Serena Pilato , Simona Mrakic-Sposta , Vittore Verratti , Carmen Santangelo , Stefano di Giacomo , Samanta Moffa , Antonella Fontana , Tiziana Pietrangelo , Federica Ciampini , Sofia Bonan , Pamela Pignatelli , Carmine Noce , Pietro di Profio , Michele Ciulla , Danilo Bondi , Fabrizio Cristiano
{"title":"Urineprint of high-altitude: Insights from analyses of urinary biomarkers and bio-physical-chemical features of extracellular vesicles","authors":"Serena Pilato , Simona Mrakic-Sposta , Vittore Verratti , Carmen Santangelo , Stefano di Giacomo , Samanta Moffa , Antonella Fontana , Tiziana Pietrangelo , Federica Ciampini , Sofia Bonan , Pamela Pignatelli , Carmine Noce , Pietro di Profio , Michele Ciulla , Danilo Bondi , Fabrizio Cristiano","doi":"10.1016/j.bpc.2024.107351","DOIUrl":"10.1016/j.bpc.2024.107351","url":null,"abstract":"<div><div>Humans exposed to altitude hypoxia experience dysfunctions of the urinary system. As a non-invasive, easily manageable and informative biological sample, urine represents a relevant matrix for detecting clinical impairments of urinary system, as well as alterations of other systems and extracellular vesicles (EVs) biology during high-altitude expeditions. Nevertheless, gaps exist in the comprehensive assessment of dysfunction, molecular burden and EVs biology due to high-altitude acute exposure. This study aimed to find a biophysical and biochemical signature of urinary EVs for hypoxia-induced changes in urinary function, putatively accompanied by an oxinflammatory burden. Urine samples of 15 participants were sampled at low and high-altitude during an Alpine project (7 women and 8 men, aged 24-to-63 years and with BMI 17.93-to-30.76 kg/m<sup>2</sup>) and analysed for: creatinin and albumin, lipid peroxidation, IL6, NO derivatives; atomic force microscopy and Raman spectroscopy were carried out after urinary EVs were isolated through sucrose-gradient ultracentrifugation. Albumin-to-creatinin ratio increased at high altitude, as did IL6 and 8-isoprostane. AFM showed a globular and flattened shape of EVs, although several samples were characterized by a lot of contaminants and EVs lost their prototypal spherical shape; EVs comprehensively maintained their morphology at high altitude. Raman spectroscopy revealed some typical phospholipidic-like pattern, often masked by contaminants of spectra that most often refer to high-altitude samples. Collectively, short-term exposure to altitude hypoxia increased renal concentrating ability, produced non-pathological impairment or renal function, and triggered an oxyinflammatory burden with heterogeneous response of NO system. The combination of AFM and Raman spectroscopy revealed that EVs collected at high altitude more likely are fused together and incorporated into a sediment matrix, and contain contaminants peaks that make the purification process less efficient. The combination of analytical procedures as in the present study offers novel possibilities to detect the biological and clinical effects of high altitude on renal system.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"316 ","pages":"Article 107351"},"PeriodicalIF":3.3,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rugiya Alieva , Anna Keshek , Timofei Zatsepin , Victor Orlov , Andrey Aralov , Elena Zavyalova
{"title":"Kinetics of i-motif folding within the duplex context","authors":"Rugiya Alieva , Anna Keshek , Timofei Zatsepin , Victor Orlov , Andrey Aralov , Elena Zavyalova","doi":"10.1016/j.bpc.2024.107350","DOIUrl":"10.1016/j.bpc.2024.107350","url":null,"abstract":"<div><div>Non-canonical nucleic acid structures possess an ability to interact selectively with proteins, thereby exerting influence over various intracellular processes. Numerous studies indicate that genomic G-quadruplexes and i-motifs are involved in the regulation of transcription. These structures are formed temporarily during the unwinding of the DNA double helix; and their direct determination is a rather difficult task. In addition, i-motif folding is pH-dependent, with most i-motifs having low stability at neutral pH. However, some genomic i-motifs with long cytosine repeats were shown to be stable at pH 7.3, suggesting their functionality within the nucleus. Here we studied pH-dependent behavior of a model i-motif with flanking sequences that forms a duplex motif. Kinetic studies on bimodular structures with cytosine residues replaced with an environment-sensitive fluorescent label reveal the stabilization of the i-motif structure near the i-motif-duplex junction. These results highlight the importance of the natural environment of i-motifs for the correct assessment of their stability.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"316 ","pages":"Article 107350"},"PeriodicalIF":3.3,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N.S. Mohd Nor Ihsan , S.F. Abdul Sani , L.M. Looi , Dharini Pathmanathan , P.L. Cheah , S.F. Chiew , Sirinart Chio-Srichan , Siriwat Soontaranon , D.A. Bradley
{"title":"Supramolecular arrangements in human amyloid tissues using SAXS","authors":"N.S. Mohd Nor Ihsan , S.F. Abdul Sani , L.M. Looi , Dharini Pathmanathan , P.L. Cheah , S.F. Chiew , Sirinart Chio-Srichan , Siriwat Soontaranon , D.A. Bradley","doi":"10.1016/j.bpc.2024.107349","DOIUrl":"10.1016/j.bpc.2024.107349","url":null,"abstract":"<div><div>Amyloid diseases are characterized by the accumulation of misfolded protein aggregates in human tissues, pose significant challenges for both diagnosis and treatment. Protein aggregations known as amyloids are linked to several neurodegenerative conditions including Alzheimer's disease, Parkinson's disease, and systemic amyloidosis. The key goal of this research is to employ Small-Angle X-ray Scattering (SAXS) to examine the supramolecular structures of amyloid aggregates in human tissues. We present the structural analysis of amyloid using SAXS, which is employed directly to analyze thin tissue samples without damaging the tissues. This technique provides size and shape information of fibrils, which can be used to generate low-resolution 2D models. The present study investigates the structural changes in amyloid fibril axial d-spacing and scattering intensity in different human tissues, including kidney, heart, thyroid, and others, while also accounting for the presence of triglycerides in these tissues. Tissue structural components were examined at momentum transfer values between q = 0.2 nm<sup>−1</sup> and 1.5 nm<sup>−1</sup>. The d-spacing is a critical parameter in SAXS that provides information about the periodic distances between structures within a sample. From the supramolecular SAXS patterns, the axial d-spacing of fibrils in amyloid tissues is prominent and exists within the 3rd to 10th order, compared to that of healthy tissues which do not have notable peak orders. The axial period of fibrils in amyloid tissues is within the scattering vector range 57.40–64.64 nm<sup>−1</sup> while in normal tissues the range is between 60.68 and 61.41 nm<sup>−1</sup>, which is 3.0 nm<sup>−1</sup> smaller than amyloid-containing tissues. Differences in d-spacing are often correlate with distinct pathological mechanisms or stages of disease progression. The application of SAXS to investigate amyloid structures in human tissues has enormous potential to further knowledge of amyloid disorders. This work will open the path for novel diagnostic instruments and therapeutic strategies meant to reduce the burden of amyloid-related diseases by offering a thorough structural examination of amyloid aggregates.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"316 ","pages":"Article 107349"},"PeriodicalIF":3.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Characterization of a novel salt- and solvent-tolerant esterase Dhs82 from soil metagenome capable of hydrolyzing estrogenic phthalate esters","authors":"Yuanyan Wang , Chunmei Deng , Xin Wang","doi":"10.1016/j.bpc.2024.107348","DOIUrl":"10.1016/j.bpc.2024.107348","url":null,"abstract":"<div><div>Esterases that can function under extreme conditions are important for industrial processing and environmental remediation. Here, we report the identification of a salt- and solvent-tolerant esterase, Dhs82, from a soil metagenomic library. Dhs82 prefers short-chain <em>p</em>-nitrophenyl (<em>p</em>-NP) esters and exhibits enzymatic activity up to 1460 ± 61 U/mg towards <em>p</em>-NP butyrate. Meanwhile, Dhs82 can catalyze the hydrolysis of dialkyl phthalate esters, especially the widely-used diethyl phthalate (DEP), dipropyl phthalate (DPP) and di-n-butyl phthalate (DBP). Importantly, as an acidic protein with negative charges dominating its surface, Dhs82 is highly active and extraordinarily stable at high salinity. This property is quite rare among previously reported esterases/hydrolases capable of degrading phthalate esters (PAEs). In addition, Dhs82 activity can be significantly enhanced in the presence of solvents over a concentration range of 10–30 % (<em>v</em>/v). Notably, Dhs82 also showed high stability towards these solvents and solvent concentrations as high as 50–60 % (<em>v</em>/v) are required to inactivate Dhs82. Furthermore, molecular docking revealed the key residues, including the catalytic triad (Ser156, His281, and Asp251) and the surrounding Gly84 and Gly85, involved in the interaction of Dhs82 with DBP, depicting how Dhs82 degrades PAEs as a family IV esterase. Together, these diverse properties make Dhs82 a valuable candidate for both basic research and biotechnological applications.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"316 ","pages":"Article 107348"},"PeriodicalIF":3.3,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Chondroblastic Osteosarcoma of the Maxilla with Poor Response to Neoadjuvant Chemotherapy: A Rare Case Report and Updated Review of Literature.","authors":"Jyotiman Nath, Anupam Das, Duncan Khanikar, Shiraj Ahmed, Kaberi Kakati","doi":"10.1007/s12070-023-04037-0","DOIUrl":"10.1007/s12070-023-04037-0","url":null,"abstract":"<p><p>Craniofacial osteosarcoma is a relatively rare disease entity. In the craniofacial region, mandible is the commonest site followed by maxilla and skull bone. Due to its rare occurrence standard treatment guidelines are not formulated as in long bone or extremity sarcoma. Here we have reported a locally advanced case of a maxillary osteosarcoma of chondroblastic variant who was initially considered for neoadjuvant chemotherapy. However there was radiological evience of disease progression. Then the patient was considered for surgery followed by adjuvant radiotherapy. A literature review of the published cases of maxillary chondroblastic osteosarcoma has also been done here.</p>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"218 1","pages":"4041-4046"},"PeriodicalIF":0.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10645781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75854990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"TPE conjugated islet amyloid polypeptide probe for detection of peptide oligomers","authors":"Hsiao-Chieh Tsai, Ching-Hong Huang, Ling-Hsien Tu","doi":"10.1016/j.bpc.2023.107129","DOIUrl":"10.1016/j.bpc.2023.107129","url":null,"abstract":"<div><p>Islet amyloid polypeptide (IAPP), also known as amylin, is a polypeptide hormone co-secreted with insulin by pancreatic β-cells. In general, IAPP is soluble and lacks a defined structure. However, under certain conditions, these peptides tend to aggregate into soluble oligomers, eventually forming insoluble amyloid fibrils with typical cross-β-sheet structures. Amylin aggregates, therefore, have been regarded as one of the hallmarks of type II diabetes (T2D). Among these aggregated species, oligomers were shown to exhibit significant cytotoxicity, leading to impaired β-cell function and reduced β-cell mass. Monitoring of oligomer appearance during IAPP fibrillation is of particular interest. In this study, we successfully grafted an aggregation-induced emission molecule, tetraphenylethylene (TPE), at the N-terminus of IAPP. By mixing a small amount of TPE-labeled IAPP with unlabeled IAPP, we were able to detect an increase in TPE fluorescence during the nucleation phase of IAPP aggregation <em>in vitro</em>. It may enable real-time monitoring of IAPP oligomer formation and is further applied in the diagnosis of T2D.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"304 ","pages":"Article 107129"},"PeriodicalIF":3.8,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72208270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lena Ostermeier , Moreno Ascani , Nicolás Gajardo-Parra , Gabriele Sadowski , Christoph Held , Roland Winter
{"title":"Leveraging liquid-liquid phase separation and volume modulation to regulate the enzymatic activity of formate dehydrogenase","authors":"Lena Ostermeier , Moreno Ascani , Nicolás Gajardo-Parra , Gabriele Sadowski , Christoph Held , Roland Winter","doi":"10.1016/j.bpc.2023.107128","DOIUrl":"10.1016/j.bpc.2023.107128","url":null,"abstract":"<div><p><span>Engineering of reaction media is an exciting alternative for modulating kinetic properties<span> of biocatalytic reactions. We addressed the combined effect of an aqueous two-phase system (ATPS) and high hydrostatic pressure on the kinetics of the </span></span><span><em>Candida boidinii</em></span><span> formate dehydrogenase-catalyzed oxidation of formate to CO</span><sub>2</sub><span>. Pressurization was found to lead to an increase of the binding affinity (decrease of </span><em>K</em><sub>M</sub><span>, respectively) and a decrease of the turnover number, </span><em>k</em><sub>cat</sub><span>. The experimental approach was supported using thermodynamic modeling with the electrolyte Perturbed-Chain Statistical Associating Fluid Theory (ePC-SAFT) equation of state to predict the liquid-liquid phase separation and the molecular crowding effect of the ATPS on the kinetic properties. The ePC-SAFT was able to quantitatively predict the </span><em>K</em><sub>M</sub>-values of the substrate in both phases at 1 bar as well as up to a pressure of 1000 bar. The framework presented enables significant advances in bioprocess engineering, including the design of processes with significantly fewer experiments and trial-and-error approaches.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"304 ","pages":"Article 107128"},"PeriodicalIF":3.8,"publicationDate":"2023-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71477690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nilusha L. Kariyawasam , Elizabeth A. Ploetz , Liskin Swint-Kruse , Paul E. Smith
{"title":"Simulated pressure changes in LacI suggest a link between hydration and functional conformational changes","authors":"Nilusha L. Kariyawasam , Elizabeth A. Ploetz , Liskin Swint-Kruse , Paul E. Smith","doi":"10.1016/j.bpc.2023.107126","DOIUrl":"10.1016/j.bpc.2023.107126","url":null,"abstract":"<div><p>The functions of many proteins are associated with interconversions among conformational substates. However, these substates can be difficult to measure experimentally, and determining contributions from hydration changes can be especially difficult. Here, we assessed the use of pressure perturbations to sample the substates accessible to the <em>Escherichia coli</em> lactose repressor protein (LacI) in various liganded forms. In the presence of DNA, the regulatory domain of LacI adopts an Open conformation that, in the absence of DNA, changes to a Closed conformation. Increasing the simulation pressure prevented the transition from an Open to a Closed conformation, in a similar manner to the binding of DNA and anti-inducer, ONPF. The results suggest the hydration of specific residues play a significant role in determining the population of different LacI substates and that simulating pressure perturbation could be useful for assessing the role of hydration changes that accompany functionally-relevant amino acid substitutions.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"304 ","pages":"Article 107126"},"PeriodicalIF":3.8,"publicationDate":"2023-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71477691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A combination of structure-based virtual screening and experimental strategies to identify the potency of caffeic acid ester derivatives as SARS-CoV-2 3CLpro inhibitor from an in-house database","authors":"Piyatida Pojtanadithee , Kulpornsorn Isswanich , Koonchira Buaban , Supakarn Chamni , Patcharin Wilasluck , Peerapon Deetanya , Kittikhun Wangkanont , Thierry Langer , Peter Wolschann , Kamonpan Sanachai , Thanyada Rungrotmongkol","doi":"10.1016/j.bpc.2023.107125","DOIUrl":"https://doi.org/10.1016/j.bpc.2023.107125","url":null,"abstract":"<div><p>Drug development requires significant time and resources, and computer-aided drug discovery techniques that integrate chemical and biological spaces offer valuable tools for the process. This study focused on the field of COVID-19 therapeutics and aimed to identify new active non-covalent inhibitors for 3CL<sup>pro</sup>, a key protein target. By combining <em>in silico</em> and <em>in vitro</em> approaches, an in-house database was utilized to identify potential inhibitors. The drug-likeness criteria were considered to pre-filter 553 compounds from 12 groups of natural products. Using structure-based virtual screening, 296 compounds were identified that matched the chemical features of SARS-CoV-2 3CL<sup>pro</sup> peptidomimetic inhibitor pharmacophore models. Subsequent molecular docking resulted in 43 hits with high binding affinities. Among the hits, caffeic acid analogs showed significant interactions with the 3CL<sup>pro</sup> active site, indicating their potential as promising candidates. To further evaluate their efficacy, enzyme-based assays were conducted, revealing that two ester derivatives of caffeic acid (<strong>4k</strong> and <strong>4l</strong>) exhibited more than a 30% reduction in 3CL<sup>pro</sup> activity. Overall, these findings suggest that the screening approach employed in this study holds promise for the discovery of novel anti-SARS-CoV-2 therapeutics. Furthermore, the methodology could be extended for optimization or retrospective evaluation to enhance molecular targeting and antiviral efficacy of potential drug candidates.</p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"304 ","pages":"Article 107125"},"PeriodicalIF":3.8,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71730275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alyssa R. Stonebraker , Rachel Hankin , Kathryn L. Kapp , Peng Li , Stephen J. Valentine , Justin Legleiter
{"title":"Charge within Nt17 peptides modulates huntingtin aggregation and initial lipid binding events","authors":"Alyssa R. Stonebraker , Rachel Hankin , Kathryn L. Kapp , Peng Li , Stephen J. Valentine , Justin Legleiter","doi":"10.1016/j.bpc.2023.107123","DOIUrl":"10.1016/j.bpc.2023.107123","url":null,"abstract":"<div><p>Toxic aggregation of pathogenic huntingtin<span><span> protein (htt) is implicated in Huntington's disease and influenced by various factors, including the first seventeen amino acids at the N-terminus (Nt17) and the presence of </span>lipid membranes<span><span>. Nt17 has a propensity to form an amphipathic α-helix in the presence of binding partners, which promotes α-helix rich oligomer<span> formation and facilitates htt/lipid interactions. Within Nt17 are multiple sites that are subject to post-translational modification, including acetylation and phosphorylation. Acetylation can occur at lysine 6, 9, and/or 15 while phosphorylation can occur at </span></span>threonine<span> 3, serine<span><span> 13, and/or serine 16. Such modifications impact aggregation and lipid<span> binding through the alteration of various intra- and intermolecular interactions. When incubated with htt-exon1(46Q), free Nt17 peptides containing </span></span>point mutations<span> mimicking acetylation or phosphorylation reduced fibril formation and altered oligomer morphologies. Upon exposure to lipid vesicles, changes to peptide/lipid complexation were observed and peptide-containing oligomers demonstrated reduced lipid interactions.</span></span></span></span></span></p></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"303 ","pages":"Article 107123"},"PeriodicalIF":3.8,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49674013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}