BioTech最新文献

{"title":"Discovery of Innate Immune Response mRNAs That Are Impacted by Structure-Specific Oral Baker's Yeast Beta Glucan Consumption.","authors":"Brian K McFarlin, John H Curtis, Jakob L Vingren, David W Hill, Elizabeth A Bridgeman","doi":"10.3390/biotech14010004","DOIUrl":"10.3390/biotech14010004","url":null,"abstract":"<p><p>The study of nutritional compounds with the potential to train the innate immune response has implications for human health. The objective of the current study was to discover by what means 6 weeks of oral baker's yeast beta glucan (BYBG) supplementation altered the mRNA expression of genes that reflect innate immune training in the absence of a physical stressor. Nineteen adults were randomly assigned to either a Wellmune^® BYBG or Placebo for 6 weeks. BYBG uniquely altered the expression of 40 mRNAs associated with Dectin-1 and trained innate immunity, the innate immune response, the pathogen-associated (PAMP) and damage-associated molecular pattern (DAMP), and the inflammatory response. The observed changes were classified as immune training rather than immune priming due to the progressive increase in the expression of myeloid immune-associated mRNA. Combined with the findings of previous research, the findings of the present study support the claim that oral BYBG supplementation may be associated with trained innate immunity during resting homeostasis. Further, the key findings associated with BYBG may reflect improved responsiveness to future infection (exogenous) and/or sterile-inflammatory (endogenous) challenge.</p>","PeriodicalId":34490,"journal":{"name":"BioTech","volume":"14 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025055","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":"Impact of <i>GAUT1</i> Gene Knockout on Cell Aggregation in <i>Arabidopsis thaliana</i> Suspension Culture.","authors":"Tatyana A Frankevich, Natalya V Permyakova, Yury V Sidorchuk, Elena V Deineko","doi":"10.3390/biotech14010002","DOIUrl":"10.3390/biotech14010002","url":null,"abstract":"<p><p>The development of efficient producers of recombinant pharmaceuticals based on plant cell suspension cultures is a pressing challenge in modern applied science. A primary limitation of plant cell cultures is their relatively low yield of the target protein. One strategy to enhance culture productivity involves reducing cell aggregation. In order to minimize cell-to-cell adhesion in culture, we used Cas9 endonuclease to knock out the <i>GAUT1</i> gene, which is a key gene of pectin biosynthesis in the genome of <i>Arabidopsis thaliana</i>. The resulting knockouts exhibited altered phenotypes and were unable to form viable plants. The suspension cell culture induced from seedlings bearing a homozygous deletion in the <i>GAUT1</i> gene displayed darker coloration and an increased number of large aggregates compared to the control. The biomass accumulation rate showed no difference from the control, while the level of recombinant GFP protein accumulation was significantly reduced. Thus, our findings indicate that disruptions in pectin synthesis and the formation of larger aggregates in the suspension cell culture adversely affect the accumulation of the target recombinant protein. Alternative targets should be sought to reduce cell aggregation levels in plant cell cultures through genome editing.</p>","PeriodicalId":34490,"journal":{"name":"BioTech","volume":"14 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025056","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":"Current Approaches for Genetic Manipulation of <i>Streptomyces</i> spp.-Key Bacteria for Biotechnology and Environment.","authors":"Sergii Krysenko","doi":"10.3390/biotech14010003","DOIUrl":"10.3390/biotech14010003","url":null,"abstract":"<p><p>Organisms from the genus <i>Streptomyces</i> feature actinobacteria with complex developmental cycles and a great ability to produce a variety of natural products. These soil bacteria produce more than 2/3 of antibiotics used in medicine, and a large variety of bioactive compounds for industrial, medical and agricultural use. Although <i>Streptomyces</i> spp. have been studied for decades, the engineering of these bacteria remains challenging, and the available genetic tools are rather limited. Furthermore, most biosynthetic gene clusters in these bacteria are silent and require strategies to activate them and exploit their production potential. In order to explore, understand and manipulate the capabilities of <i>Streptomyces</i> spp. as a key bacterial for biotechnology, synthetic biology strategies emerged as a valuable component of <i>Streptomyces</i> research. Recent advancements in strategies for genetic manipulation of <i>Streptomyces</i> involving proposals of a large variety of synthetic components for the genetic toolbox, as well as new approaches for genome mining, assembly of genetic constructs and their delivery into the cell, allowed facilitation of the turnaround time of strain engineering and efficient production of new natural products at an industrial scale, but still have strain- and design-dependent limitations. A new perspective offered recently by technical advances in DNA sequencing, analysis and editing proposed strategies to overcome strain- and construct-specific difficulties in the engineering of <i>Streptomyces</i>. In this review, challenges and recent developments of approaches for <i>Streptomyces</i> engineering are discussed, an overview of novel synthetic biology strategies is provided and examples of successful application of new technologies in molecular genetic engineering of <i>Streptomyces</i> are highlighted.</p>","PeriodicalId":34490,"journal":{"name":"BioTech","volume":"14 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025135","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":"Peptide Inhibitor Assay for Allocating Functionally Important Accessible Sites Throughout a Protein Chain: Restriction Endonuclease EcoRI as a Model Protein System.","authors":"Joji M Otaki","doi":"10.3390/biotech14010001","DOIUrl":"10.3390/biotech14010001","url":null,"abstract":"<p><p>Functionally important amino acid sequences in proteins are often located at multiple sites. Three-dimensional structural analysis and site-directed mutagenesis may be performed to allocate functional sites for understanding structure‒function relationships and for developing novel inhibitory drugs. However, such methods are too demanding to comprehensively cover potential functional sites throughout a protein chain. Here, a peptide inhibitor assay (PIA) was devised to allocate functionally important accessible sites in proteins. This simple method presumes that protein‒ligand interactions, intramolecular interactions, and dimerization interactions can be partially inhibited by high concentrations of competitive \"endogenous\" peptides of the protein of interest. Focusing on the restriction endonuclease EcoRI as a model protein system, many endogenous peptides (6mer-14mer) were synthesized, covering the entire EcoRI protein chain. Some of them were highly inhibitory, but interestingly, the nine most effective peptides were located outside the active sites, with the exception of one. Relatively long peptides with aromatic residues (F, H, W, and Y) corresponding to secondary structures were generally effective. Because synthetic peptides are flexible enough to change length and amino acid residues, this method may be useful for quickly and comprehensively understanding structure‒function relationships and developing novel drugs or epitopes for neutralizing antibodies.</p>","PeriodicalId":34490,"journal":{"name":"BioTech","volume":"14 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025134","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":"The Effects of the Combined Co-Expression of GroEL/ES and Trigger Factor Chaperones on Orthopoxvirus Phospholipase F13 Production in <i>E. coli</i>.","authors":"Iuliia A Merkuleva, Vladimir N Nikitin, Tatyana D Belaya, Egor A Mustaev, Dmitriy N Shcherbakov","doi":"10.3390/biotech13040057","DOIUrl":"10.3390/biotech13040057","url":null,"abstract":"<p><p>Heterologous protein expression often faces significant challenges, particularly when the target protein has posttranslational modifications, is toxic, or is prone to misfolding. These issues can result in low expression levels, aggregation, or even cell death. Such problems are exemplified by the expression of phospholipase p37, a critical target for chemotherapeutic drugs against pathogenic human orthopoxviruses, including monkeypox and smallpox viruses. The complex structure and broad enzymatic activity of phospholipase p37 render it toxic to host cells, necessitating specialized strategies for heterologous expression. In our study, we addressed these challenges using the vaccinia virus F13 protein as a model. We demonstrated that p37 can be effectively synthesized in <i>E. coli</i> as a GST fusion protein by co-expressing it with the GroEL/ES chaperone system and Trigger Factor chaperone.</p>","PeriodicalId":34490,"journal":{"name":"BioTech","volume":"13 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11674265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898711","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":"A Study on the Function of Arginine in the Growth, Immunity, Antioxidant Activity, and Oxygen Carrying-Capacity of Juvenile Gibel Carp (<i>Carassius auratus gibelio</i>).","authors":"Yuqun Li, Lu Zhang, Mingchun Ren, Hualiang Liang, Haifeng Mi, Dongyu Huang","doi":"10.3390/biotech13040056","DOIUrl":"10.3390/biotech13040056","url":null,"abstract":"<p><p>An eight-week trial was designed to study the effects of arginine (Arg) supplemented diets on the growth, immunity, antioxidant activity, and oxygen-carrying capacity of juvenile Gibel carp (<i>Carassius auratus gibelio</i>). A total of 300 fish (27.53 ± 0.03 g) were randomized into 15 equal groups and fed on diets with graded Arg levels: 0 (control), 0.2%, 0.4%, 0.6%, and 0.8% (<i>w</i>/<i>w</i>). The results showed that final body weight (FBW), weight gain rate (WGR), and specific growth rate (SGR) all increased and then declined with increasing levels of Arg supplementation, while feed conversion ratio (FCR) showed the opposite trend. In addition, the fish's whole-body crude protein and ash content had no remarkable difference at different levels of Arg addition (<i>p</i> > 0.05). Supplementation with 0.6% and 0.8% Arg significantly increased plasma alanine transaminase (ALT) activity (<i>p</i> < 0.05). The malondialdehyde (MDA) levels and superoxide dismutase (SOD) activities of the liver were not significantly different between the different levels of Arg supplementation (<i>p</i> > 0.05), while catalase (CAT) activity was significantly increased with 0.4% Arg supplementation levels (<i>p</i> < 0.05). The 0.8% Arg supplementation greatly increased the expression of hepatic-related genes to the Nrf2 signaling pathway, including <i>sod</i> and <i>gpx</i> (<i>p</i> < 0.05). However, the 0.8% Arg supplementation did not significantly increase the relative expression of genes related to the NF-κB signaling pathway, including <i>il-1β</i>, <i>il-8</i>, and <i>tnf-α</i> (<i>p</i> > 0.05). Similarly, the relative expression of hif-1 signaling pathway-related genes at 0.8% Arg supplementation was significantly elevated, including <i>hif-1α</i>, <i>epo</i>, and <i>vegf</i> (<i>p</i> < 0.05). Hence, Arg supplementation could promote growth and improve immune, antioxidant, and oxygen-carrying capacity in juvenile Gibel carp.</p>","PeriodicalId":34490,"journal":{"name":"BioTech","volume":"13 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11675026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898700","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":"Bioenergy Production from Sorghum Distillers Grains via Dark Fermentation.","authors":"Ching-Chun Lu, Chiu-Yue Lin","doi":"10.3390/biotech13040055","DOIUrl":"10.3390/biotech13040055","url":null,"abstract":"<p><p>Sorghum distillers grains (SDGs) produced from a sorghum liquor company were used for generating biohydrogen via dark fermentation at pH 4.5-6.5 and 55 °C with a batch test, and the biohydrogen electricity generation potential was evaluated. The experimental results show that pH markedly affects hydrogen concentration, hydrogen production rate (HPR) and hydrogen yield (HY), in that high acidic pH values result in high values. The HPR and HY ranged from 0.76 to 3.2 L/L-d and 21.4 to 62.3 mL/g chemical oxygen demand, respectively. These hydrogen production values were used to evaluate bioelectricity generation using a newly developed gas/liquid-fuel engine. The results show a new and prospective biomass source for biohydrogen production, bioelectricity generation and simultaneously solving the problem of treating SDGs when producing kaoliang liquor. Applications of the experimental results are also discussed.</p>","PeriodicalId":34490,"journal":{"name":"BioTech","volume":"13 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11674095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898701","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":"Prospects in the Use of <i>Cannabis sativa</i> Extracts in Nanoemulsions.","authors":"Ian Vitola, Carlos Angulo, Raul C Baptista-Rosas, Luis Miguel Anaya-Esparza, Zazil Yadel Escalante-García, Angélica Villarruel-López, Jorge Manuel Silva-Jara","doi":"10.3390/biotech13040053","DOIUrl":"10.3390/biotech13040053","url":null,"abstract":"<p><p><i>Cannabis sativa</i> plants have been widely investigated for their specific compounds with medicinal properties. These bioactive compounds exert preventive and curative effects on non-communicable and infectious diseases. However, <i>C. sativa</i> extracts have barely been investigated, although they constitute an affordable option to treat human diseases. Nonetheless, antioxidant, antimicrobial, and immunogenicity effects have been associated with <i>C. sativa</i> extracts. Furthermore, innovative extraction methods in combination with nanoformulations have been proposed to increase desirable compounds' availability, distribution, and conservation, which can be aided by modern computational tools in a transdisciplinary approach. This review aims to describe available extraction and nanoformulation methods for <i>C. sativa,</i> as well as its known antioxidant, antimicrobial, and immunogenic activities. Critical points on the use of <i>C. sativa</i> extracts in nanoformulations are identified and some prospects are envisaged.</p>","PeriodicalId":34490,"journal":{"name":"BioTech","volume":"13 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11674990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898708","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":"Optimized Extraction of Polyphenols from Kiwifruit Peels and Their Biological Activities.","authors":"Batoul Shkeir, Nada El Darra, Bilal Azakir, Salma Khazaal, Elie Salem Sokhn, Mohamed Koubaa, Richard G Maroun, Nicolas Louka, Espérance Debs","doi":"10.3390/biotech13040054","DOIUrl":"10.3390/biotech13040054","url":null,"abstract":"<p><p>(1) Background: Kiwifruit is a globally valued fruit. Its industrial processing produces a substantial amount of waste, particularly peels, which present an appealing potential source of bioactive compounds. This study focuses on optimizing the extraction of phenolics from kiwi peels using a water bath (WB) and infrared irradiation (IR) and assessing their biological activities. (2) Methods: Optimal conditions for polyphenol extraction from kiwifruit peels, in terms of temperature and time, were determined using Response Surface Methodology. Total phenolic content (TPC) was measured by the Folin-Ciocalteu method, and antioxidant activity was assessed utilizing the DPPH method. Antibacterial activities against <i>Bacillus cereus</i>, <i>Staphylococcus aureus</i>, <i>Escherichia coli</i>, and <i>Salmonella</i> Typhimurium were determined using the minimum inhibitory concentration (MIC). The lyophilized extract was tested for its anticancer effect on A549 lung cancer cell lines. The phytochemical profiles of the WB and IR extracts were analyzed through High-Performance Liquid Chromatography (HPLC). (3) Results: The optimal extraction conditions for the WB method were found to be 75 °C for 35 min, and 90 °C for 5 min for IR. The corresponding TPC obtained by IR was 21 mg GAE/g DM, which was 4.4 times higher than that obtained by WB (4.8 mg GAE/g DM). This indicates that IR was more efficient in extracting phenolics from kiwi peels. The antioxidant activity under the optimum conditions of WB and IR was 14 mg TE/g DM and 16 mg TE/g DM, respectively. Both the WB and IR extracts demonstrated antibacterial activity against <i>B. cereus</i> with an MIC value of 25 mg/mL. Additionally, the IR extract displayed an antibacterial effect against <i>S. aureus</i>, with an MIC value of 50 mg/mL. The WB and IR kiwi peel extracts were effective in significantly reducing A549 cell viability at 50 µg/mL and 100 µg/mL, respectively. Caffeic acid (0.54 ppm) and catechin (5.44 ppm) were the major polyphenols identified in WB and IR extracts, as determined by HPLC. (4) Conclusions: IR was more efficient in extracting phenolics from kiwi peels than WB. The findings also suggest that kiwi peel can be effectively utilized as an antioxidant, antibacterial, and anticancer agent.</p>","PeriodicalId":34490,"journal":{"name":"BioTech","volume":"13 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11674650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898704","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":"Composition, Seasonal Dynamics and Metabolic Potential of the Rhizosphere Microbiome Associated with Wild White Poplar.","authors":"Mikhail I Popchenko, Dmitry S Karpov, Natalya S Gladysh, Maxim A Kovalev, Vsevolod V Volodin, George S Krasnov, Alina S Bogdanova, Nadezhda L Bolsheva, Maria S Fedorova, Anna V Kudryavtseva","doi":"10.3390/biotech13040052","DOIUrl":"10.3390/biotech13040052","url":null,"abstract":"<p><p>The white poplar (<i>Populus alba</i>) is a dioecious woody plant with significant potential for the phytoremediation of soils. To realize this potential, it is necessary to utilize growth-promoting microorganisms. One potential source of such beneficial microorganisms is the rhizosphere community of wild-growing trees. However, the structure, dynamics, and metabolism of the rhizosphere community of wild-growing white poplar remain poorly understood. To ascertain seasonal dynamics, species diversity, and metabolic potential, we sequenced 16S rRNA genes in metagenomes derived from 165 soil samples collected in spring and autumn from the root surfaces of 102 trees situated in disparate geographical locations. The three most prevalent phyla across all samples are Proteobacteria, Actinobacteriota, and Acidobacteriota. At the order level, the most prevalent orders are Sphingomonadales and Rhizobiales. Accordingly, the families Sphingomonadaceae and Rhizobiaceae were identified as dominant. The rhizospheric microbiome exhibited substantial inter-seasonal variation. Six families, including Caulobacteraceae, Xanthomonadaceae, Chitinophagaceae, Chthoniobacteraceae, Sphingomonadaceae, and Rhizobiaceae, exhibited alterations (spring-to-autumn) across all geographical locations under study. Members of the Rhizobiaceae family, which includes nitrogen-fixing bacteria, can provide poplar with plant-available forms of nitrogen such as nitrate and ammonium. The rhizosphere microbiome may facilitate the conversion of inorganic sulfur into sulfur-containing amino acids, cysteine and methionine, that are bioavailable to plants. Furthermore, the rhizosphere microbiome is capable of synthesizing amino acids, organic acids (including Krebs cycle acids), and some lipids and sugars. Consequently, the rhizosphere community can stimulate poplar growth by providing it with readily available forms of nitrogen and sulfur, as well as building blocks for the synthesis of proteins, nucleic acids, and other macromolecules. Many of these pathways, including nitrogen fixation, were subjected to seasonal changes.</p>","PeriodicalId":34490,"journal":{"name":"BioTech","volume":"13 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11674042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898703","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}