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Apolipoprotein E elicits targetdirected miRNA degradation to maintain neuronal integrity
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作者 Jiazi Tan Chin-Tong Ong 《Neural Regeneration Research》 SCIE CAS 2025年第9期2577-2578,共2页
Apolipoprotein E has diverse functions in neurons:Apolipoprotein E(ApoE)is a glycoprotein that primarily regulates lipid metabolism and transport in the central nervous system.There are three predominant human ApoE pr... Apolipoprotein E has diverse functions in neurons:Apolipoprotein E(ApoE)is a glycoprotein that primarily regulates lipid metabolism and transport in the central nervous system.There are three predominant human ApoE protein isoforms with cysteine and arginine substitutions at amino acid positions 112 and 158 that impact their lipidation and related functions(Flowers and Rebeck,2020).ApoE2 is characterized by Cys112 and Cys158,ApoE3 by Cys112 and Arg158,whereas ApoE4 contains Arg112 and Arg158. 展开更多
关键词 METABOLISM GLYCOPROTEIN maintain
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Maintaining Resilience of Agricultural Supply Chain: International Cooperation is a Must
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作者 Liu Xinwei 《China's Foreign Trade》 2024年第4期54-56,共3页
“Inf luenced by the slow recover y of the globa l economy,the continual impact of El Niño,growing local conflicts,the prevalence of trade protectionism and other factors,this year,the global supply and demand fo... “Inf luenced by the slow recover y of the globa l economy,the continual impact of El Niño,growing local conflicts,the prevalence of trade protectionism and other factors,this year,the global supply and demand for agricultural products and trade is under pressure,and the world’s food security has been a serious challenge.Therefore,it is of great and far-reaching significance for all countries in the world to further develop international cooperation in agriculture from a strategic height,in order to maintain the resilience of the international supply chain of agriculture,and to promote mutual benefits and the common development of all parties.”Yu Jianlong,Vice President of China Council for the Promotion of International Trade(CCPIT)and Vice President of the China Chamber of International Commerce(CCIC),said at the 2024 China Agricultural Conference for International Economic and Trade Cooperation. 展开更多
关键词 AGRICULTURAL mutual maintain
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Modern Development and Maintaining Self-Developing Identity
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作者 Si Thu Tun 《China Report ASEAN》 2024年第7期62-63,共2页
Two recent trips to cities in China got me thinking a lot about China’s development and efforts to maintain its identity.While China is developing with strong momentum in every sector,it has succeeded at preserving a... Two recent trips to cities in China got me thinking a lot about China’s development and efforts to maintain its identity.While China is developing with strong momentum in every sector,it has succeeded at preserving and upholding its ancient traditions and customs.These trips showed me a country not only keen on technological and infrastructural advancement but also deeply committed to cultural preservation and promotion.In every corner of these cities,I witnessed a harmonious blend of the old and new,a testament to China’s dedication to maintaining its cultural heritage while embracing modernity. 展开更多
关键词 TRIPS PROMOTION maintain
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Research on Maintainability Evaluation Model Based on Fuzzy Theory 被引量:10
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作者 陆中 孙有朝 《Chinese Journal of Aeronautics》 SCIE EI CAS CSCD 2007年第5期402-407,共6页
Maintainability influencing attributes are analyzed, their weight and value calculating methods are given, and the maintainability fuzzy evaluation method is proposed based on the relative closeness. According to the ... Maintainability influencing attributes are analyzed, their weight and value calculating methods are given, and the maintainability fuzzy evaluation method is proposed based on the relative closeness. According to the maintenance task simulation operated in virtual environment, the maintainability virtual evaluation model is built by analyzing the maintenance task for each replaceable unit of product. At last, a case study is given based upon the main landing gear system of a certain type civil aircraft, and the result indicates that the model is suitable for maintainability qualitative evaluation and can support maintainability concurrent design. 展开更多
关键词 maintainability evaluation multiple criteria decision making fuzzy theory virtual maintenance concurrent design
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Meta-analysis of potentially confounding effect of class size on associations between object-oriented metrics and maintainability
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作者 卢红敏 周毓明 徐宝文 《Journal of Southeast University(English Edition)》 EI CAS 2008年第3期281-283,共3页
This paper uses three size metrics,which are collectable during the design phase,to analyze the potentially confounding effect of class size on the associations between object-oriented(OO)metrics and maintainability... This paper uses three size metrics,which are collectable during the design phase,to analyze the potentially confounding effect of class size on the associations between object-oriented(OO)metrics and maintainability.To draw as many general conclusions as possible,the confounding effect of class size is analyzed on 127 C++ systems and 113 Java systems.For each OO metric,the indirect effect that represents the distortion of the association caused by class size and its variance for individual systems is first computed.Then,a statistical meta-analysis technique is used to compute the average indirect effect over all the systems and to determine if it is significantly different from zero.The experimental results show that the confounding effects of class size on the associations between OO metrics and maintainability generally exist,regardless of whatever size metric is used.Therefore,empirical studies validating OO metrics on maintainability should consider class size as a confounding variable. 展开更多
关键词 OBJECT-ORIENTED metrics VALIDATION class size CONFOUNDING maintainABILITY
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Maintainability Analysis Visualization System and Its Development in AutoCAD Environment
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作者 HAO Jian-ping 1, XUE Qi 2, YU Yong-li 1 (1. Maintenance Engineering Institute, Shijiazhuang 050003, China 2. System Engineering Institute, Beijing 100101, China) 《厦门大学学报(自然科学版)》 CAS CSCD 北大核心 2002年第S1期138-,共1页
Maintainability is an important design characterist ic , and also is a design parameter. The essence of maintainability design is to ex pect and solve possible maintenance problems at early stage during product devel ... Maintainability is an important design characterist ic , and also is a design parameter. The essence of maintainability design is to ex pect and solve possible maintenance problems at early stage during product devel opment, maintainability must be designed into product simultaneously. But curren t maintainability methods do not support concurrent engineering. This paper anal yzes the deficiencies of existing maintainability technologies, and introduces t he concept of maintainability analysis visualization. The two major deficiencies are that maintainability analysis time lags behind product design, and the main tainability techniques do not accommodate modern product design concepts. After this, the infrastructure of maintainability analysis visualization system is dis cussed. The system are composed of four subsystems, they are product modeling, d isassembly process modeling, simulation and analysis, and user interface. Produc t modeling is accomplished with the capability of CAD system, disassembly proces s modeling is mainly a reason process based on assembly information. The system is integrated into AutoCAD so that designer can timely analyze their product des ign from the viewpoint of easy maintenance. Human model generation function, hum an task analysis function, tool analysis function, visibility analysis function is implemented, disassembly process planning function is still under developing. 展开更多
关键词 maintainABILITY DISASSEMBLY maintainability ana lysis GLYCEROL adsorption OXIDATION
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Softw are Maintainability Evaluation Based on Software Configuration Management Data
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作者 郝学良 刘丽 朱小冬 《Journal of Donghua University(English Edition)》 EI CAS 2016年第2期284-287,共4页
As one of the most important attributes of software quality, software maintainability has been widely recognized.However,the existing maintainability evaluation methods are mostly based on subjectively judgment. Thus ... As one of the most important attributes of software quality, software maintainability has been widely recognized.However,the existing maintainability evaluation methods are mostly based on subjectively judgment. Thus it is inapplicable or unbelievable. To evaluate software maintainability objectively,the software configuration management( SCM) data are collected to establish a maintainability model. Based on the hidden Markov chain( HMC), a three-state maintainability estimation model is constructed. To validate the feasibility of the model,a real software example of software maintenance activity is given and the result from the example shows the effectiveness of the proposed method. 展开更多
关键词 software maintainability software configuration management(SCM) hidden Markov chain(HMC) model software measurement maintainability state
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Intellectualization of Design Technique for Product Maintainability
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作者 SHIQuan SONGYi-gang CHENGZhong-hua 《International Journal of Plant Engineering and Management》 2004年第2期59-71,共13页
The basis of the two guideline lectures for maintainability design, namely''maintainability design criterions'' and ''cases compilation of maintainability design technique'' , anintelle... The basis of the two guideline lectures for maintainability design, namely''maintainability design criterions'' and ''cases compilation of maintainability design technique'' , anintellectualized architecture for combining rule-based reasoning (RBR) and case-based reasoning(CBR), is presented in this paper by analyzing from maintainability design procedure to the thoughtof our solving the maintainability design problem. Furthermore, the domain model and reasoningprocess is introduced and a representation of maintainability domain knowledge is given. Finally,the computer-aided engineering system for maintainability design (MCAES) which is based onintellectualized architecture is reported; its function and implementation is described. 展开更多
关键词 maintainABILITY maintainability design RBR/CBR
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Coronavirus disease(COVID-19):The need to maintain regular physical activity while taking precautions 被引量:17
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作者 Peijie Chen Lijuan Mao +3 位作者 George P.Nassis Peter Harmer Barbara E.Ainsworth Fuzhong Li 《Journal of Sport and Health Science》 SCIE 2020年第2期103-104,共2页
The on-going Coronavirus disease(COVID-19)outbreak in China has become the world's leading health headline and is causing major panic and public concerns.On January 30,2020,the World Health Organization(WHO)declar... The on-going Coronavirus disease(COVID-19)outbreak in China has become the world's leading health headline and is causing major panic and public concerns.On January 30,2020,the World Health Organization(WHO)declared that the new coronavirus outbreak is a public health emergency of international concern.1 The virus has already had a direct impact on more than 10 million people in the city of Wuhan and has reached other parts of China as well,posing a health threat of unknown magnitude globally.As of February 8,2020,WHO reported 34,886 confirmed cases of COVID-19 globally,with 34,589 of them occurring in China(including 6101 severe cases and 723 deaths).A total of 288 other confirmed cases(with 1 death)have been reported in 24 countries,including Japan,Australia,Germany,and United States.2 However,these daily estimates are expected to rise even higher as reports from health authorities in China3 are gathered and near real-time updates of the Johns Hopkins virus dashboard are made 4 The outbreak has caused governments in various countries to take swift and protective measures.In China,these included putting cities on lockdown,5 implementing travel wamings/bans and cancellations,6 extending national holidays,and closing schools and postponing classes7. 展开更多
关键词 globally maintain TRAVEL
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Thermal Resistance of Common Rice Maintainer and Restorer Lines to High Temperature During Flowering and Early Grain Filling Stages 被引量:5
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作者 FU Guan-fu SONG Jian +5 位作者 XIONG Jie LIAO Xi-yuan ZHANG Xiu-fu WANG Xi LE Ming-kai TAO Long-xing 《Rice science》 SCIE 2012年第4期309-314,共6页
Fifteen common rice maintainer lines and 26 high-yielding restorer lines were used to evaluate their thermal resistance and fertility during flowering and early grain filling stages. The rice plants were subjected to ... Fifteen common rice maintainer lines and 26 high-yielding restorer lines were used to evaluate their thermal resistance and fertility during flowering and early grain filling stages. The rice plants were subjected to high temperature stress (39-43 ℃) for 1-15 d from main stem flowering. Based on the heat stress index, they were divided into thermal resistant lines, semi-thermal resistant lines, semi-thermal sensitive lines and thermal sensitive lines. Therefore, the maintainer lines K22B, Bobai B and V20B belonged to thermal resistant lines, whereas 11-32B, Zhongzhe B and Zhong 9B belonged to thermal sensitive lines. For rice restorer lines, Minghui 63 had the highest thermal resistance, followed by R207, P32, P929, and the lowest thermal resistant lines P62-2-2, R8006 and P51. The correlation analysis indicated that the heat stress index was significantly correlated with seed-setting rate and abortive grain rate under heat stress, but not under natural conditions. This indicated that heat stress occurred during flowering and early grain filling stages mainly decreased the seed- setting rate and significantly increased the abortive grain rate in both rice maintainer and restorer lines. 展开更多
关键词 RICE maintainer line restorer line heat stress FERTILITY thermal resistance
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Mechanosignaling activation of TGFβmaintains intervertebral disc homeostasis 被引量:14
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作者 Qin Bian Lei Ma +10 位作者 Amit Jain Janet L Crane Khaled Kebaish Mei Wan Zhengdong Zhang X Edward Guo Paul D Sponseller Cheryle A Seguin Lee H Riley Yongjun Wang Xu Cao 《Bone Research》 SCIE CAS CSCD 2017年第1期27-40,共14页
Intervertebral disc (IVD) degeneration is the leading cause of disability with no disease-modifying treatment. IVD degeneration is associated with instable mechanical loading in the spine, but little is known about ... Intervertebral disc (IVD) degeneration is the leading cause of disability with no disease-modifying treatment. IVD degeneration is associated with instable mechanical loading in the spine, but little is known about how mechanical stress regulates nucleus notochordal (NC) cells to maintain IVD homeostasis. Here we report that mechanical stress can result in excessive integrin αvβ6-mediated activation of transforming growth factor beta (TGFβ), decreased NC cell vacuoles, and increased matrix proteoglycan production, and results in degenerative disc disease (DDD). Knockout of TGFβ type II receptor (TβRII) or integrin αv in the NC cells inhibited functional activity of postnatal NC cells and also resulted in DDD under mechanical loading. Administration of RGD peptide, TGFβ, and αvβ6-neutralizing antibodies attenuated IVD degeneration. Thus, integrin-mediated activation of TGFβ plays a critical role in mechanical signaling transduction to regulate IVD cell function and homeostasis. Manipulation of this signaling pathway may be a potential therapeutic target to modify DDD. 展开更多
关键词 Mechanosignaling activation of TGF maintains intervertebral disc homeostasis IVD
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Optimizing reliability, maintainability and testability parameters of equipment based on GSPN 被引量:3
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作者 Tingpeng Li Yue Li +1 位作者 Yanling Qian Yongcheng Xu 《Journal of Systems Engineering and Electronics》 SCIE EI CSCD 2015年第3期633-643,共11页
Reliability, maintainability and testability (RMT) are important properties of equipment, since they have important influ- ence on operational availability and life cycle costs (LCC). There- fore, weighting and op... Reliability, maintainability and testability (RMT) are important properties of equipment, since they have important influ- ence on operational availability and life cycle costs (LCC). There- fore, weighting and optimizing the three properties are of great significance. A new approach for optimization of RMT parameters is proposed. First of all, the model for the equipment operation pro- cess is established based on the generalized stochastic Petri nets (GSPN) theory. Then, by solving the GSPN model, the quantitative relationship between operational availability and RMT parameters is obtained. Afterwards, taking history data of similar equipment and operation process into consideration, a cost model of design, manufacture and maintenance is developed. Based on operational availability, the cost model and parameters ranges, an optimization model of RMT parameters is built. Finally, the effectiveness and practicability of this approach are validated through an example. 展开更多
关键词 RELIABILITY maintainABILITY TESTABILITY optimization cost model operational availability.
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Layout problem of multi-component systems arising for improving maintainability 被引量:5
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作者 罗旭 杨拥民 +2 位作者 葛哲学 温熙森 官凤娇 《Journal of Central South University》 SCIE EI CAS 2014年第5期1833-1841,共9页
To improve the mainlainability design efficiency and quality, a layout optimization method for maintainability of multi-component systems was proposed. The impact of the component layout design on system maintainabili... To improve the mainlainability design efficiency and quality, a layout optimization method for maintainability of multi-component systems was proposed. The impact of the component layout design on system maintainability was analyzed, and the layout problem for maintainability was presented. It was formulated as an optimization problem, where maintainability, layout space and distance requirement were formulated as objective functions. A multi-objective particle swarm optimization algorithm, in which the constrained-domination relationship and the update strategy of the global best were simply modified, was then used to obtain Pareto optimal solutions for the maintainability layout design problem. Finally, application in oxygen generation system of a spacecraft was studied in detail to illustrate the effectiveness and usefulness of the proposed method. The results show that the concurrent maintainability design can be carried out during the layout design process by solving the layout optimization problem for maintainability. 展开更多
关键词 maintainABILITY layout problem OPTIMIZATION multi-component system multi-objective particle swarm optimization
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Resistance Evaluation of Some Chinese Leading Rice Maintainer, Restorer lines and Their Hybrids to Magnaporthe grisea 被引量:2
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作者 ZHUXu-dong SHENYing +2 位作者 HenriADREIT JulienFROUIN DidierHARREAU 《Rice science》 SCIE 2004年第3期101-105,共5页
Six isolates of Magnaporthe grisea were selected to inoculate on 10 Chinese leading maintainer lines (B-lines), 14 restorer lines (R-lines) and their F1 hybrid plants. In the tested rice materials, R-lines were proved... Six isolates of Magnaporthe grisea were selected to inoculate on 10 Chinese leading maintainer lines (B-lines), 14 restorer lines (R-lines) and their F1 hybrid plants. In the tested rice materials, R-lines were proved to be more resistant to blast than B-lines. The resistance frequency of about 25% F1 hybrid plants was less than their parents. In addition, 26 isolates of M. grisea collected from different rice growing areas of China were inoculated on 13 new improved hybrid rice combinations. The resistance frequencies of 5 improved hybrids were better than those of the controls and leading varieties in rice production of China. 展开更多
关键词 hybrid rice maintainer line restorer line Magnaporthe grisea BLAST RESISTANCE
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Predicting the Maintainability of Open Source Software Using Design Metrics 被引量:2
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作者 ZHOU Yuming1,2, XU Baowen1,3 1. School of Computer Science and Engineering, Southeast University, Nanjing 210096, Jiangsu,China 2. Department of Computing, Hong Kong Polytechnic University, Hong Kong, China 3. Jiangsu Institute of Software Quality, Nanjing 210096, Jiangsu,China 《Wuhan University Journal of Natural Sciences》 CAS 2008年第1期14-20,共7页
This paper empirically investigates the relationships between 15 design metrics and maintainability of 148 Java open source software. The results show that size and complexity metrics are strongly related to the maint... This paper empirically investigates the relationships between 15 design metrics and maintainability of 148 Java open source software. The results show that size and complexity metrics are strongly related to the maintainability of open source software. However, cohesion and coupling, as currently captured by existing metrics, do not seem to have a significant impact on maintainability. When used together, these metrics can predict system maintainability fairly accurately (mean MREs below 30%). 展开更多
关键词 open source: object-oriented maintainABILITY METRIC PREDICTION regression
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Maintaining proton homeostasis is an essential role of the Warburg effect in proliferating cells 被引量:2
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作者 Chuangzhen Yang Binghui Li 《Cancer Biology & Medicine》 SCIE CAS CSCD 2019年第3期391-395,共5页
Non-proliferating cells efficiently generate adenosine 5’-triphosphate (ATP) through mitochondrial oxidative phosphorylation.By contrast, proliferating cells, including cancer cells, tend to rely on aerobic glycolysi... Non-proliferating cells efficiently generate adenosine 5’-triphosphate (ATP) through mitochondrial oxidative phosphorylation.By contrast, proliferating cells, including cancer cells, tend to rely on aerobic glycolysis, an inefficient way to generate energy, and this phenomenon is termed 'the Warburg effect'1,2.However, the advantage of the Warburg effect provided for proliferating cells has been unclear3.Here we propose that aerobic glycolysis may maintain proton homeostasis to benefit proliferating cells. 展开更多
关键词 maintaining PROTON HOMEOSTASIS WARBURG effect PROLIFERATING CELLS
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Development and Application of SCAR Markers for Discriminating Cytoplasmic Male Sterile Lines from Their Cognate Maintainer Lines in Indica Rice 被引量:2
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作者 LU Chao LIU Jian +4 位作者 JIANG Jian-hua Caleb Manamik BRERIA TAN He-lin Masahiko ICHII HONG De-lin 《Rice science》 SCIE 2013年第3期191-199,共9页
The DNAfragments about 1 600 bp were amplified using random amplified polymorphism DNA (RAPD) primer OPAl2 with the templates of mitochondrial DNA of Zhenshan 97A and Zhenshan 97B, and were sequenced. The nucleotide... The DNAfragments about 1 600 bp were amplified using random amplified polymorphism DNA (RAPD) primer OPAl2 with the templates of mitochondrial DNA of Zhenshan 97A and Zhenshan 97B, and were sequenced. The nucleotide sequences and lengths of the fragments from Zhenshan 97A and Zhenshan 97B showed no difference. The precise length of the fragment was 1 588 bp. Sequence characterized amplification region (SCAR) primers were then developed to discriminate the cytoplasmic male sterile (CMS) lines and their maintainer lines. A specific 1 588 bp fragment could be amplified with SCAR primers, CHI19F2/CHI19R2 and CHI20F3/CHI23R3, in the mitochondrial DNA of Zhenshan 97A, but not Zhenshan 97B. Furthermore, the specific fragment could be also amplified from the total DNA from green leaf tissues of Zhenshan 97A with SCAR primers, but not Zhenshan 97B. With the corresponding primers, the specific fragment could also be amplified from the total DNA of green leaves of other two CMS lines with wild abortive type cytoplasm (CMS-WA), namely Zhenpin A and Tianfeng A, but not in their maintainer lines. Moreover, using total DNA as template, each of the four pairs of SCAR primers could also be used to amplify the 1 588 bp fragment in CMS-ID (Indonesia paddy type) line 11-32A but not in 11-32B, and the specific fragment was amplified from the DNA of both F1 and F2 seedlings of Shanyou 63. The results of detecting the genetic purity of a man-made mixture of the seeds of Zhenshan 97A using CHI20F3/CHI23R3 were completely consistent with the phenotypes. Taken together, these results indicated that the specific 1 588 bp-fragment amplified by CHI20F3/CHI23R3 was the unique amplification products of CMS mitochondrial DNA, and could be used to distinguish CMS-WA and CMS-ID lines from their corresponding maintainer lines at the seedling stage. 展开更多
关键词 Oryza safiva cytoplasmic male sterile line maintainer line genetic purity sequence characterized amplification region marker
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Posterior quadrantic disconnection maintains the activity of isolated temporal-parietal-occipital nerve tissue: neuroprotective measures in the surgical treatment of epilepsy 被引量:4
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作者 Shaoya Yin Keke Feng +2 位作者 Mei Feng Xueqing Zhang Yuqin Zhang 《Neural Regeneration Research》 SCIE CAS CSCD 2014年第4期447-448,共2页
Extensive lesions involving the posterior quadrant of the cerebral hemisphere (temporal, parietal, and occipital lobes) induce intractable epilepsy. These patients are potential candidates for surgical treatmenttu. ... Extensive lesions involving the posterior quadrant of the cerebral hemisphere (temporal, parietal, and occipital lobes) induce intractable epilepsy. These patients are potential candidates for surgical treatmenttu. Maintenance of isolated nerve tissue activity after surgery plays a crucial role in the neuroprotective effects of neurosurgery treatment. Disconnection surgery of the posterior quadrant is used to completely isolate nerve fibers, while blood supply at the isolated lobes is maintained. Subsequently, cavities caused by cystic or necrotic nerve tissues should be reduced as much as possible, 展开更多
关键词 MRI Posterior quadrantic disconnection maintains the activity of isolated temporal-parietal-occipital nerve tissue neuroprotective measures in the surgical treatment of epilepsy EEG Figure
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Role of Fibroblast Growth Factor 19 in Maintaining Nutrient Homeostasis and Disease 被引量:3
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作者 ZHANG Jing LI Hua Ting +1 位作者 FANG Qi Chen JIA Wei Ping 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2014年第5期319-324,共6页
Fibroblast growth factor 19 (FGF19) is a kind of gut-derived postprandial hormone. As an atypical member of the FGF family, FGF19 functions as an endocrine hormone except regulating cell growth and differentiation. ... Fibroblast growth factor 19 (FGF19) is a kind of gut-derived postprandial hormone. As an atypical member of the FGF family, FGF19 functions as an endocrine hormone except regulating cell growth and differentiation. FGF19 plays a key role in coordination of liver bile acid biosynthesis and gallbladder motility, and acts as a regulator of metabolic homeostasis, including strengthening insulin sensitivity, decreasing triglyceride concentration and reducing body weight. 展开更多
关键词 FGFS acid FGFR Role of Fibroblast Growth Factor 19 in maintaining Nutrient Homeostasis and Disease
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NUMB maintains bone mass by promoting degradation of PTEN and GLI1 via ubiquitination in osteoblasts 被引量:4
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作者 Ling Ye Feng Lou +11 位作者 Fanyuan Yu Demao Zhang Chenglin Wang Fanzi Wu Xin Li Yilin Ping Xiao Yang Jing Yang Dian Chen Bo Gao Dingming Huang Peng Liu 《Bone Research》 SCIE CAS CSCD 2018年第4期368-382,共15页
The adaptor protein NUMB is involved in asymmetric division and cell fate determination and recognized as an antagonist of Notch.Previous studies have proved that Notch activation in osteoblasts contributes to a high ... The adaptor protein NUMB is involved in asymmetric division and cell fate determination and recognized as an antagonist of Notch.Previous studies have proved that Notch activation in osteoblasts contributes to a high bone mass. In this study, however, an osteopenic phenotype was found in 9-week-old mice using osteoblastic specific Col1a1–2.3-Cre to ablate both Numb and its homologue Numbl. The trabecular bone mass decreased dramatically while the cortical bone mass was unaffected. Here, the Notch signal was not activated,while the tensin homologue deleted on human chromosome 10(PTEN), which dephosphorylates phosphatidylinositide 3-kinases, was elevated, attenuating protein kinase B(Akt). The ubiquitination assay revealed that NUMB may physiologically promote PTEN ubiquitination in the presence of neural precursor cell-expressed developmentally downregulated protein 4–1. In addition, the deficiency of Numb/Numbl also activated the Hedgehog pathway through GLI1. This process was found to improve the ratio of the receptor activator of nuclear factor-k B ligand to osteoprotegerin, which enhanced the differentiation of osteoclasts and bone resorption. In conclusion, this study provides an insight into new functons of NUMB and NUMBL on bone homeostasis. 展开更多
关键词 NUMB maintains bone mass by promoting degradation of PTEN and GLI1 via ubiquitination in osteoblasts GLI RANKL
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