{"title":"Tumor Microenvironment-Responsive Zn(II)-Porphyrin Nanotheranostics for Targeted Sonodynamic Therapy.","authors":"Jiaxin Li, Zhitong Zhao, Yongchang Tian, Wenchang Liu, Peng Zhang, Li Chen","doi":"10.1021/acsbiomaterials.4c00344","DOIUrl":"10.1021/acsbiomaterials.4c00344","url":null,"abstract":"<p><p>As a novel noninvasive tumor therapy, sonodynamic therapy (SDT) attracts booming concerns. However, the limited water solubility, inadequate biocompatibility, and low targeting ability of conventional sonosensitizers significantly hinder their potential for clinical application. Herein, novel zinc(II)-porphyrin nanotheranostics (HA@Zn-TCPP) were fabricated in which the zinc(II)-porphyrin (TCPP) metal-organic framework was first constructed by a simple thermal reaction, followed by the addition of hyaluronic acid (HA) for modification. The specific targeting ability of HA facilitated the internalization of HA@Zn-TCPP within tumor cells, resulting in its preferential accumulation in tumor tissues that exhibit CD44 receptor overexpression. The acidic tumor microenvironment induced the rapid decomposition of HA@Zn-TCPP, releasing free TCPP for activating SDT. This controllable generation of reactive oxygen species (ROS) could effectively decrease damage to normal tissues. The HA@Zn-TCPP exhibited remarkable antitumor effects in experiments, achieving a tumor inhibition rate of up to 82.1% when under ultrasound. This finding provides an imperative strategy to develop novel sonosensitizers for enhanced SDT.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Omiganan-Based Synthetic Antimicrobial Peptides for the Healthcare of Infectious Endophthalmitis.","authors":"Shuo Wang, Zhan Yuin Ong, Sheng Qu, Yongjie Wang, Jingguo Xin, Zhi Zheng, Hong Wu","doi":"10.1021/acsbiomaterials.4c01544","DOIUrl":"10.1021/acsbiomaterials.4c01544","url":null,"abstract":"<p><p>Bacterial endophthalmitis is a severe infection of the aqueous or vitreous humor of the eye that can lead to permanent vision loss. Due to the rapid emergence of antibiotic resistance and dose-limiting toxicities, the standard treatment of bacterial endophthalmitis via the intravitreal injection of broad-spectrum antibiotics remains inadequate. Membrane active cationic antimicrobial peptides (AMPs) have emerged as a promising class of effective and broad-spectrum antimicrobial agents with potential to overcome antibiotic resistance. In this work, we investigate, for the first time, the use of omiganan (IK-12), a 12-amino acid indolicidin derivative for the treatment of bacterial endophthalmitis. Additionally, IK-12 was used as a template to perform amino acid rearrangements, without altering the length or type of amino acids, to yield a series of new derivative AMPs with varying extents of secondary structure formation under membrane mimicking conditions. IK-12 and its derivatives demonstrated strong and broad-spectrum antibacterial activities against a panel of clinically isolated Gram-positive and Gram-negative bacteria, including methicillin-resistant <i>Staphylococcus aureus</i> commonly implicated in bacterial endophthalmitis. Interestingly, two of the new IK-12 derivatives, IP-12 and WP-12, showed lower geometric mean minimum inhibitory concentration and higher 50% hemolysis concentration values, which effectively translated into 2- to 3.4-fold higher bacterial selectivity than the parent IK-12. Furthermore, the intravitreal injection of IK-12, IP-12, and WP-12 in a rabbit model of <i>MRSA</i>-induced endophthalmitis led to considerably improved clinical presentation and reduced recruitment of inflammatory cells. In all, these results demonstrate the potential of IK-12 and its derivatives, IP-12 and WP-12, as promising candidates for the treatment of bacterial endophthalmitis.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142490987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrada-Ioana Damian-Buda, Irem Unalan, Aldo R Boccaccini
{"title":"Combining Mesoporous Bioactive Glass Nanoparticles (MBGNs) with Essential Oils to Tackle Bacterial Infection and Oxidative Stress for Bone Regeneration Applications.","authors":"Andrada-Ioana Damian-Buda, Irem Unalan, Aldo R Boccaccini","doi":"10.1021/acsbiomaterials.4c00218","DOIUrl":"10.1021/acsbiomaterials.4c00218","url":null,"abstract":"<p><p>Bacterial infectious diseases remain one of the significant challenges in the field of bone regeneration applications. Despite the development of new antibiotics, their improper administration has led to the development of multiresistant bacterial strains. In this study, we proposed a novel approach to tackle this problem by loading clove oil (CLV), a natural antibacterial compound, into amino-functionalized mesoporous bioactive glass nanoparticles (MBGNs). The scanning electron microscopy images (SEM) revealed that amino-functionalization and CLV loading did not affect the shape and size of the MBGNs. The successful grafting of the amino groups on the MBGNs' surface and the presence of CLV in the material were confirmed by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy and zeta potential measurements. The increased CLV concentration led to a higher loading capacity, encapsulation efficiency, and antioxidant activity. The <i>in vitro</i> CLV release profile exhibited an initial burst release, followed by a controlled release over 14 days. The loading of CLV into MBGNs led to a stronger antibacterial effect against <i>E. coli</i> and <i>S. aureus</i>, while MG-63 osteoblast-like cell viability was enhanced with no morphological changes compared to the control group. In conclusion, the CLV-MBGNs nanocarriers showed promising properties <i>in vitro</i> as novel drug delivery systems, exploiting essential oils for treating bone infections and oxidative stress.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Glutaraldehyde Cross-Linking of Salt-Induced Fibrinogen Hydrogels.","authors":"Dominik Hense, Oliver I Strube","doi":"10.1021/acsbiomaterials.4c01412","DOIUrl":"10.1021/acsbiomaterials.4c01412","url":null,"abstract":"<p><p>Covalent cross-linking is a common strategy to improve the mechanical properties of biological polymers. The most prominent field of application of such materials is in medicine, for example, in the form of bioprinting, drug delivery, and wound sealants. One biological polymer of particular interest is the blood clotting protein fibrinogen. In the natural process, fibrinogen polymerizes to fibrous hydrogel fibrin. Although the material shows great potential, its costs are very high due to the required enzyme thrombin. Recently, we introduced several approaches to trigger a thrombin-free fibrillogenesis of fibrinogen to a fibrin-like material. Inspired by the natural pathway of blood clotting in which covalent cross-linking stabilizes the clot, this \"pseudofibrin\" is now developed even further by covalently cross-linking the fibers. In particular, the effect of inexpensive glutaraldehyde on fiber morphology, rheological properties, and irreversible gel dissolution is investigated. Additionally, new insights into the reaction kinetics between fibrinogen and glutaraldehyde are gained. It could be shown that the fibrous structure of pseudofibrin can be retained during cross-linking and that glutaraldehyde significantly improves rheological properties of the hydrogels. Even more important, cross-linking with glutaraldehyde can prevent dissolution of the gels at elevated temperatures.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marcin Luty, Renata Szydlak, Joanna Pabijan, Joanna Zemła, Ingrid H Oevreeide, Victorien E Prot, Bjørn T Stokke, Malgorzata Lekka, Bartlomiej Zapotoczny
{"title":"Tubulin-Targeted Therapy in Melanoma Increases the Cell Migration Potential by Activation of the Actomyosin Cytoskeleton─An In Vitro Study.","authors":"Marcin Luty, Renata Szydlak, Joanna Pabijan, Joanna Zemła, Ingrid H Oevreeide, Victorien E Prot, Bjørn T Stokke, Malgorzata Lekka, Bartlomiej Zapotoczny","doi":"10.1021/acsbiomaterials.4c01226","DOIUrl":"10.1021/acsbiomaterials.4c01226","url":null,"abstract":"<p><p>One of the most dangerous aspects of cancers is their ability to metastasize, which is the leading cause of death. Hence, it holds significance to develop therapies targeting the eradication of cancer cells in parallel, inhibiting metastases in cells surviving the applied therapy. Here, we focused on two melanoma cell lines─WM35 and WM266-4─representing the less and more invasive melanomas. We investigated the mechanisms of cellular processes regulating the activation of actomyosin as an effect of colchicine treatment. Additionally, we investigated the biophysical aspects of supplement therapy using Rho-associated protein kinase (ROCK) inhibitor (Y-27632) and myosin II inhibitor ((-)-blebbistatin), focusing on the microtubules and actin filaments. We analyzed their effect on the proliferation, migration, and invasiveness of melanoma cells, supported by studies on cytoskeletal architecture using confocal fluorescence microscopy and nanomechanics using atomic force microscopy (AFM) and microconstriction channels. Our results showed that colchicine inhibits the migration of most melanoma cells, while for a small cell population, it paradoxically increases their migration and invasiveness. These changes are also accompanied by the formation of stress fibers, compensating for the loss of microtubules. Simultaneous administration of selected agents led to the inhibition of this compensatory effect. Collectively, our results highlighted that colchicine led to actomyosin activation and increased the level of cancer cell invasiveness. We emphasized that a cellular pathway of Rho-ROCK-dependent actomyosin contraction is responsible for the increased invasive potential of melanoma cells in tubulin-targeted therapy.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Graphene-Based Wound Dressings for Wound Healing: Mechanism, Technical Analysis, and Application Status.","authors":"Shanguo Zhang, Tianyi Jiang, Ming Li, Haoxiu Sun, Hao Wu, Wenlong Wu, Yu Li, Hongyuan Jiang","doi":"10.1021/acsbiomaterials.4c01142","DOIUrl":"10.1021/acsbiomaterials.4c01142","url":null,"abstract":"<p><p>The development of novel wound dressings is critical in medical care. Graphene and its derivatives possess excellent biomedical properties, making them highly suitable for various applications in medical dressings. This review provides a comprehensive technical analysis and the current application status of graphene-based medical dressings. Initially, we discuss the chemical structure and the fabrication method of graphene and its derivatives. We then provide a detailed summary of the mechanisms by which graphene materials promote wound repair across the four stages of wound healing. Subsequently, we categorize the types of graphene-based wound dressings and analyze corresponding characteristics. Finally, we analyze the challenges encountered at present and propose solutions regarding future development trends. This paper aims to serve as a reference for further research in skin tissue engineering and the development of innovative graphene-based medical dressings.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nanoparticles Fueled by Enzyme for the Treatment of Hyperlipidemic Acute Pancreatitis.","authors":"Geer Chen, Yunfeng Huang, Haohui Yu, Junru Wang, Haobing Li, Shuqi Shen, Xingjian Zhou, Keqing Shi, Hongwei Sun","doi":"10.1021/acsbiomaterials.4c00474","DOIUrl":"10.1021/acsbiomaterials.4c00474","url":null,"abstract":"<p><p>Hyperlipidemic acute pancreatitis (HAP) is a serious inflammatory pancreatic disease commonly seen in patients with disorders of lipid metabolism. Decreasing blood triglyceride levels and proinflammatory factors can alleviate hyperlipidemic pancreatitis. The lipase that enhanced the Brownian motion of mesoporous silica in triglyceride solutions could accelerate decomposition of the lipid and improve the efficiency of absorption. In this study, we developed a mesoporous silica nanoparticle with dual modification of IL-6 aptamer and lipase for the treatment of HAP. The nanoparticle could increase the ability of particles to absorb inflammatory factor IL-6 and decompose triglycerides. For every 10 mg of the dual-modified nanoparticles, the efficiency of capturing IL-6 was approximately 9.67 pg/mL and of decomposing triglycerides was approximately 3.88 mg/mL in the plasma of HAP patients within 2 h. In summary, the mesoporous silica nanoparticle could absorb the IL-6 inflammatory factor through IL-6 aptamers and decompose triglycerides through lipase. Furthermore, based on clinically available plasma exchange technology, combined with our developed dual-modified nanoparticles, we designed an absorption device for the treatment of hyperlipidemic pancreatitis; it works to promote the treatment of hyperlipidemic pancreatitis.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yang Xiao, Xinyi Guo, Weiwei Zhang, Lequn Ma, Kewei Ren
{"title":"DNA Nanotechnology for Application in Targeted Protein Degradation.","authors":"Yang Xiao, Xinyi Guo, Weiwei Zhang, Lequn Ma, Kewei Ren","doi":"10.1021/acsbiomaterials.4c01351","DOIUrl":"10.1021/acsbiomaterials.4c01351","url":null,"abstract":"<p><p>DNA is a kind of flexible and versatile biomaterial for constructing nanostructures and nanodevices. Due to high biocompatibility and programmability and easy modification and fabrication, DNA nanotechnology has emerged as a powerful tool for application in intracellular targeted protein degradation. In this review, we summarize the recent advances in the design and mechanism of targeted protein degradation technologies such as protein hydrolysis targeted chimeras, lysosomal targeted chimeras, and autophagy based protein degradation. Subsequently, we introduce the DNA nanotechnologies of DNA cascade circuits, DNA nanostructures, and dynamic machines. Moreover, we present the latest developments in DNA nanotechnologies in targeted protein degradation. Finally, the vision and challenges are discussed.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mona Zolfaghar, Prabha Acharya, Pranav Joshi, Na Young Choi, Sunil Shrestha, Vinod Kumar Reddy Lekkala, Soo-Yeon Kang, Minseong Lee, Moo-Yeal Lee
{"title":"Cryopreservation of Neuroectoderm on a Pillar Plate and <i>In Situ</i> Differentiation into Human Brain Organoids.","authors":"Mona Zolfaghar, Prabha Acharya, Pranav Joshi, Na Young Choi, Sunil Shrestha, Vinod Kumar Reddy Lekkala, Soo-Yeon Kang, Minseong Lee, Moo-Yeal Lee","doi":"10.1021/acsbiomaterials.4c01383","DOIUrl":"10.1021/acsbiomaterials.4c01383","url":null,"abstract":"<p><p>Cryopreservation in cryovials extends cell storage at low temperatures, and advances in organoid cryopreservation improve reproducibility and reduce generation time. However, cryopreserving human organoids presents challenges due to the limited diffusion of cryoprotective agents (CPAs) into the organoid core and the potential toxicity of these agents. To overcome these obstacles, we developed a cryopreservation technique using a pillar plate platform. To demonstrate cryopreservation application to human brain organoids (HBOs), early stage HBOs were produced by differentiating induced pluripotent stem cells (iPSCs) into neuroectoderm (NE) in an ultralow attachment (ULA) 384-well plate. The NE was transferred and encapsulated in Matrigel on the pillar plate. The NE on the pillar plate was exposed to four commercially available CPAs, including the PSC cryopreservation kit, CryoStor CS10, 3dGRO, and 10% DMSO, before being frozen overnight at -80 °C and subsequently stored in a liquid nitrogen dewar. We examined the impact of the CPA type, organoid size, and CPA exposure duration on cell viability post-thaw. Additionally, the differentiation of NE into HBOs on the pillar plate was assessed using RT-qPCR and immunofluorescence staining. The PSC cryopreservation kit proved to be the least toxic for preserving the early stage HBOs on the pillar plate. Notably, smaller HBOs showed higher cell viability postcryopreservation than larger ones. An incubation period of 80 min with the PSC kit was essential to ensure optimal CPA diffusion into HBOs with a diameter of 400-600 μm. These cryopreserved early stage HBOs successfully matured over 30 days, exhibiting gene expression patterns akin to noncryopreserved HBOs. The cryopreserved early stage HBOs on the pillar plate maintained high viability after thawing and successfully differentiated into mature HBOs. This on-chip cryopreservation method could extend to other small organoids, by integrating cryopreservation, thawing, culturing, staining, rinsing, and imaging processes within a single system, thereby preserving the 3D structure of the organoids.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142490985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Payton J Martinez, Jane J Song, Jair I Castillo, John DeSisto, Kang-Ho Song, Adam L Green, Mark Borden
{"title":"Effect of Microbubble Size, Composition, and Multiple Sonication Points on Sterile Inflammatory Response in Focused Ultrasound-Mediated Blood-Brain Barrier Opening.","authors":"Payton J Martinez, Jane J Song, Jair I Castillo, John DeSisto, Kang-Ho Song, Adam L Green, Mark Borden","doi":"10.1021/acsbiomaterials.4c00777","DOIUrl":"10.1021/acsbiomaterials.4c00777","url":null,"abstract":"<p><p>Blood-brain barrier opening (BBBO) using focused ultrasound (FUS) and microbubbles (MBs) has emerged as a promising technique for delivering therapeutics to the brain. However, the influence of various FUS and MB parameters on BBBO and subsequent sterile inflammatory response (SIR) remains unclear. In this study, we investigated the effects of MB size and composition, as well as the number of FUS sonication points, on BBBO and SIR in an immunocompetent mouse model. Using MRI-guided MB + FUS, we targeted the striatum and assessed extravasation of an MRI contrast agent to assess BBBO and RNaseq to assess SIR. Our results revealed distinct effects of these parameters on BBBO and SIR. Specifically, at a matched microbubble volume dose (MVD), MB size did not affect the extent of BBBO, but smaller (1 μm diameter) MBs exhibited a lower classification of SIR than larger (3 or 5 μm diameter) MBs. Lipid-shelled microbubbles exhibited greater BBBO and a more pronounced SIR compared to albumin-shelled microbubbles, likely owing to the latter's poor <i>in vivo</i> stability. As expected, increasing the number of sonication points resulted in greater BBBO and SIR. Furthermore, correlation analysis revealed strong associations between passive cavitation detection measurements of harmonic and inertial MB echoes, BBBO, and the expression of SIR gene sets. Our findings highlight the critical role of MB and FUS parameters in modulating BBBO and subsequent SIR in the brain. These insights inform the development of targeted drug delivery strategies and the mitigation of adverse inflammatory reactions in neurological disorders.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}