Jaehoon Kim, Seulah Lee, Dong Geun Hong, Seonguk Yang, Cong So Tran, Jinsook Kwak, Min-Ju Kim, Thenmozhi Rajarathinam, Ki Wung Chung, Young-Suk Jung, Akihito Ishigami, Seung-Cheol Chang, Haeseung Lee, Hwayoung Yun, Jaewon Lee
{"title":"Amelioration of Astrocyte-Mediated Neuroinflammation by EI-16004 Confers Neuroprotection in an MPTP-induced Parkinson's Disease Model.","authors":"Jaehoon Kim, Seulah Lee, Dong Geun Hong, Seonguk Yang, Cong So Tran, Jinsook Kwak, Min-Ju Kim, Thenmozhi Rajarathinam, Ki Wung Chung, Young-Suk Jung, Akihito Ishigami, Seung-Cheol Chang, Haeseung Lee, Hwayoung Yun, Jaewon Lee","doi":"10.1007/s12017-023-08769-8","DOIUrl":"10.1007/s12017-023-08769-8","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a neurodegenerative disorder that results in motor impairment due to dopaminergic neuronal loss. The pathology of PD is closely associated with neuroinflammation, which can be characterized by astrocyte activation. Thus, targeting the inflammatory response in astrocytes might provide a novel therapeutic approach. We conducted a luciferase assay on an in-house chemical library to identify compounds with anti-inflammatory effects capable of reducing MPP<sup>+</sup>-induced NF-κB activity in astrocytes. Among the compounds identified, EI-16004, a novel 3-benzyl-N-phenyl-1H-pyrazole-5-carboxamides, exhibited a significant anti-inflammatory effect by significantly reducing MPP<sup>+</sup>-induced astrocyte activation. Biochemical analysis and docking simulation indicated that EI-16004 inhibited the MPP<sup>+</sup>-induced phosphorylation of p65 by attenuating ERK phosphorylation, and EI-16004 reduced pro-inflammatory cytokine and chemokine levels in astrocytes. In vivo studies on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model in male C57BL/6 mice showed that EI-16004 ameliorated motor impairment and protected against dopaminergic neuronal loss, and EI-16004 effectively mitigated the MPTP-induced astrocyte activation in striatum (STR) and substantia nigra (SN). These results indicate EI-16004 is a potential neuroprotective agent for the prevention and treatment of astrocyte-mediated neuroinflammatory conditions in PD.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"26 1","pages":"1"},"PeriodicalIF":3.3,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139642672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Diurnal Characteristics of the Orexin System Genes and Its Effects on Pathology at Early Stage in 3xTg-AD Mice.","authors":"Jing Yin, Chun-Mei Tuo, Kai-Yue Yu, Xiao-Hong Hu, Yan-Ying Fan, Mei-Na Wu","doi":"10.1007/s12017-023-08767-w","DOIUrl":"10.1007/s12017-023-08767-w","url":null,"abstract":"<p><p>Orexin and its receptors are closely related to the pathogenesis of Alzheimer's disease (AD). Although the expression of orexin system genes under physiological condition has circadian rhythm, the diurnal characteristics of orexin system genes, and its potential role in the pathogenesis in AD are unknown. In the present study, we hope to elucidate the diurnal characteristics of orexin system genes at the early stage of AD, and to investigate its potential role in the development of AD neuropathology. We firstly detected the mRNA levels of orexin system genes, AD risk genes and core clock genes (CCGs) in hypothalamus and hippocampus in 6-month-old male 3xTg-AD mice and C57BL/6J (wild type, WT) control mice, then analyzed diurnal expression profiles of all genes using JTK_CYCLE algorithm, and did the correlation analysis between expression of orexin system genes and AD risk genes or CCGs. In addition, the expression of β-amyloid protein (Aβ) and phosphorylated tau (p-tau) protein were measured. The results showed that the diurnal mRNA expression profiles of PPO, OX1R, OX2R, Bace2, Bmal1, Per1, Per2 and Cry1 in the hypothalamus, and gene expression of OX1R, OX2R, Bace1, Bmal1, Per1 and Cry2 in the hippocampus in 3xTg-AD mice were different from that in WT mice. Furthermore, there is positive correlation between orexin system genes and AD risk genes or CCGs in the brain in 3xTg-AD mice. In addition, the expression of Aβ and p-tau in hippocampus in 3xTg-AD mice were significantly increased, and the expression of p-tau is higher in night than in day. These results indicate that the abnormal expression profiles of orexin system genes and its interaction with AD risk genes or CCGs might exert important role in the pathogenesis of AD, which will increase the expression of Aβ and p-tau, and accelerate the development of AD.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":" ","pages":"632-643"},"PeriodicalIF":3.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41237274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeuroMolecular MedicinePub Date : 2023-12-01Epub Date: 2023-09-12DOI: 10.1007/s12017-023-08755-0
Yu Liang, Guangshang Zhong, Mingxin Ren, Tingting Sun, Yangyang Li, Ming Ye, Caiyun Ma, Yu Guo, Changqing Liu
{"title":"The Role of Ubiquitin-Proteasome System and Mitophagy in the Pathogenesis of Parkinson's Disease.","authors":"Yu Liang, Guangshang Zhong, Mingxin Ren, Tingting Sun, Yangyang Li, Ming Ye, Caiyun Ma, Yu Guo, Changqing Liu","doi":"10.1007/s12017-023-08755-0","DOIUrl":"10.1007/s12017-023-08755-0","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a common neurodegenerative disease that is mainly in middle-aged people and elderly people, and the pathogenesis of PD is complex and diverse. The ubiquitin-proteasome system (UPS) is a master regulator of neural development and the maintenance of brain structure and function. Dysfunction of components and substrates of this UPS has been linked to neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. Moreover, UPS can regulate α-synuclein misfolding and aggregation, mitophagy, neuroinflammation and oxidative stress to affect the development of PD. In the present study, we review the role of several related E3 ubiquitin ligases and deubiquitinating enzymes (DUBs) on the pathogenesis of PD such as Parkin, CHIP, USP8, etc. On this basis, we summarize the connections and differences of different E3 ubiquitin ligases in the pathogenesis, and elaborate on the regulatory progress of different DUBs on the pathogenesis of PD. Therefore, we can better understand their relationships and provide feasible and valuable therapeutic clues for UPS-related PD treatment research.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":" ","pages":"471-488"},"PeriodicalIF":3.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10211710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Increased IL-6 Levels and the Upregulation of Iron Regulatory Biomarkers Contribute to the Progression of Japanese Encephalitis Virus Infection's Pathogenesis.","authors":"Anjali Singh, Sneha Ghildiyal, Prabhaker Mishra, Gajendra Singh, Himanshu Dandu, Alok Kumar","doi":"10.1007/s12017-023-08762-1","DOIUrl":"10.1007/s12017-023-08762-1","url":null,"abstract":"<p><p>Integrated analysis of iron regulatory biomarkers and inflammatory response could be an important strategy for Japanese encephalitis viral (JEV) infection disease management. In the present study, the inflammatory response was assessed by measuring serum Interleukin-6 (IL-6) levels using ELISA, and the transcription levels of iron homeostasis regulators were analyzed via RT-PCR. Furthermore, inter-individual variation in the transferrin gene was analyzed by PCR-RFLP and their association with clinical symptoms, susceptibility, severity, and outcomes was assessed through binary logistic regression and classification and regression tree (CART) analysis. Our findings revealed elevated levels of IL-6 in serum as well as increased expression of hepcidin (HAMP), transferrin (TF), and transferrin receptor-1 (TFR1) mRNA in JEV infection cases. Moreover, we found a genetic variation in TF (rs4481157) associated with clinical symptoms of meningoencephalitis. CART analysis indicates that individuals with the wild-type TF genotype are more susceptible to moderate JEV infection, while those with the homozygous type are in the high-risk group to develop a severe JEV condition. In summary, the study highlights that JEV infection induces alteration in both IL-6 levels and iron regulatory processes, which play pivotal roles in the development of JEV disease pathologies.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":" ","pages":"596-602"},"PeriodicalIF":3.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71425509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeuroMolecular MedicinePub Date : 2023-12-01Epub Date: 2023-09-23DOI: 10.1007/s12017-023-08758-x
Alice Laschuk Herlinger, Gustavo Lovatto Michaelsen, Marialva Sinigaglia, Lívia Fratini, Gabriela Nogueira Debom, Elizandra Braganhol, Caroline Brunetto de Farias, Algemir Lunardi Brunetto, André Tesainer Brunetto, Mariane da Cunha Jaeger, Rafael Roesler
{"title":"Modulation of Viability, Proliferation, and Stemness by Rosmarinic Acid in Medulloblastoma Cells: Involvement of HDACs and EGFR.","authors":"Alice Laschuk Herlinger, Gustavo Lovatto Michaelsen, Marialva Sinigaglia, Lívia Fratini, Gabriela Nogueira Debom, Elizandra Braganhol, Caroline Brunetto de Farias, Algemir Lunardi Brunetto, André Tesainer Brunetto, Mariane da Cunha Jaeger, Rafael Roesler","doi":"10.1007/s12017-023-08758-x","DOIUrl":"10.1007/s12017-023-08758-x","url":null,"abstract":"<p><p>Medulloblastoma (MB) is a heterogeneous group of malignant pediatric brain tumors, divided into molecular groups with distinct biological features and prognoses. Currently available therapy often results in poor long-term quality of life for patients, which will be afflicted by neurological, neuropsychiatric, and emotional sequelae. Identifying novel therapeutic agents capable of targeting the tumors without jeopardizing patients' quality of life is imperative. Rosmarinic acid (RA) is a plant-derived compound whose action against a series of diseases including cancer has been investigated, with no side effects reported so far. Previous studies have not examined whether RA has effects in MB. Here, we show RA is cytotoxic against human Daoy (IC<sub>50</sub> = 168 μM) and D283 (IC<sub>50</sub> = 334 μM) MB cells. Exposure to RA for 48 h reduced histone deacetylase 1 (HDAC1) expression while increasing H3K9 hyperacetylation, reduced epidermal growth factor (EGFR) expression, and inhibited EGFR downstream targets extracellular-regulated kinase (ERK)1/2 and AKT in Daoy cells. These modifications were accompanied by increased expression of CDKN1A/p21, reduced expression of SOX2, and a decrease in proliferative rate. Treatment with RA also reduced cancer stem cell markers expression and neurosphere size. Taken together, our findings indicate that RA can reduce cell proliferation and stemness and induce cell cycle arrest in MB cells. Mechanisms mediating these effects may include targeting HDAC1, EGFR, and ERK signaling, and promoting p21 expression, possibly through an increase in H3K9ac and AKT deactivation. RA should be further investigated as a potential anticancer agent in experimental MB.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":" ","pages":"573-585"},"PeriodicalIF":3.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41127157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Targeting Pericytes for Functional Recovery in Ischemic Stroke.","authors":"Shuqi Hu, Bingjie Yang, Song Shu, Xudong He, Hongfei Sang, Xuemei Fan, Hao Zhang","doi":"10.1007/s12017-023-08748-z","DOIUrl":"10.1007/s12017-023-08748-z","url":null,"abstract":"<p><p>Pericytes surrounding endothelial cells in the capillaries are emerging as an attractive cell resource, which can show a large variety of functions in ischemic stroke, including preservation of the blood-brain barrier, regulation of immune function, and support for cerebral vasculature. These functions have been fully elucidated in previous studies. However, in recent years, increasing evidence has shown that pericytes play an important role in neurological recovery after ischemic stroke due to their regenerative function which can be summarized in two aspects according to current discoveries, one is that pericytes are thought to be multipotential themselves, and the other is that pericytes can promote the differentiation of oligodendrocyte progenitor cells (OPCs). Considering the neuroprotective treatment for stroke has not been much progressed in recent years, new therapies targeting pericytes may be a future direction. Here, we will review the beneficial effects of pericytes in ischemic stroke from two directions: the barrier and vascular functions and the regenerative functions of pericytes.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":" ","pages":"457-470"},"PeriodicalIF":3.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9443461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeuroMolecular MedicinePub Date : 2023-12-01Epub Date: 2023-08-21DOI: 10.1007/s12017-023-08750-5
Ying Zhao, Yan Lin, Bin Wang, Fuchen Liu, Dandan Zhao, Wei Wang, Hong Ren, Jiayin Wang, Zhihong Xu, Chuanzhu Yan, Kunqian Ji
{"title":"A Missense Variant in AIFM1 Caused Mitochondrial Dysfunction and Intolerance to Riboflavin Deficiency.","authors":"Ying Zhao, Yan Lin, Bin Wang, Fuchen Liu, Dandan Zhao, Wei Wang, Hong Ren, Jiayin Wang, Zhihong Xu, Chuanzhu Yan, Kunqian Ji","doi":"10.1007/s12017-023-08750-5","DOIUrl":"10.1007/s12017-023-08750-5","url":null,"abstract":"<p><p>AIFM1 is a mitochondrial flavoprotein involved in caspase-independent cell death and regulation of respiratory chain complex biogenesis. Mutations in the AIFM1 gene have been associated with multiple clinical phenotypes, but the effectiveness of riboflavin treatment remains controversial. Furthermore, few studies explored the reasons underlying this controversy. We reported a 7-year-old boy with ataxia, sensorimotor neuropathy and muscle weakness. Genetic and histopathological analyses were conducted, along with assessments of mitochondrial function and apoptosis level induced by staurosporine. Riboflavin deficiency and supplementation experiments were performed using fibroblasts. A missense c.1019T > C (p. Met340Thr) variant of AIFM1 was detected in the proband, which caused reduced expression of AIFM1 protein and mitochondrial dysfunction as evidenced by downregulation of mitochondrial complex subunits, respiratory deficiency and collapse of ΔΨm. The proportion of apoptotic cells in mutant fibroblasts was lower than controls after induction of apoptosis. Riboflavin deficiency resulted in decreased AIFM1 protein levels, while supplementation with high concentrations of riboflavin partially increased AIFM1 protein levels in variant fibroblasts. In addition, mitochondrial respiratory function of mutant fibroblasts was partly improved after riboflavin supplementation. Our study elucidated the pathogenicity of the AIFM1 c.1019T > C variant and revealed mutant fibroblasts was intolerant to riboflavin deficiency. Riboflavin supplementation is helpful in maintaining the level of AIFM1 protein and mitochondrial respiratory function. Early riboflavin treatment may serve as a valuable attempt for patients with AIFM1 variant.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":" ","pages":"489-500"},"PeriodicalIF":3.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10407320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeuroMolecular MedicinePub Date : 2023-12-01Epub Date: 2023-09-21DOI: 10.1007/s12017-023-08759-w
Antonio Gennaro Nicotera, Greta Amore, Maria Concetta Saia, Mirella Vinci, Antonino Musumeci, Valeria Chiavetta, Concetta Federico, Giulia Spoto, Salvatore Saccone, Gabriella Di Rosa, Francesco Calì
{"title":"Fibroblast Growth Factor Receptor 2 (FGFR2), a New Gene Involved in the Genesis of Autism Spectrum Disorder.","authors":"Antonio Gennaro Nicotera, Greta Amore, Maria Concetta Saia, Mirella Vinci, Antonino Musumeci, Valeria Chiavetta, Concetta Federico, Giulia Spoto, Salvatore Saccone, Gabriella Di Rosa, Francesco Calì","doi":"10.1007/s12017-023-08759-w","DOIUrl":"10.1007/s12017-023-08759-w","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) is a long-known complex neurodevelopmental disorder, and over the past decades, with the enhancement of the research genomic techniques, has been the object of intensive research activity, and many genes involved in the development and functioning of the central nervous system have been related to ASD genesis. Herein, we report a patient with severe ASD carrying a G > A de novo variant in the FGFR2 gene, determining a missense mutation. FGFR2 encodes for the ubiquitous fibroblast growth factor receptor (FGFR) type 2, a tyrosine kinase receptor implicated in several biological processes. The mutated version of this protein is known to be responsible for several variable overlapping syndromes. Even if there still is only sparse and anecdotal data, recent research highlighted a potential role of FGFR2 on neurodevelopment. Our findings provide new insights into the potential causative role of FGFR2 gene in complex neurodevelopmental disorders.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":" ","pages":"650-656"},"PeriodicalIF":3.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10721674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41143055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeuroMolecular MedicinePub Date : 2023-12-01Epub Date: 2023-09-21DOI: 10.1007/s12017-023-08756-z
Hua Fan, Yang Yang, Qianqian Bai, Dongmei Wang, Xiaofei Shi, Lele Zhang, Yanhui Yang
{"title":"Neuroprotective Effects of Sinomenine on Experimental Autoimmune Encephalomyelitis via Anti-Inflammatory and Nrf2-Dependent Anti-Oxidative Stress Activity.","authors":"Hua Fan, Yang Yang, Qianqian Bai, Dongmei Wang, Xiaofei Shi, Lele Zhang, Yanhui Yang","doi":"10.1007/s12017-023-08756-z","DOIUrl":"10.1007/s12017-023-08756-z","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS). Sinomenine (SIN), a bioactive alkaloid extracted from the Chinese medicinal plant Sinomenium acutum, has powerful anti-inflammatory and immunosuppressive therapeutic benefits. In our previous research, we found that SIN increased resistance to oxidative stress via the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in PC12 neuronal cells. However, whether SIN can improve the symptoms and pathological features of experimental autoimmune encephalomyelitis (EAE), a murine model of MS, via the Nrf2 signaling pathway remains unclear. EAE was immunized followed by SIN treatment. Then we evaluated the effects of SIN in EAE. Subsequently, primary microglia were cultured to explore the effect of SIN on microglia activation. Further, the levels of Nrf2 and its downstream molecules were detected to assess the molecular mechanisms of SIN. We demonstrated that SIN effectively ameliorated the severity of EAE, accompanied by a reduction in the demyelination, axonal damage and inhibition of inflammatory cell infiltration. Mechanistically, SIN decreased the inflammatory cytokines expression, and suppressed microglia and astrocytes activation in EAE mice. Furthermore, SIN suppressed lipopolysaccharide (LPS)-induced microglial activation and the production of pro-inflammatory factors in vitro. Moreover, SIN inhibited oxidative stress via the activation of the Nrf2 signaling pathway. Our work proves that SIN exerts its neuroprotective effects by the Nrf2-dependent anti-oxidative stress and diminishing neuroinflammation, suggesting that the \"antioxiflammation\" effect of SIN is expected to be an ideal treatment strategy for MS/EAE.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":" ","pages":"545-562"},"PeriodicalIF":3.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41133031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}