Jussara Valente Roque, Marcella Ferreira Rodrigues, Gabriel Henry M Dufrayer, Iris Medeiros Júnior, Rogério Mesquita de Carvalho, Gesiane da Silva Lima, Gabriel Franco Dos Santos, Boniek Gontijo Vaz
{"title":"Characterization and Quantification of Naphthenic Acids in Produced Water by Orbitrap MS and a Multivariate Approach.","authors":"Jussara Valente Roque, Marcella Ferreira Rodrigues, Gabriel Henry M Dufrayer, Iris Medeiros Júnior, Rogério Mesquita de Carvalho, Gesiane da Silva Lima, Gabriel Franco Dos Santos, Boniek Gontijo Vaz","doi":"10.1021/jasms.4c00172","DOIUrl":"10.1021/jasms.4c00172","url":null,"abstract":"<p><p>Naphthenic acids (NAs) naturally occur in crude oil and its associated produced water, presenting significant challenges, such as corrosion, in refinery apparatus and ecotoxicity in aquatic habitats. This study delineates a multivariate method to quantify NAs in produced water via electrospray ionization coupled with high-resolution Orbitrap mass spectrometry (ESI-Orbitrap MS). By employing liquid-liquid extraction, followed by direct infusion ESI(-)-Orbitrap MS, we characterized and quantified NAs employing a partial least-squares regression (PLS) model enhanced by the ordered predictor selection (OPS) algorithm. Thirty-six produced water samples were utilized, with 24 allocated for calibration and 12 designated for validation. The PLS-OPS model demonstrated notable accuracy in predicting NA concentrations in simulated and actual produced water samples ranging from ∼30 to 300 mg·L<sup>-1</sup>. This methodology offers a rapid yet robust alternative for quantifying NAs using mass spectrometry augmented by PLS and the OPS. Its significance is underscored by its potential to equip the petroleum industry with a swift and reliable monitoring mechanism for NAs in produced water, thereby aiding in mitigating environmental and operational risks.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chunyi Zhao, Samuel T Slocum, David H Sherman, Brandon T Ruotolo
{"title":"Time-Resolved Ion Mobility-Mass Spectrometry Reveals Structural Transitions in the Disassembly of Modular Polyketide Syntheses.","authors":"Chunyi Zhao, Samuel T Slocum, David H Sherman, Brandon T Ruotolo","doi":"10.1021/jasms.4c00181","DOIUrl":"10.1021/jasms.4c00181","url":null,"abstract":"<p><p>The type 1 polyketide synthase (PKS) assembly line uses its modular structure to produce polyketide natural products that form the basis of many pharmaceuticals. Currently, several cryoelectron microscopy (cryo-EM) structures of a multidomain PKS module have been constructed, but much remains to be learned. Here we utilize ion-mobility mass spectrometry (IM-MS) to record size and shape information and detect different conformational states of a 207 kDa didomain dimer comprised of ketosynthase (KS) and acyl transferase (AT), excised from full-length module. Furthermore, gas-phase stability differences between these different conformations are captured by collision induced unfolding (CIU) technology. Additionally, through tracking these forms as a function of time, we elucidate a detailed disassembly pathway for KS-AT dimers for the first time.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Electric Field-Modulated Electrospray Ionization Mass Spectrometry for Quantity Calibration and Mass Tracking.","authors":"Pin-Chieh Hsu, Pawel L Urban","doi":"10.1021/jasms.4c00091","DOIUrl":"10.1021/jasms.4c00091","url":null,"abstract":"<p><p>Analyses conducted by electrospray ionization (ESI) mass spectrometry (MS) typically entail performing a number of preparatory steps, which include quantity calibration and mass calibration. Quantity calibration can be affected by signal noise, while mass calibration can be affected by instrumental drift if analyses are performed over an extended period of time. Here, we present two methods for achieving these calibrations using modulation of electrospray plume by alternating electric fields and demodulating the resulting MS ion currents. For this purpose, we use an ESI source fitted with three ring electrodes between the electrospray emitter and the mass spectrometer's inlet. One of these electrodes is supplied with a sine electric signal. Optionally, a nanoESI emitter is also placed between the ring electrodes and the mass spectrometer's orifice to supply calibrant ions. The ion currents, recorded with this setup, present wave-like features. In the first variant, using a triple quadrupole mass analyzer, the ion currents are subjected to data treatment by fast Fourier transform (FFT), and the resulting FFT magnitudes are correlated with analyte concentrations to produce a calibration plot. In the second variant, using a quadrupole time-of-flight mass analyzer, the mass spectra recorded at the analyte ion current maxima are mass-checked using the <i>m</i>/<i>z</i> value of the internal standard (injected via nanoESI emitter), which appears predominantly in the time intervals corresponding to the analyte ion current minima. The setup has been characterized using simulation software and optimized. Overall, the method enables the preparation of quantity calibration plots and monitoring (minor) <i>m</i>/<i>z</i> drifts during prolonged analyses.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141092746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mei-Qing Zuo, Ge Song, Ji-Shuai Zhang, Meng-Qiu Dong, Rui-Xiang Sun
{"title":"Effect of Terminal Phosphate Groups on Collisional Dissociation of RNA Oligonucleotide Anions.","authors":"Mei-Qing Zuo, Ge Song, Ji-Shuai Zhang, Meng-Qiu Dong, Rui-Xiang Sun","doi":"10.1021/jasms.4c00149","DOIUrl":"10.1021/jasms.4c00149","url":null,"abstract":"<p><p>The increasing need for mass spectrometric analysis of RNA molecules calls for a better understanding of their gas-phase fragmentation behaviors. In this study, we investigate the effect of terminal phosphate groups on the fragmentation spectra of RNA oligonucleotides (oligos) using high-resolution mass spectrometry (MS). Negative-ion mode collision-induced dissociation (CID) and higher-energy collisional dissociation (HCD) were carried out on RNA oligos containing a terminal phosphate group on either end, both ends, or neither end. We find that terminal phosphate groups affect the fragmentation behavior of RNA oligos in a way that is dependent on the precursor charge state and the oligo length. Specifically, for precursor ions of RNA oligos of the same sequence, those with 5'- or 3'-phosphate, or both, have a higher charge state distribution and lose the phosphate group(s) in the form of a neutral (H<sub>3</sub>PO<sub>4</sub> or HPO<sub>3</sub>) or an anion ([H<sub>2</sub>PO<sub>4</sub>]<sup>-</sup> or [PO<sub>3</sub>]<sup>-</sup>) upon CID or HCD. Such a neutral or charged loss is most conspicuous for precursor ions of an intermediate charge state, e.g., 3<sup>-</sup> for 4-nt oligos or 4<sup>-</sup> and 5<sup>-</sup> for 8-nt oligos. This decreases the intensity of sequencing ions (<i>a-</i>, <i>a-B</i>, <i>b-</i>, <i>c-</i>, <i>d-</i>, <i>w-</i>, <i>x-</i>, <i>y-</i>, <i>z-</i>ions) and hence is unfavorable for sequencing by CID or HCD. Removal of terminal phosphate groups by calf intestinal alkaline phosphatase improved MS analysis of RNA oligos. Additionally, the intensity of a fragment ion at <i>m</i>/<i>z</i> 158.925, which we identified as a dehydrated pyrophosphate anion ([HP<sub>2</sub>O<sub>6</sub>]<sup>-</sup>), is markedly increased by the presence of a terminal phosphate group. These findings expand the knowledge base necessary for software development for MS analysis of RNA.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sarveenah Chandrasegaran, Jack W Klose, Tara L Pukala
{"title":"Unraveling DNA Triplex Assembly: Mass Spectrometric Investigation of Modified Triplex Forming Oligonucleotides for Enhanced Gene Targeting.","authors":"Sarveenah Chandrasegaran, Jack W Klose, Tara L Pukala","doi":"10.1021/jasms.4c00070","DOIUrl":"10.1021/jasms.4c00070","url":null,"abstract":"<p><p>Deoxyribonucleic acid triplexes have potential roles in a range of biological processes involving gene and transcriptional regulation. A major challenge in exploiting the formation of these higher-order structures to target genes <i>in vivo</i> is their low stability, which is dependent on many factors including the length and composition of bases in the sequence. Here, different DNA base modifications have been explored, primarily using native mass spectrometry, in efforts to enable stronger binding between the triplex forming oligonucleotide (TFO) and duplex target sites. These modifications can also be used to overcome pyrimidine interruptions in the duplex sequence in promoter regions of genomes, to expand triplex target sequences for antigene therapies. Using model sequences with a single pyrimidine interruption, triplex forming oligonucleotides containing locked nucleic acid base modifications were shown to have a higher triplex binding propensity than DNA-only and dSpacer-containing TFOs. However, the triplex forming ability of these systems was limited by the competitive formation of multiple higher order assemblies. Triplex forming sequences that correspond to specific gene targets from the <i>Pseudomonas aeruginosa</i> genome were also investigated, with LNA-containing TFOs the only variant able to form triplex using these sequences. This work indicates the advantages of utilizing synthetically modified TFOs to form triplex assemblies <i>in vivo</i> for potential therapeutic applications and highlights the advantages of native mass spectrometry for the study of their formation.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141873889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Special Issue in Honor of Brandon Ruotolo, Recipient of the 2023 ASMS Biemann Medal.","authors":"Jenny Brodbelt, Vicki Wysocki","doi":"10.1021/jasms.4c00339","DOIUrl":"https://doi.org/10.1021/jasms.4c00339","url":null,"abstract":"","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ewelina Sibińska, Justyna Walczak-Skierska, Adrian Arendowski, Agnieszka Ludwiczak, Aleksandra Radtke, Piotr Piszczek, Dorota Gabryś, Kinga Robotnik, Paweł Pomastowski
{"title":"Advances in LDI-MS Analysis: The Role of Chemical Vapor Deposition-Synthesized Silver Nanoparticles in Enhancing Detection of Low-Molecular-Weight Biomolecules.","authors":"Ewelina Sibińska, Justyna Walczak-Skierska, Adrian Arendowski, Agnieszka Ludwiczak, Aleksandra Radtke, Piotr Piszczek, Dorota Gabryś, Kinga Robotnik, Paweł Pomastowski","doi":"10.1021/jasms.4c00071","DOIUrl":"10.1021/jasms.4c00071","url":null,"abstract":"<p><p>In this investigation, we detail the synthesis of silver nanoparticles (AgNPs) via a precise chemical vacuum deposition (CVD) methodology, aimed at augmenting the analytical performance of laser desorption/ionization mass spectrometry (LDI-MS) for the detection of low-molecular-weight analytes. Employing a precursor supply rate of 0.0014 mg/s facilitated the formation of uniformly dispersed AgNPs, characterized by SEM and AFM to have an average diameter of 33.5 ± 1.5 nm and a surface roughness (<i>R</i><sub>a</sub>) of 11.8 nm, indicative of their homogeneous coverage and spherical morphology. XPS and SEM-EDX analyses confirmed the metallic silver composition of the nanoparticles with Ag peak splitting, reflecting the successful synthesis of metallic Ag. Comparative analytical evaluation with traditional MALDI matrices revealed that AgNPs significantly reduce signal suppression, thereby enhancing the sensitivity and specificity of LDI-MS for low-molecular-weight compounds such as triglycerides, saccharides, amino acids, and carboxylic acids. Notably, the application of AgNPs demonstrated a superior linear response for triglyceride signals with regression coefficients surpassing 0.99, markedly outperforming conventional matrices. The study further extends into quantitative analysis through nanoparticle-based laser desorption/ionization (NALDI), where AgNPs exhibited enhanced ionization efficiency, characterized by substantially lower limits of detection (LOD) and quantification (LOQ) for tested standards. Particular attention was paid to lipids with a detailed examination of their fragmentation pathways. These results highlight the significant potential of AgNPs synthesized via CVD to transform the analytical detection and quantification of low-molecular-weight compounds using NALDI. This approach offers a promising avenue for expanding the scope of analytical applications in mass spectrometry and introducing innovative methodologies for enhanced precision and sensitivity.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141974827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mirela Sarbu, Daniela G Seidler, David E Clemmer, Alina D Zamfir
{"title":"Introducing Ion Mobility Mass Spectrometry in Brain Glycosaminoglycomics: Application to Chondroitin/Dermatan Sulfate Octasaccharide Domains.","authors":"Mirela Sarbu, Daniela G Seidler, David E Clemmer, Alina D Zamfir","doi":"10.1021/jasms.4c00159","DOIUrl":"10.1021/jasms.4c00159","url":null,"abstract":"<p><p>Glycosaminoglycans (GAGs) are sulfated linear <i>O</i>-glycan chains abundantly expressed in the extracellular matrix (ECM). Among GAGs, chondroitin sulfate (CS) and dermatan sulfate (DS) play important roles at the brain level, where the distribution and location of the sulfates within the CS/DS chains are responsible for numerous biological events. The diversity of the neural hybrid CS/DS expressed in the brain and the need to elucidate their structure gave rise to considerable efforts toward the development of analytical methods able to discover novel regularly and irregularly sulfated domains. In this context, we report here the introduction of ion mobility separation (IMS) mass spectrometry (MS) in brain glycosaminoglycomics. Based on IMS MS and tandem MS (MS/MS) by collision-induced dissociation (CID), we have developed a powerful approach for the screening and structural analysis of neural CS/DS and optimized and validated the method for the structural analysis of octasaccharides that were released from brain proteoglycans by β-elimination and pooled after chain depolymerization using chondroitin AC lyase. The IMS MS data revealed the separation of CS/DS octamers into mobility families based on the amount of sulfation. Among the discovered oversulfated domains, of major biological importance is the pentasulfated-[4,5-Δ-GlcAGalNAc(IdoAGalNAc)<sub>3</sub>], for which the (-) nanoESI IMS CID MS/MS analysis disclosed through the presence of distinct drift times, the incidence of two isomers. Moreover, the generated fragment ions revealed an uncommon trisulfated motif and an uncommon pentasulfated motif. Hence, using IMS MS and CID MS/MS, novel brain-related CS/DS domains of atypical sulfation patterns were discovered and structurally characterized in detail.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142043807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Using Variable Data-Independent Acquisition for Capillary Electrophoresis-Based Untargeted Metabolomics.","authors":"Saki Kiuchi, Yasuhiro Otoguro, Tomoaki Nitta, Mi Hwa Chung, Taiki Nakaya, Yuki Matsuzawa, Katsuya Ohbuchi, Kazunori Sasaki, Hiroyuki Yamamoto, Hiroshi Tsugawa","doi":"10.1021/jasms.4c00132","DOIUrl":"10.1021/jasms.4c00132","url":null,"abstract":"<p><p>Capillary electrophoresis coupled with tandem mass spectrometry (CE-MS/MS) offers advantages in peak capacity and sensitivity for metabolic profiling owing to the electroosmotic flow-based separation. However, the utilization of data-independent MS/MS acquisition (DIA) is restricted due to the absence of an optimal procedure for analytical chemistry and its related informatics framework. We assessed the mass spectral quality using two DIA techniques, namely, all-ion fragmentation (AIF) and variable DIA (vDIA), to isolate 60-800 Da precursor ions with respect to annotation rates. Our findings indicate that vDIA, coupled with the updated MS-DIAL chromatogram deconvolution algorithm, yields higher spectral matching scores and annotation rates compared to AIF. Additionally, we evaluated a linear migration time (MT) correction method using internal standards to accurately align chromatographic peaks in a data set. Postcorrection, the data set exhibited less than 0.1 min MT drifts, a difference mostly equivalent to that of conventional reverse-phase liquid chromatography techniques. Moreover, we conducted MT prediction for metabolites recorded in mass spectral libraries and metabolite structure databases containing a total of 469,870 compounds, achieving an accuracy of less than 1.5 min root mean squares. Our platform provides a peak annotation platform utilizing MT information, accurate precursor <i>m</i>/<i>z</i>, and the MS/MS spectrum recommended by the metabolomics standards initiative. Applying this procedure, we investigated metabolic alterations in lipopolysaccharide (LPS)-induced macrophages, characterizing 170 metabolites. Furthermore, we assigned metabolite information to unannotated peaks using an <i>in silico</i> structure elucidation tool, MS-FINDER. The results were integrated into the nodes in the molecular spectrum network based on the MS/MS similarity score. Consequently, we identified significantly altered metabolites in the LPS-administration group, where glycinamide ribonucleotide, not present in any spectral libraries, was newly characterized. Additionally, we retrieved metabolites of false-negative hits during the initial spectral annotation procedure. Overall, our study underscores the potential of CE-MS/MS with DIA and computational mass spectrometry techniques for metabolic profiling.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ceder Dens, Charlotte Adams, Kris Laukens, Wout Bittremieux
{"title":"Machine Learning Strategies to Tackle Data Challenges in Mass Spectrometry-Based Proteomics.","authors":"Ceder Dens, Charlotte Adams, Kris Laukens, Wout Bittremieux","doi":"10.1021/jasms.4c00180","DOIUrl":"10.1021/jasms.4c00180","url":null,"abstract":"<p><p>In computational proteomics, machine learning (ML) has emerged as a vital tool for enhancing data analysis. Despite significant advancements, the diversity of ML model architectures and the complexity of proteomics data present substantial challenges in the effective development and evaluation of these tools. Here, we highlight the necessity for high-quality, comprehensive data sets to train ML models and advocate for the standardization of data to support robust model development. We emphasize the instrumental role of key data sets like ProteomeTools and MassIVE-KB in advancing ML applications in proteomics and discuss the implications of data set size on model performance, highlighting that larger data sets typically yield more accurate models. To address data scarcity, we explore algorithmic strategies such as self-supervised pretraining and multitask learning. Ultimately, we hope that this discussion can serve as a call to action for the proteomics community to collaborate on data standardization and collection efforts, which are crucial for the sustainable advancement and refinement of ML methodologies in the field.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}