How immune cells are spatiotemporally coordinated in the lung to effectively monitor, respond to, and resolve infection and inflammation in primed form needs to be fully illustrated. Here we apply immunocartography, a high-resolution technique that integrates spatial and single-cell RNA sequencing (scRNA-seq) through deconvolution and co-localization analyses, to the SARS-CoV-2-infected Syrian hamster model. We generate a comprehensive transcriptome map of the whole process of pulmonary infection from physiological condition, infection initiation, severe pneumonia to natural recovery at organ scale and single-cell resolution, with 142,965 cells and 45 lung lobes from 25 hamsters at 5 time points. Integrative analysis identifies that alveolar dendritic cell-T cell immunity hubs, where Ccr7+Ido1+ dendritic cells, Cd160+Cd8+ T cells, and Tnfrsf4+Cd4+ T cells physiologically co-localize, rapidly expand during SARS-CoV-2 infection, eliminate SARS-CoV-2 with the aid of Slamf9+ macrophages, and then restore to physiological levels after viral clearance. We verify the presence of these cell subpopulations in the immunity hubs in normal and SARS-CoV-2-infected hACE2 mouse models, as well as in publicly available human scRNA-seq datasets, demonstrating the potential broad relevance of our findings in lung immunity.
{"title":"Single-cell spatiotemporal analysis reveals alveolar dendritic cell-T cell immunity hubs defending against pulmonary infection.","authors":"Boyi Cong, Xuan Dong, Zongheng Yang, Pin Yu, Yangyang Chai, Jiaqi Liu, Meihan Zhang, Yupeng Zang, Jingmin Kang, Yu Feng, Yi Liu, Weimin Feng, Dehe Wang, Wei Deng, Fengdi Li, Zhiqi Song, Ziqiao Wang, Xiaosu Chen, Hua Qin, Qinyi Yu, Zhiqing Li, Shuxun Liu, Xun Xu, Nanshan Zhong, Xianwen Ren, Chuan Qin, Longqi Liu, Jian Wang, Xuetao Cao","doi":"10.1038/s41421-024-00733-5","DOIUrl":"10.1038/s41421-024-00733-5","url":null,"abstract":"<p><p>How immune cells are spatiotemporally coordinated in the lung to effectively monitor, respond to, and resolve infection and inflammation in primed form needs to be fully illustrated. Here we apply immunocartography, a high-resolution technique that integrates spatial and single-cell RNA sequencing (scRNA-seq) through deconvolution and co-localization analyses, to the SARS-CoV-2-infected Syrian hamster model. We generate a comprehensive transcriptome map of the whole process of pulmonary infection from physiological condition, infection initiation, severe pneumonia to natural recovery at organ scale and single-cell resolution, with 142,965 cells and 45 lung lobes from 25 hamsters at 5 time points. Integrative analysis identifies that alveolar dendritic cell-T cell immunity hubs, where Ccr7<sup>+</sup>Ido1<sup>+</sup> dendritic cells, Cd160<sup>+</sup>Cd8<sup>+</sup> T cells, and Tnfrsf4<sup>+</sup>Cd4<sup>+</sup> T cells physiologically co-localize, rapidly expand during SARS-CoV-2 infection, eliminate SARS-CoV-2 with the aid of Slamf9<sup>+</sup> macrophages, and then restore to physiological levels after viral clearance. We verify the presence of these cell subpopulations in the immunity hubs in normal and SARS-CoV-2-infected hACE2 mouse models, as well as in publicly available human scRNA-seq datasets, demonstrating the potential broad relevance of our findings in lung immunity.</p>","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"10 1","pages":"103"},"PeriodicalIF":13.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
How the lung achieves immune homeostasis after a pulmonary infection is not fully understood. Here, we analyzed the spatiotemporal changes in the lungs over a 2-week natural recovery from severe pneumonia in a Syrian hamster model of SARS-CoV-2 infection. We find that SARS-CoV-2 infects multiple cell types and causes massive cell death at the early stage, including alveolar macrophages. We identify a group of monocyte-derived Slamf9+ macrophages, which are induced after SARS-CoV-2 infection and resistant to impairment caused by SARS-CoV-2. Slamf9+ macrophages contain SARS-CoV-2, recruit and interact with Isg12+Cst7+ neutrophils to clear the viruses. After viral clearance, Slamf9+ macrophages differentiate into Trem2+ and Fbp1+ macrophages, contributing to inflammation resolution at the late stage, and finally replenish alveolar macrophages. These findings are validated in a SARS-CoV-2-infected hACE2 mouse model and confirmed with publicly available human autopsy single-cell RNA-seq data, demonstrating the potential role of Slamf9+ macrophages and their coordination with neutrophils in post-injury tissue repair and inflammation resolution.
{"title":"Single-cell spatiotemporal analysis of the lungs reveals Slamf9<sup>+</sup> macrophages involved in viral clearance and inflammation resolution.","authors":"Boyi Cong, Xuan Dong, Zongheng Yang, Pin Yu, Yangyang Chai, Jiaqi Liu, Meihan Zhang, Yupeng Zang, Jingmin Kang, Yu Feng, Yi Liu, Weimin Feng, Dehe Wang, Wei Deng, Fengdi Li, Zhiqi Song, Ziqiao Wang, Xiaosu Chen, Hua Qin, Qinyi Yu, Zhiqing Li, Shuxun Liu, Xun Xu, Nanshan Zhong, Xianwen Ren, Chuan Qin, Longqi Liu, Jian Wang, Xuetao Cao","doi":"10.1038/s41421-024-00734-4","DOIUrl":"10.1038/s41421-024-00734-4","url":null,"abstract":"<p><p>How the lung achieves immune homeostasis after a pulmonary infection is not fully understood. Here, we analyzed the spatiotemporal changes in the lungs over a 2-week natural recovery from severe pneumonia in a Syrian hamster model of SARS-CoV-2 infection. We find that SARS-CoV-2 infects multiple cell types and causes massive cell death at the early stage, including alveolar macrophages. We identify a group of monocyte-derived Slamf9<sup>+</sup> macrophages, which are induced after SARS-CoV-2 infection and resistant to impairment caused by SARS-CoV-2. Slamf9<sup>+</sup> macrophages contain SARS-CoV-2, recruit and interact with Isg12<sup>+</sup>Cst7<sup>+</sup> neutrophils to clear the viruses. After viral clearance, Slamf9<sup>+</sup> macrophages differentiate into Trem2<sup>+</sup> and Fbp1<sup>+</sup> macrophages, contributing to inflammation resolution at the late stage, and finally replenish alveolar macrophages. These findings are validated in a SARS-CoV-2-infected hACE2 mouse model and confirmed with publicly available human autopsy single-cell RNA-seq data, demonstrating the potential role of Slamf9<sup>+</sup> macrophages and their coordination with neutrophils in post-injury tissue repair and inflammation resolution.</p>","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"10 1","pages":"104"},"PeriodicalIF":13.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-15DOI: 10.1038/s41421-024-00730-8
Shuai Zhang, Xue Feng, Chong-Hui Li, Yuan-Ming Zheng, Meng-Ya Wang, Jun-Jie Li, Yun-Peng Dai, Naihe Jing, Jia-Wei Zhou, Gang Wang
Gaining the molecular understanding for myelination development and regeneration has been a long-standing goal in neurological research. Mutations in the transcription cofactor Mediator Med23 subunit are often associated with intellectual disability and white matter defects, although the precise functions and mechanisms of Mediator in myelination remain unclear. In this study, we generated a mouse model carrying an Med23Q649R mutation that has been identified in a patient with hypomyelination features. The MED23Q649R mouse model develops white matter thinning and cognitive decline, mimicking common clinical phenotypes. Further, oligodendrocyte-lineage specific Med23 knockout mice verified the important function of MED23 in regulating central nervous system myelination and postinjury remyelination. Utilizing the in vitro cellular differentiation assay, we found that the oligodendrocyte progenitor cells, either carrying the Q649R mutation or lacking Med23, exhibit significant deficits in their capacity to differentiate into mature oligodendrocytes. Gene profiling combined with reporter assays demonstrated that Mediator Med23 controls Sp1-directed gene programs related to oligodendrocyte differentiation and cholesterol metabolism. Integrative analysis demonstrated that Med23 modulates the P300 binding to Sp1-targeted genes, thus orchestrating the H3K27 acetylation and enhancer activation for the oligodendrocyte lineage progression. Collectively, our findings identified the critical role for the Mediator Med23 in oligodendrocyte fate determination and provide mechanistic insights into the myelination pathogenesis associated with MED23 mutations.
{"title":"Mediator MED23 controls oligodendrogenesis and myelination by modulating Sp1/P300-directed gene programs.","authors":"Shuai Zhang, Xue Feng, Chong-Hui Li, Yuan-Ming Zheng, Meng-Ya Wang, Jun-Jie Li, Yun-Peng Dai, Naihe Jing, Jia-Wei Zhou, Gang Wang","doi":"10.1038/s41421-024-00730-8","DOIUrl":"https://doi.org/10.1038/s41421-024-00730-8","url":null,"abstract":"<p><p>Gaining the molecular understanding for myelination development and regeneration has been a long-standing goal in neurological research. Mutations in the transcription cofactor Mediator Med23 subunit are often associated with intellectual disability and white matter defects, although the precise functions and mechanisms of Mediator in myelination remain unclear. In this study, we generated a mouse model carrying an Med23<sup>Q649R</sup> mutation that has been identified in a patient with hypomyelination features. The MED23<sup>Q649R</sup> mouse model develops white matter thinning and cognitive decline, mimicking common clinical phenotypes. Further, oligodendrocyte-lineage specific Med23 knockout mice verified the important function of MED23 in regulating central nervous system myelination and postinjury remyelination. Utilizing the in vitro cellular differentiation assay, we found that the oligodendrocyte progenitor cells, either carrying the Q649R mutation or lacking Med23, exhibit significant deficits in their capacity to differentiate into mature oligodendrocytes. Gene profiling combined with reporter assays demonstrated that Mediator Med23 controls Sp1-directed gene programs related to oligodendrocyte differentiation and cholesterol metabolism. Integrative analysis demonstrated that Med23 modulates the P300 binding to Sp1-targeted genes, thus orchestrating the H3K27 acetylation and enhancer activation for the oligodendrocyte lineage progression. Collectively, our findings identified the critical role for the Mediator Med23 in oligodendrocyte fate determination and provide mechanistic insights into the myelination pathogenesis associated with MED23 mutations.</p>","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"10 1","pages":"102"},"PeriodicalIF":13.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11473658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1038/s41421-024-00713-9
Yuehua Liu, Xiaoqian Nie, Xingyun Yao, Huafeng Shou, Yang Yuan, Yun Ge, Xiangmin Tong, Hsiang-Ying Lee, Xiaofei Gao
Mature erythrocytes are known to lack major histocompatibility complex (MHC) proteins. However, the presence of MHC molecules on erythrocytes has been occasionally reported, though without a defined function. In this study, we designed erythrocyte conjugated solely with a fusion protein consisting of an antigenic peptide linked to MHC class I (MHC-I) protein, termed MHC-I‒Ery. The modified erythrocyte, decorated with the peptide derived from human papillomavirus (HPV) 16 oncoprotein E6/E7, effectively activated antigen-specific CD8+ T cells in peripheral blood mononuclear cells (PBMCs) from HPV16+ cervical cancer patients. Additionally, MHC-I‒Ery monotherapy was shown to inhibit antigen-positive tumor growth in mice. This treatment immediately activated CD8+ T cells and reduced suppressive myeloid cells in the spleen, leading to systemic anti-tumor activity. Safety and tolerability evaluations of MHC-I‒Ery in non-human primates further supported its clinical potential. Our results first demonstrated that erythrocytes equipped solely with antigen peptide‒MHC-I complexes can robustly stimulate the immune system, suggesting a novel and promising approach for advancing cancer immunotherapy.
众所周知,成熟的红细胞缺乏主要组织相容性复合体(MHC)蛋白。不过,偶尔也有报道称红细胞上存在 MHC 分子,但没有明确的功能。在这项研究中,我们设计了仅与一种融合蛋白结合的红细胞,这种融合蛋白由与 MHC I 类蛋白质(MHC-I)相连的抗原肽组成,被称为 MHC-I-Ery。经修饰的红细胞上装饰有来自人类乳头瘤病毒(HPV)16 肿瘤蛋白 E6/E7 的多肽,能有效激活 HPV16+ 宫颈癌患者外周血单核细胞(PBMC)中的抗原特异性 CD8+ T 细胞。此外,MHC-I-Ery 单药疗法还能抑制抗原阳性肿瘤在小鼠体内的生长。这种疗法能立即激活 CD8+ T 细胞,减少脾脏中的抑制性髓细胞,从而产生全身抗肿瘤活性。MHC-I-Ery在非人灵长类动物中的安全性和耐受性评估进一步证实了它的临床潜力。我们的研究结果首次证明了红细胞仅配备抗原肽-MHC-I 复合物就能强有力地刺激免疫系统,为推进癌症免疫疗法提供了一种新颖而有前景的方法。
{"title":"Developing an erythrocyte‒MHC-I conjugate for cancer treatment.","authors":"Yuehua Liu, Xiaoqian Nie, Xingyun Yao, Huafeng Shou, Yang Yuan, Yun Ge, Xiangmin Tong, Hsiang-Ying Lee, Xiaofei Gao","doi":"10.1038/s41421-024-00713-9","DOIUrl":"10.1038/s41421-024-00713-9","url":null,"abstract":"<p><p>Mature erythrocytes are known to lack major histocompatibility complex (MHC) proteins. However, the presence of MHC molecules on erythrocytes has been occasionally reported, though without a defined function. In this study, we designed erythrocyte conjugated solely with a fusion protein consisting of an antigenic peptide linked to MHC class I (MHC-I) protein, termed MHC-I‒Ery. The modified erythrocyte, decorated with the peptide derived from human papillomavirus (HPV) 16 oncoprotein E6/E7, effectively activated antigen-specific CD8<sup>+</sup> T cells in peripheral blood mononuclear cells (PBMCs) from HPV16<sup>+</sup> cervical cancer patients. Additionally, MHC-I‒Ery monotherapy was shown to inhibit antigen-positive tumor growth in mice. This treatment immediately activated CD8<sup>+</sup> T cells and reduced suppressive myeloid cells in the spleen, leading to systemic anti-tumor activity. Safety and tolerability evaluations of MHC-I‒Ery in non-human primates further supported its clinical potential. Our results first demonstrated that erythrocytes equipped solely with antigen peptide‒MHC-I complexes can robustly stimulate the immune system, suggesting a novel and promising approach for advancing cancer immunotherapy.</p>","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"10 1","pages":"99"},"PeriodicalIF":13.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11443136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-24DOI: 10.1038/s41421-024-00719-3
Fan Zhai, Siming Kong, Shi Song, Qianying Guo, Ling Ding, Jiaqi Zhang, Nan Wang, Ying Kuo, Shuo Guan, Peng Yuan, Liying Yan, Zhiqiang Yan, Jie Qiao
Pre-implantation genetic testing for aneuploidy (PGT-A) is used in approximately half of in vitro fertilization cycles. Given the limited understanding of the genetics of human embryos, the current use of PGT-A is based on biologically uncertain assumptions and unvalidated guidelines, leading to the possibility of disposing of embryos with pregnancy potential. We isolated and sequenced all single cells (1133) from in vitro cultured 20 human blastocysts. We found that all blastocysts exhibited mosaicism with mitotic-induced aneuploid cells and showed an ~25% aneuploidy rate per embryo. Moreover, 70% (14/20) of blastocysts contained 'chromosome-complementary' cells, suggesting genetic mosaicism is underestimated in routine PGT-A. Additionally, the analysis of 20,945 single cells from day 8-14 embryos (in vitro cultured) and embryonic/fetal organs showed that 97% of the analyzed embryos/organs were mosaic. Over 96% of their aneuploid cells harbored ≤ 2 chromosome errors. Our findings have revealed a high prevalence of mosaicism in human embryos.
{"title":"Human embryos harbor complex mosaicism with broad presence of aneuploid cells during early development.","authors":"Fan Zhai, Siming Kong, Shi Song, Qianying Guo, Ling Ding, Jiaqi Zhang, Nan Wang, Ying Kuo, Shuo Guan, Peng Yuan, Liying Yan, Zhiqiang Yan, Jie Qiao","doi":"10.1038/s41421-024-00719-3","DOIUrl":"10.1038/s41421-024-00719-3","url":null,"abstract":"<p><p>Pre-implantation genetic testing for aneuploidy (PGT-A) is used in approximately half of in vitro fertilization cycles. Given the limited understanding of the genetics of human embryos, the current use of PGT-A is based on biologically uncertain assumptions and unvalidated guidelines, leading to the possibility of disposing of embryos with pregnancy potential. We isolated and sequenced all single cells (1133) from in vitro cultured 20 human blastocysts. We found that all blastocysts exhibited mosaicism with mitotic-induced aneuploid cells and showed an ~25% aneuploidy rate per embryo. Moreover, 70% (14/20) of blastocysts contained 'chromosome-complementary' cells, suggesting genetic mosaicism is underestimated in routine PGT-A. Additionally, the analysis of 20,945 single cells from day 8-14 embryos (in vitro cultured) and embryonic/fetal organs showed that 97% of the analyzed embryos/organs were mosaic. Over 96% of their aneuploid cells harbored ≤ 2 chromosome errors. Our findings have revealed a high prevalence of mosaicism in human embryos.</p>","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"10 1","pages":"98"},"PeriodicalIF":13.0,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11420220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-17DOI: 10.1038/s41421-024-00715-7
Wenxiao Yang, Luo Hong, Linwei Guo, Yunjin Wang, Xiangchen Han, Boyue Han, Zheng Xing, Guoliang Zhang, Hongxia Zhou, Chao Chen, Hong Ling, Zhimin Shao, Xin Hu
Metabolic dysregulation is prominent in triple-negative breast cancer (TNBC), yet therapeutic strategies targeting cancer metabolism are limited. Here, utilizing multiomics data from our TNBC cohort (n = 465), we demonstrated widespread splicing deregulation and increased spliceosome abundance in the glycolytic TNBC subtype. We identified SNRNP200 as a crucial mediator of glucose-driven metabolic reprogramming. Mechanistically, glucose induces acetylation at SNRNP200 K1610, preventing its proteasomal degradation. Augmented SNRNP200 then facilitates splicing key metabolic enzyme-encoding genes (GAPDH, ALDOA, and GSS), leading to increased lactic acid and glutathione production. Targeting SNRNP200 with antisense oligonucleotide therapy impedes tumor metabolism and enhances the efficacy of anti-PD-1 therapy by activating intratumoral CD8+ T cells while suppressing regulatory T cells. Clinically, higher SNRNP200 levels indicate an inferior response to immunotherapy in glycolytic TNBCs. Overall, our study revealed the intricate interplay between RNA splicing and metabolic dysregulation, suggesting an innovative combination strategy for immunotherapy in glycolytic TNBCs.
{"title":"Targeting SNRNP200-induced splicing dysregulation offers an immunotherapy opportunity for glycolytic triple-negative breast cancer","authors":"Wenxiao Yang, Luo Hong, Linwei Guo, Yunjin Wang, Xiangchen Han, Boyue Han, Zheng Xing, Guoliang Zhang, Hongxia Zhou, Chao Chen, Hong Ling, Zhimin Shao, Xin Hu","doi":"10.1038/s41421-024-00715-7","DOIUrl":"https://doi.org/10.1038/s41421-024-00715-7","url":null,"abstract":"<p>Metabolic dysregulation is prominent in triple-negative breast cancer (TNBC), yet therapeutic strategies targeting cancer metabolism are limited. Here, utilizing multiomics data from our TNBC cohort (<i>n</i> = 465), we demonstrated widespread splicing deregulation and increased spliceosome abundance in the glycolytic TNBC subtype. We identified SNRNP200 as a crucial mediator of glucose-driven metabolic reprogramming. Mechanistically, glucose induces acetylation at SNRNP200 K1610, preventing its proteasomal degradation. Augmented SNRNP200 then facilitates splicing key metabolic enzyme-encoding genes (<i>GAPDH</i>, <i>ALDOA</i>, and <i>GSS</i>), leading to increased lactic acid and glutathione production. Targeting SNRNP200 with antisense oligonucleotide therapy impedes tumor metabolism and enhances the efficacy of anti-PD-1 therapy by activating intratumoral CD8<sup>+</sup> T cells while suppressing regulatory T cells. Clinically, higher SNRNP200 levels indicate an inferior response to immunotherapy in glycolytic TNBCs. Overall, our study revealed the intricate interplay between RNA splicing and metabolic dysregulation, suggesting an innovative combination strategy for immunotherapy in glycolytic TNBCs.</p>","PeriodicalId":9674,"journal":{"name":"Cell Discovery","volume":"16 1","pages":""},"PeriodicalIF":33.5,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142255888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}