Bioconjugate Chemistry最新文献

{"title":"Systematic Investigation of Fatty Acids with Different Carbon-Chain Length as Albumin Binder to Improve Tumor Accumulation of Radioligands","authors":"Kazuma Nakashima,&nbsp;Mao Tanaka,&nbsp;Nobuki Kazuta,&nbsp;Shohei Tsuchihashi,&nbsp;Hiroyuki Watanabe and Masahiro Ono*,&nbsp;","doi":"10.1021/acs.bioconjchem.6c00088","DOIUrl":"10.1021/acs.bioconjchem.6c00088","url":null,"abstract":"<p >In the development of radiopharmaceuticals, high tumor accumulation is required for their diagnostic and therapeutic effectiveness. A key strategy to enhance such tumor accumulation is the incorporation of small-molecule albumin binders (ALBs) into radioligands, extending the blood circulation time through albumin interaction for efficient delivery to tumors. In this study, we systematically investigated the potential use of fatty acids (FAs) with various carbon-chain lengths (C12, C14, C16, and C18) as ALBs (FA12, FA14, FA16, and FA18). First, we synthesized four radiolabeled compounds composed of a macrocyclic radiometal chelator and various FAs ([¹¹¹In]In-DFA12, [¹¹¹In]In-DFA14, [¹¹¹In]In-DFA16, and [¹¹¹In]In-DFA18). <i>In vitro</i> albumin-binding assays and biodistribution studies using normal mice revealed a chain-length dependence: longer carbon chains led to higher albumin affinity and prolonged blood retention, with [¹¹¹In]In-DFA18 exhibiting the most favorable pharmacokinetic profile. Based on these results, we developed [¹¹¹In]In-PDFA18, a prostate-specific membrane antigen (PSMA)-targeted radioligand conjugated with FA18. Tumor accumulation of [¹¹¹In]In-PDFA18 at 24 and 96 h postinjection (p.i.) (43.70 and 52.59% injected dose (ID)/g, respectively) was markedly higher and more prolonged compared with that of the non-FA18-conjugated control radioligand, [¹¹¹In]In-PSMA-617 (14.86 and 5.36% ID/g). These findings suggest that FA18 is a promising ALB to improve the tumor accumulation of radioligands.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 7","pages":"1377–1385"},"PeriodicalIF":4.5,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148300248","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":"Rapid and Efficient Antibody–Drug Conjugate Design Using Mechanistic Bottom-Up Modeling from In Vitro to Human","authors":"Jan-Philip Kahl*,&nbsp;Judith Stein,&nbsp;Tatu Lindroos,&nbsp;Anna Kaempffe,&nbsp;Michael Krug,&nbsp;Jan Anderl,&nbsp;Harald Kolmar,&nbsp;Stefan Hecht and Stanley Sweeney-Lasch*,&nbsp;","doi":"10.1021/acs.bioconjchem.6c00049","DOIUrl":"10.1021/acs.bioconjchem.6c00049","url":null,"abstract":"<p >Antibody–drug conjugates (ADCs) are complex molecules, and many fail clinically despite promising preclinical data. Here, a modular, bottom-up modeling strategy employing mechanistic PK–PD models was developed to translate ADC efficacy and toxicity from bench to bedside and to guide ADC design. The models handle various antigens, payloads, and ADCs, validated using six ADCs (Enhertu, Kadcyla, Trodelvy, RC48, RN927C, and Datroway). Using determined cellular distribution of payloads/ADCs, payload killing parameters, and systemic parameters (assay volume, cell doubling time), ADC <i>in vitro</i> potency was predicted with 94.64% accuracy within a 2-fold range. Incorporating ADC and payload pharmacokinetic parameters enables prediction of <i>in vivo</i> efficacy comparable to cell line- and patient-derived xenograft data from the literature. Scaling parameters from mouse to human (PK, tumor volume, and tumor doubling time) led to the reproduction of clinical efficacy trends. Beyond efficacy, the approach predicts key hematologic toxicities such as neutropenia and thrombocytopenia, demonstrated for Kadcyla and Enhertu. Application to the clinically failed RN927C demonstrated how our modeling approach could have flagged issues and enabled suggestions for design modifications to widen the therapeutic window and prevent the clinical failure. In conclusion, our presented modeling strategy delivers accurate efficacy and toxicity translation from <i>in vitro</i> to humans utilizing easily accessible parameters as the foundation and deepens understanding of ADCs and their individual components, thereby supporting ADC design and candidate and patient selection and accelerating ADC development.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 7","pages":"1359–1366"},"PeriodicalIF":4.5,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148275208","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":"De Novo Lipid Switch Design for Reactive Oxygen Species-Triggered Liposomal Release","authors":"Kazi R. Shahriar,&nbsp;Mayesha B. Mustafa,&nbsp;Nathan R. Kaufman and Michael D. Best*,&nbsp;","doi":"10.1021/acs.bioconjchem.6c00265","DOIUrl":"10.1021/acs.bioconjchem.6c00265","url":null,"abstract":"<p >Liposomal nanocarriers are highly effective for drug delivery, since they shield encapsulated therapeutic cargo and enhance cellular infiltration. However, a drawback of liposomal carriers involves the limited release of contents after delivery. As such, stimulus-responsive liposomes harnessing synthetic lipid switches that trigger cargo release upon encountering disease-associated conditions have the potential to address this issue. Reactive oxygen species (ROS) have emerged as prominent target stimuli because of their upregulation in diseased cells. Lipid switches designed for liposome release are often derived from phospholipid precursors, an approach that suffers from high expense and hinders scalability because of the limited availability of phospholipids. To address this issue, we report the design and synthesis of an ROS-responsive lipid switch from first principles that does not utilize phospholipid precursors. This culminated in a scalable nonphospholipid switch that forms stable liposomes yet undergoes clean, H₂O₂-triggered degradation under aqueous oxidative conditions. Using Nile Red release, ANTS–DPX dequenching, and dynamic light scattering (DLS) experiments, we show that liposomes containing lipid switch <b>4</b> exhibit minimal basal leakage and maintain structural integrity, while H₂O₂ induces dose-dependent membrane permeabilization with characteristic changes in vesicle size. We also show that liposomes containing <b>4</b> demonstrate superior and more consistent results compared with those containing <b>6</b>, which have longer acyl chains. PC-only negative controls display no comparable response, confirming that release arises from selective boronate oxidation rather than nonspecific degradation. These results highlight the potential of a synthetically accessible, modular nonphospholipid architecture for stimulus-responsive triggered release as a practical platform for redox-responsive therapeutic delivery.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 7","pages":"1475–1482"},"PeriodicalIF":4.5,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148336965","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":"Targeted Delivery of RNA Therapeutics through Ligand Conjugation","authors":"Melgious J. Y. Ang,&nbsp;Su Seong Lee,&nbsp;Joyce Tay and Yi Yan Yang*,&nbsp;","doi":"10.1021/acs.bioconjchem.6c00266","DOIUrl":"10.1021/acs.bioconjchem.6c00266","url":null,"abstract":"<p >RNA therapies have demonstrated promising potential for a myriad of clinical treatments in treating various diseases. However, significant unresolved obstacles are achieving precise delivery to specific tissues. This Viewpoint examines the inherent obstacles encountered by ligand-functionalized oligonucleotide conjugates and RNA-LNPs and the strategies to overcome them to achieve the desired therapeutic outcomes.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 7","pages":"1323–1328"},"PeriodicalIF":4.5,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148292599","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 a High-Throughput Size-Exclusion Chromatography–Mass Spectrometry Workflow for Real-Time Monitoring of Bioconjugation of Cysteine-Based Antibody–Drug Conjugates","authors":"Zhengqi Zhang,&nbsp;Pei-Ru Jin,&nbsp;Wei Lin*,&nbsp;Tao Liang*,&nbsp;Ekaterina Deyanova,&nbsp;Rico Gunawan and Hong Ren,&nbsp;","doi":"10.1021/acs.bioconjchem.6c00182","DOIUrl":"10.1021/acs.bioconjchem.6c00182","url":null,"abstract":"<p >The manufacturing of cysteine-based antibody–drug conjugates (ADCs) requires precise control of the drug-to-antibody ratio (DAR), a critical quality attribute influencing product safety and efficacy. Conventional analytical techniques used for DAR determination, such as hydrophobic interaction chromatography (HIC) and reversed-phase high-performance liquid chromatography (RP-HPLC), are low-throughput and unsuitable for real-time process monitoring, limiting process development efficiency. To address this challenge, we developed a high-throughput size-exclusion chromatography–mass spectrometry (SEC-MS) workflow with and without postcolumn denaturation (PCD) functionality, enabling real-time monitoring of both reduction and conjugation kinetics during cysteine-based ADC manufacturing. Using a short SEC column coupled to a mass spectrometer, analysis time can be performed under 2 min per sample. This workflow was applied to rapidly optimize critical process parameters, including reductant concentration and pH during reduction, and drug-linker ratio during conjugation. The approach provided deeper mechanistic insights into reaction kinetics and supports process analytical technology (PAT)-enabled strategies for advanced process control. Overall, this high-throughput SEC-MS workflow accelerates ADC development while improving manufacturing robustness.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 7","pages":"1421–1429"},"PeriodicalIF":4.5,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148269420","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":"Enzymatic Synthesis of Glyco-DNA Equipped with Oligosaccharides and Charged Monosaccharides","authors":"Maria Dalla Pozza,&nbsp;Marc Borie-Guichot,&nbsp;Frédéric Bonhomme,&nbsp;Marc Delarue,&nbsp;Laurence A. Mulard* and Marcel Hollenstein*,&nbsp;","doi":"10.1021/acs.bioconjchem.6c00168","DOIUrl":"10.1021/acs.bioconjchem.6c00168","url":null,"abstract":"<p >The therapeutic and biotechnological utility of synthetic oligonucleotides is constrained by the limited chemical diversity of canonical nucleotides and their susceptibility to nuclease degradation. Inspired by the hypermodified genomes of bacteriophages, where 5-glycosylated pyrimidines confer protection against host restriction enzymes, we report the design and synthesis of a scaffold of 5-glycosylated 2′-deoxyuridine triphosphates (dUTPs <b>1–7</b>) bearing mono- (either neutral or charged moieties) and oligosaccharides affixed to position 5 of the nucleobase. The resulting glyco-modified nucleotides were well incorporated into DNA by different template-dependent polymerases, but much less by template-independent polymerases. While the presence of charged residues did not affect incorporation efficiency, glycan side-chain extension considerably reduced the incorporation yield of the glycosylated nucleotides. On the other hand, the saccharide appendages did not affect the serum stability of the 71-mer sequences containing the glyco-modified dUTPs and were only slightly destabilizing duplex DNA. Interestingly, the presence of short oligosaccharides highly increased the oligonucleotide stability against the BfaI endonuclease. These findings show that 5-glycosylation with short oligosaccharides could be a strategy to expand the chemical arsenal on nucleobases of DNA, offering a robust strategy for developing next-generation glyco-aptamers with enhanced endonuclease stability and novel saccharide-mediated recognition capabilities.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 7","pages":"1397–1408"},"PeriodicalIF":4.5,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148349926","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":"Artificial Intelligence for Discovery in Life Sciences","authors":"Sushovan Chanda*,&nbsp;Silvio O. Rizzoli* and Ali H. Shaib*,&nbsp;","doi":"10.1021/acs.bioconjchem.6c00230","DOIUrl":"10.1021/acs.bioconjchem.6c00230","url":null,"abstract":"<p >Artificial intelligence is becoming a transformative tool in life sciences, not just by improving the results of existing technologies but also by introducing fundamental new ways of discovery. Initially applied to denoising, segmentation, or pattern recognition, it now extends across microscopy, structural biology, protein engineering, experimental design, and hypothesis generation. In imaging, deep learning enhances fluorescence, cryo-EM, and expansion microscopy and increasingly links optical and non-optical modalities. Beyond imaging, AI accelerates fluorescent probe development, while large language models and multi-agent systems are beginning to synthesize literature, generate hypotheses, and guide experiments. We survey these developments across imaging and non-imaging domains, from microscopy and structural biology to molecular design, hypothesis generation, and autonomous experimentation. We discuss the convergence of AI with tools from chemistry to instrumentation and explain challenges in validation, interpretability, generalizability, and autonomy. We conclude that AI is beginning to connect measurement, design, and reasoning to accelerate biological discovery.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 7","pages":"1311–1322"},"PeriodicalIF":4.5,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.bioconjchem.6c00230","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148366213","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}

{"title":"Unsymmetric Heptamethine Cyanines as a General Strategy to Construct Nonaggregating Fluorophores for Biomedical Imaging","authors":"Emilia Gomez,&nbsp;Mohan Kodisana,&nbsp;Asma Harun,&nbsp;Alfredo Cardenas-Rivera,&nbsp;Yuntao Li,&nbsp;Alyssa Kornegay,&nbsp;Daniel Wherritt,&nbsp;Mohammad A. Yaseen,&nbsp;Kirsten K. Hanson,&nbsp;Indrajit Srivastava and Syed Muhammad Usama*,&nbsp;","doi":"10.1021/acs.bioconjchem.6c00026","DOIUrl":"10.1021/acs.bioconjchem.6c00026","url":null,"abstract":"<p >Heptamethine cyanine dyes are widely used as near-infrared (NIR) fluorophores in biomedical imaging. However, conventional heptamethine cyanine fluorophores are symmetric in nature, which favors fluorophore self-assembly from π–π stacking in aqueous media. This H-aggregation significantly reduces the fluorescence intensity and hampers imaging performance. Although a few nonaggregating heptamethine cyanines have been reported, no general strategy has been established for synthesizing nonaggregating heptamethine cyanine. Here, we introduce a broadly applicable approach to prevent H-aggregation by breaking the molecular symmetry of heptamethine cyanines through selective substitution along the polymethine backbone. This structural asymmetry disrupts π–π stacking interactions without adversely affecting the desirable photophysical properties of the dyes. This strategy accommodates a wide range of indolenine and polymethine substituents that enable the development of a diverse library of nonaggregating heptamethine cyanines (15 examples in total) including nonaggregating ICG analogs. One of the unsymmetrical heptamethine cyanine dyes, <b>SAT-NIR-746</b>, was further characterized for its aggregation behavior. <b>SAT-NIR-746</b> remained monomeric in water and across a range of salt concentrations, indicating strong resistance to salt-induced H-aggregation. Furthermore, a carboxylic acid derivative of <b>SAT-NIR-746</b> was converted to an NHS ester and conjugated to monoclonal antibodies (mAbs) via lysine residues. The resulting IgG-SAT-NIR-746 conjugates showed no signs of H-aggregation, further confirming the dye’s stability in both solution and protein-bound states. Finally, we show the advantages of <b>SAT-NIR-746</b> for quantitative bioimaging <i>in vitro</i>, <i>in vivo</i>, and <i>ex vivo</i> phantom imaging.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 6","pages":"1158–1171"},"PeriodicalIF":4.5,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721131","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":"Near-Infrared and Shortwave Infrared Building Blocks for Activity-Based Sensors in Animals","authors":"Tianmiao Wang,&nbsp;Xinyuan Li,&nbsp;Lei Guo and Shang Jia*,&nbsp;","doi":"10.1021/acs.bioconjchem.6c00039","DOIUrl":"10.1021/acs.bioconjchem.6c00039","url":null,"abstract":"<p >Activatable fluorescent probes operating in the near-infrared (NIR, 700–1000 nm) and shortwave-infrared (SWIR, also known as NIR-II, 1000–1700 nm) windows have become essential tools for bioimaging due to their deep tissue penetration, low background interference, and high signal-to-noise ratios. With growing numbers of such probes in the red-shifted windows developed for detection in animal models, this review summarizes how and what NIR and SWIR fluorophores can be coupled with selective triggers to create activity-based sensing NIR/NIR-II probes rather than listing probes based on their bioanalytes. To date, a variety of probes have been constructed this way, involving the modular combination of a fluorophore scaffold that defines photophysical properties, defined modification sites where caging groups are installed, and connection chemistry that links responsive moieties to the fluorophore core. Through representative examples, we illustrate how the same fluorophore can be adapted for diverse applications by varying the caging group, and how the same responsive chemistry can be implemented across different scaffolds by preserving the linkage type. This modular framework provides researchers with a practical design toolkit for constructing activatable probes for new biological targets.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 6","pages":"1089–1107"},"PeriodicalIF":4.5,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.bioconjchem.6c00039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148141939","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}

{"title":"Construction and Preliminary Evaluation of Multivalent LLP2A Derivatives Targeting VLA-4 in Melanoma","authors":"Hongyong Wang,&nbsp;Peng Zhou,&nbsp;Juntao Jiang,&nbsp;Yiyin Mao,&nbsp;Guoqing Han,&nbsp;Yaling Liu,&nbsp;Chunxiong Lu,&nbsp;Jun Wu,&nbsp;Pei Zou* and Hao Wu*,&nbsp;","doi":"10.1021/acs.bioconjchem.6c00255","DOIUrl":"10.1021/acs.bioconjchem.6c00255","url":null,"abstract":"<p >The high-affinity ligand LLP2A targeting α₄β₁ integrin (VLA-4) has shown promise for molecular imaging, but its monomeric form exhibits rapid clearance and limited tumor retention, restricting its therapeutic potential. This study aimed to develop multimeric LLP2A probes with improved tumor uptake and retention. Methods: Seven structurally distinct multimeric LLP2A derivatives were designed and synthesized, and their in vivo performance was compared with the monomeric analogue T4 in B16F10 melanoma mice using PET imaging, SPECT/CT imaging, biodistribution and therapy evaluation. Results: Among the synthesized probes, LLP2A-Pol-1 showed the highest tumor uptake (%ID/g, 7.89 ± 0.50 vs 2.40 ± 0.48 at 1 h in PET imaging; approximately 3-fold higher than the monomer) and maintained high tumor activity up to 24–48 h postinjection, markedly improving tumor retention over the monomer (%ID/mL, 2.45 ± 0.39 vs 0.17 ± 0.04 at 48 h in SPECT/CT imaging). In a B16F10 therapy study, [¹⁷⁷Lu]Lu-LLP2A-Pol-1 significantly delayed tumor growth. Conclusion: A multimeric LLP2A probe with significantly enhanced tumor uptake and retention was successfully identified, providing a promising candidate for melanoma theranostics.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry","volume":"37 6","pages":"1303–1310"},"PeriodicalIF":4.5,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147961288","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}