Current Alzheimer research最新文献

{"title":"A Look at the Etiology of Alzheimer's Disease based on the Brain Ischemia Model.","authors":"Ryszard Pluta","doi":"10.2174/0115672050320921240627050736","DOIUrl":"https://doi.org/10.2174/0115672050320921240627050736","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the frequent form of dementia in the world. Despite over 100 years of research into the causes of AD, including amyloid and tau protein, the research has stalled and has not led to any conclusions. Moreover, numerous projects aimed at finding a cure for AD have also failed to achieve a breakthrough. Thus, the failure of anti-amyloid and anti-tau protein therapy to treat AD significantly influenced the way we began to think about the etiology of the disease. This situation prompted a group of researchers to focus on ischemic brain episodes, which, like AD, mostly present alterations in the hippocampus. In this context, it has been proposed that cerebral ischemic incidents may play a major role in promoting amyloid and tau protein in neurodegeneration in AD. In this review, we summarized the experimental and clinical research conducted over several years on the role of ischemic brain episodes in the development of AD. Studies have shown changes typical of AD in the course of brain neurodegeneration post-ischemia, i.e., progressive brain and hippocampal atrophy, increased amyloid production, and modification of tau protein. In the post-ischemic brain, the diffuse and senile amyloid plaques and the development of neurofibrillary tangles characteristic of AD were revealed. The above data evidently showed that after brain ischemia, there are modifications in protein folding, leading to massive neuronal death and damage to the neuronal network, which triggers dementia with the AD phenotype.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141500104","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":"ROCK Inhibitor Fasudil Attenuates Neuroinflammation and Associated Metabolic Dysregulation in the Tau Transgenic Mouse Model of Alzheimer's Disease.","authors":"Xiaosen Ouyang, Roberto Collu, Gloria Benavides, Ran Tian, Victor Darley-Usmar, Weiming Xia, Jianhua Zhang","doi":"10.2174/0115672050317608240531130204","DOIUrl":"https://doi.org/10.2174/0115672050317608240531130204","url":null,"abstract":"<p><p>The pathological manifestations of Alzheimer's disease (AD) include not only brain amyloid β protein (Aβ) containing neuritic plaques and hyperphosphorylated tau (p-tau) containing neurofibrillary tangles but also microgliosis, astrocytosis, and neurodegeneration mediated by metabolic dysregulation and neuroinflammation.</p><p><strong>Method: </strong>While antibody-based therapies targeting Aβ have shown clinical promise, effective therapies targeting metabolism, neuroinflammation, and p-tau are still an urgent need. Based on the observation that Ras homolog (Rho)-associated kinases (ROCK) activities are elevated in AD, ROCK inhibitors have been explored as therapies in AD models. This study determines the effects of fasudil, a ROCK inhibitor, on neuroinflammation and metabolic regulation in the P301S tau transgenic mouse line PS19 that models neurodegenerative tauopathy and AD. Using daily intraperitoneal (i.p.) delivery of fasudil in PS19 mice, we observed a significant hippocampal-specific decrease of the levels of phosphorylated tau (pTau Ser202/Thr205), a decrease of GFAP+ cells and glycolytic enzyme Pkm1 in broad regions of the brain, and a decrease in mitochondrial complex IV subunit I in the striatum and thalamic regions.</p><p><strong>Results: </strong>Although no overt detrimental phenotype was observed, mice dosed with 100 mg/kg/day for 2 weeks exhibited significantly decreased mitochondrial outer membrane and electron transport chain (ETC) protein abundance, as well as ETC activities.</p><p><strong>Conclusion: </strong>Our results provide insights into dose-dependent neuroinflammatory and metabolic responses to fasudil and support further refinement of ROCK inhibitors for the treatment of AD.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141444016","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":"Artificial Intelligence in Eye Movements Analysis for Alzheimer's Disease Early Diagnosis.","authors":"Shadi Farabi Maleki, Milad Yousefi, Navid Sobhi, Ali Jafarizadeh, Roohallah Alizadehsani, Juan Manuel Gorriz-Saez","doi":"10.2174/0115672050322607240529075641","DOIUrl":"https://doi.org/10.2174/0115672050322607240529075641","url":null,"abstract":"<p><p>As the world's population ages, Alzheimer's disease is currently the seventh most common cause of death globally; the burden is anticipated to increase, especially among middle-class and elderly persons. Artificial intelligence-based algorithms that work well in hospital environments can be used to identify Alzheimer's disease. A number of databases were searched for English-language articles published up until March 1, 2024, that examined the relationships between artificial intelligence techniques, eye movements, and Alzheimer's disease. A novel non-invasive method called eye movement analysis may be able to reflect cognitive processes and identify anomalies in Alzheimer's disease. Artificial intelligence, particularly deep learning, and machine learning, is required to enhance Alzheimer's disease detection using eye movement data. One sort of deep learning technique that shows promise is convolutional neural networks, which need further data for precise classification. Nonetheless, machine learning models showed a high degree of accuracy in this context. Artificial intelligence-driven eye movement analysis holds promise for enhancing clinical evaluations, enabling tailored treatment, and fostering the development of early and precise Alzheimer's disease diagnosis. A combination of artificial intelligence-based systems and eye movement analysis can provide a window for early and non-invasive diagnosis of Alzheimer's disease. Despite ongoing difficulties with early Alzheimer's disease detection, this presents a novel strategy that may have consequences for clinical evaluations and customized medication to improve early and accurate diagnosis.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141263035","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":"Nanostructured Lipid Carriers of Donepezil Hydrochloride for the Treatment of Alzheimer's Disease.","authors":"Avinash Tekade, Ram Susar, Gajanan Kulkarni, Samiksha Surwade, Anil Gaikwad","doi":"10.2174/0115672050288659240229080535","DOIUrl":"https://doi.org/10.2174/0115672050288659240229080535","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's Disease (AD) is a long-term brain disorder that worsens over time. A cholinesterase inhibitor called Donepezil HCl (DNZ) is used to treat and control AD. Due to its failure to reach the appropriate concentration in the brain cells, its efficacy upon oral administration is limited, and thus investigation of alternative administration route is necessary.</p><p><strong>Objective: </strong>The objective of this study was to develop donepezil HCl-loaded Nanostructured Lipid Carriers (NLCs) that can bypass the blood-brain barrier and thus be directly delivered to the brain through the nasal route. This method improves availability at the site of action, reduces the negative effects of oral medication, and ensures an expedited commencement of action.</p><p><strong>Method: </strong>High-pressure homogenization and ultrasonication were used to formulate NLCs. Glyceryl Monostearate (GMS) as a solid lipid, Tween 80 as a surfactant, and Poloxamer 407 as a co-- surfactant were used. In this study, argan oil was employed as a liquid lipid as well as a penetration enhancer.</p><p><strong>Results: </strong>The chosen NLCs displayed a particle size of 137.34 ± 0.79 nm, a PDI of 0.365 ± 0.03, and a zeta potential of -10.4 mV. The selected formulation showed an entrapment efficiency of 84.05 ± 1.30% and a drug content of 77.02 ± 0.23%. The concentration of the drug in the brain after intravenous and intranasal administration of DNZ NLCs at 1 h was found to be 0.490 ± 0.007 and 4.287 ± 0.115, respectively. Thus, the concentration of DNZ achieved in the brain after intranasal administration of DNZ NLCs was approximately 9 times more than the concentration when administered by intravenous route.</p><p><strong>Conclusion: </strong>The DNZ-loaded NLCs, when administered via nasal route, showed markedly improved drug availability in the brain, suggesting an efficient drug delivery strategy to treat Alzheimer's disease.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140041277","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":"Exploring Potential of Nano-formulations in the Treatment of Alzheimer's Disease through Nasal Route.","authors":"Avinash Tekade, Prasad Kadam, Sachin Jagdale, Samiksha Surwade, Anil Gaikwad, Parth Pawar, Rushikesh Shinde","doi":"10.2174/0115672050290462240222092303","DOIUrl":"https://doi.org/10.2174/0115672050290462240222092303","url":null,"abstract":"<p><strong>Objective: </strong>Alzheimer's disease, a progressive neurodegenerative disorder, severely impacts cognitive function and daily living. The current treatment provides only symptomatic relief, and thus, disease-modifying therapies targeting underlying causes are needed. Although several potential therapies are in various stages of clinical trials, bringing a new Alzheimer's drug to market remains challenging. Hence, researchers are also exploring monoclonal antibodies, tau protein inhibitors, and anti-inflammatory drugs as treatment options. Conventionally designed dosage forms come with limitations like poor absorption, first-pass metabolism, and low bioavailability. They also cause systemic adverse effects because these designed systems do not provide target- specific drug delivery. Thus, in this review, the authors highlighted the current advancements in the development of intranasal nanoformulations for the treatment of Alzheimer's disease. This strategy of delivering anti-Alzheimer drugs through the nasal route may help to target the drug exactly to the brain, achieve rapid onset of action, avoid first-pass metabolism, and reduce the side effects and dose required for administration.</p><p><strong>Conclusion: </strong>Delivering drugs to the brain through the nasal route for treating Alzheimer's disease is crucial due to the limited efficacy of existing treatments and the profound impact of the disease on patients and their families. Thus, by exploring innovative approaches such as nose-to-brain drug delivery, it is possible to improve the quality of life for individuals living with Alzheimer's and alleviate its societal burden.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139998796","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":"Drive My CAR-AD Research here, there and Everywhere.","authors":"Juan Manuel Górriz Sáez","doi":"10.2174/156720502101240524145811","DOIUrl":"https://doi.org/10.2174/156720502101240524145811","url":null,"abstract":"","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141636394","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":"Plasma Biomarkers in Neurodegenerative Dementias: Unrevealing the Potential of Serum Oxytocin, BDNF, NPTX1, TREM2, TNF-alpha, IL-1 and Prolactin.","authors":"Yeşim Olğun, Cana Aksoy Poyraz, Melda Bozluolçay, Dildar Konukoğlu, Burç Çağrı Poyraz","doi":"10.2174/0115672050313419240520051751","DOIUrl":"10.2174/0115672050313419240520051751","url":null,"abstract":"<p><strong>Background: </strong>Dementia encompasses a range of neurodegenerative disorders characterized by cognitive decline and functional impairment. The identification of reliable biomarkers is essential for accurate diagnosis and gaining insights into the mechanisms underlying diseases.</p><p><strong>Objective: </strong>This study aimed to investigate the plasma biomarker profiles associated with Brain- Derived Neurotrophic Factor (BDNF), Oxytocin, Neuronal Pentraxin-1 (NPTX1), Triggering Receptor Expressed on Myeloid Cells 2 (TREM2), Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin- 1 (IL-1) and Prolactin in Alzheimer's disease (AD), dementia with Lewy bodies (DLB), frontotemporal dementias (FTD) and healthy controls.</p><p><strong>Methods: </strong>Serum levels of the aforementioned biomarkers were analyzed in 23 AD, 28 DLB, 15 FTD patients recruited from outpatient units and 22 healthy controls. Diagnostic evaluations followed established criteria and standardized clinical tests were conducted. Blood samples were collected and analyzed using ELISA and electrochemiluminescence immunoassay methods.</p><p><strong>Results: </strong>Serum BDNF and oxytocin levels did not significantly differ across groups. NPTX1, TREM2, TNF-alpha and IL-1 levels also did not show significant differences among dementia groups. However, prolactin levels exhibited distinct patterns, with lower levels in male DLB patients and higher levels in female AD patients compared to controls.</p><p><strong>Conclusion: </strong>The study findings suggest potential shared mechanisms in dementia pathophysiology and highlight the importance of exploring neuroendocrine responses, particularly in AD and DLB. However, further research is warranted to elucidate the role of these biomarkers in dementia diagnosis and disease progression.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158674","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":"Effects of Cycloastragenol on Alzheimer's Disease in Rats by Reducing Oxidative Stress, Inflammation, and Apoptosis.","authors":"Kadi M Alharbi, Shahad A Alshehri, Wasayf A Almarwani, Khulud K Aljohani, Ajwan Z Albalawi, Areej S Alatawi, Shekha M Al-Atwi, Lama S Alhwyty, Hanan M Hassan, Mohammed M H Al-Gayyar","doi":"10.2174/0115672050315334240508162754","DOIUrl":"10.2174/0115672050315334240508162754","url":null,"abstract":"<p><strong>Background: </strong>As individuals age, they may develop Alzheimer's disease (AD), which is characterized by difficulties in speech, memory loss, and other issues related to neural function. Cycloastragenol is an active ingredient of Astragalus trojanus and has been used to treat inflammation, aging, heart disease, and cancer.</p><p><strong>Objectives: </strong>This study aimed to explore the potential therapeutic benefits of cycloastragenol in rats with experimentally induced AD. Moreover, the underlying molecular mechanisms were also evaluated by measuring Nrf2 and HO-1, which are involved in oxidative stress, NFκB and TNF-α, which are involved in inflammation, and BCL2, BAX, and caspase-3, which are involved in apoptosis.</p><p><strong>Methods: </strong>Sprague-Dawley rats were given 70 mg/kg of aluminum chloride intraperitoneally daily for six weeks to induce AD. Following AD induction, the rats were given 25 mg/kg of cycloastragenol daily by oral gavage for three weeks. Hippocampal sections were stained with hematoxylin/ eosin and with anti-caspase-3 antibodies. The Nrf2, HO-1, NFκB, TNF-α, BCL2, BAX, and caspase-3 gene expressions and protein levels in the samples were analyzed.</p><p><strong>Results: </strong>Cycloastragenol significantly improved rats' behavioral test performance. It also strengthened the organization of the hippocampus. Cycloastragenol significantly improved behavioral performance and improved hippocampal structure in rats. It caused a marked decrease in the expression of NFκB, TNF-α, BAX, and caspase-3, which was associated with an increase in the expression of BCL2, Nrf2, and HO-1.</p><p><strong>Conclusion: </strong>Cycloastragenol improved the structure of the hippocampus in rats with AD. It enhanced the outcomes of behavioral tests, decreased the concentration of AChE in the brain, and exerted antioxidant and anti-inflammatory effects. Antiapoptotic effects were also noted, leading to significant improvements in cognitive function, memory, and behavior in treated rats.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141066503","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":"Handwriting Markers for the Onset of Alzheimer's Disease.","authors":"Yury Chernov","doi":"10.2174/0115672050299338240222051023","DOIUrl":"10.2174/0115672050299338240222051023","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's disease has an impact on handwriting (AD). Numerous researchers reported that fact. Therefore, examining handwriting characteristics could be a useful way to screen for AD. The aim of the article is to present the reliability and effectiveness of the AD-HS tool.</p><p><strong>Methods: </strong>Most of the existing studies examine either linguistic manifestations of writing or certain motor functions. However, handwriting is a complex of cognitive and motor activities. Since the influence of AD on handwriting is individual, it is important to analyze the complete set of handwriting features. The AD-HS instrument is based on this principle. Validation of the AD-HS instrument for revealing cognitive impairment in AD-diagnosed persons in comparison to the control group. The study is based on the evaluation of free handwritten texts. AD-HS includes 40 handwriting and 2 linguistic features of handwritten texts. It is based on the standard protocol for handwriting analysis. The cumulative evaluation of all features builds a quantitative AD-Indicator (ADI) as a marker of possible AD conditions. The analyzed experiment includes 53 AD-diagnosed persons and a control group of 192 handwriting specimens from the existing database.</p><p><strong>Results: </strong>AD-HS shows a distinct difference in evaluated ADI for the participants (the mean value equals 0.49) and the control group (the mean value equals 0.28).</p><p><strong>Conclusion: </strong>The handwriting marker of AD could be an effective supplement instrument for earlier screening. It is also useful when traditional biomarkers and neurological tests could not be applied. AD-HS can accompany therapy as an indication of its effect on a person.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139998797","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":"Disruptions of Gut Microbiota are Associated with Cognitive Deficit of Preclinical Alzheimer's Disease: A Cross-Sectional Study.","authors":"Binbin Yu, Guomeng Wan, Shupeng Cheng, Pengcheng Wen, Xi Yang, Jiahuan Li, Huifang Tian, Yaxin Gao, Qian Zhong, Jin Liu, Jianan Li, Yi Zhu","doi":"10.2174/0115672050303878240319054149","DOIUrl":"10.2174/0115672050303878240319054149","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's Disease (AD) is the most prevalent type of dementia. The early change of gut microbiota is a potential biomarker for preclinical AD patients.</p><p><strong>Objective: </strong>The study aimed to explore changes in gut microbiota characteristics in preclinical AD patients, including those with Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment (MCI), and detect the correlation between gut microbiota characteristics and cognitive performances.</p><p><strong>Methods: </strong>This study included 117 participants [33 MCI, 54 SCD, and 30 Healthy Controls (HC)]. We collected fresh fecal samples and blood samples from all participants and evaluated their cognitive performance. We analyzed the diversity and structure of gut microbiota in all participants through qPCR, screened characteristic microbial species through machine learning models, and explored the correlations between these species and cognitive performances and serum indicators.</p><p><strong>Results: </strong>Compared to the healthy controls, the structure of gut microbiota in MCI and SCD patients was significantly different. The three characteristic microorganisms, including <i>Bacteroides ovatus, Bifidobacterium adolescentis</i>, and <i>Roseburia inulinivorans</i>, were screened based on the best classification model (HC and MCI) having intergroup differences. <i>Bifidobacterium adolescentis</i> is associated with better performance in multiple cognitive scores and several serum indicators. <i>Roseburia inulinivorans</i> showed negative correlations with the scores of the Functional Activities Questionnaire (FAQ).</p><p><strong>Conclusion: </strong>The gut microbiota in patients with preclinical AD has significantly changed in terms of composition and richness. Correlations have been discovered between changes in characteristic species and cognitive performances. Gut microbiota alterations have shown promise in affecting AD pathology and cognitive deficit.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140290126","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}