Marine Drugs最新文献

{"title":"Enantioselectivity in Vanadium-Dependent Haloperoxidases of Different Marine Sources for Sulfide Oxidation to Sulfoxides","authors":"Yun-Han Zhang, Ya-Ting Zou, Yong-Yi Zeng, Lan Liu, Bi-Shuang Chen","doi":"10.3390/md22090419","DOIUrl":"https://doi.org/10.3390/md22090419","url":null,"abstract":"This study explores the reasons behind the variations in the enantioselectivity of the sulfoxidation of methyl phenyl sulfide by marine-derived vanadium-dependent haloperoxidases (VHPOs). Twelve new VHPOs of marine organisms were overexpressed, purified, and tested for their ability to oxidize sulfide. Most of these marine enzymes exhibited nonenantioselective behavior, underscoring the uniqueness of AnVBPO from the brown seaweed Ascophyllum nodosum and CpVBPO from the red seaweed Corallina pilulifera, which produce (R)- and (S)-sulfoxides, respectively. The enantioselective sulfoxidation pathway is likely due to direct oxygen transfer within the VHPO active site. This was demonstrated through molecular docking and molecular dynamics simulations, which revealed differences in the positioning of sulfide within AnVBPO and CpVBPO, thus explaining their distinct enantioselectivities. Nonenantioselective VHPOs probably follow a different oxidation pathway, initiating with sulfide oxidation to form a positively charged radical. Further insights were gained from studying the catalytic effect of VO43− on H2O2-driven sulfoxidation. This research improves the understanding of VHPO-mediated sulfoxidation and aids in developing biocatalysts for sulfoxide synthesis.","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"7 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of Safracin Biosynthesis and Transport in Pseudomonas poae PMA22","authors":"J. Gerardo Hernández Delgado, Miguel G. Acedos, Fernando de la Calle, Pilar Rodríguez, José Luis García, Beatriz Galán","doi":"10.3390/md22090418","DOIUrl":"https://doi.org/10.3390/md22090418","url":null,"abstract":"Pseudomonas poae PMA22 produces safracins, a family of compounds with potent broad-spectrum anti-bacterial and anti-tumor activities. The safracins’ biosynthetic gene cluster (BGC sac) consists of 11 ORFs organized in two divergent operons (sacABCDEFGHK and sacIJ) that are controlled by Pa and Pi promoters. Contiguous to the BGC sac, we have located a gene that encodes a putative global regulator of the LysR family annotated as MexT that was originally described as a transcriptional activator of the MexEF-OprN multidrug efflux pump in Pseudomonas. Through both in vitro and in vivo experiments, we have demonstrated the involvement of the dual regulatory system MexT-MexS on the BGC sac expression acting as an activator and a repressor, respectively. The MexEF-OprN transport system of PMA22, also controlled by MexT, was shown to play a fundamental role in the metabolism of safracin. The overexpression of mexEF-oprN in PMA22 resulted in fourfold higher production levels of safracin. These results illustrate how a pleiotropic regulatory system can be critical to optimizing the production of tailored secondary metabolites, not only through direct interaction with the BGC promoters, but also by controlling their transport.","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"26 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142226764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing Antioxidant Potential: Factorial Design-Based Formulation of Fucoidan and Gallic Acid-Conjugated Dextran Blends","authors":"Cynthia Haynara Ferreira Silva, Maylla Maria Correia Leite Silva, Weslley Souza Paiva, Mayara Jane Campos de Medeiros, Moacir Fernandes Queiroz, Luciana Duarte Martins Matta, Everaldo Silvino dos Santos, Hugo Alexandre Oliveira Rocha","doi":"10.3390/md22090417","DOIUrl":"https://doi.org/10.3390/md22090417","url":null,"abstract":"The role of oxidative stress in health and homeostasis has generated interest in the scientific community due to its association with cardiovascular and neurodegenerative diseases, cancer, and other diseases. Therefore, extensive research seeks to identify new exogenous antioxidant compounds for supplementation. Polysaccharides are recognized for their antioxidant properties. However, polysaccharide chemical modifications are often necessary to enhance these properties. Therefore, dextran was conjugated with gallic acid (Dex-Gal) and later combined with fucoidan A (FucA) to formulate blends aimed at achieving superior antioxidant activity compared to individual polysaccharides. A factorial design was employed to combine FucA and Dex-Gal in different proportions, resulting in five blends (BLD1, BLD2, BLD3, BLD4, and BLD5). An analysis of surface graphs from in vitro antioxidant tests, including total antioxidant capacity (TAC), reducing power, and hydroxyl radical scavenging, guided the selection of BLD4 as the optimal formulation. Tests on 3T3 fibroblasts under various conditions of oxidative stress induced by hydrogen peroxide revealed that BLD4 provided enhanced protection compared to its isolated components. The BLD4 formulation, resulting from the combination of Dex-Gal and FucA, showed promise as an antioxidant strategy, outperforming its individual components and suggesting its potential as a supplement to mitigate oxidative stress in adverse health conditions.","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"12 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142226666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Chemical Toolbox to Unveil Synthetic Nature-Inspired Antifouling (NIAF) Compounds.","authors":"Ana Rita Neves, Sara Godinho, Catarina Gonçalves, Ana Sara Gomes, Joana R Almeida, Madalena Pinto, Emília Sousa, Marta Correia-da-Silva","doi":"10.3390/md22090416","DOIUrl":"https://doi.org/10.3390/md22090416","url":null,"abstract":"<p><p>The current scenario of antifouling (AF) strategies to prevent the natural process of marine biofouling is based in the use of antifouling paints containing different active ingredients, believed to be harmful to the marine environment. Compounds called booster biocides are being used with copper as an alternative to the traditionally used tributyltin (TBT); however, some of them were recently found to accumulate in coastal waters at levels that are deleterious for marine organisms. More ecological alternatives were pursued, some of them based on the marine organism mechanisms' production of specialized metabolites with AF activity. However, despite the investment in research on AF natural products and their synthetic analogues, many studies showed that natural AF alternatives do not perform as well as the traditional metal-based ones. In the search for AF agents with better performance and to understand which molecular motifs were responsible for the AF activity of natural compounds, synthetic analogues were produced and investigated for structure-AF activity relationship studies. This review is a comprehensive compilation of AF compounds synthesized in the last two decades with highlights on the data concerning their structure-activity relationship, providing a chemical toolbox for researchers to develop efficient nature-inspired AF agents.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"22 9","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11433177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening of Lipid-Reducing Activity and Cytotoxicity of the Exometabolome from Cyanobacteria.","authors":"Rúben Luz, Rita Cordeiro, Vítor Gonçalves, Vitor Vasconcelos, Ralph Urbatzka","doi":"10.3390/md22090412","DOIUrl":"https://doi.org/10.3390/md22090412","url":null,"abstract":"<p><p>Cyanobacteria are rich producers of secondary metabolites, excreting some of these to the culture media. However, the exometabolome of cyanobacteria has been poorly studied, and few studies have dwelled on its characterization and bioactivity assessment. In this work, exometabolomes of 56 cyanobacterial strains were characterized by HR-ESI-LC-MS/MS. Cytotoxicity was assessed on two carcinoma cell lines, HepG2 and HCT116, while the reduction in lipids was tested in zebrafish larvae and in a steatosis model with fatty acid-overloaded human liver cells. The exometabolome analysis using GNPS revealed many complex clusters of unique compounds in several strains, with no identifications in public databases. Three strains reduced viability in HCT116 cells, namely Tolypotrichaceae BACA0428 (30.45%), Aphanizomenonaceae BACA0025 (40.84%), and Microchaetaceae BACA0110 (46.61%). Lipid reduction in zebrafish larvae was only observed by exposure to <i>Dulcicalothrix</i> sp. BACA0344 (60%). The feature-based molecular network shows that this bioactivity was highly correlated with two flavanones, a compound class described in the literature to have lipid reduction activity. The exometabolome characterization of cyanobacteria strains revealed a high chemodiversity, which supports it as a source for novel bioactive compounds, despite most of the time being overlooked.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"22 9","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11433081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome Analysis of a Potential Novel Vibrio Species Secreting pH-and Thermo-Stable Alginate Lyase and Its Application in Producing Alginate Oligosaccharides","authors":"Ke Bao, Miao Yang, Qianhuan Sun, Kaishan Zhang, Huiqin Huang","doi":"10.3390/md22090414","DOIUrl":"https://doi.org/10.3390/md22090414","url":null,"abstract":"Alginate lyase is an attractive biocatalyst that can specifically degrade alginate to produce oligosaccharides, showing great potential for industrial and medicinal applications. Herein, an alginate-degrading strain HB236076 was isolated from Sargassum sp. in Qionghai, Hainan, China. The low 16S rRNA gene sequence identity (<98.4%), ANI value (<71.9%), and dDDH value (<23.9%) clearly indicated that the isolate represented a potential novel species of the genus Vibrio. The genome contained two chromosomes with lengths of 3,007,948 bp and 874,895 bp, respectively, totaling 3,882,843 bp with a G+C content of 46.5%. Among 3482 genes, 3332 protein-coding genes, 116 tRNA, and 34 rRNA sequences were predicted. Analysis of the amino acid sequences showed that the strain encoded 73 carbohydrate-active enzymes (CAZymes), predicting seven PL7 (Alg1–7) and two PL17 family (Alg8, 9) alginate lyases. The extracellular alginate lyase from strain HB236076 showed the maximum activity at 50 °C and pH 7.0, with over 90% activity measured in the range of 30–60 °C and pH 6.0–10.0, exhibiting a wide range of temperature and pH activities. The enzyme also remained at more than 90% of the original activity at a wide pH range (3.0–9.0) and temperature below 50 °C for more than 2 h, demonstrating significant thermal and pH stabilities. Fe2+ had a good promoting effect on the alginate lyase activity at 10 mM, increasing by 3.5 times. Thin layer chromatography (TLC) and electrospray ionization mass spectrometry (ESI-MS) analyses suggested that alginate lyase in fermentation broth could catalyze sodium alginate to produce disaccharides and trisaccharides, which showed antimicrobial activity against Shigella dysenteriae, Aeromonas hydrophila, Staphylococcus aureus, Streptococcus agalactiae, and Escherichia coli. This research provided extended insights into the production mechanism of alginate lyase from Vibrio sp. HB236076, which was beneficial for further application in the preparation of pH-stable and thermo-stable alginate lyase and alginate oligosaccharides.","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"58 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"pH-Dependent Extraction of Antioxidant Peptides from Red Seaweed <i>Palmaria palmata</i>: A Sequential Approach.","authors":"Sakhi Ghelichi, Ann-Dorit Moltke Sørensen, Grazielle Náthia-Neves, Charlotte Jacobsen","doi":"10.3390/md22090413","DOIUrl":"https://doi.org/10.3390/md22090413","url":null,"abstract":"<p><p>This study employed a diverse approach to extract antioxidant peptides from red seaweed <i>Palmaria palmata</i>, recognized for its comparatively high protein content. Initially, an aqueous extraction of the entire seaweed was performed, followed by enzymatic hydrolysis of the solid residues prepared from the first step. The effects of three different pH levels (3, 6, and 9) during the aqueous extraction were also examined. Results indicated that the solid fraction from the sequential extraction process contained significantly higher levels of proteins and amino acids than other fractions (<i>p</i> < 0.05). Furthermore, the solid fractions (IC₅₀ ranging from 2.29 to 8.15 mg.mL^-1) demonstrated significantly greater free radical scavengers than the liquid fractions (IC₅₀ ranging from 9.03 to 10.41 mg.mL^-1 or not obtained at the highest concentration tested) at both stages of extraction (<i>p</i> < 0.05). Among the solid fractions, those produced fractions under alkaline conditions were less effective in radical scavenging than the produced fractions under acidic or neutral conditions. The fractions with most effective metal ion chelating activity were the solid fractions from the enzymatic stage, particularly at pH 3 (IC₅₀ = 0.63 ± 0.04 mg.mL^-1) and pH 6 (IC₅₀ = 0.89 ± 0.07 mg.mL^-1), which were significantly more effective than those from the initial extraction stage (<i>p</i> < 0.05). Despite no significant difference in the total phenolic content between these solid fractions and their corresponding liquid fractions (3.79 ± 0.05 vs. 3.48 ± 0.02 mg.mL^-1 at pH 3 and 2.43 ± 0.22 vs. 2.51 ± 0.00 mg.mL^-1 at pH 6) (<i>p</i> > 0.05), the observed antioxidant properties may be attributed to bioactive amino acids such as histidine, glutamic acid, aspartic acid, tyrosine, and methionine, either as free amino acids or within proteins and peptides.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"22 9","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11433066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enzymes from Fishery and Aquaculture Waste: Research Trends in the Era of Artificial Intelligence and Circular Bio-Economy.","authors":"Zied Khiari","doi":"10.3390/md22090411","DOIUrl":"https://doi.org/10.3390/md22090411","url":null,"abstract":"<p><p>In the era of the blue bio-economy, which promotes the sustainable utilization and exploitation of marine resources for economic growth and development, the fisheries and aquaculture industries still face huge sustainability issues. One of the major challenges of these industries is associated with the generation and management of wastes, which pose a serious threat to human health and the environment if not properly treated. In the best-case scenario, fishery and aquaculture waste is processed into low-value commodities such as fishmeal and fish oil. However, this renewable organic biomass contains a number of highly valuable bioproducts, including enzymes, bioactive peptides, as well as functional proteins and polysaccharides. Marine-derived enzymes are known to have unique physical, chemical and catalytic characteristics and are reported to be superior to those from plant and animal origins. Moreover, it has been established that enzymes from marine species possess cold-adapted properties, which makes them interesting from technological, economic and sustainability points of view. Therefore, this review centers around enzymes from fishery and aquaculture waste, with a special focus on proteases, lipases, carbohydrases, chitinases and transglutaminases. Additionally, the use of fishery and aquaculture waste as a substrate for the production of industrially relevant microbial enzymes is discussed. The application of emerging technologies (i.e., artificial intelligence and machine learning) in microbial enzyme production is also presented.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"22 9","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11433245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood Coagulation Activities and Influence on DNA Condition of Alginate-Calcium Composites Prepared by Freeze-Drying Technique.","authors":"Małgorzata Świerczyńska, Paulina Król, César I Hernández Vázquez, Klaudia Piekarska, Katarzyna Woźniak, Michał Juszczak, Zdzisława Mrozińska, Marcin H Kudzin","doi":"10.3390/md22090415","DOIUrl":"https://doi.org/10.3390/md22090415","url":null,"abstract":"<p><p>The aim of this research was to synthesize and characterize alginate-calcium composites using a freeze-drying method, with a focus on their potential applications in biomedicine. This study specifically explored the biochemical properties of these composites, emphasizing their role in blood coagulation and their capacity to interact with DNA. Additionally, the research aimed to assess how the cross-linking process influences the structural and chemical characteristics of the composites. Detailed analyses, including microscopic examination, surface area assessment, and atomic absorption spectrometry, yielded significant results. The objective of this study was to examine the impact of calcium chloride concentration on the calcium content in alginate composites. Specifically, the study assessed how varying concentrations of the cross-linking solution (ranging from 0.5% to 2%) influence the calcium ion saturation within the composites. This investigation is essential for understanding the physicochemical properties of the materials, including calcium content, porosity, and specific surface area. The results are intended to identify the optimal cross-linking conditions that maximize calcium enrichment efficiency while preserving the material's structural integrity. The study found that higher calcium chloride concentrations in alginate cross-linking improve the formation of a porous structure, enhanced by two-stage freeze-drying. Increased calcium levels led to a larger surface area and pore volume, and significantly higher calcium content. Furthermore, assays of activated partial thromboplastin time (aPTT) showed a reduction in clotting time for alginate composites containing calcium ions, indicating their potential as hemostatic agents. The aPTT test showed shorter clotting times with higher calcium ion concentrations, without enhanced activation of the extrinsic clotting pathway. The developed alginate material with calcium effectively supports hemostasis and reduces the risk of infection. The study also explored the capacity of these composites to interact with and modify the structure of plasmid DNA, underscoring their potential for future biomedical applications.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"22 9","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11433402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altechromone A Ameliorates Inflammatory Bowel Disease by Inhibiting NF-κB and NLRP3 Pathways","authors":"Lei Li, Jing Huang, Lixin Feng, Liyan Xu, Houwen Lin, Kechun Liu, Xiaobin Li, Rongchun Wang","doi":"10.3390/md22090410","DOIUrl":"https://doi.org/10.3390/md22090410","url":null,"abstract":"Altechromone A, also known as 2,5-dimethyl-7-hydroxychromone, is a hydroxyketone containing one hydroxyl and one ketone group. In this study, we isolated Altechromone A from the marine-derived fungus Penicillium Chrysogenum (XY-14-0-4). Previous reports show that Altechromone A has various activities including tumor suppression, antibacterial, and antiviral activities. However, there is no study about its anti-inflammatory activity in inflammatory bowel disease (IBD). Here, we assess the anti-inflammatory activity, especially in IBD, and its potential mechanism using the zebrafish model. Our results indicated that Altechromone A has anti-inflammatory activity in a CuSO4-, tail-cutting-, and LPS-induced inflammatory model in zebrafish, respectively. In addition, Altechromone A greatly reduced the number of neutrophils, improved intestinal motility and efflux efficiency, alleviated intestinal damage, and reduced reactive oxygen species production in the TNBS-induced IBD zebrafish model. The transcriptomics sequencing and real-time qPCR indicated that Altechromone A inhibited the expression of pro-inflammatory genes including TNF-α, NF-κB, IL-1, IL-1β, IL-6, and NLRP3. Therefore, these data indicate that Altechromone A exhibits therapeutic effects in IBD by inhibiting the inflammatory response.","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"12 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142211305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}