Assay and drug development technologies最新文献

{"title":"Development and Evaluation of Prednisolone Acetate-Loaded Nanostructured Lipid Carriers Integrated into pH-Triggered <i>In Situ</i> Gels for Ocular Drug Delivery.","authors":"Sheetal Devi, Vipin Saini, Navneet Mehan, Manish Kumar, Md Ali Mujtaba, Gamal Osman Elhassan, Nafis Haider, Musarrat Husain Warsi","doi":"10.1089/adt.2025.053","DOIUrl":"https://doi.org/10.1089/adt.2025.053","url":null,"abstract":"<p><p>\u0000 <i>This study aimed to enhance the therapeutic efficacy of prednisolone by developing a nanostructured lipid carrier (NLC) system for topical ocular administration and addressing the limitations of current topical therapy. Drug-loaded NLCs (prednisolone acetate [PSA1]-PSA13) were formulated using high-pressure homogenization techniques, optimized with a central composite design, and evaluated for various pharmaceutical properties. An optimization study indicates that the lipid ratio and surfactant concentration influence particle size, entrapment efficiency (EE), and drug release. The optimized NLC formulation (PSA3) was integrated into a pH-triggered <i>in situ</i> gel system and assessed for drug permeation, ocular irritation, and stability. The optimized drug-loaded NLC formulations (PSA3) exhibited a nano size of 96.80 ± 0.51 nm, achieving an EE of 84.51 ± 1.31% and a drug release rate of 95.76 ± 1.23%. The drug permeation through the goat cornea was significantly higher in the <i>in situ</i> gel (PSAG4) compared with the control (marketed PSA eye drop). Additionally, the eye irritation data indicated good ocular tolerance, while stability studies confirmed that the developed formulation remained stable at room temperature. In conclusion, the developed NLC-based <i>in situ</i> gel appears to be a promising approach to enhancing the efficacy of prednisolone in topical therapy for the successful treatment of ocular inflammation.</i>\u0000 </p>","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective Potential of Saroglitazar Against Cerebral Ischemia/Reperfusion Injury in Sprague-Dawley Rats: Targeting HMGB-1/NF-κB Pathway.","authors":"Prachi Mistry, Sanjiv Prajapati, Paridhi Vadher, Jhanvi Soni, Vijay Kevlani","doi":"10.1089/adt.2025.057","DOIUrl":"https://doi.org/10.1089/adt.2025.057","url":null,"abstract":"<p><p>\u0000 <i>Stroke is an intricate oxidative and inflammatory response resulting from cerebral ischemia followed by reperfusion injury. Complex pathophysiology of stroke poses challenges for treatment. Peroxisome proliferator-activated receptor (PPAR) expression in the rat hippocampus is markedly elevated post cerebral ischemia/reperfusion (I/R) injury. Hence, saroglitazar, a dual PPAR-α/γ agonist, was investigated against cerebral I/R injury in rats. Male Sprague-Dawley rats were subjected to bilateral common carotid artery occlusion for 30 min and reperfusion for 3 days. During the reperfusion, animals were treated with vehicle or saroglitazar once a day for 3 days. The behavioral parameters were assessed, and animals were sacrificed to measure oxidative markers (malondialdehyde, superoxide dismutase, catalase, and reduced glutathione), inflammatory markers (interleukin-6, tumor necrosis factor-α, nuclear factor kappa-light chain enhancer of activated B cells (NF-κB), and high mobility group box 1 (HMGB-1) protein, infarction, and histopathology changes. Following I/R injury, antioxidant enzymes were reduced, while nitric oxide and inflammatory markers were increased in the disease group. In the rat hippocampus, these changes led to neurobehavioral impairment and cerebral infarction. Saroglitazar improved the levels of antioxidants and reduced inflammation; 2,3,5-triphenyltetrazolium chloride stain and histopathological analysis revealed the neuroprotective effect of saroglitazar in the hippocampus region. The neuroprotective effects of saroglitazar were attributed to its activation of both PPAR-α and PPAR-γ. It improved antioxidant levels and inhibited proinflammatory cytokines by suppressing the HMGB-1/NF-κB signaling pathway. These findings underscore the potential of saroglitazar in mitigating cerebral I/R injury.</i>\u0000 </p>","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implementation of the Box-Behnken Design in the Development and Optimization of Methotrexate-Loaded Microsponges for Colon Cancer.","authors":"Mahendra Prajapati, Ranjit K Harwansh, Mohammad Akhlaquer Rahman, Rohitas Deshmukh","doi":"10.1089/adt.2024.073","DOIUrl":"10.1089/adt.2024.073","url":null,"abstract":"<p><p>\u0000 <i>Methotrexate (MTX) is an effective anticancer agent with limited water solubility, resulting in lower absorption in the gastrointestinal tract when administered orally. The present aim of the study is to construct sustained-release formulation of MTX-loaded microsponges with enhanced intestinal absorption and bioavailability using a quasi-emulsion solvent diffusion method. The Box-Behnken design (BBD) was adopted for this purpose. Particle size, encapsulation efficiency (EE), Q 2 h % (% drug release in 2 h), and Q 24 h % (% drug release in 24 h) were used as dependent factors, and polyvinyl alcohol, solvent, and stirring speed were used as independent factors. The prepared microsponges were characterized to assess their particle size and encapsulation efficacy (%). Attenuated total reflectance-Fourier transform infrared spectroscopy and differential scanning calorimetry were used to verify the compatibility study. Moreover, the cytotoxicity study was conducted on the HT-29 cell line. The optimized formulation exhibited a % encapsulation efficacy of 87.191% and a particle size of 2.176 µm. Furthermore, the optimized formulation demonstrated sustained drug release (85.71%) in Simulated Gastric Fluid (SGF) fluid at different pHs 1.2, 6.8, and 7.4. The stability study of the optimized formulation revealed good stability in terms of drug release, % encapsulation efficacy, and particle size. The results of the optimized formulation demonstrated that the viability of HT-29 colon cancer (CC) cells was dose-dependently decreased by MTX-loaded microsponges. BBD was successfully employed for the development and optimization of MTX microsponges filled in Eudragit S-100-coated hard gelatin capsule, depicting their potential release of MTX from microsponges capsule only at the colonic region and found to be potential carrier system for CC.</i>\u0000 </p>","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":" ","pages":"251-268"},"PeriodicalIF":1.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roadmap to Cytotoxicity: Exploring Assays and Mechanisms.","authors":"Kirtivardhan Singh Shekhawat, Piyush Bhatia, Kartik Bhatnagar, Swati Shandilay, Sarika Chaudhary","doi":"10.1089/adt.2024.109","DOIUrl":"10.1089/adt.2024.109","url":null,"abstract":"<p><p>\u0000 <i>Cytotoxicity assays are essential in the field of research as they enable the examination of cellular responses to stimuli and shed light on complex mechanisms involved in multiple diseases and drug development. This review covers a range of cytotoxicity assays, including trypan blue and MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assays, to more advanced techniques like caspase activity assays, Lactate dehydrogenase release assays, comet assays, and micronucleus assays for DNA damage assessment. Apart from these, other relevant assays like Alamar Blue, Bromodeoxyuridine incorporation, and clonogenic cell survival are also discussed. In this study, significance of these assays in drug development, toxicology studies, and biomedical research is discussed in detail, highlighting their role in ensuring safety and unraveling disease mechanisms. Furthermore, we explore emerging technologies such as chip-based assays, organ-on-a-chip systems, and high-throughput screening, which enhance precision and efficiency in research. Despite these advancements, challenges remain that necessitate standardization efforts and the development of more refined models. In conclusion, this review reflects on the evolving landscape of cytotoxicity assays, finding a balance between traditional methodologies and cutting-edge technologies.</i>\u0000 </p>","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":" ","pages":"217-236"},"PeriodicalIF":1.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the Role of Buzhong Yiqi Decoction on Neurogenic Bladder with Network Pharmacology, Molecular Docking, and <i>In Vitro</i> Assays.","authors":"Yixin Bao, Chun Sun","doi":"10.1089/adt.2024.028","DOIUrl":"10.1089/adt.2024.028","url":null,"abstract":"<p><p>\u0000 <i>Buzhong Yiqi decoction (BZYQD) is a traditional Chinese medicine prescription for treating neurogenic bladder (NB). However, the underlying pharmacological mechanism remains unclear. This study aims to clarify the related molecular mechanism. Molecular structure information and targets of core components of BZYQD were obtained from Traditional Chinese Medicines Systems Pharmacology Platform (TCMSP) and SwissTargetPrediction databases. Genes involved in NB were obtained from Comparative Toxicogenomics Database, DisGeNet, GeneCards, and Online Mendelian Inheritance in Man databases. The hub targets of BZYQD in NB treatment were identified by protein-protein interaction (PPI) network analysis with STRING platform and analyzed by gene ontology analysis and the Kyoto Encyclopedia of Genes and Genomics pathway enrichment analysis. Molecular docking was used to verify the binding affinity between the hub targets and the bioactive components of BZYQD. Subsequently, the neuroprotective and anti-inflammatory effects of main bioactive components of BZYQD were investigated with <i>in vitro</i> assays. A total of 131 candidate compounds and 925 predicted target genes were screened. PPI network analysis suggested that ESR1, EGFR, HSP90AA1, MAPK3, AKT1, and CASP3 were the hub targets. BZYQD treatment was associated with hypoxia inducible factor-1 (HIF-1) signaling pathway. Dehydroglyasperin C (DGC), <i>N</i>-cis-feruloyltyramine, shinpterocarpin (SHI), gancaonin M, and glyasperin B, as the main bioactive components of BZYQD, had good binding affinity with hub target proteins. DGC and SHI treatment could significantly inhibit the injury of neurons and inflammatory response of microglia stimulated by oxidized low-density lipoprotein (ox-LDL), respectively. In summary, BZYQD and its main bioactive components DGC and SHI show good potential to ameliorate the symptoms of NB.</i>\u0000 </p>","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":" ","pages":"237-250"},"PeriodicalIF":1.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced Anticancer Efficiency of Curcumin Co-Loaded Lawsone Solid Lipid Nanoparticles Against MCF-7 Breast Cancer Cell Lines: Optimization by Statistical JMP Software-Based Experimental Approach.","authors":"Shivarani Penugonda, Pranusha Beesappagari, Maddileti Repollu, Poojitha Badiginchala, Samreen Qudsiya, Chinni Usha Sree Mala, Ravi Gundawar, Bhargav Eranti","doi":"10.1089/adt.2024.125","DOIUrl":"10.1089/adt.2024.125","url":null,"abstract":"<p><p>\u0000 <i>The present study highlighted enhancing the therapeutic effectiveness of curcumin (CUR) co-loaded lawsone (LS) through a solid lipid nanoparticles (SLNs)-based delivery system. The cetyl palmitate (CP), polyethylene glycol 400 (PEG), and probe sonication time (PS) were considered as independent variables whereas particle size and % entrapment efficiency (EE) were selected as dependent variables. The CUR-LS-SLN was developed by hot emulsification followed by probe sonication. A 2³ factorial design was utilized in formulation development using JMP software version 17. Notably, the particle size and %EE of all the formulations were about 500 nm and greater than 75%, respectively. The zeta potential value was found to be -46.8 mV. From leverage plots significant and sensitive factors on particle size and %EE were identified. Contour plots led to the identification of an optimized formula whereby maintaining CP at 100 mg, PEG 400 at 6 mL, and PS at 10 min the desired particle size and %EE was achieved. TEM studies indicated the spherical shape of the particles. MTT assays of Michigan Cancer Foundation-7 (MCF-7) cells showed enhanced efficacy and greater cell inhibition of CUR-LS-SLN and combining both drugs using nanocarriers gave superior inhibition as compared with using either of the drugs evident from IC₅₀ values of 3.7, 9.4, and 2.5 μM, respectively, for CUR, LS, and CUR-LS-SLN. The cells in the combination mostly had irregular cell walls and cell shrinkage was noted and greater cell reduction was also seen. It was found that the enhanced cytotoxicity effect of MCF-7 cells on the developed formulation was attributed to the drug's synergistic actions, more efficient nanocarrier internalizations, and sustained drug release from the formulation. Stability studies indicated that the optimized SLN was stable for 6 months.</i>\u0000 </p>","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":" ","pages":"269-279"},"PeriodicalIF":1.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Potential Molecular Targets of Doxorubicin for Application in Skin Cancer: A Network Pharmacology and Molecular Docking Perspective.","authors":"Sonali Karhana, Sanjula Baboota, Mohd Ashif Khan, Javed Ali","doi":"10.1089/adt.2024.083","DOIUrl":"https://doi.org/10.1089/adt.2024.083","url":null,"abstract":"<p><p>\u0000 <i>The primary objective was to find the pharmacological targets of doxorubicin and their mechanisms of action, with a dual focus on their therapeutic relevance in skin cancer treatment and their potential involvement in resistance to doxorubicin in cancer cells. The targets of skin cancer and potential targets of doxorubicin were searched from multiple databases. Common targets were chosen using the GeneVenn tool and then imported into the STRING database to construct a protein-protein interaction network. Topological factors were evaluated with Cytoscape to identify core targets. FunRich was used to identify the signaling pathways, molecular functions, cellular components, and biological processes involving the top targets. Molecular docking was conducted using the Molecular Operating Environment software. The top five target genes identified as therapeutic targets of doxorubicin for treatment of skin cancer are poly(ADP-ribose) polymerase, epidermal growth factor receptors, heat shock protein 90 alpha family class A member 1, Harvey rat sarcoma viral oncogene homolog, and mammalian target of rapamycin. In addition, doxorubicin-induced resistance mechanisms were also predicted. Further research on innovative methods of delivering doxorubicin to maximize its effectiveness in treating skin cancer and to prevent the development of resistance to the drug is necessary.</i>\u0000 </p>","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted Drug Delivery with Nanosponges and Nanocrystals: Innovations, Formulation Strategies, and Applications.","authors":"Preeti Aneja, Rajender Guleria, Dev Prakash Dahiya","doi":"10.1089/adt.2025.026","DOIUrl":"https://doi.org/10.1089/adt.2025.026","url":null,"abstract":"<p><p>\u0000 <i>The neoteric advancement in nanotechnology accompanied the development of targeted drug delivery system. The utmost muddle facing the investigators is targeted drug delivery to specific sites. The unfolding of a new nanoparticle carrier called nanosponges should label these problems. The finding out of nanosponges has become a significant step in overcoming certain problems essentially as drug toxicity; impoverish drug's availability and release of drug in a foreseeable fashion as they can take in both hydrophilic and hydrophobic drug. Nanosponges constitute a porous structure in nature that has the sole ability to entrap the drug moieties and offers merit of desired release. Nanosponges are mini sponges that can circulate in the body to make it to the specific site and cohere on the surface to release the drug in a controlled and predictable manner. Similarly, afresh invented medications have been come across to poorly water-soluble drug, which may be applicable in resolving the solubility problem by nanocrystallization via nanocrystals. This review will cover nanosponges and nanocrystals, as well as the diverse methodologies employed in their formulation, characterization, and their applications. The study also throws light on medically authorized nanosponges and nanocrystals, including those already developed that can elicit a significant outcome helpful in clinical studies as well as used by various research workers for their upcoming studies.</i>\u0000 </p>","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of Anti-Inflammatory Activity via Diclofenac Sodium-Based Nanostructured-Lipid Carriers: Physical Characterization and <i>In Vivo</i> Assessment.","authors":"Alok Pratap Singh, Dinesh Puri, Iti Chauhan, Amulya Jindal, Jayendra Kumar, Nitish Kumar, Madhu Verma, Mohd Yasir, Sonakshi Antal, Priya Dhiman, Prasoon Kumar Saxena","doi":"10.1089/adt.2025.004","DOIUrl":"https://doi.org/10.1089/adt.2025.004","url":null,"abstract":"<p><p>\u0000 <i>Diclofenac sodium (DS) is categorized under the nonsteroidal anti-inflammatory class of drugs that also belongs to biopharmaceutical classification system (BCS) class II. It has limited dissolution parameters which also resist the total bioavailability but it has a good transdermal permeability characteristic and the pharmacokinetic parameters of DS make it suitable for the formulation of nanostructured-lipid carrier (NLC)-based gel transdermal delivery. The research aimed to design and develop a drug-delivery system (DDS), i.e., DS-NLCs incorporated in gel to modulate its anti-inflammatory action via skin. The formulation was optimized using Taguchi's approach and the resultant NLCs were thoroughly characterized, including assessments for viscosity, zeta potential, particle size, and morphological evaluation. Furthermore, particular investigations were carried out for DS-NLCs, including drug encapsulation efficiency, <i>ex vivo</i> release properties in Phosphate Buffer Saline at pH 7.4, and an <i>in vivo</i> skin irritation test. 5-FUNLCs had a mean size of 339 ± 25 nm and were spherical-shaped particles. With an encapsulation effectiveness of 84%, the NLCs were found to have effectively loaded drugs. Moreover, these NLCs demonstrated a sustained release characteristic that persisted for a maximum of 24 h, suggesting their potential for gradual and regulated drug release. Lipid components demonstrated good stability over 90 days and were biocompatible with the DS. Furthermore, compared with the usual formulation, topical gel loaded with NLC (GNLC) containing DS considerably suppresses edema in the <i>in vivo</i> result, suggesting that the developed formulation has superior anti-inflammatory efficacy. These NLCs provide prolonged release and better drug solubility, both of which boost therapeutic outcomes and control the drug's anti-inflammatory potential. The study's conclusion emphasizes DS-NLC's potential as a cutting edge and effective medication delivery technology. The results indicate the need for more preclinical research, which presents an effective direction for developing a more potent and well-tolerated therapeutic strategy.</i>\u0000 </p>","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Letter:</i> Addressing False Positives in High-Throughput Screening: A Call for Better Predictive Models.","authors":"Dilpreet Singh","doi":"10.1089/adt.2025.035","DOIUrl":"https://doi.org/10.1089/adt.2025.035","url":null,"abstract":"","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}