Journal of Alzheimer's disease : JAD最新文献

{"title":"Highly Specific and Sensitive Target Binding by the Humanized pS396-Tau Antibody hC10.2 Across a Wide Spectrum of Alzheimer's Disease and Primary Tauopathy Postmortem Brains.","authors":"L. Helboe, N. Rosenqvist, C. Volbracht, L. Pedersen, J. T. Pedersen, Søren Christensen, J. Egebjerg, C. Christoffersen, B. Bang-Andersen, T. Beach, G. Serrano, J. Falsig","doi":"10.3233/jad-220125","DOIUrl":"https://doi.org/10.3233/jad-220125","url":null,"abstract":"BACKGROUND\u0000Deposits of hyperphosphorylated tau fibrils are hallmarks of a broad spectrum of tauopathies, including Alzheimer's disease (AD).\u0000\u0000\u0000OBJECTIVE\u0000To investigate heterogeneity of tau pathology across brain extracts from a broad selection of different tauopathies and examine the binding properties of the humanized pS396-tau antibody hC10.2 and six other anti-tau antibodies.\u0000\u0000\u0000METHODS\u000076 individual tauopathy tissue samples were analyzed in a battery of assays: immunohistochemistry, ELISA, tau aggregation assay, western blot, [3H]PI-2620 and [3H]MK-6240 tau tracer binding, and aggregated seeding activity in RD_P301S HEK293T Biosensor cells. The efficiency of seven anti-tau antibodies to engage with pathological tau species was directly compared.\u0000\u0000\u0000RESULTS\u0000Our data indicate that a strong correlation existed between the tau tracer binding, amount of tau aggregates, pS396-tau phosphorylation, and seeding activity. The hC10.2 antibody, which has entered clinical development, effectively engaged with its epitope across all individual cases of mid-stage and late AD, and primary tauopathies. hC10.2 was superior compared to other phospho- and total tau antibodies to prevent seeded tau aggregation in the biosensor cells. hC10.2 effectively depleted hyperphosphorylated and aggregated tau species across all tauopathy samples proportionally to the amount of tau aggregates. In AD samples, hC10.2 bound to ghost tangles which represent extracellular pathological tau species.\u0000\u0000\u0000CONCLUSION\u0000S396 hyperphosphorylation is a feature of the formation of seeding-competent tau across different tauopathies and it is present both in intra- and extracellular pathological tau. hC10.2 represents an excellent candidate for a hyperphosphorylation-selective therapeutic tau antibody for the treatment of AD and primary tauopathies.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"104 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129080444","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":"Erratum to: Association Between Body Mass Index and Incident Dementia Among Community-Dwelling Older Adults: The Shanghai Aging Study.","authors":"","doi":"10.3233/jad-229004","DOIUrl":"https://doi.org/10.3233/jad-229004","url":null,"abstract":"","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"18 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131998834","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":"Cattle Encephalon Glycoside and Ignotin Ameliorate Palmitoylation of PSD-95 and Enhance Expression of Synaptic Proteins in the Frontal Cortex of a APPswe/PS1dE9 Mouse Model of Alzheimer's Disease.","authors":"Yinghan Zhang, Ya-zhuo Hu, Zhi-Tao Han, Y. Geng, Zheng Xia, Yongsheng Zhou, Zhenfu Wang, Yuanyuan Wang, Eryan Kong, Xiaoning Wang, J. Jia, Hong-Hong Zhang","doi":"10.3233/jad-220009","DOIUrl":"https://doi.org/10.3233/jad-220009","url":null,"abstract":"BACKGROUND\u0000Synaptic abnormalities in synaptic proteins are the initial hallmarks of Alzheimer's disease (AD). The higher level of palmitoylation of synaptic proteins was closely associated with amyloid-β (Aβ) in AD. Cattle encephalon glycoside and ignotin (CEGI) have been shown to act as multitarget neurotrophic agents in APPswe/PS1dE9 (APP/PS1) transgenic AD mice. However, it is not clear whether CEGI can influence Aβ deposition or whether it does so by the regulation of protein palmitoylation and expression of synaptic proteins in transgenic AD mice.\u0000\u0000\u0000OBJECTIVE\u0000In this study, we investigated the roles of CEGI in modulating postsynaptic density protein 95 (PSD-95) palmitoylation, Aβ pathologies, and expression of synaptic-associated proteins in APP/PS1 mice.\u0000\u0000\u0000METHODS\u0000Five-month-old APP/PS1 mice were treated intraperitoneally with 6.6 mL/kg of CEGI for 6 weeks. At the end of the treatment period, APP/PS1 mice were subjected to Morris water maze to test their cognitive functions. Acyl-biotinyl exchange (ABE) for PSD-95 palmitoylation, immunofluorescent staining for expression of PSD-95, N-methyl-D-aspartic acid receptor subunit 2B (NR2B), and synaptotagmin 1 (SYT1) were assessed in mouse brain sections.\u0000\u0000\u0000RESULTS\u0000CEGI treatment in APP/PS1 mice significantly reduced Aβ deposition, relieved memory deficits, and decreased PSD-95 palmitoylation while markedly increasing the expression of PSD-95, NR2B, and SYT1 in the frontal cortex. There was a significant correlation between Aβ expression and PSD-95 palmitoylation in APP/PS1 mice.\u0000\u0000\u0000CONCLUSION\u0000Our findings demonstrate that CEGI improved AD-like neuropathology, possibly by inhibiting PSD-95 palmitoylation, improving learning memory, and enhancing expression of synaptic-associated proteins, representing a potential therapy for AD treatment.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"12 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114528047","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":"Aberrant Cross-Tissue Functional Connectivity in Alzheimer's Disease: Static, Dynamic, and Directional Properties.","authors":"Xingxing Zhang, Qing Guan, Yingjia Li, Jianfeng Zhang, Wanlin Zhu, Yuejia Luo, Haobo Zhang","doi":"10.3233/jad-215649","DOIUrl":"https://doi.org/10.3233/jad-215649","url":null,"abstract":"BACKGROUND\u0000BOLD signals in the gray matter (GM) and white matter (WM) are tightly coupled. However, our understanding of the cross-tissue functional network in Alzheimer's disease (AD) is limited.\u0000\u0000\u0000OBJECTIVE\u0000We investigated the changes of cross-tissue functional connectivity (FC) metrics for the GM regions susceptible to AD damage.\u0000\u0000\u0000METHODS\u0000For each GM region in the default mode (DMN) and limbic networks, we obtained its low-order static FC with any WM region, and the high-order static FC between any two WM regions based on their FC pattern similarity with multiple GM regions. The dynamic and directional properties of cross-tissue FC were then acquired, specifically for the regional pairs whose low- or high-order static FCs showed significant differences between AD and normal control (NC). Moreover, these cross-tissue FC metrics were correlated with voxel-based GM volumes and MMSE in all participants.\u0000\u0000\u0000RESULTS\u0000Compared to NC, AD patients showed decreased low-order static FCs between the intra-hemispheric GM-WM pairs (right ITG-right fornix; left MoFG-left posterior corona radiata), and increased low-order static, dynamic, and directional FCs between the inter-hemispheric GM-WM pairs (right MTG-left superior/posterior corona radiata). The high-order static and directional FCs between the left cingulate bundle-left tapetum were increased in AD, based on their FCs with the GMs of DMN. Those decreased and increased cross-tissue FC metrics in AD had opposite correlations with memory-related GM volumes and MMSE (positive for the decreased and negative for the increased).\u0000\u0000\u0000CONCLUSION\u0000Cross-tissue FC metrics showed opposite changes in AD, possibly as useful neuroimaging biomarkers to reflect neurodegenerative and compensatory mechanisms.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129707818","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":"Ethnic-Specific Type 2 Diabetes Risk Factor PAX4 R192H Is Associated with Attention-Specific Cognitive Impairment in Chinese with Type 2 Diabetes.","authors":"S. Ang, Serena Low, T. Ng, Clara S. H. Tan, K. Ang, Ziliang Lim, W. Tang, T. Subramaniam, C. Sum, S. Lim","doi":"10.3233/jad-220036","DOIUrl":"https://doi.org/10.3233/jad-220036","url":null,"abstract":"BACKGROUND\u0000Type 2 diabetes mellitus (T2DM) has been shown to increase the risks of cognitive decline and dementia. Paired box gene 4 (PAX4), a transcription factor for beta cell development and function, has recently been implicated in pathways intersecting Alzheimer's disease and T2DM.\u0000\u0000\u0000OBJECTIVE\u0000In this report, we evaluated the association of the ethnic-specific PAX4 R192H variant, a T2DM risk factor for East Asians which contributes to earlier diabetes onset, and cognitive function of Chinese T2DM patients.\u0000\u0000\u0000METHODS\u0000590 Chinese patients aged 45-86 from the SMART2D study were genotyped for PAX4 R192H variation using Illumina OmniExpress-24 Array. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) which had been validated in the Singapore population was administered to assess five cognitive domains: immediate memory, visuospatial/constructional, language, attention, and delayed memory. Multiple linear regression was used to assess the association of the R192H risk allele and cognitive domains.\u0000\u0000\u0000RESULTS\u0000Patients with two PAX4 R192H risk alleles showed significantly lower attention index score (β= -8.46, 95% CI [-13.71, -3.21], p = 0.002) than patients with wild-type alleles after adjusting for age, gender, diabetes onset age, HbA1c, body-mass index, renal function, lipid profiles, systolic blood pressure, metformin usage, smoking history, education level, Geriatric Depression Scale score, and presence of APOEɛ4 allele.\u0000\u0000\u0000CONCLUSION\u0000Ethnic-specific R192H variation in PAX4 is associated with attention-specific cognitive impairment in Chinese with T2DM. Pending further validation studies, determining PAX4 R192H genotype may be helpful for early risk assessment of early-onset T2DM and cognitive impairment to improve diabetes care.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"148 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126898274","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":"A Cobalt-Containing Compound as a Stronger Inhibitor than Galantamine to Inhibit Acetylcholinesterase Activity: A New Drug Candidate for Alzheimer's Disease Treatment.","authors":"Mohadeseh Kalari, Zeinab Abbasi, M. D. Shasaltaneh, A. Khaleghian, Z. Moosavi-Nejad","doi":"10.3233/JAD-215588","DOIUrl":"https://doi.org/10.3233/JAD-215588","url":null,"abstract":"BACKGROUND\u0000Acetylcholinesterase (AChE) regulates the transmission of neural messages by hydrolyzing acetylcholine in synaptic spaces.\u0000\u0000\u0000OBJECTIVE\u0000The effects of many AChE inhibitors have been evaluated in the treatment of Alzheimer's disease, but the present study examined a synthetic complex containing cobalt (SC) for the first time in the field of enzyme activity to evaluate enzyme inhibitory function.\u0000\u0000\u0000METHODS\u0000Ellman's test was applied. AChE function was assessed in the presence of SC through docking and molecular dynamics analyses. The second structure of AChE was studied through circular dichroism (CD) spectroscopy.\u0000\u0000\u0000RESULTS\u0000Several enzymatic methods were utilized for the kinetics of AChE, which indicated the non-Michaelis and positive homotropic behavior of AChE in the absence of inhibitors (Hill coefficient = 1.33). However, the existence of inhibitors did not eliminate this homotropic state, and even AChE had a more sigmoidal shape than the galantamine at the presence of SC. Based on the CD spectroscopy results, AChE structure changed in the existence of inhibitors and substrates. Bioinformatics analysis revealed SC bonding to the channel of active site AChE. The number of hydrogen bonds was such that the flexibility of the enzyme protein structure due to inhibitor binding reduced AChE function.\u0000\u0000\u0000CONCLUSION\u0000The results reflected that AChE exhibited a non-Michaelis and positive homotropic behavior, leading to a more inhibitory effect on the SC than the galantamine. The positive homotropic behavior of AChE was intensified due to the alteration in AChE protein structure by binding SC to hydrophobic region in the active site pathway and impressing Trp84.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"4 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125309050","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":"Experimental Periodontitis Deteriorates Cognitive Function and Impairs Insulin Signaling in a Streptozotocin-Induced Alzheimer's Disease Rat Model.","authors":"L. Duan, X. Qian, Qin Wang, Lan Huang, S. Ge","doi":"10.3233/JAD-215720","DOIUrl":"https://doi.org/10.3233/JAD-215720","url":null,"abstract":"BACKGROUND\u0000With advancements in periodontal medicine, the relationship between periodontitis and systemic diseases has garnered increasing attention. Recently, emerging evidence has indicated that periodontitis may be involved in the pathogenesis of Alzheimer's disease (AD).\u0000\u0000\u0000OBJECTIVE\u0000To assess the impact of experimental periodontitis on cognitive function deficits in a rat model of streptozotocin-induced AD and determine the mechanisms underlying these effects.\u0000\u0000\u0000METHODS\u0000Rats were randomly assigned to the control (C), experimental periodontitis (P), Alzheimer's disease (AD), and experimental periodontitis with streptozotocin-induced AD (AD-P) groups. Experimental periodontitis was induced using ligation and coating with Porphyromonas gingivalis. In the AD-P group, AD was induced by intracerebroventricular injection of streptozotocin after 6 weeks of experimental periodontitis induction.\u0000\u0000\u0000RESULTS\u0000Compared with the group C rats, those in group P exhibited alveolar bone resorption, learning and memory function impairment, and decreased insulin sensitivity and insulin signaling-related protein expression. Glial cell activation and cognitive impairment in streptozotocin-induced groups with significantly increased phosphorylated tau levels were more pronounced relative to the C group. The number of neurons and insulin sensitivity and insulin signaling-related protein expression in group AD-P rats were lower than those in the AD alone group, while the expressions of glial fibrillary acidic protein, tau phosphorylation, interleukin-6, and cyclooxygenase-2 were significantly increased.\u0000\u0000\u0000CONCLUSION\u0000Periodontitis may be a risk factor exacerbating cognitive deficits in an AD-like neurodegenerative context, possibly by impairing the insulin signaling pathway and stimulating gliosis and neuroinflammation.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"11 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131544074","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":"Impact of Sarcopenia on Decline in Quality of Life in Older People with Mild Cognitive Impairment.","authors":"H. Umegaki, Yusuke Suzuki, H. Komiya, Kazuhisa Watanabe, M. Nagae, Y. Yamada","doi":"10.3233/JAD-220123","DOIUrl":"https://doi.org/10.3233/JAD-220123","url":null,"abstract":"Quality of life (QOL) was assessed using the EQ-5D twice in 1 year in 57 older community-dwelling people (age 79.1±5.9 years) with mild cognitive impairment in a memory clinic. Screening for sarcopenia at the initial assessment revealed 40.1% of participants (23/57) were sarcopenic. QOL declined in 33.3% of participants (19/57) after around 1 year. Multiple logistic regression analysis showed that sarcopenia was associated with a decline in QOL around 1 year after initial assessment. Sarcopenia may be a risk factor for decline in QOL in older people with mild cognitive impairment.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"21 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"117264784","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":"Neighborhood Social Cohesion and Dementia-Related Stigma Among Mothers of Adolescents in the Pre- and Current COVID-19 Period: An Observational Study Using Population-Based Cohort Data.","authors":"M. Nakanishi, S. Yamasaki, S. Ando, K. Endo, M. Richards, M. Hiraiwa-Hasegawa, K. Kasai, A. Nishida","doi":"10.3233/JAD-220043","DOIUrl":"https://doi.org/10.3233/JAD-220043","url":null,"abstract":"BACKGROUND\u0000Middle-aged adults may be the ideal target group for dementia-related stigma reduction interventions to encourage the utilization of services among those who may become family caregivers. Neighborhood social cohesion may diminish dementia-related stigma, particularly in terms of perceived public attitudes. The COVID-19 pandemic can further negatively impact perceived public stigma.\u0000\u0000\u0000OBJECTIVE\u0000To investigate the association between neighborhood social cohesion and dementia-related stigma during the pre- and current COVID-19 period.\u0000\u0000\u0000METHODS\u0000We employed a cross-sectional design using data from a large population-based cohort, the Tokyo Teen Cohort, in Japan. Overall, 2,469 mothers of 16-year-old adolescents self-completed a questionnaire comprising nine dementia-related stigma questions evaluating perceived public and personal attitudes. Neighborhood social cohesion was assessed using a five-item instrument. The participants were divided into two groups according to the time of assessment: prior to the pandemic's onset (February 2019-March 2020) and during the pandemic (April 2020-July 2021). A multiple regression analysis of stigma was performed using neighborhood social cohesion as an independent variable, and caring experience, age, educational level, and working status as covariates.\u0000\u0000\u0000RESULTS\u0000Personal and perceived public stigma were significantly lower in participants who perceived greater neighborhood social cohesion. However, level of personal and perceived public stigma did not differ between pre- and during the pandemic period.\u0000\u0000\u0000CONCLUSION\u0000Neighborhood social cohesion may be a modifiable factor for dementia-related stigma. A localized intervention to enhance social cohesion in the neighborhood community would promote the utilization of services among those who may become family caregivers.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"48 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134487704","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":"Expression of Olfactory-Related Genes in the Olfactory Epithelium of an Alzheimer's Disease Mouse Model.","authors":"M. Narukawa, Y. Mori, Riko Nishida, Suzuka Takahashi, T. Saito, T. Saido, T. Misaka","doi":"10.3233/JAD-220213","DOIUrl":"https://doi.org/10.3233/JAD-220213","url":null,"abstract":"Using an amyloid precursor protein (App) gene knock-in (KI) mouse of Alzheimer's disease (AD), we investigated the expression of olfactory-related genes in olfactory impairment caused by AD. We observed the change in olfactory behavior in the App-KI mice. There was no significant difference, however, in the mRNA expression levels of olfactory-related genes between the olfactory epithelia of wild-type (WT) and App-KI mice. Amyloid-β deposition was confirmed throughout the olfactory pathway in App-KI mice, but not in WT mice. These show that the change in olfactory behavior in the App-KI mice might cause by the impairment of the olfactory pathway.","PeriodicalId":219895,"journal":{"name":"Journal of Alzheimer's disease : JAD","volume":"24 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126462316","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}