Journal of Chromatography A最新文献

{"title":"Magnetic C18-modified mesoporous silica as an efficient adsorbent for dispersive solid phase microextraction of cardiac glycosides in human plasma","authors":"Jia Chen ,&nbsp;Run-qin Wang ,&nbsp;Bei-bei Guo ,&nbsp;Li Yang ,&nbsp;Shuang Hu","doi":"10.1016/j.chroma.2026.466736","DOIUrl":"10.1016/j.chroma.2026.466736","url":null,"abstract":"<div><div>A magnetic mesoporous silica (SBA-15)-based dispersive solid phase microextraction was first proposed and introduced for simultaneous analysis of four cardiac glycosides (including deslanoside, lanatoside C, digoxin, and digitoxin) in human plasma coupled with HPLC-UV. In this study, magnetic C₁₈-modified SBA-15 (SBA-15/C₁₈/Fe₃O₄) was used as the extractant, which was prepared and characterized using a suite of techniques including Fourier transform infrared spectroscopy, transmission electron microscopy, N₂ adsorption-desorption, vibrating sample magnetometer, scanning electron microscopy, energy-dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy. The influencing parameters of the extraction were investigated and optimized. The adsorption process of SBA-15/C₁₈/Fe₃O₄ followed the Langmuir isotherm and pseudo-second-order kinetic models. The adsorbent also exhibited excellent thermal and chemical stability, alongside good reusability. Under the optimum experimental conditions, the proposed method demonstrated satisfactory performance with good linearity (8-3200 ng/mL for deslanoside and 1.6-640 ng/mL for lanatoside C, digoxin and digitoxin with the correlation coefficients no less than 0.9987), high precision (0.8%&lt;RSD&lt;9.7%) and accuracy (-10.3%&lt;RE&lt;8.4%), and acceptable extraction recoveries (56.5%-71.0%). In addition, an absence of matrix effect was observed for the proposed method when applied to human plasma, while satisfactory lower limits of quantification (8 ng/mL for deslanoside and 1.6 ng/mL for lanatoside C, digoxin and digitoxin) and stability were obtained. Overall, owing to its simplicity, efficiency, quickness and eco-friendliness, the developed method serves as a promising alternative for determining cardiac glycosides in complex biological matrices.</div></div>","PeriodicalId":347,"journal":{"name":"Journal of Chromatography A","volume":"1771 ","pages":"Article 466736"},"PeriodicalIF":4.0,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146071099","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":"Editorial on the 12th international conference on countercurrent chromatography – CCC2024, Rio de Janeiro, RJ, Brazil","authors":"Gilda Guimarães Leitão ,&nbsp;Martha Knight","doi":"10.1016/j.chroma.2026.466778","DOIUrl":"10.1016/j.chroma.2026.466778","url":null,"abstract":"","PeriodicalId":347,"journal":{"name":"Journal of Chromatography A","volume":"1771 ","pages":"Article 466778"},"PeriodicalIF":4.0,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146199887","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":"The role of particle size distribution on permeability and efficiency of slurry-packed liquid chromatography columns","authors":"Fabrice Gritti","doi":"10.1016/j.chroma.2026.466729","DOIUrl":"10.1016/j.chroma.2026.466729","url":null,"abstract":"<div><div>This review critically examines past and recent studies addressing the intrinsic role of particle size distribution (PSD) in high-performance liquid chromatography (HPLC), with a focus on speed and efficiency. The discussion integrates theoretical models of bed permeability and plate height with experimental evidence to assess the influence of PSD on column permeability and chromatographic resolution. Overall, most findings indicate that PSD has little or no intrinsic impact on key performance metrics, including column permeability, longitudinal diffusion, short-range axial dispersion, and solid–liquid mass transfer, when comparing randomly packed beds of monodisperse and polydisperse particles under equivalent conditions of bed porosity and mean diameters: the Sauter mean diameter for permeability and eddy dispersion and the squared volume-weighted mean particle diameter for slow intraparticle diffusion and high speeds. Rather than reducing particle size polydispersity, efforts should prioritize improved packing methodologies and particle morphologies to minimize long-range structural heterogeneities across the column diameter. While random sphere packings remain the current standard, monodisperse particles may offer some potential for next-generation column technology by enabling highly ordered particulate systems known to deliver superior resolution.</div></div>","PeriodicalId":347,"journal":{"name":"Journal of Chromatography A","volume":"1771 ","pages":"Article 466729"},"PeriodicalIF":4.0,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077296","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":"Analysis of deamination impurity of PS-ONs by chemical derivatization of the enzymatic digest and LC-MS/MS","authors":"Chenyue Zhu ,&nbsp;Chuanxiang Yao ,&nbsp;Huiting Qin ,&nbsp;Wei Zhang ,&nbsp;Xinyue Zheng ,&nbsp;Siying Zheng ,&nbsp;Xinyuan Ye ,&nbsp;Ying Xiong ,&nbsp;Lili Jiang ,&nbsp;Sen Li ,&nbsp;Meiqin Wang ,&nbsp;Hongliang Jiang ,&nbsp;Zhifeng Du","doi":"10.1016/j.chroma.2026.466753","DOIUrl":"10.1016/j.chroma.2026.466753","url":null,"abstract":"<div><div>The presence of deamination impurities in phosphorothioate oligonucleotides (PS-ONs) presents a significant challenge to quality control, as their detection is complicated by minimal mass differences from the parent molecule and difficulties in chromatographic separation. Herein, a bottom-up strategy based on enzymatic digestion, chemical derivatization, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was proposed for the sensitive qualitative and quantitative analysis of trace cytosine deamination in PS-ONs. Fomivirsen (FMVS) and its deamination impurity were used as models. The method involved digestion with S1 nuclease, followed by derivatization of the 5’-phosphorothioate in digests with N-(tert-butyldimethylsilyl)-N-methyltrifluoroacetamide (MTBSTFA) to enhance chromatographic retention and mass spectrometric response. This approach effectively eliminated the need for ion-pairing (IP) reagents. The mass shift upon deamination was amplified in the smaller digested fragments, and a unique isotopic pattern in the derivatized products, specifically, the decrease of the first isotopic peak and the increase of the second isotopic peak was exploited for quantification. The method demonstrated excellent linearity over a weight ratio of deamination product to prototype range from 0.05:1 to 0.9:1. Satisfactory accuracy (80–120%) and precision (RSD &lt; 15%) were achieved. Furthermore, the precise deamination site (C8) within a sample containing 10% deamination impurities was successfully identified. Thus, this method provides a powerful tool for profiling deamination impurities in PS-ONs, with potential applications in quality control, stability studies, and the characterization of other nucleic acid modifications.</div></div>","PeriodicalId":347,"journal":{"name":"Journal of Chromatography A","volume":"1771 ","pages":"Article 466753"},"PeriodicalIF":4.0,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146071100","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":"Utilization of dextran grafting to prepare high-performance wood monolith for efficient bioseparation","authors":"Fei Wang ,&nbsp;Yuting Ren ,&nbsp;Ran Song ,&nbsp;Guiru Chen ,&nbsp;Hongyu Wang ,&nbsp;Luying Wang ,&nbsp;Jing Liu ,&nbsp;Jiandu Lei","doi":"10.1016/j.chroma.2026.466755","DOIUrl":"10.1016/j.chroma.2026.466755","url":null,"abstract":"<div><div>Developing sustainable and efficient separation technologies is crucial for achieving a green transformation in the bioprocessing industry. This study proposes an innovative chromatographic material that utilizes abundant pine wood as raw material. It employs a dextran grafting strategy to functionalize the substrate, resulting in the preparation of high-capacity anion-exchange monolithic columns. This method serves as a robust sustainability strategy, converting low-value biomass into high-value separation media. The optimized monolithic material exhibits a static adsorption capacity of 122.1 mg g^-1 for bovine serum albumin and a dynamic capacity of over 97 mg g^-1. Leveraging the natural convective channels within wood, the material achieves rapid binding kinetics and exhibits excellent column permeability of 1.12 × 10^-10 m². Its exceptional reusability (over 100 cycles) and long-term stability further demonstrate its practicality and economic viability. We validated its practical application value by successfully purifying target proteins from complex mixtures. This work integrates fundamental material innovation with scalable bioprocessing technology to provide a sustainable, high-performance, and cost-effective platform for purifying proteins and other high-value bioproducts.</div></div>","PeriodicalId":347,"journal":{"name":"Journal of Chromatography A","volume":"1771 ","pages":"Article 466755"},"PeriodicalIF":4.0,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111747","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":"Polyethyleneimine hydrogel-silica composite with embedded silver nanoparticles as a multifunctional stationary phase for HPLC","authors":"Feng Hu,&nbsp;Qian Zhao,&nbsp;Qiaoling Liu,&nbsp;Yuefei Zhang,&nbsp;Wei Chen,&nbsp;Sheng Tang","doi":"10.1016/j.chroma.2026.466800","DOIUrl":"10.1016/j.chroma.2026.466800","url":null,"abstract":"<div><div>The development of chromatographic stationary phases remains a persistent focus of scientific inquiry, as their functions and properties directly determine separation efficiency and application scope. Although hydrogel-based stationary phases exhibit prominent advantages such as customizable functionalities and multiple interaction sites, their inherent defects of poor mechanical strength and significant swelling tendency severely restrict their practical implementation in HPLC analysis. Thus, developing novel hydrogel-based stationary phases with excellent mechanical stability and efficient separation capability has become a key demand in this field. In this study, polyethyleneimine (PEI) hydrogel and silver nanoparticles (AgNPs) were successively anchored onto the silica microspheres to prepare a designed AgNPs/PEI nanocomposite hydrogel-functionalized silica stationary phase (AgNPs/PEI hydrogel@SiO₂). By virtue of the strong coordination between the high-density amino groups in PEI and Ag⁺, stable anchoring of metal precursors and uniform dispersion of AgNPs were achieved, while the cross-linking degree of hydrogel was enhanced, simultaneously solving the problems of insufficient mechanical properties of hydrogel-based stationary phases. The AgNPs/PEI hydrogel@SiO₂ stationary phase integrated multiple separation mechanisms and successfully achieved baseline separation of positional isomers, vitamins, nucleosides, and sulfonamides. Notably, the sulfonamides exhibited a typical mixed-mode chromatographic behavior, demonstrating superior retention strength and selectivity on the AgNPs/PEI hydrogel@SiO₂ column compared to the commercial XAmide column. Ultimately, the AgNPs/PEI hydrogel@SiO₂ was successfully applied to the detection of sulfonamides in lotion and lake water, confirming its reliability and accuracy for real sample analysis. This work introduces an innovative design concept for multifunctional HPLC stationary phases, overcoming the limitations of traditional hydrogel-based materials. With its excellent mechanical stability, versatile separation capabilities, and adaptability to complex samples, the AgNPs/PEI nanocomposite hydrogel offers an efficient solution for analyzing intricate systems, highlighting its significant scientific value and broad application potential in HPLC analysis.</div></div>","PeriodicalId":347,"journal":{"name":"Journal of Chromatography A","volume":"1771 ","pages":"Article 466800"},"PeriodicalIF":4.0,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146256934","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 multiresidue analytical procedure for legacy and emerging organic contaminants in marine sediments: Method development, validation, and application","authors":"Imma Tolosa,&nbsp;David Huertas,&nbsp;Brigid Carr,&nbsp;Philippe Bersuder","doi":"10.1016/j.chroma.2026.466772","DOIUrl":"10.1016/j.chroma.2026.466772","url":null,"abstract":"<div><div>This study developed and validated a multiresidue analytical procedure for sediment samples, targeting both legacy contaminants regulated under the UN Stockholm Convention on Persistent Organic Pollutants (POPs) and emerging contaminants of concern to marine ecosystems. The focus was on emerging plastic additives and flame retardants, such as phthalate esters (PAEs) and organophosphate esters (OPEs), for which limited data exists regarding their global presence or fate in the marine environment.</div><div>The methodology targets 6 marker PCBs, 20 organochlorinated pesticides (OCPs), 14 PBDEs, 17 alternative halogenated flame retardants (aHFRs), 19 PAEs, and 17 OPEs. The optimized procedure involves microwave extraction with a mixture of n-hexane and dichloromethane, sulfur clean-up with copper, and silica SPE fractionation to separate legacy POPs and aHFRs from PAEs and OPEs. Gas chromatography coupled with triple quadrupole mass spectrometry (GC-MS/MS) was used to measure the target analytes within two isolated fractions. Method validation included recovery yields in matrix-spiked sediments, reproducibility, repeatability, and blank optimization. Recoveries of PAEs and OPEs at 20-30 ng g⁻¹ ranged within 62–120% for the majority of analytes with RSD&lt; 25%. Method detection limits for PAEs and OPEs ranged from 0.03 ng/g to 12 ng/g dw, influenced by background contamination variability.</div><div>The validated method was applied to marine sediment samples, including reference materials from the International Atomic Energy Agency (IAEA), providing preliminary data on the occurrence of these compounds in the marine environment. Integrating the analysis of PAEs and OPEs into existing procedures for legacy contaminants offers a cost-effective approach to expanding data availability for emerging organic pollutants.</div></div>","PeriodicalId":347,"journal":{"name":"Journal of Chromatography A","volume":"1771 ","pages":"Article 466772"},"PeriodicalIF":4.0,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146155652","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":"Corrigendum to “A green and practical strategy for therapeutic drug monitoring of teicoplanin A2 components in human plasma using functionalized liquid film solvent bar microextraction coupled with high-performance liquid chromatography–ultraviolet detection” [Journal of Chromatography A 1768 (2026) 466673]","authors":"Jie Tian ,&nbsp;Yi-fang Zhang ,&nbsp;Yu-feng Sun ,&nbsp;Dou Yan ,&nbsp;Shuang Hu ,&nbsp;Rong-rong Xing ,&nbsp;Run-qin Wang ,&nbsp;Li Yang ,&nbsp;Xuan Chen","doi":"10.1016/j.chroma.2026.466777","DOIUrl":"10.1016/j.chroma.2026.466777","url":null,"abstract":"","PeriodicalId":347,"journal":{"name":"Journal of Chromatography A","volume":"1771 ","pages":"Article 466777"},"PeriodicalIF":4.0,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146199892","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":"Comparative study of zwitterionic Cinchonane-based ion-exchangers for liquid chromatographic enantioseparations of free fluorinated tryptophanes: mechanistic and thermodynamic insights under green mobile phase conditions","authors":"Dániel Tanács ,&nbsp;Gábor Németi ,&nbsp;Róbert Berkecz ,&nbsp;Zsolt Bozsó ,&nbsp;Gábor K. Tóth ,&nbsp;Wolfgang Lindner ,&nbsp;Antal Péter ,&nbsp;István Ilisz","doi":"10.1016/j.chroma.2026.466811","DOIUrl":"10.1016/j.chroma.2026.466811","url":null,"abstract":"&lt;div&gt;&lt;div&gt;In recent years, growing awareness of environmental sustainability has driven the search for eco-friendly alternatives in analytical chemistry. In liquid chromatography, this includes replacing traditional organic solvents like acetonitrile (MeCN) with greener options that comply with environmental standards while maintaining chromatographic performance. In this study, we describe in a comparative manner the performance of four &lt;em&gt;Cinchona&lt;/em&gt; alkaloid-based ion-exchangers for the enantioresolution of fluorinated tryptophan analogs, applying dimethyl carbonate (DMC) as a green alternative to MeCN. Quinine- and quinidine-based zwitterionic chiral stationary phases (CSPs), namely ZWIX(+), ZWIX(–), ZWIX(+A), and ZWIX(–A) were utilized with binary mobile phase systems consisting of methanol (MeOH), MeCN, and DMC. To the best of our knowledge, this is the first report of the &lt;em&gt;Cinchona&lt;/em&gt; alkaloid-based ion-exchangers applied with DMC-based mobile phase systems.&lt;/div&gt;&lt;div&gt;In polar ionic mode using MeOH/MeCN and MeOH/DMC mobile phases similar retention characteristics were obtained on all the &lt;em&gt;Cinchona&lt;/em&gt;-based columns. Under the same eluent conditions, higher retention factors were observed in the presence of DMC, and in both systems, increasing the proportion of the less polar component (MeCN or DMC) in the mobile phase resulted in a significant increase in retention for all investigated tryptophan analogs, due to stronger interactions with the stationary phase. The stoichiometric displacement model described the dependence of retention on the counterion concentration with good accuracy in both mobile phase systems, and the more negative slopes observed in the case of DMC indicate the formation of stronger ionic interactions. Unlike in the MeCN-based system, the DMC-based eluents showed a general decrease in both enantioselectivity and resolution for most analytes as the DMC content increased on all four columns. Given the substantial difference in polarity between MeCN and DMC, notable variations in enantioselectivity were anticipated. Surprisingly, only modest deviations were detected when comparing mobile phases containing MeCN to those with DMC. Despite the similar chromatographic properties observed for the two solvents, the thermodynamic studies revealed significant differences between the two mobile phase systems. For MeCN-based eluents, retention times slightly decreased with temperature on most CSPs, in contrast, with DMC-based eluents, retention times increased for all analytes on all CSPs as temperature rose. Interesetingly, enantioselectivity changed differently on the studied CSPs; enthalpically driven separations were observed in the MeCN-containing systems on all zwitterionic CSPS, whereas several entropically driven separations were observed in the DMC-containing systems on the ZWIX(–) CSP. The elution order of the enantiomers remained unchanged, regardless of replacing MeCN with the greener solvent DMC or varying","PeriodicalId":347,"journal":{"name":"Journal of Chromatography A","volume":"1771 ","pages":"Article 466811"},"PeriodicalIF":4.0,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146225058","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":"Molecularly imprinted magnetic covalent organic framework for selective extraction of metformin in health products","authors":"Nan Wang ,&nbsp;Hao Qi ,&nbsp;Shi-Lei Ji ,&nbsp;Lu-Liang Wang","doi":"10.1016/j.chroma.2026.466803","DOIUrl":"10.1016/j.chroma.2026.466803","url":null,"abstract":"<div><div>Selective detection of metformin (Glucophage) as an undeclared adulterant in health products is hampered by the complexity of sample matrices and the limitations of conventional adsorbents. While molecularly imprinted polymers (MIPs) offer specificity, they often suffer from low capacity and slow mass transfer. To overcome these challenges, a hierarchical adsorbent by grafting MIPs onto magnetic covalent organic frameworks (MCOFs) was engineered. MIPs@MCOFs substrate provided extensive surface area for high-density imprinting, while the magnetic core facilitates easy separation. MIPs@MCOFs exhibited high adsorption capacity (55.49 mg/g) and adsorption rate (40 min ) for Met. Based on this material, a reliable MSPE-HPLC method was established. It exhibited a wide linear range (5–10 , 000 μg/L), a low detection limit (1.1 μg/L), and satisfactory precision with intra- and inter-day RSDs below 2.2% and 6.5%, respectively. The method was validated for analyzing real samples, offering a powerful solution for combating illegal pharmaceutical adulteration in the health product industry.</div></div>","PeriodicalId":347,"journal":{"name":"Journal of Chromatography A","volume":"1771 ","pages":"Article 466803"},"PeriodicalIF":4.0,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146218169","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}