Current pharmaceutical biotechnology最新文献

{"title":"Genomic Insights into Bacterial Antimicrobial Resistance Transmission and Mitigation Strategies.","authors":"Alexandru Stefan Barcan, Rares Andrei Barcan, Emanuel Vamanu","doi":"10.2174/0113892010304596240629102419","DOIUrl":"https://doi.org/10.2174/0113892010304596240629102419","url":null,"abstract":"<p><p>The rapid emergence and global spread of antimicrobial resistance in recent years have raised significant concerns about the future of modern medicine. Superbugs and multidrugresistant bacteria have become endemic in many parts of the world, raising the specter of untreatable infections. The overuse and misuse of antimicrobials over the past 80 years have undoubtedly contributed to the development of antimicrobial resistance, placing immense pressure on healthcare systems worldwide. Nonetheless, the molecular mechanisms underlying antimicrobial resistance in bacteria have existed since ancient times. Some of these mechanisms and processes have served as the precursors of current resistance determinants, highlighting the ongoing arms race between bacteria and their antimicrobial adversaries. Moreover, the environment harbors many putative resistance genes, yet we cannot still predict which of these genes will emerge and manifest as pathogenic resistance phenotypes. The presence of antibiotics in natural habitats, even at sub-inhibitory concentrations, may provide selective pressures that favor the emergence of novel antimicrobial resistance apparatus and, thus, underscores the need for a comprehensive understanding of the factors driving the persistence and spread of antimicrobial resistance. As the development of antimicrobial strategies that evade resistance is urgently needed, a clear perception of these critical factors could ultimately pave the way for the design of innovative therapeutic targets.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Applications of CRISPR in Parasitology.","authors":"Phoebe Yon Ern Tee, Sylvester Yee Chun Chu, Chloe Chien Yee Kok, Mun Foo, Clarence Zhen Jin Tan, Jhi Biau Foo, Fazleen Haslinda Mohd Hatta, Li Kar Stella Tan, Sharina Hamzah","doi":"10.2174/0113892010316710240626042205","DOIUrl":"https://doi.org/10.2174/0113892010316710240626042205","url":null,"abstract":"<p><p>Clustered Regions of Interspersed Palindromic Repeat (CRISPR)-based techniques have been utilized in various research areas, including agriculture, biotechnology, and medicine. With the use of a short sequence guide RNA and CRISPR-associated (Cas) protein, this technique allows for robust, site-specific manipulation of the genome, aiding researchers in making important biomedical discoveries and scientific advancements. In this review, we explored the applications of CRISPR/Cas systems in the field of parasitology for the identification and validation of novel functional genes, diagnosis of parasitic infections, reduction of parasite virulence, and the disruption of disease transmission. We also discussed how CRISPR can be used for the development of therapeutics, vaccines, and drug discovery. Furthermore, the challenges and future perspectives of this technology are also highlighted.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancements of Glucose Monitoring Biosensor: Current State, Generations of Technological Progress, and Innovation Dynamics.","authors":"Arpita Dua, Abhijit Debnath, Kunal Kumar, Rupa Mazumder, Avijit Mazumder, Rajesh Singh, Saloni Mangal, Jahanvi Sanchitra, Fahad Khan, Soumya Tripathi, Sukriti Vishwas, Hema Chaudhary, Parul Sharma, Shikha Srivastava","doi":"10.2174/0113892010305386240625072535","DOIUrl":"https://doi.org/10.2174/0113892010305386240625072535","url":null,"abstract":"<p><p>Glucose monitoring is essential for managing diabetes, and continuous glucose monitoring biosensors can offer real-time monitoring with little invasiveness. However, challenges remain in improving sensor accuracy, selectivity, and overall performance. This article aims to review current trends and recent advancements in glucose-monitoring biosensors while evaluating their benefits and limitations for diabetes monitoring. An analysis of current literature on transdermal glucose sensors was conducted, focusing on detection techniques, novel nanomaterials, and integrated sensor systems. Recent research has led to advancements in electrochemical, optical, electromagnetic, and sonochemical sensors for transdermal glucose detection. The use of novel nanomaterials and integrated sensor designs has improved sensitivity, selectivity, and accuracy. However, issues like calibration requirements, motion artifacts, and skin irritation persist. Transdermal glucose sensors show promise for non-invasive, convenient diabetes monitoring but require further enhancements to address limitations in accuracy, reliability, and biocompatibility. Continued research and innovation focusing on sensor materials, designs, and surface chemistry is needed to optimize biosensor performance and utility. The study offers a comprehensive analysis of the present status of technological advancement and highlights areas that need more research.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer Antibody Engineering: Comparison of Mammalian, Yeast, Bacterial, Plants, Cell-free and Hybridoma Expression Systems.","authors":"Ming Guan Ng, Hui Ying Tan, Pei Ying Ng, Rhun Yian Koh, Kenny Gah Leong Voon, Soi Moi Chye","doi":"10.2174/0113892010307146240626080746","DOIUrl":"https://doi.org/10.2174/0113892010307146240626080746","url":null,"abstract":"<p><strong>Background: </strong>Cancer is a significant issue worldwide. Generally, commercially available treatments, such as surgery, radiotherapy, and chemotherapy, are associated with undesirable complications. Hence, immunotherapy serves as a crucial alternative to those treatment options.</p><p><strong>Objective: </strong>This modality is aimed to boost the immune system through the application of engineered antibodies, which can be produced using recombinant DNA technology.</p><p><strong>Results: </strong>The discussion of the technologies leads to an introduction of the single-chain variable fragment (scFv). Thereafter, the advantages, disadvantages, and challenges associated with different expression systems, such as mammalian cells, yeast cells, bacterial cells, plant cells, and phage display were discussed comprehensively.</p><p><strong>Conclusion: </strong>Furthermore, conventional approaches such as hybridoma and modern approaches such as cell-free protein synthesis (CFPS) and simple colony assays are included. In short, this article has compiled evidence relating to each display system and may serve as a reference for those who aim to explore antibody engineering using one of the methods listed in this article.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pseudomonas aeruginosa Recombinant L-asparaginase: PEGylation with Low Molecular Weight Polyethylene Glycol, Molecular Dynamics Simulation, In vitro and In vivo Serum half-life and Biochemical Characterization.","authors":"Rawan Alshamy, Nefertiti El-Nikhely, Hisham Nematalla, Mohamed Elkewedi, Eman Abdallah Mahran, Hesham Saeed","doi":"10.2174/0113892010309260240624072408","DOIUrl":"https://doi.org/10.2174/0113892010309260240624072408","url":null,"abstract":"<p><strong>Background: </strong>Microbial L-asparaginase (L-ASNase, EC 3.5.1.1) is a pivotal biopharmaceutical drug-protein that catalyzes the hydrolysis of the non-essential amino acid L-asparagine (L-Asn) into L-aspartic acid (L-Asp) and ammonia , resulting in deplenishing the cellular L-Asn pool, which leads to the ultimate death of the L-asparagine synthetase (L-ASNS) deficient cancerous cells.</p><p><strong>Objective: </strong>This study aimed to investigate the impact of conjugating low molecular weight polyethylene glycol to recombinant P. aeruginosa L-ASNase by examining the pharmacokinetic properties, affinity towards the substrate, and enzyme stability prior to and following the reaction.</p><p><strong>Methods: </strong>The recombinant P. aeruginosa L-ASNase was affinity purified and then PEGylated by attaching polyethylene glycol (MW= 330 Da) site-specifically to the protein's N-terminus end. After which, the PEGylated L-ASNase was examined by SDS-PAGE (15%), FTIR, and UV/Vis spectrophotometry and subsequently biochemically characterized.</p><p><strong>Results: </strong>The Km and Vmax values of free P. aeruginosa rL-ASNase were determined to be 0.318 ±1.76 mM and 2915 μmol min-1and following the PEGylation, they were found to be 0.396 ±1.736 mM and 3193 μmol min-1, respectively. Polyethylene glycol (330 Da) has markedly enhanced LASNase thermostability at 37, 45, 50, and 55 °C, as opposed to the free enzyme, which retained 19.5% after 1 h of incubation at 37 °C. The PEGylated L-ASNase was found to be stable upon incubation with human serum for 28 h, in contrast to the sharp decline in the residual bioactivity of the free rL-ASNase after 4 h incubation. Accordingly, an in vivo study was used for validation, and it demonstrated that PEGylated rL-ASNase exhibited longer bioactivity for 24 h, while the free form's activity vanished entirely from the rats' blood sera after 8 h. Molecular dynamics simulation indicated that PEG (330 Da) has affected the hydrodynamic volume of L-ASNase and increased its structural stability. Docking analysis has explored the position of PEG with respect to binding sites and predicted a similar binding affinity to that of the free enzyme.</p><p><strong>Conclusion: </strong>For the first time, recombinant L-ASNase was modified by covalently attaching PEG (330 Da). The resultant novel proposed PEGylated rL-ASNase with remarkably increased stability and prolonged in vivo half-life duration, which could be considered an alternative to mitigate the high molecular weight of PEGylation's drawbacks.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanosponges-Road Less Explored Changing Drug Delivery Approach: An Explicative Review.","authors":"Shankhadip Nandi, Dipanjan Karati, Swarupananda Mukherjee","doi":"10.2174/0113892010307169240619061808","DOIUrl":"https://doi.org/10.2174/0113892010307169240619061808","url":null,"abstract":"<p><p>Nanotechnology exhibits a wide range of applications in the domain of disease therapy, diagnosis, biological detection, and environmental safeguards. The cross-linked polymeric nanosponges (NSs) are a nanoscale drug carrier system with a 3D porous structure and high entrapment efficacy. NSs up to the fourth generation are currently accessible and can serve as a delivery system for both hydrophilic and hydrophobic drugs. The delivery system exhibits superiority over alternative methods due to its ability to achieve controlled and targeted drug delivery. The colloidal structure of NSs facilitates the encapsulation of a wide range of agents such as proteins and peptides, enzymes, antineoplastic drugs, volatile oil, vaccines, DNA, etc. NSs efficiently overcome the challenges associated with drug toxicity and poor aqueous solubility. NS formulations have been explored for various applications like gaseous encapsulation, enzyme immobilization, antifungal therapy, poison absorbent, water purification, etc. This review provides a comprehensive analysis regarding methods of synthesis, distinct polymeric NSs, mechanism of drug release, factors affecting NS development, applications, and patents filed in the field of NSs. Herein, the recently developed NS formulations, their potential in cancer therapy, and current progressions of NS for SARS-CoV-2 management are also deliberated with special attention, focusing on the significant challenges and future directions.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preparation and Evaluation of Nanoemulsion Formulation Containing Kojic Acid and Kojyl 3-aminopropylphosphonic Acid.","authors":"Nai-Fang Chang, Pey-Shiuan Wu, Hsiang-Ju Yang, Ya-Min Zheng, Chih-Chien Lin","doi":"10.2174/0113892010310230240615112928","DOIUrl":"https://doi.org/10.2174/0113892010310230240615112928","url":null,"abstract":"<p><strong>Background: </strong>The kojyl 3-aminopropylphosphonic acid (KAP) was synthesized by kojic acid (KA) with a 3-aminopropylphosphonic acid. Which is more stable than KA and showed better skin penetration and anti-pigmentation efficacy in melanocytes. However, up till now, there have been no studies aimed at incorporating KAP into an emulsion system and evaluating its effectiveness.</p><p><strong>Objective: </strong>We develop a novel skin-lightening agent using KAP as the active ingredient and a low-cytotoxic nanoemulsion as the delivery system in this study.</p><p><strong>Method: </strong>The sorbitan monooleate and polysorbate surfactants with polyethylene glycol (PEG) co-surfactant were used to generate a nanoemulsion system.</p><p><strong>Result: </strong>The transparency and particle size stability over various storage times indicate that the formulated nanoemulsions are suitable for long-term storage. Besides, results demonstrate that the anti-pigmentation function of KA and KAP-containing nanoemulsions (NE-KA and NEKAP) evidently outperformed that of the non-packed KA and KAP group. Despite having the lowest concentration among other treatments, NE-KAP was able to reduce melanin content to approximately 80% of the blank.</p><p><strong>Conclusion: </strong>Our findings suggest that this newly developed nanoemulsion containing KAP could potentially serve as a sustainable alternative to hydroquinone for treating dermal hyperpigmentation disorders in future applications.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GC-MS/MS Analysis and Wound Repair Potential of Urtica dioica Essential Oil: In silico Modeling and In vivo Study in Rats.","authors":"Ahlem Chira, Yassine Kadmi, Riadh Badraoui, Kaïss Aouadi, Fahad Alhawday, Mariem Boudaya, Kamel Jamoussi, Choumous Kallel, Abdelfattah El Feki, Adel Kadri, Mongi Saoudi","doi":"10.2174/0113892010304346240619061848","DOIUrl":"https://doi.org/10.2174/0113892010304346240619061848","url":null,"abstract":"<p><strong>Background: </strong>The study aimed to assess the antioxidant and wound healing properties of Urtica dioica essential oil (UDEO) through a comprehensive evaluation involving in silico, in vitro, and in vivo analyses. The phytochemistry of UDEO was also investigated to identify trace compounds crucial.</p><p><strong>Methods: </strong>Various injection methods of the multimode inlet (MMI) in chromatography were investigated to attain lower instrumental detection limits. Subsequently, in silico studies were employed to delve deeper into the potential biological activities of the identified compounds. Standard antioxidative tests, encompassing ABTS•+ and TAC, were performed. In vivo tests centered on wound healing were implemented using rat models. The rats were randomly allocated to four groups: saline solution, vaseline vehicle, cytol centella, and 5% UDEO ointment. Wound healing progress was evaluated through a chromatic study.</p><p><strong>Results: </strong>Gas chromatography combined with triple quadrupole mass spectrometry (GC-MS/MS) analysis revealed the presence of 97 thermolabile compounds in UDEO. Subsequent in silico studies unveiled the potential of identified compounds to inhibit COX-2, TNF-α, and IL-6, suggesting a possible enhancement of anti-inflammatory responses and healing processes. In vitro tests elucidated the notable antioxidant capacity of UDEO, a finding reinforced by wound healing data, revealing a substantial closure rate of 89% following the topical application of UDEO. Notably, fibrinogen and C-reactive protein (CRP) levels were significantly reduced, indicating minimized oxidative stress damage compared to control. Additionally, UDEO exhibited an increase in antioxidant enzyme activities compared to control.</p><p><strong>Conclusion: </strong>The study concludes that UDEO possesses significant antioxidant and wound-healing properties, supported by its rich phytochemical composition. The findings suggest its potential application in therapeutic interventions for oxidative stress and inflammatory conditions.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiviral Effect of Ferula Plants and their Potential for Treatment of COVID-19: A Comprehensive Review.","authors":"Raziyeh Mohammadi, Hasan Forouzanfar, Hossein Rahimi, Seyed-Mahdi Mohamadi-Zarch, Khadijah Jamhiri, Seyyed Majid Bagheri","doi":"10.2174/0113892010285343240530040218","DOIUrl":"https://doi.org/10.2174/0113892010285343240530040218","url":null,"abstract":"<p><p>Viral diseases have always been a threat to mankind throughout history, and many people have lost their lives due to the epidemic of these diseases. In recent years, despite the progress of science, we are still witnessing a pandemic of dangerous diseases such as COVID-19 all over the world, which can be a warning for humanity. Ferula is a genus of flowering plants commonly found in Central Asia, and its species have shown antiviral activity against a variety of viruses, including respiratory syncytial virus, Herpes simplex virus type 1, influenza, human immunodeficiency virus, hepatitis B, and coronaviruses. In this study, we intend to review the antiviral effects of Ferula plants, emphasizing the therapeutic potential of these plants in the treatment of COVID-19. Google, PubMed, Web of Science, and Scopus databases were searched to review the relevant literature on the antiviral effect of Ferula or its isolated compounds. The search was performed using the keywords Ferula, antiviral, Coronaviruses, respiratory syncytial virus, Herpes simplex virus type 1, influenza, human immunodeficiency virus, and hepatitis B. According to the reviewed articles and available scientific evidence, it was determined that the plants of this genus have strong antiviral effects. Also, clinical studies have shown that some species, such as Ferula assa-foetida, can be used effectively in the treatment of COVID-19. Ferula plants have inhibitory effects on various viruses, making them an attractive alternative to conventional antiviral agents. Therefore, these plants are a natural source of valuable compounds that can help us fight infectious diseases.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biotechnological Breakthroughs in Resveratrol Synthesis and Health Advancements.","authors":"Ravi K Mittal, Gaurav Krishna, Raghav Mishra, Vikram Sharma","doi":"10.2174/0113892010297228240612112520","DOIUrl":"https://doi.org/10.2174/0113892010297228240612112520","url":null,"abstract":"<p><p>This academic review examines the latest biotechnology methods for resveratrol synthesis. We aim to study the health advantages of resveratrol consumption beyond synthesis and demonstrate its potential as a therapeutic agent. An extensive examination of the current state of literature was performed, employing a diverse range of scholarly databases with the purpose of collating pertinent information and conducting in-depth research on the subject matter. The main goal was to find and assess research on resveratrol's health effects and the latest biotechnology methods for synthesizing it. This review paper discusses resveratrol synthesis methods, including their efficacy and current advances. The findings highlight the significant potential of biotechnological methods in improving both the synthesis of resveratrol and its beneficial effects on health. Our comprehensive analysis substantiates the importance of biotechnological methodologies in synthesizing resveratrol. The literature review highlights resveratrol's therapeutic properties, which have been scientifically approved for the prevention and treatment of various ailments, such as cardiovascular disease, metabolic illnesses, cancer, aging, and immunomodulation.</p>","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}