Cell systemsPub Date : 2025-05-21Epub Date: 2025-05-07DOI: 10.1016/j.cels.2025.101292
Yiyi Liu, Yu-Yu Cheng, Jaron Thompson, Zhichao Zhou, Eugenio I Vivas, Matthew F Warren, Julie M DuClos, Karthik Anantharaman, Federico E Rey, Ophelia S Venturelli
{"title":"Decoding the role of the arginine dihydrolase pathway in shaping human gut community assembly and health-relevant metabolites.","authors":"Yiyi Liu, Yu-Yu Cheng, Jaron Thompson, Zhichao Zhou, Eugenio I Vivas, Matthew F Warren, Julie M DuClos, Karthik Anantharaman, Federico E Rey, Ophelia S Venturelli","doi":"10.1016/j.cels.2025.101292","DOIUrl":"10.1016/j.cels.2025.101292","url":null,"abstract":"<p><p>The arginine dihydrolase pathway (arc operon) provides a metabolic niche by transforming arginine into metabolic byproducts. We investigate the role of the arc operon in probiotic Escherichia coli Nissle 1917 on human gut community assembly and health-relevant metabolite profiles. By stabilizing environmental pH, the arc operon reduces variability in community composition in response to pH perturbations and frequently enhances butyrate production in synthetic communities. We use a tailored machine learning model for microbiomes to predict community assembly in response to variation in initial media pH and arc operon activity. This model uncovers the pH- and arc operon-dependent interactions shaping community assembly. Human gut species display altered colonization dynamics in response to the arc operon in the murine gut. In sum, our framework to quantify the contribution of a specific pathway to microbial community assembly and metabolite production can reveal new engineering strategies. A record of this paper's transparent peer review process is included in the supplemental information.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101292"},"PeriodicalIF":0.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell systemsPub Date : 2025-05-21DOI: 10.1016/j.cels.2025.101295
Michael A Skinnider, Katja Luck, M Shahid Mukhtar, Martin Garrido-Rodriguez, Julio Saez-Rodriguez, Jolanda van Leeuwen, Pedro Beltrao, Anne-Ruxandra Carvunis, Mikko Taipale, Andrew Emili, Martha L Bulyk, Nevan J Krogan
{"title":"What is the current bottleneck in mapping molecular interaction networks?","authors":"Michael A Skinnider, Katja Luck, M Shahid Mukhtar, Martin Garrido-Rodriguez, Julio Saez-Rodriguez, Jolanda van Leeuwen, Pedro Beltrao, Anne-Ruxandra Carvunis, Mikko Taipale, Andrew Emili, Martha L Bulyk, Nevan J Krogan","doi":"10.1016/j.cels.2025.101295","DOIUrl":"https://doi.org/10.1016/j.cels.2025.101295","url":null,"abstract":"","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":"16 5","pages":"101295"},"PeriodicalIF":0.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell systemsPub Date : 2025-05-21Epub Date: 2025-04-10DOI: 10.1016/j.cels.2025.101260
Caleb R Perez, Andrea Garmilla, Avlant Nilsson, Hratch M Baghdassarian, Khloe S Gordon, Louise G Lima, Blake E Smith, Marcela V Maus, Douglas A Lauffenburger, Michael E Birnbaum
{"title":"Library-based single-cell analysis of CAR signaling reveals drivers of in vivo persistence.","authors":"Caleb R Perez, Andrea Garmilla, Avlant Nilsson, Hratch M Baghdassarian, Khloe S Gordon, Louise G Lima, Blake E Smith, Marcela V Maus, Douglas A Lauffenburger, Michael E Birnbaum","doi":"10.1016/j.cels.2025.101260","DOIUrl":"10.1016/j.cels.2025.101260","url":null,"abstract":"<p><p>The anti-tumor function of engineered T cells expressing chimeric antigen receptors (CARs) is dependent on signals transduced through intracellular signaling domains (ICDs). Different ICDs are known to drive distinct phenotypes, but systematic investigations into how ICD architectures direct T cell function-particularly at the molecular level-are lacking. Here, we use single-cell sequencing to map diverse signaling inputs to transcriptional outputs, focusing on a defined library of clinically relevant ICD architectures. Informed by these observations, we functionally characterize transcriptionally distinct ICD variants across various contexts to build comprehensive maps from ICD composition to phenotypic output. We identify a unique tonic signaling signature associated with a subset of ICD architectures that drives durable in vivo persistence and efficacy in liquid, but not solid, tumors. Our findings work toward decoding CAR signaling design principles, with implications for the rational design of next-generation ICD architectures optimized for in vivo function.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101260"},"PeriodicalIF":0.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12097926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144058812","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}
Cell systemsPub Date : 2025-05-21Epub Date: 2025-04-11DOI: 10.1016/j.cels.2025.101261
Tancredi Massimo Pentimalli, Simon Schallenberg, Daniel León-Periñán, Ivano Legnini, Ilan Theurillat, Gwendolin Thomas, Anastasiya Boltengagen, Sonja Fritzsche, Jose Nimo, Lukas Ruff, Gabriel Dernbach, Philipp Jurmeister, Sarah Murphy, Mark T Gregory, Yan Liang, Michelangelo Cordenonsi, Stefano Piccolo, Fabian Coscia, Andrew Woehler, Nikos Karaiskos, Frederick Klauschen, Nikolaus Rajewsky
{"title":"Combining spatial transcriptomics and ECM imaging in 3D for mapping cellular interactions in the tumor microenvironment.","authors":"Tancredi Massimo Pentimalli, Simon Schallenberg, Daniel León-Periñán, Ivano Legnini, Ilan Theurillat, Gwendolin Thomas, Anastasiya Boltengagen, Sonja Fritzsche, Jose Nimo, Lukas Ruff, Gabriel Dernbach, Philipp Jurmeister, Sarah Murphy, Mark T Gregory, Yan Liang, Michelangelo Cordenonsi, Stefano Piccolo, Fabian Coscia, Andrew Woehler, Nikos Karaiskos, Frederick Klauschen, Nikolaus Rajewsky","doi":"10.1016/j.cels.2025.101261","DOIUrl":"10.1016/j.cels.2025.101261","url":null,"abstract":"<p><p>Tumors are complex ecosystems composed of malignant and non-malignant cells embedded in a dynamic extracellular matrix (ECM). In the tumor microenvironment, molecular phenotypes are controlled by cell-cell and ECM interactions in 3D cellular neighborhoods (CNs). While their inhibition can impede tumor progression, routine molecular tumor profiling fails to capture cellular interactions. Single-cell spatial transcriptomics (ST) maps receptor-ligand interactions but usually remains limited to 2D tissue sections and lacks ECM readouts. Here, we integrate 3D ST with ECM imaging in serial sections from one clinical lung carcinoma to systematically quantify molecular states, cell-cell interactions, and ECM remodeling in CN. Our integrative analysis pinpointed known immune escape and tumor invasion mechanisms, revealing several druggable drivers of tumor progression in the patient under study. This proof-of-principle study highlights the potential of in-depth CN profiling in routine clinical samples to inform microenvironment-directed therapies. A record of this paper's transparent peer review process is included in the supplemental information.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101261"},"PeriodicalIF":0.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell systemsPub Date : 2025-05-21Epub Date: 2025-04-21DOI: 10.1016/j.cels.2025.101266
Lei Tang, Jinsong Zhang, Yanqiu Shao, Yifan Wei, Yuzhe Li, Kang Tian, Xiang Yan, Changjiang Feng, Qiangfeng Cliff Zhang
{"title":"Joint analysis of chromatin accessibility and gene expression in the same single cells reveals cancer-specific regulatory programs.","authors":"Lei Tang, Jinsong Zhang, Yanqiu Shao, Yifan Wei, Yuzhe Li, Kang Tian, Xiang Yan, Changjiang Feng, Qiangfeng Cliff Zhang","doi":"10.1016/j.cels.2025.101266","DOIUrl":"10.1016/j.cels.2025.101266","url":null,"abstract":"<p><p>Biological analyses conducted at the single-cell scale have revealed profound impacts of heterogeneity and plasticity of chromatin states and gene expression on physiology and cancer. Here, we developed Parallel-seq, a technology for simultaneously measuring chromatin accessibility and gene expression in the same single cells. By combining combinatorial cell indexing and droplet overloading, Parallel-seq generates high-quality data in an ultra-high-throughput fashion and at a cost two orders of magnitude lower than alternative technologies (10× Multiome and ISSAAC-seq). We applied Parallel-seq to 40 lung tumor and tumor-adjacent clinical samples and obtained over 200,000 high-quality joint scATAC-and-scRNA profiles. Leveraging this large dataset, we characterized copy-number variations (CNVs) and extrachromosomal circular DNA (eccDNA) heterogeneity in tumor cells, predicted hundreds of thousands of cell-type-specific regulatory events, and identified enhancer mutations affecting tumor progression. Our analyses highlight Parallel-seq's power in investigating epigenetic and genetic factors driving cancer development at the cell-type-specific level and its utility for revealing vulnerable therapeutic targets.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101266"},"PeriodicalIF":0.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell systemsPub Date : 2025-05-21Epub Date: 2025-04-01DOI: 10.1016/j.cels.2025.101244
Kun Wang, Zhaolian Lu, Zeqi Yao, Xionglei He, Zheng Hu, Da Zhou
{"title":"Single-cell phylodynamic inference of stem cell differentiation and tumor evolution.","authors":"Kun Wang, Zhaolian Lu, Zeqi Yao, Xionglei He, Zheng Hu, Da Zhou","doi":"10.1016/j.cels.2025.101244","DOIUrl":"10.1016/j.cels.2025.101244","url":null,"abstract":"<p><p>Phylodynamic inference (PI) quantifies population dynamics and evolutionary trajectories using phylogenetic trees. Single-cell lineage tracing enables phylogenetic tree reconstruction for thousands of cells in multicellular organisms, facilitating PI at the cellular level. However, cell differentiation and somatic evolution challenge the direct application of existing PI frameworks to somatic tissues. We introduce scPhyloX, a computational framework modeling structured cell populations by leveraging single-cell phylogenetic trees to infer tissue development and tumor evolution dynamics. A key advancement is its ability to infer time-varying parameters, capturing dynamic biological processes. Simulations demonstrate scPhyloX's accuracy in scenarios including tissue development, disease treatment, and tumor growth. Application to three real datasets reveals insights into somatic dynamics: cycling stem cell overshoot in fly organ development, clonal expansion of multipotent hematopoietic progenitors during human aging, and pronounced subclonal selection in early colorectal tumorigenesis. scPhyloX thus provides a computational approach for investigating somatic tissue development and evolution.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101244"},"PeriodicalIF":0.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell systemsPub Date : 2025-05-21Epub Date: 2025-05-01DOI: 10.1016/j.cels.2025.101265
Julie C Dixon, Christopher L Frick, Chantelle L Leveille, Philip Garrison, Peyton A Lee, Saurabh S Mogre, Benjamin Morris, Nivedita Nivedita, Ritvik Vasan, Jianxu Chen, Cameron L Fraser, Clare R Gamlin, Leigh K Harris, Melissa C Hendershott, Graham T Johnson, Kyle N Klein, Sandra A Oluoch, Derek J Thirstrup, M Filip Sluzewski, Lyndsay Wilhelm, Ruian Yang, Daniel M Toloudis, Matheus P Viana, Julie A Theriot, Susanne M Rafelski
{"title":"Colony context and size-dependent compensation mechanisms give rise to variations in nuclear growth trajectories.","authors":"Julie C Dixon, Christopher L Frick, Chantelle L Leveille, Philip Garrison, Peyton A Lee, Saurabh S Mogre, Benjamin Morris, Nivedita Nivedita, Ritvik Vasan, Jianxu Chen, Cameron L Fraser, Clare R Gamlin, Leigh K Harris, Melissa C Hendershott, Graham T Johnson, Kyle N Klein, Sandra A Oluoch, Derek J Thirstrup, M Filip Sluzewski, Lyndsay Wilhelm, Ruian Yang, Daniel M Toloudis, Matheus P Viana, Julie A Theriot, Susanne M Rafelski","doi":"10.1016/j.cels.2025.101265","DOIUrl":"10.1016/j.cels.2025.101265","url":null,"abstract":"<p><p>To investigate how cellular variations arise across spatiotemporal scales in a population of identical healthy cells, we performed a data-driven analysis of nuclear growth variations in hiPS cell colonies as a model system. We generated a 3D timelapse dataset of thousands of nuclei over multiple days and developed open-source tools for image and data analysis and feature-based timelapse data exploration. Together, these data, tools, and workflows comprise a framework for systematic quantitative analysis of dynamics at individual and population levels, and the analysis further highlights important aspects to consider when interpreting timelapse data. We found that individual nuclear volume growth trajectories arise from short-timescale variations attributable to their spatiotemporal context within the colony. We identified a time-invariant volume compensation relationship between nuclear growth duration and starting volume across the population. Notably, we discovered that inheritance plays a crucial role in determining these two key nuclear growth features while other growth features are determined by their spatiotemporal context and are not inherited.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101265"},"PeriodicalIF":0.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12221235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053835","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}
Cell systemsPub Date : 2025-05-21Epub Date: 2025-04-10DOI: 10.1016/j.cels.2025.101262
Ziv Avizemer, Carlos Martí-Gómez, Shlomo Yakir Hoch, David M McCandlish, Sarel J Fleishman
{"title":"Evolutionary paths that link orthogonal pairs of binding proteins.","authors":"Ziv Avizemer, Carlos Martí-Gómez, Shlomo Yakir Hoch, David M McCandlish, Sarel J Fleishman","doi":"10.1016/j.cels.2025.101262","DOIUrl":"10.1016/j.cels.2025.101262","url":null,"abstract":"<p><p>Some protein-binding pairs exhibit extreme specificities that functionally insulate them from homologs. Such pairs evolve mostly by accumulating single-point mutations, and mutants are selected if they exhibit sufficient affinity. Until now, finding a fully functional single-mutation path connecting orthogonal pairs could only be achieved by full enumeration of intermediates and was restricted to pairs that were mutationally close. We present a computational framework for discovering single-mutation paths with low molecular strain and apply it to two orthogonal bacterial endonuclease-immunity pairs separated by 17 interfacial mutations. By including mutations that bridge identities that could not be exchanged by single-nucleotide mutations, we discovered a strain-free 19-mutation path that was fully functional in vivo. The change in binding preference occurred remarkably abruptly, resulting from only one radical mutation in each partner. Furthermore, each of the specificity-switch mutations increased fitness, demonstrating that functional divergence could be driven by positive Darwinian selection.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101262"},"PeriodicalIF":7.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052046","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}
Cell systemsPub Date : 2025-04-16Epub Date: 2025-03-20DOI: 10.1016/j.cels.2025.101239
Cameron T Flower, Chunmei Liu, Hui-Yu Chuang, Xiaoyang Ye, Hanjun Cheng, James R Heath, Wei Wei, Forest M White
{"title":"Signaling and transcriptional dynamics underlying early adaptation to oncogenic BRAF inhibition.","authors":"Cameron T Flower, Chunmei Liu, Hui-Yu Chuang, Xiaoyang Ye, Hanjun Cheng, James R Heath, Wei Wei, Forest M White","doi":"10.1016/j.cels.2025.101239","DOIUrl":"10.1016/j.cels.2025.101239","url":null,"abstract":"<p><p>A major contributor to poor sensitivity to anti-cancer kinase inhibitor therapy is drug-induced cellular adaptation, whereby remodeling of signaling and gene regulatory networks permits a drug-tolerant phenotype. Here, we resolve the scale and kinetics of critical subcellular events following oncogenic kinase inhibition and preceding cell cycle re-entry, using mass spectrometry-based phosphoproteomics and RNA sequencing (RNA-seq) to monitor the dynamics of thousands of growth- and survival-related signals over the first minutes, hours, and days of oncogenic BRAF inhibition in human melanoma cells. We observed sustained inhibition of the BRAF-ERK axis, gradual downregulation of cell cycle signaling, and three distinct, reversible phase transitions toward quiescence. Statistical inference of kinetically defined regulatory modules revealed a dominant compensatory induction of SRC family kinase (SFK) signaling, promoted in part by excess reactive oxygen species, rendering cells sensitive to co-treatment with an SFK inhibitor in vitro and in vivo, underscoring the translational potential for assessing early drug-induced adaptive signaling. A record of this paper's transparent peer review process is included in the supplemental information.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101239"},"PeriodicalIF":0.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12045616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674913","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}
Cell systemsPub Date : 2025-04-16Epub Date: 2025-03-13DOI: 10.1016/j.cels.2025.101205
Nathan B Wang, Brittany A Lende-Dorn, Adam M Beitz, Patrick Han, Honour O Adewumi, Timothy M O'Shea, Kate E Galloway
{"title":"Proliferation history and transcription factor levels drive direct conversion to motor neurons.","authors":"Nathan B Wang, Brittany A Lende-Dorn, Adam M Beitz, Patrick Han, Honour O Adewumi, Timothy M O'Shea, Kate E Galloway","doi":"10.1016/j.cels.2025.101205","DOIUrl":"10.1016/j.cels.2025.101205","url":null,"abstract":"<p><p>The sparse and stochastic nature of conversion has obscured our understanding of how transcription factors (TFs) drive cells to new identities. To overcome this limit, we develop a tailored, high-efficiency conversion system that increases the direct conversion of fibroblasts to motor neurons 100-fold. By tailoring the cocktail to a minimal set of transcripts, we reduce extrinsic variation, allowing us to examine how proliferation and TFs synergistically drive conversion. We show that cell state-as set by proliferation history-defines how cells interpret the levels of TFs. Controlling for proliferation history and titrating each TF, we find that conversion correlates with levels of the pioneer TF Ngn2. By isolating cells by both their proliferation history and Ngn2 levels, we demonstrate that levels of Ngn2 expression alone are insufficient to predict conversion rates. Rather, proliferation history and TF levels combine to drive direct conversion. Finally, increasing the proliferation rate of adult human fibroblasts generates morphologically mature induced human motor neurons at high rates.</p>","PeriodicalId":93929,"journal":{"name":"Cell systems","volume":" ","pages":"101205"},"PeriodicalIF":0.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630934","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}