Darya A. Rastrepaeva , Dmitry A. Argunov , Ilya A. Puchkin , Dmitry V. Yashunsky , Vadim B. Krylov , Nikolay E. Nifantiev
{"title":"Synthesis of branched heterooligosaccharides related to Aspergillus galactomannan containing short Galf side chains","authors":"Darya A. Rastrepaeva , Dmitry A. Argunov , Ilya A. Puchkin , Dmitry V. Yashunsky , Vadim B. Krylov , Nikolay E. Nifantiev","doi":"10.1016/j.carres.2024.109360","DOIUrl":"10.1016/j.carres.2024.109360","url":null,"abstract":"<div><div>The members of a widespread <em>Aspergillus</em> fungi genus cause various diseases including the invasive aspergillosis with high morbidity and mortality rates, especially for immunosuppressed patients. One of the main carbohydrate structures on the surface of their cell wall is the galactomannan (GM) which is used in diagnostic kits for the detection of specific types of aspergillosis. However, limited specificity of currently available test systems urges the need for their further improvement. Herein we report the first synthesis of branched heterosaccharides related to GM and containing α-(1→2)-/α-(1→6)-linked tetramannoside backbone chain bearing one galactofuranoside unit or its β-(1→5)-linked dimer. The preparation of conjugates of the obtained spacered oligosaccharides with BSA is also performed to produce tools for the assessment the specificity of anti-<em>Aspergillus</em> immune response and to select antibodies suitable for the development of novel diagnostic kits that may discriminate distinct types of aspergillosis.</div></div>","PeriodicalId":9415,"journal":{"name":"Carbohydrate Research","volume":"549 ","pages":"Article 109360"},"PeriodicalIF":2.4,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881438","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}
Sara El Asri , Reda Ben Mrid , Zakia Zouaoui , Zoulfa Roussi , Abdelhamid Ennoury , Mohamed Nhiri , Fatiha Chibi
{"title":"Advances in structural modification of fucoidans, ulvans, and carrageenans to improve their biological functions for potential therapeutic application","authors":"Sara El Asri , Reda Ben Mrid , Zakia Zouaoui , Zoulfa Roussi , Abdelhamid Ennoury , Mohamed Nhiri , Fatiha Chibi","doi":"10.1016/j.carres.2024.109358","DOIUrl":"10.1016/j.carres.2024.109358","url":null,"abstract":"<div><div>Marine sulfated polysaccharides constitute a class of bioactive polymers commonly found in cell walls of macroalgae. Among these macromolecular substances, fucoidans, ulvans, and carrageenans have attracted considerable attention providing interesting therapeutic properties affected by a combination of various structural factors, such as sulfation pattern, molecular weight, monosaccharide composition, and glycosidic linkages. Remarkably, chemical modification, enzymatic hydrolysis and crosslinking are promising approaches for developing the application of these polysaccharides through enhancement and/or addition of new biological properties. This paper reviews the recent advances on these structure modification methods on fucoidans, ulvans, and carrageenans. The physical, chemical and biological properties influenced by the addition of functional groups are also discussed. In addition, an overview of specific enzymes selectively producing oligosaccharides with improved bioactivities as well as ionic and covalent cross-linking strategies are provided. These targeted methods have the potential to develop novel compounds with outstanding biodegradability and biocompatibility, along with low toxicity suitable for diverse applications in biomedical fields, including drug delivery.</div></div>","PeriodicalId":9415,"journal":{"name":"Carbohydrate Research","volume":"549 ","pages":"Article 109358"},"PeriodicalIF":2.4,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881434","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}
Roshani Gandhi , Nishant Chopade , Prashant K. Deshmukh , Rahul G. Ingle , Minal Harde , Sameer Lakade , Mahesh P. More , Rahul S. Tade , Mahesh S. Bhadane
{"title":"Unveiling cyclodextrin conjugation as multidentate excipients: An exploratory journey across industries","authors":"Roshani Gandhi , Nishant Chopade , Prashant K. Deshmukh , Rahul G. Ingle , Minal Harde , Sameer Lakade , Mahesh P. More , Rahul S. Tade , Mahesh S. Bhadane","doi":"10.1016/j.carres.2024.109357","DOIUrl":"10.1016/j.carres.2024.109357","url":null,"abstract":"<div><div>The discovery of branched molecules like dextrin by Schardinger in 1903 marked the inception of cyclodextrin (CD) utilization, catalyzing its journey from laboratory experimentation to widespread commercialization within the pharmaceutical industry. CD, a cyclic oligosaccharide containing glucopyranose units, acts as a versatile guest molecule, forming inclusion complexes (ICs) with various host molecules. Computational studies have become instrumental in elucidating the intricate interactions between β-CD and guest molecules, enabling the prediction of binding energy, forces, affinity, and complex stability. The computational approach has established robust correlations with experimental outcomes, enhancing our understanding of CD-mediated complexation phenomena. This comprehensive review delves into the CD based Inclusion complex (CDIC) formation and a myriad of components, including drug molecules, amino acids, vitamins, and volatile oils. These complexes find applications across diverse industries, ranging from pharmaceuticals to nutraceuticals, food, fragrance, and beyond. In the pharmaceutical realm, β- CDICs offer innovative solutions for enhancing drug solubility, stability, and bioavailability, thus overcoming formulation challenges associated with poorly water-soluble drugs. Furthermore, the versatility of CDs extends beyond pharmaceuticals, with applications in the encapsulation of phytoactive compounds in nutraceuticals and the enhancing flavor, aroma in food and fragrance industries. This review underscores the pivotal role of CDs conjugation in modern drug delivery systems, emphasizing the importance of interdisciplinary approaches that integrate computational modeling with experimental validation. As the pharmaceutical landscape continues to evolve, CDs-based formulations stand poised to drive innovation and address the ever-growing demand for efficacious and patient-friendly drug delivery solutions.</div></div>","PeriodicalId":9415,"journal":{"name":"Carbohydrate Research","volume":"549 ","pages":"Article 109357"},"PeriodicalIF":2.4,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871485","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}
Juan Song , Guangzhong Tu , Yue Liu , Si Liu , Yuting Zhang , Wenxi Yang , Xu Pang , Xiaojuan Chen , Haizhen Liang , Jie Zhang , Baiping Ma
{"title":"Hydroxyl groups introducing NMR strategy for structural elucidation of a heptasaccharide isolated from Trillium tschonoskii","authors":"Juan Song , Guangzhong Tu , Yue Liu , Si Liu , Yuting Zhang , Wenxi Yang , Xu Pang , Xiaojuan Chen , Haizhen Liang , Jie Zhang , Baiping Ma","doi":"10.1016/j.carres.2024.109359","DOIUrl":"10.1016/j.carres.2024.109359","url":null,"abstract":"<div><div>A heptasaccharide was isolated from an active fraction of <em>Trillium tschonoskii</em> using HILIC and high-temperature PGC chromatography methods. UHPLC-Q/TOF-MS analysis gave this oligosaccharide a degree of polymerization (DP) of 7 and MS/MS showed that it has a six-carbon aldehyde glucan structure with the possible chain 1 → 4 connected. The structure was determined by series 1D and 2D NMR in two solvents D<sub>2</sub>O and DMSO‑<em>d</em><sub>6</sub>. Using <sup>1</sup>H resonances of the –OH groups as the starting point and HSQC-TOCSY on the covalent structure definition for structural elucidation allowed this heptasaccharide to be uncovered. This heptasaccharide was elucidated as maltoheptaose via complete assignment of <sup>1</sup>H and <sup>13</sup>C with jigsaw H–C–OH pieces produced by HSQC-TOCSY at increasing mixing time. The significance of identifying maltoheptaose in <em>Trillium tschonoskii</em> indicates the high potential of –OH introducing strategy for other oligosaccharides' structural determination with relatively higher DP.</div></div>","PeriodicalId":9415,"journal":{"name":"Carbohydrate Research","volume":"549 ","pages":"Article 109359"},"PeriodicalIF":2.4,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876341","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}
Anju Joseph , S. Umamaheswari , Miriam Cecilia Vassou
{"title":"Bacterial cellulose: A versatile biomaterial for biomedical application","authors":"Anju Joseph , S. Umamaheswari , Miriam Cecilia Vassou","doi":"10.1016/j.carres.2024.109350","DOIUrl":"10.1016/j.carres.2024.109350","url":null,"abstract":"<div><div>Bacterial cellulose, a unique biomaterial produced by several bacteria, has garnered biomedical interest to its versatility. This could be used in healthcare packaging, and textiles. Bacterial cellulose extraction is effective and affordable since it lacks lignin and hemicellulose. In wound healing, tissue engineering, drug delivery, and regenerative medicine, this material's unique properties have drawn interest. Bacterial cellulose has been studies as a skin substitute for severe burns and non-woven bandages for persistent wounds. In addition, bacterial cellulose has been used to make artificial skin, blood arteries, and wound dressings. Bacterial cellulose is ideal for biopolymer production due to its clean chemical composition, nano-fibrillar structure, and crystalline characteristics. This review explores the processing, content, characteristics, and applications of bacterial cellulose, revealing its function in tissue regeneration and disease resistance. Through careful inquiry and analysis, this work seeks to comprehend bacterial cellulose and its impact on biomedical research and technology.</div></div>","PeriodicalId":9415,"journal":{"name":"Carbohydrate Research","volume":"552 ","pages":"Article 109350"},"PeriodicalIF":2.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628182","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}
Zuchao Ma , Harry E. Ensley , Douglas W. Lowman , Michael D. Kruppa , David L. Williams
{"title":"Recent advances in chemical synthesis of phosphodiester linkages found in fungal mannans","authors":"Zuchao Ma , Harry E. Ensley , Douglas W. Lowman , Michael D. Kruppa , David L. Williams","doi":"10.1016/j.carres.2024.109325","DOIUrl":"10.1016/j.carres.2024.109325","url":null,"abstract":"<div><div>Fungal mannans are located on the exterior of the fungal cell wall, where they interact with the environment and, ultimately, the human host. Mannans play a major role in shaping the innate immune response to fungal pathogens. Understanding the phosphodiester linkage and mannosyl repeat units in the acid-labile portion of mannans is crucial for comprehending their structure/activity relationships and for development of anti-fungal vaccines and immunomodulators. The phosphodiester linkages connect the acid-stable and acid-labile portions of the mannan polymer. Phosphate groups are attached to positions 4 and/or 6 of mannosyl repeat units in the acid-stable portion and to position 1 of mannosyl repeat units in the acid-labile portion. This review focuses on the synthesis of phosphodiester linkages as an approach to the development of mannan glycomimetics, which are based on natural product fungal mannans. Development of successful synthetic strategies for the phosphodiester linkages may enable the production of mannan glycomimetics that elicit anti-fungal immune responses against existing and emerging fungal pathogens, such as <em>Candida albicans</em> and <em>Candida auris</em>.</div></div>","PeriodicalId":9415,"journal":{"name":"Carbohydrate Research","volume":"547 ","pages":"Article 109325"},"PeriodicalIF":2.4,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142722419","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":"Chemical extension and glycodendrimer formation of the matriglycan decasaccharide, -(3Xylα1-3GlcAβ1)5- and its affinity for laminin","authors":"Kota Kotera , Ren Miyamoto , Gakuto Mochizuki , Takahiro Tamura , Noriyoshi Manabe , Yoshiki Yamaguchi , Jun-ichi Tamura","doi":"10.1016/j.carres.2024.109328","DOIUrl":"10.1016/j.carres.2024.109328","url":null,"abstract":"<div><div>Muscle tissue is stabilized by the strong interaction between laminin and matriglycan. Matriglycan is a polysaccharide composed of the repeating disaccharide, -3Xylα1-3GlcAβ1-, and is a pivotal part of the core M3 <em>O</em>-mannosyl glycan. Patients with muscular dystrophy cannot synthesize matriglycan or the core M3 <em>O</em>-mannosyl glycan due to a defect in or the lack of glycosyltransferases owing to glycan synthesis. Therefore, a supply of matriglycan may be a powerful tool for reconstructing muscle tissue in these patients. We herein report the synthesis of a matriglycan-repeating decasaccharide and a dendrimer comprising three branches of the decasaccharide. The glycan was regio- and stereoselectively synthesized by the stepwise addition of the corresponding disaccharide unit. The immobilized decasaccharide and glycodendrimer bound to laminin-G-like domains 4 and 5 of laminin-α2. The dissociation constants of the decasaccharide and dendrimer obtained from bio-layer interferometry were estimated to be 4.4 × 10<sup>−8</sup> M and 6.8 × 10<sup>−8</sup> M, respectively, showing higher affinity than those of a matriglycan-repeating hexasaccharide (1.6 × 10<sup>−7</sup> M) and the dendrimer (1.8 × 10<sup>−7</sup> M).</div></div>","PeriodicalId":9415,"journal":{"name":"Carbohydrate Research","volume":"547 ","pages":"Article 109328"},"PeriodicalIF":2.4,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702510","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}
Nozomi Ishii , Andrea Mascherpa , Antony J. Fairbanks
{"title":"Synthesis of a heptasaccharide N-glycan comprising two mannose-6-phosphate residues","authors":"Nozomi Ishii , Andrea Mascherpa , Antony J. Fairbanks","doi":"10.1016/j.carres.2024.109327","DOIUrl":"10.1016/j.carres.2024.109327","url":null,"abstract":"<div><div>A deprotected biantennary high mannose heptasaccharide <em>N</em>-glycan comprising two mannose-6-phosphate residues was synthesised as a putative ligand for the mannose 6-phosphate receptors, using a convergent [3 + 4] glycosylation strategy.</div></div>","PeriodicalId":9415,"journal":{"name":"Carbohydrate Research","volume":"547 ","pages":"Article 109327"},"PeriodicalIF":2.4,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702509","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}
Yasemin Tantan , Özlem Kaplan , Kevser Bal , Sema Şentürk , Emine Büşra Eker Fidan , Sibel Çelik , Kamber Demir , Mehmet Koray Gök
{"title":"Tricine-modified chitosan as a strategy for enhancing hydrophilicity and gene delivery","authors":"Yasemin Tantan , Özlem Kaplan , Kevser Bal , Sema Şentürk , Emine Büşra Eker Fidan , Sibel Çelik , Kamber Demir , Mehmet Koray Gök","doi":"10.1016/j.carres.2024.109326","DOIUrl":"10.1016/j.carres.2024.109326","url":null,"abstract":"<div><div>In this study, we investigated the effect of chitosan modification with tricine on transfection efficiency by preserving its ability to form complexes with plasmid DNA (pDNA) and increasing its hydrophilicity. The inherent limitations of chitosan, such as poor solubility at physiological pH, insufficient cellular uptake, and strong ionic interactions with pDNA, typically result in low transfection efficiency. To overcome these challenges, Tricine, a hydrophilic molecule containing a secondary amine group, was conjugated to chitosan. Chitosan of three different molecular weights (low, medium, and high) was modified with tricine. Structural characterization of the modified chitosan was conducted using Fourier Transformed Infrared Spectroscopy (FTIR) and Nuclear Magnetic Resonance (NMR) analyses. The effects of tricine modification were assessed in terms of hydrophilicity/hydrophobicity, proton buffering capacity, particle size, PDI and zeta potential. Tricine modified low molecular weight chitosan nanoparticles (nLMWChi<sub>Tri</sub>), which exhibit suitable properties for gene transfer studies, were evaluated regarding pDNA complexation ability, cytotoxicity and <em>in vitro</em> transfection efficiency. The results demonstrated that tricine modification enhanced the gene transfer potential of chitosan, making it competitive with the commercial transfection agent Lipofectamine™ 2000 and offering a promising strategy for non-viral gene therapy applications. Furthermore, the biocompatibility and biodegradability of chitosan, combined with the improved hydrophilicity provided by tricine, makes nLMWChi<sub>Tri</sub> a safer and more sustainable option for repeated use in gene delivery, overcoming the major limitations associated with other synthetic vectors such as Lipofectamine™ 2000.</div></div>","PeriodicalId":9415,"journal":{"name":"Carbohydrate Research","volume":"547 ","pages":"Article 109326"},"PeriodicalIF":2.4,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695292","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}
Andrea Iovine , Andrei V. Filatov , Anastasiya A. Kasimova , Nowshin S. Sharar , Stephanie J. Ambrose , Andrey S. Dmitrenok , Mikhail M. Shneider , Anna M. Shpirt , Andrei V. Perepelov , Yuriy A. Knirel , Ruth M. Hall , Cristina De Castro , Johanna J. Kenyon
{"title":"Structure of the K58 capsular polysaccharide produced by Acinetobacter baumannii isolate MRSN 31468 includes Pse5Ac7Ac that is 4-O-acetylated by a phage-encoded acetyltransferase","authors":"Andrea Iovine , Andrei V. Filatov , Anastasiya A. Kasimova , Nowshin S. Sharar , Stephanie J. Ambrose , Andrey S. Dmitrenok , Mikhail M. Shneider , Anna M. Shpirt , Andrei V. Perepelov , Yuriy A. Knirel , Ruth M. Hall , Cristina De Castro , Johanna J. Kenyon","doi":"10.1016/j.carres.2024.109324","DOIUrl":"10.1016/j.carres.2024.109324","url":null,"abstract":"<div><div>Capsular polysaccharide (CPS), a heteropolymeric carbohydrate structure present on the cell surface of most isolates of the bacterial pathogen <em>Acinetobacter baumannii</em>, is a major virulence determinant<em>.</em> Here, the CPS produced by <em>A. baumannii</em> MRSN 31468, which carries the KL58 CPS biosynthesis locus, was studied by sugar analysis, one- and two-dimensional <sup>1</sup>H and <sup>13</sup>C NMR spectroscopy. The structure was found to consist of a repeating tetrasaccharide K-unit that includes glucose (d-Glc<em>p</em>), galactose (d-Gal<em>p</em>), <em>N</em>-acetyl-galactosamine (d-Gal<em>p</em>NAc), and 5,7-diacetamido-3,5,7,9-tetradeoxy-<span>l</span>-<em>glycero</em>-<span>l</span>-<em>manno</em>-non-2-ulosonic acid (5,7-di-<em>N</em>-acetylpseudaminic acid; Pse5Ac7Ac). The CPS has a branched repeating unit with the disaccharide →3)-β-d-Glc-(1→3)-β-d-GalNAc-(1→ as the mainchain and O-6 of the Glc unit substituted with the disaccharide β-Pse5Ac7Ac-(2→6)-α-d-Gal, and Pse5Ac7Ac is partially acetylated at O-4. The presence of Pse5Ac7Ac in the K58 structure is consistent with the presence of <em>psaA-F</em> genes in KL58, which are responsible for Pse5Ac7Ac synthesis. 4-O-acetylation of Pse5Ac7Ac was traced to an acetyltransferase, Atr44<em>,</em> which was found to be closely related to Atr29 that similarly decorates Pse5Ac7Ac with 4OAc in the K46-type CPS. Atr44 like Atr29 is encoded by a gene found in a prophage. The K58 CPS produced by MRSN 31468 did not include the 8-epimer of Pse5Ac7Ac (5,7-di-<em>N</em>-acetyl-8-epipseudaminic acid; 8ePse5Ac7Ac) found in the closely related CPS from BAL062 that also carries KL58. Hence, the gene(s) for conversion of Pse5Ac7Ac to 8ePse5Ac7Ac must lie elsewhere.</div></div>","PeriodicalId":9415,"journal":{"name":"Carbohydrate Research","volume":"547 ","pages":"Article 109324"},"PeriodicalIF":2.4,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695285","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}