BiointerphasesPub Date : 2022-11-01DOI: 10.1116/6.0003879
Chenyang Zhang, Zhiyao Fang, Kaixuan Wang, Jia Wang, Xianyao Wan
{"title":"Role of iron in the treatment of sepsis.","authors":"Chenyang Zhang, Zhiyao Fang, Kaixuan Wang, Jia Wang, Xianyao Wan","doi":"10.1116/6.0003879","DOIUrl":"https://doi.org/10.1116/6.0003879","url":null,"abstract":"<p><p>Iron is an important microelement in human and microbial life activities. During the pathophysiological process of sepsis, iron metabolism changes and the body undergoes a series of changes to fight microbial infection. Meanwhile, alterations in iron metabolism during sepsis lead to the development of some diseases, such as transfusion-induced siderosis and anemia. In recent years, several studies have demonstrated the use of iron-chelating agents to fight microbial infections, and new antimicrobial agents have been developed using \"Trojan horse\" and siderophores immunity. In addition, the use of iron-based nanomaterials as drug delivery systems for gene delivery may be applied to the treatment of sepsis in the future. In this review, we describe the pathophysiological changes in the development and course of sepsis, focusing on the potential of iron in the treatment of sepsis.</p>","PeriodicalId":9053,"journal":{"name":"Biointerphases","volume":"19 6","pages":""},"PeriodicalIF":1.6,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiointerphasesPub Date : 2022-11-01DOI: 10.1116/6.0003872
Dingkun Zhang, Xin Li, Wen Zheng, Luolan Gui, Wenjuan Zeng, Yu Zeng, Yin Yang, Rong Fan, Yang Lu, Yueqiu Liu, Xinyi Hu, Ning Mao, Junwen Guan, Tao Li, Jingqiu Cheng, Hao Yang, Meng Gong
{"title":"Probing the biocompatibility of Mo2C nanosheet through an integrated metabolomics approach: Toward boosting energy metabolism.","authors":"Dingkun Zhang, Xin Li, Wen Zheng, Luolan Gui, Wenjuan Zeng, Yu Zeng, Yin Yang, Rong Fan, Yang Lu, Yueqiu Liu, Xinyi Hu, Ning Mao, Junwen Guan, Tao Li, Jingqiu Cheng, Hao Yang, Meng Gong","doi":"10.1116/6.0003872","DOIUrl":"https://doi.org/10.1116/6.0003872","url":null,"abstract":"<p><p>An Mo2C nanosheet is an important two-dimensional nanomaterial with distinguished catalytic activity in biochemical applications. However, detailed information on Mo2C-induced changes in metabolic shifts, biosafety, and molecular mechanisms is insufficient. Integrated metabolomics (including aqueous metabolomics, lipidomics, and spatial metabolomics) has provided an excellent choice with massive bioinformation. In addition, the notion of \"nanometabolomics\" was first proposed and utilized to refer to these metabolomics studies on the biosafety, biocompatibility, and biological response of nanomaterials. Nanometabolomics innovatively combined nanoscience and metabolomics with massive bioinformation at the molecular level. For instance, in this work, nanometabolomics specialized in probing an Mo2C-induced metabolic shift of human umbilical vein endothelial cells (HUVECs) through integrated metabolomics. Furthermore, integrated metabolomics was used to examine the metabolic shift of HUVECs at the metabolome and lipidome levels, as well as the spatial distribution of different metabolites. The findings demonstrated that high doses (1 mg/ml) of an Mo2C nanosheet might produce an immediate improvement in HUVECs' energy metabolism, which was closely related to the improved morphology and function of mitochondria. The integrated metabolomics outcomes of this unique \"Mo2C-cell\" system increased our understanding of an Mo2C nanosheet. The proposed new word \"nanometabolomics\" could also be considered an excellent notion in representing nanomaterial-involved metabolomics studies.</p>","PeriodicalId":9053,"journal":{"name":"Biointerphases","volume":"19 6","pages":""},"PeriodicalIF":1.6,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiointerphasesPub Date : 2022-11-01DOI: 10.1116/6.0003970
Paul Schulan, Kristian Wende, Thomas von Woedtke, Klaus-Dieter Weltmann, Sander Bekeschus, Ramona Clemen
{"title":"Oxidative modifications control aberrant tyrosine kinase activity.","authors":"Paul Schulan, Kristian Wende, Thomas von Woedtke, Klaus-Dieter Weltmann, Sander Bekeschus, Ramona Clemen","doi":"10.1116/6.0003970","DOIUrl":"https://doi.org/10.1116/6.0003970","url":null,"abstract":"<p><p>Therapy resistance is a major reason for the fatal consequences of cancer. The tumor microenvironment (TME) often is associated with the production of excess reactive oxygen species (ROS). ROS are capable of introducing oxidative post-translational modifications (oxPTMs) to proteins targeted in cancer therapy, such as tyrosine kinases (TKs), and ROS could render their functionality. However, little is known about the occurrence or magnitude of such processes, partially because mimicking the TME producing several short-lived ROS types at once is technically challenging. Gas plasma technology, a partially ionized gas generating a multitude of ROS types simultaneously and at high concentrations, was used to model pro-oxidative conditions in the TME and study the functional consequences in three TKs (epidermal growth factor receptor, sarcoma, and vascular endothelial growth factor receptor 2) targeted clinically. TKs dissolved in liquids were exposed to gas plasma, and a drastic reduction in their activity was observed. Hypothesizing that this was due to gas plasma-generated ROS, plasma-treated TKs were analyzed by high-resolution mass spectrometry for the type and quantity of oxPTM types using an in-house database. Preferred oxidation targets were identified as sulfur-containing and aromatic amino acids. OxPTMs were detected on amino acid residues that have important structural or catalytic functions in TKs, such as the adenosine triphosphate-binding site, but also on amino acid residues that are targets for therapeutic applications, such as TK inhibitors. While the practical relevance of these findings remains to be discovered, our results suggest that excessive ROS concentrations potentially contribute to TK activity reduction in the TME. The mass spectrometry data are available via ProteomeXchange with identifier PXD056912.</p>","PeriodicalId":9053,"journal":{"name":"Biointerphases","volume":"19 6","pages":""},"PeriodicalIF":1.6,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiointerphasesPub Date : 2022-10-10DOI: 10.1116/6.0002058
Jing-Yi Zhang, Nihad Cheraga, Ning-Ping Huang
{"title":"3D cell/scaffold model based on aligned-electrospun-nanofiber film/hydrogel multilayers for construction of anisotropic engineered tissue.","authors":"Jing-Yi Zhang, Nihad Cheraga, Ning-Ping Huang","doi":"10.1116/6.0002058","DOIUrl":"https://doi.org/10.1116/6.0002058","url":null,"abstract":"<p><p>Many tissues have a three-dimensional (3D) anisotropic structure compatible with their physiological functions. Engineering an in vitro 3D tissue having the natural structure and functions is a hotspot in tissue engineering with application for tissue regeneration, drug screening, and disease modeling. Despite various designs that have successfully guided the cellular alignment, only a few of them could precisely control the orientation of each layer in a multilayered construct or achieve adequate cell contact between layers. This study proposed a design of a multilayered 3D cell/scaffold model, that is, the cell-loaded aligned nanofiber film/hydrogel (ANF/Gel) model. The characterizations of the 3D cell-loaded ANF/Gel model in terms of design, construction, morphology, and cell behavior were systematically studied. The ANF was produced by efficiently aligned electrospinning using a self-designed, fast-and-easy collector, which was designed based on the parallel electrodes and modified with a larger gap area up to about 100 cm<sup>2</sup>. The nanofibers generated by this simple device presented numerous features like high orientation, uniformity in fiber diameter, and thinness. The ANF/Gel-based cell/scaffold model was formed by encapsulating cell-loaded multilayered poly(lactic-co-glycolic acid)-ANFs in hydrogel. Cells within the ANF/Gel model showed high viability and displayed aligned orientation and elongation in accordance with the nanofiber orientation in each film, forming a multilayered tissue having a layer spacing of 60 μm. This study provides a multilayered 3D cell/scaffold model for the in vitro construction of anisotropic engineered tissues, exhibiting potential applications in cardiac tissue engineering.</p>","PeriodicalId":9053,"journal":{"name":"Biointerphases","volume":"17 5","pages":"051002"},"PeriodicalIF":2.1,"publicationDate":"2022-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10416333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiointerphasesPub Date : 2022-08-03DOI: 10.1116/6.0001981
Wenxu Han, Ziqi Wei, Terri A Camesano
{"title":"New antimicrobial peptide-antibiotic combination strategy for Pseudomonas aeruginosa inactivation.","authors":"Wenxu Han, Ziqi Wei, Terri A Camesano","doi":"10.1116/6.0001981","DOIUrl":"https://doi.org/10.1116/6.0001981","url":null,"abstract":"<p><p>Novel antimicrobials or new treatment strategies are urgently needed to treat Pseudomonas aeruginosa (P. aeruginosa) related infections and especially to address the problem of antibiotic resistance. We propose a novel strategy that combines the human antimicrobial peptide (AMP) LL37 with different antibiotics to find synergistic AMP-antibiotic combinations against P. aeruginosa strains in vitro. Our results showed that LL37 exhibited synergistic inhibitory and bactericidal effects against P. aeruginosa strains PAO1 and PA103 when combined with the antibiotics vancomycin, azithromycin, polymyxin B, and colistin. In addition, LL37 caused strong outer membrane permeabilization, as demonstrated through measurement of an increased uptake of the fluorescent probe N-phenyl-1-naphthylamine. The membrane permeabilization effects appear to explain why it was easier to rescue the effectiveness of the antibiotic toward the bacteria because the outer membrane of P. aeruginosa exhibits barrier function for antibiotics. Furthermore, the change in the zeta potential was measured for P. aeruginosa strains with the addition of LL37. Zeta potentials for P. aeruginosa strains PAO1 and PA103 were -40.9 and -10.9 mV, respectively. With the addition of LL37, negative zeta potentials were gradually neutralized. We found that positively charged LL37 can interact with and neutralize the negatively charged bacterial outer membrane through electrostatic interactions, and the process of neutralization is believed to have contributed to the increase in outer membrane permeability. Finally, to further illustrate the relationship between outer membrane permeabilization and the uptake of antibiotics, we used LL37 to make the outer membrane of P. aeruginosa strains more permeable, and minimum inhibitory concentrations (MICs) for several antibiotics (colistin, gentamicin, polymyxin B, vancomycin, and azithromycin) were measured. The MICs decreased were twofold to fourfold, in general. For example, the MICs of azithromycin and vancomycin decreased more than fourfold when against P. aeruginosa strain PAO1, which were the greatest decrease of any of the antibiotics tested in this experiment. As for PA103, the MIC of polymyxin B2 decreased fourfold, which was the strongest decrease seen for any of the antibiotics tested in this experiment. The increased uptake of antibiotics not only demonstrates the barrier role of the outer membrane but also validates the mechanism of synergistic effects that we have proposed. These results indicate the great potential of an LL37-antibiotic combination strategy and provide possible explanations for the mechanisms behind this synergy.</p>","PeriodicalId":9053,"journal":{"name":"Biointerphases","volume":"17 4","pages":"041002"},"PeriodicalIF":2.1,"publicationDate":"2022-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10442099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiointerphasesPub Date : 2022-05-01DOI: 10.1116/6.0001670
Rodrigo Paes Vila Real, T. N. Pansani, L. M. Cardoso, C. A. de Souza Costa, F. G. Basso
{"title":"Titanium alkalinization improves response of osteoblasts to zoledronic acid.","authors":"Rodrigo Paes Vila Real, T. N. Pansani, L. M. Cardoso, C. A. de Souza Costa, F. G. Basso","doi":"10.1116/6.0001670","DOIUrl":"https://doi.org/10.1116/6.0001670","url":null,"abstract":"This investigation is aimed to determine the effect of the modification of titanium surface with NaOH on the metabolism of osteoblasts treated with zoledronic acid (ZA). Machined and NaOH-treated titanium disks were used. Surfaces were characterized by scanning electron microscopy, confocal microscopy, and x-ray photoelectron spectroscopy (XPS) analysis. Human osteoblasts were seeded onto the disks. After 24 h, cells were treated with ZA at 5 μM for 7 days. At this point, cell viability, collagen synthesis, total protein production, alkaline phosphatase activity, and mineral nodule deposition were assessed. The results of surface roughness were descriptively and statistically analyzed (t-Student), while the XPS results were qualitatively described. Cell metabolism data were analyzed by the analysis of variance two-way and Tukey tests at a 5% significance level. The results demonstrated that NaOH-treatment increased surface roughness (p < .05) and confirmed the presence of sodium titanate and a pH switch on the NaOH-treated disks. This modification also resulted in higher cell viability, collagen synthesis, total protein production, and alkaline phosphatase by osteoblasts when compared to cells seeded onto machined disks (p < 0.05). In the presence of ZA, all cellular metabolism and differentiation parameters were significantly reduced for cells seeded on both surfaces (p < 0.05); however, the cells seeded onto modified surfaces showed higher values for these parameters, except for mineral nodule deposition (p < 0.05). NaOH modification improved cell adhesion and metabolism of osteogenic cells even in the presence of ZA. The surface modification of titanium with NaOH solution may be an interesting strategy to improve metabolism and differentiation of osteoblasts and accelerate osseointegration process, mainly for tissues exposed to ZA.","PeriodicalId":9053,"journal":{"name":"Biointerphases","volume":"17 3 1","pages":"031004"},"PeriodicalIF":2.1,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41416431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiointerphasesPub Date : 2022-05-01DOI: 10.1116/6.0001859
Zhan Chen
{"title":"Early sum frequency generation vibrational spectroscopic studies on peptides and proteins at interfaces.","authors":"Zhan Chen","doi":"10.1116/6.0001859","DOIUrl":"https://doi.org/10.1116/6.0001859","url":null,"abstract":"This paper summarizes the early research results on studying proteins and peptides at interfaces using sum frequency generation (SFG) vibrational spectroscopy. SFG studies in the C-H stretching frequency region to examine the protein side-chain behavior and in the amide I frequency region to investigate the orientation and conformation of interfacial peptides/proteins are presented. The early chiral SFG research and SFG isotope labeling studies on interfacial peptides/proteins are also discussed. These early SFG studies demonstrate the feasibility of using SFG to elucidate interfacial molecular structures of peptides and proteins in situ, which built a foundation for later SFG investigations on peptides and proteins at interfaces.","PeriodicalId":9053,"journal":{"name":"Biointerphases","volume":"17 3 1","pages":"031202"},"PeriodicalIF":2.1,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"63540916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiointerphasesPub Date : 2022-05-01DOI: 10.1116/6.0001812
P. Dietrich, Marit Kjærvik, E. Willneff, W. Unger
{"title":"In-depth analysis of iodine in artificial biofilm model layers by variable excitation energy XPS and argon gas cluster ion sputtering XPS.","authors":"P. Dietrich, Marit Kjærvik, E. Willneff, W. Unger","doi":"10.1116/6.0001812","DOIUrl":"https://doi.org/10.1116/6.0001812","url":null,"abstract":"Here, we present a study on agarose thin-film samples that represent a model system for the exopolysaccharide matrix of biofilms. Povidone-iodide (PVP-I) was selected as an antibacterial agent to evaluate our x-ray photoelectron spectroscopy (XPS)-based methodology to trace specific marker elements, here iodine, commonly found in organic matrices of antibiotics. The in-depth distribution of iodine was determined by XPS analyses with variable excitation energies and in combination with argon gas cluster ion beam sputter cycles. On mixed agarose/PVP-I nanometer-thin films, both methods were found to solve the analytical task and deliver independently comparable results. In the mixed agarose/PVP-I thin film, we found the outermost surface layer depleted in iodine, whereas the iodine is homogeneously distributed in the depth region between this outermost surface layer and the interface between the thin film and the substrate. Depletion of iodine from the uppermost surface in the thin-film samples is assumed to be caused by ultrahigh vacuum exposure resulting in a loss of molecular iodine (I2) as reported earlier for other iodine-doped polymers.","PeriodicalId":9053,"journal":{"name":"Biointerphases","volume":"17 3 1","pages":"031002"},"PeriodicalIF":2.1,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49353164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiointerphasesPub Date : 2022-05-01DOI: 10.1116/6.0001746
Anouck L. S. Burzava, M. Jasieniak, Michaelia P Cockshell, N. Voelcker, C. Bonder, H. J. Griesser, E. Moore
{"title":"Attachment of endothelial colony-forming cells onto a surface bearing immobilized anti-CD34 antibodies: Specific CD34 binding versus nonspecific binding.","authors":"Anouck L. S. Burzava, M. Jasieniak, Michaelia P Cockshell, N. Voelcker, C. Bonder, H. J. Griesser, E. Moore","doi":"10.1116/6.0001746","DOIUrl":"https://doi.org/10.1116/6.0001746","url":null,"abstract":"Cardiovascular disease is a leading cause of death worldwide; however, despite substantial advances in medical device surface modifications, no synthetic coatings have so far matched the native endothelium as the optimal hemocompatible surface for blood-contacting implants. A promising strategy for rapid restoration of the endothelium on blood-contacting biomedical devices entails attracting circulating endothelial cells or their progenitors, via immobilized cell-capture molecules; for example, anti-CD34 antibody to attract CD34+ endothelial colony-forming cells (ECFCs). Inherent is the assumption that the cells attracted to the biomaterial surface are bound exclusively via a specific CD34 binding. However, serum proteins might adsorb in-between or on the top of antibody molecules and attract ECFCs via other binding mechanisms. Here, we studied whether a surface with immobilized anti-CD34 antibodies attracts ECFCs via a specific CD34 binding or a nonspecific (non-CD34) binding. To minimize serum protein adsorption, a fouling-resistant layer of hyperbranched polyglycerol (HPG) was used as a \"blank slate,\" onto which anti-CD34 antibodies were immobilized via aldehyde-amine coupling reaction after oxidation of terminal diols to aldehydes. An isotype antibody, mIgG1, was surface-immobilized analogously and was used as the control for antigen-binding specificity. Cell binding was also measured on the HPG hydrogel layer before and after oxidation. The surface analysis methods, x-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry, were used to verify the intended surface chemistries and revealed that the surface coverage of antibodies was sparse, yet the anti-CD34 antibody grafted surface-bound ECFCs very effectively. Moreover, it still captured the ECFCs after BSA passivation. However, cells also attached to oxidized HPG and immobilized mIgG1, though in much lower amounts. While our results confirm the effectiveness of attracting ECFCs via surface-bound anti-CD34 antibodies, our observation of a nonspecific binding component highlights the importance of considering its consequences in future studies.","PeriodicalId":9053,"journal":{"name":"Biointerphases","volume":"17 3 1","pages":"031003"},"PeriodicalIF":2.1,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46153501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiointerphasesPub Date : 2022-05-01DOI: 10.1116/6.0001851
S. Hosseinpour
{"title":"Dos and don'ts tutorial for sample alignment in sum frequency generation spectroscopy.","authors":"S. Hosseinpour","doi":"10.1116/6.0001851","DOIUrl":"https://doi.org/10.1116/6.0001851","url":null,"abstract":"This Tutorial aims to provide a concise yet practical guideline for different scenarios that one may face in a sum frequency generation (SFG) spectroscopy laboratory, especially when it comes to sample alignment. The effort is made to reconstruct the real and often challenging sample alignment conditions for a broad range of liquid or solid samples interfacing solid, liquid, or gas phases, with a pedagogical approach. Both newcomer operators of an SFG setup without a strong experience in nonlinear spectroscopy and the more experienced SFG users can utilize the approaches that are provided in this Tutorial for an easier and more reliable sample alignment in their SFG laboratories.","PeriodicalId":9053,"journal":{"name":"Biointerphases","volume":"17 3 1","pages":"031203"},"PeriodicalIF":2.1,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42177378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}