MedComm – Biomaterials and Applications最新文献

{"title":"A hydrogel miscible azelaic acid-ionic liquids for the treatment of acne vulgaris: Enhanced solubility and skin retention","authors":"Zhezheng Fang,&nbsp;Xianzi Zheng,&nbsp;Yanyun Ma,&nbsp;Wei Wu,&nbsp;Yi Lu","doi":"10.1002/mba2.70000","DOIUrl":"https://doi.org/10.1002/mba2.70000","url":null,"abstract":"<p>Azelaic acid (AzA) is a natural dicarboxylic acid used to treat acne vulgaris but is greatly limited by poor aqueous solubility. This study aims to enhance the solubility and skin retention of AzA by ionic liquids (ILs). AzA-ILs were synthesized by a decomposition reaction with amine compounds. AzA-ILs synthesized with Tris-(hydroxymethyl)-aminomethane ([AzA][Tris]) and meglumine ([AzA][Meg]) at a molar ratio of 1:2 were liquid at room temperature and miscible with water. ¹H-NMR and FT-IR confirmed the synthesis of AzA-ILs. [AzA][Tris] got higher transdermal transport and skin retention of AzA than [AzA][Meg]. ZEN has a lower viscosity and better spreadability than Carbomer and thus was adopted as the gel matrix. [AzA][Tris] was also miscible with the ZEN matrix at any concentration. Hydrogels containing 10% (w/w) AzA exhibited the highest transdermal transport and skin retention among hydrogels with higher or lower concentrations of AzA. AzA-IL hydrogel (10%, w/w) obtained similar therapeutic efficacy but lower skin irritation than the Finacea® (a marketed hydrogel of 15% AzA). In conclusion, ILs greatly enhanced the aqueous solubility of AzA to develop transparent hydrogel and skin retention to achieve good treatment for acne vulgaris.</p>","PeriodicalId":100901,"journal":{"name":"MedComm – Biomaterials and Applications","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mba2.70000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143110778","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":"Unwinding matters: WED domain determines Cas9 activity by accelerating DNA unwinding and R-loop formation","authors":"Mei Luo,&nbsp;Shaohua Yao","doi":"10.1002/mba2.107","DOIUrl":"https://doi.org/10.1002/mba2.107","url":null,"abstract":"&lt;p&gt;In a recent &lt;i&gt;Cell&lt;/i&gt; paper,&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Amy R. Eggers and colleagues from Jennifer A. Doudna's laboratory elucidated the mechanism by which an engineered CRISPR-Cas9 system significantly enhances editing efficiency by accelerating DNA unwinding and R-loop formation. The discovery and development of CRISPR-Cas9 gene editing technology have significantly revolutionized our ability to manipulate genomic sequences across a wide variety of species, as well as in clinical therapeutics. However, the efficiency of Cas9 proteins, especially the miniature ones, is generally low, requiring further improvement. In this article, the authors demonstrated that WED domain is a dominant determinant of target DNA unwinding and R-loop formation and its engineering improved genome-editing efficiency and expand PAM preference.&lt;/p&gt;&lt;p&gt;When binding to their target DNA sequences under the direction of PAM interaction and the guidance of single guide RNAs (sgRNA), Cas9 proteins separates the nontarget strand of the sgRNA from its target strand to form an R-loop structure. Subsequently, the cleavage activity domain of Cas9 cuts the DNA at this location, resulting in a double-strand break (Figure Fig 1). This process largely relies on the helicase activity of Cas9 to unwind the double-stranded target DNA into single strands for cutting. Evidence have shown that the formation of the R-loop is the rate-limiting step in this process.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Therefore, accelerating DNA unwinding and R-loop formation may be a potential strategy to improve CRISPR-Cas9 efficiency. Moreover, considering the size constraints imposed by certain delivery methods for in vivo applications, such as AAV, more compact Cas9 variants, including saCas9, cjCas9, and Nme2Cas9 have earned increasing interest. However, the activity of these editors generally lower than their larger orthologues, for example spCas9, which limited their applications.&lt;/p&gt;&lt;p&gt;In a previous study, the authors from the same lab evolved a Geobacillus stearothermophilus Cas9 (GeoCas9) using a bacterial double-plasmid selection system.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; The resulting evolved iGeoCas9 exhibited more than one hundred-fold improvement in the editing of mammalian genomes. However, its molecular basis remains unclear. Through cryo-electron microscopy structural analysis, the current study found that the three amino acids mutations in the WED domain significantly enhance the electrostatic interactions between iGeoCas9 and the DNA strand. This alteration may facilitate the separation of DNA strands and the formation of the R-loop before cutting. Additionally, the PAM recognition preference of iGeoCas9 is more relaxed compared to that of WT-GeoCas9. One possible hypothesis is that the mutations in the WED domain alter its interactions with the DNA backbone, leading to nonnative PAM recognition and cutting activity. To test this hypothesis, the authors conducted enzymatic activity assays using several muta","PeriodicalId":100901,"journal":{"name":"MedComm – Biomaterials and Applications","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mba2.107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142868970","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":"Biomimetic nanosystems based on cell membranes (BNCMs) for cancer immunotherapy","authors":"Yixi Wang,&nbsp;Xianzhou Huang,&nbsp;Qinjie Wu,&nbsp;Changyang Gong","doi":"10.1002/mba2.106","DOIUrl":"https://doi.org/10.1002/mba2.106","url":null,"abstract":"<p>With the development of nanosystems, they are gradually utilized to ameliorate diverse cancer therapies. Specifically for immunotherapy, most nanosystems are elaborately designed to initiate the self-sustaining “cancer immunity cycle (CIC)” to elicit the immune response. However, owing to the highly complex circulatory environment, nanosystems may face issues like nonspecific nanoparticle uptake and rapid clearance, leaving enormous room for advancement. For employing the biomimetic design in nanosystems, biomimetic nanosystems based on cell membranes (BNCMs) inherit various functional molecules from source cells, permitting precise tumor targeting, enhancing blood circulation, and conferring more desired functionality for a more robust immune response. To take full advantage of the BNCMs, understanding their functions in cancer immunotherapy is essential. In this review, the unique properties of BNCMs derived from various cells and main preparation strategies are introduced. Subsequently, the recent advances of BNCMs for improving cancer immunotherapy are discussed from the aspects of their roles in particular stages of the CIC, and the working mechanisms of the outer cell membranes are highlighted. Finally, along with the analysis of existing bottlenecks for clinical translation, some suggestions for the future development of BNCMs are put forward.</p>","PeriodicalId":100901,"journal":{"name":"MedComm – Biomaterials and Applications","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mba2.106","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142860972","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 osteogenic effect of mesenchymal stem cells regulated by photo-crosslinked hydrogels with tunable elastic modulus","authors":"Haifu Sun,&nbsp;Chen Qian,&nbsp;Kai Chen,&nbsp;Yu Wang,&nbsp;Yuqing Yang,&nbsp;Yonggang Li,&nbsp;Fan Xu,&nbsp;Liang Chen,&nbsp;Kun Li,&nbsp;Youzhi Hong,&nbsp;Yusen Qiao,&nbsp;Dechun Geng","doi":"10.1002/mba2.105","DOIUrl":"https://doi.org/10.1002/mba2.105","url":null,"abstract":"<p>Biomimicry is the enduring pursuit in the field of bone implants, wherein bio-materials with adjustable elastic modulus and porosity, the same as natural bone, offer a novel strategy for developing and applying new bone repair materials. Conventional biomaterials are often used to repair bone defects without complete consideration of structural and functional osseointegration, leading to interface repair failure. In this study, organic-inorganic interpenetrating network technology was employed using varying amounts of nano-hydroxyapatite (nHAP) and methacrylated gelatin (GelMA) and osteogenic growth peptide (OGP) to construct biomimetic bones with low, medium, and high nano-hydroxyapatite content (GelMA-c-OGP/nHAP). As the concentration of nano-hydroxyapatite increases, comprehensive evaluations of the biomimetic materials were conducted using osteogenic ability tests, Micro-CT scans, nanoindentation tests, and mechanical tests. The developed biomimetic structural material exhibits well-controlled mechanical properties. Compared to natural bone trabeculae, this biomimetic material not only maintains the organic and inorganic ratio of natural bone but also demonstrates exceptional mechanical load-bearing capabilities. Additionaly，this scaffold exhibits good porosity and mechanical properties. It enhances cell adhesion, integrates perfectly with bone tissue, and demonstrates excellent osteogenic ability both in vitro and in vivo. This study lays the foundation for constructing biomimetic scaffolds with adjustable mechanical properties, presenting high prospects for applications in the field of tissue engineering.</p>","PeriodicalId":100901,"journal":{"name":"MedComm – Biomaterials and Applications","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mba2.105","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763960","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":"Recent advances and perspectives of multifunctional nanogels in biomedical applications","authors":"Bicheng Han,&nbsp;Zideng Dai,&nbsp;Hangrong Chen","doi":"10.1002/mba2.104","DOIUrl":"https://doi.org/10.1002/mba2.104","url":null,"abstract":"<p>Nanogels (NGs) are considered as a kind of nanoscale hydrogels (&lt;200 nm) endowing with the functions of both nanomaterials and hydrogels. In the last 20 years, NGs have garnered significant attention due to their versatility and adaptability. Herein, a comprehensive overview of the latest advancements and current research status of NGs is provided, with a particular focus on the synthesis strategies involving physical and chemical cross-linking methods, as well as the advantages of NGs in drug loading and responsive release. Based on the diverse design strategies of NGs, four key biomedical applications, including inflammation therapy, regenerative medicine, bioimaging and tumor therapy are further summarized and discussed. Moreover, the existed inherent challenges facing NGs are proposed, while highlighting their potential to revolutionize therapeutic and diagnostic approaches. Finally, we look forward to the further development and promising potentials of NGs in biomedical applications. This review aims to serve as a valuable reference for researchers, providing some insights into the evolving landscape of NGs and their potential in advanced biomedical applications.</p>","PeriodicalId":100901,"journal":{"name":"MedComm – Biomaterials and Applications","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mba2.104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749216","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":"Application of biomaterials in cardiac tissue engineering: Current status and prospects","authors":"Dongshan Zhang,&nbsp;Rui He,&nbsp;Ying Qu,&nbsp;Chuan He,&nbsp;Bingyang Chu","doi":"10.1002/mba2.103","DOIUrl":"https://doi.org/10.1002/mba2.103","url":null,"abstract":"<p>Cardiovascular diseases have become one of the leading causes of death and illness worldwide, posing significant challenges to global health. Due to the limited regenerative capacity of the heart, conventional approaches to treating heart diseases have demonstrated limited effectiveness. Therefore, leveraging biomaterials and biotechnologies in cardiac tissue engineering has emerged as a promising therapeutic strategy. This review aims to summarize the various characteristics of biomaterials in cardiac tissue engineering and their significance in addressing heart diseases. We categorize biomaterials into natural, synthetic, and conductive types based on their sources and unique properties, focusing on their applications in cardiac tissue engineering. We then present current applications of biomaterials in cardiac tissue engineering, followed by a discussion of existing challenges such as long-term material stability, biocompatibility, adverse reactions, and precise application methodologies. Additionally, we provide insights into potential strategies for overcoming these challenges, aiming to enhance the effectiveness and safety of biomaterials in cardiac tissue engineering applications. Finally, this review highlights the potential of emerging biomaterials and technologies, underscoring the critical role of interdisciplinary collaboration in driving innovation and progress in cardiac tissue engineering.</p>","PeriodicalId":100901,"journal":{"name":"MedComm – Biomaterials and Applications","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mba2.103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674065","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":"Recent advances in the application of functional hydrogels in skin wound healing","authors":"Zhongwu Bei,&nbsp;Jing Zheng","doi":"10.1002/mba2.101","DOIUrl":"https://doi.org/10.1002/mba2.101","url":null,"abstract":"<p>The effective treatment of skin wounds has long posed a significant challenge in the medical field, impacting patient comfort, quality of life, and the rate and outcome of wound healing. With continuous advancements in science and technology, novel materials have emerged, providing new possibilities for skin wound treatment. Among these, multifunctional hydrogels have shown considerable potential in promoting skin wound healing as a type of wound dressing material. This review systematically examines the progress in the application of multifunctional hydrogels in skin wound healing. Initially, the structure and composition of the skin are introduced. Subsequently, skin wounds are classified, and the wound-healing process is discussed in detail. Traditional and modern dressings are then categorized, with a particular emphasis on the characteristics and applications of hydrogel dressings. The various functions of hydrogels in skin wound healing, including antibacterial, antioxidant, hemostatic, adhesive, stimulus-responsive, and wound status monitoring, are reviewed. The paper concludes with a summary of the existing research gaps and provides insights into the future development directions of multifunctional hydrogels. This review aims to guide the preparation of hydrogel wound dressings and offer theoretical references for the exploration of next-generation functional hydrogels.</p>","PeriodicalId":100901,"journal":{"name":"MedComm – Biomaterials and Applications","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mba2.101","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142664902","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":"Effect of different calcium sulfate aspect ratios and chitosan addition methods on the interface properties of calcium sulfate/chitosan composite bone cement","authors":"Liuyun Jiang,&nbsp;Chunyan Tang,&nbsp;Shuo Tang,&nbsp;Yuqing Wang,&nbsp;Qi Ouyang,&nbsp;Xiang Hu","doi":"10.1002/mba2.99","DOIUrl":"https://doi.org/10.1002/mba2.99","url":null,"abstract":"<p>It is a great challenge to improve the properties of pure calcium sulfate bone cement. Here, two calcium sulfate hemihydrate powders with different aspect ratios were prepared, and three chitosan addition methods were adopted to investigate the effect on the surface and interface properties of calcium sulfate/chitosan composite bone cement. The results showed that it lacked chemical bond between chitosan and calcium sulfate, and the short rod calcium sulfate displayed better interface adhesion with chitosan owing to its smaller size, so it possessed shorter setting time, better compressive strength and slower degradation than the long rod calcium sulfate, while the biocompatibility had no remarkable difference. Moreover, chitosan solution as liquid phase was a better solidification mode than citric acid, and calcium sulfate/chitosan composite as solid phase was the worst mode because of poor interface compatibility. Conclusively, it was a simple, low-cost, and effective preparation process to choose short rod calcium sulfate powder as solid phase and 1 wt% chitosan solution as liquid phase, which could achieve calcium sulfate/chitosan composite bone cement with the best properties, including setting time, compressive strength, degradation rate, and biocompatibility, displaying a promising application in bone defect repair.</p>","PeriodicalId":100901,"journal":{"name":"MedComm – Biomaterials and Applications","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mba2.99","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142555440","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":"Metal-organic frameworks-based nanomedicines to promote cancer immunotherapy: Recent advances and future directions","authors":"Chenqian Feng,&nbsp;Xiaoyan Liang,&nbsp;Rangrang Fan,&nbsp;Min Mu,&nbsp;Liangxue Zhou,&nbsp;Gang Guo","doi":"10.1002/mba2.96","DOIUrl":"https://doi.org/10.1002/mba2.96","url":null,"abstract":"<p>Cancer immunotherapy uses the body's immune system to fight tumors by restoring natural antitumor responses. Metal-organic frameworks (MOFs), characterized by their unique crystalline porous structures formed from metal ions linked by organic ligands, offer a promising solution. Recent studies have unveiled the potential of MOFs in cancer immunotherapy. The exceptional porosity and surface area, coupled with their extraordinary thermal and chemical stability, bring significant advantages for efficient drug loading and delivery of immunotherapeutic agents. The adaptability of MOFs further enhances the controlled release of immunotherapeutic drugs within target cells and increases tumor sensitivity to other therapies such as photodynamic, photothermal, and radiotherapy. This multifunctional carrier contributes to modulating the tumor microenvironment and reactivating antitumor immunity, providing a comprehensive strategy for cancer treatment. In this review, we summarize the applications of MOFs in immune checkpoint blockade, immunomodulator delivery, and cancer vaccine delivery, and discuss existing challenges in their use for immunotherapy. This discussion aims to offer insights for developing better treatments and enhancing the efficacy of immunotherapy.</p>","PeriodicalId":100901,"journal":{"name":"MedComm – Biomaterials and Applications","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mba2.96","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451739","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":"Research progress of hydrogels in the prevention of pelvic inflammatory disease","authors":"Yile Xiao,&nbsp;Teng Ma,&nbsp;Haoming Wu,&nbsp;Qiao Su,&nbsp;Yayu Zhou,&nbsp;Bingnan Zhou,&nbsp;Keyi Yang,&nbsp;Zhengguang Pu,&nbsp;Wanyue Feng,&nbsp;Xin Yong,&nbsp;Huili Zhu,&nbsp;Xulin Hu","doi":"10.1002/mba2.100","DOIUrl":"https://doi.org/10.1002/mba2.100","url":null,"abstract":"<p>Pelvic inflammatory disease (PID) is a critical global health concern with the potential to lead to adverse outcomes, including infertility and chronic pelvic pain. Since PID is often caused by ascending vaginal infections or urinary tract infections, understanding the treatment of both is critical to preventing PID. Meanwhile, the emergence of drug-resistant and persistently infected strains poses a growing challenge. This review discusses current clinical treatments for the prevention of PID from the physiologic basis of PID, as well as summarizes the advantages and research progress of hydrogels in the prevention of PID. In contrast to conventional treatments, hydrogels serve as excellent vehicles for vaginal drug delivery, maintaining the presence of the drug at the target site and controlling its release. In the context of urinary tract infections (UTIs), hydrogels are employed primarily as coatings on catheters to prevent and treat catheter-associated UTIs. Finally, this review summarizes the limitations of hydrogels in PID prevention and future directions for development with the aim of elucidating avenues for clinical treatment of PID and informing further research.</p>","PeriodicalId":100901,"journal":{"name":"MedComm – Biomaterials and Applications","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mba2.100","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142430399","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}