Yunxiao Li, Bin Zhou, Jiayu Zhang, Yuenan Yang, Qianqian Cui
{"title":"miR-421-Loaded Chitosan Nanoparticles Suppress the Malignant Characteristics of Colorectal Cancer Cells","authors":"Yunxiao Li, Bin Zhou, Jiayu Zhang, Yuenan Yang, Qianqian Cui","doi":"10.1166/jbn.2024.3790","DOIUrl":"https://doi.org/10.1166/jbn.2024.3790","url":null,"abstract":"Rectal cancer (RC) is a destructive cancer and long-term chemotherapy often leads to decreased drug sensitivity. This study investigates the role of chitosan nanoparticles (NPs) carrying miR-421 in RC and the mechanism underlying its inhibitory effect on malignant characteristics of\u0000 RC cells through Wnt/β-catenin signaling pathway. miR-421-loaded chitosan NPs were prepared, and then HR8348 cells were divided into model group, control group, chitosan NPs group (nano-group), miR-421 group and chitosan NPs carrying miR-421 group (nano+miR-421 group), Wnt1 overexpression\u0000 group (pc-Wnt1 group), Wnt1 inhibition group (si-Wnt1 group), and nano+miR-421+si-Wnt1 group, in which the cells received corresponding treatment. After treatment,Wnt1/β-catenin and c-Myc expression in RC cells was detected and the target gene of miR-421 was identified. Various\u0000 experiments were conducted to assess the malignant biological behavior of RC cells. Chitosan NPs carrying miR-421 significantly suppressed migration and proliferation of RC cells and promoted apoptosis. The advent of miR-421 inhibited the increase of Wnt1/β-catenin expression,\u0000 while Wnt1 inhibitor, as such, controlled characteristics of RC cells, and the inhibitory role of chitosan NPs carrying miR-421 was the most prominent. The bioinformatics software RegRNA 2.0 predicted Wnt1/β-catenin as the specific target gene regulated by miR-421. Chitosan NPs\u0000 loaded with miR-421 effectively inhibit RC cell growth through blocking the Wnt1/β-catenin signaling pathway and down-regulating the expression of c-Myc.","PeriodicalId":15260,"journal":{"name":"Journal of biomedical nanotechnology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140086204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Effect of Silk Fibroin/Poly(Lactic-Co-Glycolic Acid) Nanofiber Coating on Porous Calcium Phosphate-Based Composites for Osteoporosis Application","authors":"Qiao Ren, Qinggui Li, Ligang Qian","doi":"10.1166/jbn.2024.3785","DOIUrl":"https://doi.org/10.1166/jbn.2024.3785","url":null,"abstract":"This study observed whether the silk fibroin/poly lactic-co-glycolic acid (SF/PLGA) nanofiber membrane three-dimensionally coated with porous calcium phosphate-based composite can promote the proliferation of osteoblasts, thereby improving osteoporosis. The SF/PLGA nanofiber membrane\u0000 was used to three-dimensionally coated with the porous calcium phosphate-based composite to analyze proliferation of osteoblasts, hFOB1.19 expressions by Western blot, activity change of hFOB1.19 by CCK-8 assay. The morphology was observed with an electron microscope. Alizarin Red staining\u0000 showed that the SF/PLGA nanofiber membrane three-dimensionally coated with porous calcium phosphatebased composite promoted osteogenic differentiation and upregulated the expression of osteogenic related genes. It inhibited adipogenic differentiation and the expression of adipogenic genes.\u0000 SF/PLGA composite material promoted the viability of osteoblasts hFOB1.19, upregulatedGLUT3, downregulated the expression of various apoptosis-related proteins in hFOB1.19. SF/PLGA composite material can reduce the apoptosis efficiency of osteoblasts, promote the proliferation of osteoblasts,\u0000 and inhibit apoptosis, thereby improving osteoporosis.","PeriodicalId":15260,"journal":{"name":"Journal of biomedical nanotechnology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140091489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zequn Zhang, Chen Meng, Zhigong Wang, Yan Huang, X. Lü
{"title":"The Effect of Silver Nanoparticles on the Electrical Activity of PC12 Quasi-Neuronal Networks and the Comparison of Two Microelectrode Array-Based Neural Signal Analysis Methods","authors":"Zequn Zhang, Chen Meng, Zhigong Wang, Yan Huang, X. Lü","doi":"10.1166/jbn.2024.3792","DOIUrl":"https://doi.org/10.1166/jbn.2024.3792","url":null,"abstract":"Our research group previously proposed the voltage thresholdmeasurement method (VTMM) based on the microelectrode array (MEA), and used VTMM to prove that PC12 cells, as a simpler cell culture, can be used as an alternative cell model to examine the effects of external factors on cytotoxicity\u0000 and electrical excitability of neurons. However, there is no comparison between VTMM and the commonly used MEA neural signal analysis method, and no researchers have used the commonly used analysis method to study the spontaneous electrical signals of PC12 quasi-neuronal networks. This research\u0000 aims to compare the characteristics and results of two MEA-based neural signal analysis methods. For the first time, the changes in spike frequency of the PC12 networks after exposure to various concentrations of silver nanoparticles for different durations was studied by means of MEA analysis\u0000 method. It is found that due to the low intensity of spontaneous activity of PC12 networks, the commonly used analysis method is not suitable for the study of electrical activity of PC12 networks. Under the action of silver nanoparticles, the results of VTMM are consistent with those of the\u0000 commonly used MEA analysis method, and VTMM has the advantages of being suitable for more kinds of neuron networks, short culture time, concise and rapid data analysis.","PeriodicalId":15260,"journal":{"name":"Journal of biomedical nanotechnology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140084369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Tarawneh, Arkan H. Al Nawafleh, Moaz M. Altarawneh, Hakim AL Garalleh, Abdulkareem Afandi, Louai A. Maghrabi, Ahmed Ali Husein Qwasmeh, Hatem Abdullah Al Ameryeen, Bilal S. Algnamat, Yarub Al-Douri
{"title":"Preparation and Characterization of Functionalized Multi-Walled Carbon Nanotubes (f-MWCNTs) Incorporated in Gelatin-Based Hydrogel Nanocomposites","authors":"M. Tarawneh, Arkan H. Al Nawafleh, Moaz M. Altarawneh, Hakim AL Garalleh, Abdulkareem Afandi, Louai A. Maghrabi, Ahmed Ali Husein Qwasmeh, Hatem Abdullah Al Ameryeen, Bilal S. Algnamat, Yarub Al-Douri","doi":"10.1166/jbn.2024.3796","DOIUrl":"https://doi.org/10.1166/jbn.2024.3796","url":null,"abstract":"This study prepared gelatin/functionalized multi-walled carbon nanotube (f-MWCNT) nanocomposites with different f-MWCNT concentrations using a simple solution casting method. For each f-MWCNT concentration of the gelatin/f-MWCNT nanocomposites, permittivity parameters were measured\u0000 at five different locations on the sample surface. Cole–Cole graphs were obtained by plotting the imaginary permittivity as a function of the real permittivity. The Havriliak–Negami model was used to obtain the value of alpha, since the shape is a quasi-skewed semicircle. The average\u0000 relaxation time was τ = 12.6 ps and was roughly constant with the addition of f-MWCNTs. Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) images showed increased interactions between the carbon nanotubes and polymers.","PeriodicalId":15260,"journal":{"name":"Journal of biomedical nanotechnology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140084119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Protein–Protein Interaction Network Construction and Differential miRNA Target Gene Prediction in Ovarian Cancer by Bioinformatics Analysis","authors":"Suwei Lan, Jiming Bai, Zhengmao Zhang, Qing Li, Xin-gao Wang, Peng-Hua Cui","doi":"10.1166/jbn.2024.3800","DOIUrl":"https://doi.org/10.1166/jbn.2024.3800","url":null,"abstract":"Our research focused on investigating genetic changes in ovarian cancer (OV) by constructing a protein–protein interaction network. In addition, we utilized data mining techniques that were specifically tailored for OV. To gather differentially expressed miRNAs, we accessed the\u0000 GEO database. The differential expression was administrated using R language. We used three different bioinformatics algorithms to identify the candidate genes of the altered microRNAs. Using Cytoscape, we created a vision constructure between these miRNAs and the corresponding goals. This\u0000 allowed us to identify specific hub genes. To validate our findings, we confirmed the presence of essential genes and autophagy-related genes in both the GEPIA and TCGA databases. Through this process, we were able to pinpoint the connection between them. In total, we identified nine miRNAs\u0000 that showed differential expression. Together, these miRNAs predicted the presence of 488 objective gene. Among them, the FOS demonstrated statistical significance when evaluated in both the GEPIA and TCGA. Importantly, it should be highlighted that FOS has been linked to ovarian cancer\u0000 prognosis.","PeriodicalId":15260,"journal":{"name":"Journal of biomedical nanotechnology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140087659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Reversing Sunitinib Resistance Facilitated by ITGA1 Through the PI3K/Akt/Bcl-2 Pathway Using Nano Co-Delivery System in Renal Cell Carcinoma","authors":"Suxian Hu, Yi Duan, Liting Wang, Jian Yu, Qianqian Guo, Yourong Duan, Ying Sun, Zhihua Wu","doi":"10.1166/jbn.2024.3794","DOIUrl":"https://doi.org/10.1166/jbn.2024.3794","url":null,"abstract":"For genitourinary cancers, renal cell carcinoma (RCC) is the third leading cause of death, while target drug resistance has always been a difficult problem. Integrin alpha 1 (ITGA1) is a member of the integrin family, which is significant for the pathogenesis, development, and drug\u0000 resistance of various malignant tumors. However, it remains unclear for the ITGA1 functions in renal cell carcinoma sunitinib resistance. In this study, we found that the ITGA1 gene facilitates renal cell carcinoma sunitinib resistance through the PI3K/Akt/Bcl-2 signaling pathway. Based on\u0000 this, we developed a co-delivery system designated as Su/Si-PEAL NPs for the synergistic delivery of ITGA1 small interfering RNA (siRNA) and sunitinib using monomethoxy polyethylene glycol-polylactic acid/glycolic acid-poly-L-lysine triblock copolymer (mPEG-PLGA-PLL, PEAL) as the backbone\u0000 material. Furthermore, the results of a series of functional experiments confirmed that this codelivery system was capable of downregulating the expression of ITGA1 and enhancing the sensitivity of 786-O-R cells to sunitinib. This co-delivery system could be an efficient approach for reversing\u0000 sunitinib resistance in renal cell carcinoma.","PeriodicalId":15260,"journal":{"name":"Journal of biomedical nanotechnology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140089680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ghulam Jilany Khan, Sajal Salman, Zhu Chen, Song Li, Hui Chen, Yan Deng, Nongyue He
{"title":"Non-Muscle Myosin IIC as a Prognostic and Therapeutic Target in Cancer","authors":"Ghulam Jilany Khan, Sajal Salman, Zhu Chen, Song Li, Hui Chen, Yan Deng, Nongyue He","doi":"10.1166/jbn.2024.3799","DOIUrl":"https://doi.org/10.1166/jbn.2024.3799","url":null,"abstract":"Cancer metastasis is associated with epithelial-mesenchymal transition (EMT), and NMII is linked to EMT. Calcium sensitization through ROCK activates myosin II, contributing to metastasis. NMII undergoes phosphorylation at Thr18/Ser19, affecting its function and involvement in processes\u0000 like exocytosis, apoptosis, and transcellular intravasations. Inhibition of myosin II ATPase activity blocks cytokinesis, highlighting its role in cell cycle regulation. NMII has distinct binding motifs and sites for regulation, including Thr18/Ser19 via kinases/phosphatases, Ser1/Ser2/Thr9\u0000 via phosphokinase C, and involvement in cytokinesis via contractile ring formation. These characteristics make NMII a potential therapeutic target. NMII-C is found to be less expressive in glioma (40% low expression, 60% high expression), not showing prognostic value. However, in stomach cancer\u0000 (35–65% expression) and renal cancer (40–60% expression), NMII-C appears to have prognostic significance. NMII-C’s prognostic value has not been reported in various other cancers, including thyroid, lung, liver, colorectal, urothelial, endometrial, head and neck, melanoma,\u0000 prostate, testicular, pancreatic, breast, cervical, and ovarian cancers, highlighting a need for further research in these areas. Some pharmacological agents such as Blebbistatin, DT-13, Statins, and Y27632 have shown promising potential against NMII-C in cancer therapy, with positive results\u0000 in pre-clinical studies and ongoing clinical trials. Understanding the specific functions and regulation of NMII isoforms, particularly NMII-C, may provide valuable insights into the development of targeted cancer therapies. Additionally, the study suggests that NMII-C may have prognostic\u0000 importance in specific cancer stages, offering a foundation for further exploration of NMII-C’s mechanisms of action for future medical interventions.","PeriodicalId":15260,"journal":{"name":"Journal of biomedical nanotechnology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140088818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Detection of Hepatoma Serum Marker CD105 with Hemin/Graphene/Aptamer Nanoprobes","authors":"Desong Xia, Xiyu Liu, Yuhan Liao, Huiling Wang, Yanmei Li, Jian He, Jing Zhang, Liping Zhong, Yuhuan Wang","doi":"10.1166/jbn.2024.3791","DOIUrl":"https://doi.org/10.1166/jbn.2024.3791","url":null,"abstract":"CD105 is a serum marker of hepatoma. In this study, we established a stable detection platform constructed using a hemin-graphene-aptamer complex (HGN-apt) by optimizing the ratio of graphene, hemin, and aptamer. We also optimized CD105 detection conditions. The detection limit of this\u0000 platform is 5.5 ng/mL, enabling sensitive detection of CD105. These experiments facilitate an innovative approach for the construction of a detection platform with high sensitivity and an expanded detection range using an HGN-apt probe, enabling specific detection of the serum hepatoma marker\u0000 CD105. Our findings provide an important foundation for early diagnosis of hepatomas, and would therefore help to alleviate patient suffering, including mental and economic burdens. Our platform also offers a quantitative indicator for the prognosis of hepatomas.","PeriodicalId":15260,"journal":{"name":"Journal of biomedical nanotechnology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140083945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Biomedical Application of CT Assisted CBCT 3D Imaging Technology in Oral Implantation","authors":"Xu Wang, Lanlan Zhu","doi":"10.1166/jbn.2024.3780","DOIUrl":"https://doi.org/10.1166/jbn.2024.3780","url":null,"abstract":"In the field of oral implantology, our goals were to investigate the diagnostic utility of traditional CT imaging technology and 3D CBCT imaging technology based on the Internet of Things (IoT) dental Computed Tomography assisted CBCT, as well as to compare and contrast their respective\u0000 advantages. 72 patients were split evenly between two groups: a control group with 35 participants and a study group with 37 participants. (1) Surgical indexes: The operation time of the control group was (27.96+4.64) minutes and (14.08+3.14) minutes, and the intraoperative blood loss was\u0000 (16.36+2.95) ml and (5.85+0.64) ml, respectively. The time it took to do the procedure in the experimental group was (14.08+3.14) minutes. In the group that was under examination, both the total amount of time spent operating and the amount of blood lost during the procedure were significantly\u0000 lower (P <0.05). (2) Dental function: There were no statistically significant variations in dental beauty, comfort, chewing, or retention between the two groups before surgery (P >0.05). This was determined by comparing the results of the dental examinations. After surgery,\u0000 the dental function of the research group was significantly greater than that of the control group, and the difference between the two groups was statistically significant (P <0.05). (3) Theraputic effect: the effective rate of the treatment in the control group was 85.71 percent,\u0000 while the effective rate in the study group was 94.59%. (4) Quality of life: when compared with the control group, the comprehensive quality of life of physiological, social, emotional, and cognitive functions in the research group was higher, and the difference was statistically significant\u0000 (P < 0.05); (5) Satisfaction: the control group’s level of satisfaction was 80.00%, while the study group’s level of satisfaction was 94.59%. (6) Cost: the cost of the treatment in the research group was significantly lower than the cost of the treatment in the control\u0000 group. As a result, the dental computed tomography assisted cone beam computed tomography (CBCT) 3D imaging technology based on the internet of things should be considered for implementation.","PeriodicalId":15260,"journal":{"name":"Journal of biomedical nanotechnology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140085810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lei Yang, Yue Zhang, Jiansong Wu, Lei Wang, Shan Liu, Li Zhou, Jigang Zhang, Chengxin Li
{"title":"Inhibition of HaCaT Proliferation and Imiquimod-Induced Psoriasis by Calcipotriol Through Regulation of the Glutathione/Glutathione Peroxidase 4 Pathway","authors":"Lei Yang, Yue Zhang, Jiansong Wu, Lei Wang, Shan Liu, Li Zhou, Jigang Zhang, Chengxin Li","doi":"10.1166/jbn.2024.3777","DOIUrl":"https://doi.org/10.1166/jbn.2024.3777","url":null,"abstract":"Psoriasis is a chronic and recurrent skin disease characterized by aberrant proliferation and differentiation of keratinocyte cells. Although calcipotriol has been employed in the clinical management of psoriasis, no association between the anti-inflammatory mechanism and iron death\u0000 has been reported. Therefore, we assume that calcipotriol may down-regulate cell activity and suppress the expression of tissue inflammatory factors by regulating the glutathione (GSH) and glutathione peroxidase 4 (GPX4) pathway, thereby alleviating tissue inflammation and ameliorating psoriasis\u0000 symptoms. The experimental groups consisted of a control group, a model group, a Calcipotriol group, and a Calcipotriol+Ferrostatin-1 group. In vitro experiments, a lipopolysaccharides-induced HaCaT cell model was established. In vivo experiments, an imiquimod-induced psoriasis\u0000 mice model was constructed. The results showed that calcipotriol effectively downregulated the expression of GPX4 and GSH, thereby inhibiting HaCaT cell proliferation through modulation of Ki-67 protein expression and DNA breakage. Ferrostatin-1 could partially reverse these effects. Additionally,\u0000 calcipotriol downregulated the expression of GPX4 and GSH in skin tissues and upregulated the expression of long-chain acyl-CoA synthetase 4 by suppressing the levels of SLC7A11 and ferritin, leading to promote the accumulation of ROS and ferroptosis. Moreover, calcipotriol demonstrated inhibitory\u0000 effects on the inflammatory mediators and attenuated skin inflammation. Therefore, calcipotriol effectively ameliorated psoriatic lesions. In conclusion, this study revealed that calcipotriol exerts its therapeutic potential by promoting cellular clearance and suppressing tissue inflammation\u0000 through upregulation of ferroptosis progression. Therefore, this study provides new therapeutic drugs and functions for the treatment of psoriasis.","PeriodicalId":15260,"journal":{"name":"Journal of biomedical nanotechnology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139812364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}