Heng Zhang, Xi Lan, Liquan Cai, Xunfeng Gao, Feng Gao, Dan Yu, Jinlong Zhang, Jinhui Zhang, Qinwen Tai
{"title":"miR-215-5p Plays a Key Role in Suppressing Vascular Invasion and Recurrence in Hepatocellular Carcinoma by Blocking Vasculogenic Mimicry.","authors":"Heng Zhang, Xi Lan, Liquan Cai, Xunfeng Gao, Feng Gao, Dan Yu, Jinlong Zhang, Jinhui Zhang, Qinwen Tai","doi":"10.31083/j.fbe1601006","DOIUrl":"10.31083/j.fbe1601006","url":null,"abstract":"<p><strong>Background: </strong>This research explores the significance of miR-215-5p and vasculogenic mimicry (VM) in forecasting the prognosis for hepatocellular carcinoma (HCC).</p><p><strong>Methods: </strong>We analyzed HCC-associated miRNA expression profiles using data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Samples included tissue and blood from 80 early-stage HCC patients and serum from 120 healthy individuals. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was employed to measure miR-215-5p and zinc finger E-box binding homeobox 2 (<i>ZEB2</i>) gene expressions. Hematoxylin and eosin (H&E) and CD34/Periodic Acid-Schiff (PAS) double staining assessed VM presence in HCC tissue sections. Bioinformatics tools predicted interactions between miR-215-5p and <i>ZEB2</i>, confirmed through luciferase reporter assays. We also examined the impact of miR-215-5p or <i>ZEB2</i> overexpression on HCC cell invasion, migration, and VM formation using scratch, Transwell invasion assays, and Matrigel 3D cultures.</p><p><strong>Results: </strong>Bioinformatics analysis indicated that miR-215-5p was under-expressed in HCC, particularly in cases with vascular invasion, which correlated with worse patient outcomes. In contrast, <i>ZEB2</i>, targeted by miR-215-5p, was overexpressed in HCC. RT-qPCR validated these expression patterns in HCC tissues. Among the HCC patients, 38 were VM positive and 42 VM negative. Logistic regression highlighted a negative correlation between miR-215-5p levels and VM positivity in HCC tissues and a positive correlation for <i>ZEB2</i> with VM positivity and tumor vascular invasion. Lower miR-215-5p levels were linked to increased HCC recurrence and metastasis. Both bioinformatics analysis and luciferase assays demonstrated a direct interaction between miR-215-5p and <i>ZEB2</i>. Enhancing miR-215-5p levels reduced <i>ZEB2</i> expression, consequently diminishing invasion, migration, and VM formation of the HCC cells <i>in vitro</i>.</p><p><strong>Conclusions: </strong>miR-215-5p expression inversely correlates with VM occurrence in HCC tissues, while <i>ZEB2</i> expression shows a direct correlation. By targeting <i>ZEB2</i>, miR-215-5p may hinder VM in HCC tissues, helping to prevent vascular invasion and HCC recurrence. Thus, miR-215-5p emerges as a vital prognostic indicator for predicting vascular invasion and recurrence in HCC.</p>","PeriodicalId":73068,"journal":{"name":"Frontiers in bioscience (Elite edition)","volume":"16 1","pages":"6"},"PeriodicalIF":0.0,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140308179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Fluorescence Polarization Assays for Organic Compounds in Food Safety.","authors":"Liliya I Mukhametova, Sergei A Eremin","doi":"10.31083/j.fbe1601004","DOIUrl":"10.31083/j.fbe1601004","url":null,"abstract":"<p><p>Elevated concentrations of toxic organic compounds observed in food products pose serious dangers to human health. Both natural and artificial pollutants can cause food contamination. The stages of food production, packaging, transportation, and storage can also largely cause the appearance of undesirable substances in food products. The health consequences of ingesting food containing toxic contaminants range from mild gastroenteritis to deaths resulting from dysfunctional internal organs and neurological syndromes. The World Health Organization (WHO) sets recommendations for the content of such chemicals in food, including a minimum allowable concentration considered safe for human consumption. However, the control of food products from chemical pollutants is necessary. Moreover, fast, sensitive, and inexpensive methods are needed to detect them at the point of need. Currently, immune analysis methods are most widely used to determine pollutants in food. The development of fluorescence polarization immunoassay (FPIA) methods in a competitive format is a powerful and modern tool for detecting organic molecules in various matrices, thereby making FPIA methods useful for food safety applications. Due to the availability of portable devices for measuring the fluorescence polarization signal, FPIA methods can be used at the point of need. The variety of fluorescent labels and recognizing elements (receptors, monoclonal and polyclonal antibodies, and nanobodies) permits fluorescence polarization (FP) assays to detect significantly lower limits of organic substances. The FP assay is a homogeneous, fast, and quantitative method. The development of various formats of FP assays makes them promising in determining food pollutants. This review summarizes publications on FP analyses for detecting organic contaminants (pesticides, hormones, toxins, antibiotics, and other pharmaceuticals) in food products during 2018-2023. Further, it demonstrates the prospects for using this method to determine pollutants at the point of need and for detecting high molecular weight substances, fungi, and bacterial infections during food safety inspections.</p>","PeriodicalId":73068,"journal":{"name":"Frontiers in bioscience (Elite edition)","volume":"16 1","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140308167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Xrn1 Exoribonuclease-An Intrinsic Marker of Yeast Population Growth.","authors":"Tomas Grousl, Tomas Vomastek","doi":"10.31083/j.fbe1601001","DOIUrl":"10.31083/j.fbe1601001","url":null,"abstract":"<p><strong>Background: </strong>Xrn1 exoribonuclease is the major mRNA degradation enzyme in <i>Saccharomyces cerevisiae.</i> In exponentially growing cells, Xrn1 is localised in the yeast cells and directs the degradation of mRNA molecules. Xrn1 is gradually deposited and presumably inactivated in the processing bodies (P-bodies) as the yeast population ages. Xrn1 can also localise to the membrane compartment of the arginine permease Can1/eisosome compartment at the yeast plasma membrane. This localisation correlates with the metabolic (diauxic) shift from glucose fermentation to respiration, although the relevance of this Xrn1 localisation remains unknown.</p><p><strong>Methods: </strong>We monitored the growth rates and morphology of Xrn1-green fluorescent protein (GFP) cells compared to wild-type and Δ<i>xrn1</i> cells and observed the Xrn1-GFP localisation pattern in different media types for up to 72 hours using fluorescence microscopy.</p><p><strong>Results: </strong>We present the dynamic changes in the localisation of Xrn1 as a versatile tool for monitoring the growth of yeast populations at the single-cell level using fluorescence microscopy.</p><p><strong>Conclusions: </strong>The dynamic changes in the localisation of Xrn1 can be a versatile tool for monitoring the growth of yeast populations at the single-cell level. Simultaneously, Xrn1 localisation outside of P-bodies in post-diauxic cells supports its storage and cytoprotective function, yet the role of P-bodies in cell metabolism has still not yet been entirely elucidated.</p>","PeriodicalId":73068,"journal":{"name":"Frontiers in bioscience (Elite edition)","volume":"16 1","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140308181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Soy-Based Tempeh as a Functional Food: Evidence for Human Health and Future Perspective.","authors":"Gianluca Rizzo","doi":"10.31083/j.fbe1601003","DOIUrl":"10.31083/j.fbe1601003","url":null,"abstract":"<p><p>Tempeh is an Indonesian traditional food made from fermented soybeans, which offers wide culinary use in East Asian countries. Similar to all fermented foods, its preparation offers the purpose of food preservation. However, preclinical studies have highlighted that microbial action leads to a modification in the nutritional composition of the food's matrix. Although there is a wide availability of data on the beneficial effect of soy, tempeh remains relatively unexplored, perhaps due to its limited diffusion in the world, which limits its research availability. However, available data suggest that tempeh may confer beneficial health effects due to the high bioavailability of nutrients and phytochemicals, showing ameliorative action on oxidative stress, glycaemic control, and blood lipid levels. Furthermore, the high biological value of tempeh means it can be used to optimize protein and caloric intake in athletes, vegetarians, and children. Moreover, the microbial fermentation used in the production of tempeh, in addition to improving the bioavailability of minerals, proteins, fibre, vitamins, and isoflavones, produces biopeptides whose biological effect is currently of great interest. Tempeh can be employed in traditional preparations as well as second-generation foods, such as plant-based meat substitutes, to provide functional and nutritional properties and a higher eco-friendly option compared to animal foods. This review aims to provide an overview of tempeh's properties, regarding human data and future research perspectives.</p>","PeriodicalId":73068,"journal":{"name":"Frontiers in bioscience (Elite edition)","volume":"16 1","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140308180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Madiha Nazir, Attia Iram, Deniz Cekmecelioglu, Ali Demirci
{"title":"Approaches for Producing Fungal Cellulases Through Submerged Fermentation.","authors":"Madiha Nazir, Attia Iram, Deniz Cekmecelioglu, Ali Demirci","doi":"10.31083/j.fbe1601005","DOIUrl":"10.31083/j.fbe1601005","url":null,"abstract":"<p><p>Fungal cellulases are the most sought-after biological molecules produced from microbial sources in the last four decades. Owing to their emerging applications in the bioenergy industry for hydrolyzing cellulose, for which they are the most abundant source on this planet, research trends are shifting heavily toward adapting to submerged fermentation. However, filamentous fungal species, which are efficient cellulase producers, are well-adapted to low-moisture solid support as the substrate, such as in nature. Therefore, various fermentation strategies are currently being investigated to adapt them to submerged fermentation for large and high-quality production of cellulases. Emerging research trends, such as the use of inexpensive feedstocks, nutrient and/or culture optimization, innovative bioreactor designs, microparticle-assisted fungal growth, and innovative genetic engineering approaches, are some of the recent efforts by researchers to exploit the full potential of these biological molecules. This review discusses some of these strategies and their success rates in various research conditions. In addition, specific focus was provided to both increasing the market value of cellulases and the innovative strategies required to enhance their production on an industrial scale.</p>","PeriodicalId":73068,"journal":{"name":"Frontiers in bioscience (Elite edition)","volume":"16 1","pages":"5"},"PeriodicalIF":0.0,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140308165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mujahid Alam, P Stephen Baenziger, Katherine Frels
{"title":"Emerging Trends in Wheat (<i>Triticum</i> spp.) Breeding: Implications for the Future.","authors":"Mujahid Alam, P Stephen Baenziger, Katherine Frels","doi":"10.31083/j.fbe1601002","DOIUrl":"10.31083/j.fbe1601002","url":null,"abstract":"<p><p>Wheat (<i>Triticum</i> spp and, particularly, <i>T. aestivum</i> L.) is an essential cereal with increased human and animal nutritional demand. Therefore, there is a need to enhance wheat yield and genetic gain using modern breeding technologies alongside proven methods to achieve the necessary increases in productivity. These modern technologies will allow breeders to develop improved wheat cultivars more quickly and efficiently. This review aims to highlight the emerging technological trends used worldwide in wheat breeding, with a focus on enhancing wheat yield. The key technologies for introducing variation (hybridization among the species, synthetic wheat, and hybridization; genetically modified wheat; transgenic and gene-edited), inbreeding (double haploid (DH) and speed breeding (SB)), selection and evaluation (marker-assisted selection (MAS), genomic selection (GS), and machine learning (ML)) and hybrid wheat are discussed to highlight the current opportunities in wheat breeding and for the development of future wheat cultivars.</p>","PeriodicalId":73068,"journal":{"name":"Frontiers in bioscience (Elite edition)","volume":"16 1","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140308166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Atefehsadat Mortazavi, Mehdi Hassanshahian, Eyhab Ali, Mohammed N Fenjan, Ahmed Alawadi, Ali Alsalamy
{"title":"Isolation and Identification of Phenol-Degrading Bacteria from Iranian Soil and Leaf Samples.","authors":"Atefehsadat Mortazavi, Mehdi Hassanshahian, Eyhab Ali, Mohammed N Fenjan, Ahmed Alawadi, Ali Alsalamy","doi":"10.31083/j.fbe1504029","DOIUrl":"10.31083/j.fbe1504029","url":null,"abstract":"<p><strong>Background: </strong>By considering the importance and role of soil in the health of humanity, it is important to remove the presence of harmful compounds, such as phenol.</p><p><strong>Methods: </strong>In this study, four types of soil and leaf samples were collected from Kerman, Iran, and the amounts of heterotrophic and degradation bacteria were determined using the serial dilution and most probable number (MPN) methods. The amount of removed phenol was investigated using the Gibbs method with different concentrations of phenol. Then, an isolate with the highest percentage of phenol degradation was identified as the superior strain using 16 sRNA sequencing. The effects of the different factors, such as the carbon source (1% molasses and 1 g glucose), nitrogen source (0.1 g yeast extract), mixed culture, and time (14 and 28 days), on the biodegradation ability of the superior strain was investigated.</p><p><strong>Results: </strong>A total of 18 bacterial strains were isolated from the samples. Isolate B3 had the highest rate (75%) of phenol degradation, at a concentration of 1000 ppm, meaning it was identified as the superior strain. The molecular analysis results identified this isolate as the <i>Comamonas testosteroni</i> strain F4. This bacterium can degrade 89% of the phenol at 30 °C, 180 rpm, and 800 ppm over 28 days. <i>C. testosteroni</i> did not show a favorable phenol degradation ability in the presence of the investigated carbon sources, while this ability was also reduced in mixed cultures.</p><p><strong>Conclusions: </strong><i>C. testosteroni</i> bacterial strain isolated from soil samples of pistachio orchards in Kerman, Iran, has a favorable ability to biodegrade phenol.</p>","PeriodicalId":73068,"journal":{"name":"Frontiers in bioscience (Elite edition)","volume":"15 4","pages":"29"},"PeriodicalIF":0.0,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139076066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Blanca Sáenz de Miera, Raquel Cañadas, María González-Miquel, Emilio J González
{"title":"Recovery of Phenolic Compounds from Orange Peel Waste by Conventional and Assisted Extraction Techniques Using Sustainable Solvents.","authors":"Blanca Sáenz de Miera, Raquel Cañadas, María González-Miquel, Emilio J González","doi":"10.31083/j.fbe1504030","DOIUrl":"10.31083/j.fbe1504030","url":null,"abstract":"<p><strong>Background: </strong>The valorization of orange peel waste (OPW) through the extraction of bioactive compounds is a clear example of the circular economy. OPW contains many value-added compounds, among which bioactive phenolic compounds (flavonoids and phenolic acids) could be extracted and used for industrial applications, such as pharmaceuticals or cosmetics.</p><p><strong>Methods: </strong>In this work, the extraction of phenolic compounds from orange peel was carried out by conventional (orbital shaker) and assisted (ultrasound and microwave) extraction techniques using deionized water, 80% (v/v) ethanol in water, and ethyl acetate as solvents. The effect of temperature, extraction time, and type of technique was evaluated and discussed following spectrophotometric (total phenolic content and total flavonoid content) and high-performance liquid chromatography (HPLC) analyses of the extracts.</p><p><strong>Results: </strong>The most effective extraction in terms of efficiency was achieved by microwave-assisted extraction using 80% (v/v) ethanol in water as the extraction solvent, at 373 K for 6 min, which obtained 7.2 ± 0.1 mg gallic acid equivalent (GAE)/g OPW and 13.3 ± 0.1 mg quercetin equivalent (QE)/g OPW, with the main bioactive compound extracted being hesperidin (58.2 ± 0.2 mg/g OPW). The most effective extraction in terms of energy consumption was achieved using ultrasound-probe-assisted extraction, yielding 8.8 ± 0.0 mg GAE/g OPW; 17.1 ± 0.1 mg QE/g OPW; 40.0 ± 0.2 mg hesperidin/g OPW, with an energy consumption of 18 kJ.</p><p><strong>Conclusions: </strong>Ultrasound and microwave-assisted extractions can be considered efficient extraction technologies for the valorization of OPW as they reduce extraction time and energy consumption and increase extraction yield.</p>","PeriodicalId":73068,"journal":{"name":"Frontiers in bioscience (Elite edition)","volume":"15 4","pages":"30"},"PeriodicalIF":0.0,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139076067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ibrahim Bello, Adewale Adeniyi, Taofeek Mukaila, Ewumbua Monono, Ademola Hammed
{"title":"Biological Ammonia Production via Anaerobic Fermentation of Soy Meal Protein.","authors":"Ibrahim Bello, Adewale Adeniyi, Taofeek Mukaila, Ewumbua Monono, Ademola Hammed","doi":"10.31083/j.fbe1504027","DOIUrl":"10.31083/j.fbe1504027","url":null,"abstract":"<p><strong>Background: </strong>Conventional ammonia production methods, notably the energy-intensive Haber-Bosch process, are costly and contribute substantially to about 2% of the world's CO2 emissions. This study focuses on the biological approach to convert protein to ammonia via hyper-ammonia-producing bacteria (HAB) fermentation.</p><p><strong>Methods: </strong>A consortium of ruminal microbes was employed in this work to ferment soybean meal protein under varying processing conditions. The parameters investigated included pH (7-11), inoculum concentrations (1-10%), substrate concentrations (5-20%), and fermentation time (0-168 h).</p><p><strong>Results: </strong>Optimal conditions for microbial growth and biological ammonia production were observed at pH 7, fermentation duration of 72 h, inoculum concentration of 10%, and substrate concentration of 10%. ~8000 mg/L biological ammonia was produced following HAB fermentation.</p><p><strong>Conclusions: </strong>By leveraging the capabilities of rumen HAB, this study contributes to the ongoing efforts to develop environmentally friendly processes for ammonia production that will mitigate both economic and environmental concerns associated with traditional methods.</p>","PeriodicalId":73068,"journal":{"name":"Frontiers in bioscience (Elite edition)","volume":"15 4","pages":"27"},"PeriodicalIF":0.0,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139076064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Role of the Microbiome in Inflammation and Carcinogenesis.","authors":"Agata Jabłońska-Trypuć","doi":"10.31083/j.fbe1504028","DOIUrl":"10.31083/j.fbe1504028","url":null,"abstract":"<p><p>Inflammation has been confirmed to exist in the tumor microenvironment, while the risk of cancer occurrence increases in cases of chronic inflammation. It is estimated that approximately 10% to 20% of cancers are associated with chronic infections and attendant inflammation. Bacteria, both pathogenic and commensal, viruses, and fungi actively participate in the development and maintenance of inflammation and tumor growth in humans. The exposome, which is a sum of human environmental exposures, such as industrial diet, consumed drugs, and toxins, affects the composition and function of the human microbiome, which could lead to dysbiosis and disorders in tissue homeostasis through different mechanisms, including the intensification of the immune response, activation and abnormal proliferation, and disruption to epithelial barrier integrity. Presently, science remains at the stage of revealing the complexity associated with the mechanisms involved in building relationships that cover the microbiome-inflammation-tumor, yet it is already known how important it is to care for microbial homeostasis of the organism.</p>","PeriodicalId":73068,"journal":{"name":"Frontiers in bioscience (Elite edition)","volume":"15 4","pages":"28"},"PeriodicalIF":0.0,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139076069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}