Experimental Neurology最新文献

{"title":"Intestinal dysbiosis causes spatial memory impairment in alcohol-exposed male mice by inducing neuroinflammation","authors":"","doi":"10.1016/j.expneurol.2024.115028","DOIUrl":"10.1016/j.expneurol.2024.115028","url":null,"abstract":"<div><div>Alcohol abuse damages the brain and triggers cognitive impairment. Intestinal dysbiosis has recently been shown to be involved in psychiatric disorders, which suggests the possibility of intestine-to-brain interactions in the development of alcohol abuse. In this study, chronic intermittent alcohol exposure (CIAE) model was established in C57BL/6 male mice and the spatial memory were detected by Barnes maze (<em>n</em> = 16/group). The fecal microbiota and its metabolites were detected by 16S rDNA sequencing and non-target liquid chromatograph mass spectrometer (LC-MS) (<em>n</em> = 8/group). Effects of alcohol on intestinal barrier and blood-brain barrier (BBB) permeability were detected by Evens blue leakage assay (<em>n</em> = 4/group), and the activation state of microglia and TLR4 expression were conducted by immunofluorescence co-localization (<em>n</em> = 4/group). The morphological changes of microglia were analyzed with Image J Analyze Skeleton software, and the protein levels of TLR4 and inflammatory factors were detected by Western Blot (<em>n</em> = 8/group). Results indicated that alcohol alters the components of fecal microbiota and metabolites, and damages the intestinal barrier and BBB, leading to spatial memory impairment in mice. By giving mice specific prebiotics (<em>n</em> = 16/group), we pointed out that increased endotoxin coming from Gram negative bacteria such as lipopolysaccharides (LPS) cross the BBB to activate microglia and inflammatory pathways in the prefrontal cortical (PFC) and hippocampus (HIP), releasing inflammatory factors and resulting in neuroinflammation. Thus, the fecal microbiota seems to be a potential target in the management of alcoholic brain disease.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142555013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gypenoside XLIX alleviates sepsis-associated encephalopathy by targeting PPAR-α","authors":"","doi":"10.1016/j.expneurol.2024.115027","DOIUrl":"10.1016/j.expneurol.2024.115027","url":null,"abstract":"<div><div>Sepsis-related systemic inflammation is a deadly condition with high rates of morbidity and mortality. There is evidence that sepsis affects the brain, and the most frequent organ dysfunction linked to sepsis is sepsis-associated encephalopathy. Sepsis-related brain damage can drastically reduce a patient's chances of survival. However, a specific treatment for sepsis-associated encephalopathy is not currently available. Consequently, to treat the brain damage caused by sepsis, investigating novel therapeutic strategies is imperative. After establishing the CLP-induced mouse SAE model, we treated the mice with Gyp-XLIX and evaluated apoptosis, neuroinflammation, brain damage, and oxidative stress in the brain tissue of each group of mice. Furthermore, the protective effects of Gyp-XLIX on LPS-treated BV-2 cells were assessed. We discovered that Gyp-XLIX treatment increased the survival rate of CLP-treated mice, alleviated SAE-related cerebral nerve abnormalities, and decreased blood–brain barrier breakdown, all of which could better preserve brain tissue in vivo. Furthermore, we identified associated proteins and found that Gyp-XLIX may reduce oxidative stress, cell apoptosis, and inflammation in the brain tissues of SAE mice. This observation was further validated in vitro. We established that Gyp-XLIX alleviates SAE by targeting PPAR-α. These findings may be important for the clinical applicability of Gyp-XLIX in SAE treatment. We found that Gyp-XLIX can alleviate brain injury in SAE by targeting PPAR-α and is a potential protective agent for SAE.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142555014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zebrafish as a model organism to study sporadic Alzheimer's disease: Behavioural, biochemical and histological validation","authors":"","doi":"10.1016/j.expneurol.2024.115034","DOIUrl":"10.1016/j.expneurol.2024.115034","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a global burden to the healthcare system with no viable treatment options till date. Rodents and primates have been extensively used as models for understanding AD pathogenesis and identifying therapeutic targets. However, the focus is now shifting towards developing alternate models. Zebrafish is emerging as a preferred model for neurodegenerative conditions because of its simple nervous system, highly conserved genome and short duration required to model disease condition. The present study is aimed to develop streptozotocin (STZ)-induced model of sporadic AD (sAD) in zebrafish. STZ was administered to adult zebrafish (4–6 mo) at different doses (1 to 50 mg/kg body weight, intracerebroventricularly). Kaplan-Meier survival analysis revealed time and dose dependent mortality in the zebrafish administered with STZ. Based on survival analysis, 1 to 10 mg/kg body weight of STZ was selected for behavioural, molecular and histological studies. STZ administered fish had anxiety-like and stress behaviour in novel tank and light/dark preference tests. STZ-induced cognitive and memory deficits assessed using novel object recognition and spatial alternation tests. Further, expression of markers of amyloidogenic pathway (<em>appa</em> and <em>bace1</em>) were increased in terms of mRNA and protein levels in a time and dose dependent manner following STZ administration. However, expression of non-amyloidogenic pathway mediator (<em>adam10</em>) was reduced at both mRNA and protein level. Histological assessment using hematoxylin and eosin, and Nissl stain revealed loss of neurons in STZ administered fish. The ratio of phosphor-tau^ser396/total-tau was increased in STZ administered fish. Based on these findings, 5 mg/kg body weight of STZ was found to be most appropriate dose to exhibit sAD phenotype. Mass spectrometric analysis confirmed the presence of amyloid beta oligomers in brains of STZ administered fish. Transmission electron microscopy also showed the presence of higher order insoluble amyloid fibrils with twists. Immunohistochemical analysis revealed amyloid beta deposits in brain of STZ administered fish. Golgi-cox staining indicated decreased number of dendrites, whereas microglia had increased density, span ratio, soma area and lacunarity. The results of the present study demonstrate presence of AD hallmarks and phenotype in zebrafish 7 days post STZ administration (5 mg/kg). The study validates the potential of STZ-induced sAD in zebrafish as a reliable model for studying pathophysiology and rapid screening of therapeutic molecules against sAD.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GSK-3β inhibitor amplifies autophagy-lysosomal pathways by regulating TFEB in Parkinson's disease models","authors":"","doi":"10.1016/j.expneurol.2024.115033","DOIUrl":"10.1016/j.expneurol.2024.115033","url":null,"abstract":"<div><div>Parkinson's disease (PD), a common neurodegenerative disorder characterized by degeneration of the substantia nigra and a marked increase in Lewy bodies in the brain, primarily manifests as motor dysfunction. Glycogen synthase kinase-3 beta (GSK-3β) is known to play a critical role in various pathological processes of neurodegenerative diseases. However, the impact of GSK-3β inhibitors on PD progression and the underlying molecular mechanisms responsible for the effects have not been fully elucidated. Using in vitro and mouse models of 1-methyl-4-phenylpyridine (MPP⁺)-or methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD, we found that inhibition of GSK-3β activity alleviated mitochondrial damage, cell apoptosis, and neuronal cell loss by promoting the nuclear translocation of transcription factor EB (TFEB), thereby amplifying the autophagy-lysosomal pathway (ALP). Importantly, siRNA silencing of the TFEB gene impaired the GSK-3β inhibitor-mediated activation of the ALP pathway, thus negating the metabolic support required for neuronal functional improvement. Short-term treatment with the GSK-3β inhibitor significantly ameliorated motor dysfunction and improved motor coordination in model mice with MPTP-induced PD. GSK-3β inhibition increased the ALP and TFEB activities in the mice, thereby reducing α-synuclein aggregation and neuronal damage. In conclusion, our study demonstrates that inhibition of GSK-3β activity can delay the pathological processes of PD via promotion of the TFEB–ALP pathway, potentially providing a novel therapeutic target for this neurodegenerative disorder.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TREM1 induces microglial ferroptosis through the PERK pathway in diabetic-associated cognitive impairment","authors":"","doi":"10.1016/j.expneurol.2024.115031","DOIUrl":"10.1016/j.expneurol.2024.115031","url":null,"abstract":"<div><div>Ferroptosis is involved in neurodegenerative disorders including diabetes-associated cognitive impairment (DACI). As central immune cells, microglia have strong siderophilic properties. However, the role of iron deposition in microglia and the underlying regulatory mechanism remains unclear in DACI. Here, we established high glucose (HG) model in BV2/HMC3 cells and diabetes model in C57BL/6 J mice with HFD and STZ. Transmission Electron Microscopy, Western blot, assay kits of Fe²⁺, GSH/GSSG, MDA and ROS were carried out <em>in vitro</em>. Prussian blue staining, Western blot and immunofluorescence were implemented <em>in vivo</em>. Y-maze and novel object recognition were performed to assess cognitive performance. LP17 was used to inhibit TREM1 (triggering receptor expressed on myeloid cells 1) specifically <em>in vivo and vitro</em>. We found excessively deposited iron and significant reduction in antioxidants in hippocampal microglia of mice with DACI, concomitant with increased TREM1 (a microglia-specific inflammatory amplifier). Furthermore, LP17 (TREM1 specific inhibitor) ameliorated cognitive impairment caused by HFD/STZ through relieving iron accumulation and antioxidant inactivation. <em>In vitro</em>, ferroptosis was induced by HG in mice microglia-BV2 and human microglia-HMC3 cells, which could be blocked by a ferroptosis inhibitor-Fer-1 and LP17. Moreover, PERK pathway of endoplasmic reticulum stress was activated by HG, and then reversed by PERK inhibitor GSK2606414 and LP17 followed by improved ferroptosis in HG-cultured BV2. In summary, our results indicated that TREM1 effectively aggravates T2DM-associated microglial iron accumulation through the PERK pathway of ERS, which contributes to antioxidant inactivation and lipid peroxidation, eventually, massively boosted ROS result in microglial ferroptosis. The mechanism elucidation in our study may shed light on targeted therapy of DACI.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rotating magnetic field improves cognitive and memory impairments in APP/PS1 mice by activating autophagy and inhibiting the PI3K/AKT/mTOR signaling pathway","authors":"","doi":"10.1016/j.expneurol.2024.115029","DOIUrl":"10.1016/j.expneurol.2024.115029","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a geriatric disorder that can be roughly classified into sporadic AD and hereditary AD. The latter is strongly associated with genetic factors, and its treatment poses greater challenges compared to sporadic AD. Rotating magnetic fields (RMF) is a non-invasive treatment known to have diverse biological effects, including the modulation of the central nervous system and aging. However, the impact of RMF on hereditary AD and its underlying mechanism remain unexplored. In this study, we exposed APP/PS1 mice to RMF (2 h/day, 0.2 T, 4 Hz) for a duration of 6 months. The results demonstrated that RMF treatment significantly ameliorated their cognitive and memory impairments, attenuated neuronal damage, and reduced amyloid deposition. Furthermore, RNA-sequencing analysis revealed a significant enrichment of autophagy-related genes and the PI3K/AKT-mTOR signaling pathway. Western blotting further confirmed that RMF activated autophagy and suppressed the phosphorylation of proteins associated with the PI3K/AKT/mTOR signaling pathway in APP/PS1 mice. These protective effects and the underlying mechanism were also observed in Aβ₂₅_–₃₅-exposed HT22 cells. Collectively, our findings indicate that RMF improves cognitive and memory dysfunction in APP/PS1 mice by activating autophagy and inhibiting the PI3K/AKT/mTOR signaling pathway, thus highlighting the potential of RMF as a clinical treatment for hereditary AD.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination treatment with cilostazol and isosorbide mononitrate attenuates microemboli-mediated vascular cognitive impairment and improves imaging and plasma biomarkers in diabetic rats","authors":"","doi":"10.1016/j.expneurol.2024.115030","DOIUrl":"10.1016/j.expneurol.2024.115030","url":null,"abstract":"<div><div>Diabetes is a major risk factor for all types of dementia. The underlying reasons are not fully understood, and preventive therapeutic strategies are lacking. Previously we have shown that diabetic but not control rats developed a progressive cognitive decline in a microemboli (ME) model of vascular contributions to cognitive impairment &amp; dementia (VCID). Given the cerebrovascular dysfunction is a mutual pathological change between diabetes and VCID, we hypothesized that the cognitive impairment in this ME model can be prevented by improving the endothelial function in diabetes. Our treatment paradigm was based on the LACI-2 Trial which assessed the efficacy of isosorbide mononitrate (ISMN) and cilostazol (Cil) treatments in small vessel disease progression. Control and diabetic rats were treated with ISMN/Cil or vehicle for 4 weeks, then injected with cholesterol crystal ME and the behavioral outcomes were monitored. Brain microstructure integrity was assessed by diffusion MRI. Plasma biomarkers were assessed using angiogenesis, neurology and amyloid β 42/40 panels recommended by the MarkVCID consortium. Behavioral deficits and the loss of tissue integrity previously observed in untreated diabetic rats were not noted in the treated animals in this study. Treatment improved tissue perfusion but there were no differences in plasma biomarkers. These results suggest that restoration of endothelial function with ISMN/Cil before ME injection prevented the possible deleterious effects of ME in diabetic rats by improving the endothelial integrity and it is a practical preventive and therapeutic strategy for VCID.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142554999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Border-associated macrophages: From physiology to therapeutic targets in Alzheimer's disease","authors":"","doi":"10.1016/j.expneurol.2024.115021","DOIUrl":"10.1016/j.expneurol.2024.115021","url":null,"abstract":"<div><div>Border-associated macrophages (BAMs) constitute a highly heterogeneous group of central nervous system-resident macrophages at the brain boundaries. Despite their significance, BAMs have mainly been overlooked compared to microglia, resulting in a limited understanding of their functions. However, recent advancements in single-cell immunophenotyping and transcriptomic analyses of BAMs have revealed a previously unrecognized complexity in these cells, in addition to their critical roles under non-pathological conditions and diseases like Alzheimer's disease (AD), Parkinson's disease, glioma, and ischemic stroke. In this review, we discuss the origins, self-renewal capabilities, and extensive heterogeneity of BAMs, and clarify their important physiological functions such as immune monitoring, waste removal and vascular permeability regulation. We also summarize experimental evidence linking BAMs to the progression of AD. Finally, we review therapeutic strategies targeting brain innate immune cells mainly focusing on strategies aimed at modulating BAMs to treat AD and evaluate their potential in clinical applications.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of vildagliptin conjugated monometallic nanoparticles and bimetallic nanocomposites on diabetes-induced cognitive deficit","authors":"","doi":"10.1016/j.expneurol.2024.115026","DOIUrl":"10.1016/j.expneurol.2024.115026","url":null,"abstract":"<div><div>Oxidative stress is one of the major causes of different metabolic disorders, including diabetes, cardiovascular diseases, neurodegenerative diseases and cancers. Some metabolic disorders like diabetes mellitus leads to secondary complications after micro and macrovascular complications. Some of the most prevalent neurodegenerative diseases, like cognitive impairment and Alzheimer's disease, are found in chronic diabetic patients. The present study is designed to understand the mechanism of interconnection between diabetes mellitus and cognitive deficit using the alloxan model of diabetes-induced cognitive deficit in the rat model. The alloxan monohydrate produces reactive oxygen species, producing superoxide free radicals, hydrogen peroxide and hydroxyl radicals. The hydroxyl radicals ultimately cause the death of beta cells, causing diabetes. Hence, the correlation of oxidative stress and neurodegeneration in cognitive impairment is the trigger for this study. In the present study, we investigate the ameliorative effect of vildagliptin (VLD) and its conjugated nanoparticles against alloxan-associated brain damage due to oxidative stress. The gold (Au), selenium (Se) nanoparticles, and bimetallic (Se@Au) nanocomposites of VLD are synthesized and assessed for improvement in their brain availability. The in-vitro antioxidant evaluation of the VLD and nanoparticles is done using DPPH, ABTS, and FRAP assay. The memory-related neurobehavioral studies, in-vivo antioxidant studies, in-vivo biochemical studies, and histopathological examinations are evaluated in rat brains. The VLD and its nanoformulations exhibited in-vitro and in-vivo antioxidant properties significantly (<em>p</em> &lt; 0.01). They reduced the activity of AChE and nitrite in the alloxan diabetic rats. The bimetallic Se@Au VLDNCs displayed a more protective effect than VLD, VLD–AuNPs, and VLD–SeNPs.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting PTEN in ischemic stroke: From molecular mechanisms to therapeutic potentials","authors":"","doi":"10.1016/j.expneurol.2024.115023","DOIUrl":"10.1016/j.expneurol.2024.115023","url":null,"abstract":"<div><div>Ischemic stroke remains a leading cause of mortality and disability worldwide, driven by complex pathophysiological mechanisms, including excitotoxicity, oxidative stress, apoptosis, and neuroinflammation. PTEN (Phosphatase and tensin homolog deleted on chromosome 10) plays a crucial role in these processes, influencing key signaling pathways such as PI3K/Akt and mTOR. This review aims to explore PTEN's multifaceted functions in ischemic stroke, examining its interactions with non-coding RNAs, involvement in mitophagy and immune suppression, and overall impact on cellular homeostasis. We will investigate various therapeutic strategies targeting PTEN, including synthetic drugs, natural products, and exosome-based therapies enriched with specific miRNAs. Additionally, we will assess the potential of non-pharmaceutical interventions such as electroacupuncture, exercise, transcranial direct current stimulation (tDCS), and therapeutic hypothermia in modulating PTEN activity to enhance cererbroprotection and functional recovery. By elucidating these aspects, this review aims to inspire and motivate the audience in their research and clinical practice, highlighting PTEN as a promising therapeutic target and paving the way for developing effective treatments for ischemic stroke.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}