{"title":"Going Above and Beyond: Achieving High Contrast and Higher Offset through Carbon Dot-Based diaCEST MRI Contrast Agent.","authors":"Shalini Pandey, Arindam Ghosh","doi":"10.1021/cbmi.4c00086","DOIUrl":"10.1021/cbmi.4c00086","url":null,"abstract":"<p><p>Diamagnetic CEST (diaCEST) MRI contrast agents (CAs) have recently gained immense popularity by virtue of the fact that contrast can be switched on or off by merely changing a few experimental parameters, even after the agent is administered. However, the low efficiency and small solute-solvent offset of the contrast-generating exchangeable protons have so far prevented them from becoming a practical option for in vivo applications. Low efficiency demands high dosage, while small offset invites unwanted interference from the endogenous metabolites present in the human body. So far, the strategy for finding efficient diaCEST CAs involved searching for suitable molecules in which the exchangeable protons resonate as far as possible from water and have an optimum exchange rate. Very little effort has been devoted toward designing or converting to an efficient one from a less efficient existing CA. It was recently shown that hydrothermally synthesized carbon nanodots (CDs) have the ability to enhance contrast efficiency and to tune the pH response of certain diaCEST CAs. Here we show that a suitable combination of the synthesis technique and synthesis parameters can simultaneously enhance solute-solvent offset and contrast efficiency. In particular, we demonstrate 300% enhancement in offset and 100% enhancement in efficiency following the formation of carbon-dots from a urea-citric acid mixture.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"3 2","pages":"123-131"},"PeriodicalIF":0.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525160","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}
{"title":"Going Above and Beyond: Achieving High Contrast and Higher Offset through Carbon Dot-Based diaCEST MRI Contrast Agent","authors":"Shalini Pandey, and , Arindam Ghosh*, ","doi":"10.1021/cbmi.4c0008610.1021/cbmi.4c00086","DOIUrl":"https://doi.org/10.1021/cbmi.4c00086https://doi.org/10.1021/cbmi.4c00086","url":null,"abstract":"<p >Diamagnetic CEST (diaCEST) MRI contrast agents (CAs) have recently gained immense popularity by virtue of the fact that contrast can be switched on or off by merely changing a few experimental parameters, even after the agent is administered. However, the low efficiency and small solute–solvent offset of the contrast-generating exchangeable protons have so far prevented them from becoming a practical option for in vivo applications. Low efficiency demands high dosage, while small offset invites unwanted interference from the endogenous metabolites present in the human body. So far, the strategy for finding efficient diaCEST CAs involved searching for suitable molecules in which the exchangeable protons resonate as far as possible from water and have an optimum exchange rate. Very little effort has been devoted toward designing or converting to an efficient one from a less efficient existing CA. It was recently shown that hydrothermally synthesized carbon nanodots (CDs) have the ability to enhance contrast efficiency and to tune the pH response of certain diaCEST CAs. Here we show that a suitable combination of the synthesis technique and synthesis parameters can simultaneously enhance solute–solvent offset and contrast efficiency. In particular, we demonstrate 300% enhancement in offset and 100% enhancement in efficiency following the formation of carbon-dots from a urea–citric acid mixture.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"3 2","pages":"123–131 123–131"},"PeriodicalIF":0.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.4c00086","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473732","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}
{"title":"Application of Nanomaterials in Early Imaging and Advanced Treatment of Atherosclerosis.","authors":"Qianru Zhou, Yujie Wang, Guangxiang Si, Xingbiao Chen, Dan Mu, Bing Zhang","doi":"10.1021/cbmi.4c00064","DOIUrl":"10.1021/cbmi.4c00064","url":null,"abstract":"<p><p>Atherosclerosis (AS) is a serious disease that poses a significant threat to the global population. In this review, we analyze the development of AS from multiple perspectives, aiming to elucidate its molecular mechanisms. We also focus on imaging techniques and therapeutic approaches, highlighting the crucial role of nanomaterials in both imaging and therapy for AS. By leveraging their compatibility and targeting capabilities, nanomaterials can be integrated with traditional medical imaging and therapeutic agents to achieve targeted drug delivery, controlled release, and precise localization and imaging of atherosclerotic plaques.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"3 2","pages":"51-76"},"PeriodicalIF":0.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525158","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}
Qianru Zhou, Yujie Wang, Guangxiang Si, Xingbiao Chen, Dan Mu* and Bing Zhang*,
{"title":"Application of Nanomaterials in Early Imaging and Advanced Treatment of Atherosclerosis","authors":"Qianru Zhou, Yujie Wang, Guangxiang Si, Xingbiao Chen, Dan Mu* and Bing Zhang*, ","doi":"10.1021/cbmi.4c0006410.1021/cbmi.4c00064","DOIUrl":"https://doi.org/10.1021/cbmi.4c00064https://doi.org/10.1021/cbmi.4c00064","url":null,"abstract":"<p >Atherosclerosis (AS) is a serious disease that poses a significant threat to the global population. In this review, we analyze the development of AS from multiple perspectives, aiming to elucidate its molecular mechanisms. We also focus on imaging techniques and therapeutic approaches, highlighting the crucial role of nanomaterials in both imaging and therapy for AS. By leveraging their compatibility and targeting capabilities, nanomaterials can be integrated with traditional medical imaging and therapeutic agents to achieve targeted drug delivery, controlled release, and precise localization and imaging of atherosclerotic plaques.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"3 2","pages":"51–76 51–76"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.4c00064","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473677","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}
Audrey Van Heest, Yuzhen Wang, Liang Zhang, Lucy A Phillips, Samuel D Karsen, Christine Nelson, Heather L Knight, Stuart J Perper, Stephen O'Brien, Meghan Clements, Victor Z Sun, Andrew Goodearl, Annette Schwartz Sterman, Soumya Mitra
{"title":"Quantitative Assessment of Pulmonary Fibrosis in a Murine Model via a Multimodal Imaging Workflow.","authors":"Audrey Van Heest, Yuzhen Wang, Liang Zhang, Lucy A Phillips, Samuel D Karsen, Christine Nelson, Heather L Knight, Stuart J Perper, Stephen O'Brien, Meghan Clements, Victor Z Sun, Andrew Goodearl, Annette Schwartz Sterman, Soumya Mitra","doi":"10.1021/cbmi.4c00065","DOIUrl":"10.1021/cbmi.4c00065","url":null,"abstract":"<p><p>Disease-recapitulating animal models are valuable tools in preclinical development for the study of compounds. In the case of fibrotic pulmonary diseases such as idiopathic pulmonary fibrosis (IPF), the bleomycin model of lung injury in the mouse is widely used. To evaluate bleomycin-induced changes in the lung, we employed a quantitative, multimodal approach. Using in vivo microcomputed tomography (μCT), we demonstrated radiographic changes associated with disease progression in aeration levels of the lung parenchyma. There exists an unmet need for a quantitative, high-resolution imaging probe to detect pulmonary fibrosis, particularly that can differentiate between inflammatory and fibrotic components of the disease. Matrix remodeling and overexpression of extracellular matrix (ECM) proteins such as collagen and fibronectin are hallmarks of organ fibrosis. A splice variant of fibronectin containing extra domain A (FnEDA) is of particular interest in fibrosis due to its high level of expression in diseased tissue, which is confirmed here using immunohistochemistry (IHC) in mouse and human lungs. An antibody against FnEDA was evaluated for use as an imaging tool, particularly by using in vivo single-photon emission computed tomography (SPECT) and ex vivo near-infrared (NIR) fluorescence imaging. These data were further corroborated with histological tissue staining and fibrosis quantitation based on a Modified Ashcroft (MA) score and a digital image analysis of whole slide lung tissue sections. The fusion of these different approaches represents a robust integrated workflow combining anatomical and molecular imaging technologies to enable the visualization and quantitation of disease activity and treatment response with an inhibitor of the TGFβ signaling pathway.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"3 2","pages":"85-94"},"PeriodicalIF":0.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525161","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}
Audrey Van Heest, Yuzhen Wang, Liang Zhang, Lucy A. Phillips, Samuel D. Karsen, Christine Nelson, Heather L. Knight, Stuart J. Perper, Stephen O’Brien, Meghan Clements, Victor Z. Sun, Andrew Goodearl, Annette Schwartz Sterman and Soumya Mitra*,
{"title":"Quantitative Assessment of Pulmonary Fibrosis in a Murine Model via a Multimodal Imaging Workflow","authors":"Audrey Van Heest, Yuzhen Wang, Liang Zhang, Lucy A. Phillips, Samuel D. Karsen, Christine Nelson, Heather L. Knight, Stuart J. Perper, Stephen O’Brien, Meghan Clements, Victor Z. Sun, Andrew Goodearl, Annette Schwartz Sterman and Soumya Mitra*, ","doi":"10.1021/cbmi.4c0006510.1021/cbmi.4c00065","DOIUrl":"https://doi.org/10.1021/cbmi.4c00065https://doi.org/10.1021/cbmi.4c00065","url":null,"abstract":"<p >Disease-recapitulating animal models are valuable tools in preclinical development for the study of compounds. In the case of fibrotic pulmonary diseases such as idiopathic pulmonary fibrosis (IPF), the bleomycin model of lung injury in the mouse is widely used. To evaluate bleomycin-induced changes in the lung, we employed a quantitative, multimodal approach. Using in vivo microcomputed tomography (μCT), we demonstrated radiographic changes associated with disease progression in aeration levels of the lung parenchyma. There exists an unmet need for a quantitative, high-resolution imaging probe to detect pulmonary fibrosis, particularly that can differentiate between inflammatory and fibrotic components of the disease. Matrix remodeling and overexpression of extracellular matrix (ECM) proteins such as collagen and fibronectin are hallmarks of organ fibrosis. A splice variant of fibronectin containing extra domain A (FnEDA) is of particular interest in fibrosis due to its high level of expression in diseased tissue, which is confirmed here using immunohistochemistry (IHC) in mouse and human lungs. An antibody against FnEDA was evaluated for use as an imaging tool, particularly by using in vivo single-photon emission computed tomography (SPECT) and ex vivo near-infrared (NIR) fluorescence imaging. These data were further corroborated with histological tissue staining and fibrosis quantitation based on a Modified Ashcroft (MA) score and a digital image analysis of whole slide lung tissue sections. The fusion of these different approaches represents a robust integrated workflow combining anatomical and molecular imaging technologies to enable the visualization and quantitation of disease activity and treatment response with an inhibitor of the TGFβ signaling pathway.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"3 2","pages":"85–94 85–94"},"PeriodicalIF":0.0,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.4c00065","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473676","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}
Sithurandi Ubeysinghe, Chloe O Sebilleau, Waruna Thotamune, Chathuri Rajarathna, Samuel Azibere, Mithila Tennakoon, John L Payton, Randy S Sprague, R Scott Martin, Steven J Sucheck, Ajith Karunarathne
{"title":"Recombinant-Chemosynthetic Biosensors for Probing Cell Surface Signaling of Red Blood Cells and Other Cells.","authors":"Sithurandi Ubeysinghe, Chloe O Sebilleau, Waruna Thotamune, Chathuri Rajarathna, Samuel Azibere, Mithila Tennakoon, John L Payton, Randy S Sprague, R Scott Martin, Steven J Sucheck, Ajith Karunarathne","doi":"10.1021/cbmi.4c00067","DOIUrl":"10.1021/cbmi.4c00067","url":null,"abstract":"<p><p>The complex signaling mechanisms in red blood cells (RBCs) enable them to adapt to physiological stresses such as exposure to low O<sub>2</sub> levels, metabolic demands, oxidative stress, and shear stress. Since Ca<sup>2+</sup> is a crucial determinant of RBC fate, various ion channels, pumps, and exchangers regulate the delicate balance of Ca<sup>2+</sup> influx and efflux in RBCs. Elevated intracellular Ca<sup>2+</sup> can activate processes such as membrane phospholipid scrambling and alter RBC deformability, which is essential for effective capillary transit. However, the dynamic information about Ca<sup>2+</sup> regulation in RBCs is limited. Although static mapping and bioanalytical methods have been utilized, the absence of a nucleus and the presence of hemoglobin create challenges for real-time probing of RBC signaling, necessitating innovative approaches. This work introduces a synthetic chemistry-recombinant protein-based strategy to assemble sensors at genetically intact healthy human RBC surfaces for measuring dynamic signaling. Using this approach, we measured autocrine regulation of RBC Ca<sup>2+</sup> influx in response to low O<sub>2</sub> tension-induced ATP release. The study also explores the utilization of synthetic glycosylphosphatidylinositol (GPI) anchor mimics and sortagging for targeting sensors to the surfaces of primary as well as immortalized cells. This demonstrated the wide applicability of this approach to probe dynamic signaling in intact cells.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"3 2","pages":"95-110"},"PeriodicalIF":0.0,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525162","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}
Sithurandi Ubeysinghe, Chloe O. Sebilleau, Waruna Thotamune, Chathuri Rajarathna, Samuel Azibere, Mithila Tennakoon, John L. Payton, Randy S. Sprague, R. Scott Martin, Steven J. Sucheck* and Ajith Karunarathne*,
{"title":"Recombinant–Chemosynthetic Biosensors for Probing Cell Surface Signaling of Red Blood Cells and Other Cells","authors":"Sithurandi Ubeysinghe, Chloe O. Sebilleau, Waruna Thotamune, Chathuri Rajarathna, Samuel Azibere, Mithila Tennakoon, John L. Payton, Randy S. Sprague, R. Scott Martin, Steven J. Sucheck* and Ajith Karunarathne*, ","doi":"10.1021/cbmi.4c0006710.1021/cbmi.4c00067","DOIUrl":"https://doi.org/10.1021/cbmi.4c00067https://doi.org/10.1021/cbmi.4c00067","url":null,"abstract":"<p >The complex signaling mechanisms in red blood cells (RBCs) enable them to adapt to physiological stresses such as exposure to low O<sub>2</sub> levels, metabolic demands, oxidative stress, and shear stress. Since Ca<sup>2+</sup> is a crucial determinant of RBC fate, various ion channels, pumps, and exchangers regulate the delicate balance of Ca<sup>2+</sup> influx and efflux in RBCs. Elevated intracellular Ca<sup>2+</sup> can activate processes such as membrane phospholipid scrambling and alter RBC deformability, which is essential for effective capillary transit. However, the dynamic information about Ca<sup>2+</sup> regulation in RBCs is limited. Although static mapping and bioanalytical methods have been utilized, the absence of a nucleus and the presence of hemoglobin create challenges for real-time probing of RBC signaling, necessitating innovative approaches. This work introduces a synthetic chemistry–recombinant protein-based strategy to assemble sensors at genetically intact healthy human RBC surfaces for measuring dynamic signaling. Using this approach, we measured autocrine regulation of RBC Ca<sup>2+</sup> influx in response to low O<sub>2</sub> tension-induced ATP release. The study also explores the utilization of synthetic glycosylphosphatidylinositol (GPI) anchor mimics and sortagging for targeting sensors to the surfaces of primary as well as immortalized cells. This demonstrated the wide applicability of this approach to probe dynamic signaling in intact cells.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"3 2","pages":"95–110 95–110"},"PeriodicalIF":0.0,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.4c00067","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473758","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}
{"title":"Fluorogenic Tetrazine Bioorthogonal Probes for Advanced Application in Bioimaging and Biomedicine","authors":"Wuyu Mao, Ping Dong, Wei Du* and Haoxing Wu*, ","doi":"10.1021/cbmi.4c0009510.1021/cbmi.4c00095","DOIUrl":"https://doi.org/10.1021/cbmi.4c00095https://doi.org/10.1021/cbmi.4c00095","url":null,"abstract":"<p >A variety of bioorthogonal chemical tools have been developed and widely used in the study of biological phenomena in situ. Tetrazine bioorthogonal chemistry exhibits ultrafast reaction kinetics, excellent biocompatibility, and precise optical regulatory capabilities. Fluorogenic tetrazine bioorthogonal probes have achieved particularly diverse applications in bioimaging and disease diagnosis and treatment. This Viewpoint briefly introduces the characteristics and advantages of tetrazine bioorthogonal chemistry, some design strategies of fluorogenic tetrazine probes, and the status of applications of these tools to in vivo imaging, as well as disease diagnosis and treatment. Finally, we discuss challenges and propose future trends in the field of fluorogenic tetrazine probes. This Viewpoint offers insights into the development of new bioorthogonal tools for chemical biology research and for the design of new drugs.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"3 1","pages":"1–4 1–4"},"PeriodicalIF":0.0,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.4c00095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143085749","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}
{"title":"Fluorogenic Tetrazine Bioorthogonal Probes for Advanced Application in Bioimaging and Biomedicine.","authors":"Wuyu Mao, Ping Dong, Wei Du, Haoxing Wu","doi":"10.1021/cbmi.4c00095","DOIUrl":"10.1021/cbmi.4c00095","url":null,"abstract":"<p><p>A variety of bioorthogonal chemical tools have been developed and widely used in the study of biological phenomena in situ. Tetrazine bioorthogonal chemistry exhibits ultrafast reaction kinetics, excellent biocompatibility, and precise optical regulatory capabilities. Fluorogenic tetrazine bioorthogonal probes have achieved particularly diverse applications in bioimaging and disease diagnosis and treatment. This Viewpoint briefly introduces the characteristics and advantages of tetrazine bioorthogonal chemistry, some design strategies of fluorogenic tetrazine probes, and the status of applications of these tools to in vivo imaging, as well as disease diagnosis and treatment. Finally, we discuss challenges and propose future trends in the field of fluorogenic tetrazine probes. This Viewpoint offers insights into the development of new bioorthogonal tools for chemical biology research and for the design of new drugs.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"3 1","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069404","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}