Kameel Zuniga, Marc Thompson, Preeti J Muire, Nicholas Clay, S L Rajasekhar Karna, Logan Leatherman, Rebecca Lopez, Tao You, Krystle Harm, Jerod Brammer, Joseph Wenke, Robert Christy, Christine Kowalczewski
{"title":"Development and Characterization of a Collagen-Based Three-Dimensional In Vitro Model to Mimic Biofilm Formation in a Wound Bed.","authors":"Kameel Zuniga, Marc Thompson, Preeti J Muire, Nicholas Clay, S L Rajasekhar Karna, Logan Leatherman, Rebecca Lopez, Tao You, Krystle Harm, Jerod Brammer, Joseph Wenke, Robert Christy, Christine Kowalczewski","doi":"10.1021/acsabm.5c00100","DOIUrl":"https://doi.org/10.1021/acsabm.5c00100","url":null,"abstract":"<p><p>Current studies using in vitro biofilm culturing systems have been instrumental at elucidating wound biofilm formation but fail to account for the diverse environment that bacteria are exposed to within the host. In the current study, we recapitulated this wound biofilm microenvironment by creating a hydrogel composed of collagen, thrombin, fibrinogen, meat broth, and FBS and subsequently infected the scaffolds with UAMS-1. We characterized the material properties of the hydrogel (noninfected) and found no significant differences in the storage modulus when fibrin was added to the collagen hydrogel. When infected with UAMS-1, temporal growth and polysaccharide formation were observed through plating, SEM, and histological staining, indicative of biofilm formation. PCR analysis revealed heightened expression of adhesion-associated genes with no increase in expression of metabolic genes, indicating significant increase in the formation of a robust biofilm over time. Vancomycin was ineffective in eradicating the already-developed biofilm, whereas the total CFUs in rifampin-treated models decreased significantly compared to those in the untreated group. Although it was not significant, an increase in SCVs was observed in the rifampin-treated group, suggesting that rifampin may create a harsher environment against the <i>Staphylococcus aureus</i>, allowing the increase in more resistant bacteria. The persistence of an infection in our rifampin-treated 3D in vitro wound model indicates an increased similarity to the host environment compared to that of a static biofilm model.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155277","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}
Sarah Defrançois, Alexandre Barras, Mickaël Maton, Patrice Woisel, Feng Hildebrand, Nicolas Blanchemain, Rabah Boukherroub, Joël Lyskawa
{"title":"<i>In Vitro</i> Evaluation of Antibacterial Properties of NIR-Light Responsive Alginate Hydrogels Embedding Polydopamine Nanoparticles.","authors":"Sarah Defrançois, Alexandre Barras, Mickaël Maton, Patrice Woisel, Feng Hildebrand, Nicolas Blanchemain, Rabah Boukherroub, Joël Lyskawa","doi":"10.1021/acsabm.5c00481","DOIUrl":"https://doi.org/10.1021/acsabm.5c00481","url":null,"abstract":"<p><p>Bacterial infections are one of the most serious health problems worldwide and represent a significant threat to humans. In this article, we designed an injectable alginate-based hydrogel embedding polydopamine nanoparticles (nPDA) and applied it as a (nano)phototherapeutic agent and nanocarrier for photodynamic (PDT) and photothermal (PTT) therapies with the perspective of treating bacterial infections and overcoming microbial resistance. For this purpose, nPDA were functionalized with Chlorin e6 as a photosensitizer and embedded in an alginate hydrogel to apply the PDT treatment. The photothermal properties of nPDA were exploited for the \"on demand\" local release of antibiotics such as Ciprofloxacin (for Gram-negative bacteria) and Rifampicin (for Gram-positive bacteria) to address respectively <i>Escherichia coli</i> and <i>Staphylococcus</i>s <i>aureus</i> as these antimicrobial-resistant pathogens are commonly found in bacterial infections. <i>In vitro</i> experiments have shown that PDT and PTT treatments were both highly efficient for the treatment of <i>S. aureus</i>, leading to the complete eradication of this bacterium. On the contrary, PDT was less effective for treating <i>E. coli</i>, while PTT revealed an excellent antibacterial activity toward this pathogen.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155241","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}
Yingying Nie, Cewen Hu, Xinyue Huang, Huajing Zeng, Zhilong Wang, Jiachen Liang, Jizeng Wang
{"title":"Accelerating Wound Healing through a Mechano-Electric Synergistic Conductive Hydrogel.","authors":"Yingying Nie, Cewen Hu, Xinyue Huang, Huajing Zeng, Zhilong Wang, Jiachen Liang, Jizeng Wang","doi":"10.1021/acsabm.5c00523","DOIUrl":"https://doi.org/10.1021/acsabm.5c00523","url":null,"abstract":"<p><p>To address the challenge of achieving faster wound healing, we present an innovative approach using hydrogel wound dressings that leverage the mechano-electric synergistic effect. This method incorporates piezoelectric zinc oxide nanoparticles (ZnO NPs) and conductive carbon nanotubes (CNTs) into a thermosensitive poly(<i>N</i>-isopropylacrylamide) (PNIPAM) hydrogel matrix. The engineered hydrogel demonstrates exceptional mechanical strength, optimal swelling properties, enhanced antibacterial activity, and excellent biocompatibility and biosafety. Upon application to a wound site, the hydrogel undergoes temperature-induced centripetal contraction, which enhances the wound closure process. Moreover, the morphological changes in the hydrogel caused by self-contraction and alterations in skin shape can trigger a piezoelectric effect, generating stable and lasting bioelectric signals that promote fibroblast migration. Consequently, a wound approximately 1 cm<sup>2</sup> in size can nearly completely heal within 14 days, thanks to the hydrogel's multifaceted therapeutic potential, including anti-inflammatory effects, promotion of cell migration, induction of fibroblast-to-myofibroblast differentiation, and enhancement of angiogenesis. This breakthrough represents a significant advancement over conventional hydrogel wound dressings, offering considerable promise for clinical application.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155245","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}
Ali Zare Narimani, Amir Landarani-Isfahani, Mehrnaz Bahadori, Majid Moghadam, Shahram Tangestaninejad, Iraj Mohammadpoor-Baltork, Valiollah Mirkhani
{"title":"Covalent Immobilization of Lipase on NH<sub>2</sub>-MIL-125(Ti) through Ugi Reaction for Biodiesel Production.","authors":"Ali Zare Narimani, Amir Landarani-Isfahani, Mehrnaz Bahadori, Majid Moghadam, Shahram Tangestaninejad, Iraj Mohammadpoor-Baltork, Valiollah Mirkhani","doi":"10.1021/acsabm.5c00321","DOIUrl":"https://doi.org/10.1021/acsabm.5c00321","url":null,"abstract":"<p><p>In this study, heterogeneous biocatalysts were produced by successfully synthesizing the metal-organic framework (MOF) NH<sub>2</sub>-MIL-125(Ti) as a support, followed by the chemical stabilization of the lipase enzyme using the Ugi four-component reaction (Lipase-NH<sub>2</sub>-MIL-125), resulting in a stabilization efficiency of 87%. The amine group in MOF plays one of the reactants in the Ugi reaction, and a firm covalent bond is created between the enzyme and the support, which avoids enzyme leaching and leads to a stable biocatalyst. Enzyme efficiency, reusability, pH, and temperature stability of Lipase-NH<sub>2</sub>-MIL-125 have been investigated, and their high performance has been proven for the biocatalyst. The biodiesel production process using oleic acid has been utilized to evaluate the catalytic activity of the designed biocatalyst, and different parameters have been optimized. The results confirmed the good activity of Lipase-NH<sub>2</sub>-MIL-125 in biodiesel production, and even after 6 cycles, the activity slightly decreased, which confirmed the stability of the biocatalyst during the reaction.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148653","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}
MacAulay Harvey, Anupama Ghimire, Richard Cisek, Laurent Kreplak, Jan K Rainey, Danielle Tokarz
{"title":"Polarization-Resolved Second Harmonic Generation Microscopy of Silk Fibers Is Sensitive to β-Sheet Orientation and Molecular Structure.","authors":"MacAulay Harvey, Anupama Ghimire, Richard Cisek, Laurent Kreplak, Jan K Rainey, Danielle Tokarz","doi":"10.1021/acsabm.5c00541","DOIUrl":"https://doi.org/10.1021/acsabm.5c00541","url":null,"abstract":"<p><p>Spider silk biomaterials have generated significant interest due to their high strength, biocompatibility, and biodegradability. However, the complex multiscale structure of silk fibers creates difficulties in investigating the relationship between the structure and mechanical properties in silks. Previous work has shown that silks at the focus of an ultrafast laser produce a significant second harmonic generation (SHG) signal. This presents an exciting opportunity since polarization-resolved SHG microscopy (PSHG) is a technique that has shown high sensitivity local molecular structure and organization in several biological samples. However, applications of PSHG to silks have been impeded by the lack of a theoretical model relating silk molecular structure and organization to its PSHG response. Here, a theoretical model of PSHG from silk materials is presented, which relates β-sheet organization within silk fibers to experimentally measurable parameters. Based on this, we present evidence that postspin stretching in ethanol induces planar alignment of the β-sheets within recombinant spider silk fibers, and the molecular structure and degree of axial alignment of β-sheets are highly dependent on the level of postspin stretching. Overall, this work demonstrates the significant potential for the application of PSHG to map the local structure of silk fibers, providing opportunities for the investigation of silk-based biomaterials.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155280","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":"Photodynamic Evaluation of A<sub>2</sub>BC Aminoporphyrins: Synthesis, Characterization, and Cellular Impact.","authors":"Nivedita Rana, Pankaj Kumar Chaudhary, Ramasare Prasad, Muniappan Sankar","doi":"10.1021/acsabm.5c00411","DOIUrl":"https://doi.org/10.1021/acsabm.5c00411","url":null,"abstract":"<p><p>This study focuses on the design and evaluation of a series of A<sub>2</sub>BC aminoporphyrins, featuring electron-donating substituents like pyrene, carbazole, and phenothiazine to enhance their photophysical and biological performance. Detailed characterization through spectroscopic methods, single-crystal X-ray diffraction, and computational analyses revealed insights into their electronic structure and planarity. Photophysical investigations revealed characteristic Soret and Q bands, along with tunable fluorescence and excited-state lifetimes influenced by the <i>meso</i> substituents. Biological evaluation was conducted using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays and fluorescence microscopy to assess the photodynamic therapeutic efficacy against T24 bladder cancer cells. The porphyrins exhibited pronounced photocytotoxicity upon 660 nm light activation, attributed to reactive oxygen species (ROS) generation. Cellular analysis, including acridine orange/ethidium bromide and 4',6-diamidino-2-phenylindole staining, confirmed apoptosis induction through chromatin condensation and nuclear fragmentation. The findings highlight the potential of these porphyrins as effective photosensitizers for photodynamic therapy, demonstrating enhanced stability and ROS generation efficiency.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144148654","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":"Identification and Classification of Functional Split G-Quadruplexes Using Machine Learning-Guided Activity Screening.","authors":"Pranotosh Das, Avimanyu Das, Manish Debnath","doi":"10.1021/acsabm.5c00215","DOIUrl":"https://doi.org/10.1021/acsabm.5c00215","url":null,"abstract":"<p><p>Split G-quadruplexes are considered excellent tools for biosensing and diagnostics, but splitting G-quadruplexes may often lead to a loss of function, limiting their effectiveness. This study aims to identify and classify functional split G-quadruplexes based on the ability of the G-quadruplex motif to generate a fluorescence turn-on response and undergo phase separation. A series of split G-quadruplexes were designed, and their characterization was conducted using fluorescence spectroscopy, fluorescence microscopy, UV-vis spectroscopy, and circular dichroism to investigate their functional properties (fluorogenic response, phase separation, and DNAzyme activity). Multivariate analysis and machine learning-based pattern recognition revealed that structural changes due to the splitting of G4-forming sequences correlate with their ability to form phase-separated condensates, which enhance their fluorogenic and DNAzyme activity. The machine learning-based activity screening was used to identify split G-quadruplexes, which may have high, moderate, or low functional activity. This integrative approach provides a predictive framework for engineering functionally active split G-quadruplexes and establishes a platform for their application in molecular diagnostics.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140885","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":"<i>Salmonella</i>-Derived Fluorescent Carbon Dots for Reprogramming Tumor-Associated Macrophages and Enhancing Tumor Photodynamic Therapy.","authors":"Pei-Jie Zhang, Dong Zhou, Zi-Wei Yang, Yong-Guo Hu, Meng-Wen Ma, Jin-Xuan Fan, Yuan-Di Zhao, Jia-Hua Zou","doi":"10.1021/acsabm.5c00624","DOIUrl":"https://doi.org/10.1021/acsabm.5c00624","url":null,"abstract":"<p><p>Carbon dots (CDs) are used as photosensitizers for the photodynamic therapy of tumors while retaining the specific functional groups and biochemical properties of carbon precursors. However, the short-wavelength excitation of photosensitizers limits their application in the photodynamic therapy of tumors. Upconversion nanoparticles (UCNPs) effectively solve the problem of low penetration of photosensitizers due to short-wavelength excitation by converting low-energy near-infrared light into high-energy ultraviolet light or visible light. In this paper, carbon dots were prepared by a hydrothermal method using <i>Salmonella</i> and alendronic acid as raw materials, while the phosphate groups on the surface of carbon dots were coordinated with upconversion nanoparticles (UCNPs) to form UCNP@CD nanoprobes. Under the irradiation of an 808 nm laser, the emitted light from upconversion nanoparticles (UCNPs) can further catalyze carbon dots (CDs) to enhance the generation of reactive oxygen species for killing tumor cells. Meanwhile, carbon dots reprogrammed M2 macrophages into M1 macrophages to improve the tumor immunosuppressive microenvironment. The UCNP@CD nanoprobes were used for tumor-associated macrophage reprogramming and photodynamic therapy of tumors, which provides an effective strategy for multimodal synergistic tumor treatment.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135882","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}
Yusai Zhao, Xiaoqing Chen, Hengwei Zhang, Yifan Ge, Di Li
{"title":"Reversal Drug Resistance of Tumor Cells by Manipulating its Membrane Heterogeneity through High Spatially Resolved Heating.","authors":"Yusai Zhao, Xiaoqing Chen, Hengwei Zhang, Yifan Ge, Di Li","doi":"10.1021/acsabm.5c00605","DOIUrl":"https://doi.org/10.1021/acsabm.5c00605","url":null,"abstract":"<p><p>Multidrug resistance (MDR) presents a substantial challenge to the therapeutic efficacy of cancer chemotherapy. A common trait of drug-resistant cells is decreased cell membrane permeability, hindering the uptake of therapeutic agents. Additionally, these cells frequently overexpress drug efflux pumps that actively expel the drugs, leading to reduced intracellular accumulation. In this study, we introduce a high spatially resolved, domain-specific, mild heating strategy to counteract drug resistance using DNA nanodevices. This strategy aims to manipulate the membrane heterogeneity by increasing cell membrane permeability and decreasing the expression of drug efflux pumps. The DNA nanodevices (termed DNA nanoheaters) with specific domain affinity anchor distinct cell membrane domains (raft/nonraft) and elevate the local lipid environmental temperature upon near-infrared (NIR) laser exposure. This elevation in local lipid temperature modifies key biophysical membrane features of Doxorubicin-resistant tumor cells, resulting in a two-order magnitude decrease in IC<sub>50</sub>. Notably, our approach diverges from conventional methods that depend on the delivery of pharmacological reversal agents. Instead, we emphasize modulating the membrane properties of drug-resistant cells through mild physical stimuli, offering a potential reduction in systemic toxicity associated with chemotherapy.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135884","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}
Soumya Saroj, Akshaya Kana Veedu, Chandrasekhar Reddy U, Nalini Venkatesan, Abhishek K Verma, Muraleedharan Kannoth Manheri
{"title":"Modulation of Doxorubicin-Induced ROS Accumulation in Cardiomyocytes Using Ibuprofen-Conjugated Synthetic Lipids as Carriers.","authors":"Soumya Saroj, Akshaya Kana Veedu, Chandrasekhar Reddy U, Nalini Venkatesan, Abhishek K Verma, Muraleedharan Kannoth Manheri","doi":"10.1021/acsabm.4c01932","DOIUrl":"https://doi.org/10.1021/acsabm.4c01932","url":null,"abstract":"<p><p>Conjugation of an NSAID such as ibuprofen to the head group of oxanorbornane-based lipids and the use of their aggregates as carriers for doxorubicin (Dox) are discussed here. These conjugates were characterized by various spectroscopic techniques, including 2D-NMR, and insights into their assembly were gathered through PXRD, AFM, SEM, DLS, and qNano techniques. Free lipids as well as their formulations (lipid:cholesterol:Dox in a 3:1.5:2 molar ratio) showed a high tendency to form solid lipid particles, which was verified by TEM analysis. The presence of the ibuprofen unit led to an increase in interlipid spacing and a characteristic change in their packing. Active loading through a pH gradient allowed us to achieve high drug entrapment and a controlled release profile. The formulation <b>AT3.3</b>, prepared by this method, showed a Dox entrapment of ∼90%, with a controlled release of ∼18% by the end of 24 h; only ∼66% of the entrapped Dox was released by the end of 5 days. Cytotoxicity studies in NIH3T3 cells and hemolytic assay results showed that these lipids and their formulations have a good safety profile. Results from flow cytometry experiments in A549 cells revealed that the formulation <b>AT3.3</b> induces effects similar to free Dox, with cell cycle arrest predominantly at the S phase and G<sub>2</sub>/M phase. At the same time, the response from the blank formulation was comparable to that of the control. Confocal microscopy studies in NIH3T3 and A549 cells showed that free Dox gets localized mainly in the nucleus, while the use of the carrier (<b>AT3.3</b>) causes significant localization of the drug on the cytoplasmic side as well. ROS induction due to free Dox and its formulation (<b>AT3.3</b>) in cardiomyocytes and A549 cells was also compared, and the results showed a protective effect in cardiomyocytes when using this formulation.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131784","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}