OpenNano最新文献

{"title":"A microfluidic application for mass production of drug-loaded polymeric microspheres for a long-acting injectable with IVL-DrugFluidic®, a novel microfluidic microsphere manufacturing platform technology","authors":"Chan Hee Chon ,&nbsp;Ju Hee Kim ,&nbsp;Hyunseung On,&nbsp;Jiwoong Choi,&nbsp;Sanghun Lee,&nbsp;Euidon Han","doi":"10.1016/j.onano.2023.100153","DOIUrl":"10.1016/j.onano.2023.100153","url":null,"abstract":"<div><p>Long acting injectables (LAIs) using polymeric microspheres has been developed to increase patient compliance and reduce side effects. Among many methods for manufacturing polymeric microspheres, microfluidics technology is known to have excellent characteristics in that the produced polymeric microspheres have perfect spherical shape without surface defect and uniform size, and thus have outstanding efficacy without initial burst. However, the mass production of polymeric microspheres was not realized by the inherent limitation that microfluidics is suitable for small quantity manufacturing. Overcoming such limitations, we could show mass production of finasteride-loaded polymeric microspheres (PLGA 7525) for LAIs using our microfluidic manufacturing platform technology, IVL-DrugFluidic®. The microfluidic channels used in manufacturing were optimized through computational fluid dynamics (CFD) simulation to minimize the flow variation between microchannels and eliminated disturbance outside of microchannels by resistance channels. In addition, the solvent removal was improved by applying the baffle and foam breaker system. Therefore, microspheres were mass-produced in the GMP manufacturing environment in perfect spherical shape, smooth surface, and even size distribution. The encapsulation efficiency was almost 100% and the residual solvent was under the Standard of regulation. In the clinical trial using microspheres mass-produced by IVL-DrugFluidic®, we confirmed that the drug release was stably maintained for a month, the target period without initial burst. It was also confirmed that the drug release by dose of microspheres was uniformly proportional. In conclusion, the microsphere manufacturing platform technology, IVL-DrugFluidic® has been proven to be an appropriate system for mass production of polymeric microspheres optimized for LAIs through physicochemical characteristics and clinical trial.</p></div>","PeriodicalId":37785,"journal":{"name":"OpenNano","volume":"12 ","pages":"Article 100153"},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42202654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D printing of microbots, characterisation, and utilisation in combination with allicin against C. albicans biofilms","authors":"Harinash Rao ,&nbsp;Pei Pei Chong ,&nbsp;Priya Madhavan","doi":"10.1016/j.onano.2023.100160","DOIUrl":"10.1016/j.onano.2023.100160","url":null,"abstract":"<div><p>A major driving factor for antimicrobial resistance which leads to treatment failure for microbial infections ascribed to <em>C. albicans</em> are the formation of biofilms. 3D printing is a rapidly evolving innovation which could revolutionize drug delivery based on its unprecedented opportunity for targeted and improved delivery. Herein, we designed and 3D printed microbots via two photon-polymerisation. Subsequently, characterisation was performed and the activity of microbots independently and in combination with allicin against <em>C. albicans</em> biofilms were investigated. The microbots independently did not affect <em>C. albicans</em> biofilm formation and adhesion nor was there any significant synergistic interaction between microbots and allicin combination. However, this study has pioneered the utilisation of microbots for microbiological applications such as in combination with an antimicrobial to target biofilms. These prototype microbots will act as a guide for the next generation of microbots which will be functionalised to disrupt biofilms magnetically, enhancing allicin delivery and activity.</p></div>","PeriodicalId":37785,"journal":{"name":"OpenNano","volume":"12 ","pages":"Article 100160"},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49052514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dunaliella salina chitosan nanoparticles as a promising wound healing vehicles: In-vitro and in-vivo study","authors":"Farouk K. El-Baz ,&nbsp;Abeer Salama ,&nbsp;Sami I. Ali ,&nbsp;Hadeer A. El-Hashemy","doi":"10.1016/j.onano.2023.100165","DOIUrl":"10.1016/j.onano.2023.100165","url":null,"abstract":"<div><p><em>Dunaliella salina</em>, a green microalga, is among the main sources of bioactive β-carotene and zeaxanthin. Hence, it will be investigated for its antioxidant effectiveness in wound healing. The current study's objective is to create new chitosan nanoparticle loaded <em>D. salina</em> hexane: ethyl acetate extract (HEAE-CNPs) and methanol extract (ME-CNPs) to be used in accelerating wound healing <em>in-vivo.</em> Double emulsion technique was utilized to prepare the nanoparticles. The prepared HEAE-CNPs and ME-CNPs were examined for <em>in-vitro</em> release and <em>in-vivo</em> wound healing efficacy in Wistar rats. Results confirmed that <em>D. salina</em> hexane:ethyl acetate extract (HEAE) contains 19.167 mg/g β-carotene and 16.196 mg/g zeaxanthin, whereas the extract of methanol (ME) contains only small amounts of zeaxanthin 0.313 mg/g as quantified by HPLC. The <em>D. salina</em> loaded chitosan gel greatly slowed the total carotenoids release, according to the <em>in-vitro</em> release assays, in comparison with <em>D. salina</em> nanoparticle dispersion with a particle size in the nanorange. By decreasing factor alpha (TNF-α) of tumor necrosis and increasing vascular endothelial growth factor (VEGF) and collagen skin contents, both HEAE-CNPs and ME-CNPs demonstrated wound healing and regeneration.</p></div>","PeriodicalId":37785,"journal":{"name":"OpenNano","volume":"12 ","pages":"Article 100165"},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44536764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactoferrin functionalized concave cube Au nanoparticles as biocompatible antibacterial agent","authors":"Shakil Ahmed Polash ,&nbsp;Amir Hamza ,&nbsp;Md. Monir Hossain ,&nbsp;Chaitali Dekiwadia ,&nbsp;Tanushree Saha ,&nbsp;Ravi Shukla ,&nbsp;Vipul Bansal ,&nbsp;Satya Ranjan Sarker","doi":"10.1016/j.onano.2023.100163","DOIUrl":"10.1016/j.onano.2023.100163","url":null,"abstract":"<div><p>Gold nanoparticles (AuNPs) are one of the most extensively studied nanomaterials and their distinct physicochemical properties make them suitable for versatile applications. Herein, we synthesized concave cube-shaped gold nanoparticles (CCAuNPs) and functionalized them with lactoferrin (Lf), a natural antimicrobial protein, through electrostatic interaction as well as weak covalent formation. The functionalization of CCAuNPs was confirmed through UV–Visible (<em>i.e.</em>, bathochromic shift of the surface plasmon resonance peak by 7 nm), Fourier transform infrared (FTIR) and X-ray diffraction (XRD) spectroscopy, and their surface zeta potential. The concave cusp of CCAuNPs was confirmed through atomic force microscopy (AFM). The Lf-functionalized CCAuNPs (Lf-CCAuNPs) exhibited superior antibacterial propensity against a series of bacteria when compared to that of CCAuNPs. However, they didn't demonstrate any antibacterial activity against <em>Lactobacillus plantarum</em>, one of the key beneficial gut bacteria. The lipid peroxidation (LPO) assay confirmed the oxidation of fatty acids in the bacterial membrane upon interaction with AuNPs, which made the bacterial membrane porous. The resultant membrane-impaired dead bacteria were visualized through CellTox™ Green assay as well as the Trypan Blue dye exclusion assay. Both the nanoparticles demonstrated excellent hemocompatibility as well as biocompatibility (both <em>in vitro</em> and <em>in vivo</em>) as confirmed by MTT assay and the levels of important functional biomarkers of liver (<em>e.g.</em>, ALT, AST, and ALP) and kidney (<em>e.g.</em>, creatinine, uric acid, and BUN) in the serum. Overall, Lf-CCAuNPs with excellent hemocompatibility, and biocompatibility can be deployed as potential antibacterial agents to tackle the menace of pathogenic bacteria.</p></div>","PeriodicalId":37785,"journal":{"name":"OpenNano","volume":"12 ","pages":"Article 100163"},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49547949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyaluronic acid/chitosan-coated poly (lactic-co-glycolic acid) nanoparticles to deliver single and co-loaded paclitaxel and temozolomide for CD44+oral cancer cells","authors":"Malak Hassn Mesrati ,&nbsp;Asilah Ahmad Tajudin ,&nbsp;Mas Jaffri Masarudin ,&nbsp;Mohammed Numan Alamassi ,&nbsp;Asma Y. Abuhamad ,&nbsp;Amir Syahir","doi":"10.1016/j.onano.2023.100166","DOIUrl":"https://doi.org/10.1016/j.onano.2023.100166","url":null,"abstract":"<div><p>Oral cancer has a poor survival rate despite comprehensive therapy. Current treatments result in acute side effects and fail to eliminate an aggressive group of cells overexpressing CD44. Such cells are capable of tumour initiating, self-renewal, invasion and metastasis, resulting in tumour relapse and resistance. This study aims to synthesise and characterise hyaluronic acid/chitosan-coated poly (lactic-co-glycolic acid) nanoparticles and assess their effectiveness in delivering Paclitaxel and Temozolomide to human tongue squamous cell carcinoma cell line that expresses high CD44 levels, in terms of cell cytotoxicity and apoptosis. This study also assesses the coordinated administration of Paclitaxel and Temozolomide and whether they exhibit significant synergistic cell inhibition effects with reduced introduced drug concentration if co-delivered simultaneously. Nanoparticles were synthesised with solvent evaporation method and characterised to assess their size, homogeneity, and zeta potential. Cell viability assay and real-time cell analysis were performed to examine the cell inhibitory effect of the drug-loaded nanoparticles. Cell apoptosis and cell cycle alteration were detected, and reactive oxygen species induction, mitochondrial membrane potential, and expressed genes associated with cell inhibition and death were evaluated. The synthesised nanoparticles had a nano-sized diameter of 260.40±11.54 nm, a positive zeta potential of +14.31±1.37 mV and a low polydispersity index value of 0.15±0.03. Paclitaxel, Temozolomide, and their combination have inhibited cell proliferation with half maximal inhibitory concentrations of 4 nM, 1000 μM and 2nM:300 μM, respectively. Compared to free drugs, the single-loaded and co-loaded drugs induced more cytotoxicity. Paclitaxel and Temozolomide showed a considerable synergistic inhibitory effect which was discovered to be more significant when the drugs were loaded in the nanoparticles. Drug-loaded nanoparticles were verified to induce higher cell apoptosis rates, cell proportion arrested at the S-phase of the cell cycle, reactive oxygen species generation, mitochondrial collapse and expression of genes associated with cellular inhibition and death than free drugs. These results demonstrate that the established nanoparticles could be a potential candidate for oral cancer therapy since they could deliver and improve the efficacy of single and dual drugs against oral cancer cells.</p></div>","PeriodicalId":37785,"journal":{"name":"OpenNano","volume":"12 ","pages":"Article 100166"},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49762259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lab-scale siRNA and mRNA LNP manufacturing by various microfluidic mixing techniques – an evaluation of particle properties and efficiency","authors":"David C. Jürgens ,&nbsp;Leonie Deßloch ,&nbsp;Diana Porras-Gonzalez ,&nbsp;Joshua Winkeljann ,&nbsp;Sebastian Zielinski ,&nbsp;Matthias Munschauer ,&nbsp;Andreas L. Hörner ,&nbsp;Gerald Burgstaller ,&nbsp;Benjamin Winkeljann ,&nbsp;Olivia M. Merkel","doi":"10.1016/j.onano.2023.100161","DOIUrl":"10.1016/j.onano.2023.100161","url":null,"abstract":"<div><p>Lipid Nanoparticles (LNPs) are promising drug delivery systems for various RNAs such as small interfering (siRNA) and messenger RNA (mRNA). Microfluidic mixing is a common technique to encapsulate RNA in LNPs. However, high flow rates and lipid concentrations are used for LNP formation to control LNP size as well as RNA encapsulation efficiency. We investigated the feasibility of downscaling siRNA and mRNA LNP manufacturing to save materials and enable a broader access to this technology. To optimize such a down-scaled procedure, we evaluated physicochemical nanoparticle characteristics including hydrodynamic diameter, zeta potential, particle concentration, encapsulation efficiency, and recovery for LNPs produced with three different microfluidic methods. We observed differences in nanoparticle characteristics and <em>in vitro</em> performance regarding cellular uptake, gene silencing, and mRNA expression. We determined the gene knockdown ability of the best siRNA LNPs formulation <em>ex vivo</em> using precision-cut lung slices to highlight the translational character of LNPs for inhalation and observed comparable efficacy as with a commercially available transfection reagent.</p></div>","PeriodicalId":37785,"journal":{"name":"OpenNano","volume":"12 ","pages":"Article 100161"},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43261691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How to outsmart the cold tumor microenvironment: Design of STING ligand nanoparticles for improved cancer immunotherapy","authors":"Marija Petrovic ,&nbsp;Stoyan Tankov ,&nbsp;Martin Kiening ,&nbsp;Yakkala Chakradhar ,&nbsp;Duran Rafael ,&nbsp;Paul R. Walker ,&nbsp;Gerrit Borchard ,&nbsp;Olivier Jordan","doi":"10.1016/j.onano.2023.100157","DOIUrl":"10.1016/j.onano.2023.100157","url":null,"abstract":"","PeriodicalId":37785,"journal":{"name":"OpenNano","volume":"12 ","pages":"Article 100157"},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48802694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifunctional chitosan/carbon dots/sodium alginate/zinc oxide double-layer sponge hydrogel with high antibacterial, mechanical and hemostatic properties","authors":"Reza Monfared-Hajishirkiaee ,&nbsp;Hamide Ehtesabi ,&nbsp;Shima Najafinobar ,&nbsp;Zahra Masoumian","doi":"10.1016/j.onano.2023.100162","DOIUrl":"10.1016/j.onano.2023.100162","url":null,"abstract":"<div><p>Due to the fact that bacterial contamination of wounds is the cause of increased morbidity and mortality today, various antimicrobial wound dressings are developing to prevent wound contamination. In addition, an ideal wound dressing should have proper mechanical and hemostatic properties to maintain wound healing conditions. Here, a double-layer sponge hydrogel nanocomposite wound dressing was designed and manufactured by combining zinc oxide nanoparticles (ZnO<img>NPs) with different concentrations in the hydrogel layer and green carbon dots in the sponge layer. The surface morphology of two layers was investigated using a scanning electron microscope. X-ray diffraction proved the presence of ZnO<img>NPs. Physical tests showed a decrease in water absorption and water vapor transmission rate and an increase in blood absorption in the presence of ZnO. The sponge layer showed suitable absorption support in the presence of carbon dots. By combining nanoparticles in both layers, the mechanical properties were greatly enhanced. The sponge hydrogel with the highest concentration of ZnO showed excellent inhibition of 41 mm against <em>Pseudomonas aeruginosa</em> bacteria and 25 mm of inhibition against <em>Staphylococcus aureus</em>. Finally, in vitro blood clotting and animal tests confirmed the increase in the hemostatic power of the sponge hydrogel with the maximum concentration of ZnO.</p></div>","PeriodicalId":37785,"journal":{"name":"OpenNano","volume":"12 ","pages":"Article 100162"},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42928288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytotoxicity and biocompatibility of Meropenem-loaded graphene oxide and its antibacterial effects against carbapenem-resistant Gram-negative bacteria","authors":"Mohammad Yousef Memar ,&nbsp;Yalda Rahbar Saadat ,&nbsp;Solmaz Maleki Dizaj ,&nbsp;Mina Yekani ,&nbsp;Seyyedeh Mina Hejazian ,&nbsp;Bahram Niknafs ,&nbsp;Sepideh Zununi Vahed ,&nbsp;Simin Sharifi","doi":"10.1016/j.onano.2023.100155","DOIUrl":"10.1016/j.onano.2023.100155","url":null,"abstract":"<div><p>The rising prevalence of multidrug-resistant (MDR) bacteria, mainly Gram-negative bacteria, challenges their effective treatment. Graphene oxide (GO) represents antibacterial activities; however, the synergistic effect of GO with conventional antibiotics remains unclarified. Here, meropenem-loaded GO (Mrp-GO) was prepared and its physicochemical and biocompatibility properties along with its inhibitory effect against carbapenem-resistant Gram-negative bacteria were evaluated. Cytotoxicity of Mrp-GO on human bone marrow-derived mesenchymal stem cells (hBM-MSCs) was examined as well. The prepared nanoparticles had suitable and acceptable physicochemical properties. The antibacterial activity of Mrp-GO increased in comparison to the GO and Mrp alone. Moreover, the Mrp-GO had low hemolytic effects at the concentrations required for bacterial inhibition. The cell viability of hBM-MSCs at toxic Mrp-GO concentrations for bacterial isolates was almost 90–100%. The combination of nanostructure and conventional antibiotics can be a promising treatment modality against carbapenem-resistant Gram-negative bacteria.</p></div>","PeriodicalId":37785,"journal":{"name":"OpenNano","volume":"12 ","pages":"Article 100155"},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49290986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in nanoparticles-based approaches in cancer theranostics","authors":"Muhammad Akmal Raheem ,&nbsp;Muhammad Ajwad Rahim ,&nbsp;Ijaz Gul ,&nbsp;Xiaoyun Zhong ,&nbsp;Chufan Xiao ,&nbsp;Haihui Zhang ,&nbsp;Jiazhang Wei ,&nbsp;Qian He ,&nbsp;Muhammad Hassan ,&nbsp;Can Yang Zhang ,&nbsp;Dongmei Yu ,&nbsp;Vijay Pandey ,&nbsp;Ke Du ,&nbsp;Runming Wang ,&nbsp;Sanyang Han ,&nbsp;Yuxing Han ,&nbsp;Peiwu Qin","doi":"10.1016/j.onano.2023.100152","DOIUrl":"10.1016/j.onano.2023.100152","url":null,"abstract":"<div><p>In recent years, the incidence and mortality rate of cancer is raising worldwide. Traditional approaches for cancer patient management including surgery, chemotherapy, radiotherapy, and targeted therapies provide unsatisfactory results and are often associated with adverse reactions. Over the last few decades, nanotechnology has been a rapidly emerging area of theragnostic in clinical research. It plays a vital role as a bridge between the science and technology of miscellaneous nanoparticles (NPs) and nanomedicine. In general, NPs with a range of sizes of 1–100 nm are thought to be acceptable for cancer medications. NPs may enhance the consistency and solubility of therapeutic drugs to obtain site-specific targeting, controlled release, and safe for healthy organs. NPs have the benefit of pathophysiological properties, enhanced permeability and retention (EPR) effects, and an advantage in cancer targeting. Furthermore, theranostic nanoparticles have been established having incorporated diagnostics and therapy in a single system that might provide more personalized treatment with optimal doses and monitoring the distribution, targeting, and response to therapy by using imaging tools. In this review, we have discussed the classes of nanoparticles, targeting approaches, and implications of NPs for cancer theranostics with recent examples.</p></div>","PeriodicalId":37785,"journal":{"name":"OpenNano","volume":"12 ","pages":"Article 100152"},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46331103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}