ACS Applied Bio Materials最新文献

{"title":"Noninvasive Monitoring of Palmitoyl Hexapeptide-12 in Human Skin Layers: Mechanical Interaction with Skin Components and Its Potential Skincare Benefits.","authors":"Cosimo Ligorio, Elham Tavasoli, Nevena Karaman-Jurukovska, Abraham Ittycheri, Anna M Kotowska, Mohammed H Khan, David J Scurr, Shovit A Gupta, Leah V Moogan, Jaime Emmetsberger, Fake Lu, Guy K German, Tom Mammone, Alvaro Mata","doi":"10.1021/acsabm.4c01816","DOIUrl":"https://doi.org/10.1021/acsabm.4c01816","url":null,"abstract":"<p><p>Self-assembling peptides (SAPs) represent a rich source of building blocks that interact with biological structures. For instance, cosmetic SAPs like Palmitoyl hexapeptide-12 have gained increasing interest for their anti-aging properties. However, their short-term impact on the skin composition and mechanics remains unclear. In this study, a battery of label-free techniques is exploited to objectively monitor the effects of Palmitoyl hexapeptide-12 on human skin. Orbital trapping secondary ion mass spectrometry (OrbiSIMS) is used to discern between Palmitoyl hexapeptide-12 sol and gel forms, tracking its self-assembly and penetration within full-thickness human skin. Palmitoyl hexapeptide-12 is shown to permeate both stratum corneum and epidermal layers, initiating gel formation by harnessing endogenous ions. Hence, the ability of the peptide to strengthen and repair the skin barrier after delipidation is also demonstrated through a high-throughput mechanical characterization and stimulated Raman scattering (SRS). Finally, the co-assembling properties of Palmitoyl hexapeptide-12 with native skin molecules are shown via <i>in vitro</i> tests and <i>ex vivo</i> histology. This study establishes a methodological benchmark for measuring the effects of cosmetic peptides on skin mechanics and hydration, introducing a platform to design SAPs capable of harnessing native skin molecules to create \"biocooperative\" structures with cosmetic benefits.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439275","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":"Sustained-Release H₂S Nanospheres Regulate the Inflammatory Microenvironment of Wounds, Promote Angiogenesis and Collagen Deposition, and Accelerate Diabetic Wound Healing.","authors":"Bao Hou, Weiwei Cai, Shijie Zhang, Anjing Xu, Yuanyuan Wen, Yutong Wang, Xuexue Zhu, Fangming Wang, Lin Pan, Liying Qiu, Haijian Sun","doi":"10.1021/acsabm.4c01955","DOIUrl":"https://doi.org/10.1021/acsabm.4c01955","url":null,"abstract":"<p><p>Diabetic wounds are blocked in the inflammatory stage, growth factors are degraded, and blood vessels are difficult to regenerate, leading to continuous necrosis and nonhealing of the wound. Hydrogen sulfide (H₂S) plays an important role in the pathophysiological process of wound healing and has a long history of treating skin diseases. Although the sulfide salt solution is the preferred donor of exogenous H₂S, its rapid release rate, excess production, and difficulty in accurately controlling the dose limit its use. Herein, we developed H₂S sustained-release nanospheres NaHS@MS@LP for the treatment of diabetic wounds. NaHS@MS@LP nanosphere was composed of a NaHS-loaded mesoporous silicon core and a DSPE-PEG liposome outer membrane. When NaHS@MS@LP nanospheres were used to treat the wound of diabetic rats, mesoporous silicon was delivered into the cells and the loaded NaHS slowly released H₂S through hydrolysis, participating in all stages of wound healing. In conclusion, NaHS@MS@LP nanospheres regulated the inflammatory microenvironment of wound skin by inducing the transformation of macrophages into M2 type and promoted angiogenesis and collagen deposition to accelerate wound healing in diabetic rats. Our findings provide strategies for the treatment of chronic wounds, including but not limited to diabetic wounds.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447286","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":"M3-DPPE Liposomal Nanoparticles Encapsulating CLEC12A Enhance CD206-Mediated Endocytosis and Efficacy in the Collagen-Induced Arthritis Model.","authors":"Shulin Luo, Junfeng Cai, Feng Yin, Laiya Lu, Zheng Liu, Yunxia Wang, Xiaocong Fu, Shuangfeng Ding, Naoya Kojima, Min Ma","doi":"10.1021/acsabm.4c01139","DOIUrl":"10.1021/acsabm.4c01139","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the efficacy of M3-DPPE liposomal nanoparticles encapsulated with mRNA encoding cytokines (M3-mRNAs) in targeting macrophages for the treatment of inflammation-induced joint injury.</p><p><strong>Methods: </strong><i>in vitro</i>, M3-mRNAs were administered to peritoneal exudate macrophages (PEMs), and the uptake was assessed using flow cytometry. The mechanism of uptake was investigated by blocking the CLEC12A pathway with M3-SiCLEC12A and observing CD206-mediated endocytosis. In vivo, the distribution of Dir-labeled M3-drugs was monitored using IVIS imaging, and its accumulation in inflammatory and noninflammatory areas was evaluated. The therapeutic potential was evaluated in collagen-induced arthritis (CIA) model mice by assessing macrophage polarization, joint pathology, and cytokine expression.</p><p><strong>Results: </strong><i>in vitro</i> studies demonstrated that M3-mRNAs were taken up significantly by PEMs via CD206-mediated endocytosis. In vivo imaging showed that Dir-labeled M3-drugs accumulated predominantly in inflammatory areas and subsequently in bone injury joints. Treatment with M3-drugs in collagen-induced arthritis model mice increased the population of F4/80+ and F4/80+/CD206+ M2 macrophages in inflamed joints, leading to reduced joint fibrosis and modulation of cytokine levels, including decreased pro-inflammatory cytokines (IL-6, IL-1β, TNF-α, and INF-γ) and increased anti-inflammatory cytokines (IL-10 and TGF-β).</p><p><strong>Conclusions: </strong>M3-SiCLEC12A enhanced CD206-mediated endocytosis of M3-mRNAs and M3-drugs in macrophages, promoting the production of corresponding proteins and modulating the immune microenvironment. This treatment approach shows promise in repairing inflammation-induced bone and joint injury by balancing pro-inflammatory and anti-inflammatory cytokines. However, further research is required to address drug tolerance and safety concerns and minimize potential side effects before clinical application in autoimmune diseases caused by inflammation.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"1002-1016"},"PeriodicalIF":4.6,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963206","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":"Probing the Self-Aggregation of l-Tryptophan into Spherical Microstructures and Their Selective Interactions with Bilirubin.","authors":"Aarya, Anna Sebastian, Kavya P, Supratik Sen Mojumdar","doi":"10.1021/acsabm.4c01486","DOIUrl":"10.1021/acsabm.4c01486","url":null,"abstract":"<p><p>The aggregation of proteins, peptides and amino acids has been a keen subject of interest owing to their implications in metabolic disorders. In this work, we investigated the self-aggregation of the unmodified aromatic amino acid l-tryptophan (Trp) into unusual spherical microstructures. Using fluorescence spectroscopy and field emission scanning electron microscopy (FE-SEM), we detail the time-dependent transformation of monomeric tryptophan into spherical aggregates with distinct fluorescence characteristics (λ_ex = 345 nm, λ_em = 430 nm) compared to the monomer. Notably, the fluorescence intensity of these aggregates is selectively quenched in the presence of bilirubin, demonstrating exceptional sensitivity in the picomolar concentration range. The developed assay proved applicable and reliable for real sample analysis. Thermodynamic parameters derived from temperature-dependent fluorescence intensity measurements indicated that the aggregation process is spontaneous and driven by noncovalent interactions. Further evidence of bilirubin's strong association with the aggregates was obtained through competitive interaction studies with human serum albumin (HSA). This work offers insights into the aggregation behavior of single aromatic amino acids and their potential applications in detecting critical analytes.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"1157-1166"},"PeriodicalIF":4.6,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996005","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":"Ultrasound-Activated Copper Matrix Nanosonosensitizer for Cuproptosis-Based Synergy Therapy.","authors":"Qiao Yu, Jie Zhou, Qianqian Tao, Yong Liu, Hong Zhou, Bin Kang, Jing-Juan Xu","doi":"10.1021/acsabm.4c01710","DOIUrl":"10.1021/acsabm.4c01710","url":null,"abstract":"<p><p>Cuproptosis exhibits enormous application prospects in treatment. However, cuproptosis-based therapy is impeded by the limited intracellular copper ions, the nonspecific delivery, uncontrollable release, and chelation of endogenous overproduced glutathione (GSH). In this work, an ultrasound-triggered nanosonosensitizer (p-TiO₂-Cu(I)) was constructed for Cu(I) delivery, on-demand release, GSH consumption, and deeper tissue response. When the nanomedicine was internalized into the tumor cells, ultrasound (US) induced the nanosonosensitizer to produce reactive oxygen species (ROS) to achieve sonodynamic therapy (SDT). GSH, acting as a hole trapping agent, improved the efficiency of SDT. Meanwhile, the downgrade of GSH was beneficial to cuproptosis and oxidative damage-based SDT in return. What is more, the US could regulate the release behavior of Cu(I). Cu(I) bonded to mitochondrial proteins and then aggregated the lipoylated protein, bringing about the turbulence of the tricarboxylic acid cycle. The combination of SDT and cuproptosis showed high matching to induce efficient cuproptosis and may inspire other cuproptosis-based nanosonosensitizer designs.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"1503-1510"},"PeriodicalIF":4.6,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062125","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":"Antimicrobial Polymer via ROMP of a Bioderived Tricyclic Oxanorbornene Lactam Derivative.","authors":"Mohamed A Yassin, Hartmut Komber, Mohamed Naguib, Mohamed Abdelraof, Dietmar Appelhans, Brigitte Voit","doi":"10.1021/acsabm.4c01924","DOIUrl":"10.1021/acsabm.4c01924","url":null,"abstract":"<p><p>The rapid emergence of multidrug-resistant (MDR) bacteria represents a critical global health threat, underscoring the urgent need for alternative antimicrobial strategies beyond conventional antibiotics. In this study, we report the synthesis of novel biobased antimicrobial polymers bearing quaternary ammonium salts, derived from sustainable feedstocks, maleic anhydride, dimethylaminobenzaldehyde, and furfurylamine. The functional tricyclic oxanorbornene lactam monomer is polymerized via ring opening metathesis polymerization, yielding well-defined polymers with controlled molar masses and low dispersity. Structural characterization is performed using 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, and the polymerization kinetics is monitored by online ¹H NMR spectroscopy. The quaternized biobased polymers demonstrate potent broad-spectrum antimicrobial activity against three clinically isolated MDR bacterial strains. They exhibit minimum inhibitory concentrations (MICs) that are significantly lower than those of several conventional antibiotics while also showing low hemolytic activity toward mammalian cells. This study highlights the potential of bioderived ROMP polymers as promising, sustainable antimicrobial polymers for combating the growing threat of antimicrobial resistance.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"1720-1731"},"PeriodicalIF":4.6,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995966","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":"Selective Recognition of Oncogene Promoter C-Myc G-Quadruplex: Design, Synthesis, and In Vitro Evaluation of Naphthalimide and Imidazo[1,2-<i>a</i>]pyrazines for Their Anticancer Activity.","authors":"Palak Sharma, Kamaldeep Paul","doi":"10.1021/acsabm.4c01666","DOIUrl":"10.1021/acsabm.4c01666","url":null,"abstract":"<p><p>c-Myc is a transcription factor that is overexpressed in most human cancers. Despite its challenging nature, we have developed a series of naphthalimide-imidazopyrazine conjugates to target c-Myc. The library of synthesized derivatives was tested for their anticancer activity against a nine-panel of cancer cell lines. Compound <b>8eb</b> showed excellent cytotoxicity against all the tested cancer cell lines, with the range of growth inhibition from -98.79% to 96.62% at a single-dose concentration of 10^-5 M. Further, <b>8eb</b> was employed for a 5-dose assay against the same cancer cell lines, which showed efficacy at varying concentrations with an MG-MID GI₅₀ value of 2.61 μM. Biophysical studies were performed to explore the interaction of <b>8eb</b> with c-Myc <i>Pu</i>27 over ct-DNA, oncogene promotor <i>Pu</i>22, and human telomere, with a binding constant value of 1.3 × 10⁷ M^-1. Additionally, experiments were performed to get insights into the interaction mechanism between <b>8eb</b> and the c-Myc oncogene promoter. A molecular docking study unveiled the stacking of the compound with G4 DNA through groove binding, where very few reports are available, with a favorable binding energy of -9.2 kcal/mol. Moreover, the pharmacokinetic study and HOMO-LUMO energy gap analysis underscored the potency of the active candidate. The compound's binding ability toward HSA was also assessed, where results suggested effective binding of the compound to HSA, revealing its potential for easy delivery to the target site. The above findings suggested that these newly synthesized candidates with potent anticancer activity offer a promising avenue as G4 DNA c-Myc stabilizers.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"1377-1396"},"PeriodicalIF":4.6,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021269","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":"Solid-State Precipitation of Silver Nanoparticles Nucleated during Al Anodizing: Mechanism and Antibacterial Properties.","authors":"Teo Atz-Dick, Renato de Castro Valente, Thiago Vignoli Machado, Fabiana Horn, Luís F P Dick","doi":"10.1021/acsabm.4c01694","DOIUrl":"10.1021/acsabm.4c01694","url":null,"abstract":"<p><p>This study presents an innovative approach to creating antibacterial aluminum surfaces by combining the antibacterial properties of silver nanoparticles (Ag NPs) with the nanoarchitecture of anodized aluminum oxide in one step. An Al-Ag alloy containing 10 wt % Ag was synthesized and anodized in 0.3 M oxalic acid. Ag NPs precipitated in the solid state during anodization, resulting in a porous nanocomposite structure. Comprehensive characterization using SEM, TEM, and EDS revealed a 43 μm thick oxide layer with uniformly distributed nanopores of approximately 100 nm in diameter. Ag NPs with diameters ranging from 2 to 14 nm precipitated dispersed on the surface, inside pores, and within the Al₂O₃ matrix. Antibacterial properties were evaluated against <i>Escherichia coli</i>. The anodized Al-Ag surface demonstrated robust antibacterial activity after short incubation times (up to 1 × 10⁸ CFU/ml after 3 h). The enhanced antibacterial properties are attributed to the optimal size and distribution of Ag NPs and the potential physical bactericidal effect of the nanoporous structure. This strategy for the precipitation of Ag NPs in the solid state could be used to fabricate high-touch surfaces in hospitals.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"1466-1474"},"PeriodicalIF":4.6,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11836923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gold Mesoporous Silica-Coated Nanoparticles for Quantifying and Qualifying Mesenchymal Stem Cell Distribution; a Proof-of-Concept Study in Large Animals.","authors":"Lotte C C Smeets, Ezgi Sengun, Chloe Trayford, Bram van Cranenbroek, Marien I de Jonge, Katiuscia Dallaglio, Matthias C Hütten, Mark Schoberer, Daan R M G Ophelders, Tim G A M Wolfs, Renate G van der Molen, Sabine van Rijt","doi":"10.1021/acsabm.4c01714","DOIUrl":"10.1021/acsabm.4c01714","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) have demonstrated promising therapeutic potential across a wide range of diseases including (multi) organ injury in neonates. Despite the reported preclinical successes of MSC therapy, a major challenge in their clinical translation is a limited understanding of their biodistribution after administration. This knowledge gap needs to be addressed to allow clinical implementation. Accordingly, in this study, we propose that silica-coated gold nanoparticles (AuMS) are a promising tool for in vivo MSC tracing. This study explores the use of AuMS for both qualitative and quantitative MSC tracking in vivo after intravenous (I.V.) administration in a translational ovine model of preterm birth. Additionally, we assess the impact of AuMS labeling on the immunomodulatory functions of MSC, which play an important role in the therapeutic potency of these cells. Quantitative and qualitative assessment of AuMS-labeled MSC was performed in vivo using fluorescent microscopy and inductively coupled plasma mass spectrometry (ICP-MS), respectively. AuMS localization in the liver, spleen, and lung was demonstrated. In vitro studies showed that AuMS cellular uptake occurs within 6 h and remains internalized up to 72 h. Labeled MSC maintained their immune phenotype and did not alter their immunomodulatory capacity and proliferation abilities. Overall, we demonstrate that AuMS is a promising, biocompatible nanoprobe for MSC tracing up to 72 h post-I.V. administration.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"1511-1523"},"PeriodicalIF":4.6,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11836931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143121650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wool Fabric with an Improved Durable Biological Resistance Using a Coumarin Derivative.","authors":"Marwa Abou-Taleb, Eslam R El-Sawy, Mohamed S Abdel-Aziz, Hosam El-Sayed","doi":"10.1021/acsabm.4c01786","DOIUrl":"10.1021/acsabm.4c01786","url":null,"abstract":"<p><p>Wool is the most widely used proteinic natural fiber in the clothing industry by virtue of its versatile properties. Unfortunately, wool, as a natural fiber, is more susceptible to attack by microorganisms and moths, which may cause harm to the fiber and human health. That is why the antimicrobial and mothproof finishing of natural textiles is of prime importance to the textile and clothing industry. Herein, wool fabric was treated with the synthesized 6-aminocoumarin adopting the pad-dry-cure technique with or without a cross-linker. The treated wool fabric was evaluated for its antimicrobial activity against <i>Staphylococcus aureus</i> and <i>Escherichia coli</i>. The treated wool fabric was also tested for moth-proofing performance against <i>Tineola Bisselliella</i> through assessing the fabric weight loss. Various analyses were conducted to assign the alteration in the structure of the treated wool fibers, viz., urea-bisulfite solubility, carboxylic content, Fourier transform infrared spectroscopy, and X-ray diffraction pattern (XRD). Scanning electron microscopy displayed the surface of wool fabric before and after treatment. Some physical and mechanical properties were also assessed. Results revealed that treated wool fabric showed a bacterial resistance to Gram +ve and Gram -ve bacteria, in addition to its improved resistance to moth larvae attack without deterioration in the fabric's inherent properties.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"1664-1674"},"PeriodicalIF":4.6,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996042","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}