Nanomedicine : nanotechnology, biology, and medicine最新文献

{"title":"Withaferin A and Withanolide A-mediated silver nanoparticles target bacterial motility, metabolism, and stress adaptation in E. coli","authors":"Moumita Sil ,&nbsp;Anamitra Goswami ,&nbsp;Dipro Mukherjee ,&nbsp;Nabanita Mukherjee ,&nbsp;Igor Polikarpov ,&nbsp;Arunava Goswami ,&nbsp;Moupriya Nag ,&nbsp;Dibyajit Lahiri","doi":"10.1016/j.nano.2025.102846","DOIUrl":"10.1016/j.nano.2025.102846","url":null,"abstract":"<div><div>Biogenic silver nanoparticles (Bio-AgNPs) were synthesized using <em>Withania somnifera</em> root extract and evaluated for their antimicrobial and biosafety profiles. LC-MS confirmed key withanolides, including Withaferin A. The nanoparticles exhibited a UV–Vis peak at 446 nm, a crystalline core size of ∼15.65 nm, a hydrodynamic diameter of ∼134.85 nm, and a zeta potential of −25.29 mV. Bio-AgNPs showed potent antibacterial activity against <em>Escherichia coli</em> K12, with MICs between 156.25 and 312.5 ppm and superior efficacy to AgNO₃. RNA-seq analysis revealed downregulation of flagellar genes (<em>flgD</em>, <em>flgG</em>, <em>fliC</em>), maltose transporters (<em>malK</em>, <em>malF</em>, <em>lamB</em>), and citrate metabolism (<em>citT</em>, <em>citD</em>), indicating impaired motility and nutrient uptake. Upregulation of metal efflux (<em>cusF</em>, <em>cusB</em>) and electron transport (<em>fixA</em>, <em>fixB</em>) genes reflected oxidative stress response. Cytotoxicity assays on WI-38 and HEK-293 cells showed &gt;80 % viability up to 156.25 ppm. These findings support Bio-AgNPs as biocompatible, plant-derived antimicrobials effective against Gram-negative bacteria.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"68 ","pages":"Article 102846"},"PeriodicalIF":4.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144696586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual-scavenging Mn₃O₄-PEI nanoparticles targeting ROS and cfDNA for acute pancreatitis therapy.","authors":"Xin Bao, Guang Xin, Qilong Zhou, Tao Wang, Xinrui Xu, Lijuan Feng, Chengyu Wan, Fangyuan Jing, Yijiang Liu, Yangbo Liu, Xiaoting Chen, Wen Huang","doi":"10.1016/j.nano.2025.102848","DOIUrl":"https://doi.org/10.1016/j.nano.2025.102848","url":null,"abstract":"<p><p>Acute pancreatitis (AP) is a common inflammatory disease that seriously threatens people's lives and health. Excessive reactive oxygen species (ROS) and cell-free DNA (cfDNA) are significant contributors to the advancement of AP. In this study, a nanoparticle with a dual function to clear ROS and cfDNA was developed for the treatment of acute pancreatitis. Cationic polyethyleneimine (PEI) was used to modify Mn₃O₄, resulting in the creation of Mn₃O₄-PEI nanoparticles, which exhibited strong binding to cfDNA and the ability to scavenge ROS. In vitro, Mn₃O₄-PEI showed significant inhibition of ROS and cfDNA-induced inflammation and demonstrated therapeutic effects in a model of acute pancreatitis induced by sodium taurocholate (STC). This research introduces a new nanomedicine approach for the treatment of AP.</p>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":" ","pages":"102848"},"PeriodicalIF":4.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antioxidative fullerol prevents bone loss due to its anti-osteoclastogenic and pro-osteogenic activities","authors":"Xinlin Yang ,&nbsp;Alyssa Costello ,&nbsp;Guowei Shang ,&nbsp;Hongjian Liu ,&nbsp;Weicheng Wang ,&nbsp;Changle Ren ,&nbsp;Peng Xu ,&nbsp;Abhijit Dighe ,&nbsp;Quanjun Cui","doi":"10.1016/j.nano.2025.102847","DOIUrl":"10.1016/j.nano.2025.102847","url":null,"abstract":"<div><h3>Purpose</h3><div>Previous studies have demonstrated a role for oxidative stress in promoting osteoclastogenesis and bone loss. This study aimed to assess the ability of fullerol, a powerful nano-antioxidant, to prevent bone loss and promote osteogenesis, and additionally provide novel insight into mechanisms of action.</div></div><div><h3>Methods</h3><div>Osteoclastogenesis assays were conducted in murine progenitor cells stimulated with receptor activator of nuclear factor kappa-B ligand (RANKL), with and without fullerol. The cells were stained to detect the presence of osteoclastic markers and RT-PCR was used to measure the expression of osteoclastic genes. To assess osteogenesis, stem cells were incubated in osteogenic medium with or without fullerol, as well as with an inhibitor of p38-MAPK, then stained to determine mineralization. RT-PCR was used to measure osteoblastic gene expression. In the animal model, rabbits were injected with methylprednisolone with or without fullerol, or a control. Animals were later euthanized and spine fragments underwent imaging assessment.</div></div><div><h3>Results</h3><div>Fullerol prevented formation of osteoclasts in RAW264.7 cells exposed to RANKL as well as the expression of osteoclastic genes TRAP, CATK, and MMP9. D1 cells exposed to fullerol displayed an increase in extracellular matrix mineralization and expression of osteoblastic genes. However, when fullerol was added in the presence of a p38-MAPK inhibitor, its effects on mineralization were attenuated. In a rabbit model of steroid-induced osteoporosis, simultaneous injection of fullerol reduced vertebral bone loss, decreased trabecular separation, and increased trabecular number.</div></div><div><h3>Conclusion</h3><div>Fullerol shows early potential for use in osteoporosis therapy, due to its ability to inhibit osteoclast formation and stimulate osteogenesis.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"68 ","pages":"Article 102847"},"PeriodicalIF":4.2,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144680196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of human non-small cell lung cancer histology samples by atomic force microscopy","authors":"Lasma Bugovecka MSc ,&nbsp;Sergejs Isajevs PhD, MD ,&nbsp;Uldis Malinovskis MSc ,&nbsp;Andis Liepins ,&nbsp;Aiga Adrijanova MSc ,&nbsp;Donats Erts PhD","doi":"10.1016/j.nano.2025.102844","DOIUrl":"10.1016/j.nano.2025.102844","url":null,"abstract":"<div><div>This study utilized atomic force microscopy (AFM) to analyze intraoperative frozen histology samples from 26 patients with non-small cell lung cancer tissue, specifically adenocarcinoma and squamous cell carcinoma. Clear and measurable structural differences were identified between tumor cell regions and stroma of the two subtypes. Nuclear region morphologies varied among cell groups – ranging from indistinct nuclear regions in stromal tumor cells to partially torn nuclei in non-cancerous bronchial epithelial cells. This observation may indicate differences in nuclear structure characteristics. Compared to control samples, stromal regions of both cancer types exhibited denser coverage of striated fibrils with a 67 nm periodicity characteristic to collagen. Standard surface roughness tests on randomly selected sites within sections (tumor and non-malignant) suggest potential for distinguishing malignant from control histology samples. Combining atomic force microscopy with histopathological analysis may offer additional structural insight into lung tissue alterations associated with malignancy.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"68 ","pages":"Article 102844"},"PeriodicalIF":4.2,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In situ miniemulsions of glimepiride using D-optimal mixture design-in silico, in vitro and in vivo studies","authors":"Niserga D. Sawant M.Pharm ,&nbsp;Bandoo C. Chatale Ph.D. ,&nbsp;Namita D. Desai Ph.D.","doi":"10.1016/j.nano.2025.102842","DOIUrl":"10.1016/j.nano.2025.102842","url":null,"abstract":"<div><h3>Purpose</h3><div>Glimepiride, a BCS class II oral hypoglycaemic drug shows dissolution rate limited absorption. Oral <em>in situ</em> miniemulsions can improve Glimepiride solubility by enhancing dissolution rate for faster absorption, subsequently rapid onset of action and reducing variations in oral bioavailability for effective control of blood glucose levels.</div></div><div><h3>Methods</h3><div>Capryol 90, Tween 20, PEG 400 and stearyl amine were used to develop <em>in situ</em> miniemulsions of Glimepiride using D-Optimal mixture design. <em>In silico</em> molecular modelling studies were performed to understand role of stearyl amine in modifying Glimepiride solubility. <em>In situ</em> miniemulsions were characterized for globule size, zeta potential, polydispersity index, drug content, pH and accelerated aging. Further, the optimized <em>in situ</em> miniemulsions were converted into granules by adsorbing on Syloid XDP 3150.</div></div><div><h3>Results</h3><div>Molecular dynamics simulation confirmed that stearyl amine enhanced Glimepiride solubility in Capryol 90. DSC thermograms revealed amorphous state of Glimepiride while <em>in vitro</em> release studies indicated &gt;90 % Glimepiride release from <em>in situ</em> miniemulsions and granules as compared to suspensions at the end of 10 min. <em>Ex vivo</em> studies performed on non-everted gut sacs from Wistar rats displayed greater <em>ex vivo</em> intestinal permeability of Glimepiride from the developed granules than suspensions. <em>In vivo</em> studies in male Wistar rats revealed that developed Glimepiride granules showed statistically significant (<em>p</em> &lt; 0.001) decrease in blood glucose levels as compared to conventional marketed tablets of Glimepiride.</div></div><div><h3>Conclusions</h3><div>The present research work holds potential in delivering <em>in situ</em> miniemulsions of Glimepiride for effective treatment of diabetes and proposes novelty for enhancing oral bioavailability.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"68 ","pages":"Article 102842"},"PeriodicalIF":4.2,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sequential flash nanocomplexation and flash nanoprecipitation enables scalable assembly of doxorubicin-loaded nanoparticles","authors":"Yuanmuhuang Long BS ,&nbsp;Sachin V. Kammula BS ,&nbsp;Yicheng Zhang PhD ,&nbsp;Hai-Quan Mao PhD","doi":"10.1016/j.nano.2025.102843","DOIUrl":"10.1016/j.nano.2025.102843","url":null,"abstract":"<div><div>The study presents the sequential flash nanocomplexation (FNC)–flash nanoprecipitation (FNP) process as a scalable method for producing polymeric nanoparticles (NPs) with controlled encapsulation and release of doxorubicin (DOX). In the FNC step, DOX is first crosslinked with tannic acid (TA), then stabilized by human serum albumin (HSA) via hydrogen bonding, forming uniform DOX-TA-HSA nanocomplexes. The nanocomplexes are then encapsulated into poly(ethylene glycol)-<em>b</em>-poly(lactic acid-<em>co</em>-glycolic acid) (PEG-<em>b</em>-PLGA) dissolved in various water-miscible organic solvents through FNP. Solvent selection significantly influenced the release rate, with dimethyl sulfoxide (DMSO) enabling sustained release for up to two weeks. Additionally, the optimized process demonstrated excellent reproducibility and scalability, with minimal batch-to-batch variations. This NP assembly process is complemented by scalable purification with the tangential flow filtration (TFF) method, showing preserved size distribution and DOX release kinetics. This study underscores the technical advantages and translational potential of the FNC–FNP process for nanotherapeutic manufacturing.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"68 ","pages":"Article 102843"},"PeriodicalIF":4.2,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advanced ocular drug delivery in microgravity: Nanotherapeutic applications as cardiovascular and ophthalmic countermeasures","authors":"Ryung Lee ,&nbsp;Joshua Ong ,&nbsp;Ethan Waisberg ,&nbsp;Rahul Kumar ,&nbsp;Alex Ngo ,&nbsp;Thomas H. Mader ,&nbsp;John Berdahl ,&nbsp;Umesh C. Karandikar ,&nbsp;Alessandro Grattoni ,&nbsp;Andrew G. Lee","doi":"10.1016/j.nano.2025.102845","DOIUrl":"10.1016/j.nano.2025.102845","url":null,"abstract":"<div><div>Extended space missions significantly affect astronaut health, leading to various systemic and ocular conditions. The ocular surface and cardiovascular system are particularly susceptible to the unique environment within the spacecraft. This can often lead to pathologic issues such as radiation-induced accelerated atherosclerosis (RIAA), spaceflight-associated neuro-ocular syndrome (SANS) and spaceflight-associated dry eye syndrome (SADES). While traditional treatments for SADES, such as artificial tears and lubricants, provide short-term relief, they may lose effectiveness during long-duration spaceflight. In this context, nanomedicine offers promising solutions for the controlled and targeted delivery of therapeutics, including drugs and biologics. This review assesses the spectrum of ocular health and cardiovascular changes in astronauts, highlights the limitations of existing therapeutic measures, and explores how nanotechnology-based approaches can overcome these limitations by significantly enhancing drug delivery in microgravity. We further discuss the need for rigorous validation to improve the management of ocular and cardiovascular in future space exploration.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"68 ","pages":"Article 102845"},"PeriodicalIF":4.2,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultrasound-assisted green synthesis of gold nanoparticles using Pelargonium graveolens leaf extract: Antibacterial activity and microfluidic evaluation of mechanistic effects","authors":"Zinab Moradi Alvand PhD ,&nbsp;Fateme Aghamir PhD ,&nbsp;Hasan Rafati PhD","doi":"10.1016/j.nano.2025.102841","DOIUrl":"10.1016/j.nano.2025.102841","url":null,"abstract":"<div><div>Green chemistry enables sustainable, innovative, and efficient nanomaterial synthesis advancements. In this work, a green synthesis approach was employed to produce gold nanoparticles (Au NPs) using an ultrasound-assisted method with aqueous <em>Pelargonium graveolens</em> leaf extract. The resulting Au NPs were characterized by UV–Vis spectroscopy, X-ray diffraction, dynamic light scattering, and transmission electron microscopy, confirming cubic, stable particles with an average size of ∼41.5 nm, a zeta potential of +19.4 mV, and an absorption peak at 525 nm. Antibacterial activities of both the Au NPs and plant extract were evaluated against <em>B. subtilis</em>, <em>S. aureus</em>, <em>E. coli</em>, and <em>P. aeruginosa</em>, using conventional and microfluidic assays. Au NPs demonstrated superior efficacy (e.g., MIC for <em>E. coli</em> 1.56 μg/mL). Nucleic acid and protein leakage assays indicated greater membrane disruption in the microfluidic system compared to the conventional method. SEM imaging revealed substantial bacterial cell wall disruption, validating the significant antibacterial mechanisms of biosynthesized Au NPs.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"68 ","pages":"Article 102841"},"PeriodicalIF":4.2,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Measurement of cell electrical signal by dual-probe atomic force microscopy","authors":"Xingyue Wang ,&nbsp;Kaige Qu ,&nbsp;Rui Wang ,&nbsp;Zuobin Wang ,&nbsp;Baohua Jia","doi":"10.1016/j.nano.2025.102838","DOIUrl":"10.1016/j.nano.2025.102838","url":null,"abstract":"<div><div>The conduction of electrical signal plays critical roles in neuron activities. The capacity of atomic force microscopy to establish physical contacts at the nanoscale and offer higher spatial resolution compared to conventional electrical recording methods, such as patch clamp, significantly enhances our understanding and analysis capabilities. This capability enables the direct visualization and precise quantification of the electrical properties within specific cellular membrane regions. In this study, we use conductive probes in our self-developed dual-probe atomic force microscope system as nanoelectrodes to measure the electrical signals of SH-SY5Y cell. Given that SH-SY5Y cells exhibit neuron-like properties and are relevant to human neurological diseases, researching these cells provides valuable insights into neuronal behavior and pathology. In dual-probe atomic force microscope, one probe is responsible for sending stimulation signals to the cells, while the other probe receives transmitted information from the cell. By modulating the pressure applied by the tip to the cell membrane, the effects on SH-SY5Y cells at different contact depths and time intervals were investigated, along with the monitoring of cellular potential changes. The changes in cell potential were detected. Two different nonlinear electrical characteristics were observed, which indicate the cell membrane exhibits adaptability and self-repair ability, achieved by regulating the state of ion channels to ensure membrane potential stability. These results provide a new way to stimulate and study the electrical characteristics and physiological behaviors of cells and other biological samples, potentially revealing new insights of neuron activities.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"68 ","pages":"Article 102838"},"PeriodicalIF":4.2,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144554007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SERS liquid biopsy in colorectal cancer detection and treatment response: Revealing metabolic memory post-radiochemotherapy","authors":"David Andras MD, PhD ,&nbsp;Stefania D. Iancu PhD ,&nbsp;Ramona G. Cozan PhD student ,&nbsp;Markus Zetes PhD student ,&nbsp;George Crisan PhD student ,&nbsp;Codruta F. Buldus MD, PhD ,&nbsp;Iulia Andras MD, PhD ,&nbsp;Vasile Bintintan MD, PhD ,&nbsp;George C. Dindelegan MD, PhD ,&nbsp;Nicolae Leopold PhD","doi":"10.1016/j.nano.2025.102840","DOIUrl":"10.1016/j.nano.2025.102840","url":null,"abstract":"<div><div>This study investigates the potential of using surface-enhanced Raman scattering (SERS) serum analysis to assess the response of rectal adenocarcinoma (READ) patients to preoperative radiochemotherapy (RCT). A univariate classification approach differentiated RCT responders (R) from non-responders (NR) with 73 % accuracy. In addition, a classifier trained to differentiate colon cancer from healthy controls was independently applied to the R and NR groups. Using this model, Random Forest identified 86 % of NR samples as cancerous, aligning closely with histopathological findings. Notably, the SERS metabolic profile of the majority of the R sample more closely resembled that of cancer pathology than of healthy controls, suggesting the presence of residual cancer-related metabolic activity, despite the diagnosis of near complete tumor regressions based on histopathology. This user independent classification approach underscores the potential of SERS-based clinical spectroscopy as a non-invasive support tool for predicting tumor response in colorectal cancer.</div></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"68 ","pages":"Article 102840"},"PeriodicalIF":4.2,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}