Daniella Dos Santos Courrol, Carla Regina Borges Lopes, Camila Bueno Pacheco Pereira, Marcia Regina Franzolin, Flávia Rodrigues de Oliveira Silva, Lilia Coronato Courrol
{"title":"Tryptophan Silver Nanoparticles Synthesized by Photoreduction Method: Characterization and Determination of Bactericidal and Anti-Biofilm Activities on Resistant and Susceptible Bacteria.","authors":"Daniella Dos Santos Courrol, Carla Regina Borges Lopes, Camila Bueno Pacheco Pereira, Marcia Regina Franzolin, Flávia Rodrigues de Oliveira Silva, Lilia Coronato Courrol","doi":"10.1177/1178646919831677","DOIUrl":"https://doi.org/10.1177/1178646919831677","url":null,"abstract":"<p><p>The high rates of antibiotics use in hospitals have resulted in a condition where multidrug-resistant pathogens have become a severe threat to the human health worldwide. Therefore, there is an increasing necessity to identify new antimicrobial agents that can inhibit the multidrug-resistant bacteria and biofilm formation. In this study, antibacterial and anti-biofilm activities of tryptophan silver nanoparticles (TrpAgNP) were investigated. The TrpAgNPs were synthesized by photoreduction method, and the influence of irradiation time and concentration of reagents were analyzed. The nanoparticles were characterized by transmission electron microscopy, Zeta Potential and (UV)-absorption spectra. The antibacterial activity of TrpAgNPs was tested for antibiotic-resistant and susceptible pathogens, <i>Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Citrobacter freundii, Klebsiella pneumoniae, Salmonella typhimurium, and Pseudomonas aeruginosa</i>, evaluating the influence of photoreduction parameters in bactericidal effect. The results have shown that TrpAgNPs solutions with lower tryptophan/silver nitrate (AgNO<sub>3</sub>) ratio and higher AgNO<sub>3</sub> concentration have higher bactericidal action against bacteria with inhibition of ~100% in almost all studied bacterial strains. The antimicrobial activity of TrpAgNPs within biofilms generated under static conditions of antibiotic-resistant and susceptible strains of <i>S. aureus, S. epidermidis, E. coli, K. pneumoniae, C. freundii</i>, and <i>P. aeruginosa</i> was also investigated. The results showed that TrpAgNPs have an inhibitory effect against biofilm formation, exceeding 50% in the case of Gram-negative bacteria (<i>E. coli, K. pneumoniae, C. freundii</i>, and <i>P. aeruginosa</i>-54.8% to 98.8%). For Gram-positive species, an inhibition of biofilm formation of 68.7% to 72.2 % was observed for <i>S. aureus</i> and 20.0% to 40.2% for <i>S. epidermidis</i>.</p>","PeriodicalId":520654,"journal":{"name":"International journal of tryptophan research : IJTR","volume":" ","pages":"1178646919831677"},"PeriodicalIF":4.4,"publicationDate":"2019-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1178646919831677","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37185234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Felicita F Jusof, Supun M Bakmiwewa, Silvia Weiser, Lay Khoon Too, Richard Metz, George C Prendergast, Stuart T Fraser, Nicholas H Hunt, Helen J Ball
{"title":"Investigation of the Tissue Distribution and Physiological Roles of Indoleamine 2,3-Dioxygenase-2.","authors":"Felicita F Jusof, Supun M Bakmiwewa, Silvia Weiser, Lay Khoon Too, Richard Metz, George C Prendergast, Stuart T Fraser, Nicholas H Hunt, Helen J Ball","doi":"10.1177/1178646917735098","DOIUrl":"https://doi.org/10.1177/1178646917735098","url":null,"abstract":"<p><p>Indoleamine 2,3-dioxygenase-2 (IDO2) is 1 of the 3 enzymes that can catalyze the first step in the kynurenine pathway of tryptophan metabolism. Of the 2 other enzymes, tryptophan 2,3-dioxygenase is highly expressed in the liver and has a role in tryptophan homeostasis, whereas indoleamine 2,3-dioxygenase-1 (IDO1) expression is induced by inflammatory stimuli. Indoleamine 2,3-dioxygenase-2 is reportedly expressed comparatively narrow, including in liver, kidney, brain, and in certain immune cell types, and it does not appear to contribute significantly to systemic tryptophan catabolism under normal physiological conditions. Here, we report the identification of an alternative splicing pattern, including the use of an alternative first exon, that is conserved in the mouse <i>Ido1</i> and <i>Ido2</i> genes. These findings prompted us to assess IDO2 protein expression and enzymatic activity in tissues. Our analysis, undertaken in <i>Ido2<sup> +/+</sup></i> and <i>Ido2<sup>-/-</sup></i> mice using immunohistochemistry and measurement of tryptophan and kynurenine levels, suggested an even more restricted pattern of tissue expression than previously reported. We found IDO2 protein to be expressed in the liver with a perinuclear/nuclear, rather than cytoplasmic, distribution. Consistent with earlier reports, we found <i>Ido2 <sup>-/-</sup></i> mice to be phenotypically similar to their <i>Ido2<sup>+/+</sup></i> counterparts regarding levels of tryptophan and kynurenine in the plasma and liver. Our findings suggest a specialized function or regulatory role for IDO2 associated with its particular subcellular localization.</p>","PeriodicalId":520654,"journal":{"name":"International journal of tryptophan research : IJTR","volume":" ","pages":"1178646917735098"},"PeriodicalIF":4.4,"publicationDate":"2017-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1178646917735098","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35624701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
David B Ramsden, Rosemary H Waring, David J Barlow, Richard B Parsons
{"title":"Nicotinamide <i>N</i>-Methyltransferase in Health and Cancer.","authors":"David B Ramsden, Rosemary H Waring, David J Barlow, Richard B Parsons","doi":"10.1177/1178646917691739","DOIUrl":"https://doi.org/10.1177/1178646917691739","url":null,"abstract":"<p><p>Over the past decade, the roles of nicotinamide <i>N</i>-methyltransferase and its product 1-methyl nicotinamide have emerged from playing merely minor roles in phase 2 xenobiotic metabolism as actors in some of the most important scenes of human life. In this review, the structures of the gene, messenger RNA, and protein are discussed, together with the role of the enzyme in many of the common cancers that afflict people today.</p>","PeriodicalId":520654,"journal":{"name":"International journal of tryptophan research : IJTR","volume":" ","pages":"1178646917691739"},"PeriodicalIF":4.4,"publicationDate":"2017-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1178646917691739","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39814406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Aspects of Tryptophan and Nicotinamide Adenine Dinucleotide in Immunity: A New Twist in an Old Tale.","authors":"Hector Rodriguez Cetina Biefer, Anju Vasudevan, Abdallah Elkhal","doi":"10.1177/1178646917713491","DOIUrl":"https://doi.org/10.1177/1178646917713491","url":null,"abstract":"Increasing evidence underscores the interesting ability of tryptophan to regulate immune responses. However, the exact mechanisms of tryptophan’s immune regulation remain to be determined. Tryptophan catabolism via the kynurenine pathway is known to play an important role in tryptophan’s involvement in immune responses. Interestingly, quinolinic acid, which is a neurotoxic catabolite of the kynurenine pathway, is the major pathway for the de novo synthesis of nicotinamide adenine dinucleotide (NAD+). Recent studies have shown that NAD+, a natural coenzyme found in all living cells, regulates immune responses and creates homeostasis via a novel signaling pathway. More importantly, the immunoregulatory properties of NAD+ are strongly related to the overexpression of tryptophan hydroxylase 1 (Tph1). This review provides recent knowledge of tryptophan and NAD+ and their specific and intriguing roles in the immune system. Furthermore, it focuses on the mechanisms by which tryptophan regulates NAD+ synthesis as well as innate and adaptive immune responses.","PeriodicalId":520654,"journal":{"name":"International journal of tryptophan research : IJTR","volume":" ","pages":"1178646917713491"},"PeriodicalIF":4.4,"publicationDate":"2017-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1178646917713491","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35126964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Giuseppe Corano Scheri, Saeid Najafi Fard, Ivan Schietroma, Andrea Mastrangelo, Claudia Pinacchio, Noemi Giustini, Sara Serafino, Gabriella De Girolamo, Eugenio Nelson Cavallari, Maura Statzu, Luca Laghi, Annamaria Vullo, Giancarlo Ceccarelli, Vincenzo Vullo, Gabriella d'Ettorre
{"title":"Modulation of Tryptophan/Serotonin Pathway by Probiotic Supplementation in Human Immunodeficiency Virus-Positive Patients: Preliminary Results of a New Study Approach.","authors":"Giuseppe Corano Scheri, Saeid Najafi Fard, Ivan Schietroma, Andrea Mastrangelo, Claudia Pinacchio, Noemi Giustini, Sara Serafino, Gabriella De Girolamo, Eugenio Nelson Cavallari, Maura Statzu, Luca Laghi, Annamaria Vullo, Giancarlo Ceccarelli, Vincenzo Vullo, Gabriella d'Ettorre","doi":"10.1177/1178646917710668","DOIUrl":"https://doi.org/10.1177/1178646917710668","url":null,"abstract":"<p><strong>Background: </strong>To date, no data are available regarding the effects of probiotics on the pathway of tryptophan/serotonin metabolism among human immunodeficiency virus (HIV) 1-infected individuals. Because a condition of dysbiosis might be responsible for the altered use of tryptophan described in this population, the aim of this study was to investigate the link between probiotic supplementation and serotonin levels in combined antiretroviral therapy-treated patients and the subsistence of an interplay with inflammation.</p><p><strong>Methods: </strong>We conducted a pilot study that included 8 HIV-positive subjects. We collected blood and fecal samples before and after 6 months of probiotic supplementation, to measure the level of serotonin in serum and tryptophan in stool, the expression of CD38 and HLA-DR on peripheral CD4+ T lymphocytes (as immune activation markers), the expression of indoleamine 2,3-dioxygenase 1 messenger RNA (mRNA) and IFN-γ mRNA (as markers of tryptophan metabolism and systemic inflammation).</p><p><strong>Results: </strong>After probiotic supplementation, we observed a significant increase in concentration of serum serotonin (<i>P</i> = .008) and a decreased level of tryptophan in plasma. Moreover, a significant reduction in CD38 and HLA-DR expression on the surface of peripheral CD4+ T cells (<i>P</i> = .008) and a reduced expression of indoleamine 2,3-dioxygenase 1 mRNA on peripheral blood mononuclear cells (<i>P</i> = .04) were observed.</p><p><strong>Conclusions: </strong>Considering that this probiotic (Vivomixx® in EU; Visbiome® in USA) has an influence on tryptophan metabolism, larger studies on this topic are needed.</p>","PeriodicalId":520654,"journal":{"name":"International journal of tryptophan research : IJTR","volume":" ","pages":"1178646917710668"},"PeriodicalIF":4.4,"publicationDate":"2017-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1178646917710668","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35082684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Kynurenine Pathway of Tryptophan Metabolism: Regulatory and Functional Aspects.","authors":"Abdulla A-B Badawy","doi":"10.1177/1178646917691938","DOIUrl":"https://doi.org/10.1177/1178646917691938","url":null,"abstract":"<p><p>Regulatory and functional aspects of the kynurenine (K) pathway (KP) of tryptophan (Trp) degradation are reviewed. The KP accounts for ~95% of dietary Trp degradation, of which 90% is attributed to the hepatic KP. During immune activation, the minor extrahepatic KP plays a more active role. The KP is rate-limited by its first enzyme, Trp 2,3-dioxygenase (TDO), in liver and indoleamine 2,3-dioxygenase (IDO) elsewhere. TDO is regulated by glucocorticoid induction, substrate activation and stabilization by Trp, cofactor activation by heme, and end-product inhibition by reduced nicotinamide adenine dinucleotide (phosphate). IDO is regulated by IFN-γ and other cytokines and by nitric oxide. The KP disposes of excess Trp, controls hepatic heme synthesis and Trp availability for cerebral serotonin synthesis, and produces immunoregulatory and neuroactive metabolites, the B<sub>3</sub> \"vitamin\" nicotinic acid, and oxidized nicotinamide adenine dinucleotide. Various KP enzymes are undermined in disease and are targeted for therapy of conditions ranging from immunological, neurological, and neurodegenerative conditions to cancer.</p>","PeriodicalId":520654,"journal":{"name":"International journal of tryptophan research : IJTR","volume":" ","pages":"1178646917691938"},"PeriodicalIF":4.4,"publicationDate":"2017-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1178646917691938","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34966704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Interactions of Tryptophan and Its Catabolites With Melatonin and the Alpha 7 Nicotinic Receptor in Central Nervous System and Psychiatric Disorders: Role of the Aryl Hydrocarbon Receptor and Direct Mitochondria Regulation.","authors":"George Anderson, Michael Maes","doi":"10.1177/1178646917691738","DOIUrl":"https://doi.org/10.1177/1178646917691738","url":null,"abstract":"<p><p>Recent work indicates an intimate interaction of the tryptophan catabolite (TRYCAT) pathways with the melatonergic pathways, primarily via TRYCAT pathway induction taking tryptophan away from the production of serotonin, which is a necessary precursor for the melatonergic pathways. The alpha 7 nicotinic receptor may be significantly modulated by this interaction, given its inactivation by the TRYCAT, kynurenic acid, and its induction by melatonin. Similarly, the aryl hydrocarbon receptor is activated by both kynurenic acid and kynurenine, leading to CYP1A2 and melatonin metabolism, whereas melatonin may act to inhibit the aryl hydrocarbon receptor. These 2 receptors and pathways may therefore be intimately linked, with relevance to a host of intracellular processes of clinical relevance. In this article, these interactions are reviewed. Interestingly, mitochondria may be a site for direct interactions of these pathways and receptors, suggesting that their differential induction may not only be modulating neuronal, glia, and immune cell processes and activity but also be directly acting to regulate mitochondrial functioning. This is likely to have significant consequences as to how an array of diverse central nervous system and psychiatric conditions are conceptualized and treated.</p>","PeriodicalId":520654,"journal":{"name":"International journal of tryptophan research : IJTR","volume":" ","pages":"1178646917691738"},"PeriodicalIF":4.4,"publicationDate":"2017-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1178646917691738","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34966703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Relationships between Salivary Melatonin Levels, Quality of Sleep, and Stress in Young Japanese Females.","authors":"Yasuhiro Ito, Tadayuki Iida, Yuumi Yamamura, Mayu Teramura, Yasushi Nakagami, Kaoru Kawai, Yoichi Nagamura, Ryoji Teradaira","doi":"10.4137/IJTR.S11760","DOIUrl":"https://doi.org/10.4137/IJTR.S11760","url":null,"abstract":"<p><p>A decrease in the quality of sleep is believed to cause anxiety and worsen depression. Comparisons of salivary melatonin levels with different factors including quality of sleep, state and trait anxieties, and depression, were conducted to examine whether there is a relationship between melatonin, presumably associated with sleep, and psychological stress. The saliva of healthy young females was collected during the daytime and before they went to bed at night (when they were awake and resting in a sitting position), and salivary melatonin levels were measured. The quality of sleep was scored using the Pittsburgh Sleep Quality Index (PSQI)-a questionnaire method. State and trait anxieties, and depression were scored using other questionnaire methods: the State-Trait Anxiety Inventory (STAI) and Self-Rating Depression Scale (SDS), respectively. The following findings were obtained: (1) Salivary melatonin levels measured during the daytime and before going to bed were higher in females with a high depression score, compared to those with a low score, and there was a correlation between the depression scores and salivary melatonin levels measured at night; and (2) salivary melatonin levels measured before going to bed at night (in a sitting position) were higher in females with a high state anxiety score, suggesting a correlation between state anxiety scores and salivary melatonin levels during the night. Both depression and a sense of anxiety are forms of psychological stress. Therefore, it is assumed that, when a person is under psychological stress, the action of melatonin as a ligand on its receptor is reduced. Meaning psychological stress may induce oxidative stress in the body. On the other hand, no correlation was noted between the quality of sleep and salivary melatonin levels during the night, presumably because saliva was collected when the subjects were awake and sitting, rather than sleeping. </p>","PeriodicalId":520654,"journal":{"name":"International journal of tryptophan research : IJTR","volume":" ","pages":"75-85"},"PeriodicalIF":4.4,"publicationDate":"2013-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/IJTR.S11760","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40279721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nutritional aspect of tryptophan metabolism.","authors":"Tsutomu Fukuwatari, Katsumi Shibata","doi":"10.4137/IJTR.S11588","DOIUrl":"https://doi.org/10.4137/IJTR.S11588","url":null,"abstract":"<p><p>Mammals, including humans, can synthesize the vitamin nicotinamide from tryptophan in the liver. The resultant nicotinamide is distributed to non-hepatic tissues. We have studied the effects of changes in tryptophan-nicotinamide metabolism on niacin nutritional status. The liver plays a critical role in nicotinamide supply. Animal studies showed that the tryptophan-nicotinamide pathway is affected by physiological conditions, the presence of disease, nutrients, hormones, and chemicals. Human studies have shown that 1 mg of nicotinamide is produced from 67 mg of tryptophan intake, and that the conversion ratio of tryptophan to nicotinamide is enhanced from mid to late pregnancy. These findings have contributed to the determination of dietary reference intakes for niacin recommended in the Dietary Reference Intakes for Japanese 2010. Our findings suggest that the conversion of nicotinamide from tryptophan is important in maintaining niacin nutrition. </p>","PeriodicalId":520654,"journal":{"name":"International journal of tryptophan research : IJTR","volume":" ","pages":"3-8"},"PeriodicalIF":4.4,"publicationDate":"2013-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/IJTR.S11588","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39973537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exploitation of the IDO Pathway in the Therapy of Rheumatoid Arthritis.","authors":"Richard O Williams","doi":"10.4137/IJTR.S11737","DOIUrl":"https://doi.org/10.4137/IJTR.S11737","url":null,"abstract":"<p><p>Indoleamine 2,3-dioxygenase (IDO) is the first and rate-limiting step along the kynurenine pathway and is thought to play a key role in immune homeostasis through depletion of tryptophan and accumulation of kynurenines. In this review we summarize recent research into the possibility of harnessing the IDO pathway for the therapy of rheumatoid arthritis. Inhibition of IDO activity, or knockout of the gene encoding IDO, was shown to cause an increase in the severity of collagen-induced arthritis, an animal model of rheumatoid arthritis. The increased severity of disease was associated with elevated numbers of pathogenic Th1 and Th17 cells in the joints and draining lymph nodes. In another study, analysis of the kinetics of expression of downstream kynurenine pathway enzymes during the course of arthritis revealed a potential role for tryptophan metabolites in resolution of arthritis. Furthermore, the therapeutic administration of L-kynurenine or [3,4-dimethoxycinnamonyl]-anthranilic acid (a synthetic derivative of 3-hydroxy-anthranilic acid) significantly reduced both clinical and histological progression of experimental arthritis. These findings raise the possibility of exploiting the IDO pathway for the therapy of autoimmune disease. </p>","PeriodicalId":520654,"journal":{"name":"International journal of tryptophan research : IJTR","volume":" ","pages":"67-73"},"PeriodicalIF":4.4,"publicationDate":"2013-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/IJTR.S11737","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39972845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}