Henry T. Beaman, Ellen Shepherd, J. Satalin, S. Blair, H. Ramcharran, S. Serinelli, L. Gitto, Katheryn Shi Dong, David Fikhman, G. Nieman, S. Schauer, M. B. Monroe
{"title":"Hemostatic Shape Memory Polymer Foams With Improved Survival in a Lethal Traumatic Hemorrhage Model","authors":"Henry T. Beaman, Ellen Shepherd, J. Satalin, S. Blair, H. Ramcharran, S. Serinelli, L. Gitto, Katheryn Shi Dong, David Fikhman, G. Nieman, S. Schauer, M. B. Monroe","doi":"10.2139/ssrn.3864497","DOIUrl":"https://doi.org/10.2139/ssrn.3864497","url":null,"abstract":"Although there are many hemostatic agents available for use on the battlefield, uncontrolled hemorrhage is still the primary cause of preventable death. Current hemostatic dressings include QuikClot® Combat Gauze (QCCG) and XStat®, which have inadequate success in reducing mortality. To address this need, a new hemostatic material was developed using shape memory polymer (SMP) foams, which demonstrate biocompatibility, rapid clotting, and shape recovery to fill the wound site. SMP foam hemostatic efficacy was examined in a lethal, noncompressible porcine liver injury model over 6 hours following injury. Wounds were packed with SMP foams, XStat, or QCCG and compared in terms of time to bleeding cessation, total blood loss, and animal survival. The hemostatic material properties and in vitro blood interactions were also characterized. SMP foams decreased blood loss and active bleeding time in comparison with XStat and QCCG. Most importantly, SMP foams increased the 6-hour survival rate by 50% and 37% (vs. XStat and QCCG, respectively) with significant increases in survival times. Based upon in vitro characterizations, this result is attributed to the low stiffness and shape filling capabilities of SMP foams. This study demonstrates that SMP foams have promise for improving upon current clinically available hemostatic dressings and that hemostatic material properties are important to consider in designing devices for noncompressible bleeding control.","PeriodicalId":8928,"journal":{"name":"Biomaterials eJournal","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81284566","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}
Rongrong Guo, Menghui Liao, Xiaofeng Ma, Yangnan Hu, X. Qian, M. Xiao, Xia Gao, R. Chai, Mingliang Tang
{"title":"Cochlear Implant-Based Electric-Acoustic Stimulation Modulates Neural Stem Cell-Derived Neural Regeneration","authors":"Rongrong Guo, Menghui Liao, Xiaofeng Ma, Yangnan Hu, X. Qian, M. Xiao, Xia Gao, R. Chai, Mingliang Tang","doi":"10.2139/ssrn.3762217","DOIUrl":"https://doi.org/10.2139/ssrn.3762217","url":null,"abstract":"Cochlear implantation is considered to be the best therapeutic method for profound sensorineural hearing loss, but insufficient numbers of functional spiral ganglion neurons hinder the clinical effects of cochlear implantation. Stem cell transplantation has the potential to provide novel strategies for spiral ganglion neuron regeneration after injury. However, some obstacles still need to be overcome, such as low survival and uncontrolled differentiation. Several novel technologies show promise for modulating neural stem cell behaviors to address these issues. Here, a device capable of electrical stimulation was designed by combining a cochlear implant with a graphene substrate. Neural stem cells (NSCs) were cultured on the graphene substrate and subjected to electrical stimulation transduced from sound waves detected by the cochlear implant. Cell behaviors were studied, and this device showed good biocompatibility for NSCs. More importantly, electric-acoustic stimulation with higher frequencies and amplitudes induced NSC death and apoptosis, and electric-acoustic stimulation could promote NSCs to proliferate and differentiate into neurons only when low-frequency stimulation was supplied. The present study provides experimental evidence for understanding the regulatory role of electric-acoustic stimulation on NSCs and highlights the potentials of the above-mentioned device in stem cell therapy for hearing loss treatment.","PeriodicalId":8928,"journal":{"name":"Biomaterials eJournal","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87990882","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}
Li Liu, Xianxian Liang, Xiangxian Xu, Xiang Zhang, Jun Wen, Kun Chen, Xiaodan Su, Zhaogang Teng, Guangming Lu, Jian Xu
{"title":"Magnetic Mesoporous Embolic Microspheres in Transcatheter Arterial Chemoembolization for Liver Cancer","authors":"Li Liu, Xianxian Liang, Xiangxian Xu, Xiang Zhang, Jun Wen, Kun Chen, Xiaodan Su, Zhaogang Teng, Guangming Lu, Jian Xu","doi":"10.2139/ssrn.3757902","DOIUrl":"https://doi.org/10.2139/ssrn.3757902","url":null,"abstract":"Transcatheter arterial chemoembolization (TACE) is the main treatment for liver cancer. Although many embolic agents have been exploited in TACE, embolic agents combining embolization, drug loading, and imaging properties have not yet been constructed. Herein, we report a new magnetic mesoporous embolic microsphere that can simultaneously be loaded with doxorubicin (Dox), block vessels, and be observed by magnetic resonance imaging (MRI). The microspheres were prepared by decorating magnetic polystyrene/Fe3O4 particles with mesoporous organosilica microparticles (denoted as PS/Fe3O4@MONs). The PS/Fe3O4@MONs were uniformly spherical and large (50 μm), with a high specific surface area, uniform mesopores, and a Dox loading capacity of 460.8 μg mg-1. Dox-loaded PS/Fe3O4@MONs (PS/Fe3O4@MON@Dox) effectively inhibited liver cancer cell growth. A VX2 rabbit liver tumor model was constructed to study the efficacy of TACE with PS/Fe3O4@MON@Dox. In vivo, PS/Fe3O4@MON@Dox could be smoothly delivered through an arterial catheter to achieve chemoembolization. Moreover, PS/Fe3O4@MON@Dox and residual tumor parenchyma could be distinguished on MRI, which is of great significance for evaluating the efficacy of TACE. Histopathology showed that PS/Fe3O4@MON@Dox could be deposited in the tumor vessels, completely blocking the blood supply. Overall, PS/Fe3O4@MON@Dox showed good drug loading, embolization and imaging performance as well as potential for use in TACE. STATEMENT OF SIGNIFICANCE: : Transcatheter arterial chemoembolization (TACE) is the main treatment for liver cancer. Although many embolic agents have been exploited in TACE, embolic agents combining embolization, drug-loading, and imaging properties have not yet been constructed. In this work, we prepared magnetic mesoporous microspheres as a new embolic agent that can simultaneously load doxorubicin (Dox), block blood vessels and enable magnetic resonance imaging. Overall, this new embolic microsphere-mediated TACE strategy for liver cancer showed good therapeutic effects, and the PS/Fe3O4@MON@Dox embolic microspheres provide a new avenue for improving the efficacy of TACE for liver cancer and postoperative evaluation.","PeriodicalId":8928,"journal":{"name":"Biomaterials eJournal","volume":"77 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83319700","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":"Examining How Different Carbon Entry Point Affects Recombinant Protein Production from Ethylene Glycol in Bacillus Subtilis","authors":"Wenfa Ng","doi":"10.2139/ssrn.3814484","DOIUrl":"https://doi.org/10.2139/ssrn.3814484","url":null,"abstract":"Recombinant protein production is the first application task for nascent genetic engineering efforts in 1970s. Since then, a variety of basic science and process engineering approaches have been used in improving recombinant protein production. Given that protein production could serve as marker for how well rewired metabolism is functioning, possibility exists in using it to highlight the most suitable pathway for assimilating a particular unconventional substrate. To this end, different pathways with different carbon entry point in central carbon metabolism could be constructed, with fluorescence of a green fluorescent protein as readout. Good carbon entry point should ideally lead to even distribution of substrate flux to all precursors feeding amino acid synthesis, and should result in strong fluorescence intensity and high protein production. This perspective critically examines the literature for prior work on the above hypothesis in relation to utilization of ethylene glycol by Bacillus subtilis. A literature review suggests that the hypothesis is novel, and provides additional information that modulation of global regulatory protein (transcription factor) may serve as ancillary factors promoting high recombinant protein production.","PeriodicalId":8928,"journal":{"name":"Biomaterials eJournal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85488027","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}
S. B. Bon, Irene Chiesa, D. Morselli, M. D. Esposti, P. Fabbri, C. De Maria, Tommaso Foggi Viligiardi, A. Morabito, G. Giorgi, L. Valentini
{"title":"Printable Smart 3D Architectures of Regenerated Silk on Poly(3- Hydroxybutyrate-Co-3-Hydroxyvalerate)","authors":"S. B. Bon, Irene Chiesa, D. Morselli, M. D. Esposti, P. Fabbri, C. De Maria, Tommaso Foggi Viligiardi, A. Morabito, G. Giorgi, L. Valentini","doi":"10.2139/ssrn.3805241","DOIUrl":"https://doi.org/10.2139/ssrn.3805241","url":null,"abstract":"In this study, we report the fabrication of two different three-dimensional (3D) architectures of regenerated silk (RS) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) with embedded functionalities. 3D printed cylinders with an internal layer of PHBV and an external of calcium ions (Ca++) or potassium nitrate (KNO3) modified RS were designed to control the radial shrinkage, water uptake and compression strength. Such cylinders were then used as sutureless thermoresponsive clips, measuring the bursting resistance once applied on an anastomized porcine intestine. Experimental data are supported by finite element simulations that model the tube contraction, demonstrating the possibility to program the shape-changing behavior of 3D printed structures. Printing RS on PHBV, we obtained responsive 3D grids to external force with self-powering properties. The synergic effect obtained by combining materials on appropriate architectures paves the way to potential clinical applications ranging from monitoring of vital signs to sutureless sealant patches.","PeriodicalId":8928,"journal":{"name":"Biomaterials eJournal","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79739718","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}
Yao Chen, Jia Ren, Yufeng Sun, Weiwei Liu, Xiaolong Lu, S. Guan
{"title":"Efficacy of Graphene Nanosheets on the Plasma Sprayed Hydroxyapatite Coating: Improved Strength, Toughness and In-Vitro Bioperformance With Osteoblast","authors":"Yao Chen, Jia Ren, Yufeng Sun, Weiwei Liu, Xiaolong Lu, S. Guan","doi":"10.2139/ssrn.3805229","DOIUrl":"https://doi.org/10.2139/ssrn.3805229","url":null,"abstract":"Abstract Graphene nanosheet (GNS) reinforced HA coating on Ti6Al4V substrate, fabricated using plasma spray, was developed for biomedical applications. Microstructural observation corroborated that the adding GNSs homogeneously distributed in the GNS/HA coating with typical lamellar structure featured by GNSs acting as binder between the discrete HA splats. Meanwhile, GNSs were observed to get in direct contact with HA matrix and form a clean GNS-HA interface without interfacial product. Results of various indentation tests showed simultaneous improvement in both indentation yield strength (~379 MPa) and fracture toughness (0.78 ± 0.17 MPam1/2), mainly attributing to synergetic toughening and strengthening mechanisms associated with the adding GNSs such as load transfer, GNS pull-out, inter-layer sliding of a GNS, crack branching, GNS bridging and crack deflection. In addition, the GNS/HA coating exhibited improved biocompatible with MG-63 cell in terms of its attachment, adhesion strength, proliferation and differentiation. Hence, the GNS/HA composite coating with improved strength, toughness and enhanced biocompatibility makes it a promising candidate for bone regeneration and implantation.","PeriodicalId":8928,"journal":{"name":"Biomaterials eJournal","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81529793","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}
S. Martelli, M. Giorgi, Enrico Dall' Ara, E. Perilli
{"title":"Damage Tolerance and Toughness of Elderly Human Femora","authors":"S. Martelli, M. Giorgi, Enrico Dall' Ara, E. Perilli","doi":"10.2139/ssrn.3726342","DOIUrl":"https://doi.org/10.2139/ssrn.3726342","url":null,"abstract":"Observations of elastic instability of trabecular bone cores supported the analysis of cortical thickness for predicting bone fragility of the hip in people over 60 years of age. Here, we falsified the hypothesis that elastic instability causes minimal energy fracture by analyzing with a micrometric resolution the deformation and fracture behavior of entire femora. Femur specimens were obtained from elderly women aged between 66 - 80 years. Microstructural images of the proximal femur where obtained under 3 - 5 progressively increased loading steps and after fracture. Bone displacements, strain, load bearing and energy absorption capacity were analyzed. Elastic instability of the cortex appeared at early loading stages in regions of peak compression. No elastic instability of trabecular bone was observed. The subchondral bone displayed local crushing in compression at early loading steps and progressed to 8 - 16% compression before fracture. The energy absorption capacity was proportional to the displacement. Stiffness decreased to near-zero values before fracture. Three-fourth of the fracture energy (10.2 - 20.2 J) was dissipated in the final 25% force increment. Fracture occurred in regions of peak tension and shear, adjacent to the location of peak compression, appearing immediately before fracture. Minimal permanent deformation was visible along the fracture surface. Elastic instability modulates the interaction between cortical and trabecular bone promoting an elastically stable fracture behavior of the femur organ, load bearing capacity, toughness, and damage tolerance. These findings will advance current methods for predicting hip fragility.","PeriodicalId":8928,"journal":{"name":"Biomaterials eJournal","volume":"196 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77082068","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}
Phanwipa Wongphan, Theeraphorn Panrong, N. Harnkarnsujarit
{"title":"Effects of Modified Starch on Morphology, Properties and Biodegradation of Thermoplastic Cassava Starch and Pbat Blown Films for Food Packaging","authors":"Phanwipa Wongphan, Theeraphorn Panrong, N. Harnkarnsujarit","doi":"10.2139/ssrn.3936308","DOIUrl":"https://doi.org/10.2139/ssrn.3936308","url":null,"abstract":"Modified starch enhanced the compatibility and modified the properties of thermoplastic starch (TPS) and polybutylene adipate terephthalate (PBAT) biodegradable films. Native (NS), acetylated (AS), octenyl-succinated (OS) and hydroxypropylated (HS) starch were compounded with PBAT via extrusion. PBAT/TPS (40/60 and 50/50 ratios) blend films were produced by blown-film extrusion and characterized for morphology, crystallinity, thermomechanical properties, mechanical and barrier properties. Topographic and scanning electron micrographs showed diverse dispersion and morphologies of starch granules depending on hydrophobicity that governed interface exposure between incompatible polymers. Hydrophilic starch formed phase separated fibrous-like networks entangled in PBAT at higher TPS ratios. Hydrophobic OS starch improved compatibility and interaction with PBAT, greatly modifying mechanical and barrier properties (82-89%). TPS slightly increased α-relaxation temperature and modified arrangements of aromatic structures in PBAT, involving C-H and C-O bonding, subsequently influencing crystallinity of PBAT and the starch phase. Biodegradation of the blend films was dependent on hydrophilicity of starch, giving the fastest degradation in NS and HS. Findings indicated that hydrophobically modified starch improved compatibility with PBAT for biodegradable packaging, while film properties were highly dependent on the morphology of blend matrices.","PeriodicalId":8928,"journal":{"name":"Biomaterials eJournal","volume":"47 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79116032","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}
G. Cerqueni, A. Scalzone, C. Licini, P. Gentile, M. Mattioli-Belmonte
{"title":"Insights into Oxidative Stress in Bone Tissue and Novel Challenges for Biomaterials","authors":"G. Cerqueni, A. Scalzone, C. Licini, P. Gentile, M. Mattioli-Belmonte","doi":"10.2139/ssrn.3751572","DOIUrl":"https://doi.org/10.2139/ssrn.3751572","url":null,"abstract":"The presence of Reactive Oxygen Species (ROS) in bone can influence resident cells behaviour as well as the extra-cellular matrix composition and the tissue architecture. Aging, in addition to excessive overloads, unbalanced diet, smoking, predisposing genetic factors, lead to an increase of ROS and, if it is accompanied with an inappropriate production of scavengers, promotes the generation of oxidative stress that encourages bone catabolism. Furthermore, bone injuries can be triggered by numerous events such as road and sports accidents or tumour resection. Although bone tissue possesses a well-known repair and regeneration capacity, these mechanisms are inefficient in repairing large size defects and bone grafts are often necessary. ROS play a fundamental role in response after the implant introduction and can influence its success. This review provides insights on the mechanisms of oxidative stress generated by an implant in vivo and suitable ways for its modulation. The local delivery of active molecules, such as polyphenols, enhanced bone biomaterial integration evidencing that the management of the oxidative stress is a target for the effectiveness of an implant. Polyphenols have been widely used in medicine for cardiovascular, neurodegenerative, bone disorders and cancer, thanks to their antioxidant and anti-inflammatory properties. In addition, the perspective of new smart biomaterials and molecular medicine for the oxidative stress modulation in a programmable way, by the use of ROS responsive materials or by the targeting of selective molecular pathways involved in ROS generation, will be analysed and discussed critically.","PeriodicalId":8928,"journal":{"name":"Biomaterials eJournal","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76496742","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}
Tanaya Walimbe, Tima Dehghani, A. Casella, Jenny B. Lin, Aijun Wang, A. Panitch
{"title":"Proangiogenic Collagen Binding Glycan Therapeutic Promotes Endothelial Cell Health: Potential Application for the Treatment of Ischemic Wounds","authors":"Tanaya Walimbe, Tima Dehghani, A. Casella, Jenny B. Lin, Aijun Wang, A. Panitch","doi":"10.2139/ssrn.3746791","DOIUrl":"https://doi.org/10.2139/ssrn.3746791","url":null,"abstract":"Peripheral artery disease and endothelial cell dysfunction due to diabetes contribute to impaired neovascularization and poor healing of ischemic wounds. Treatments addressing this underlying ischemia that remain effective in the highly proteolytic diabetic wound environment are urgently needed to increase the rate of wound healing and reduce diabetes-related lower-limb amputations. Our lab has previously designed a collagen-targeted glycan therapeutic (DS-SILY) capable of protecting collagen-based scaffolds from matrix metalloproteinase (MMP) mediated degradation. Building upon this targeted technology, we designed the next generation glycan therapy, termed LXW7-DS-SILY (LDS), to also contain proangiogenic capabilities. By exploiting αvβ3 integrin-mediated VEGF signaling using our previously identified αvβ3 integrin targeted peptide (LXW7), we propose an alternative strategy to overcome shortcomings of traditional growth factor therapy. In this study, we describe the synthesis and optimization of LDS variants and evaluate their angiogenic potential in vitro and in vivo. LDS displayed binding to collagen and endothelial cells. In vitro, the LDS variant with 6 LXW7 peptides increased endothelial cell proliferation, migration, and tubule formation through increased VEGFR2 phosphorylation compared to non-treated controls. In vivo in a chick chorioallantoic membrane (CAM) assay, LDS laden collagen hydrogels increased blood vessel formation by 43% in comparison to organism matched blank hydrogels. Overall, these findings demonstrate the potential of a robust proangiogenic targeted therapeutic for the treatment of ischemic diabetic wounds.","PeriodicalId":8928,"journal":{"name":"Biomaterials eJournal","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81958210","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}