Carbohydrate Research最新文献

{"title":"Preparation of a thioxoimidazolidin-linked sialoside BSA conjugate for the inhibition of influenza virus","authors":"Haijuan Qin ,&nbsp;Zhiwei Huang ,&nbsp;Xue Mi ,&nbsp;Shuai Zhang ,&nbsp;Han-Yu Liu ,&nbsp;Jia-Ning Wang ,&nbsp;Mingming Xue ,&nbsp;Zhiqi Lao ,&nbsp;Yang Yang","doi":"10.1016/j.carres.2024.109287","DOIUrl":"10.1016/j.carres.2024.109287","url":null,"abstract":"<div><div>A novel thioxoimidazolidin-linked sialoside bovine serum albumin (<strong>WM-BSA</strong>) conjugate was synthesized and evaluated as an inhibitor of influenza virus hemagglutinin (HA) and neuraminidase (NA). The multivalent conjugate was prepared by the attachment of thioxoimidazolidin-sialoside monomer (<strong>WM</strong>) to BSA <em>via</em> adipate linker. Surface plasmon resonance analysis revealed that <strong>WM-BSA</strong> exhibited potent binding to recombinant influenza HA and NA proteins, with dissociation constants in the submicromolar range. <strong>WM-BSA</strong> also demonstrated inhibitory activities in the low micromolar range against HA and NA proteins from multiple influenza strains. Investigation of cytopathic effects in infected MDCK cells indicated that <strong>WM-BSA</strong> possessed antiviral activity with EC₅₀ values of 35–55 μM. The multivalent presentation of sialosides on the BSA scaffold significantly enhanced both the binding affinity and degree of inhibition compared to the monomeric compound <strong>WM</strong>. These results demonstrate the potential of multivalent sialoside-protein conjugate as a platform for developing novel anti-influenza agent.</div></div>","PeriodicalId":9415,"journal":{"name":"Carbohydrate Research","volume":"545 ","pages":"Article 109287"},"PeriodicalIF":2.4,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sulfated xylogalactofucans from Spatoglossum asperum: Production, structural features and antiviral activity","authors":"Shuvam Mukherjee ,&nbsp;Mathias E. Chemen ,&nbsp;Saikat Pal ,&nbsp;Luana E. Piccini ,&nbsp;Subrata Jana ,&nbsp;Elsa B. Damonte ,&nbsp;Bimalendu Ray ,&nbsp;Cybele C. Garcia ,&nbsp;Sayani Ray","doi":"10.1016/j.carres.2024.109286","DOIUrl":"10.1016/j.carres.2024.109286","url":null,"abstract":"<div><div>In cultured cells, herpes simplex virus (HSV) infectivity is successfully inhibited by sulfated polysaccharides. Herein, we utilized an amalgamated extraction-sulfation procedure to produce two xylogalactofucan sulfates (S203 and S204) from <em>Spatoglossum asperum</em> using ClSO₃H.Pyr/DMF and SO₃.Pyr/DMF reagents, respectively. Among these xylogalactofucans, the 17 ± 12 kDa polymer (S203) with 14 % sulfate exhibited activity on several HSV variants, including an acyclovir-resistant HSV-1 strain. This is the first report of the anti-HSV activity of a sulfated xylogalactofucan of <em>S. asperum</em>. The effective concentration 50 % (EC₅₀) value of S203 against HSV-1 strain F was 0.6 μg/mL with a selectivity index of 833. The backbone of this polymer (S203) is made up mostly of (1 → 4)-linked-α-<em>l</em>-Fuc<em>p</em> units having sulfate groups typically at O–3 and sometimes at O–2 positions. Oligosaccharides containing Xyl, Gal and Fuc units confirms that they are an integral part of a single polymer, another novelty of this study.</div><div>The EC₅₀ values of the native xylogalactofucan (S202) and the SO₃.Pyr/DMF modified polymer (S204), containing 2 % and 6 % sulfates, were &gt;100 and 3.3 μg/mL, respectively. Introduction of sulfate groups enhanced their capability to inhibit the infection of cells by HSV-1. These findings suggest feasibility of inhibiting HSV attachment to cells by blocking viral entry with polysaccharide having specific structure.</div></div>","PeriodicalId":9415,"journal":{"name":"Carbohydrate Research","volume":"545 ","pages":"Article 109286"},"PeriodicalIF":2.4,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of human GnT-IV family activity by the lectin domain","authors":"Naoko Osada ,&nbsp;Masamichi Nagae ,&nbsp;Takahiro Yamasaki ,&nbsp;Anne Harduin-Lepers ,&nbsp;Yasuhiko Kizuka","doi":"10.1016/j.carres.2024.109285","DOIUrl":"10.1016/j.carres.2024.109285","url":null,"abstract":"<div><div><em>N</em>-Glycan branching critically regulates glycoprotein functions and is involved in various diseases. Among the glycosyltransferases involved in <em>N</em>-glycan branching is the human <em>N</em>-acetylglucosaminyltransferase-IV (GnT-IV) family, which has four members: GnT-IVa, GnT-IVb, GnT-IVc, and GnT-IVd. GnT-IVa and GnT-IVb have glycosyltransferase activity that generates the type-2 diabetes-related β1,4-GlcNAc branch on the α1,3-Man arm of <em>N</em>-glycans, whereas GnT-IVc and GnT-IVd do not. Recently, this enzyme family was found to have a unique lectin domain in the C-terminal region, which is essential for enzyme activity toward glycoprotein substrates but not toward free <em>N</em>-glycans. Furthermore, interaction between the lectin domain of GnT-IV and <em>N</em>-glycan attached to GnT-IV enables self-regulation of GnT-IV activity, indicating that the lectin domain plays a unique and pivotal role in the regulation of GnT-IV activity. In this review, we summarize the GnT-IV family's biological functions, selectivity for glycoprotein substrates, and regulation of enzymatic activity, with a focus on its unique C-terminal lectin domain.</div></div>","PeriodicalId":9415,"journal":{"name":"Carbohydrate Research","volume":"545 ","pages":"Article 109285"},"PeriodicalIF":2.4,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of trisaccharide antigens featuring colitose, abequose and fucose residues and assessment of antibody binding on antigen arrays","authors":"Nikita M. Podvalnyy ,&nbsp;Lisa Crone ,&nbsp;Daniela Paganini ,&nbsp;Michael B. Zimmermann ,&nbsp;Thierry Hennet","doi":"10.1016/j.carres.2024.109283","DOIUrl":"10.1016/j.carres.2024.109283","url":null,"abstract":"<div><div>Deoxy-hexose sugars, such as rhamnose and quinovose, and the dideoxy-hexoses colitose, abequose, and tyvelose are highly antigenic given that they are absent from animal glycoconjugates. To investigate the specificity of antibodies towards structurally similar carbohydrate epitopes found in bacteria, we synthesized trisaccharides containing colitose, abequose, and fucose motifs. Each trisaccharide was designed with a spacer ending with a primary amino group. These trisaccharide constructs were immobilized on O-succinimide coated glass slides alongside bacterial lipopolysaccharides (LPS) containing colitose, abequose, and fucose residues. We compared the recognition of the synthetic trisaccharides and natural LPS including structurally related epitopes by monoclonal and polyclonal antibodies targeting bacterial LPS. Additionally, we used arrays displaying the synthetic trisaccharides and natural LPS to assess the variability of IgA reactivity from breast milk samples towards the carbohydrate antigens. The results obtained underlined the cross-reactivity of polyclonal antibodies towards structurally related carbohydrate antigens and revealed a broad reactivity of breast milk-derived IgA towards the carbohydrate antigens tested. The significant cross-reactivity of antibodies towards structurally related LPS antigens may lead to false-positive detection of bacterial serotypes when used for diagnostic purposes.</div></div>","PeriodicalId":9415,"journal":{"name":"Carbohydrate Research","volume":"545 ","pages":"Article 109283"},"PeriodicalIF":2.4,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-yield production of completely linear dextrans and isomalto-oligosaccharides by a truncated dextransucrase from Ligilactobacillus animalis TMW 1.971","authors":"Oliver Müller,&nbsp;Daniel Wefers","doi":"10.1016/j.carres.2024.109284","DOIUrl":"10.1016/j.carres.2024.109284","url":null,"abstract":"<div><div>Several lactic acid bacteria are capable of producing water-soluble exopolysaccharides such as dextran from sucrose by using glucansucrases. Several recombinant glucansucrases were described, however, yields were often limited and most dextrans were branched at position <em>O</em>3. In this study, the dextransucrase from <em>Ligilactobacillus animalis</em> TMW 1.971 was recombinantly produced without its <em>N</em>-terminal variable region and used for dextran synthesis. The enzyme expressed well and showed very high total as well as transferase activities compared to other glucansucrases. It was able to transfer nearly all glucose from sucrose to oligo- and polymeric products under certain conditions (about 95 % of glucose transferred). The high efficiency of the enzyme made it possible to obtain absolute dextran yields of up to 214.9 g/L from a 1.5 M sucrose solution. Structural characterization of the products showed that the dextrans produced have a rather low molecular weight, a narrow size distribution, and are completely linear. Furthermore, we showed that various low molecular weight dextrans or 1,6-linked isomalto-oligosaccharides can be efficiently produced by acid hydrolysis. Overall, we demonstrated that <em>Ligilactobacillus animalis</em> TMW 1.971 dextransucrase can be used to efficiently synthesize dextrans with a quite unique structural composition. The dextrans produced have a high potential for further applications such as synthesis of copolymers or size standards with a very defined molecular structure.</div></div>","PeriodicalId":9415,"journal":{"name":"Carbohydrate Research","volume":"545 ","pages":"Article 109284"},"PeriodicalIF":2.4,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Base-free trifluoroacetylation: From methyl glucopyranoside to cellulose nanofibers","authors":"Robert J. Nicholas,&nbsp;Nosa B. Idahagbon,&nbsp;Alexander Wei","doi":"10.1016/j.carres.2024.109282","DOIUrl":"10.1016/j.carres.2024.109282","url":null,"abstract":"<div><div>Trifluoroacetic anhydride (TFAA) reacts smoothly with low molecular weight carbohydrates and cellulose nanofibers (CNFs) under base-free conditions. Methyl α- and β-<span>d</span>-glucopyranoside were used as model compounds to optimize reaction conditions, which were then applied to lyophilized CNFs for surface modification. ATR-IR spectroscopy and powder X-ray diffraction were employed to characterize the modified CNFs. Trifluoroacetylation for 4 h yields a degree of substitution (DS) of 0.4 acyl groups per anhydroglucose unit while maintaining a crystallinity index near 50 %. DS values were quantified by gravimetry, acid–base titration after saponification, and a novel approach utilizing solution ¹⁹F NMR spectroscopy which offers greater accuracy than the other techniques. This study presents an efficient, base-free method for derivatizing carbohydrates as well as surface functionalization of CNFs with trifluoroacetyl groups, potentially expanding their application in fiber-reinforced thermoplastic composites.</div></div>","PeriodicalId":9415,"journal":{"name":"Carbohydrate Research","volume":"545 ","pages":"Article 109282"},"PeriodicalIF":2.4,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142324103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and pharmacological evaluation of nature-inspired phenacyl glycosides","authors":"Emmanilo Delar ,&nbsp;Yanis Tigherghar ,&nbsp;Laurie Girard ,&nbsp;Mohamed Haddad ,&nbsp;Charles Ramassamy ,&nbsp;Jean Legault ,&nbsp;Charles Gauthier","doi":"10.1016/j.carres.2024.109281","DOIUrl":"10.1016/j.carres.2024.109281","url":null,"abstract":"<div><div>Phenylethanoid glycosides are a well-studied class of bioactive compounds found throughout the plant kingdom. In contrast, research on the synthesis and pharmacological activity of phenacyl glycosides, a specific subgroup of phenylethanoid glycosides with a ketone functionality at the alpha position of the phenol ring, has been limited. In this study, we report the synthesis, cytotoxic, antiviral, and anti-inflammatory evaluation of a series of 18 4′-hydroxyphenacyl glycosides. These compounds consist of six different sugar residues (<em>β</em>-<span>d</span>-glucose, <em>β</em>-<span>d</span>-galactose, <em>α</em>-<span>l</span>-arabinose, <em>β</em>-<span>d</span>-xylose, <em>α</em>-<span>l</span>-rhamnose, and <em>β</em>-<span>d</span>-glucuronic acid) and display three distinct methoxylation patterns at the phenacyl ring, similar to the substitution motifs of anthocyanins. We obtained the target phenacyl glycosides in high yield and stereoselectivity through the coupling of benzoyl-protected trichloroacetimidate glycosyl donors and corresponding acetophenones. Our work represents the first total synthesis of the natural products 4′-hydroxyphenacyl-<em>β</em>-<span>d</span>-glucopyranoside (<strong>1</strong>) and 4′-hydroxy-3′-methoxyphenacyl-<em>β</em>-<span>d</span>-glucopyranoside (<strong>2</strong>). None of the phenacyl glycosides showed cytotoxicity against the tested cell lines. Notably, several of the synthesized compounds exhibited antiviral activity, with natural product <strong>2</strong> being the most active against herpes simplex virus type 1, while phenacyl arabinoside <strong>9</strong> and natural product <strong>2</strong> were the most active against human coronavirus OC43. Natural product <strong>2</strong> significantly inhibited the production of interleukin-6 in lipopolysaccharide-stimulated microglia cells. Overall, our findings highlight the importance of the sugar residue and phenacyl ring substitution pattern in modulating the antiviral activity of phenacyl glycosides. Natural product <strong>2</strong> and phenacyl arabinoside <strong>9</strong> emerge as promising leads for the development of antiviral agents.</div></div>","PeriodicalId":9415,"journal":{"name":"Carbohydrate Research","volume":"545 ","pages":"Article 109281"},"PeriodicalIF":2.4,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142356698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of 2,3-diazido-2,3-dideoxy-β-d-mannosides and 2,3-diazido-2,3-dideoxy-β-d-mannuronic acid via stereoselective anomeric O-alkylation","authors":"Rama Banjara,&nbsp;Prakash Thapa,&nbsp;Shailja Hitesh Kela,&nbsp;Fenglang Wu,&nbsp;Jianglong Zhu","doi":"10.1016/j.carres.2024.109279","DOIUrl":"10.1016/j.carres.2024.109279","url":null,"abstract":"<div><div>Stereoselective synthesis of 2,3-diazido-2,3-dideoxy-β-<span>d</span>-mannosides has been accomplished via Cs₂CO₃-mediated anomeric <em>O</em>-alkylation of 2,3-diazido-2,3-dideoxy-β-<span>d</span>-mannoses with primary electrophiles. Selective oxidation of the C6 primary alcohol of the 2,3-diazido-2,3-dideoxy-β-<span>d</span>-mannoside successfully produced corresponding 2,3-diazido-2,3-dideoxy-β-<span>d</span>-mannuronic acid.</div></div>","PeriodicalId":9415,"journal":{"name":"Carbohydrate Research","volume":"545 ","pages":"Article 109279"},"PeriodicalIF":2.4,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142320210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficient synthesis for each of the eight stereoisomers of the iminosugars lentiginosine and 1,4-dideoxy-1,4-imino-D-arabinitol (DAB)","authors":"Louis J. Liotta,&nbsp;Jessica Antoine,&nbsp;Leighanne A. Brammer Basta,&nbsp;Andrew S. Campbell,&nbsp;Gabrielle Y. Cole,&nbsp;Kristen A. Demick Brazile,&nbsp;Natalie M. Dogal Gardner,&nbsp;Megan E. Fitzgerald,&nbsp;Jean E.K. Francois,&nbsp;Brian M. French,&nbsp;Sara L. Garafola,&nbsp;Catherine A. Giannetti,&nbsp;Eve A. Granatosky,&nbsp;Alycen M. Harney,&nbsp;James T. Hummel,&nbsp;Andrew P. Joyce,&nbsp;Mitchell H. Keylor,&nbsp;Jasmine A. Khubchandani,&nbsp;Claudia Korzeniecki,&nbsp;Diana C. Lieberman,&nbsp;Kerstin L. Tougas","doi":"10.1016/j.carres.2024.109280","DOIUrl":"10.1016/j.carres.2024.109280","url":null,"abstract":"<div><div>Herein, we describe the efficient, diastereoselective syntheses of the iminosugars 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) <strong>1b</strong>, lentiginosine <strong>3a</strong>, and the seven stereoisomers of each of these iminosugars starting from 4-benzoyl-6-deoxy-6-iodoglycopyranosides <strong>47</strong> with yields ranging from 38 % to 68 % for the DAB and isomers <strong>1a-1h</strong> and from 44 % to 89 % for the lentiginosine and isomers <strong>3a-3h</strong>. We also report the syntheses of the eight stereoisomers of the 4-benzoyl-6-deoxy-6-iodoglycopyranosides <strong>47</strong> from commercially available sugars. Key to the iminosugar syntheses is a single multistep reaction that converts the 4-benzoyl-6-deoxy-6-iodoglycopyranosides <strong>47</strong> to a vinyl pyrrolidine through a one-pot zinc mediated reductive elimination, followed by a reductive amination and finally an intramolecular nucleophilic substitution. Strategic selection of the amine utilized in the reductive amination and the functionalization of the intermediate carbon-carbon double bond provides access to a vast array of iminosugars.</div></div>","PeriodicalId":9415,"journal":{"name":"Carbohydrate Research","volume":"545 ","pages":"Article 109280"},"PeriodicalIF":2.4,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142320209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Purification and characterization of α-fucosidase from Dichostereum sordulentum 1488","authors":"Lorena Herrera ,&nbsp;María Eugenia Cedrés ,&nbsp;Paula Rodríguez Bonnecarrere ,&nbsp;Cecilia Giacomini","doi":"10.1016/j.carres.2024.109278","DOIUrl":"10.1016/j.carres.2024.109278","url":null,"abstract":"<div><div>Biological glycans mediate several physiological processes, thus altered glycosylation patterns can lead to different diseases such as autoimmune, infectious, chronic anti-inflammatory diseases, or even cancer. In fact, alterations in fucosylation in either N- or <em>O</em>-glycans are among the most frequent changes in glycosylation patterns associated with cancer. Therefore, elucidation of the role of glycoconjugate glycans is essential for understanding the development of pathologies where they are involved. In this sense glycosidases are excellent tools, since they catalyse the selective removal of sugar residues, allowing the evaluation of changes in their biological role due to glycan removal. This work describes the purification and characterization of a α-fucosidase from the fungus <em>Dichostereum sordulentum</em> 1488. It is a homodimer with a molecular weight of 214 kDa and optimum pH and temperature of 4.0 and 70 °C respectively. It has a K_M of 0.27 mM and V_Max of 3.3 μmoles PNP/min per mg for the substrate <em>p</em>-nitrophenyl-α-<span>l</span>-fucopyranoside, showing a substrate inhibition profile. It showed high specificity for the hydrolysis of fucose linked by α-(1,2) bonds. The identification, purification, and characterization of this new α-fucosidase is highly relevant for enlarging the availability of glycosidases for use as tools for glycan elucidation.</div></div>","PeriodicalId":9415,"journal":{"name":"Carbohydrate Research","volume":"545 ","pages":"Article 109278"},"PeriodicalIF":2.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}