Alison J. Hobro*, Takatoshi Sakaguchi, Shizuo Akira and Nicholas I. Smith*,
{"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*, Takatoshi Sakaguchi, Shizuo Akira and Nicholas I. Smith*, ","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":"2 8","pages":"577–583 577–583"},"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}
Yawen Zhang, Weiyue Wu, Hongdou Shen, Juan Xu, Qing Jiang, Xiaodong Han, Pingqiang Cai
{"title":"Subdiffraction Imaging of Cleared and Expanded Large-Scale Tissues.","authors":"Yawen Zhang, Weiyue Wu, Hongdou Shen, Juan Xu, Qing Jiang, Xiaodong Han, Pingqiang Cai","doi":"10.1021/cbmi.4c00013","DOIUrl":"https://doi.org/10.1021/cbmi.4c00013","url":null,"abstract":"<p><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":"2 8","pages":"542-559"},"PeriodicalIF":0.0,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142548910","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}
Nancy Sharma, Walaa Mohammad, Xavier Le Guével, Asifkhan Shanavas
{"title":"Gold Nanoclusters as High Resolution NIR-II Theranostic Agents.","authors":"Nancy Sharma, Walaa Mohammad, Xavier Le Guével, Asifkhan Shanavas","doi":"10.1021/cbmi.4c00021","DOIUrl":"https://doi.org/10.1021/cbmi.4c00021","url":null,"abstract":"<p><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":"2 7","pages":"462-480"},"PeriodicalIF":0.0,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142548907","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}
Amita Vaidya, Aman Shankardass, Megan Buford, Ryan Hall, Peter Qiao, Helen Wang, Songqi Gao, Jiaoti Huang, Michael F. Tweedle and Zheng-Rong Lu*,
{"title":"MR Molecular Imaging of Extradomain-B Fibronectin for Assessing Progression and Therapy Resistance of Prostate Cancer","authors":"Amita Vaidya, Aman Shankardass, Megan Buford, Ryan Hall, Peter Qiao, Helen Wang, Songqi Gao, Jiaoti Huang, Michael F. Tweedle and Zheng-Rong Lu*, ","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":"2 8","pages":"560–568 560–568"},"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":"In Vivo Assessment of Individual and Total Proteinuria in Zebrafish Larvae Using the Solvatochromic Compound ZMB741.","authors":"Tsuyoshi Nomoto, Aoi Mori, Kayoko Yamada, Fumihiro Terami, Akiyoshi Shimizu, Toshio Tanaka","doi":"10.1021/cbmi.4c00029","DOIUrl":"10.1021/cbmi.4c00029","url":null,"abstract":"<p><p>The robustness of blood filtration in the kidney is supported by two major functions: the molecular sieve of the glomerulus and reabsorption of the proximal tubules. Detecting glomerular dysfunction is challenging because of the compensatory nature of proximal tubule reabsorption. To facilitate pathophysiological studies of the vertebrate kidney, zebrafish pronephroi are used, owing to their simple glomerular and proximal tubular configuration. In this study, a solvatochromic dye with an affinity for plasma proteins was used to detect urinary proteins leaking into the ureter of zebrafish. Aristolochic acid exposure to fertilized eggs of transgenic zebrafish expressing green fluorescent protein from the proximal tubules to the excretory pore induced concentration-dependent renal dysfunction. The solvatochromic dye ZMB741 was applied via static immersion to analyze leaked dye-plasma-protein complexes in the ureter; their axial distribution was imaged by using confocal microscopy. The effect of resveratrol, an attenuator of aristolochic acid nephropathy, was further analyzed. This method enables individual-level analysis of podocytopathy, a mild glomerular disease that does not necessarily lead to the excretion of proteinuria. Moreover, it will be useful for pathophysiological studies of renal function and the identification of potential therapeutic drugs.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"2 11","pages":"755-764"},"PeriodicalIF":0.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11600188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752146","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":"In Vivo Assessment of Individual and Total Proteinuria in Zebrafish Larvae Using the Solvatochromic Compound ZMB741","authors":"Tsuyoshi Nomoto, Aoi Mori, Kayoko Yamada, Fumihiro Terami, Akiyoshi Shimizu and Toshio Tanaka*, ","doi":"10.1021/cbmi.4c0002910.1021/cbmi.4c00029","DOIUrl":"https://doi.org/10.1021/cbmi.4c00029https://doi.org/10.1021/cbmi.4c00029","url":null,"abstract":"<p >The robustness of blood filtration in the kidney is supported by two major functions: the molecular sieve of the glomerulus and reabsorption of the proximal tubules. Detecting glomerular dysfunction is challenging because of the compensatory nature of proximal tubule reabsorption. To facilitate pathophysiological studies of the vertebrate kidney, zebrafish pronephroi are used, owing to their simple glomerular and proximal tubular configuration. In this study, a solvatochromic dye with an affinity for plasma proteins was used to detect urinary proteins leaking into the ureter of zebrafish. Aristolochic acid exposure to fertilized eggs of transgenic zebrafish expressing green fluorescent protein from the proximal tubules to the excretory pore induced concentration-dependent renal dysfunction. The solvatochromic dye ZMB741 was applied via static immersion to analyze leaked dye–plasma–protein complexes in the ureter; their axial distribution was imaged by using confocal microscopy. The effect of resveratrol, an attenuator of aristolochic acid nephropathy, was further analyzed. This method enables individual-level analysis of podocytopathy, a mild glomerular disease that does not necessarily lead to the excretion of proteinuria. Moreover, it will be useful for pathophysiological studies of renal function and the identification of potential therapeutic drugs.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"2 11","pages":"755–764 755–764"},"PeriodicalIF":0.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.4c00029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142694449","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}
Hong Liang, Ya-Jun Wang, Yixin Liu, Wei Liu, Baohong Liu* and Yan-Jun Liu*,
{"title":"Microtopography-Induced Nuclear Deformation Triggers Chromatin Reorganization and Cytoskeleton Remodeling","authors":"Hong Liang, Ya-Jun Wang, Yixin Liu, Wei Liu, Baohong Liu* and Yan-Jun Liu*, ","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":"2 7","pages":"481–489 481–489"},"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}
Petr S. Sherin*, Markus Rueckel* and Marina K. Kuimova*,
{"title":"Fluorescent Molecular Rotors Quantify an Adjuvant-Induced Softening of Plant Wax","authors":"Petr S. Sherin*, Markus Rueckel* and Marina K. Kuimova*, ","doi":"10.1021/cbmi.4c00005","DOIUrl":"10.1021/cbmi.4c00005","url":null,"abstract":"<p >Epicuticular wax is the outmost layer of plant leaves that protects them from desiccation and penetration of harmful reagents. There is an intense industrial effort in the development of softening agents, adjuvants, that can adjust the permeability of the wax toward pesticides and, thus, play an important role in sustainable agriculture. However, mechanistic understanding of the structure and dynamic properties within the plant wax, particularly upon the application of adjuvants, is currently lacking. In this work, we demonstrate that fluorescence lifetime imaging microscopy (FLIM) combined with molecular rotors, fluorescent probes sensitive to viscosity, can directly probe the microviscosity of amorphous and crystalline phases of model plant wax layers. Moreover, this approach is able to quantify the changes in viscosity in both phases upon the addition of water and adjuvant solutions on top of the wax. We show that water permeation mostly perturbs the crystalline phase of the wax, while our chosen adjuvant, Plurafac LF431, mainly softens the amorphous phase of the wax. Our technique provides a facile and quantitative way to monitor dynamic properties within plant waxes with diffraction-limited resolution and reveals the effect of organic substances on wax structure and rigidity, crucial for designing next-generation agents to improve agricultural efficiency.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"2 6","pages":"453–461"},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.4c00005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141003966","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}
Yaroslav Balytskyi*, Nataliia Kalashnyk, Inna Hubenko, Alina Balytska and Kelly McNear,
{"title":"Enhancing Open-World Bacterial Raman Spectra Identification by Feature Regularization for Improved Resilience against Unknown Classes","authors":"Yaroslav Balytskyi*, Nataliia Kalashnyk, Inna Hubenko, Alina Balytska and Kelly McNear, ","doi":"10.1021/cbmi.4c00007","DOIUrl":"https://doi.org/10.1021/cbmi.4c00007","url":null,"abstract":"<p >The combination of deep learning techniques and Raman spectroscopy shows great potential offering precise and prompt identification of pathogenic bacteria in clinical settings. However, the traditional closed-set classification approaches assume that all test samples belong to one of the known pathogens, and their applicability is limited since the clinical environment is inherently unpredictable and dynamic, unknown, or emerging pathogens may not be included in the available catalogs. We demonstrate that the current state-of-the-art neural networks identifying pathogens through Raman spectra are vulnerable to unknown inputs, resulting in an uncontrollable false positive rate. To address this issue, first we developed an ensemble of ResNet architectures combined with the attention mechanism that achieves a 30-isolate accuracy of 87.8 ± 0.1%. Second, through the integration of feature regularization by the Objectosphere loss function, our model both achieves high accuracy in identifying known pathogens from the catalog and effectively separates unknown samples drastically reducing the false positive rate. Finally, the proposed feature regularization method during training significantly enhances the performance of out-of-distribution detectors during the inference phase improving the reliability of the detection of unknown classes. Our algorithm for Raman spectroscopy empowers the identification of previously unknown, uncataloged, and emerging pathogens ensuring adaptability to future pathogens that may surface. Moreover, it can be extended to enhance open-set medical image classification, bolstering its reliability in dynamic operational settings.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"2 6","pages":"442–452"},"PeriodicalIF":0.0,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.4c00007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141474776","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":"Fluorescence Imaging Using Deep-Red Indocyanine Blue, a Complementary Partner for Near-Infrared Indocyanine Green","authors":"Rananjaya S. Gamage, and , Bradley D. Smith*, ","doi":"10.1021/cbmi.4c00008","DOIUrl":"10.1021/cbmi.4c00008","url":null,"abstract":"<p >Indocyanine Blue (ICB) is the deep-red pentamethine analogue of the widely used clinical near-infrared heptamethine cyanine dye Indocyanine Green (ICG). The two fluorophores have the same number of functional groups and molecular charge and vary only by a single vinylene unit in the polymethine chain, which produces a predictable difference in spectral and physicochemical properties. We find that the two dyes can be employed as a complementary pair in diverse types of fundamental and applied fluorescence imaging experiments. A fundamental fluorescence spectroscopy study used ICB and ICG to test a recently proposed Förster Resonance Energy Transfer (FRET) mechanism for enhanced fluorescence brightness in heavy water (D<sub>2</sub>O). The results support two important corollaries of the proposal: (a) the strategy of using heavy water to increase the brightness of fluorescent dyes for microscopy or imaging is most effective when the dye emission band is above 650 nm, and (b) the magnitude of the heavy water florescence enhancement effect for near-infrared ICG is substantially diminished when the ICG surface is dehydrated due to binding by albumin protein. Two applied fluorescence imaging studies demonstrated how deep-red ICB can be combined with a near-infrared fluorophore for paired agent imaging in the same living subject. One study used dual-channel mouse imaging to visualize increased blood flow in a model of inflamed tissue, and a second mouse tumor imaging study simultaneously visualized the vasculature and cancerous tissue in separate fluorescence channels. The results suggest that ICB and ICG can be incorporated within multicolor fluorescence imaging methods for perfusion imaging and hemodynamic characterization of a wide range of diseases.</p>","PeriodicalId":53181,"journal":{"name":"Chemical & Biomedical Imaging","volume":"2 5","pages":"384–397"},"PeriodicalIF":0.0,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/cbmi.4c00008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141018311","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}