Department of Clinical Psychology Shanghai Pudong New Area Mental Health CenterTongji University School of MedicineShanghaiChina shanghai Key Laboratory of Psychotic Disorders Brain Health InstituteNational Center for Mental DisordersShanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina State Key Laboratory of Cognitive Neuroscience and Learning and IDG/McGovern Institute for Brain Research Bejing Normal UniversityBeijingChina

Background Anorexia nervosa(AN)has been characterised as a psychiatric disorder associated with increased ***,it remains difficult to predict treatment response in patients with *** cognitive abilities are known to be resistant to *** has been established that the frontoparietal control network(FPCN)is the direct counterpart of the executive control ***,the resting-state brain activity of the FPCN may serve as a biomarker to predict treatment response in *** The study aimed to investigate the association between resting-state functional connectivity(RSFC)of the FPCN,clinical symptoms and treatment response in patients with *** In this case-control study,79 female patients with AN and no prior treatment from the shanghai Mental Health Center and 40 matched healthy controls(HCs)were recruited from January 2015 to March *** participants completed the Questionnaire Versionof the Eating Disorder Examination(version 6.0)to assess the severity of their eating disorder ***,RSFC data were obtained from all participants at baseline by functional magnetic resonance *** with AN underwent routine outpatient treatment at the 4th and 12th week,during which time their clinical symptoms were evaluated using the same measures as at *** Among the 79 patients,40 completed the 4-week follow-up and 35 completed the 12-week *** RSFC from the right posterior parietal cortex(PPC)and dorsolateral prefrontal cortex(diPFC)increased in 79 patients with AN vs 40 HCs after controlling for depression and anxiety *** multiple linear regression,the RSFC of the PPC to the inferior frontal gyrus was found to be a significant factor for self-reported eating disorder symptoms at baseline and the treatment response to cognitive preoccupations about eating and body image,after controlling for age,age of onset and body mass *** RSFC in the dIPFC to the middle temporal gyrus and the

关键词： symptoms routine prevention

Amino acid 1-209 is essential for PDX-1-mediated repression of human CMV IE promoter activity

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Acta Pharmacologica Sinica 2006年第11期27卷 1495-1503页

作者： Jing CHEN~1 lei CHEN~2 Ge LI~1 Lu CHENG~1 Yin HUANG~1 Jia-xin ZHANG~1 Wei-wei FAN~1 Da-ru LU~(1,3)1 State Key Laboratory of Genetic Engineering,Institute of Genetics,school of Life sciences,fudan university,shanghai 200433,china 2 International Cooperation Laboratory on Signal Transduction,Eastern Hepatobiliary Surgery Institute,Second Military Medical university,225 Changhai Road,shanghai 200438,china. State Key Laboratory of Genetic Engineering Institute of Genetics School of Life Sciences Fudan University Shanghai China International Cooperation Laboratory on Signal Transduction Eastern Hepatobiliary Surgery Institute Second Military Medical University Shanghai China

Aim:To explore the different roles of pancreatic duodenal homeobox factors-1(PDX-1)domains in PDX-1 mediated repression of human cytomegalovirus imme-diately early(CMV IE)***:A series of truncated PDX-1 mutantswere *** binding of PDX-1 and CMV IE promoter was identified byelectrophoretic mobility shift assay(EMSA).The dual-reporter assay was ap-plied to examine the repression activities of PDX-1 mutants on CMV IE *** addition,RNAi technology was used to specifically knock down the endog-enous PDX-1 ***:The reporter assay indicated that compared tothe mock controls(pEGFP-N2),overexpression of PDX-1 resulted in a 41% de-crease of CMV IE promoter activity in the 293 cells(P<0.05)and 43% decrease inHeLa cells(P<0.05),and the repression levels of various truncated mutants playedon CMV IE promoter were *** knock down of the endogenousPDX-1 expression significantly restored the activity of CMV IE *** that domain 3 is necessary for nuclear localization and DNA bind-ing activity of ***,binding of PDX-1 alone to CMV IE promoter wasnot sufficient to inhibit its transcriptional activity,and other domains of PDX-1presented were also ***:Our data suggested that the DNAbinding activity of PDX-1 domain 3 and the cooperative binding of PDX-1 domain1/2 with other proteins were required for PDX-1 mediated repression of CMV IEpromoter.

关键词： CMV Immediately Early promoter pancreatic duodenal homeobox factors-Ⅰ down regulation