Bioengineering & Translational Medicine最新文献

{"title":"MHCI trafficking signal-based mRNA vaccines strengthening immune protection against RNA viruses","authors":"Yupei Zhang,&nbsp;Songhui Zhai,&nbsp;Shugang Qin,&nbsp;Yuting Chen,&nbsp;Kepan Chen,&nbsp;Zhiying Huang,&nbsp;Xing Lan,&nbsp;Yaoyao Luo,&nbsp;Guohong Li,&nbsp;Hao Li,&nbsp;Xi He,&nbsp;Meiwan Chen,&nbsp;Zhongwei Zhang,&nbsp;Xingchen Peng,&nbsp;Xin Jiang,&nbsp;Hai Huang,&nbsp;Xiangrong Song","doi":"10.1002/btm2.10709","DOIUrl":"10.1002/btm2.10709","url":null,"abstract":"<p>The major histocompatibility complex class I (MHCI) trafficking signal (MITD) plays a pivotal role in enhancing the efficacy of mRNA vaccines. However, there was a lack of research investigating its efficacy in enhancing immune responses to RNA virus infections. Here, we have developed an innovative strategy for the formulation of mRNA vaccines. This approach involved the integration of MITD into the mRNA sequence encoding the virus antigen. Mechanistically, MITD-based mRNA vaccines can strengthen immune protection by mimicking the dynamic trafficking properties of MHCI molecule and thus expand the memory specific B and T cells. The model MITD-based mRNA vaccines encoding binding receptor-binding domain (RBD) of SARS-CoV-2 were indeed found to achieve protective duration, optimal storage stability, broad efficacy, and high safety.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10709","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141986247","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":"Activated neutrophils: A next generation cellular immunotherapy","authors":"Ninad Kumbhojkar,&nbsp;Samir Mitragotri","doi":"10.1002/btm2.10704","DOIUrl":"10.1002/btm2.10704","url":null,"abstract":"<p>Cell therapies are at the forefront of novel therapeutics. Neutrophils, despite being the most populous immune cells in human blood circulation, are not considered a viable option for cellular therapies because of their short lifespan and poor understanding of their role in the pathophysiology of various diseases. In inflammatory conditions, neutrophils exhibit an activated phenotype. Activation brings about significant changes to neutrophil biology such as increased lifespan, inflammatory cytokine secretion, and enhanced effector functions. Activated neutrophils also possess the potential to stimulate the downstream immune response and are described as essential effectors in the immune response to tumors. This makes activated neutrophils an interesting candidate for cell therapies. Here, we review the biology of activated neutrophils in detail. We discuss the different ways neutrophils can be activated and the effect they have on other immune cells for stimulation of downstream immune response. We review the conditions where activated neutrophil therapy can be therapeutically beneficial and discuss the challenges associated with their eventual translation. Overall, this review summarizes the current state of understanding of neutrophil-based immunotherapies and their clinical potential.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10704","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141980696","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":"Immunotherapy against glioblastoma using backpack-activated neutrophils","authors":"Tatsuya Fukuta,&nbsp;Ninad Kumbhojkar,&nbsp;Supriya Prakash,&nbsp;Suyog Shaha,&nbsp;A. Da Silva-Candal,&nbsp;Kyung Soo Park,&nbsp;Samir Mitragotri","doi":"10.1002/btm2.10712","DOIUrl":"10.1002/btm2.10712","url":null,"abstract":"<p>Immune checkpoint inhibitors (ICIs) represent new therapeutic candidates against glioblastoma multiforme (GBM); however, their efficacy is clinically limited due to both local and systemic immunosuppressive environments. Hence, therapeutic approaches that stimulate local and systemic immune environments can improve the efficacy of ICIs. Here, we report an adoptive cell therapy employing neutrophils (NE) that are activated via surface attachment of drug-free disk-shaped backpacks, termed Cyto-Adhesive Micro-Patches (CAMPs) for treating GBM. CAMP-adhered neutrophils (NE/CAMPs) significantly improved the efficacy of an anti-PD1 antibody (aPD-1) in a subcutaneous murine GBM model (GL261). A combination of NE/CAMPs and aPD-1 completely regressed subcutaneous GL261 tumors in mice. The efficacy of NE/CAMPs against GBM was also tested in an orthotopic GL261 model. Neutrophil's ability to migrate into the brain was not affected by CAMP attachment, and intracerebral NE/CAMP accumulation was observed in mice-bearing orthotopic GBM. The combination treatment of NE/CAMPs and aPD-1 activated systemic immune responses mediated by T cells and showed improved therapeutic responses compared with aPD-1 alone in the orthotopic GBM model. These results suggest that immunomodulation with NE/CAMPs offers a potential approach for the treatment of GBM by combination with ICIs.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10712","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141980705","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":"Human adipose-derived multipotent stromal cells enriched with IL-10 modRNA improve diabetic wound healing: Trigger the macrophage phenotype shift","authors":"Yuxin Zhang,&nbsp;Wei Wang,&nbsp;Liang Chen,&nbsp;Heng Wang,&nbsp;Dong Dong,&nbsp;Jingjing Zhu,&nbsp;Yu Guo,&nbsp;Yiqun Zhou,&nbsp;Tianyi Liu,&nbsp;Wei Fu","doi":"10.1002/btm2.10711","DOIUrl":"10.1002/btm2.10711","url":null,"abstract":"<p>Diabetic wounds present a significant challenge in regenerative medicine due to impaired healing, characterized by prolonged inflammation and deficient tissue repair, primarily caused by a skewed pro-inflammatory macrophage phenotype. This study investigates the therapeutic potential of interleukin-10 (IL-10) chemically modified mRNA (modRNA)-enriched human adipose-derived multipotent stromal cells (hADSCs) in a well-established murine model of diabetic wounds. The modRNAs used in this study were chemically modified using N1-methylpseudouridine-5′-triphosphate (m1Ψ) by substituting uridine-5-triphosphate. In vitro experiments demonstrated that IL-10 modRNA-transfected hADSCs effectively modulated macrophage polarization towards an anti-inflammatory phenotype. In vivo experiments with a well-established murine model demonstrated that transplantation of hADSCs^modIL-10 on postoperative day 5 (POD5) significantly improved wound healing outcomes, including accelerated wound closure, enhanced re-epithelialization, promoted M2 polarization, improved collagen deposition, and increased neovascularization. This study concludes that IL-10 modRNA-enriched hADSCs offer a promising therapeutic approach for diabetic wound healing, with the timing of IL-10 administration playing a crucial role in its effectiveness. These cells modulate macrophage polarization and promote tissue repair, demonstrating their potential for improving the management of diabetic wounds.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10711","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141904608","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":"Bilayer 3D co-culture platform inducing the differentiation of normal fibroblasts into cancer-associated fibroblast like cells: New in vitro source to obtain cancer-associated fibroblasts","authors":"Yeon Ju Kim,&nbsp;Hyeon Song Lee,&nbsp;Dohyun Kim,&nbsp;Hwa Kyung Byun,&nbsp;Woong Sub Koom,&nbsp;Won-Gun Koh","doi":"10.1002/btm2.10708","DOIUrl":"10.1002/btm2.10708","url":null,"abstract":"<p>This study presents a novel in vitro bilayer 3D co-culture platform designed to obtain cancer-associated fibroblasts (CAFs)-like cells. The platform consists of a bilayer hydrogel structure with a collagen/polyethylene glycol (PEG) hydrogel for fibroblasts as the upper layer and an alginate hydrogel for tumor cells as the lower layer. The platform enabled paracrine interactions between fibroblasts and cancer cells, which allowed for selective retrieval of activated fibroblasts through collagenase treatment for further study. Fibroblasts remained viable throughout the culture periods and showed enhanced proliferation when co-cultured with cancer cells. Morphological changes in the co-cultured fibroblasts resembling CAFs were observed, especially in the 3D microenvironment. The mRNA expression levels of CAF-related markers were significantly upregulated in 3D, but not in 2D co-culture. Proteomic analysis identified upregulated proteins associated with CAFs, further confirming the transformation of normal fibroblasts into CAF within the proposed 3D co-culture platform. Moreover, co-culture with CAF induced radio- and chemoresistance in pancreatic cancer cells (PANC-1). Survival rate of cancer cells post-irradiation and gemcitabine resistance increased significantly in the co-culture setting, highlighting the role of CAFs in promoting cancer cell survival and therapeutic resistance. These findings would contribute to understanding molecular and phenotypic changes associated with CAF activation and provide insights into potential therapeutic strategies targeting the tumor microenvironment.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10708","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141895220","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":"Mesenchymal stem cells for osteoarthritis: Recent advances in related cell therapy","authors":"Jianjing Lin,&nbsp;Jingtao Huang,&nbsp;Zilu Jiao,&nbsp;Mengyuan Nian,&nbsp;Canfeng Li,&nbsp;Yali Dai,&nbsp;Shicheng Jia,&nbsp;Xintao Zhang","doi":"10.1002/btm2.10701","DOIUrl":"10.1002/btm2.10701","url":null,"abstract":"<p>Osteoarthritis (OA) is a degenerative joint disease that affects the entire joint and has been a huge burden on the health care system worldwide. Although traditional therapy and targeted cartilage cell therapy have made significant progress in the treatment of OA and cartilage regeneration, there are still many problems. Mesenchymal stem cells from various tissues are the most studied cell type and have been used in preclinical and clinical studies of OA, because they are more widely available, have a greater capacity for in <i>vitro</i> expansion, and have anti-inflammatory and immunomodulatory properties compared to autologous chondrocytes. This article will systematically review the latest developments in these areas. It may provide new insights for improving OA and cartilage regeneration.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10701","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141895221","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":"Sperm quality analyzer: A portable LED array microscope with dark-field imaging","authors":"Meng Shao,&nbsp;Changxu Li,&nbsp;Xiaohao Ma,&nbsp;Haoyu Pan,&nbsp;Zeyu Ke,&nbsp;Rui Liu,&nbsp;Zhiguo Zhang,&nbsp;Min-Cheng Zhong,&nbsp;Yi Wang,&nbsp;Zhensheng Zhong,&nbsp;Fengya Lu,&nbsp;Xunbin Wei,&nbsp;Jinhua Zhou","doi":"10.1002/btm2.10703","DOIUrl":"10.1002/btm2.10703","url":null,"abstract":"<p>Sperm quality analysis plays an important role in diagnosing infertility, which is widely implemented by computer-assisted sperm analysis (CASA) of sperm-swimming imaging from commercial phase-contrast microscopy. A well-equipped microscope comes with a high cost, increasing the burden of assessment, and it also occupies a large volume. For point-of-care testing (POCT) of sperm quality, these factors are confronted with the challenges of low-cost and portable instruments. In this study, an encoded light-emitting diode (LED) array illumination is employed to achieve a portable microscope with multicontrast imaging for sperm quality analysis. This microscopy has dimensions of 16.5 × 14.0 × 25.0 cm, and its dark-field (DF) imaging provides high-contrast sperm image data which is suitable for CASA. According to DF imaging, we developed a software of LabCASA, which can used to assess the motility characteristics of sperm. Compared with TrackMate, the difference in motility parameters from our software was less than 10% in the coefficient of variation (CV). The sperm motility parameters vary with the chamber temperature, which further confirms the reliability of our system with DF imaging. The DF imaging provides strong robustness for tracking sperm's motion under different microscopes. For assessment of the motility parameters, our system can work at a lower cost with a plastic structure. This system with DF imaging is suitable for portable POCT of sperm quality analysis, which is highly cost-effective in resource-constrained circumstances.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 6","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10703","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141880163","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":"Insights into the mechanisms, regulation, and therapeutic implications of extracellular matrix stiffness in cancer","authors":"Ximo Zhang,&nbsp;Abdullah Al-Danakh,&nbsp;Xinqing Zhu,&nbsp;Dan Feng,&nbsp;Linlin Yang,&nbsp;Haotian Wu,&nbsp;Yingying Li,&nbsp;Shujing Wang,&nbsp;Qiwei Chen,&nbsp;Deyong Yang","doi":"10.1002/btm2.10698","DOIUrl":"10.1002/btm2.10698","url":null,"abstract":"<p>The tumor microenvironment (TME) is critical for cancer initiation, growth, metastasis, and therapeutic resistance. The extracellular matrix (ECM) is a significant tumor component that serves various functions, including mechanical support, TME regulation, and signal molecule generation. The quantity and cross-linking status of ECM components are crucial factors in tumor development, as they determine tissue stiffness and the interaction between stiff TME and cancer cells, resulting in aberrant mechanotransduction, proliferation, migration, invasion, angiogenesis, immune evasion, and treatment resistance. Therefore, broad knowledge of ECM dysregulation in the TME might aid in developing innovative cancer therapies. This review summarized the available information on major ECM components, their functions, factors that increase and decrease matrix stiffness, and related signaling pathways that interplay between cancer cells and the ECM in TME. Moreover, mechanotransduction alters during tumorogenesis, and current drug therapy based on ECM as targets, as well as future efforts in ECM and cancer, are also discussed.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10698","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141877357","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":"Development of a biocompatible 3D hydrogel scaffold using continuous liquid interface production for the delivery of cell therapies to treat recurrent glioblastoma","authors":"Lauren Kass,&nbsp;Morrent Thang,&nbsp;Yu Zhang,&nbsp;Cathleen DeVane,&nbsp;Julia Logan,&nbsp;Addis Tessema,&nbsp;Jillian Perry,&nbsp;Shawn Hingtgen","doi":"10.1002/btm2.10676","DOIUrl":"10.1002/btm2.10676","url":null,"abstract":"<p>Glioblastoma (GBM) is the most common primary malignant brain tumor diagnosed in adults, carrying with it an extremely poor prognosis and limited options for effective treatment. Various cell therapies have emerged as promising candidates for GBM treatment but fail in the clinic due to poor tumor trafficking, poor transplantation efficiency, and high systemic toxicity. In this study, we design, characterize, and test a 3D-printed cell delivery platform that can enhance the survival of therapeutic cells implanted in the GBM resection cavity. Using continuous liquid interface production (CLIP) to generate a biocompatible 3D hydrogel, we demonstrate that we can effectively seed neural stem cells (NSCs) onto the surface of the hydrogel, and that the cells can proliferate to high densities when cultured for 14 days <i>in vitro</i>. We show that NSCs seeded on CLIP scaffolds persist longer than freely injected cells in vivo, proliferating to 20% higher than their original density in 6 days after implantation. Finally, we demonstrate that therapeutic fibroblasts seeded on CLIP more effectively suppress tumor growth and extend survival in a mouse model of LN229 GBM resection compared to the scaffold or therapeutic cells alone. These promising results demonstrate the potential to leverage CLIP to design hydrogels with various features to control the delivery of different types of cell therapies. Future work will include a more thorough evaluation of the immunological response to the material and improvement of the printing resolution for biocompatible aqueous resins.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 6","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10676","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141862171","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":"The search for an optimal tissue-engineered urethra model for clinical application based on preclinical trials in male animals: A systematic review and meta-analysis","authors":"Natalia Chepelova,&nbsp;Guzel Sagitova,&nbsp;Daniel Munblit,&nbsp;Aleksandr Suvorov,&nbsp;Andrey Morozov,&nbsp;Anastasia Shpichka,&nbsp;Peter Glybochko,&nbsp;Peter Timashev,&nbsp;Denis Butnaru","doi":"10.1002/btm2.10700","DOIUrl":"10.1002/btm2.10700","url":null,"abstract":"<p>Tissue engineering has emerged as a promising avenue for reconstructive urology, though only a limited number of tissue-engineered urethral constructs have advanced to clinical testing. Presently, there exists a dearth of agreement regarding the most promising constructs deserving of implementation in clinical practice. The objective of this review was to provide a comprehensive analysis of preclinical trials findings of a tissue-engineered urethra and to identify the most promising constructs for future translation into clinical practice. A systematic search of the Pubmed, Scopus, and PMC databases was conducted in accordance with the PRISMA statement. Manuscripts published in English between 2015 and 2022, reporting on the methodology for creating a tissue-engineered urethra, assessing the regenerative potential of the scaffold in a male animal model, and evaluating the clinical and histological outcomes of treatment, were included. A total of 48 manuscripts met the inclusion criteria, with 12 being eligible for meta-analysis. Meta-analysis revealed no significant benefit of any matrix type in terms of complication rates. However, acellular matrices demonstrated significant advantage over cellular matrices in case of no postoperative stricture formation (odds ratio = 0.06 [95% CI 0.01; 0.23], <i>p</i> &lt; 0.01). Among all subgroups (animal models and scaffold types), the usage of acellular matrices resulted in advantageous effects. The meta-regression analysis did not show a significant impact of defect length (β1 = −0.02 [−0.28; 0.23], <i>p</i> = 0.86). We found that decellularized materials may carry less relevance for urethral reconstruction due to unfavorable preclinical outcomes. Natural polymers, used independently or with synthetic materials, resulted in better postoperative outcomes in animals compared to purely synthetic constructs. Acellular scaffolds showed promising outcomes, matching or exceeding cellular constructs. However, more studies are needed to confirm their clinical effectiveness.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"9 6","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10700","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141755275","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}