{"title":"BMSCs-Derived Extracellular VesiclemiR-29a-3p Improved the Stability of Rat Myasthenia Gravis by Regulating Treg/Th17 Cells.","authors":"Zhongben Tang,Meiqiu Chen,Chen Chen,Chao Fan,Jiaxian Huang","doi":"10.1080/08820139.2024.2404629","DOIUrl":"https://doi.org/10.1080/08820139.2024.2404629","url":null,"abstract":"INTRODUCTIONMyasthenia gravis (MG) is an autoimmune disorder. Microvesicle-derived miRNAs have been implicated in autoimmune diseases. However, the role of microvesicle-derived miR-29a-3p in MG remains poorly understood. This study aimed to investigate the therapeutic effect and mechanism of miR-29a-3p derived from stem cell microvesicles (MVs) on experimental autoimmune myasthenia gravis (EAMG) rats.METHODSEAMG was induced in rats by injection of the subunit of the rat nicotinic anti-acetylcholine receptor (AChR) R97-116 peptide.Besides the control group, EAMG rats were randomly allocated into the EAMG model group, MV group, MV-NC-agomir group, and MV- miR-29a-3p-agomir group.RESULTSOur results found that BMSCs-MV promoted miR-29a-3p expression in gastrocnemius of EAMG rats. Bone marrow mesenchymal stem cells (BMSCs) derived microvesicle miR-29a-3p improved the hanging ability and swimming time of EMGA rats and weakened the degree of muscle fiber atrophy. Furthermore, microvesicles from miR-29a-3p overexpressing BMSCs reduced the content of AchR-Ab in the serum of EAMG rats. BMSC-derived microvesicle miR-29a-3p further suppressed the expression of IFN-γ and enhanced the IL-4 and IL-10 in the serum of EAMG rats by restoring the Th17/Treg cells balance.DISCUSSIONBMSCs-derived microvesicle miR-29a-3p improved the stability of rat myasthenia gravis by regulating Treg/Th17 cells. It may be an effective treatment for MG.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":"10 1","pages":"1-17"},"PeriodicalIF":2.8,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elizabeta Lohova,Mara Pilmane,Ksenija Šerstņova,Ivars Melderis,Łukasz Gontar,Maksymilian Kochański,Andzelika Drutowska,Gergely Maróti,Beatriz Prieto-Simón
{"title":"Analysis of Inflammatory and Regulatory Cytokines in the Milk of Dairy Cows with Mastitis: A Comparative Study with Healthy Animals.","authors":"Elizabeta Lohova,Mara Pilmane,Ksenija Šerstņova,Ivars Melderis,Łukasz Gontar,Maksymilian Kochański,Andzelika Drutowska,Gergely Maróti,Beatriz Prieto-Simón","doi":"10.1080/08820139.2024.2404623","DOIUrl":"https://doi.org/10.1080/08820139.2024.2404623","url":null,"abstract":"Bovine mastitis remains a major problem in the global dairy cattle industry. The acute invasion of udder by pathogens induces innate immune response as the first defence mechanism in subclinical and clinical mastitis. The aim of the study was to determine inflammatory and regulatory cytokines IL-2, IL-4, TGF-β1, IL-17A, beta-defensin 3 and IL-10 and their potential changes in milk of dairy cows with subclinical and clinical mastitis, and to compare the findings with healthy animals. Milk samples from 15 holstein Friesian breed cows were used in the study. Cows were divided into three groups based on their health status (5 healthy, 5 subclinical and 5 clinical animals). All samples were tested using immunohistochemistry to evaluate IL-2, IL-4, IL-10, IL17A, TGF-β1 and β-Def 3 proteins. Expression of all proteins was detected in all milk samples. High expression of IL-2, IL-4, IL17A, TGF-β1 was detected in healthy cows' milk and in milk of cows with subclinical and clinical mastitis. However, expression of IL-10 and β-Def 3 in milk samples of healthy cows was significantly higher compared to the milk of cows with subclinical and clinical mastitis (p < .001). IL-10 and β-Def 3 can be considered as informative biomarkers in diagnosis of subclinical and clinical mastitis.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":"210 1","pages":"1-25"},"PeriodicalIF":2.8,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Neha Majety,Rizwan Ahmed,Rafid Al-Hallaf,Prajita Paul,Adebola Giwa,Joseph Heinemann,Zainab Agha,Cherry Choong,Thomas Donner,Chunfa Jie,Abdel Rahim A Hamad
{"title":"Invariant VD and DJ Motifs Define a Novel Class of Human Antibodies and TCRs Prototyped by antigen receptors of Dual-Expresser Lymphocytes.","authors":"Neha Majety,Rizwan Ahmed,Rafid Al-Hallaf,Prajita Paul,Adebola Giwa,Joseph Heinemann,Zainab Agha,Cherry Choong,Thomas Donner,Chunfa Jie,Abdel Rahim A Hamad","doi":"10.1080/08820139.2024.2383736","DOIUrl":"https://doi.org/10.1080/08820139.2024.2383736","url":null,"abstract":"INTRODUCTIONDual-expressing lymphocytes (DEs) are unique immune cells that express both B cell receptors (BCRs, surface antibody) and T cell receptors (TCRs). In type 1 diabetes, DE antibodies are predominated by one antibody (x-mAb), an IgM monoclonal antibody with a germline-encoded CDR3 that recognizes self-reactive TCRs. We explored if x-mAb and its interacting TCRs have distinct structural features.METHODSUsing bioinformatics, we compared x-mAb and its most common interacting TCRαβ to billions of antigen receptor sequences to determine if they were unique or randomly generated.RESULTSX-mAb represents a unique class of human antibodies with a conserved CDR3 sequence (CARx1-4DTAMVYYFYDW), consisting of a fixed DJH motif (DTAMVYYFDYW) paired with various VH genes. A public TCRβ clonotype (CASSPGTEAFF) associated with x-mAb on DEs features two invariant segments, VβD (CASSPGT) and DJβ (PGTEAFF), key to two large families of public TCRβ clonotypes-CASSPGT-Jβx and CASSPGT-Jβx-formed by recombining the VβD motif with Jβ genes and the DJβ motif with Vβ genes. B cells also use CASSPGT as a VHD motif for public IGH clonotypes (CASSPGT-Jβx).DISCUSSIONDEs, unlike conventional T and B cells, use invariant motifs to create public antibodies and TCRs, a trait previously seen only in cartilaginous fish.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":"24 1","pages":"1-16"},"PeriodicalIF":2.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Potential Antiallergic Activity of Two Chemically/Enzymatically-Modified Natural Products Against Active Atopic and Systemic Anaphylaxes in CD1 Mice Models","authors":"Gamal Ramadan, Gehan Waheed, Hend A. Mohammed","doi":"10.1080/08820139.2024.2401551","DOIUrl":"https://doi.org/10.1080/08820139.2024.2401551","url":null,"abstract":"Anaphylaxis is a globally increasing allergic reaction that is often fatal. Recently, our previous study reported the possibility of using the modified natural products “sodium R-lipoate (NaRLA) an...","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":"283 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142216582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Camel Whey Protein and Baicalein Suppressed Mast Cell Degranulation in Mice Models of IgE- and Non-IgE-Mediated Anaphylaxes: Potential Mechanisms on Downstream Cell Signaling of Mast Cells.","authors":"Hend Abbas,Gamal Badr,Gamal Ramadan,Sahar Sobhy Abd-Elhalem","doi":"10.1080/08820139.2024.2400538","DOIUrl":"https://doi.org/10.1080/08820139.2024.2400538","url":null,"abstract":"INTRODUCTIONNovel treatments are being researched to develop more safe and effective protective medications for anaphylaxis. Camel whey protein (CWP) and baicalein (BAC, one of the major flavones) have multiple beneficial properties including anti-inflammatory and antioxidant activities.METHODSThe current study investigated/compared the therapeutic protection of repeated intragastric administration of CWP (100 mg/kg body weight, as an animal extract) and BAC (10 mg/kg body weight, as a plant extract), before the challenge with ovalbumin (OVA) or receiving the compound 48/80 (C48/80), against mice models for IgE-independent and dependent anaphylaxes. Besides, their effects on mast cells (MCs) downstream cell signaling were explored.RESULTSThe results revealed that CWP and BAC reduced the mortality rate, as compared with a MCs stabilizer \"sulfasalazine (SSZ, 100 mg/kg body weight, intraperitoneally),\" in both mice models. Furthermore, they prevented the MCs degranulation and significantly reduced (p < .05) lung tissue levels of cell signaling (p-AKT, p-ERK, and p-IκBα). Additionally, they decreased histamine, tryptase, leukotriene C4, prostaglandin D2, interleukin (IL)-4, and IL-10 levels in broncho-alveolar and peritoneal lavages in systemic anaphylaxis mice models. They also restored the stabilization of peritoneal MCs membrane in inverted light microscopy results accompanied by amelioration of the lung histology.DISCUSSIONThe present study provided evidence for the protective therapeutic effect of CWP and BAC against anaphylaxis. As a result, CWP and BAC may be used as preventative supplemented regimens for both non-vegetarian and vegetarian consumers to treat allergy through downregulation of MCs signal transduction pathways, and hence controlling the production of inflammatory mediators.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":"36 1","pages":"1-18"},"PeriodicalIF":2.8,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142216581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Relationship Between Serum and Tissue Levels of IL-13 and TYK2 in Colorectal Cancer Patients.","authors":"Zahra Mozooni,Alireza Shahmohammadi,Nafiseh Golestani,Leyla Bahadorizadeh","doi":"10.1080/08820139.2024.2399581","DOIUrl":"https://doi.org/10.1080/08820139.2024.2399581","url":null,"abstract":"INTRODUCTIONColorectal cancer (CRC) is a third cause of death worldwide. The immune system plays a significant role in the tumor microenvironment and identifying its components involved in cancer development can aid in finding new biomarkers for prognosis, treatment monitoring, and immune-based therapies. Interleukin 13 (IL-13) is a cytokine produced by immune cells that has been implicated in tumor invasion, proliferation, and metastasis. Previous studies have shown that IL-13 causes the phosphorylation of Tyrosine kinase 2 (TYK2), which may contribute to the development and progression of cancer. This study investigated the levels expression of IL-13 and TYK2 in the tissue and serum of CRC patients and explored their possible association with pathological and clinical factors.METHODS105 patients with CRC and 105 healthy individuals were involved in the study. Tissue and blood samples were collected. The quantitative Real-Time PCR (qRT-PCR) technique was used to assess the expression levels of the IL-13 and TYK2 CRC tissue samples in comparison with the adjacent control tissue.RESULTThe expression levels of IL-13 were lower and TYK2 were found to be higher in CRC tissue compared to normal tissue. Additionally, serum levels of IL-13 were decreased in CRC patients while TYK2 levels were elevated. A significant negative correlation was found between the expression levels of IL-13 in both serum and tissue and the cancer stage.CONCLUSIONThese results suggest that IL-13 and TYKMay 2 play essential roles in CRC development and progression and may serve as potential biomarkers for early detection and treatment.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":"220 1","pages":"1-14"},"PeriodicalIF":2.8,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142216586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hana Askri,Hela Kallèl,Samia Rourou,Mohamed Ali Snoussi,Jihene Lachheb
{"title":"Analytical Methods for Evaluating the Immunogenicity of Recombinant Rabies Virus Glycoprotein Expressed in the Yeast Komagataella phaffii.","authors":"Hana Askri,Hela Kallèl,Samia Rourou,Mohamed Ali Snoussi,Jihene Lachheb","doi":"10.1080/08820139.2024.2399589","DOIUrl":"https://doi.org/10.1080/08820139.2024.2399589","url":null,"abstract":"BACKGROUNDRabies is a fatal viral disease preventable by vaccination. The multiple-dose regimens, along with the high production costs of current rabies vaccines, limit their use in rabies-endemic countries with developing economies and consequently there is a need for new efficacious, low-cost rabies vaccines. This study investigates the immunogenicity of recombinant rabies virus glycoprotein (rRABVG), expressed in the yeast Komagataella phaffii (K. phaffii), as a candidate subunit rabies vaccine.METHODSMonoclonal antibodies were used to confirm neutralizing epitopes presence on the rRABVG. The rRABVG potency was estimated by antigen quantification methods using ELISA and SRID. Serological methods, specifically ELISA and RFFIT, were applied to investigate the immune response of mice groups immunized with rRABVG varying doses, with or without adjuvant.RESULTSThe potency estimated by antigen quantification was dependent on the method employed. Active immunization assessment using ELISA was effective when the solid-phase antigen is the rRABVG. The RFFIT data indicated that a single adjuvanted dose of 20 µg rRABVG is sufficient for virus-neutralizing antibodies induction at a protective level of 0.5 IU/mL within 10 days post immunization.CONCLUSIONThese data demonstrate that K. phaffii produced rRABVG is immunoactive and could be an attractive candidate to develop a low-cost subunit rabies vaccine.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":"57 1","pages":"1-22"},"PeriodicalIF":2.8,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142216585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"miR-34a-5p Predicts the Risk of Diabetic Neuropathic Pain and Mediates Neuroinflammation in Microglia via Targeting ENPP3.","authors":"Peiguo Zhang,Chenghua Wang,Chengxia Li,Jing Wang","doi":"10.1080/08820139.2024.2400550","DOIUrl":"https://doi.org/10.1080/08820139.2024.2400550","url":null,"abstract":"INTRODUCTIONThe pathogenesis of diabetic neuropathic pain (DNP) is complex involving various processes, which need exploring reliable biomarkers for its early detection and severity prediction.METHODSStudy enrolled 181 patients diagnosed with diabetes, among which 74 patients developed DNP. Serum miR-34a-5p levels were compared between DNP patients and non-DNP patients by polymerase chain reaction (PCR), and the potential of miR-34a-5p in predicting the risk and discriminating patients with DNP was evaluated. The regulatory effect of miR-34a-5p on the inflammation, proliferation, and polarization of microglia was evaluated in HMC3 cells treated with high glucose.RESULTSUpregulated miR-34a-5p was identified as a risk factor and discriminated DNP patients miR-34a-5p was positively correlated with the levels of triglyceride (r = 0.797), fasting blood glucose (r = 0.840), and glycated hemoglobin (r = 0.894) of DNP patients. In HMC3 cells, the high-glucose-induced inflammation, promoted cell growth and caused polarization. The knockdown of miR-34a-5p showed the significant protective effect of microglia activation by high glucose, which was reversed by silencing ENPP3.DISCUSSIONmiR-34a-5p served as a biomarker for the prediction and early detection of DNP and mediated microglia inflammation caused by DNP via modulating ENPP3.","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":"53 1","pages":"1-11"},"PeriodicalIF":2.8,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142216584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Describing Elephants: An Update on the Immunopathology of Multisystem Inflammatory Syndrome in Children.","authors":"Sarah van den Berg, Thomas Sun","doi":"10.1080/08820139.2024.2363833","DOIUrl":"10.1080/08820139.2024.2363833","url":null,"abstract":"<p><p>First described in 2020, multi-system inflammatory syndrome in children (MIS-C) is an, initially life-threatening, disease characterised by severe inflammation and following exposure to SARS-CoV-2. The immunopathology of MIS-C involves a hyperinflammation characterised by a cytokine storm and activation of both the innate and adaptive immune system, eventually leading to multi-organ failure. Several etiological theories are described in literature. Firstly, it is suggested that the gut plays an important role in the translocation of microbial products to the systemic circulation. Additionally, the production of autoantibodies that develop after the initial infection with SARS-CoV-2 might lead to many of its broad clinical symptoms. Finally, the superantigen theory where non-specific binding of the SARS-CoV-2 spike glycoprotein to the T-cell receptor leads to a subsequent activation of T cells, generating a powerful immune response. Despite the sudden outbreak of MIS-C and alarming messages, as of 2024, cases have declined drastically and subsequently show a less severe clinical spectrum. However, subacute cases not meeting current diagnostic criteria might be overlooked even though they represent a valuable research population. In the future, research should focus on adjusting these criteria to better understand the broad pathophysiology of MIS-C, aiding early detection, therapy, and prediction.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"962-974"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wei Zhang, Chengcheng Fan, Zhongxue Yi, Tao Du, Nana Wang, Weizhu Tian, Qian Pan, Xiande Ma, Zhe Wang
{"title":"TMEM79 Ameliorates Cerebral Ischemia/Reperfusion Injury Through Regulating Inflammation and Oxidative Stress via the Nrf2/NLRP3 Pathway.","authors":"Wei Zhang, Chengcheng Fan, Zhongxue Yi, Tao Du, Nana Wang, Weizhu Tian, Qian Pan, Xiande Ma, Zhe Wang","doi":"10.1080/08820139.2024.2354268","DOIUrl":"10.1080/08820139.2024.2354268","url":null,"abstract":"<p><strong>Background: </strong>Cerebral ischemia/reperfusion injury (CIRI) is still a complicated disease with high fatality rates worldwide. Transmembrane Protein 79 (TMEM79) regulates inflammation and oxidative stress in some other diseases.</p><p><strong>Methods: </strong>CIRI mouse model was established using C57BL/6J mice through middle cerebral artery occlusion-reperfusion (MCAO/R), and BV2 cells were subjected to oxygen and glucose deprivation/reoxygenation (OGD/R) to simulate CIRI. Brain tissue or BV2 cells were transfected or injected with lentivirus-carried TMEM79 overexpression vector. The impact of TMEM79 on CIRI-triggered oxidative stress was ascertained by dihydroethidium (DHE) staining and examination of oxidative stress indicators. Regulation of TMEM79 in neuronal apoptosis and inflammation was determined using TUNEL staining and ELISA.</p><p><strong>Results: </strong>TMEM79 overexpression mitigated neurological deficit induced by MCAO/R and decreased the extent of cerebral infarct. TMEM79 prevented neuronal death in brain tissue of MCAO/R mouse model and suppressed inflammatory response by reducing inflammatory cytokines levels. Moreover, TMEM79 significantly attenuated inflammation and oxidative stress caused by OGD/R in BV2 cells. TMEM79 facilitated the activation of Nrf2 and inhibited NLRP3 and caspase-1 expressions. Rescue experiments indicated that the Nrf2/NLRP3 signaling pathway mediated the mitigative effect of TMEM79 on CIRI in vivo and in vitro.</p><p><strong>Conclusion: </strong>Overall, TMEM79 was confirmed to attenuate CIRI via regulating the Nrf2/NLRP3 signaling pathway.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"872-890"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141160849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}