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Activity of T Cells Stimulated by Hemagglutinin-neuraminidase of Newcastle Disease Virus in vivo

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Chemical Research in Chinese Universities 2011年第3期27卷 455-460页

作者： piao Bing-guo LI Xiao SUN Li-li KAN Shi-fu LIU Lei HUANG Hai-yan YANG guo-hua WANG Yu-hang WANG Zhuo-yue SUN Jiu-hua piao Yun-feng JIN Ning-yi The First Hospital of Jilin University Changehun 130021 P. R. ChinA Genetic Engineering Laboratory of PLA 3. Key Laboratory of Jilin Province for Zoonosis Prevention and Control Military Veterinary Institute Academy of Military Medical Sciences of PLA Changehun 130062 P. R. China Key Laboratory of Jilin Province for Zoonosis Prevention and Control Military Veterinary Institute Academy of Military Medical Sciences of PLA Changchun 130062 P. R. China Department of Gastroenterology 209 Hospital of PLA Mudanjiang 157000 P. R. China Head and Neck Surgery Tumor Hospital of Jilin Province Changchun 130001 P R. China

To investigate the stimulated activity of T cells and the anti-tumor properties of hemagglutinin-neuraminidase（HN） of Newcastle disease virus（NDV） strain Changchun（NDVcc）, the expression of HN gene in hepatoma cells（human HepG-2 and mouse H22 cells） infected with the recombinant adenovirus（Ad-HN） was identified by Western blot analysis and flow cytometry. Sialidase activity of NDVcc HN expressed by Ad-HN was assayed by the periodate-resorcinol method. The in vivo anti-tumor effects of NDVcc HN were evaluated in the H22 solid tumor model. Regional lymph nodes of the mouse model treated with Ad-HN were removed to harvest T lymphocytes and evaluating the specific cytotoxicity of cytotoxic T lymphocyte（CTL） and natural killer（NK） cells by an L-lactate dehydrogenase（LDH） assay, in the mean time, the secretion of cytokines was analyzed by enzyme linked immunosorbent assays（ELISA）. The results show that NDVcc HN was effectively expressed by Ad-HN in HepG-2 and H22 cells. The sialidase activity assay showed that Ad-HN significantly reduced sialic acid level of the hepatoma cells compared with the cells infected the empty adenovirus vector（Ad-mock）. When treated with Ad-HN, the growth of subcutaneous H22 primary tumors in C57BL/6 mice was suppressed, and the mean mice survival increased. In addition, the treatment of Ad-HN elicited strong NK and CTL responses, and high levels of Th1 cytokines, such as IL-2 and IFN-γ. In conclusion, NDVcc HN effectively elicits T cell-mediate anti-tumor cytotoxicity via sialidase activity and may be a novel strategy for cancer immunotherapy.

关键词： Newcastle disease virus Hemagglutinin-neuraminidase Hepatoma T Cell Anti-tumor immunity

Cytosolic phospholipase A2α modulates cell-matrix adhesion via the FAK/paxillin pathway in hepatocellular carcinoma

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Cancer Biology & Medicine 2019年第2期16卷 377-390页

作者： piao guo Yuchao He Lu Chen Lisha Qi Dongming Liu Ziye Chen Manyu Xiao Liwei Chen Yi Luo Ning Zhang Hua guo Department of Tumor Cell Biology Department of Hepatobiliary Cancer Department of Pathology Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer/ Key Laboratory of Cancer Prevention and Therapy Tianjin Tianjin's Clinical Research Center for Cancer Tianjin 300060 China

Objective: To explore the effect of cytosolic phospholipase A2α(cPLA2α) on hepatocellular carcinoma(HCC) cell adhesion and the underlying ***: Cell adhesion, detachment, and hanging-drop assays were utilized to examine the effect of cPLA2α on the cell-matrix and cell-cell adhesion. Downstream substrates and effectors of cPLA2α were screened via a phospho-antibody *** signaling pathways were identified by the functional annotation tool DAVID. Candidate proteins were verified using Western blot and colocalization was investigated via immunofluorescence. Western blot and immunohistochemistry were used to detect protein expression in HCC tissues. Prognosis evaluation was conducted using Kaplan-Meier and Cox-proportional hazards regression ***: Our findings showed that cPLA2α knockdown decreases cell-matrix adhesion but increases cell-cell adhesion in HepG2 cells. Microarray analysis revealed that phosphorylation of multiple proteins at specific sites were regulated by cPLA2α. These phosphorylated proteins were involved in various biological processes. In addition, our results indicated that the focal adhesion pathway was highly enriched in the cPLA2α-relevant signaling pathway. Furthermore, cPLA2α was found to elevate phosphorylation levels of FAK and paxillin, two crucial components of focal adhesion. Moreover, localization of p-FAK to focal adhesions in the plasma membrane was significantly reduced with the downregulation of cPLA2α. Clinically, cPLA2α expression was positively correlated with p-FAK levels. Additionally, high expression of both cPLA2α and p-FAK predicted the worst prognoses for HCC ***: Our study indicated that cPLA2α may promote cell-matrix adhesion via the FAK/paxillin pathway, which partly explains the malignant cPLA2α phenotype seen in HCC.

关键词： Hepatocellular carcinoma cytosolic phospholipase A2α cell-matrix adhesion FAK paxillin

Periostin mediates epithelial-mesenchymal transition through the MAPK/ERK pathway in hepatoblastoma

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Cancer Biology & Medicine 2019年第1期16卷 89-99页

作者： Lu Chen Xiangdong Tian Wenchen Gong Bo Sun Guangtao Li Dongming Liu piao guo Yuchao He Ziye Chen Yuren Xia Tianqiang Song Hua guo Department of Tumor Cell Biology Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and TherapyTianjin Tianjin's Clinical Research Center for Cancer

Objective: The aim of the present study was to analyze the prognostic factors in patients with hepatoblastoma(HB) in our single center and to evaluate periostin(POSTN) expression in HB and its association with clinicopathological variables. In addition, the underlying mechanism of how POSTN promotes HB progression was ***: POSTN expression was investigated in HB tumors by immunohistochemistry(IHC), immunofluorescence(IF) and Western blot(WB). The association among POSTN expression, clinicopathological features and overall survival(OS) was also evaluated. The migration and adhesion ability of HB cells were measured using chemotaxis and cell-matrix adhesion assays,respectively. Epithelial-mesenchymal transition(EMT)-associated markers and activation of the ERK pathway were detected by ***: HB patients had poor prognosis which displayed lymph node metastasis, vascular invasion, POSTN and vimentin expression. POSTN expression was also associated with lymph node metastasis. Furthermore, overexpressed POSTN promoted migration and the adhesive ability of HB cells in vitro. In addition, we demonstrated that POSTN activated the MAPK/ERK pathway, upregulated the expression of Snail and decreased the expression of OVOL2. Finally, POSTN promoted the expression of EMT-associated ***: POSTN might modulate EMT via the ERK signaling pathway, thereby promoting cellular migration and *** study also suggests that POSTN may serve as a therapeutic biomarker in HB patients.

关键词： Periostin hepatoblastoma EMT MAPK/ERK

The role of bone marrow-derived cells in the origin of liver cancer revealed by single-cell sequencing

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Cancer Biology & Medicine 2020年第1期17卷 142-153页

作者： Lu Chen Xianfu Yi piao guo Hua guo Ziye Chen Chunyu Hou Lisha Qi Yongrong Wang Chengwen Li Peng Liu Yucun Liu Yuanfu Xu Ning Zhang The concrete information of affiliations should be presented for instanceDepartment of Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin's Clinical Research Center for CancerTianjin 300070China School of Biomedical Engineering and Technology Tianjin Medical UniversityTianjin 300070China The Center for Translational Cancer Research Peking University First HospitalBeijing 100034China State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China CAMS Key Laboratory for Prevention and Control of Hematological Disease Treatment Related Infection Tianjin 300020China Cytogenetics Laboratory Institute of Hematology and Blood Diseases HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300020China

Objective:Epithelial cancers often originate from progenitor cells,while the origin of hepatocellular carcinoma(HCC)is still ***,one of the deadliest cancers,is closely linked with liver injuries and chronic inflammation,which trigger massive infiltration of bone marrow-derived cells(BMDCs)during liver ***:To address the possible roles of BMDCs in HCC origination,we established a diethylnitrosamine(DEN)-induced HCC model in bone marrow transplanted *** and frozen tissue immunofluorescence were used to verify DENinduced HCC in the pathology of the *** cellular origin of DEN-induced HCC was further studied by single cell sequencing,single-cell nested PCR,and immunofluorescence-fluorescence in situ ***:Studies by using single cell sequencing and biochemical analysis revealed that HCC cells in these mice were coming from donor mice BMDCs,and not from recipient ***,the copy numbers of mouse orthologs of several HCC-related genes previously reported in human HCC were also altered in our mouse ***-induced HCCs exhibited a similar histological phenotype and genomic profile as human ***:These results suggested that BMDCs are an important origin of HCC,which provide important clues to HCC prevention,detection,and treatments.

关键词： Hepatocellular carcinoma bone marrow-derived cells(BMDCs) origination genome sequencing copy number alteration

Identification of TMEM159 as a biomarker of glioblastoma progression based on immune characteristics

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BIOCELL 2024年第8期48卷 1241-1263页

作者： JI SHI YE ZHANG YI CHEN TANGJUN guo HAOZHE piao Graduate School Dalian Medical UniversityDalian116000China Department of Neurosurgery Liaoning Cancer Hospital&InstituteShenyang110042China Department of Neurosurgery Affiliated Hospital of Xuzhou Medical UniversityXuzhou221000China

Background:Glioblastoma multiforme(GBM)is the most general malignancy of the primary central nervous system that is characterized by high aggressiveness and *** protein 159(TMEM159)is an endoplasmic reticulum protein that can form oligomers with *** TMEM159-seipin complex decides the site of lipid droplet(LD)formation,and the formation of LDs is a marker of ***,the role of TMEM159 in the progression of GBM has not been investigated to ***:In this study,we examined the genes that may be associated with patient prognosis in GBM by bioinformatics analyses,and identified the key genes that affect the development of GBM using single-cell RNA sequencing *** biological functions of TMEM159 in GBM cells were additionally assessed by clone formation and transwell assays as well as using a model of chick embryo chorioallantois membrane(CAM)and western *** association between TMEM159 and epidermal growth factor receptor(EGFR)was finally analyzed in GBM ***:A prognostic model was established and validated for predicting the *** curve analysis showed a critical difference in the prognosis of the high-and low-risk groups predicted by the prognostic *** results demonstrated that TMEM159 affected the proliferation and invasion of GBM *** chick embryo CAM assays demonstrated that the inhibition of TMEM159 expression reduced angiogenesis in the CAM ***:The prognostic model achieved good predictive potential for high-risk *** findings also revealed that TMEM159 might be an important prognostic factor for GBM,indicating that the protein may be a promising therapeutic target for suppressing the development of GBM.

关键词： Single-cell RNA sequencing Glioblastoma TMEM159 EGFR Angiogenesis

Anti-tumor Effects of a Recombinant Fowlpox Virus Expressing Apoptin on Human Cervical Carcinoma in Vivo and in Vitro

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Chemical Research in Chinese Universities 2011年第4期27卷 646-650页

作者： ZHU Ji-hong LI Xiao SUN Li-li ZHANG Mu-chun KAN Shi-fu LIU Lei HUANG Hai-yan YANG guo-hua piao Bing-guo JIN Ning-yi Department of Gynecology and Obstetrics the First Hospital of Jilin University Changchun 130021 P. R. China Laboratory of Genetic Engineering of PLA Academy of Military Medical Sciences Changchun 130062 P. R. China Department of Head and Neck Surgery Tumor Hospital of Jilin Province Changchun 130012 P R. China Department of Urology China-Japan Union Hospital of Jilin University Changchun 130033 P. R. China Department of Gastroenterology the First Hospital of Jilin University Changchun 130021 P. R. China

Apoptin is a chicken anemia virus-derived,p53-independent,bcl-2-insensitive apoptotic protein with the ability to specifically induce apoptosis of various human tumor cells,but not of normal diploid *** explore the application of apoptin in tumor gene therapy,we used a recombinant fowlpox virus expressing apoptin protein （vFV-Apoptin） to investigate the anti-tumor effectes of vFV-Apoptin on human cervical carcinoma（HeLa） cells in vivo and in vitro through 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide（MTT） assay,acridine orage/ethidium bromide（AO/EB） and annexin V staining test,*** results show that vFV-Apoptin inhibites the proliferation of HeLa cells in vitro through inducing the apoptosis of HeLa cells,and the inhibition effect of vFV-Apoptin has a dose-effect and time-effect *** results of animal models show that vFV-Apoptin significantly inhibits tumor growth,extends the lifespan of animals and improves the mean *** results indicate that vFV-Apoptin has a potential application in the tumor gene therapy.

关键词： Apoptin gene Chicken anemia virus Human cervical carcinoma Anti-tumor effect

A holistic perspective on Earth system science

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Science China Earth Sciences 2024年第10期67卷 3013-3040页

作者： Yongfei ZHENG Zhengtang guo Nianzhi JIAO Mu MU Shilong piao Suiyan FU Dinghui YANG Maoyan ZHU State Key Laboratory of Lithospheric and Environmental Coevolution School of Earth and Space SciencesUniversity of Science and Technology of ChinaHefei 230026China State Key Laboratory of Lithospheric and Environmental Coevolution Institute of Geology and GeophysicsChinese Academy of SciencesBeijing 100029China School of Ocean and Earth Sciences Xiamen UniversityXiamen 361102China Department of Atmospheric and Oceanic Sciences Fudan UniversityShanghai 200438China School of Environment Peking UniversityBeijing 100871China School of Earth and Space Sciences Peking UniversityBeijing 100871China Department of Mathematical Sciences Tsinghua UniversityBeijing 100084China Nanjing Institute of Geology and Palaeontology Chinese Academy of SciencesNanjing 210008China

Earth system can be categorized into three parts, solid Earth system, surface Earth system, and Sun-Earth space system. These three subsystems not only have mutual transmission and coupling relationships in both energy and matter but also involve multiple scales from microscopic to macroscopic. Earth system science is characterized by its globality and unity with a holistic view and a systematic view at multiple scales in both space and time. It focuses not only on the physical, chemical and biological interactions between various geospheres but also on the properties, behaviors, processes, and mechanisms of the entire Earth and its spheres. Although significant progress has been made in the study of internal disciplines of these three subsystems,there is still insufficient understanding of their overall behavior and interactions between individuals, thus facing challenges of different types and levels. The solid Earth system is composed of the crust, mantle, and core. Existing observational techniques struggle to penetrate deep into the mantle, making direct observation and data acquisition difficult;the extreme environments within Earth, such as high temperature, high pressure, and strong magnetic fields, also pose great challenges to observational equipment and scientific experiments. The surface Earth system is an open complex mega-system, in which there are complex interactions and feedback mechanisms among its geospheres(such as atmosphere, hydrosphere, biosphere, pedosphere and lithosphere), leading to difficulties in understanding of its overall behavior and long-term evolution. Biological activities have become increasingly significant in affecting the surface Earth system. The coupling between the internal and external Earth systems becomes more complex. Distinguishing and quantifying the impacts of Earth spherical interactions and biological activities on the surface Earth system is a major challenge. The Sun-Earth space system involves multiple physical

关键词： Earth's interior Earth's exterior Geospheres Energy exchange Material transfer

Signal space transform and multidimensional information joint processing for moving target

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Chinese Journal of Acoustics 2024年第1期43卷 23-48页

作者： SHI Yunjia piao Shengchun guo Junyuan ZHANG Liu Acoustic Science and Technology Laboratory Harbin Engineering UniversityHarbin 150001 Key Laboratory of Marine Information Acquisition and Security(Harbin Engineering University) Ministry of Industry and Information TechnologyHarbin 150001 College of Underwater Acoustic Engineering Harbin Engineering UniversityHarbin 150001

A signal space transform method for detection of line spectrum signals radiated by moving target is *** time-frequency analysis and beamforming processing,a three-dimensional(3D)time-frequency-azimuth signal space is obtained in the array coordinate *** certain target course angle,this 3D signal space is transformed to the time-frequency-relative bearing spectrum signal space in the target coordinate *** theoretical derivation,simulation,and experimental data processing are *** findings demonstrate that the method is capable of converting the target line spectrum signal 3D trajectory to a 2D trajectory on the corresponding slice in the transformed signal space and signal processing gain of multi-dimensional information joint processing is obtained easier than in 3D signal space.

关键词： system. moving transformed

Induction of Effective Antitumor Immune Response by Combined Administration of hIL-18 and NDV HN

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Chemical Research in Chinese Universities 2011年第5期27卷 836-840页

作者： HUANG Hai-yan MENG Xiang-wei LI Xiao SUN Li-li KAN Shi-fu LIU Lei piao Bing-guo YANG guo-hua WANG Zhuo-yue WANG Yu-hang QI Yan-xin JIN Ning-yi Department of Gastroenterology the First Hospital of Jilin University Changchun 130021 P. R. China Laboratory of Genetic Engineering of PLA Military Veterinary Institute Academy of Military Medical Sciences Changchun 130062 P. R. China Key Laboratory of Jilin Province for Zoonosis Prevention and Control Military Veterinary Institute Academy of Military Medical Sciences Changchun 130062 P. R. China Department of Head and Neck Surgery Tumor Hospital of Jilin Province Changchun 130012 P. R. China Digestive lnternal Medicine Xuzhou Center Hospital Xuzhou 221009 P. R. China

To analyze the antitumor potential and mechanism of action of simultaneous Newcastle disease virus （NDV） hemagglutinin-neuraminidase（HN） and human interleukin 18（hIL-18） gene transfer in C57BL/6 mice with H22 hepatoma,the mouse model with H22 hepatoma was established in C57BL/6 mice, and the antitumor effects of the combined application of NDV HN and hIL-18 were evaluated in vivo. The results show that the growth of established tumors in mice immunized with adenovirus（Ad）-HN in conjunction with Ad-hIL-18 was significantly inhibited compared with that in mice immunized with Ad-HN, Ad-hIL-18 alone, or the empty vector（Ad-mock）. Furthermore, the immunization of mice with Ad-HN in conjunction with Ad-hIL-18 elicited strong natural killer activity and H22 tumor-specific cytotoxic T lymphocyte（CTL） responses in vivo. In addition, T cells from the lymph nodes of mice immunized with Ad-hIL-18 or Ad-HN＋Ad-hIL-18 secreted high levels of the Th1 cytokine IL-2 and interferon-γ （IFN-γ）, indicating that the regression of tumor cells is related to a Th1-type dominant immune response. These results demonstrate that vaccination with NDV HN together with hIL-18 may be a novel and powerful strategy for cancer immunotherapy.

关键词： Newcastle disease virus Human interleukin 18(hlL-18) Hemagglutinin-neuraminidase(HN) Hepatoma Antitumor immunity