Chemical & Biomedical Imaging最新文献

{"title":"First Year of Chemical & Biomedical Imaging: Reflection and Prospect","authors":"Wenxi Lei, Juanjuan Jia, Deju Ye and Zijian Guo*, ","doi":"10.1021/cbmi.4c00043","DOIUrl":"https://doi.org/10.1021/cbmi.4c00043","url":null,"abstract":"","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.4c00043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141474750","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":"Non-Small Cell Lung Cancer Imaging Using a Phospholipase A2 Activatable Fluorophore","authors":"Michael C. Hart,&nbsp;Ritesh K. Isuri,&nbsp;Drew Ramos,&nbsp;Sofya A. Osharovich,&nbsp;Andrea E. Rodriguez,&nbsp;Stefan Harmsen,&nbsp;Grace C. Dudek,&nbsp;Jennifer L. Huck,&nbsp;David E. Holt,&nbsp;Anatoliy V. Popov,&nbsp;Sunil Singhal and Edward J. Delikatny*,&nbsp;","doi":"10.1021/cbmi.4c0002610.1021/cbmi.4c00026","DOIUrl":"https://doi.org/10.1021/cbmi.4c00026https://doi.org/10.1021/cbmi.4c00026","url":null,"abstract":"<p >Lung cancer, the most common cause of cancer-related death in the United States, requires advanced intraoperative detection methods to improve evaluation of surgical margins. In this study we employed DDAO-arachidonate (DDAO-A), a phospholipase A2 (PLA2) activatable fluorophore, designed for the specific optical identification of lung cancers in real-time during surgery. The <i>in vitro</i> fluorescence activation of DDAO-A by porcine sPLA2 was tested in various liposomal formulations, with 100 nm extruded EggPC showing the best overall characteristics. Extruded EggPC liposomes containing DDAO-A were tested for their stability under various storage conditions, demonstrating excellent stability for up to 4 weeks when stored at −20 °C or below. Cell studies using KLN 205 and LLC1 lung cancer cell lines showed DDAO-A activation was proportional to cell number. DDAO-A showed preferential activation by human recombinant cPLA2, an isoform highly specific to arachidonic acid-containing lipids, when compared to a control probe, DDAO palmitate (DDAO-P). <i>In vivo</i> studies with DBA/2 mice bearing KLN 205 lung tumors recapitulated these results, with preferential activation of DDAO-A relative to DDAO-P following intratumoral injection. Topical application of DDAO-A-containing liposomes to human (n = 10) and canine (n = 3) lung cancers <i>ex vivo</i> demonstrated the preferential activation of DDAO-A in tumor tissue relative to adjacent normal lung tissue, with fluorescent tumor-to-normal ratios (TNR) of up to 5.2:1. The combined results highlight DDAO-A as a promising candidate for clinical applications, showcasing its potential utility in intraoperative and back-table imaging and topical administration during lung cancer surgeries. By addressing the challenge of residual microscopic disease at resection margins and offering stability in liposomal formulations, DDAO-A emerges as a potentially valuable tool for advancing precision lung cancer surgery and improving curative resection rates.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.4c00026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141959230","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":"Non-Small Cell Lung Cancer Imaging Using a Phospholipase A2 Activatable Fluorophore.","authors":"Michael C Hart, Ritesh K Isuri, Drew Ramos, Sofya A Osharovich, Andrea E Rodriguez, Stefan Harmsen, Grace C Dudek, Jennifer L Huck, David E Holt, Anatoliy V Popov, Sunil Singhal, Edward J Delikatny","doi":"10.1021/cbmi.4c00026","DOIUrl":"10.1021/cbmi.4c00026","url":null,"abstract":"<p><p>Lung cancer, the most common cause of cancer-related death in the United States, requires advanced intraoperative detection methods to improve evaluation of surgical margins. In this study we employed DDAO-arachidonate (DDAO-A), a phospholipase A2 (PLA2) activatable fluorophore, designed for the specific optical identification of lung cancers in real-time during surgery. The <i>in vitro</i> fluorescence activation of DDAO-A by porcine sPLA2 was tested in various liposomal formulations, with 100 nm extruded EggPC showing the best overall characteristics. Extruded EggPC liposomes containing DDAO-A were tested for their stability under various storage conditions, demonstrating excellent stability for up to 4 weeks when stored at -20 °C or below. Cell studies using KLN 205 and LLC1 lung cancer cell lines showed DDAO-A activation was proportional to cell number. DDAO-A showed preferential activation by human recombinant cPLA2, an isoform highly specific to arachidonic acid-containing lipids, when compared to a control probe, DDAO palmitate (DDAO-P). <i>In vivo</i> studies with DBA/2 mice bearing KLN 205 lung tumors recapitulated these results, with preferential activation of DDAO-A relative to DDAO-P following intratumoral injection. Topical application of DDAO-A-containing liposomes to human (n = 10) and canine (n = 3) lung cancers <i>ex vivo</i> demonstrated the preferential activation of DDAO-A in tumor tissue relative to adjacent normal lung tissue, with fluorescent tumor-to-normal ratios (TNR) of up to 5.2:1. The combined results highlight DDAO-A as a promising candidate for clinical applications, showcasing its potential utility in intraoperative and back-table imaging and topical administration during lung cancer surgeries. By addressing the challenge of residual microscopic disease at resection margins and offering stability in liposomal formulations, DDAO-A emerges as a potentially valuable tool for advancing precision lung cancer surgery and improving curative resection rates.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11267604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762579","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":"Gold Nanoclusters as High Resolution NIR-II Theranostic Agents","authors":"Nancy Sharma,&nbsp;Walaa Mohammad,&nbsp;Xavier Le Guével* and Asifkhan Shanavas*,&nbsp;","doi":"10.1021/cbmi.4c0002110.1021/cbmi.4c00021","DOIUrl":"https://doi.org/10.1021/cbmi.4c00021https://doi.org/10.1021/cbmi.4c00021","url":null,"abstract":"<p >In the realm of nanomaterials, atomically precise quasi-molecular gold nanoclusters (AuNCs) play a prime role due to their unique, stable, and highly tunable optical properties. They are extensively structure-engineered for modulation of surface electronic states toward long wavelength photoluminescence, particularly in the NIR-II (1000 to 1700 nm) window. Contrast agents with NIR-II emission can potentially transform optical imaging in terms of higher spatial resolution, deeper tissue penetration, and reduced tissue autofluorescence. These advantages allow real-time imaging in living organisms for observing disease progression and treatment response. In this short review, we discuss origin of NIR-II emission in rationally designed AuNCs and their application toward high resolution imaging of vasculatures and hard and soft tissue structures for identification of pathological conditions such as stroke and injury. Further, recent employment of these AuNCs in the rapidly growing field of tumor theranostics is also summarized. Final remarks are provided on the scope for improvement in their optical properties and persisting challenges for clinical translation.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.4c00021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141959070","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":"Insight into Single-Molecule Imaging Techniques for the Study of Prokaryotic Genome Maintenance","authors":"Nischal Sharma,&nbsp;Antoine M. van Oijen,&nbsp;Lisanne M. Spenkelink* and Stefan H. Mueller*,&nbsp;","doi":"10.1021/cbmi.4c0003710.1021/cbmi.4c00037","DOIUrl":"https://doi.org/10.1021/cbmi.4c00037https://doi.org/10.1021/cbmi.4c00037","url":null,"abstract":"<p >Genome maintenance comprises a group of complex and interrelated processes crucial for preserving and safeguarding genetic information within all organisms. Key aspects of genome maintenance involve DNA replication, transcription, recombination, and repair. Improper regulation of these processes could cause genetic changes, potentially leading to antibiotic resistance in bacterial populations. Due to the complexity of these processes, ensemble averaging studies may not provide the level of detail required to capture the full spectrum of molecular behaviors and dynamics of each individual biomolecule. Therefore, researchers have increasingly turned to single-molecule approaches, as these techniques allow for the direct observation and manipulation of individual biomolecules, and offer a level of detail that is unattainable with traditional ensemble methods. In this review, we provide an overview of recent in vitro and in vivo single-molecule imaging approaches employed to study the complex processes involved in prokaryotic genome maintenance. We will first highlight the principles of imaging techniques such as total internal reflection fluorescence microscopy and atomic force microscopy, primarily used for in vitro studies, and highly inclined and laminated optical sheet and super-resolution microscopy, mainly employed in in vivo studies. We then demonstrate how applying these single-molecule techniques has enabled the direct visualization of biological processes such as replication, transcription, DNA repair, and recombination in real time. Finally, we will showcase the results obtained from super-resolution microscopy approaches, which have provided unprecedented insights into the spatial organization of different biomolecules within bacterial organisms.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.4c00037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276387","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":"Subdiffraction Imaging of Cleared and Expanded Large-Scale Tissues","authors":"Yawen Zhang,&nbsp;Weiyue Wu,&nbsp;Hongdou Shen,&nbsp;Juan Xu,&nbsp;Qing Jiang*,&nbsp;Xiaodong Han* and Pingqiang Cai*,&nbsp;","doi":"10.1021/cbmi.4c0001310.1021/cbmi.4c00013","DOIUrl":"https://doi.org/10.1021/cbmi.4c00013https://doi.org/10.1021/cbmi.4c00013","url":null,"abstract":"<p >The quest for high spatial resolution in molecular identification is critical across various domains, including physiology, pathology, and pharmaceutical research. Super-resolution microscopy has made strides by surpassing the Abbe diffraction limit, but it relies on sophisticated equipment and is limited by the sample size to handle. Expansion microscopy, an emerging technique, has broadened the scope of subdiffraction imaging. It chemically preserves tissues at a large scale and physically enlarges them 4–20 times linearly, enabling super-resolution observation. This review begins by exploring the foundational concepts of tissue clearing and the latest methodologies in the field. It then delves into the core tenets of expansion microscopy, covering a range of protocols. The review spotlights advancements in enhancing resolution, improving labeling efficiency, and ensuring isotropic tissue expansion. Finally, the review offers insights into the prospective evolution of expansion microscopy. It emphasizes the potential role of machine learning in refining image quality and in the autonomous extraction of data, which could revolutionize the way we visualize and understand biological tissues.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.4c00013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142075685","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":"Insight into Single-Molecule Imaging Techniques for the Study of Prokaryotic Genome Maintenance.","authors":"Nischal Sharma, Antoine M van Oijen, Lisanne M Spenkelink, Stefan H Mueller","doi":"10.1021/cbmi.4c00037","DOIUrl":"https://doi.org/10.1021/cbmi.4c00037","url":null,"abstract":"<p><p>Genome maintenance comprises a group of complex and interrelated processes crucial for preserving and safeguarding genetic information within all organisms. Key aspects of genome maintenance involve DNA replication, transcription, recombination, and repair. Improper regulation of these processes could cause genetic changes, potentially leading to antibiotic resistance in bacterial populations. Due to the complexity of these processes, ensemble averaging studies may not provide the level of detail required to capture the full spectrum of molecular behaviors and dynamics of each individual biomolecule. Therefore, researchers have increasingly turned to single-molecule approaches, as these techniques allow for the direct observation and manipulation of individual biomolecules, and offer a level of detail that is unattainable with traditional ensemble methods. In this review, we provide an overview of recent in vitro and in vivo single-molecule imaging approaches employed to study the complex processes involved in prokaryotic genome maintenance. We will first highlight the principles of imaging techniques such as total internal reflection fluorescence microscopy and atomic force microscopy, primarily used for in vitro studies, and highly inclined and laminated optical sheet and super-resolution microscopy, mainly employed in in vivo studies. We then demonstrate how applying these single-molecule techniques has enabled the direct visualization of biological processes such as replication, transcription, DNA repair, and recombination in real time. Finally, we will showcase the results obtained from super-resolution microscopy approaches, which have provided unprecedented insights into the spatial organization of different biomolecules within bacterial organisms.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11423410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332201","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":"Correlative Quantitative Raman Chemical Imaging and MCR–ALS in Mouse NASH Model Reveals Direct Relationships between Diet and Resultant Liver Pathology","authors":"Alison J. Hobro*,&nbsp;Takatoshi Sakaguchi,&nbsp;Shizuo Akira and Nicholas I. Smith*,&nbsp;","doi":"10.1021/cbmi.4c0002710.1021/cbmi.4c00027","DOIUrl":"https://doi.org/10.1021/cbmi.4c00027https://doi.org/10.1021/cbmi.4c00027","url":null,"abstract":"<p >Raman imaging has the capability to provide unlabeled, spatially aware analysis of chemical components, with no <i>a priori</i> assumptions. Several lifestyle diseases such as nonalcoholic steatohepatitis (NASH) can appear in the liver as changes in the nature, abundance, and distribution of lipids, proteins, and other biomolecules and are detectable by Raman imaging. In order to identify which of these liver-associated changes occur as a direct result of the diet and which are secondary effects, we developed correlative imaging and analysis of diet and liver samples. Oleic acid was found to be a direct contributor to NASH liver composition, whereas protein and collagen distributions were found to be affected in a manner consistent with early fibrotic transformation, as a secondary consequence of the high-fat diet.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.4c00027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142075684","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":"MR Molecular Imaging of Extradomain-B Fibronectin for Assessing Progression and Therapy Resistance of Prostate Cancer","authors":"Amita Vaidya,&nbsp;Aman Shankardass,&nbsp;Megan Buford,&nbsp;Ryan Hall,&nbsp;Peter Qiao,&nbsp;Helen Wang,&nbsp;Songqi Gao,&nbsp;Jiaoti Huang,&nbsp;Michael F. Tweedle and Zheng-Rong Lu*,&nbsp;","doi":"10.1021/cbmi.4c0000210.1021/cbmi.4c00002","DOIUrl":"https://doi.org/10.1021/cbmi.4c00002https://doi.org/10.1021/cbmi.4c00002","url":null,"abstract":"<p >Accurate assessment and characterization of the progression and therapy response of prostate cancer are essential for precision healthcare of patients diagnosed with the disease. MRI is a clinical imaging modality routinely used for diagnostic imaging and treatment planning of prostate cancer. Extradomain B fibronectin (EDB-FN) is an oncofetal subtype of fibronectin highly expressed in the extracellular matrix of aggressive cancers, including prostate cancer. It is a promising molecular target for the detection and risk-stratification of prostate cancer with high-resolution MR molecular imaging (MRMI). In this study, we investigated the effectiveness of MRMI with an EDB-FN specific contrast agent MT218 for assessing the progression and therapy resistance of prostate cancer. Low grade LNCaP prostate cancer cells became an invasive phenotype LNCaP-CXCR2 with elevated EDB-FN expression after acquisition of the C-X-C motif chemokine receptor 2 (CXCR2). MT218-MRMI showed brighter signal enhancement in LNCaP-CXCR2 tumor xenografts with a ∼2-fold contrast-to-noise (CNR) increase than in LNCaP tumors in mice. Enzalutamide-resistant C4-2-DR prostate cancer cells were more invasive, with higher EDB-FN expression than parental C4-2 cells. Brighter signal enhancement with a ∼2-fold CNR increase was observed in the C4-2-DR xenografts compared to that of C4-2 tumors in mice with MT218-MRMI. Interestingly, when invasive PC3 prostate cancer cells developed resistance to paclitaxel, the drug-resistant PC3-DR cells became less invasive with reduced EDB-FN expression than the parental PC3 cells. MT218-MRMI detected reduced brightness in the PC3-DR xenografts with more than 2-fold reduction of CNR compared to PC3 tumors in mice. The signal enhancement in all tumors was supported by the immunohistochemical staining of EDB-FN with the G4 monoclonal antibody. The results indicate that MRMI of EDB-FN with MT218 has promise for detection, risk stratification, and monitoring the progression and therapy response of invasive prostate cancer.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.4c00002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142075683","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":"Microtopography-Induced Nuclear Deformation Triggers Chromatin Reorganization and Cytoskeleton Remodeling","authors":"Hong Liang,&nbsp;Ya-Jun Wang,&nbsp;Yixin Liu,&nbsp;Wei Liu,&nbsp;Baohong Liu* and Yan-Jun Liu*,&nbsp;","doi":"10.1021/cbmi.4c0003510.1021/cbmi.4c00035","DOIUrl":"https://doi.org/10.1021/cbmi.4c00035https://doi.org/10.1021/cbmi.4c00035","url":null,"abstract":"<p >Cells can adapt to diverse topographical substrates through contact guidance, which regulates the cellular and nuclear morphologies and functions. How adaptive deformation of the cell body and nucleus coordinates to protect genetic material within mechanical microenvironments remains poorly understood. In this study, we engineered micrometer-level narrow-spacing micropillars to mimic constricted extracellular topographies in vivo, enabling us to explore variances in the nuclear architecture, cytoskeleton distribution, and chromatin conformation. The results showed that the area and volume of cell nuclei were distinctly smaller on micropillar topography. Actin and vimentin densely encapsulated the micropillars surrounding the nucleus, effectively segregating it from the micropillars. Additionally, nucleo-cytoskeleton lamin A/C exhibited a polarized distribution at the protrusion of the deformed nuclei. Notably, the degree of heterochromatin was altered in response to significant nuclear deformation, leading to a downregulation trend in H3K9me3 expression. These findings suggest that mechanical constraints imposed by microtopography profoundly influence cell behaviors, providing insights into disease diagnosis and therapeutic interventions in vivo.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.4c00035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141959308","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}