Molecular Therapy. Methods & Clinical Development最新文献_第5页

Efficacy of HSV-TK/GCV system suicide gene therapy using SHED expressing modified HSV-TK against lung cancer brain metastases. 表达改良HSV-TK的SHED对肺癌脑转移的自杀基因治疗效果

IF 4.7

Molecular Therapy. Methods & Clinical Development Pub Date : 2022-07-06 eCollection Date: 2022-09-08 DOI: 10.1016/j.omtm.2022.07.001

Tomoya Oishi, Masahiko Ito, Shinichiro Koizumi, Makoto Horikawa, Taisuke Yamamoto, Satoru Yamagishi, Tomohiro Yamasaki, Tetsuro Sameshima, Tetsuro Suzuki, Haruhiko Sugimura, Hiroki Namba, Kazuhiko Kurozumi

{"title":"Efficacy of HSV-TK/GCV system suicide gene therapy using SHED expressing modified HSV-TK against lung cancer brain metastases.","authors":"Tomoya Oishi, Masahiko Ito, Shinichiro Koizumi, Makoto Horikawa, Taisuke Yamamoto, Satoru Yamagishi, Tomohiro Yamasaki, Tetsuro Sameshima, Tetsuro Suzuki, Haruhiko Sugimura, Hiroki Namba, Kazuhiko Kurozumi","doi":"10.1016/j.omtm.2022.07.001","DOIUrl":"https://doi.org/10.1016/j.omtm.2022.07.001","url":null,"abstract":"Lung cancer is one of the most common cancers, and the number of patients with intracranial metastases is increasing. Previously, we developed an enzyme prodrug suicide gene therapy based on the herpes simplex virus thymidine kinase (HSV-TK)/ganciclovir (GCV) system using various mesenchymal stem cells to induce apoptosis in malignant gliomas through bystander killing effects. Here, we describe stem cells from human exfoliated deciduous teeth (SHED) as gene vehicles of the TK/GCV system against a brain metastasis model of non-small cell lung cancer (NSCLC). We introduced the A168H mutant TK (TKA168H) into SHED to establish the therapeutic cells because of the latent toxicity of wild type. SHED expressing TKA168H (SHED-TK) exhibited chemotaxis to the conditioned medium of NSCLC and migrated toward implanted NSCLC in vivo. SHED-TK demonstrated a strong bystander effect in vitro and in vivo and completely eradicated H1299 NSCLC in the brain. SHED-TK cells implanted intratumorally followed by GCV administration significantly suppressed the growth of H1299 and improved survival time. These results indicate that the TKA168H variant is suitable for establishing therapeutic cells and that intratumoral injection of SHED-TK followed by GCV administration may be a useful strategy for therapeutic approaches.","PeriodicalId":517056,"journal":{"name":"Molecular Therapy. Methods & Clinical Development","volume":" ","pages":"253-265"},"PeriodicalIF":4.7,"publicationDate":"2022-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e0/4d/main.PMC9307584.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40633434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Sendai F/HN pseudotyped lentiviral vector transduces human ciliated and non-ciliated airway cells using α 2,3 sialylated receptors. 仙台F/HN假型慢病毒载体利用α 2,3唾液化受体转染人纤毛和非纤毛气道细胞。

IF 4.7

Molecular Therapy. Methods & Clinical Development Pub Date : 2022-07-06 eCollection Date: 2022-09-08 DOI: 10.1016/j.omtm.2022.07.002

Rosie J Munday, Tiziana Coradin, Rachael Nimmo, Yatish Lad, Stephen C Hyde, Kyriacos Mitrophanos, Deborah R Gill

{"title":"Sendai F/HN pseudotyped lentiviral vector transduces human ciliated and non-ciliated airway cells using α 2,3 sialylated receptors.","authors":"Rosie J Munday, Tiziana Coradin, Rachael Nimmo, Yatish Lad, Stephen C Hyde, Kyriacos Mitrophanos, Deborah R Gill","doi":"10.1016/j.omtm.2022.07.002","DOIUrl":"https://doi.org/10.1016/j.omtm.2022.07.002","url":null,"abstract":"A lentiviral vector (LV) pseudotype derived from the fusion (F) and hemagglutinin-neuraminidase (HN) glycoproteins of a murine respirovirus (Sendai virus) facilitates efficient targeting of murine lung in vivo. Since targeting of the human lung will depend upon the availability and distribution of receptors used by F/HN, we investigated transduction of primary human airway cells differentiated at the air-liquid interface (ALI). We observed targeting of human basal, ciliated, goblet, and club cells, and using a combination of sialidase enzymes and lectins, we showed that transduction is dependent on the availability of sialylated glycans, including α2,3 sialylated N-acetyllactosamine (LacNAc). Transduction via F/HN was 300-fold more efficient than another hemagglutinin-based LV pseudotype derived from influenza fowl plague virus (HA Rostock), despite similar efficiency reported in murine airways in vivo. Using specific glycans to inhibit hemagglutination, we showed this could be due to a greater affinity of F/HN for α2,3 sialylated LacNAc. Overall, these results highlight the importance of identifying the receptors used in animal and cell-culture models to predict performance in the human airways. Given the reported prevalence of α2,3 sialylated LacNAc on human pulmonary cells, these results support the suitability of the F/HN pseudotype for human lung gene therapy applications.","PeriodicalId":517056,"journal":{"name":"Molecular Therapy. Methods & Clinical Development","volume":" ","pages":"239-252"},"PeriodicalIF":4.7,"publicationDate":"2022-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40633433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Natural variations in AAVHSC16 significantly reduce liver tropism and maintain broad distribution to periphery and CNS. AAVHSC16的自然变异显著降低肝向性，并保持广泛分布于外周和中枢神经系统。

IF 4.7

Molecular Therapy. Methods & Clinical Development Pub Date : 2022-06-30 eCollection Date: 2022-09-08 DOI: 10.1016/j.omtm.2022.06.013

Laura J Smith, Lindsay A Schulman, Samantha Smith, Laura Van Lieshout, Carmen M Barnes, Liana Behmoiras, Meghan Scarpitti, Monicah Kivaa, Khanh L Duong, Ludo O Benard, Jeff L Ellsworth, Nancy Avila, Deiby Faulkner, April Hayes, Jason Lotterhand, Jose Israel Rivas, Arnold V Sengooba, Alec Tzianabos, Albert B Seymour, Omar L Francone

{"title":"Natural variations in AAVHSC16 significantly reduce liver tropism and maintain broad distribution to periphery and CNS.","authors":"Laura J Smith, Lindsay A Schulman, Samantha Smith, Laura Van Lieshout, Carmen M Barnes, Liana Behmoiras, Meghan Scarpitti, Monicah Kivaa, Khanh L Duong, Ludo O Benard, Jeff L Ellsworth, Nancy Avila, Deiby Faulkner, April Hayes, Jason Lotterhand, Jose Israel Rivas, Arnold V Sengooba, Alec Tzianabos, Albert B Seymour, Omar L Francone","doi":"10.1016/j.omtm.2022.06.013","DOIUrl":"https://doi.org/10.1016/j.omtm.2022.06.013","url":null,"abstract":"Adeno-associated viruses derived from human hematopoietic stem cells (AAVHSCs) are naturally occurring AAVs. Fifteen AAVHSCs have demonstrated broad biodistribution while displaying differences in transduction. We examine the structure-function relationships of these natural amino acid variations on cellular binding. We demonstrate that AAVHSC16 is the only AAVHSC that does not preferentially bind to terminal galactose. AAVHSC16 contains two unique amino acids, 501I and 706C, compared with other AAVHSCs. Through mutagenesis, we determined that residue 501 contributes to the lack of galactose binding. Structural analysis revealed that residue 501 is in proximity to the galactose binding pocket, hence confirming its functional role in galactose binding. Biodistribution analysis of AAVHSC16 indicated significantly less liver tropism in mice and non-human primates compared with other clade F members, likely associated with overall binding differences observed in vitro. AAVHSC16 maintained robust tropism to other key tissues in the peripheral and central nervous systems after intravenous injection, including to the brain, heart, and gastrocnemius. Importantly, AAVHSC16 did not induce elevated liver enzyme levels in non-human primates after intravenous injection at high doses. The unique glycan binding and tropism of AAVHSC16 makes this naturally occurring capsid an attractive candidate for therapies requiring less liver tropism while maintaining broad biodistribution.","PeriodicalId":517056,"journal":{"name":"Molecular Therapy. Methods & Clinical Development","volume":" ","pages":"224-238"},"PeriodicalIF":4.7,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0a/a8/main.PMC9287613.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40633301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

T cells isolated from G-CSF-treated multiple myeloma patients are suitable for the generation of BCMA-directed CAR-T cells. 从g - csf治疗的多发性骨髓瘤患者中分离的T细胞适合生成bcma定向CAR-T细胞。

IF 4.7

Molecular Therapy. Methods & Clinical Development Pub Date : 2022-06-22 eCollection Date: 2022-09-08 DOI: 10.1016/j.omtm.2022.06.010

Anthony M Battram, Aina Oliver-Caldés, Maria Suárez-Lledó, Miquel Lozano, Miquel Bosch I Crespo, Núria Martínez-Cibrián, Joan Cid, David F Moreno, Luis Gerardo Rodríguez-Lobato, Alvaro Urbano-Ispizua, Carlos Fernández de Larrea

{"title":"T cells isolated from G-CSF-treated multiple myeloma patients are suitable for the generation of BCMA-directed CAR-T cells.","authors":"Anthony M Battram, Aina Oliver-Caldés, Maria Suárez-Lledó, Miquel Lozano, Miquel Bosch I Crespo, Núria Martínez-Cibrián, Joan Cid, David F Moreno, Luis Gerardo Rodríguez-Lobato, Alvaro Urbano-Ispizua, Carlos Fernández de Larrea","doi":"10.1016/j.omtm.2022.06.010","DOIUrl":"https://doi.org/10.1016/j.omtm.2022.06.010","url":null,"abstract":"Autologous cell immunotherapy using B cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR)-T cells is an effective novel treatment for multiple myeloma (MM). This therapy has only been used for relapsed and refractory patients, at which stage the endogenous T cells used to produce the CAR-T cells are affected by the immunosuppressive nature of advanced MM and/or side effects of previous therapies. An alternative pool of \"fitter\" T cells is found in leukocytoapheresis products that are routinely collected to obtain hematopoietic progenitor cells for autologous stem cell transplantation (ASCT) early in the treatment of MM. However, to mobilize the progenitor cells, patients are dosed with granulocyte colony-stimulating factor (G-CSF), which is reported to adversely affect T cell proliferation, function, and differentiation. Here, we aimed to first establish whether G-CSF treatment negatively influences T cell phenotype and to ascertain whether previous exposure of T cells to G-CSF is deleterious for anti-BCMA CAR-T cells. We observed that G-CSF had a minimal impact on T cell phenotype when added in vitro or administered to patients. Moreover, we found that CAR-T cell fitness and anti-tumor activity were unaffected when generated from G-CSF-exposed T cells. Overall, we showed that ASCT apheresis products are a suitable source of T cells for anti-BCMA CAR-T cell manufacture.","PeriodicalId":517056,"journal":{"name":"Molecular Therapy. Methods & Clinical Development","volume":" ","pages":"207-223"},"PeriodicalIF":4.7,"publicationDate":"2022-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40633302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Emerging therapeutic potential of adeno-associated virus-mediated gene therapy in liver fibrosis. 腺相关病毒介导的肝纤维化基因治疗的新治疗潜力。

IF 4.7

Molecular Therapy. Methods & Clinical Development Pub Date : 2022-06-22 eCollection Date: 2022-09-08 DOI: 10.1016/j.omtm.2022.06.009

Fang-Tian Bu, Peng-Cheng Jia, Yan Zhu, Ya-Ru Yang, Hong-Wu Meng, Yi-Hui Bi, Cheng Huang, Jun Li

{"title":"Emerging therapeutic potential of adeno-associated virus-mediated gene therapy in liver fibrosis.","authors":"Fang-Tian Bu, Peng-Cheng Jia, Yan Zhu, Ya-Ru Yang, Hong-Wu Meng, Yi-Hui Bi, Cheng Huang, Jun Li","doi":"10.1016/j.omtm.2022.06.009","DOIUrl":"https://doi.org/10.1016/j.omtm.2022.06.009","url":null,"abstract":"Liver fibrosis is a wound-healing response that results from various chronic damages. If the causes of damage are not removed or effective treatments are not given in a timely manner, it will progress to cirrhosis, even liver cancer. Currently, there are no specific medical therapies for liver fibrosis. Adeno-associated virus (AAV)-mediated gene therapy, one of the frontiers of modern medicine, has gained more attention in many fields due to its high safety profile, low immunogenicity, long-term efficacy in mediating gene expression, and increasingly known tropism. Notably, increasing evidence suggests a promising therapeutic potential for AAV-mediated gene therapy in different liver fibrosis models, which helps to correct abnormally changed target genes in the process of fibrosis and improve liver fibrosis at the molecular level. Moreover, the addition of cell-specific promoters to the genome of recombinant AAV helps to limit gene expression in specific cells, thereby producing better therapeutic efficacy in liver fibrosis. However, animal models are considered to be powerless predictive of tissue tropism, immunogenicity, and genotoxic risks in humans. Thus, AAV-mediated gene therapy will face many challenges. This review systemically summarizes the recent advances of AAV-mediated gene therapy in liver fibrosis, especially focusing on cellular and molecular mechanisms of transferred genes, and presents prospective challenges.","PeriodicalId":517056,"journal":{"name":"Molecular Therapy. Methods & Clinical Development","volume":" ","pages":"191-206"},"PeriodicalIF":4.7,"publicationDate":"2022-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cb/18/main.PMC9271983.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40610949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Erratum: Long-Term Metabolic Correction of Phenylketonuria by AAV-Delivered Phenylalanine Amino Lyase. 误读:aav递送的苯丙氨酸解氨基酶对苯丙酮尿的长期代谢纠正。

IF 4.7

Molecular Therapy. Methods & Clinical Development Pub Date : 2022-06-17 eCollection Date: 2022-09-08 DOI: 10.1016/j.omtm.2022.06.008

Rui Tao, Lin Xiao, Lifang Zhou, Zhaoyue Zheng, Jie Long, Lixing Zhou, Minghai Tang, Biao Dong, Shaohua Yao

引用次数: 0

Liver gene therapy: The magic bullet for the sick lung. 肝脏基因治疗:治疗肺部疾病的灵丹妙药。

IF 4.7

Molecular Therapy. Methods & Clinical Development Pub Date : 2022-06-15 eCollection Date: 2022-09-08 DOI: 10.1016/j.omtm.2022.05.004

Nicola Brunetti-Pierri

引用次数: 0

Evaluation of parameters for efficient purification and long-term storage of herpes simplex virus-based vectors. 单纯疱疹病毒载体高效纯化和长期储存参数的评价。

IF 4.7

Molecular Therapy. Methods & Clinical Development Pub Date : 2022-06-13 eCollection Date: 2022-09-08 DOI: 10.1016/j.omtm.2022.06.007

Seiji Kuroda, Yoshitaka Miyagawa, Makoto Sukegawa, Taro Tomono, Motoko Yamamoto, Kumi Adachi, Gianluca Verlengia, William F Goins, Justus B Cohen, Joseph C Glorioso, Takashi Okada

{"title":"Evaluation of parameters for efficient purification and long-term storage of herpes simplex virus-based vectors.","authors":"Seiji Kuroda, Yoshitaka Miyagawa, Makoto Sukegawa, Taro Tomono, Motoko Yamamoto, Kumi Adachi, Gianluca Verlengia, William F Goins, Justus B Cohen, Joseph C Glorioso, Takashi Okada","doi":"10.1016/j.omtm.2022.06.007","DOIUrl":"https://doi.org/10.1016/j.omtm.2022.06.007","url":null,"abstract":"Replication competent oncolytic herpes simplex virus (HSV) vectors have been used extensively to treat solid tumors with promising results. However, highly defective HSV vectors will be needed for applications that require sustained therapeutic gene expression in the absence of vector-related toxicity or inflammation. These vectors require complementing cell lines for their manufacture, creating significant challenges to achieve high yields of infectious virus particles. We recently described an improved upstream process for the production of a non-cytotoxic HSV vector for gene therapy applications. Here, we sought to optimize the downstream conditions for purification and long-term storage of the same vector, JΔNI5. We compared different methods to remove cellular impurities and concentrate the vector by monitoring both physical and biological titers, resulting in the establishment of optimal conditions for vector production. To optimize the long-term storage parameters for non-cytotoxic HSV vectors, we evaluated vector stability at low temperature and sensitivity to freeze-thaw cycles. We report that suboptimal purification and storage methods resulted in loss of vector viability. Our results describe effective and reproducible protocols for purification and storage of HSV vectors for pre-clinical studies.","PeriodicalId":517056,"journal":{"name":"Molecular Therapy. Methods & Clinical Development","volume":" ","pages":"132-143"},"PeriodicalIF":4.7,"publicationDate":"2022-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/40/20/main.PMC9249677.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40568523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Erratum: Cell-penetrating peptides enhance the transduction of adeno-associated virus serotype 9 in the central nervous system. 勘误:细胞穿透肽增强9型血清腺相关病毒在中枢神经系统的转导。

IF 4.7

Molecular Therapy. Methods & Clinical Development Pub Date : 2022-06-10 eCollection Date: 2022-09-08 DOI: 10.1016/j.omtm.2021.11.014

Yuan Meng, Dong Sun, Yiyan Qin, Xiaoyi Dong, Guangzuo Luo, Ying Liu

引用次数: 0

Amelioration of experimental tendinopathy by lentiviral CD44 gene therapy targeting senescence-associated secretory phenotypes. 针对衰老相关分泌表型的慢病毒CD44基因治疗改善实验性肌腱病变。

IF 4.7

Molecular Therapy. Methods & Clinical Development Pub Date : 2022-06-10 eCollection Date: 2022-09-08 DOI: 10.1016/j.omtm.2022.06.006

Shih-Yao Chen, I-Ming Jou, Po-Yen Ko, Kai-Lan Hsu, Wei-Ren Su, Li-Chieh Kuo, Pei-Yuan Lee, Chao-Liang Wu, Po-Ting Wu

{"title":"Amelioration of experimental tendinopathy by lentiviral CD44 gene therapy targeting senescence-associated secretory phenotypes.","authors":"Shih-Yao Chen, I-Ming Jou, Po-Yen Ko, Kai-Lan Hsu, Wei-Ren Su, Li-Chieh Kuo, Pei-Yuan Lee, Chao-Liang Wu, Po-Ting Wu","doi":"10.1016/j.omtm.2022.06.006","DOIUrl":"https://doi.org/10.1016/j.omtm.2022.06.006","url":null,"abstract":"CD44 exerts anti-senescence effects in many disease models. We examined senescence in tendinopathy and the effect of CD44 on senescence-associated secretory phenotypes (SASPs). Senescent markers were determined in human tendinopathic long head of bicep (LHB) and normal hamstring tendons. CD44 gene transfer in rat tendinopathic tenocytes stimulated with interleukin (IL)-1β and a rat Achilles tendinopathy model were performed using lentiviral vectors. Expression levels of p53, p21, and p16 and senescence-associated β-galactosidase (SA-β-gal) activity were positively correlated with the severity of human tendinopathy and were higher in rat and human tendinopathic tenocytes than in normal controls. CD44 overexpressed tenocyte transfectants exhibited reduced levels of IL-6, matrix metalloproteinases (MMPs), cyclooxygenase (COX)-2, p53, p21, p16, SA-β-gal, and phospho-nuclear factor (NF)-κB, whereas their collagen type I alpha 1 (COL1A1) and tenomodulin (tnmd) levels were increased when compared with control transfectants under IL-1β-stimulated conditions. In the animal model, CD44 overexpression lowered the ultrasound and histology scores and expression levels of the senescent and SASP markers COX-2 and phospho-NF-κB. Bromodeoxyuridine (BrdU)- and tnmd-positive cell numbers were increased in the LVCD44-transduced tendinopathic tendons. Senescence is positively correlated with tendinopathic severity, and CD44 overexpression may protect the tendinopathic tendons from SASPs via anti-inflammation and maintenance of extracellular matrix homeostasis.","PeriodicalId":517056,"journal":{"name":"Molecular Therapy. Methods & Clinical Development","volume":" ","pages":"157-168"},"PeriodicalIF":4.7,"publicationDate":"2022-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/99/fd/main.PMC9254001.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40514387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2