Frontiers in bioscience (Landmark edition)最新文献

{"title":"Functional and Mechanistic Insights into the Fatty-Acid CoA Ligase FadK in <i>Escherichia coli</i>.","authors":"Dafeng Liu, Ablikim Abdiriyim, Lvxia Zhang, Feng Yu","doi":"10.31083/FBL36701","DOIUrl":"https://doi.org/10.31083/FBL36701","url":null,"abstract":"<p><strong>Background: </strong><i>Escherichia coli</i> (<i>E. coli</i>) is a common opportunistic bacterial pathogen in both human and animal populations. Fatty acids serve as the central carbon and energy source, a process mediated by fatty acid-coenzyme A (CoA) ligases encoded by <i>fad</i> genes such as <i>FadK</i>. However, the function and the mechanism of FadK remain unclear.</p><p><strong>Methods: </strong>The three-dimensional structure of FadK was modeled using AlphaFold2. After expression and purification, monomeric FadK was successfully isolated. The enzymatic activity was assayed, and real-time quantitative polymerase chain reaction (RT-qPCR) was performed to quantify <i>FadK</i> expression levels.</p><p><strong>Results: </strong>In enzymatic assays of fatty acid CoA ligase activity, caprylic acid was found to be the optimal substrate for FadK. We determined the optimal catalytic conditions for FadK, which include a pH of 7.4, ATP concentration of 0.6 mM, CoA concentration of 0.8 mM, and Mg²⁺ concentration of 0.8 mM at 37 °C. Notably, the activity of FadK showed a decrease with increasing concentrations of dodecyl-AMP, which was further confirmed by the RT-qPCR results.</p><p><strong>Conclusions: </strong>Our findings will serve as a fundamental framework for the development of innovative therapeutics that target <i>E. coli</i> infections.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 4","pages":"36701"},"PeriodicalIF":3.3,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042445","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}

{"title":"DTC-m6Am: A Framework for Recognizing N6,2'-O-dimethyladenosine Sites in Unbalanced Classification Patterns Based on DenseNet and Attention Mechanisms.","authors":"Hui Huang, Fenglin Zhou, Jianhua Jia, Huachun Zhang","doi":"10.31083/FBL36603","DOIUrl":"https://doi.org/10.31083/FBL36603","url":null,"abstract":"<p><strong>Background: </strong>m⁶Am is a specific RNA modification that plays an important role in regulating mRNA stability, translational efficiency, and cellular stress response. m⁶Am's precise identification is essential to gain insight into its functional mechanisms at transcriptional and post-transcriptional levels. Due to the limitations of experimental assays, the development of efficient computational tools to predict m⁶Am sites has become a major focus of research, offering potential breakthroughs in RNA epigenetics. In this study, we present a robust and reliable deep learning model, DTC-m6Am, for identifying m⁶Am sites across the transcriptome.</p><p><strong>Methods: </strong>Our proposed DTC-m6Am model first represents RNA sequences by One-Hot coding to capture base-based features and provide structured inputs for subsequent deep learning models. The model then combines densely connected convolutional networks (DenseNet) and temporal convolutional network (TCN). The DenseNet module leverages its dense connectivity property to effectively extract local features and enhance information flow, whereas the TCN module focuses on capturing global time series dependencies to enhance the modeling capability for long sequence features. To further optimize feature extraction, the Convolutional Block Attention Module (CBAM) is used to focus on key regions through spatial and channel attention mechanisms. Finally, a fully connected layer is used for the classification task to achieve accurate prediction of the m⁶Am site. For the data imbalance problem, we use the focal loss function to balance the learning effect of positive and negative samples and improve the performance of the model on imbalanced data.</p><p><strong>Results: </strong>The deep learning-based DTC-m6Am model performs well on all evaluation metrics, achieving 87.8%, 50.3%, 69.1%, 41.1%, and 76.5% for sensitivity (Sn), specificity (Sp), accuracy (ACC), Mathew's correlation coefficient (MCC), and area under the curve (AUC), respectively, on the independent test set.</p><p><strong>Conclusions: </strong>We critically evaluated the performance of DTC-m6Am using 10-fold cross-validation and independent testing and compared it to existing methods. The MCC value of 41.1% was achieved when using the independent test, which is 19.7% higher than the current state-of-the-art prediction method, m6Aminer. The results indicate that the DTC-m6Am model has high accuracy and stability and is an effective tool for predicting m⁶Am sites.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 4","pages":"36603"},"PeriodicalIF":3.3,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993736","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}

{"title":"Unveiling RNA Editing by ADAR and APOBEC Protein Gene Families.","authors":"Alexander Modestov, Anton Buzdin, Maria Suntsova","doi":"10.31083/FBL26298","DOIUrl":"https://doi.org/10.31083/FBL26298","url":null,"abstract":"<p><p>RNA editing is a crucial post-transcriptional modification that alters the transcriptome and proteome and affects many cellular processes, including splicing, microRNA specificity, stability of RNA molecules, and protein structure. Enzymes from the adenosine deaminase acting on RNA (ADAR) and apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) protein families mediate RNA editing and can alter a variety of non-coding and coding RNAs, including all regions of mRNA molecules, leading to tumor development and progression. This review provides novel insights into the potential use of RNA editing parameters, such as editing levels, expression of <i>ADAR</i> and <i>APOBEC</i> genes, and specifically edited genes, as biomarkers for cancer progression, distinguishing it from previous studies that focused on isolated aspects of RNA editing mechanisms. The methodological section offers clues to accelerate high-throughput analysis of RNA or DNA sequencing data for the identification of RNA editing events.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 4","pages":"26298"},"PeriodicalIF":3.3,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036239","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}

{"title":"Targeting Platelet Activating Factor Signaling for Therapeutic Benefits in Neurodegenerative Disorders.","authors":"Theodora Adamantidi, Andreas M Grabrucker, Alexandros Tsoupras","doi":"10.31083/FBL38300","DOIUrl":"https://doi.org/10.31083/FBL38300","url":null,"abstract":"<p><p>Neurodegenerative disorders (NDs), including dementia, Alzheimer's disease (AD), and Parkinson's disease (PD), are age-related diseases closely associated with chronic inflammation, oxidative stress, gene mutations, autoimmune-derived inflammation, and other external risk factors. They are characterized by progressive neuronal loss, cognitive decline, and/or motor dysfunction, with chronic inflammation being a key player in intensifying NDs' occurrence. One of the most important molecular inflammatory mediators linking inflammation to NDs is the platelet-activating factor (PAF) and its pivotal signaling for regulating neuroinflammation, apoptosis, and neuronal damage. Dysregulation of PAF activity and metabolism/levels, along with overexpression of its receptor (PAF-R) have been associated with exacerbated inflammatory responses, further aggravating neurodegeneration. This article highlights the role of PAF in neurodegeneration, with a particular focus on novel insights into the potential medicinal use of PAF inhibitors for the prevention and treatment of neurodegenerative diseases. We evaluate the recently proposed concept of targeting the PAF signaling pathway through either natural and/or synthetic inhibitors or a combination of both. It explores the potential of these inhibitors to offer significant preventative and therapeutic benefits against NDs, likely through anti-inflammatory anti-aging effects and by slowing down the disease progression and preserving cognitive and motor dysfunction. Current status and future perspectives of such therapeutic approaches are also discussed.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 4","pages":"38300"},"PeriodicalIF":3.3,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043958","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}

{"title":"Macrophage Notch1 Participates in LPS-Induced Acute Lung Injury via Regulating CCR5 Expression in Mice.","authors":"Ruiyu Zhang, Hui Du, Zhi Liu, Yuxi Lei, Huizhi Hu, Junwen Zheng, Pu Yang, Dongchi Zhao","doi":"10.31083/FBL37430","DOIUrl":"https://doi.org/10.31083/FBL37430","url":null,"abstract":"<p><strong>Background: </strong>As pivotal immunoregulatory sentinels in pulmonary defense systems, alveolar macrophages (AMs) play dual roles in mediating inflammatory responses and tissue repair processes during various phases of inflammatory cascades. The present investigation focuses on elucidating the regulatory influence of Notch pathway activation within AM populations on the pathophysiological mechanisms underlying acute lung injury (ALI) development.</p><p><strong>Methods: </strong>To investigate the regulatory roles of Notch intracellular domain (NICD) and C-C chemokine receptor type 5 (CCR5) in pulmonary inflammation, an ALI model was established through lipopolysaccharide (LPS) administration. Complementary studies used macrophage-specific Notch1 knockout mice and immortalized bone marrow-derived macrophages (iBMDMs). Molecular profiling of CCR5 and inflammatory mediators was performed through real-time quantitative reverse transcription PCR (qRT-PCR) and immunofluorescence staining. Functional assessments of macrophage migration were carried out using scratch wound healing assays and transwell migration assays.</p><p><strong>Results: </strong>In the LPS-induced ALI model, pulmonary tissues exhibited elevated expression of both NICD and CCR5. Conversely, Notch1 knockout mice attenuated CCR5 expression, reduced macrophage infiltration and downregulated transcription of pro-inflammatory mediators compared to wild-type controls (<i>p</i> < 0.05). Lung injury was milder in the Notch1-deficient mice model compared to wild mice (<i>p</i> < 0.05). <i>In vitro</i> experiments demonstrated that inhibiting the Notch pathway in macrophages reduced CCR5 expression and attenuated CCL5-induced macrophage migration.</p><p><strong>Conclusion: </strong>Notch signaling regulates macrophage infiltration and the inflammatory response by modulating CCR5 expression in ALI induced by LPS.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 4","pages":"37430"},"PeriodicalIF":3.3,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060336","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}

{"title":"Socs3a is Dispensable for Zebrafish Hematopoiesis and is Required for Neuromast Formation.","authors":"Mohamed Luban Sobah, Clifford Liongue, Alister C Ward","doi":"10.31083/FBL36537","DOIUrl":"https://doi.org/10.31083/FBL36537","url":null,"abstract":"<p><strong>Background: </strong>Suppressor of cytokine signaling (SOCS)3 is a regulatory protein that participates in an important negative feedback loop downstream of several critical cytokines, especially members of the interleukin-6 (IL-6) family. As a result, SOCS3 has been shown to impact the development and function of blood and immune cells. Zebrafish harbor duplicates of SOCS3, Socs3a and Socs3b, both of which possess conserved functional domains.</p><p><strong>Methods: </strong>This study explored the role of zebrafish Socs3a by creating a whole genome knockout using CRISPR/Cas9, with a focus on hematopoiesis and neuromast formation.</p><p><strong>Results: </strong>A zebrafish Socs3a knockout mutant was successfully generated. Characterization of this mutant revealed that normal hematopoiesis was not impacted nor was neutrophils lacking Socs3a displayed normal responses to injury or their production during emergency granulopoiesis. Neuromast formation was severely impacted in Socs3a knockout zebrafish.</p><p><strong>Conclusions: </strong>Zebrafish Socs3a mutants display normal hematopoiesis and myeloid function, but the formation of the lateral line neuromast was affected by the absence of Socs3a.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 4","pages":"36537"},"PeriodicalIF":3.3,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045308","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}

{"title":"Role of Tumor-Associated Macrophages in Breast Cancer Immunotherapy.","authors":"Yan He, Quan Liu, Zhihao Luo, Qian Hu, Li Wang, Zifen Guo","doi":"10.31083/FBL26995","DOIUrl":"https://doi.org/10.31083/FBL26995","url":null,"abstract":"<p><p>Breast cancer (BC) is the second leading cause of death among women worldwide. Immunotherapy has become an effective treatment for BC patients due to the rapid development of medical technology. Considerable breakthroughs have been made in research, marking the beginning of a new era in cancer treatment. Among them, various cancer immunotherapies such as immune checkpoint inhibitors (ICIs), cancer vaccines, and adoptive cell transfer are effective and have good prospects. The tumor microenvironment (TME) plays a crucial role in determining the outcomes of tumor immunotherapy. Tumor-associated macrophages (TAMs) are a key component of the TME, with an immunomodulatory effect closely related to the immune evasion of tumor cells, thereby affecting malignant progression. TAMs also significantly affect the therapeutic effect of ICIs (such as programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors). TAMs are composed of multiple heterogeneous subpopulations, including M1 phenotypes macrophages (M1) and M2 phenotypes macrophages (M2). Furthermore, they mainly play an M2-like role and moderate a variety of harmful consequences such as angiogenesis, immunosuppression, and metastasis. Therefore, TAMs have become a key area of focus in the development of tumor therapies. However, several tumor immunotherapy studies demonstrated that ICIs are effective only in a small number of solid cancers, and tumor immunotherapy still faces relevant challenges in the treatment of solid tumors. This review explores the role of TAMs in BC immunotherapy, summarizing their involvement in BC development. It also explains the classification and functions of TAMs, outlines current tumor immunotherapy approaches and combination therapies, and discusses the challenges and potential strategies for TAMs in immuno-oncology treatments.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 4","pages":"26995"},"PeriodicalIF":3.3,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043996","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}

{"title":"Brown Algae: Uncovering the Secrets of Evolutionary Genomics and Multicellularity.","authors":"Gabriel Žoldák","doi":"10.31083/FBL37380","DOIUrl":"https://doi.org/10.31083/FBL37380","url":null,"abstract":"","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 4","pages":"37380"},"PeriodicalIF":3.3,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043995","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}

{"title":"Aerobic Exercise Ameliorates Alzheimer's Disease-Like Pathology by Regulating Hepatic Phagocytosis of Aβ.","authors":"Qing Wang, Feng-Rui Hu, Xing-Chun Gou, Shan Wang, Nai-Chun Ji","doi":"10.31083/FBL36597","DOIUrl":"https://doi.org/10.31083/FBL36597","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a neurodegenerative disease which significantly and negatively affects families and society. Aerobic exercise serves as a non-pharmacological strategy, potentially safeguarding against cognitive decline and lowering the risk of AD. However, how aerobic exercise ameliorates AD remains unknown. This study investigated the effects of two types of aerobic exercise, including aerobic interval training (AIT) and aerobic continuous training (ACT), on cognitive and exploratory function, brain histopathology, and hepatic amyloid beta (Aβ) clearance in amyloid precursor protein/presenilin-1 double transgenic (APP/PS1) transgenic mice.</p><p><strong>Methods: </strong>Twenty-four six-month-old male APP/PS1 transgenic mice (body weight: 20-22 g) were used to establish the AD model. APP/PS1 transgenic mice were randomly assigned to one of the three groups: rest (AD group, n = 8), aerobic interval training (AIT group, n = 8), and aerobic continuous training (ACT group, n = 8). The exploration ability and anxiety of AD mice were measured using the open-field test. Learning and memory of AD mice were detected using the novel object recognition test, Y-maze test, and Morris water maze test. Neuronal damage was analyzed using hematoxylin and eosin staining and Nissl staining. Aβ deposition in the brain was detected using a thioflavin-S fluorescence assay and immunofluorescence. The mechanisms underlying hepatic Aβ clearance were investigated using an immunofluorescence assay and western blotting. Data were analyzed using one-way ANOVA with Tukey's post hoc test, and <i>p</i> < 0.05 was deemed statistically significant.</p><p><strong>Results: </strong>The results revealed that both AIT and ACT improved the recognition memory and exploration ability of mice after 8 weeks of intervention. Additionally, both forms of aerobic exercise significantly mitigated neuronal damage and Aβ deposition in the brain and improved the hepatic clearance of Aβ.</p><p><strong>Conclusions: </strong>Our findings indicated that AIT and ACT can improve cognitive deficits in APP/PS1 mice, potentially by increasing the hepatic phagocytic capacity of Aβ. Hepatic clearance of Aβ may serve as a supplementary mechanism by which aerobic exercise can improve AD.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 4","pages":"36597"},"PeriodicalIF":3.3,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042741","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}

{"title":"VSIG4 Alleviates Intracranial Hemorrhage Injury by Regulating Oxidative Stress and Neuroinflammation in Macrophages via the NRF2/HO-1 Signaling Pathway.","authors":"Haofan Lu, Yuntao Li, Yonggang Zhang, Wen Qin, Zhongzhou Su, Sheng Qiu, Lifang Zheng","doi":"10.31083/FBL37810","DOIUrl":"https://doi.org/10.31083/FBL37810","url":null,"abstract":"<p><strong>Background: </strong>Oxidative stress and neuroinflammation are important secondary injury mechanisms in intracranial hemorrhage (ICH). V-set and immunoglobulin domain-containing 4 (VSIG4) has an inhibitory effect on oxidative stress and the inflammatory response. This study aimed to explore the possible role of VSIG4 in ICH-related neuropathology.</p><p><strong>Methods: </strong>In this study, VSIG4 levels were investigated in an ICH mouse model and lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Moreover, we examined oxidative stress levels, pro-inflammatory cytokine production, neuronal damage, inflammatory cell activation, brain water content, and neurological function. We performed these assays in ICH mice and macrophages with different VSIG4 levels. Additionally, the critical role of the nuclear factor erythroid 2 related factor 2/heme oxygenase-1 (NRF2/HO-1) signaling pathway in VSIG4 function was verified.</p><p><strong>Results: </strong>VSIG4 ameliorated neurological deficits in ICH mice (<i>p</i> < 0.01), alleviated cerebral edema (<i>p</i> < 0.05), and increased glutathione (<i>p</i> < 0.05) and decreased superoxide dismutase (SOD) levels (<i>p</i> < 0.01) in the perihematomal area and LPS-stimulated RAW264.7 cells. It also reduced Malondialdehyde (MDA) accumulation (<i>p</i> < 0.01), alleviated oxidative stress, and decreased interleukin-1β (IL-1β) (<i>p</i> < 0.01) and tumor necrosis factor-alpha (TNF-α) levels (<i>p</i> < 0.01), thereby attenuating the inflammatory response. Additionally, treatment of LPS-stimulated RAW264.7 cells with VSIG4 resulted in less damage to HT22 cells (<i>p</i> < 0.05). To further validate the involvement of the NRF2/HO-1 pathway in VSIG4-mediated neuroprotection, brusatol (an NRF2 inhibitor) was administered.</p><p><strong>Conclusion: </strong>Our study demonstrates the neuroprotective effect and mechanism of action of VSIG4 in ICH.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 4","pages":"37810"},"PeriodicalIF":3.3,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029978","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}