Bioimpacts最新文献

{"title":"Spirulina: A promising opportunity to overcome neuropathic pain challenges in chronic kidney disease patients.","authors":"Zahra Nazari Taloki","doi":"10.34172/bi.32856","DOIUrl":"https://doi.org/10.34172/bi.32856","url":null,"abstract":"","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"15 ","pages":"32856"},"PeriodicalIF":2.2,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12913205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146229269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gold nanoparticle based fluorescent aptasensors: A chemical and biological detection perspective.","authors":"Zahra Hashemi, Tayebeh Hashemi, Azam Samadi, Elaheh Rahimpour","doi":"10.34172/bi.31387","DOIUrl":"10.34172/bi.31387","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>In recent decades, the development of simple and reliable techniques for detecting chemical and biological molecules has gained considerable importance. These methods have found extensive applications in different fields, including medicine, biotechnology, food safety, and environmental monitoring. Among these, aptasensors have attracted significant attention owing to their exceptional selectivity, high sensitivity, and versatility in targeting a wide range of analytes. Integrating aptasensors with nanotechnology, particularly gold nanoparticles (Au NPs), has revolutionized the efficiency and performance of these devices. Au NPs, with their unique features like as high surface-to-volume ratio, chemical stability, and extraordinary optical properties, serve as powerful tools for enhancing the aptasensor's capabilities. These features enable signal amplification, reduction of nonspecific interference, and enhancement of accuracy and sensitivity.</p><p><strong>Methods: </strong>This review focuses on recent advances in fluorescent aptasensors amplified by Au NPs. It analyzes the various experiments undertaken to develop and apply these sensors and concludes with a discussion of the technology's future prospects.</p><p><strong>Results: </strong>The findings establish the capability of aptamer-Au NP hybrids to detect a broad spectrum of analytes-including mycotoxins, antibiotics, pesticides, heavy metals, and disease biomarkers-with exceptional sensitivity.</p><p><strong>Conclusion: </strong>This review emphasizes the powerful potential of aptamer-Au NP hybrids for biosensing applications and suggests a path for future work to move this technology from the lab into practical use.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"15 ","pages":"31387"},"PeriodicalIF":2.2,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12705285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145775770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resolvin D1 alleviates lipopolysaccharide-induced <i>in vitro</i> corneal inflammation by modulating macrophage polarization through upregulation of c-Fos expression.","authors":"Qin Qin, Yinru Wang, Yajun Liu, Weiwei An, Zifang He, Feifei Chen, Xinxuan Cheng, Deyan Chen, Zhenggao Xie","doi":"10.34172/bi.32639","DOIUrl":"10.34172/bi.32639","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>Bacterial keratitis refers to a prevalent sight-threatening ophthalmologic infection. Owing to the challenge of antimicrobial resistance in treating bacterial keratitis, novel therapeutic strategies are needed. Resolvin D1 (RvD1), an endogenous lipid mediator, exhibits anti-inflammatory and immune-regulatory effects. The present study was aimed at investigating whether RvD1 alleviates lipopolysaccharide-induced inflammation to protect corneal fibroblasts and explore its potential mechanisms.</p><p><strong>Methods: </strong>In this study, Raw264.7 cells were polarized towards M1 or M2 macrophages by the addition of lipopolysaccharides LPS or interleukin (IL)-4, respectively, and were treated with or without RvD1. Flow cytometry and Western blot were used to determine the expression of M1 and M2-related markers. EdU assay and trans-well assay were performed to detect the proliferation and migration ability of corneal fibroblasts. Bioinformatics analysis (GO and KEGG) of RNA-seq was applied to explore the RvD1-related signaling pathways. siRNA-c-Fos was further used to confirm the role of Fos expression in RvD1-mediated macrophage polarization. Flow cytometry and Western blotting analysis were performed to demonstrate that RvD1 alleviated LPS-induced inflammation by suppressing M1 macrophage polarization, facilitating M2 macrophage polarization, and increasing corneal fibroblast proliferation. Bioinformatics analysis identified PI3K-AKT, IL-17, and MAPK signaling pathways as potential targets of RvD1 in corneal inflammation.</p><p><strong>Results: </strong>Enrichment analysis indicated that the RvD1 target gene showed a strong relationship to the regulation of macrophage polarization. RvD1 highly upregulated M2 macrophages by promoting c-Fos expression and enhanced the proliferation and migration of mouse corneal fibroblasts through modulating c-Fos expression.</p><p><strong>Conclusion: </strong>Our findings reveal that RvD1 conferred protective effects against LPS-induced inflammation by enhancing M2 macrophage polarization through the promotion of c-Fos expression. Thus, RvD1 may be a potential therapeutic compound for enhancing corneal fibroblast proliferation and migration while attenuating inflammation.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"15 ","pages":"32639"},"PeriodicalIF":2.2,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12705284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145775822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An efficacious opportunity for diagnosis and treatment of cancers: Radiolabeled fibroblast activation protein (FAP) inhibitors.","authors":"Nasim Vahidfar, Ayuob Aghanejad","doi":"10.34172/bi.33007","DOIUrl":"10.34172/bi.33007","url":null,"abstract":"<p><p>Despite the revolutionized diagnostic effect of fluorine-18 -fludeoxyglucose ([¹⁸F]-FDG) as a positron emission tomography (PET) radiotracer in oncological divisions, lack of specificity and sensitivity in discovery of some tumor subtypes was inevitable. Fibroblast activation protein (FAP) is overexpressed in a vast majority of neoplasms, particularly in more than 90% of epithelial tumors which could be an appropriate target for evaluation of tumor's molecular and metabolic functions by FAP inhibitor (FAPI) ligands. Considerably extensive radiolabeled FAPIs have been investigated during clinical trials for diagnostic as well as theranostic applications with encouraging outcomes. In the same cancers, PET/CT imaging by FAPIs are demonstrating to be valuable alternative to [¹⁸F]-FDG in assessment of cancers in which [¹⁸F]-FDG PET performance is suboptimal due to [¹⁸F]-FDG high background uptake or relatively low avidity. Furthermore, the propensity to specifically target FAP expression through FAP-targeted medications or radiotracer therapy creates prospects for image-guided treatment in both cancer and non-cancer indications. FAPI PET will remain a fascinating field of study in the future years.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"15 ","pages":"33007"},"PeriodicalIF":2.2,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12663746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145649838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allosteric ligand-driven smart nanoconjugates for mutation-selective EGFR targeting: A precision approach to overcoming tyrosine kinase inhibitor resistance.","authors":"Dilpreet Singh, Akshay Kumar, Vir Vikram Sharma","doi":"10.34172/bi.31475","DOIUrl":"10.34172/bi.31475","url":null,"abstract":"<p><p>The development of targeted therapies against epidermal growth factor receptor (EGFR) has transformed the clinical management of EGFR-driven malignancies, especially non-small cell lung cancer (NSCLC). However, the therapeutic benefit of ATP-competitive tyrosine kinase inhibitors (TKIs) is often undermined by acquired resistance mutations such as T790M and C797S, which either enhance ATP affinity or preclude covalent drug binding. Allosteric inhibition of EGFR has emerged as a promising alternative, leveraging cryptic, mutation-specific binding pockets to achieve superior selectivity and reduced off-target toxicity. Allosteric ligands, particularly those targeting the αC-helix adjacent clefts, have shown potent activity against drug-resistant EGFR isoforms but suffer from suboptimal pharmacokinetics and systemic stability. To overcome these limitations, smart nanoconjugates functionalized with allosteric inhibitors have been developed to enhance targeted delivery, improve intracellular trafficking, and facilitate stimuli-responsive drug release. These nanosystems are capable of co-delivering synergistic agents such as siRNA or CRISPR-Cas9 payloads, amplifying pathway suppression and delaying resistance onset. Surface modification strategies, including PEGylation and bioorthogonal ligand conjugation, further improve circulation half-life and tumor accumulation via active and passive targeting. This review systematically discusses the molecular basis of EGFR allosteric inhibition, engineering principles of nanocarrier platforms, including immunogenicity, scale-up feasibility, and regulatory complexities.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"15 ","pages":"31475"},"PeriodicalIF":2.2,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12705286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145775474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes-derived mesenchymal stem cells in corneal regeneration: Properties and challenges.","authors":"Ning Yao, Qian Zhang, Rongli Zhao, Xuemei Yang, Misbah Ullah Khan, Yan Dai","doi":"10.34172/bi.32495","DOIUrl":"10.34172/bi.32495","url":null,"abstract":"<p><p>The field of mesenchymal stem cell (MSC) therapy has grown rapidly over the last ten years. MSCs' regenerative, and immunomodulatory properties have led to extensive research into them as therapeutic agents for the cell-based management of chronic ocular diseases. However, poor biocompatibility, penetration, and transport to the target ocular tissues restrict the use of MSC-based treatment. The involvement of exosomes in MSC biological functions has been clarified by a growing body of research, which also indicates that MSC-derived extracellular vesicles (EVs) have similar anti-inflammatory, anti-apoptotic, tissue-repairing, neuroprotective, and immunomodulatory qualities as MSCs. Recent developments in exosomes produced from MSCs may help address the difficulties MSC therapy faces. MSC-derived exosomes' nanoscale size enables them to quickly cross biological barriers and enter immune-privileged organs. This enables the effective delivery of therapeutic factors, like trophic and immunomodulatory agents, to ocular tissues that are normally difficult for both conventional therapy and MSC transplantation to target. Furthermore, mesenchymal stem cell transplantation hazards are reduced when EVs are used. The properties of EVs produced by MSCs and their biological roles in corneal regeneration are the main topics of this review of the literature.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"15 ","pages":"32495"},"PeriodicalIF":2.2,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12663748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145649849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hierarchical classification of anterior cruciate ligament using deep learning for athletes healthcare.","authors":"Xuejiao Yan, Lei Xiao","doi":"10.34172/bi.31060","DOIUrl":"10.34172/bi.31060","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>Accurate and automated assessment of anterior cruciate ligament (ACL) injuries in MR images is essential for athlete healthcare and rapid diagnosis of knee injuries. However, challenges such as the small size of the ligament, variations in MR image quality, and complex anatomical structures complicate the classification process.</p><p><strong>Methods: </strong>In this study, we propose a hierarchical deep learning model for the detection and classification of ACL injuries. The model consists of two main phases: ACL segmentation and injury classification. In the first phase, we employ an encoder-decoder architecture with attention mechanisms to accurately identify the ACL region in MR images, while suppressing background noise. Skip connections are used to preserve spatial details and improve segmentation accuracy. In the second phase, the segmented ACL region is input into a hierarchical convolutional neural network (CNN) for classification. Dense blocks are incorporated to maximize feature reuse, while max-pooling and global average pooling (GAP) layers help to reduce overfitting and improve feature extraction.</p><p><strong>Results: </strong>The proposed method was evaluated on a knee MRI dataset and compared with other state-of-the-art approaches. Our model demonstrated high accuracy in both segmentation and classification tasks, owing to the integration of attention mechanisms and hierarchical feature extraction.</p><p><strong>Conclusion: </strong>This approach offers a robust solution for the automated assessment of ACL injuries, providing clinicians and sports medicine specialists with a reliable tool for more efficient and accurate diagnosis.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"15 ","pages":"31060"},"PeriodicalIF":2.2,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12663749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145649903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic engineering frontiers in cell manipulation-based tissue engineering: A comprehensive review.","authors":"Amirhossein Mohammadi, Mohammad Ali Heydari, Zahra Jamalpoor","doi":"10.34172/bi.30973","DOIUrl":"10.34172/bi.30973","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>A new era of regenerative medicine has been ushered in by the combination of tissue engineering and genetic engineering, offering unprecedented opportunities to address the growing demand for functional tissue replacements. This narrative review explores cutting-edge approaches in cell manipulation-based tissue engineering through the lens of genetic engineering, highlighting the transformative potential of this synergy.</p><p><strong>Methods: </strong>We critically examine the application of advanced genetic engineering techniques, including CRISPR-Cas9, TALENs, and synthetic biology, in modifying cellular behaviors and functions for tissue engineering. The review encompasses a diverse range of engineered tissues, from cartilage and bone to cardiac, neural, skin, and vascular constructs, elucidating how genetic manipulation enhances their functionality and physiological relevance. We further investigate the integration of these genetic approaches with emerging technologies such as 3D-bioprinting, microfluidics, and smart biomaterials, which collectively expand the horizons of complex tissue fabrication.</p><p><strong>Results: </strong>The review delves into pioneering trends, including in vivo genetic engineering for tissue regeneration and the development of patient-specific engineered tissues, discussing their implications for personalized medicine. We address the field's challenges, including long-term genetic stability, scalability, and off-target effects, while also considering the ethical implications and evolving regulatory landscape of genetically engineered tissues. Emerging technologies in genetic engineering, including base editing and synthetic genetic circuits, have been explored for their potential to create \"smart\" tissues capable of dynamic environmental responses. The review also highlights the synergistic potential of combining genetic engineering with stem cell technologies to enhance tissue functionality and immunological compatibility.</p><p><strong>Conclusion: </strong>This comprehensive review concludes by underscoring the transformative impact of genetic engineering on cell manipulation-based tissue engineering. While significant challenges persist, the rapid advancements in this field herald a future where genetically tailored, functional tissue constructs could revolutionize regenerative medicine, offering new hope for addressing critical unmet medical needs.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"15 ","pages":"30973"},"PeriodicalIF":2.2,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12663751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145649896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autophagy stimulation influenced the angiogenesis and metastasis behavior of human triple-negative breast cancer cells.","authors":"Zahra Abbasi-Malati, Çığır Biray Avci, Parisa Khanicheragh, Zeinab Aliyari Serej, Maryam Sabour Takanlou, Leila Sabour Takanlou, Seyed Ghader Azizi, Reza Rahbarghazi, Zohreh Sanaat, Nafiseh Didar Khosrowshahi, Hassan Amini, Rasoul Hosseinpour","doi":"10.34172/bi.32624","DOIUrl":"10.34172/bi.32624","url":null,"abstract":"<p><p></p><p><strong>Introduction: </strong>Breast cancer (BC) is a devastating condition with high morbidity and mortality rates in females. Autophagy is an early-stage cell response against stressful conditions. Emerging data have revealed the autophagy-angiogenesis interaction in terms of tumor development and metastasis.</p><p><strong>Methods: </strong>Here, the angiogenesis behavior of human MDA-MB-231 cells was monitored after modulation of autophagy response in the presence of free 3-methyladenine (3-MA), metformin (Met), or drug-loaded exosomes (3-MA@Exos and Met@Exos). Orthotopic transplantation was done using human BC cell-laden alginate/gelatin (Alg/Gel) microspheres in mice after treatment with Met and/or 3-MA.</p><p><strong>Results: </strong>Met, and/or Met@Exos increased the cell migration rate and promoted human endothelial cell migration compared to the control cells (<i>P</i><0.05). However, these features were blunted in 3-MA and 3-MA@Exos groups (<i>P</i><0.05). Flow cytometry analysis revealed that the drug loading into Exos did not influence internalization capacity or cell survival (<i>P</i>>0.05). ELISA revealed that vascular endothelial growth factor (VEGF) levels were reduced in Met and 3-MA-treated cells, with more pronounced reductions in the free 3-MA groups. Real-time PCR analysis showed diminished expression of several angiogenesis-related genes, except for platelet endothelial cell adhesion molecule-1 (PECAM-1) in the Met@Exos, 3-MA, and 3-MA@Exos groups. Met treatment increased the metastasis and tumor formation in mice mammary glands after orthotopic transplantation of BC tumoroids.</p><p><strong>Conclusion: </strong>These data indicate that autophagy modulation can alter the angiogenesis and metastatic behavior of human BC cells <i>in vitro</i> and <i>in vivo</i>. Exos are valid bio-shuttles for the delivery of autophagy modulators in CSC-targeted therapies.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"15 ","pages":"32624"},"PeriodicalIF":2.2,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12663750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145649865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of artificial intelligence in enhancing breast cancer screening and diagnosis: A review of current advances.","authors":"Faezeh Firuzpour, MohammadAli Heydari, Cena Aram, Ali Alishvandi","doi":"10.34172/bi.30984","DOIUrl":"10.34172/bi.30984","url":null,"abstract":"<p><p>Breast cancer (BCA) remains the most prevalent cancer globally and the leading cause of cancer-related mortality among women, with rising incidence rates driven by genetic, lifestyle, and environmental factors. Early detection through precise screening is essential to improve prognosis and survival; yet, challenges persist, especially in resource-limited areas. Recent advances in Artificial Intelligence (AI), particularly machine learning and deep learning algorithms, have illustrated significant potential to enhance breast cancer screening, diagnosis, and treatment personalization. This review highlights the multifaceted role of AI in BCA management, encompassing its applications in image-based screening modalities, genomic and immunologic profiling, and drug discovery. AI-driven approaches offer diagnostic accuracy, cost-effectiveness, time-saving, and individualized treatment regimens. Despite promising developments, further research is crucial to overcome current challenges and regulatory hurdles in clinical settings. This article highlights the positive aspects of AI technologies in advancing BCA care and the importance of continued interdisciplinary research to optimize their implementations in breast cancer workflows.</p>","PeriodicalId":48614,"journal":{"name":"Bioimpacts","volume":"15 ","pages":"30984"},"PeriodicalIF":2.2,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12663752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145649876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}