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      • Long-circulating siRNA nanoparticles for validating Prohibitin1-targeted non-small cell lung cancer treatment

        Zhu, Xi,Xu, Yingjie,Solis, Luisa M.,Tao, Wei,Wang, Liangzhe,Behrens, Carmen,Xu, Xiaoyang,Zhao, Lili,Liu, Danny,Wu, Jun,Zhang, Ning,Wistuba, Ignacio I.,Farokhzad, Omid C.,Zetter, Bruce R.,Shi, Jinjun National Academy of Sciences 2015 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.112 No.25

        <P><B>Significance</B></P><P>This study developed a new generation lipid–polymer hybrid nanoparticle platform for effective systemic delivery of small interfering RNA (siRNA) to tumors, which represents a challenging hurdle for the widespread application of RNA interference (RNAi) in cancer research and therapy. With promising in vivo features such as long blood circulation, high tumor accumulation, and effective gene silencing, the hybrid siRNA nanoparticles were successfully used to reveal and validate a putative therapeutic target, Prohibitin1 (PHB1), in non-small cell lung cancer treatment. In vivo antitumor efficacy results and human tissue microarray analysis further suggested the feasibility of utilizing PHB1 siRNA nanoparticles as a novel therapeutic agent. This hybrid RNAi nanoparticle platform may serve as a valuable tool for validating potential cancer targets and developing new cancer therapies.</P><P>RNA interference (RNAi) represents a promising strategy for identification and validation of putative therapeutic targets and for treatment of a myriad of important human diseases including cancer. However, the effective systemic in vivo delivery of small interfering RNA (siRNA) to tumors remains a formidable challenge. Using a robust self-assembly strategy, we develop a unique nanoparticle (NP) platform composed of a solid polymer/cationic lipid hybrid core and a lipid-poly(ethylene glycol) (lipid-PEG) shell for systemic siRNA delivery. The new generation lipid–polymer hybrid NPs are small and uniform, and can efficiently encapsulate siRNA and control its sustained release. They exhibit long blood circulation (<I>t</I><SUB>1/2</SUB> ∼8 h), high tumor accumulation, effective gene silencing, and negligible in vivo side effects. With this RNAi NP, we delineate and validate the therapeutic role of Prohibitin1 (PHB1), a target protein that has not been systemically evaluated in vivo due to the lack of specific and effective inhibitors, in treating non-small cell lung cancer (NSCLC) as evidenced by the drastic inhibition of tumor growth upon PHB1 silencing. Human tissue microarray analysis also reveals that high PHB1 tumor expression is associated with poorer overall survival in patients with NSCLC, further suggesting PHB1 as a therapeutic target. We expect this long-circulating RNAi NP platform to be of high interest for validating potential cancer targets in vivo and for the development of new cancer therapies.</P>

      • Expression and Role of ICAM-1 in the Occurrence and Development of Hepatocellular Carcinoma

        Zhu, Xi-Wen,Gong, Jian-Ping Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.3

        Intercellular adhesion molecule-1 (ICAM-1) is a member of the immunoglobulin superfamily, its main function being to participate in recognition and adhesion between cells. ICAM-1 is considered closely related to occurrence, development, metastasis and invasion process of hepatocellular carcinoma (HCC). A variety of inflammatory cytokines and stimulus affect its expression through the nuclear factor-kappa B (NF-${\kappa}B$) signal transduction pathway. In the initial stage of inflammation, hepatocirrhosis and tumor development, ICAM-1 is expressed differently, and has varied effects on different cells to promote occurrence of malignancy and metastasis. ICAM-1 has diagnostic significance for AFP-negative or suspected HCC, and may be a prognositic significance. It is thus widely used in studies as a biomarker which reflects cancer cells metastasis as well as curative effect of drugs. Many new treatments of HCC may be based on the effects of ICAM-1 on different levels of function.

      • KCI등재

        Joint Estimation in Batch Culture by Using Unscented Kalman Filter

        Xi Zhu,Enmin Feng 한국생물공학회 2012 Biotechnology and Bioprocess Engineering Vol.17 No.6

        The disturbances caused by uncertain factors are inevitable in microbial fermentation. In this paper, we study the joint estimation problem for state and parameter in the bio-dissimulation process of glycerol to 1,3-PD in batch culture. Based on the nonlinear stochastic dynamic system model, we establish the corresponding iteration equations of Joint Unscented Kalman Filter (UKF) by referring to the Extended Kalman Filter (EKF), which is generally applied in microbial fermentation. Through numerical computation, both the state estimations and the uncertain model parameter estimations are obtained. Furthermore, the results of different parameter identification methods are compared. The results show that Joint UKF is more feasible for the process of controlling the glycerol fermentation. The disturbances caused by uncertain factors are inevitable in microbial fermentation. In this paper, we study the joint estimation problem for state and parameter in the bio-dissimulation process of glycerol to 1,3-PD in batch culture. Based on the nonlinear stochastic dynamic system model, we establish the corresponding iteration equations of Joint Unscented Kalman Filter (UKF) by referring to the Extended Kalman Filter (EKF), which is generally applied in microbial fermentation. Through numerical computation, both the state estimations and the uncertain model parameter estimations are obtained. Furthermore, the results of different parameter identification methods are compared. The results show that Joint UKF is more feasible for the process of controlling the glycerol fermentation.

      • BCR/ABL mRNA Targeting Small Interfering RNA Effects on Proliferation and Apoptosis in Chronic Myeloid Leukemia

        Zhu, Xi-Shan,Lin, Zi-Ying,Du, Jing,Cao, Guang-Xin,Liu, Gang Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.12

        Background: To investigate the effects of small interference RNA (siRNA) targeting BCR/ABL mRNA on proliferation and apoptosis in the K562 human chronic myeloid leukemia (CML) cell line and to provide a theoretical rationale and experimental evidence for its potential clinical application for anti-CML treatment. Materials and Methods: The gene sequence for BCR/ABL mRNA was found from the GeneBank. The target gene site on the BCR/ABL mRNA were selected according to Max-Planck-Institute (MPI) and rational siRNA design rules, the secondary structure of the candidate targeted mRNA was predicted, the relevant thermodynamic parameters were analyzed, and the targeted gene sequences were compared with BLAST to eliminate any sequences with significant homology. Inhibition of proliferation was evaluated by MTT assay and colony-formation inhibiting test. Apoptosis was determined by flow cytometry (FCM) and the morphology of apoptotic cells was identified by Giemsa-Wright staining. Western blotting was used to analyze the expression of BCR/ABL fusion protein in K562 cells after siRNA treatment. Results: The mRNA local secondary structure calculated by RNA structure software, and the optimal design of specific siRNA were contributed by bioinformatics rules. Five sequences of BCR/ABL siRNAs were designed and synthesized in vitro. Three sequences, siRNA1384, siRNA1276 and siRNA1786, which showed the most effective inhibition of K562 cell growth, were identified among the five candidate siRNAs, with a cell proliferative inhibitory rate nearly 50% after exposure to 12.5nmol/L~50nmol/L siRNA1384 for 24,48 and 72 hours. The 50% inhibitory concentrations ($IC_{50}$) of siRNA1384, siRNA1276 and siRNA1786 for 24hours were 46.6 nmol/L, 59.3 nmol/L and 62.6 nmol/L, respectively, and 65.668 nmol/L, 76.6 nmol/L, 74.4 nmol/L for 72 hours. The colony-formation inhibiting test also indicated that, compared with control, cell growth of siRNA treated group was inhibited. FCM results showed that the rate of cell apoptosis increased 24 hours after transfecting siRNA. The results of annexinV/PI staining indicated that the rate of apoptosis imcreased (1.53%, 15.3%, 64.5%, 57.5% and 21.5%) following treamtne with siRNAs (siRNA34, siRNA372, siRNA1384, siRNA1276 and siRNA1786). Morphological analysis showed td typical morphologic changes of apoptosis such as shrunken, fragmentation nucleus as well as "apoptotic bodies" after K562 cell exposure to siRNA. Western blot analysis showed that BCR/ABL protein was reduced sharply after a single dose of 50nmol/L siRNA transfection. Conclusions: Proliferation of K562 cells was remarkbly inhibited by siRNAs (siRNA1384, siRNA1276 and siRNA1786) in a concentration-dependent manner in vitro, with effective induction of apoptosis at a concentration of 50 nmol/L. One anti-leukemia mechanism in K562 cells appeared that BCR/ABL targeted protein was highly down-regulated. The siRNAs (siRNA1384, siRNA1276 and siRNA1786) may prove valuable in the treatment of CML.

      • 지하 공공공간의 휴게시설 사용에 관한 연구 - 부산 서면역 시설물의 사례연구 -

        주시펑(Zhu, Xi-Peng),김수정(Kim, Soo-Jeong),박수빈(Park, Soo-Ben) 한국주거학회 2023 한국주거학회 학술대회논문집 Vol.35 No.1

        This study aims to analyze the user behavior of a subway station rest space in an urban space. Taking the fountain plaza near the Seomyeon subway station in Busan as the object of study, user behaviors were classified into three categories: necessary, optional, and social activities through on-site observation and literature review, and the needs of the physical environment for different types of activities were assessed. Improvement measures for public facilities are also proposed. The results of the study found that the current subway station rest spaces lack public facilities that support users’ resting activities and social activities, thus leading to an unbalanced subway environment and low user satisfaction. Therefore, this paper suggests that public facilities in the rest area in subway stations should be suitable for different types of activities and to enhance the connection between subway stations and the surrounding environment.

      • KCI등재
      • KCI등재

        An improved horizontally reversible plow design based on virtual assembly semantics and constraint

        Lin Zhu,Shuang-Shuang Peng,Yin-Yin Qi,Xi Cheng,Wen-Feng Zhang,Liang-Yuan Xu,De-Quan Zhu 대한기계학회 2016 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.30 No.1

        There exit model errors in the constructed Horizontally reversible plough (HRP) structure through Interference check technique (ICT). This is basically due to missing parts and geometric interference and, hence, has significantly adverse effects in improving HRP. In thispaper an improved design to refine the three dimensional (3D) model of HRP is implemented by using Virtual assembly technology(VAT). To achieve this, the authors propose a combined virtual assembly semantics and constraint for assembly planning and simulationof HRP in the commercial software, e.g., SolidWorks. First, the assembly planning of HRP was captured with a semantics-based model,including spatial position, assembly orientation, type and parameters of the semantic entities; secondly, the assembly simulation of HRPwas performed by using constraint-based VAT, e.g. component grasping, moving and releasing; finally, the obtained HRP model wasverified through ICT again. The results demonstrate that not any model error exists in the refined 3D HRP model any longer and thatsemantics and constrain based VAT can support the interactive operation more effectively and accurately than those with geometric constraints. This technique was previously used for HRP model. Based on the refined 3D HRP model, the design improvement of Remotecylinder base (RCB), an important component of HRP, will be forthcoming in a future paper.

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