Analytical and Bioanalytical Chemistry最新文献

{"title":"Application of separation and configuration identification of the four tetrabenazine stereoisomers in determining their pharmacokinetics.","authors":"Jianxin Li, Haoran Li, Kai Liu, Alan Kueichieh Chang, Ying Pei, Wenbao Liu, Jiao Ai, Nan Wang, Yuhui Liu, Zhen Jiang, Lijiang Chen, Xiao Liang","doi":"10.1007/s00216-025-05813-3","DOIUrl":"https://doi.org/10.1007/s00216-025-05813-3","url":null,"abstract":"<p><p>Tetrabenazine (TBZ) is used in the treatment of psychiatric diseases, and it works by inhibiting vesicular monoamine transporter 2 (VMAT2) protein to exert a curative effect. TBZ is administered as the mixture of stereoisomers in clinical treatment. TBZ has two chiral centers, and therefore, it has four stereoisomers, and this greatly makes it difficult to separate the stereoisomers and to identify their configurations because of their high susceptibility to structural transformation. This study aims to develop a method to resolve TBZ into four individual peaks, corresponding to the four stereoisomers (1-4). Based on the different binding affinities between TBZ stereoisomers and VMAT2, the UF-UHPLC-QQQ/MS method is used to determine the absolute configuration of TBZ stereoisomers 1 and 2. Molecular docking simulations are used to verify the accuracy of UF-UHPLC-QQQ/MS. The configurations of stable stereoisomers 3 and 4 were confirmed by electron circular dichroism (ECD). The established analytical method was applied to determine the pharmacokinetics of each TBZ stereoisomer in vivo. It was found that the stereoisomer 1 (3R,11bR-TBZ) showed better bioavailability and more excretion than the other stereoisomers. The results of tissue distribution experiments indicated a much higher content of 3R,11bR-TBZ in the brain, suggesting that it may better penetrate the blood-brain barrier and exert its therapeutic effects there. The paper addresses the complex problem of separating and identifying stereoisomers with multiple chiral centers, which is a significant challenge in pharmaceutical chemistry. And this work could provide a basis for the preparation of TBZ stereoisomers and a reference for the method of separating drugs with multichiral centers and identifying unstable drugs based on their configurations.</p>","PeriodicalId":462,"journal":{"name":"Analytical and Bioanalytical Chemistry","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584239","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":"Predicting bone aging using spatially offset Raman spectroscopy: a longitudinal analysis on mice.","authors":"Hongmei Dou, Wendong Sun, Shuo Chen, Keren Chen","doi":"10.1007/s00216-025-05819-x","DOIUrl":"https://doi.org/10.1007/s00216-025-05819-x","url":null,"abstract":"<p><p>Osteoporosis, a global health concern, poses an increasing challenge due to the aging population. While dual-energy X-ray absorptiometry (DXA) scans measuring bone mineral density (BMD) remain the clinical standard for osteoporosis diagnosis, this method's inability to detect changes in bone chemical composition limits its effectiveness in early diagnosis. This study applies Raman spectroscopy on examining bone aging in Senescence Accelerated Mouse Prone 6 (SAMP6) mice compared to their senescence-resistant controls (SAMR1) over an age period from 6 to 10 months. We performed Raman spectroscopic analysis on mouse tibiae both transcutaneously and on exposed bone. Leave-one-out cross-validation combined with partial least squares regression (LOOCV-PLSR) was applied to analyze Raman spectra to predict age, BMD, and maximum torque (MT) as determined by biomechanical testing. Our results revealed significant correlations between Raman spectroscopic predictions and reference values, particularly for age determination. To our knowledge, this study represents the first demonstration of transcutaneous Raman spectroscopy for accurate bone aging prediction, showing a strong correlation with established reference measurements.</p>","PeriodicalId":462,"journal":{"name":"Analytical and Bioanalytical Chemistry","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571871","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":"Publisher Correction: Robust discrimination between closely related species of salmon based on DNA fragments.","authors":"Debra Ellisor, Mary Gregg, Angela Folz, Antonio Possolo","doi":"10.1007/s00216-025-05800-8","DOIUrl":"https://doi.org/10.1007/s00216-025-05800-8","url":null,"abstract":"","PeriodicalId":462,"journal":{"name":"Analytical and Bioanalytical Chemistry","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565580","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":"Development of amyloid β (1-42) certified reference material NMIJ CRM 6210-a.","authors":"Kazumi Saikusa, Tomoya Kinumi, Megumi Kato","doi":"10.1007/s00216-025-05797-0","DOIUrl":"https://doi.org/10.1007/s00216-025-05797-0","url":null,"abstract":"<p><p>Amyloid β is a well-known peptide biomarker for Alzheimer's disease. Various methods for amyloid β such as immunological assays have been reported. It is important to establish metrological traceability using a certified reference material (CRM) at the highest level in the calibration hierarchy to assess equivalence of measured values obtained from each method. Herein, we developed a CRM for amyloid β, named as NMIJ CRM 6210-a, with a concentration traceable to the International System of Units (SI). This CRM comprises a lyophilized synthetic peptide with a human amyloid β (1-42) sequence (hereafter, amyloid β) and includes oxidated, deamidated, and isomerized forms of amyloid β. Two certified values were assigned for the mass concentration of total amyloid β (a mixture of amyloid β and its oxidized, deamidated, and isomerized forms) and amyloid β, determined via amino acid analyses with two different hydrolysis methods with different liquid chromatography mass spectrometry methods coupled to isotope-dilution mass spectrometry on the reconstituted solution of the candidate material with (1.00 <math><mo>±</mo></math> 0.01) g of 0.1% ammonia aqueous solution. The quantitative results obtained from amino acid analyses were converted into mass concentration using the density and molar mass, resulting in certified values of (46 <math><mo>±</mo></math> 11) mg/L for total amyloid β and (42.6 <math><mo>±</mo></math> 7.0) mg/L for amyloid β, respectively. The amyloid β content in total amyloid β was determined by calculating the relative area percentage using liquid chromatography with ultraviolet detection. Furthermore, the storage stability of this CRM was evaluated along with its stability in use, both of which were shown to be stable.</p>","PeriodicalId":462,"journal":{"name":"Analytical and Bioanalytical Chemistry","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555527","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":"Covalent organic framework derived single-atom copper nanozymes for the detection of amyloid-β peptide and study of amyloidogenesis.","authors":"Yuxin Wei, Qingqing Bai, Xinlu Ning, Xiaofan Bai, Jie Lv, Meng Li","doi":"10.1007/s00216-024-05683-1","DOIUrl":"10.1007/s00216-024-05683-1","url":null,"abstract":"<p><p>Sensitive and accurate detection of the amyloid-β (Aβ) monomer is of fundamental significance for early diagnosis of Alzheimer's disease (AD). Herein, inspired by the specific Cu-Aβ monomer coordination, a cutting-edge colorimetric assay based on single-atom Cu anchored N-doped carbon nanospheres (Cu-NCNSs) was developed for Aβ monomer detection and an amyloidogenesis study. By directly pyrolyzing Cu²⁺-incorporated covalent organic frameworks (COFs), the resulting Cu-NCNSs with a high loading of Cu (8.04 wt %) exhibited outstanding peroxidase-like activity. The strong binding affinity of Aβ monomer to Cu-NCNSs effectively inhibited their catalytic activity, providing the basis for the colorimetric assay. The Cu-NCNSs-based sensor showed a detection limit of 1.182 nM for Aβ monomer, surpassing traditional techniques in terms of efficiency, accuracy and simplicity. Moreover, the system was successfully utilized for Aβ monomer detection in rat cerebrospinal fluid (CSF). Notably, the distinct inhibitory effects of monomeric and aggregated Aβ species on the catalytic activity of Cu-NCNSs were allowed for monitoring of the dynamic aggregation process of Aβ. Compared to thioflavin T (ThT), the most widely used amyloid dye, the detection system exhibited greater sensitivity towards toxic Aβ oligomers, which was crucial for early AD diagnosis and treatment. Our work not only sheds light on the rational design of highly active single-atom nanozymes from COFs but also expands the potential applications of nanozymes in early disease diagnosis.</p>","PeriodicalId":462,"journal":{"name":"Analytical and Bioanalytical Chemistry","volume":" ","pages":"1081-1092"},"PeriodicalIF":3.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833591","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":"AuNPs/GO/Pt microneedle electrochemical sensor for in situ monitoring of hydrogen peroxide in tomato stems in response to wounding stimulation.","authors":"Xiaolong Yang, Doudou Huo, Yiran Tian, Xingliu Geng, Liang Xu, Daji Zhong, Rong Zhou, Songzhi Xu, Yali Zhang, Lijun Sun","doi":"10.1007/s00216-024-05728-5","DOIUrl":"10.1007/s00216-024-05728-5","url":null,"abstract":"<p><p>Hydrogen peroxide (H₂O₂) is a critical signaling molecule with significant roles in various physiological processes in plants. Understanding its regulation through in situ monitoring could offer deeper insights into plant responses and stress mechanisms. In this study, we developed a microneedle electrochemical sensor to monitor H₂O₂ in situ, offering deeper insights into plant stress responses. The sensor features a platinum wire (100 µm diameter) modified with graphene oxide (GO) and gold nanoparticles (AuNPs) as the working electrode, an Ag/AgCl wire (100 µm diameter) as the reference electrode, and an untreated platinum wire (100 µm diameter) as the counter electrode. This innovative design enhances sensitivity and selectivity through the high catalytic activity of AuNPs, increased surface area from GO, and the superior conductivity of platinum. Operating at a low potential of -0.2 V to minimize interference, the sensor detects H₂O₂ concentrations from 10 to 1000 µM with high accuracy. In situ monitoring of H₂O₂ dynamics in tomato stems under the wounding stimulation reveals that H₂O₂ concentration increases as the sensor approaches the wound site, indicating localized production and transport of H₂O₂. This approach not only improves H₂O₂ monitoring in plant systems but also paves the way for exploring its generation, transport, and elimination mechanisms.</p>","PeriodicalId":462,"journal":{"name":"Analytical and Bioanalytical Chemistry","volume":" ","pages":"1067-1079"},"PeriodicalIF":3.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027641","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":"Quantitative analysis of Δ⁸- and Δ⁹-tetrahydrocannabinol metabolites and isomers: a rapid assay in urine by LC-MS/MS.","authors":"Marco Ballotari, Michael T Truver, Nayana A Sojin, Lauren A Agliano, Rhea Parimoo, Jennifer L Hoyer, Amie J Goodin, Deepthi S Varma, Chris W Chronister, Kay Roussos-Ross, Bruce A Goldberger","doi":"10.1007/s00216-025-05738-x","DOIUrl":"10.1007/s00216-025-05738-x","url":null,"abstract":"<p><p>An increasing number of cannabis-related products have become available and entered the market, particularly those containing cannabidiol (CBD) and Δ⁸-tetrahydrocannabinol (Δ⁸-THC). Analytical methods for cannabinoids in urine have been described extensively in the literature. However, methods providing good resolution for distinguishing interferences from THC positional isomers are needed. The aim of this project was to develop and validate a liquid chromatography with tandem mass spectrometry (LC-MS/MS) method to quantitate a broad panel of cannabinoids in authentic urine specimens. The method was optimized to quantitate Δ⁸-THC and Δ⁹-THC, 11-OH-Δ⁸-THC and 11-OH-Δ⁹-THC, Δ⁸-THC-COOH and Δ⁹-THC-COOH, CBD, 7-COOH-CBD, CBG, and CBN, and validated with the guidance of the American Academy of Forensic Sciences Standards Board (ASB) Standard 036. The validated assay was then used to evaluate urine samples collected over various time points from female patients (N = 69) enrolled in a study assessing prevalence of marijuana/CBD use during pregnancy from November 2022 to May 2024. Δ⁸- and Δ⁹- isomers were chromatographically resolved and successfully separated. For all analytes, the lower limit of quantitation (LLOQ) was determined to be 10 ng/mL, and the upper limit of quantitation (ULOQ) was 1000 ng/mL. In the authentic samples, the most frequently detected analyte was Δ⁹-THC-COOH, with a median concentration of 278 ng/mL (n = 38). Δ⁹-THC and 11-OH-Δ⁹-THC were detected with a median concentration of 42.4 ng/mL (n = 5) and 65.7 ng/mL (n = 34), respectively. Δ⁸-THC-COOH was detected in n = 3 specimens, with a median concentration of 25.5 ng/mL. The study provided a rapid assay for the analysis of cannabinoids in urine.</p>","PeriodicalId":462,"journal":{"name":"Analytical and Bioanalytical Chemistry","volume":" ","pages":"1507-1518"},"PeriodicalIF":3.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021701","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":"Enhanced solid-liquid synergistic microextraction of nine bisphenols in serum using polyaniline functionalized metal-organic framework nanocomposites/methyl tert-butyl ether.","authors":"Zirong Lan, Linlin Ma, Yanjun Yu, Jiang Qing, Taoyu Meng, Wenli Zhou, Zhou Xu, Mao Long Chen, Li Wen, Yunhui Cheng, Libing Wang, Li Ding","doi":"10.1007/s00216-025-05752-z","DOIUrl":"10.1007/s00216-025-05752-z","url":null,"abstract":"<p><p>Bisphenols, as a new class of environmental endocrine disruptors (EED), can interfere with the endocrine system of the human body and lead to various diseases. In this study, a novel polyaniline functionalized metal-organic framework (PANI@MIL-101@HF) was synthesized by utilizing hollow fibers (HF) as the the immobilization carrier, and combined with methyl tert-butyl ether (MTBE) for solid-liquid cooperative adsorption to determine bisphenols (BPs) in serum samples. The immobilized adsorbent exhibited excellent high stability and hydrophobicity. Furthermore, the inclusion of amino and benzene rings in PANI enhanced the adsorption efficiency of BPs through π-π and hydrogen bond interactions. Surprisingly, owing to the synergies of size exclusion effect of the MIL-101 and HF, the exclusion rate of protein reached as high as 99.2-99.9%. Based on its excellent adsorption properties and protein exclusion effect, the immobilized adsorbent PANI@MIL-101@HF was successfully used as a new restricted material for the high extraction performance with solid-liquid synergy of nine bisphenols (BPs) in serum samples. The operation process has also become more convenient without centrifuging. Integrated with ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), the nine BPs in serum samples have a wide linear range (2-200 ng mL^-1) with low quantitative limits of 0.02 ng mL^-1, and the recoveries ranged from 84.65 to 112.56%. The proposed method could be widely applied in convenient, green, and sensitive detection of endocrine disruptors from serum samples.</p>","PeriodicalId":462,"journal":{"name":"Analytical and Bioanalytical Chemistry","volume":" ","pages":"1619-1634"},"PeriodicalIF":3.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073370","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":"Quantification of mycophenolic acid in plasma by isotope dilution liquid chromatography-tandem mass spectrometry candidate reference method.","authors":"Jing Lin, Min Shen, Ting Yu, Huimin Wang, Jingjue Pan, Gaipeng Huang, Quanle Li","doi":"10.1007/s00216-025-05750-1","DOIUrl":"10.1007/s00216-025-05750-1","url":null,"abstract":"<p><p>Accurate measurements of plasma mycophenolic acid (MPA) are essential for therapeutic drug monitoring in transplant recipients and autoimmune diseases. The performance of plasma mycophenolic acid routine methods remains highly variable that calls for a candidate reference measurement procedure (cRMP) to improve the standardization of plasma mycophenolic acid measurements. In this study, sample preparation was based on protein precipitation with methanol followed by further dilution. The mycophenolic acid was quantified by the isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) with electrospray ionization in positive ion mode. According to the Clinical and Laboratory Standards Institute (CLSI) documents C62-A and C50-A, the basic analytical performance of the candidate reference method was verified, such as linearity, limit of quantification, matrix effect, precision, accuracy, and uncertainty. Moreover, the candidate reference measurement procedure was compared with the routine liquid chromatography-tandem mass spectrometry (LC-MS/MS) method in a clinical laboratory. Based on the data, the mycophenolic acid in human plasma was well detected by ID-LC-MS/MS. No apparent interferences were found with the mycophenolic acid measurement. The calibration curve for the mycophenolic acid was linear in the concentration range of 0.1-50 μg/mL with a correlation coefficient of 0.9999 under the optimum experimental conditions. This method was sensitive because the low limit of quantitation (LOQ) was 0.05 μg/mL. The recoveries of MPA were 98.11-98.95%. The intra-day and inter-day coefficients of variations (CV) of our method were ≤ 1.53% and ≤ 0.51%, respectively. No obvious matrix effect was observed. There was a good correlation between this method and the clinical routine LC-MS/MS method. To sum up, we established and validated a reliable plasma MPA method using ID-LC/MS/MS. The desirable accuracy and precision of this method enable it to serve as a promising cRMP to improve the standardization for plasma MPA routine measurements.</p>","PeriodicalId":462,"journal":{"name":"Analytical and Bioanalytical Chemistry","volume":" ","pages":"1607-1617"},"PeriodicalIF":3.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187883","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":"A process monitoring microreactor assembly for real-time reaction analysis using inline near-infrared spectroscopy and chemometrics.","authors":"Lukas Mahler, Pascal Desel, Marcel Sladkov, Andreas Roppertz, Christian Mayer, Martin Jaeger","doi":"10.1007/s00216-025-05779-2","DOIUrl":"10.1007/s00216-025-05779-2","url":null,"abstract":"<p><p>The occurrence of highly exothermic and potential runaway reactions represents a significant hazard to workers, facilities, and the surrounding ecosystem. Due to their high reaction velocity, these reactions often prove difficult to monitor. In many instances, the recorded data result from several single-quantity sensors, such as temperature and pressure sensors. Yet, deviations from the anticipated process, and thus potentially hazardous reaction parameters, may only be identified by the combination of the sensor data, leaving the cause of the deviations unexplained. In this study, a custom-built microreactor in combination with in-line near-infrared spectroscopy and off-line gas chromatography was employed to allow monitoring of the acid-catalyzed esterification of acetic acid and methanol. Using a near-infrared spectrometer in conjunction with partial least squares regression models, reactant and product concentrations could be determined at various residence times and temperatures. This approach enabled the safe and efficient investigation of previously unexamined parameter ranges and the expansion of the design space of experiments. The near-infrared spectra were subjected to principal component analysis classification in order to obtain additional qualitative information. The conversions and space-time yields of the microreactor could be calculated from the obtained data. The values indicated that the microreactor design delivered yields up to twice as high as those of commonly used batch reactors. This study hence demonstrates the efficacy of spectroscopic methods for reaction monitoring in microreactors and their potential for application in micro process analytical technologies.</p>","PeriodicalId":462,"journal":{"name":"Analytical and Bioanalytical Chemistry","volume":" ","pages":"1431-1439"},"PeriodicalIF":3.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}