{"title":"Visualised genotyping assay with oral swabs in a closed tube by nested invasive reaction assisted with gold nanoparticle probes","authors":"Yijun Li, Wei Wei, Yi Ma, Jingwen Shan, Yanan Chu, LiKun Zhang, Danni Liu, Xueping Ma, Guohua Zhou, Haiping Wu","doi":"10.1049/nbt2.12123","DOIUrl":"10.1049/nbt2.12123","url":null,"abstract":"<p>Single nucleotide polymorphism (SNP) typing is crucial for drug dosage and disease progression. Therefore, a simple and convenient genotyping assay is essential for personalised medicine. Herein, we developed a non-invasive, closed-tube, and visualised method for genotyping. In this method, oral swabs were lysed to directly perform PCR coupled with nested invasive reaction and visualisation based on gold nanoparticle probes in a closed tube. The strategy for genotyping assay depends on the single base recognition property of invasive reaction. This assay allowed quick and simple sample preparation and the detection of 25 copies/μL of <i>CYP2C19*2</i> and 100 copies/μL of <i>CYP2C19*3</i> within 90 min. Further, 20 oral swab samples for <i>CYP2C19*2</i> and <i>CYP2C19*3</i> were correctly typed, which agreed with pyrosequencing, indicating that this method has great potential for SNP typing in source-limited regions to guide personalised medicine.</p>","PeriodicalId":13393,"journal":{"name":"IET nanobiotechnology","volume":"17 3","pages":"281-288"},"PeriodicalIF":2.3,"publicationDate":"2023-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ietresearch.onlinelibrary.wiley.com/doi/epdf/10.1049/nbt2.12123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9836771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Junjie Zhao, Niu Niu, Fan Yang, Haitao Liu, Weibo Qi
{"title":"Preparation, characterisation, and in vitro cancer-suppression function of RNA nanoparticles carrying miR-301b-3p Inhibitor","authors":"Junjie Zhao, Niu Niu, Fan Yang, Haitao Liu, Weibo Qi","doi":"10.1049/nbt2.12120","DOIUrl":"10.1049/nbt2.12120","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Multidrug resistance is the biggest barrier on the way to chemotherapy for lung adenocarcinoma (LUAD). For some LUAD patients with cisplatin (DDP) resistance and poor prognoses, the authors put forward RNA nanoparticles (NPs) carrying miR-301b-3p Inhibitor.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The NPs were composed of miR-301b-3p, A549 aptamer (A549apt), and Cyanine 5 in a bottom-up manner with a 3-way-junction (3WJ) structure. Diameter, assembly process, and morphology of NPs were observed by Dynamic Light Scattering, Native-Polyacrylamide Gel Electrophoresis, and Atomic Force Microscopy. Cell internalisation, toxicity, proliferation, migration, invasion, and apoptosis were assayed by confocal laser scanning microscope, CCK8, colony formation assay, Transwell, western blot, and flow cytometry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>3WJ-apt-miR was evenly distributed, with diameter of 19.61 ± 0.49 nm and triangular branching structures. The accurate delivery of this NP in vivo was ensured by A549 aptamer featuring specific targeting, with smaller side effects than traditional chemotherapy. Such nanomaterials were effectively internalized by cancer cells, with normal cell activity intact. Cancer cell proliferation, invasion, and migration were suppressed, and DDP sensitivity was enhanced, causing DNA damage and facilitating apoptosis of DDP-resistant cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Based on RNA self-assembling, the authors researched the effect of miRNA on DDP sensitivity in LUAD regarding gene regulation. 3WJ-apt-miR paves the way for clinical tumour therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13393,"journal":{"name":"IET nanobiotechnology","volume":"17 3","pages":"224-233"},"PeriodicalIF":2.3,"publicationDate":"2023-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/53/74/NBT2-17-224.PMC10190642.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9487651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evaluation of the parameters affecting the loading of anticancer drug Paclitaxel on coated gold nanoparticles for breast cancer treatment","authors":"Afrooz kharazmi, Neda Attaran","doi":"10.1049/nbt2.12121","DOIUrl":"10.1049/nbt2.12121","url":null,"abstract":"<p>The purpose of this study is the design and synthesis of gold nanoparticles (GNPs) conjugated with paclitaxel and to investigate the parameters affecting the stability of synthesised nanoparticles with drug delivery capability. Here, synthesised GNPs were coated with polyethylene glycol. Then these particles were conjugated with paclitaxel under different conditions and the physical and structural characteristics, as well as the factors affecting the loading of paclitaxel on nanoparticles, were evaluated by ultraviolet spectrophotometer, fourier transform infrared spectroscopy, transmission electron microscopy, dynamic light scattering and zeta potential apparatus. It was found that pegylated GNPs have a limited loading capacity at the time of 24 h of incubation and the Paclitaxel loading was observed to be pH dependent. The use of these particles in the treatment of breast cancer (MCF7) was also investigated using the MTT test. It was determined that the survival percentage of MCF7 cells in the presence of paclitaxel-bound nanoparticles decreases to about 55% at the maximum measured concentration (690 μM).</p>","PeriodicalId":13393,"journal":{"name":"IET nanobiotechnology","volume":"17 3","pages":"234-245"},"PeriodicalIF":2.3,"publicationDate":"2023-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ietresearch.onlinelibrary.wiley.com/doi/epdf/10.1049/nbt2.12121","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9487176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Anionic liposomes prepared without organic solvents for effective siRNA delivery","authors":"Xiu Han, Yan Lu, Zhaoluo Xu, Yanan Chu, Xueping Ma, Haiping Wu, Bingjie Zou, Guohua Zhou","doi":"10.1049/nbt2.12117","DOIUrl":"10.1049/nbt2.12117","url":null,"abstract":"Abstract Currently, organic solvents are necessary for the preparation of anionic liposomes for siRNA delivery. The removal of organic solvent is time‐consuming and the residual organic solvent is not only a hidden danger, but also affects the stability of anionic liposomes. Glycerol, which is physiologically compatible and does not need to be removed, is used to promote the dispersion of lipids and the formation of anionic liposomes. Additionally, the preparation process is simple and not time‐consuming. The results showed that anionic liposomes, which were typically spherical with a particle size of 188.9 nm were successfully prepared with glycerol. And with the help of Ca2+, siRNA was encapsulated in anionic liposomes. The highest encapsulation efficiency at 2.4 mM Ca2+ reached 91%. And the formation of calcium phosphate could promote the endosomal escape of siRNA effectively. The results from cell viability showed that the anionic liposomes had no obvious cytotoxicity. It was also verified that anionic liposomes could improve the resistance of siRNA against degradation. Additionally, siRNA delivered by anionic liposomes could play an effective role in knockout. Therefore, anionic liposomes prepared with glycerol will be a safe and effective delivery platform for siRNA and even other nucleic acid drugs.","PeriodicalId":13393,"journal":{"name":"IET nanobiotechnology","volume":"17 3","pages":"269-280"},"PeriodicalIF":2.3,"publicationDate":"2023-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/28/47/NBT2-17-269.PMC10190622.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9481811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Samaneh Montazeri, Ali Rastegari, Zohreh Mohammadi, Mahboobeh Nazari, Maryam Yousefi, Fatemeh Yazdi Samadi, Somayeh Najafzadeh, Mehdi Aghsami
{"title":"Chitosan nanoparticle loaded by epidermal growth factor as a potential protein carrier for wound healing: In vitro and in vivo studies","authors":"Samaneh Montazeri, Ali Rastegari, Zohreh Mohammadi, Mahboobeh Nazari, Maryam Yousefi, Fatemeh Yazdi Samadi, Somayeh Najafzadeh, Mehdi Aghsami","doi":"10.1049/nbt2.12116","DOIUrl":"10.1049/nbt2.12116","url":null,"abstract":"<p>Epidermal growth factor (EGF) can be efficiently used in wound healing process; but the main obstacle of its clinical use is its susceptibility to proteolysis and maintaining its effective concentration in the site of action. In this study, chitosan nanoparticles containing EGF is formulated using a simple method to increase its stability in physiological pH as well as protect its biological activity and effectiveness in wound healing process. Nanoparticles with different ratios of chitosan/EGF were prepared and evaluated in vitro and in vivo. Obtained results showed nanoparticles with 2:1 ratio of chitosan/EGF were able to release 80% of encapsulated protein after 12 h. Cell proliferation study demonstrated that prepared nanoparticles could protect EGF functionality in physiological pH. In vivo results showed that nanoparticles with 2:1 ratio of chitosan/EGF could significantly accelerate the wound closure-rate, re-epithelialisation and collagen deposition. In conclusion, the designed nanoparticles in optimal ratio can be considered as a potential vehicle for EGF delivery to wounds with the aim of improving healing process.</p>","PeriodicalId":13393,"journal":{"name":"IET nanobiotechnology","volume":"17 3","pages":"204-211"},"PeriodicalIF":2.3,"publicationDate":"2023-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/42/9f/NBT2-17-204.PMC10190615.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9481310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Junru Lu, Yuqi Sheng, Weiheng Qian, Min Pan, Xiangwei Zhao, Qinyu Ge
{"title":"scRNA-seq data analysis method to improve analysis performance","authors":"Junru Lu, Yuqi Sheng, Weiheng Qian, Min Pan, Xiangwei Zhao, Qinyu Ge","doi":"10.1049/nbt2.12115","DOIUrl":"10.1049/nbt2.12115","url":null,"abstract":"<p>With the development of single-cell RNA sequencing technology (scRNA-seq), we have the ability to study biological questions at the level of the individual cell transcriptome. Nowadays, many analysis tools, specifically suitable for single-cell RNA sequencing data, have been developed. In this review, the currently commonly used scRNA-seq protocols are discussed. The upstream processing flow pipeline of scRNA-seq data, including goals and popular tools for reads mapping and expression quantification, quality control, normalization, imputation, and batch effect removal is also introduced. Finally, methods to evaluate these tools in both cellular and genetic dimensions, clustering and differential expression analysis are presented.</p>","PeriodicalId":13393,"journal":{"name":"IET nanobiotechnology","volume":"17 3","pages":"246-256"},"PeriodicalIF":2.3,"publicationDate":"2023-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1a/cb/NBT2-17-246.PMC10190501.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9487142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Synergistic effects of 3D chitosan-based hybrid scaffolds and mesenchymal stem cells in orthopaedic tissue engineering","authors":"Ping Qi, Zhaohui Ning, Xiuju Zhang","doi":"10.1049/nbt2.12103","DOIUrl":"10.1049/nbt2.12103","url":null,"abstract":"<p>Restoration of damaged bone and cartilage tissue with biomaterial scaffolds is an area of interest in orthopaedics. Chitosan is among the low-cost biomaterials used as scaffolds with considerable biocompability to almost every human tissue. Considerable osteoconductivity, porosity, and appropriate pore size distribution have made chitosan an appropriate scaffold for loading of stem cells and a good homing place for differentiation of stem cells to bone tissue. Moreover, the similarity of chitosan to glycosaminoglycans and its potential to be used as soft gels, which could be lasting more than 1 week in mobile chondral defects, has made chitosan a polymer of interest in repairing bone and cartilage defects. Different types of scaffolds using chitosan in combination with mesenchymal stem cells (MSCs) are discussed. MSCs are widely used in regenerative medicine because of their regenerative ability, and recent line evidence reviewed demonstrated that the combination of MSCs with a combination of chitosan with different materials, including collagen type 1, hyaluronic acid, Poly(L-lacticacid)/gelatin/β-tricalcium phosphate, gamma-poly[glutamic acid] polyelectrolyte/titanium alloy, modified Poly(L-Lactide-co-Epsilon-Caprolactone), calcium phosphate, β-glycerophosphate hydrogel/calcium phosphate cement (CPC), and CPC-Chitosan-RGD, can increase the efficacy of using MSCs, and chitosan-based stem cell delivery can be a promising method in restoration of damaged bone and cartilage tissue.</p>","PeriodicalId":13393,"journal":{"name":"IET nanobiotechnology","volume":"17 2","pages":"41-48"},"PeriodicalIF":2.3,"publicationDate":"2023-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ietresearch.onlinelibrary.wiley.com/doi/epdf/10.1049/nbt2.12103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9325829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Fabrication of nano-encapsulated angelica (Heracleum persicum) essential oil for enriching dairy dessert: Physicochemical, rheological and sensorial properties","authors":"Narin Mhemmedamin Nanakali","doi":"10.1049/nbt2.12112","DOIUrl":"10.1049/nbt2.12112","url":null,"abstract":"<p>In this study, the nanoemulsions containing angelica essential oil (AEO) was used as a novel nano-carrier for enrichment of dairy dessert. Firstly, oil-in-water nanoemulsions were prepared by different levels of GE (1%, 5%, 10%, and 15%) as the dispersed phase, Tween 80 as surfactant with a constant surfactant to essential oil ratio (1:1), and distillated water as a continuous phase. Droplet size, free radical scavenging capacity, antimicrobial activity against gram-positive (<i>Staphylococcus aureus</i> (<i>25923 ATCC</i>)) and gram-negative (<i>Escherichia coli H7 O157 (700728 ATCC</i>)) were evaluated for produced nanoemulsions. The mean droplet size of nanoemulsion increased from 75 to 95 nm and antioxidant capacity also enhanced from 15.4% to 30.2% by increasing AEO level from 1% to 15%. Antimicrobial analysis by disk diffusion methods for nanoemulsions containing different levels of AEO cleared that nanoemulsions with high levels of AEO showed the stronger antimicrobial activity against both used bacteria and especially more activity against <i>Staphylococcus aureus</i>. The results of the total count and yeast and mould count show that the nanoemulsions with different levels of AEO have been effective on the number of microorganisms, particularly during storage. The incorporation of pure essential oil and nanoemulsions with different levels of AEO did not affect significantly the pH of different dessert samples however, they affected the dry matter and free radical scavenging capacity. Adding of nanoemulsions with different levels of AEO to the desserts had a considerable effect on the rheological properties including apparent viscosity, Gʹ, G\", Tan <i>δ</i> and complex viscosity and all samples showed shear-thining behaviour. Results from organoleptic characteristics (taste, odour colour, mouthfeel and total acceptance) showed that enriched samples by nanoemulsions, particularly with higher level of AEO had higher sensorial scores. In general, samples containing free AEO (not encapsulated) had the lower scores in all organoleptic characteristics.</p>","PeriodicalId":13393,"journal":{"name":"IET nanobiotechnology","volume":"17 3","pages":"171-181"},"PeriodicalIF":2.3,"publicationDate":"2023-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ietresearch.onlinelibrary.wiley.com/doi/epdf/10.1049/nbt2.12112","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9482263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The inhibition of ORMDL3 prevents Alzheimer's disease through ferroptosis by PERK/ATF4/HSPA5 pathway","authors":"Yankun Shao, Yilin Xu, Huang Di, Xinxiu Shi, Yingying Wang, Hongyu Liu, Lina Song","doi":"10.1049/nbt2.12113","DOIUrl":"10.1049/nbt2.12113","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Alzheimer's disease (AD) is a neurodegenerative disease with high incidence and widespread attention. There is currently no clear clarification of the pathogenesis. However, ORMDL3 causes ferroptosis in AD, and the potential mechanisms remain unclear. So, this study explore the function of ORMDL3 on ferroptosis in AD and its potential regulatory mechanisms. APPswe/PS1dE9 mice and C57BL/6 mice were induced into the mice model. The murine microglial BV-2 cells also were induced into the vitro model. In serum samples of AD patients, ORMDL3 mRNA expression levels were upregulated. The serum ORMDL3 levels expression was positively related to the ADL score or MoCA score in AD patients. The serum ORMDL3 expression level was positively related to MMSE score or Hcy levels in AD patients. The mRNA expression of ORMDL3 in the hippocampal tissue of the mice model of AD was upregulated at one, four and eight months. The protein expression of ORMDL3 was upregulated in the mice model of AD. ORMDL3 promoted Alzheimer's disease, and increased oxidative response and ferroptosis in a model of AD. PERK/ATF4/HSPA5 pathway is one important signal pathway for the effects of ORMDL3 in a model of AD. Collectively, these data suggested that ORMDL3 promoted oxidative response and ferroptosis in a model of AD by the PERK/ATF4/HSPA5 pathway, which might be a novel target spot mechanism of ferroptosis in AD and may serve as a regulator of AD-induced ferroptosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13393,"journal":{"name":"IET nanobiotechnology","volume":"17 3","pages":"182-196"},"PeriodicalIF":2.3,"publicationDate":"2023-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/99/d3/NBT2-17-182.PMC10190607.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9836189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Optically driven microtools with an antibody-immobilised surface for on-site cell assembly","authors":"Shuntaro Mori, Takumi Ito, Hidekuni Takao, Fusao Shimokawa, Kyohei Terao","doi":"10.1049/nbt2.12114","DOIUrl":"10.1049/nbt2.12114","url":null,"abstract":"<p>To enable the accurate reproduction of organs in vitro, and improve drug screening efficiency and regenerative medicine research, it is necessary to assemble cells with single-cell resolution to form cell clusters. However, a method to assemble such forms has not been developed. In this study, a platform for on-site cell assembly at the single-cell level using optically driven microtools in a microfluidic device is developed. The microtool was fabricated by SU-8 photolithography, and antibodies were immobilised on its surface. The cells were captured by the microtool through the bindings between the antibodies on the microtool and the antigens on the cell membrane. Transmembrane proteins, CD51/61 and CD44 that facilitate cell adhesion, commonly found on the surface of cancer cells were targeted. The microtool containing antibodies for CD51/61 and CD44 proteins was manipulated using optical tweezers to capture HeLa cells placed on a microfluidic device. A comparison of the adhesion rates of different surface treatments showed the superiority of the antibody-immobilised microtool. The assembly of multiple cells into a cluster by repeating the cell capture process is further demonstrated. The geometry and surface function of the microtool can be modified according to the cell assembly requirements. The platform can be used in regenerative medicine and drug screening to produce cell clusters that closely resemble tissues and organs in vivo.</p>","PeriodicalId":13393,"journal":{"name":"IET nanobiotechnology","volume":"17 3","pages":"197-203"},"PeriodicalIF":2.3,"publicationDate":"2023-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f3/78/NBT2-17-197.PMC10190638.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9481291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}