Ali Imran Abid PhD , Guillaume Conzatti PhD , Florence Toti PhD , Nicolas Anton PhD , Thierry Vandamme PhD
{"title":"Mesenchymal stem cell-derived exosomes as cell free nanotherapeutics and nanocarriers","authors":"Ali Imran Abid PhD , Guillaume Conzatti PhD , Florence Toti PhD , Nicolas Anton PhD , Thierry Vandamme PhD","doi":"10.1016/j.nano.2024.102769","DOIUrl":"10.1016/j.nano.2024.102769","url":null,"abstract":"<div><p>Many strategies for regenerating the damaged tissues or degenerating cells are employed in regenerative medicine. Stem cell technology is a modern strategy of the recent approaches, particularly the use of mesenchymal stem cells (MCSs). The ability of MSCs to differentiate as well as their characteristic behaviour as paracrine effector has established them as key elements in tissue repair (Shaer et al., 2014<span><sup>1</sup></span>). Recently, extracellular vesicles (EVs) shed by MSCs have emerged as a promising cell free therapy (Citation}Rani, S., Ryan, A. E., Griffin, M. D., and Ritter, T., 2015<span><sup>2</sup></span>). This comprehensive review encompasses MSCs-derived exosomes and their therapeutic potential as nanotherapeutics. We also discuss their potency as drug delivery nano-carriers in comparison with liposomes. A better knowledge of EVs behaviour in vivo and of their mechanism of action are key to determine parameters of an optimal formulation in pilot studies and to establish industrial processes.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"61 ","pages":"Article 102769"},"PeriodicalIF":4.2,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1549963424000388/pdfft?md5=c0be17492409b70cb143942a63ed1a16&pid=1-s2.0-S1549963424000388-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446650","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":"Modification of mesenchymal stromal cells with silibinin-loaded PLGA nanoparticles improves their therapeutic efficacy for cutaneous wound repair","authors":"Ningfei Shen MSc , Anna Polyanskaya MSc , Xiaoli Qi PhD , Aya Al Othman MSc , Anastasia Permyakova PhD , Marina Volkova PhD , Alexandre Mezentsev PhD , Mikhail Durymanov PhD","doi":"10.1016/j.nano.2024.102767","DOIUrl":"10.1016/j.nano.2024.102767","url":null,"abstract":"<div><p>The use of mesenchymal stromal cells (MSCs) for treating chronic inflammatory disorders, wounds, and ischemia-reperfusion injuries has shown improved healing efficacy. However, the poor survival rate of transplanted cells due to oxidative stress in injured or inflamed tissue remains a significant concern for MSC-based therapies. In this study, we developed a new approach to protect MSCs from oxidative stress, thereby improving their survival in a wound microenvironment and enhancing their therapeutic effect. We produced PLGA nanoparticles loaded with the cytoprotective phytochemical silibinin (SBN), and used them to modify MSCs. Upon internalization, these nanoformulations released SBN, activating the Nrf2/ARE signaling pathway, resulting in threefold reduction in intracellular ROS content and improved cell survival under oxidative stress conditions. Modification of MSCs with SBN-loaded PLGA nanoparticles increased their survival upon transplantation to full-thickness cutaneous wounds and improved wound healing. This study suggests that MSC modification with cytoprotective nanoparticles could be a promising approach for improving wound healing.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"61 ","pages":"Article 102767"},"PeriodicalIF":4.2,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437281","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}
Cristina Stavilă PhD student , Dumitru Daniel Herea PhD , Mihaela Camelia Zară PhD , George Stoian PhD , Anca Emanuela Minuti PhD , Luminița Labușcă PhD - MD , Marian Grigoraș PhD , Horia Chiriac PhD , Nicoleta Lupu PhD , Adriana Petrovici PhD student , Adriana Aniță PhD - MD , Dragos Aniță PhD - MD
{"title":"Enhancement of chemotherapy effects by non-lethal magneto-mechanical actuation of gold-coated magnetic nanoparticles","authors":"Cristina Stavilă PhD student , Dumitru Daniel Herea PhD , Mihaela Camelia Zară PhD , George Stoian PhD , Anca Emanuela Minuti PhD , Luminița Labușcă PhD - MD , Marian Grigoraș PhD , Horia Chiriac PhD , Nicoleta Lupu PhD , Adriana Petrovici PhD student , Adriana Aniță PhD - MD , Dragos Aniță PhD - MD","doi":"10.1016/j.nano.2024.102766","DOIUrl":"10.1016/j.nano.2024.102766","url":null,"abstract":"<div><p>Remote magneto-mechanical actuation (MMA) of magnetic nanoparticles (MNP) is emerging as a promising therapy method in oncology. However, translation to the clinic faces the challenge of whole-body action and the reluctance about indiscriminate mechanical action of the nanoparticles on tumor and healthy cells. Here, we show how the MMA method based on magnetically-rotated gold-coated MNP boosts only the activity of an unbound antitumor drug, without physical damage of cells via MNP. Therefore, in clinical practice, the effect of antitumor drug can be safely increased systemically while maintaining drug concentrations at current doses.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"60 ","pages":"Article 102766"},"PeriodicalIF":4.2,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1549963424000352/pdfft?md5=78865600aecf94690c303cb654fad111&pid=1-s2.0-S1549963424000352-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432359","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}
Xin Mao MD , Yaming Du MD , Rubo Sui MD , Xiaodong Yu MD , Yue Zhu MD , Meiyi Huang MD
{"title":"Quercetin conjugated PSC-derived exosomes to inhibit intimal hyperplasia via modulating the ERK, Akt, and NF-κB signaling pathways in the rat carotid artery post balloon injury","authors":"Xin Mao MD , Yaming Du MD , Rubo Sui MD , Xiaodong Yu MD , Yue Zhu MD , Meiyi Huang MD","doi":"10.1016/j.nano.2024.102763","DOIUrl":"10.1016/j.nano.2024.102763","url":null,"abstract":"<div><p>The primary challenge in percutaneous coronary interventions for vascular restenosis is the occurrence of restenosis, which is defined by the excessive proliferation of neointimal tissue. Herein, our research team suggests that exosomes obtained from PSC, when paired with quercetin (Q@PSC-E), successfully reduce neointimal hyperplasia in a Sprague-Dawley rat model. Furthermore, the physical properties of the synthesized Q@PSC-E were examined using UV–vis, DLS, and FT-IR characterization techniques. The rats were subjected to balloon injury (BI) utilizing a 2-Fr Fogarty arterial embolectomy balloon catheter. Intimal hyperplasia and the degree of VSMC proliferation were evaluated using histological analysis in the rat groups that received a dosage of Q@PSC-E at 30 mg/kg/d. Significantly, Q@PSC-E inhibited cell proliferation through a pathway that does not include lipoxygenase, as demonstrated by [<sup>3</sup>H] thymidine incorporation, MTT, and flow cytometry studies. Additionally, the data indicate that Q@PSC-E hinders cell proliferation by targeting particular events that promote cell growth, including the activation of Akt and NF-κB, disruption of cell-cycle progression and also obstructs the ERK signaling pathway.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"61 ","pages":"Article 102763"},"PeriodicalIF":4.2,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141427232","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}
Jingyu Zhang MSc , Xuexiao Li MSc , Ming Cheng MD , Kaichen Wan MSc , Shangcheng Yan MSc , Wei Peng MSc , Guangxin Duan MD , Yongyou Wu MD , Ling Wen MD
{"title":"MoO3-X nanodots coated suture for combating surgical site infection via antibacterial and anti-inflammatory properties","authors":"Jingyu Zhang MSc , Xuexiao Li MSc , Ming Cheng MD , Kaichen Wan MSc , Shangcheng Yan MSc , Wei Peng MSc , Guangxin Duan MD , Yongyou Wu MD , Ling Wen MD","doi":"10.1016/j.nano.2024.102757","DOIUrl":"10.1016/j.nano.2024.102757","url":null,"abstract":"<div><p>Surgical site infection (SSI) significantly affects patient recovery time, health outcomes and quality of life which is closely associated with the use of implants or mesh. Sutures are the most frequently used implants that play a significant role in the development of SSI. Studies have demonstrated that the administration of effective bactericidal and anti-inflammatory treatments can significantly decrease the incidence of SSI. To address this concern, a versatile suture was engineered by coating MoO<sub>3-X</sub> nanodots in this study. The incorporation of MoO<sub>3-X</sub> nanodots endowed the suture with desirable antibacterial and anti-inflammatory properties that were evaluated in <em>in vitro</em> and <em>in vivo</em> experiments. The results showed its remarkable ability to facilitate wound healing and prevent SSI through its dual action of combating bacterial infection and reducing inflammation. These findings highlight the promising potential of this multifunctional surgical suture as a versatile tool to promote better outcomes in surgical procedures.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"60 ","pages":"Article 102757"},"PeriodicalIF":4.2,"publicationDate":"2024-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141420002","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}
Zhihui Zhu MSc , Pan Qiao MSc , Mengyu Liu MSc , Fangfang Sun MSc , Meilin Geng MSc , Hanchun Yao PhD
{"title":"Blocking the utilization of carbon sources via two pathways to induce tumor starvation for cancer treatment","authors":"Zhihui Zhu MSc , Pan Qiao MSc , Mengyu Liu MSc , Fangfang Sun MSc , Meilin Geng MSc , Hanchun Yao PhD","doi":"10.1016/j.nano.2024.102764","DOIUrl":"10.1016/j.nano.2024.102764","url":null,"abstract":"<div><p>Glucose oxidase (GOx) is often used to starvation therapy. However, only consuming glucose cannot completely block the energy metabolism of tumor cells. Lactate can support tumor cell survival in the absence of glucose. Here, we constructed a nanoplatform (Met@HMnO<sub>2</sub>-GOx/HA) that can deplete glucose while inhibiting the compensatory use of lactate by cells to enhance the effect of tumor starvation therapy. GOx can catalyze glucose into gluconic acid and H<sub>2</sub>O<sub>2</sub>, and then HMnO<sub>2</sub> catalyzes H<sub>2</sub>O<sub>2</sub> into O<sub>2</sub> to compensate for the oxygen consumed by GOx, allowing the reaction to proceed sustainably. Furthermore, metformin (Met) can inhibit the conversion of lactate to pyruvate in a redox-dependent manner and reduce the utilization of lactate by tumor cells. Met@HMnO<sub>2</sub>-GOx/HA nanoparticles maximize the efficacy of tumor starvation therapy by simultaneously inhibiting cellular utilization of two carbon sources. Therefore, this platform is expected to provide new strategies for tumor treatment.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"61 ","pages":"Article 102764"},"PeriodicalIF":4.2,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141398167","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}
Wei Zhao PhD , Zhenshan Jia PhD , William A. Bauman MD , Yiwen Qin BA , Yuanzhen Peng BA , Zihao Chen MS , Christopher P. Cardozo MD , Dong Wang PhD , Weiping Qin MD, Ph.D
{"title":"Targeted-delivery of nanomedicine-enabled methylprednisolone to injured spinal cord promotes neuroprotection and functional recovery after acute spinal cord injury in rats","authors":"Wei Zhao PhD , Zhenshan Jia PhD , William A. Bauman MD , Yiwen Qin BA , Yuanzhen Peng BA , Zihao Chen MS , Christopher P. Cardozo MD , Dong Wang PhD , Weiping Qin MD, Ph.D","doi":"10.1016/j.nano.2024.102761","DOIUrl":"10.1016/j.nano.2024.102761","url":null,"abstract":"<div><p>To date, no therapy has been proven to be efficacious in fully restoring neurological functions after spinal cord injury (SCI). Systemic high-dose methylprednisolone (MP) improves neurological recovery after acute SCI in both animal and human. MP therapy remains controversial due to its modest effect on functional recovery and significant adverse effects. To overcome the limitation of MP therapy, we have developed a <em>N</em>-(2-hydroxypropyl) methacrylamide copolymer-based MP prodrug nanomedicine (Nano-MP) that can selectively deliver MP to the SCI lesion when administered systemically in a rat model of acute SCI. Our in vivo data reveal that Nano-MP is significantly more effective than free MP in attenuating secondary injuries and neuronal apoptosis. Nano-MP is superior to free MP in improving functional recovery after acute SCI in rats. These data support Nano-MP as a promising neurotherapeutic candidate, which may provide potent neuroprotection and accelerate functional recovery with improved safety for patients with acute SCI.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"60 ","pages":"Article 102761"},"PeriodicalIF":5.4,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317769","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}
Erin L. Mills PhD , Yelixza I. Avila PhD , Damian Beasock PhD , Yasmine Radwan PhD , Samantha R. Suptela PhD , Ian Marriott PhD , Kirill A. Afonin PhD , M. Brittany Johnson PhD
{"title":"Immunostimulatory nucleic acid nanoparticles (NANPs) augment protective osteoblast and osteoclast type I interferon responses to Staphylococcus aureus","authors":"Erin L. Mills PhD , Yelixza I. Avila PhD , Damian Beasock PhD , Yasmine Radwan PhD , Samantha R. Suptela PhD , Ian Marriott PhD , Kirill A. Afonin PhD , M. Brittany Johnson PhD","doi":"10.1016/j.nano.2024.102762","DOIUrl":"10.1016/j.nano.2024.102762","url":null,"abstract":"<div><p>Recalcitrant staphylococcal osteomyelitis may be due, in part, to the ability of <em>Staphylococcus aureus</em> to invade bone cells. However, osteoclasts and osteoblasts are now recognized to shape host responses to bacterial infection and we have recently described their ability to produce IFN-β following <em>S. aureus</em> infection and limit intracellular bacterial survival/propagation. Here, we have investigated the ability of novel, rationally designed, nucleic acid nanoparticles (NANPs) to induce the production of immune mediators, including IFN-β, following introduction into bone cells. We demonstrate the successful delivery of representative NANPs into osteoblasts and osteoclasts via endosomal trafficking when complexed with lipid-based carriers. Their delivery was found to differentially induce immune responses according to their composition and architecture via discrete cytosolic pattern recognition receptors. Finally, the utility of this nanoparticle technology was supported by the demonstration that immunostimulatory NANPs augment IFN-β production by <em>S. aureus</em> infected bone cells and reduce intracellular bacterial burden.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"60 ","pages":"Article 102762"},"PeriodicalIF":5.4,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141311164","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":"Reconstruction of TNF-α with specific isoelectric point released from SPIONs basing on variable charge to enhance pH-sensitive controlled-release","authors":"Lin Yan Ph.D , Yadi Chen M.Sc , Shihao Zhang M.Sc , Chunjie Zhu Ph.D , Shangying Xiao M.Sc , Haishan Xia M.Sc , Xiaohua Chen M.Sc , Dan Guo Ph.D , Xiaohua Lv M.Sc , Lei Rao Ph.D , Manjiao Zhuang Ph.D","doi":"10.1016/j.nano.2024.102758","DOIUrl":"10.1016/j.nano.2024.102758","url":null,"abstract":"<div><p>The clinical application of tumor necrosis factor-α (TNF-α) is limited by its short half-life, subeffective concentration in the targeted area and severe systemic toxicity. In this study, the recombinant polypeptide S4-TNF-α was constructed and coupled with chitosan-modified superparamagnetic iron oxide nanoparticles (S4-TNF-α-SPIONs) to achieve pH-sensitive controlled release and active tumor targeting activity. The isoelectric point (pI) of S4-TNF-α was reconstructed to approach the pH of the tumor microenvironment. The negative-charge S4-TNF-α was adsorbed to chitosan-modified superparamagnetic iron oxide nanoparticles (CS-SPIONs) with a positive charge through electrostatic adsorption at physiological pH. The acidic tumor microenvironment endowed S4-TNF-α with a zero charge, which accelerated S4-TNF-α release from CS-SPIONs. Our studies showed that S4-TNF-α-SPIONs displayed an ideal pH-sensitive controlled release capacity and improved antitumor effects. Our study presents a novel approach to enhance the pH-sensitive controlled-release of genetically engineered drugs by adjusting their pI to match the pH of the tumor microenvironment.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"60 ","pages":"Article 102758"},"PeriodicalIF":5.4,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296470","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}
Wararat Chiangjong Ph.D. , Jirawan Panachan M.S. , Sujitra Keadsanti Ph.D. , David S. Newburg Ph.D. , Ardythe L. Morrow Ph.D. , Suradej Hongeng M.D. , Somchai Chutipongtanate M.D., Ph.D.
{"title":"Development of red blood cell-derived extracellular particles as a biocompatible nanocarrier of microRNA-204 (REP-204) to harness anti-neuroblastoma effect","authors":"Wararat Chiangjong Ph.D. , Jirawan Panachan M.S. , Sujitra Keadsanti Ph.D. , David S. Newburg Ph.D. , Ardythe L. Morrow Ph.D. , Suradej Hongeng M.D. , Somchai Chutipongtanate M.D., Ph.D.","doi":"10.1016/j.nano.2024.102760","DOIUrl":"10.1016/j.nano.2024.102760","url":null,"abstract":"<div><p>Neuroblastoma (NB) is the most common extracranial solid tumor in the pediatric population with a high degree of heterogeneity in clinical outcomes. Upregulation of the tumor suppressor miR-204 in neuroblastoma is associated with good prognosis. Although miR-204 has been recognized as a potential therapeutic candidate, its delivery is unavailable. We hypothesized that REP-204, the red blood cell-derived extracellular particles (REP) with miR-204 loading, can suppress neuroblastoma cells in vitro. After miR-204 loading by electroporation, REP-204, but not REP carriers, inhibited the viability, migration, and 3D spheroid growth of neuroblastoma cells regardless of MYCN amplification status. SWATH-proteomics revealed that REP-204 treatment may trigger a negative regulation of mRNA splicing by the spliceosome, suppression of amino acid metabolism and protein production, and prevent SLIT/ROBO signaling-mediated cell migration, to halt neuroblastoma tumor growth and metastasis. The therapeutic efficacy of REP-204 should be further investigated in preclinical models and clinical studies.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"60 ","pages":"Article 102760"},"PeriodicalIF":5.4,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1549963424000297/pdfft?md5=ef23c07d03b9cd57361c33044a34dce6&pid=1-s2.0-S1549963424000297-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296469","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}