Translational Neurodegeneration最新文献

{"title":"Beyond amyloid: nanobody-mediated neuroinflammatory therapy for Alzheimer's disease.","authors":"Soukaina Amniouel, Jessica Suh, Wei Zheng, Qi Zhang","doi":"10.1186/s40035-025-00513-5","DOIUrl":"https://doi.org/10.1186/s40035-025-00513-5","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is one of the most common and devastating neurodegenerative diseases, characterized by accumulation of amyloid-beta (Aβ) plaques, neurofibrillary tangles of tau protein, and persistence of neuroinflammation, leading to progressive cognitive decline, loss of independence, emotional and financial strain on families, and significant societal costs. Current anti-amyloid treatments are partly successful in removing Aβ amyloid, but often lead to increased inflammation. This leads to limited therapeutic efficacy and causes side effects such as amyloid-related imaging abnormalities. In addition, they do not address neuroinflammation in AD patients. In this review, we discuss a new therapeutic strategy that combines single-domain antibodies (sdAbs, nanobodies) against Aβ fibrils and anti-inflammatory drugs and applies them to the regions of neuroinflammation associated with the plaques in AD patients. This strategy aims to control the function of activated microglia and astrocytes, thereby avoiding unnecessary immunosuppression. We also discuss the unique features of sdAbs, including small size, good tissue penetration, and lack of Fc-mediated immune reactions, as well as relevant payloads (i.e., small molecules, biologics, and nanoparticles) and delivery systems. This immunomodulatory therapy targets the plaques specifically and therefore represents a promising opportunity to improve amyloid clearance and target the inflammatory components of AD, potentially improving the therapeutic efficacy of the disease.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"14 1","pages":"51"},"PeriodicalIF":15.2,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145287125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The medial septum-hippocampus-lateral septum circuitry in spatial memory: linking healthy function to early Alzheimer's disease and translational opportunities.","authors":"Yujie Song, Junjun Ni, Hong Qing, Zhenzhen Quan","doi":"10.1186/s40035-025-00511-7","DOIUrl":"10.1186/s40035-025-00511-7","url":null,"abstract":"<p><p>Hippocampus (HPC)-associated spatial memory deficits are one of the earliest symptoms of Alzheimer's disease (AD). Current pharmacological treatments only alleviate the symptoms but do not prevent disease progression. The emergence of neuromodulation technology suggests that specific neural circuits are potential therapeutic targets for AD. Current studies have analyzed the medial septum (MS)-HPC and the HPC-lateral septum (LS) circuitries separately. A comprehensive understanding of their synergistic effects and overall dysregulation in AD remains limited. In this review, we will integrate anatomical and functional evidence to give an overview of the role of the MS-HPC-LS circuitry in spatial memory, the mechanisms of AD-related dysregulation, and therapeutic strategies targeting the circuitry, specially focusing on molecular interventions (receptor modulation) and bioengineering strategies (circuit-specific stimulation).</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"14 1","pages":"50"},"PeriodicalIF":15.2,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced synaptic vesicle protein 2A in extracellular vesicles and brains of Alzheimer's disease: associations with Aβ, tau, synaptic proteins and APOE ε4.","authors":"Jana Nussbaumer, Aatmika Barve, Valentin Zufferey, Jeanne Espourteille, Tunahan Kirabali, Uwe Konietzko, Daniel Razansky, Axel Rominger, Agneta Nordberg, Luc Buée, Morvane Colin, Roger M Nitsch, Christoph Hock, Kevin Richetin, Ruiqing Ni","doi":"10.1186/s40035-025-00508-2","DOIUrl":"10.1186/s40035-025-00508-2","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is characterized by accumulation of amyloid-β (Aβ) plaques, tau neurofibrillary Tangles and synaptic dysfunction. The aim of this study was to map the distributions of synaptic vesicle protein 2A (SV2A) and other synaptic proteins in the brain and the brain-derived extracellular vesicles (BDEVs) of AD patients, analyze their associations with Aβ, tau, and the apolipoprotein E (APOE) ε4 allele, and investigate the biological role of SV2A.</p><p><strong>Methods: </strong>Mass spectrometry-based proteomics of BDEVs and immunohistochemistry staining were conducted on postmortem brain samples from 57 AD patients and 48 nondemented controls. The levels of SV2A, synaptophysin (SYP), and other synaptic proteins in the brain tissues and the BDEVs, and their associations with Aβ, tau (phospho-tau and Braak stages), other proteins and the APOE ε4 allele, were analyzed.</p><p><strong>Results: </strong>SV2A levels were significantly lower in AD patients than in nondemented controls, particularly in the hippocampus and entorhinal cortex. APOE ε4 carriers presented further reductions in SV2A levels compared with noncarriers. The SV2A levels in BDEVs and brain tissues were positively correlated with SYP levels and negatively correlated with Aβ and phospho-tau levels. Reductions in SV2A were associated with decreased levels of other synaptic proteins, such as synaptotagmins, GAP43, and SNAP25. SV2A emerged as a central hub with interactions with proteins from subnetworks related to synaptic vesicle formation and fusion.</p><p><strong>Conclusion: </strong>SV2A levels in brain tissues and BDEVs are reduced in AD patients, particularly in those carrying the APOE ε4 allele, and are correlated with Aβ and tau pathologies. SV2A may serve as a valuable biomarker for monitoring synaptic dysfunction and progression in AD.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"14 1","pages":"48"},"PeriodicalIF":15.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12459057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the glymphatic system: Aβ accumulation and phototherapy strategies across different stages of Alzheimer's disease.","authors":"Danrui Zhao, Junting Wang, Yirui Zhu, Hao Zhang, Chenkang Ni, Zhuowen Zhao, Jingyu Dai, Rongqiao He, Guangzhi Liu, Cheng Gan, Shouzi Zhang, Zhiqian Tong","doi":"10.1186/s40035-025-00510-8","DOIUrl":"10.1186/s40035-025-00510-8","url":null,"abstract":"<p><p>The glymphatic system serves as the brain's clearance system. It deteriorates with age and is a significant contributor to the onset and progression of Alzheimer's disease (AD). Modulating cerebrospinal fluid (CSF)-based clearance and targeting key components of the glymphatic system, such as aquaporin-4, can enhance amyloid-beta (Aβ) clearance. Light therapy is emerging as a potential AD treatment approach, which involves the use of visible and near-infrared light at specific wavelengths (630/680/808/850/1070 nm), photosensitive proteins, and sensory stimulation at particular frequencies (e.g., 40 Hz). This phototherapy strategy can broadly influence the intracerebral fluid dynamics, including cerebral blood flow, CSF, and interstitial fluid (ISF), as well as structures related to the glymphatic system, such as vascular endothelial cells, glial cells, and neurons. Additionally, it may directly or indirectly inhibit Aβ accumulation by modulating endogenous small molecules, thereby improving cognitive function. Our previous research demonstrated that 630-nm red light can inhibit Aβ cross-linking by clearing endogenous formaldehyde and promoting ISF drainage. Notably, Aβ accumulation exhibits distinct characteristics at different phases of AD, accompanied by varying features of glymphatic system impairment. In the early stages, deep brain regions are significantly affected, whereas in the late stages, accumulation primarily occurs in the paracentral, precentral, and postcentral cortices. Owing to the limited penetration depth of light, this may pose a challenge to the clinical efficacy of phototherapy. Therefore, different stages of AD may require tailored phototherapeutic strategies. Meanwhile, it is important to acknowledge the ongoing controversies associated with lymphovenous anastomosis, a procedure that targets the glymphatic system. Therefore, this article reviews the characteristics of glymphatic system impairment across various AD stages and the mechanisms by which effective phototherapies modulate the glymphatic system. Potential phototherapeutic strategies corresponding to different stages of Aβ accumulation are also proposed.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"14 1","pages":"49"},"PeriodicalIF":15.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12459067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glycosylation in neuroinflammation: mechanisms, implications, and therapeutic strategies for neurodegenerative diseases.","authors":"Shenglan Cheng, Bo Xiao, Zhaohui Luo","doi":"10.1186/s40035-025-00506-4","DOIUrl":"10.1186/s40035-025-00506-4","url":null,"abstract":"<p><p>Neuroinflammation is a key pathological mechanism underlying neurodegenerative diseases, and intricately interacts with protein glycosylation. Emerging evidence suggests that aberrant glycosylation disrupts immune homeostasis, activates microglia, and promotes the release of inflammatory mediators, thereby exacerbating neuroinflammatory responses. In addition, the inflammatory microenvironment can further dysregulate glycosylation patterns, creating a vicious cycle that amplifies disease pathology. Although the regulatory role of glycosylation in neuroinflammation associated with neurodegenerative diseases has been recognized, the precise molecular and cellular mechanisms remain incompletely understood. This review systematically examines the complex crosstalk between glycosylation and neuroinflammation, with a particular focus on the critical roles of glycosylation in key neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis. We explore how glycosylation abnormalities contribute to disease pathogenesis through effects on immune recognition, protein aggregation, and cellular functions. Understanding the molecular underpinnings of these diseases may pave the way for the development of therapeutic strategies targeting glycosylation pathways, ultimately improving clinical outcomes for patients.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"14 1","pages":"47"},"PeriodicalIF":15.2,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145125976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disarming COX-1 to disrupt Alzheimer's inflammatory trajectory: preclinical insights and translational promise.","authors":"Gilda Loffredo, Marcello D'Amelio","doi":"10.1186/s40035-025-00509-1","DOIUrl":"10.1186/s40035-025-00509-1","url":null,"abstract":"","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"14 1","pages":"46"},"PeriodicalIF":15.2,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanisms of mitochondrial quality control.","authors":"Wensheng Li, Yuran Gui, Cuiping Guo, Yuting Huang, Yi Liu, Xuan Yu, Huiliang Zhang, Jianzhi Wang, Rong Liu, Yacoubou Abdoul Razak Mahaman, Qiuhong Duan, Xiaochuan Wang","doi":"10.1186/s40035-025-00505-5","DOIUrl":"https://doi.org/10.1186/s40035-025-00505-5","url":null,"abstract":"<p><p>Mitochondria produce adenosine triphosphate (ATP), the main source of cellular energy. To maintain normal function, cells rely on a complex mitochondrial quality control (MQC) system that regulates mitochondrial homeostasis, including mitochondrial dynamics, mitochondrial dynamic localization, mitochondrial biogenesis, clearance of damaged mitochondria, oxygen radical scavenging, and mitochondrial protein quality control. The MQC system also involves coordination of other organelles, such as the endoplasmic reticulum, lysosomes, and peroxisomes. In this review, we discuss various ways by which the MQC system maintains mitochondrial homeostasis, highlight the relationships between these pathways, and characterize the life cycle of individual mitochondria under the MQC system.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"14 1","pages":"45"},"PeriodicalIF":15.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Restoration of CB1 receptor function in hippocampal GABAergic neurons rescues memory deficits in Huntington's disease models.","authors":"Nadia Di Franco, Iker Bengoetxea de Tena, Andrea Sanchez-Ruiz, Alba Pereda-Velarde, Ferran Enfedaque, Candela Gónzalez-Arias, Lluis Maria Miquel Rio, Analia Bortolozzi, Rafael Rodriguez-Puertas, Carlos Costas-Insua, Laura Molina-Porcel, Anna Vazquez-Oliver, Andres Ozaita, Manuel Guzmán, Gertrudis Perea, Silvia Ginés","doi":"10.1186/s40035-025-00500-w","DOIUrl":"10.1186/s40035-025-00500-w","url":null,"abstract":"<p><strong>Background: </strong>Dysregulation of the endocannabinoid system (eCBS) and the loss of CB1 receptors (CB1R) in the basal ganglia are well-established hallmarks of Huntington's disease (HD). As a result, significant research efforts have focused on targeting the eCBS to alleviate motor disturbances associated with the disease. Beyond its role in motor control, the eCBS is a complex signaling network critically involved in regulating learning and memory. Despite this, the potential involvement of eCBS dysfunction in the cognitive decline characteristic of HD, often manifested well before motor dysfunction, has remained largely unexplored.</p><p><strong>Methods: </strong>CB1R expression in the hippocampus was evaluated in both human HD samples and HD mouse models (R6/1 and Hdh^Q7/Q111 models, including both sexes) using Western blotting, immunohistochemistry, and radioligand binding assays. To restore CB1R function, CB1R agonist WIN-55212-2 was systemically administered, or viral vectors encoding CB1R were locally infused into the hippocampus of HD mice. A multidisciplinary approach combining behavioral, biochemical, electrophysiological, and morphological analyses, was employed to investigate the molecular mechanisms underlying the effects of CB1R activation in the context of HD-related cognitive dysfunction.</p><p><strong>Results: </strong>In both human HD samples and HD mouse models, CB1R protein levels were reduced in the hippocampus, accompanied by structural synaptic alterations and impairment in spatial, recognition and working memory. Moreover, hippocampal depolarization-induced suppression of inhibition was significantly disrupted in R6/1 mice. Administration of WIN-55212-2 successfully restored these synaptic and cognitive deficits. Immunohistochemical analysis revealed that the CB1R decrease was specifically localized to GABAergic interneurons within the hippocampus. Notably, targeted restoration of CB1R expression in these interneurons via viral vector delivery was sufficient to rescue hippocampal-dependent memory deficits in HD mice.</p><p><strong>Conclusion: </strong>This study suggests that impaired CB1R function in hippocampal GABAergic interneurons contributes to memory dysfunction in HD.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"14 1","pages":"44"},"PeriodicalIF":15.2,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12376758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell-specific copper dyshomeostasis mechanism in Alzheimer's disease.","authors":"Michael Okafor, Peter Faller, Nicolas Vitale","doi":"10.1186/s40035-025-00504-6","DOIUrl":"https://doi.org/10.1186/s40035-025-00504-6","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by progressive decline of cognitive functions, yet its underlying aetiology remains elusive. While amyloid-β (Aβ) and tau pathologies have been extensively studied, emerging evidence suggests that metal and especially copper dyshomeostasis may also play a crucial role in the pathogenesis of AD. This review explores the intricate relationship between copper and AD, shedding light on the multifaceted mechanisms through which copper dysregulation contributes to neurodegeneration. We delve into the impact of copper ions on Aβ aggregation, tau phosphorylation, and oxidative stress, providing a comprehensive overview of the molecular pathways involved. Furthermore, we discuss the interplay between different brain cell types and the impact Cu dysregulation may have on them. The therapeutic implications of targeting copper dysregulation for AD treatment are also addressed, emphasizing the potential of copper-modulating agents in ameliorating cognitive decline. In summary, this review discusses copper dyshomeostasis as a central player in the intricate tapestry of AD pathology, offering new insights and avenues for therapeutic interventions.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"14 1","pages":"42"},"PeriodicalIF":15.2,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cyclooxygenase-1 deletion in 5 × FAD mice protects against microglia-induced neuroinflammation and mitigates cognitive impairment.","authors":"Jie Wang, Hong Ni, Yu Wang, Luyao Wei, Hanqing Ding, Zhongzhao Guo, Hao Pan, Ying Yu, Jia Luo, Weidong Pan, Deheng Wang, Zun-Ji Ke","doi":"10.1186/s40035-025-00501-9","DOIUrl":"https://doi.org/10.1186/s40035-025-00501-9","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a neurodegenerative disease with major symptoms including memory and learning deficits. Neuroinflammation associated with reactive microglia promotes AD progression. These reactive microglia secrete prostaglandins, which are synthesized through the enzymatic activity of cyclooxygenase (COX)-1 and COX-2. Here, we aimed to elucidate the specific mechanisms of COX1 in AD pathogenesis and its interactions with neuroinflammatory processes.</p><p><strong>Methods: </strong>We conducted backcrossing between COX-1 knockout (KO) and 5 × FAD mice to evaluate the effect of COX-1 deficiency on neuroinflammation. In addition, single-cell sequencing and microarray datasets from public databases and ingenuity pathway analysis in vitro were employed to explore gene expression profiles in the brains of AD mice.</p><p><strong>Results: </strong>We identified a significant upregulation of COX-1 in 5 × FAD mice, with expression specifically localized to microglia in an age-dependent manner. Additionally, COX-1 KO alleviated neuroinflammation and accumulation of Aβ plaques, subsequently improving cognitive behavior in 5 × FAD mice. Moreover, microglia exhibited an amoeboid morphology in 5 × FAD mice, whereas in age-matched 5 × FAD/COX-1 KO mice, microglia had a ramified appearance. Additionally, our study demonstrated a pharmacological approach that inhibits the prostaglandin E2 (PGE2)/EP2 receptors via inhibition of the cAMP-PKA-NFκB-p65 pathway and NLRP3 inflammasome activation, producing similar beneficial effects as observed in COX-1 KO mice.</p><p><strong>Conclusion: </strong>Our findings indicate that targeting the COX-1/PGE2/EP2 signaling pathway may alleviate neuroinflammation and impede AD progression. Moreover, the EP2 receptor presents a promising pharmacological target for mitigating the pathological effects associated with COX-1 activity in AD patients.</p>","PeriodicalId":23269,"journal":{"name":"Translational Neurodegeneration","volume":"14 1","pages":"43"},"PeriodicalIF":15.2,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}