Journal of Biological Inorganic Chemistry最新文献

{"title":"Magnetic interactions between metal sites in complex enzymes.","authors":"Biplab K Maiti, Isabel Moura, José J G Moura","doi":"10.1007/s00775-025-02120-1","DOIUrl":"https://doi.org/10.1007/s00775-025-02120-1","url":null,"abstract":"<p><p>Magnetic interactions between iron-sulfur (Fe/S) clusters and transition metal centers such as nickel, molybdenum, and copper play a central role in the function of key metalloenzymes. These interactions, which arise from electronic coupling, spin exchange, and spatial arrangement, directly influence redox behavior and catalytic efficiency. This review highlights three distinct complex enzymes-[NiFe] hydrogenases, mononuclear molybdenum-containing xanthine oxidase (XO) family, and [NiFe] and [MoCu] carbon monoxide dehydrogenases (CODHs)-as paradigms for understanding (Fe/S)-metal center interactions. In [NiFe] hydrogenases, (Fe/S) clusters serve as electron relays that magnetically interact with the catalytic [NiFe] active site. In XO-type enzymes, a mononuclear Mo center is functionally and magnetically coupled to nearby Fe/S clusters, modulating substrate reduction and electron transfer. Similarly, in CODHs, both [NiFe]-and [MoCu]-dependent variants exhibit strong magnetic communication between metal active sites and surrounding Fe/S clusters, crucial for CO₂/CO interconversion. Advanced spectroscopic approaches, particularly electron paramagnetic resonance (EPR) and related techniques, combined with theoretical modelling, have provided deep insights into the electronic structures and dynamic interactions within these metalloenzymes. Understanding these magnetic interactions not only sheds light on fundamental electron-transfer and enzymatic mechanisms but also guides the design of bioinspired catalysts and energy-conversion technologies.</p>","PeriodicalId":603,"journal":{"name":"Journal of Biological Inorganic Chemistry","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disulfide-based 2-pyridyl-hydrazone prochelators induce iron deprivation and oxidative stress in ovarian cancer cells.","authors":"Jacob B Fussell, Jake P Shaw, Madison A Grams, Yu-Shien Sung, Ren-Hua Jheng, Andrei V Astashkin, Elisa Tomat","doi":"10.1007/s00775-025-02119-8","DOIUrl":"https://doi.org/10.1007/s00775-025-02119-8","url":null,"abstract":"<p><p>Alterations of iron homeostasis are characteristic of malignant behavior and have been associated with poor prognosis in ovarian cancer patients. Iron-binding chelators are currently under investigation as potential cancer therapeutics because they allow manipulation of iron availability and redox chemistry. In addition, the design of prochelator systems enables the release of iron-binding chelators upon cell entry and therefore the sequestration of intracellular (rather than systemic) iron. We report the synthesis and biological evaluation of disulfide-based prochelators featuring a 2-pyridyl-hydrazone motif and resulting in a tridentate (S,N,N) donor set as found in several antiproliferative chelators (e.g., Triapine, Dp44mT, DpC, COTI-2). Upon disulfide reduction and iron(II) coordination, the chelators stabilize ferric complexes that are redox-active in neutral aqueous conditions. Symmetric prochelator (PH3-S)₂ and glucose conjugate G6PH3 have antiproliferative, pro-apoptotic effects in A2780 ovarian carcinoma cells. Both compounds sequester intracellular iron and impact the expression of the transferrin receptor TfR1 and the iron storage protein ferritin. Oxidative stress is found to be a component of the mechanism of action of these prochelators. Accordingly, the preformed iron complex FePH3 also leads to apoptosis and iron dysregulation, and its toxicity is enhanced when the antioxidant capacity of the cells is impaired. The incorporation of the 2-pyridyl-hydrazone motif in disulfide-based prochelators therefore combines iron sequestration with pro-oxidant effects that could enhance the pharmacological profile of this chelation approach for cancer applications.</p>","PeriodicalId":603,"journal":{"name":"Journal of Biological Inorganic Chemistry","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Au(I)-based compounds inhibit nsp14/nsp10 and nsp13 (helicase) to exert anti-SARS-CoV-2 properties.","authors":"Jingxin Chen, Xueying Wei, Chun-Lung Chan, Kaiming Tang, Shuofeng Yuan, Hongyan Li, Hongzhe Sun","doi":"10.1007/s00775-025-02118-9","DOIUrl":"https://doi.org/10.1007/s00775-025-02118-9","url":null,"abstract":"<p><p>Au(I) compounds have long been associated with medicine for the treatment of various diseases, especially auranofin has been used for the treatment of rheumatoid arthritis. In addition, Au(I) based compounds also exhibit anti-cancer, anti-bacteria properties. The recent prevalence of the COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has aroused attention to investigate the antiviral potential of Au(I) compounds. Herein we demonstrate the pan-anti-SARS-CoV-2 activity of Au(I) metallodrugs in mammalian cells. We synthesized a panel of Au(I)-based compounds and found that these compounds could effectively inhibit the exoribonuclease and methyltransferase activities of SARS-CoV-2 nsp14/nsp10 complex, and the ATPase and DNA unwinding activities of SARS-CoV-2 nsp13 (helicase). Mechanistic studies reveal that Au(I) can not only displace the critical Zn(II) ions from nsp14/nsp10 complex and nsp13 but also changes the secondary and quaternary structure of nsp14 and perturbate the DNA unwinding of nsp13 by disrupting the ATP binding. This study illustrates a multi-target feature Au(I) compounds/drug agents for the viruses, highlighting their potential as pan-anti-SARS-CoV-2 (or relevant viruses) agents.</p>","PeriodicalId":603,"journal":{"name":"Journal of Biological Inorganic Chemistry","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinorganic chemistry: where from and where to?","authors":"Clotilde Policar","doi":"10.1007/s00775-025-02112-1","DOIUrl":"https://doi.org/10.1007/s00775-025-02112-1","url":null,"abstract":"<p><p>Bioinorganic chemistry is a multidisciplinary field that bridges the apparent divide between inorganic chemistry and biology. The very name \"bioinorganic\" is an intriguing oxymoron, as \"inorganic\" chemistry traditionally refers to the study of the inanimate world, while the \"bio\" prefix refers to living systems. Bioinorganic chemistry focuses on metallic systems within biological environments, with the dual aims of better understanding these natural systems and leveraging the solutions developed through evolution to design new industrial or therapeutic applications. As a close cousin of the field of metallomics, bioinorganic chemistry shares the fundamental principles that underpin metallomics' systemic analyses of metal-containing biomolecules. In this article, we trace the historical development of bioinorganic chemistry, highlighting its recent advancements and outlining future research challenges in this dynamic interdisciplinary area.</p>","PeriodicalId":603,"journal":{"name":"Journal of Biological Inorganic Chemistry","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Organotin(IV) carboxylates-derivatives of bexarotene: synthesis, characterization, anti/prooxidant activity, and high cytotoxicity.","authors":"D A Burmistrova, N P Pomortseva, N T Berberova, N R Almyasheva, M A Kiskin, A I Poddel'sky, A S Vashurin, I V Smolyaninov","doi":"10.1007/s00775-025-02117-w","DOIUrl":"https://doi.org/10.1007/s00775-025-02117-w","url":null,"abstract":"<p><p>New organotin(IV) mono- and bis-carboxylate complexes derivatives of Bexarotene (bex), viz. R₃Sn(bex) (where R = Ph (1); Cy (2); nBu (3)), and R₂Sn(bex)₂ (where R = Et (4), tBu (5), Ph (6)) were synthesized. Compounds were fully characterized using spectroscopic techniques. The molecular structure for the Ph₃Sn(bex) (1) in crystalline form was established by single-crystal X-ray diffraction. Electrochemical properties of tin complexes and bexarotene were investigated by cyclic voltammetry. The target compounds are characterized by the high oxidation potentials in the mixture of aprotic solvents. The anti/prooxidant activity of the complexes and bexarotene in the lipid peroxidation process and in the reaction of the DNA oxidative damage was studied in vitro. Excellent cell growth inhibition against A549, HCT 116 and MCF-7 cancer cells was observed for triorganotin (IV) carboxylates with IC₅₀ values mostly under the submicromolar concentration range and there are more effective than bexarotene or cisplatin.</p>","PeriodicalId":603,"journal":{"name":"Journal of Biological Inorganic Chemistry","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contrasting secondary coordination sphere effects on spin density distribution in Red vs. Blue Cu azurin.","authors":"Casey Van Stappen, Edward Reijerse, Sonia Chabbra, Alexander Schnegg, Yi Lu","doi":"10.1007/s00775-025-02116-x","DOIUrl":"https://doi.org/10.1007/s00775-025-02116-x","url":null,"abstract":"<p><p>Metalloproteins tune the electronic properties of metal active sites through a combination of primary and secondary coordination sphere effects (PCS and SCS) to efficiently perform an array of redox chemistry, including electron transfer (ET) and catalysis. A major influence of these effects is the anisotropic spatial distribution of redox-active molecular orbitals (RAMOs), which in turn dictates redox chemistry of the metalloproteins. While much progress has been made in understanding the SCS effects on RAMOs in individual native metalloproteins, it has been difficult to experimentally examine the influence of the same SCS effects on RAMOs with different spatial distributions. Taking advantage of our recent studies of SCS effect on blue copper azurin from Pseudomonas aeruginosa (Blue CuAz) and its M121H/H46E variant that closely mimic the red copper protein (Red CuAz), in which their RAMOs are dominated by either Cu-S_π or Cu-S_σ interactions, respectively, we herein compare and contrast how the same SCS modifications impact the electronic and geometric structures of blue and red Cu center in the same protein scaffold. Specifically, we expand our understanding of unpaired electron distribution at the Cu-binding site of Red CuAz and its SCS N47S, F114P, and F114N mutations using ¹H and ¹⁴N electron-nuclear double resonance (ENDOR) spectroscopy, and then further combine these data sets with recent studies and DFT calculations to provide insight into how these mutations differentially (or similarly) impact electronic structure in Red vs. Blue CuAz. We find that electrostatics produce similar effects in both Red and Blue CuAz, where the introduction of dipole moments in the vicinity of Cu and S produces changes in spin density distribution and of the same sign and comparable magnitude. However, disruption of H-bonding with S through the F114P mutation leads to opposing effects in Red vs. Blue CuAz, which we propose arise from differences in the conformation of Cys112 sidechain adapted in the absence the stabilizing S_C112⋯H-N backbone interaction.</p>","PeriodicalId":603,"journal":{"name":"Journal of Biological Inorganic Chemistry","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determination of silver(I)-binding sites in canonical B-DNA by NMR spectroscopy.","authors":"Tabea Lenz, Uroš Javornik, Marian Hebenbrock, Janez Plavec, Jens Müller","doi":"10.1007/s00775-025-02115-y","DOIUrl":"https://doi.org/10.1007/s00775-025-02115-y","url":null,"abstract":"<p><p>The interaction of metal ions with nucleic acids was studied by determining the initial binding sites of Ag⁺ ions at unmodified B-DNA by NMR spectroscopy. In particular, NMR spectra were recorded of the Dickerson-Drew dodecamer sequence in the presence of different ratios of Ag⁺ ions to DNA. The data indicate that the coordination of the first three Ag⁺ ions per duplex preferentially takes place inside the B-DNA helix rather than at other possible binding sites such as the negatively charged phosphate backbone and/or the endocyclic N7 position of purine residues. Larger DNA aggregates are formed in the presence of excess Ag⁺ ions, as indicated by the formation of a precipitate and by significant changes in the circular dichroism spectra. As shown by a titration with chloride ions, the Ag⁺ ions are only loosely bound to the nucleic acids and can be released by precipitation of AgCl.</p>","PeriodicalId":603,"journal":{"name":"Journal of Biological Inorganic Chemistry","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro cellular and molecular plus in silico studies of a substituted bipyridine-coordinated Zn(II) ion: cytotoxicity, ROS-induced apoptosis, anti-metastasis, and BAX/BCL2 genes expression.","authors":"Marzieh Anjomshoa, Bagher Amirheidari, Mehdi Sahihi, Jan Janczak, Hamid Forootanfar, Alireza Farsinejad, Yasaman Abolhassani, Somayyeh Karami-Mohajeri","doi":"10.1007/s00775-025-02114-z","DOIUrl":"https://doi.org/10.1007/s00775-025-02114-z","url":null,"abstract":"<p><p>A new dimethyl-substituted bipyridine-Zn(II) complex (^2Mebpy-Zn) was synthesized and structurally characterized. Single-crystalline structure of the complex was elucidated as [Zn(^2Mebpy)₃](ClO₄)₂∙1.5(dioxane) by X-ray diffraction, where ^2Mebpy is 4,4'-dimethyl-2,2'-bipyridine. The three-dimensional electrostatic potential maps (3D ESP) were plotted for [Zn(^2Mebpy)₃]²⁺ cation and [Zn(^2Mebpy)₃](ClO₄)₂ molecule. In vitro cytotoxicity studies indicated significant cytotoxicity of ^2Mebpy-Zn against both breast (MCF-7) and glioblastoma (U-87) cancer cells relative to normal murine embryo cells (NIH/3T3). The results are indicative of a superior selectivity toward MCF-7 over the other cell lines as confirmed by IC₅₀ value of 5.1 ± 0.5 µM after 48 h. Interestingly, MCF-7 and U-87 cells death induced by ^2Mebpy-Zn mostly proceed through an apoptotic pathway which probably associates with the overproduction of reactive oxygen species (ROS). The Zn(II) complex suppressed the metastatic affinity of MCF-7 cells by blocking migration as well as formation of colonies. Also, the expression of two opponent apoptosis-relevant genes (BAX and BCL2) measured by real-time polymerase chain reaction (qPCR) experiments indicated that ^2Mebpy-Zn could potentially trigger apoptotic cell death. Moreover, ^2Mebpy-Zn could cleave hydrolytically the pUC19 DNA without the need to add any external agent. Finally, the binding affinity of two enantiomers of ^2Mebpy-Zn toward cancer therapeutic targets, such as anti-apoptotic proteins, estrogen receptor α, tubulin, and topoisomerase II, was studied by in silico molecular docking. In conclusion, ^2Mebpy-Zn can be introduced as a potential therapeutic agent in breast cancer and indicates that other metal complexes with bipyridine derivatives can also exhibit promising anticancer effects.</p>","PeriodicalId":603,"journal":{"name":"Journal of Biological Inorganic Chemistry","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electron spin resonance in microalgae whole-cells to monitor hydrogen production","authors":"Silvia Pizzanelli,&nbsp;Emanuela Pitzalis,&nbsp;Simone Botticelli,&nbsp;Fabrizio Machetti,&nbsp;Cecilia Faraloni,&nbsp;Giovanni La Penna","doi":"10.1007/s00775-025-02113-0","DOIUrl":"10.1007/s00775-025-02113-0","url":null,"abstract":"<p>Unicellular algae can produce pure hydrogen gas from water and sun-light. We observed <i>Chlorella vulgaris</i> whole cells when they produce hydrogen using X-band continuous-wave electron spin resonance (ESR). Whole-cell spectroscopy is particularly useful in those cases where purified enzymes are sensitive to oxidant air conditions. By tuning cell preparation, the microwave power, the temperature, the time of air exposure, we could isolate from the background signal candidate markers of hydrogen production. Our observations indicate the presence of a species consistent mainly with an intermediate <span>({hbox {Fe}_{3}hbox {S}_{4}{^{+}}})</span> cluster when hydrogen production is high, but not maximal, and when FeS cluster oxidation has just begun. The optimal conditions to detect the above marker by ESR have been identified. Our investigation paves the way to extensive statistical analysis of cellular conditions in future studies using whole-cell ESR.</p>","PeriodicalId":603,"journal":{"name":"Journal of Biological Inorganic Chemistry","volume":"30 3","pages":"229 - 240"},"PeriodicalIF":2.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00775-025-02113-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polyoxometalates bind multiple targets involved in Alzheimer’s disease","authors":"Karin Ben Zaken,&nbsp;Rivka Bouhnik,&nbsp;Naama Omer,&nbsp;Naamah Bloch,&nbsp;Abraham O. Samson","doi":"10.1007/s00775-025-02111-2","DOIUrl":"10.1007/s00775-025-02111-2","url":null,"abstract":"<div><p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by brain aggregates of amyloid-β (Aβ) plaques and Tau tangles. Despite extensive research, effective therapy for AD remains elusive. Polyoxometalates (POMs), a class of inorganic compounds with diverse chemical structures and properties, are emerging as potential candidates for AD treatment due to their ability to target key molecular players implicated in disease pathogenesis, such as Aβ, acetylcholinesterase (AChE) and butyryl acetylcholinesterase (BChE). Here, we use molecular docking to predict the binding pose and affinities of POMs to 10 top targets associated with AD. First, we validate our method by replicating experimentally known binding of POMs to Aβ (Δ<i>G</i> = – 9.67 kcal/mol), AChE (Δ<i>G</i> = – 9.39 kcal/mol) and BChE (Δ<i>G</i> = – 10.86 kcal/mol). Then, using this method, we show that POM can also bind β-secretase 1 (BACE1, Δ<i>G</i> = – 10.14 kcal/mol), presenilin 1 (PSEN1, Δ<i>G</i> = – 10.65 kcal/mol), presenilin 2 (PSEN2, Δ<i>G</i> = – 7.94 kcal/mol), Amyloid Precursor Protein (APP, Δ<i>G</i> = – 7.26 kcal/mol), Apolipoprotein E (APOE4, Δ<i>G</i> = – 10.05 kcal/mol), Microtubule-Associated Protein Tau (MAPT, Δ<i>G</i> = – 5.28 kcal/mol) depending on phosphorylation, and α-synuclein (SNCA, Δ<i>G</i> = – 7.64 kcal/mol). Through such binding, POMs offer the potential to mitigate APP cleavage, Aβ oligomer neurotoxicity, Aβ aggregation, thereby attenuating disease progression. Overall, our molecular docking study represents a powerful tool in the discovery of POM-based therapeutics for AD, facilitating the development of novel treatments for AD.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":603,"journal":{"name":"Journal of Biological Inorganic Chemistry","volume":"30 3","pages":"299 - 309"},"PeriodicalIF":2.7,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00775-025-02111-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}