MedChemComm最新文献

{"title":"Kupffer cell M2-like polarization increases liver metastatic burden via the uptake of exosomal KRAS mutant protein from hypoxic colorectal carcinoma cells","authors":"Yu You, Zhihao Feng, Jiao Lu, Jie Xu, Ke You, Fuyao Liu, Tianzhu Wu, Hua Song and Zuojin Liu","doi":"10.1039/D5MD00897B","DOIUrl":"10.1039/D5MD00897B","url":null,"abstract":"<p > <em>Background</em>: this study investigates the metastasis-promoting effect of colorectal carcinoma cell-derived exosomes in liver metastasis, M2-like polarization of Kupffer cells, and the underlying mechanism. <em>Methods</em>: mouse liver metastasis models were established to determine the involvement of CRC-derived exosomes in liver metastasis. The DIR and PKH26 fluorescent labeling strategies were utilized to trace the distribution of CRC-derived exosomes <em>in vivo</em>. GO and KEGG analyses of differentially expressed genes revealed the key cellular regulator and KRAS-induced signaling in CRC liver metastasis. The phenotype of Kupffer cells was determined by IHC and IF. <em>In vitro</em> model HMDMs were used to explore polarization phenotype and therapeutic effects of GSK690693 (AKT inhibitor) inhibited AKT. <em>Results</em>: exosomal mutant KRAS induced AKT signaling in the process of Kupffer cell M2-like polarization, promoting CRC liver metastasis. AKT inhibitors might potentially be used as a therapeutic approach to prevent liver metastasis in CRC. <em>Conclusion</em>: our findings reveal that exosomal mutant KRAS drives Kupffer cell M2-like polarization <em>via</em> the hyperactivation of AKT signaling, establishing this axis as a key mediator of colorectal cancer liver metastasis. Pharmacological inhibition of AKT effectively disrupts this immunosuppressive reprogramming, proposing targeted AKT blockade as a promising strategy to intercept the metastatic niche in CRC patients.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 3","pages":" 1521-1536"},"PeriodicalIF":3.597,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of novel progesterone-heterocyclic conjugates and their encapsulated polymeric nanoparticles as potential CDK8 inhibitors: lung cytotoxicity evaluation, gene expression, and molecular docking","authors":"Yasmin Y. Omar, Ghada F. Elmasry, Dina S. El-kady, Ahmed A. Abd-Rabou, Samir M. El-Moghazy, Fadi M. Awadallah, Gamal A. Elmegeed and Ghada H. Elsayed","doi":"10.1039/D5MD00794A","DOIUrl":"10.1039/D5MD00794A","url":null,"abstract":"<p >CDK8 is overexpressed in many cancers and represents a potential target for developing new anticancer agents. To identify promising antineoplastic compounds as CDK8 inhibitors, progesterone-heterocyclic conjugates were synthesized through multicomponent reactions (MCRs), verified by spectroscopic and analytical data, and they were then encapsulated into CS-PEG nanoparticles to enhance their activity and efficacy. The <em>in vitro</em> anticancer activity of synthesized progesterone heterocyclic derivatives in free and CS-PEG nanoform was assessed on A549 cells using the neutral red uptake test. Compared to Doxorubicin values (IC<small>₅₀</small> = 11.74 and 10.14 μM for free and CS-PEG nanoform, respectively), compounds <strong>4e</strong>, <strong>4b</strong>, <strong>4f</strong>, <strong>13</strong>, <strong>15</strong>, <strong>8b</strong>, <strong>12</strong>, and <strong>4d</strong>, in free form (IC<small>₅₀</small> = 3.63, 4.46, 5.49, 5.62, 9.54, 9.77, 10.47, and 10.96 μM, respectively) and in CS-PEG nanoform (IC<small>₅₀</small> = 3.20, 3.54, 3.83, 5.28, 7.09, 9.43, 9.65, and 9.88 μM, respectively), showed higher inhibitory activity on A549 growth. Notably, compounds <strong>4e</strong> and <strong>4f</strong> showed significant inhibition of CDK8 enzyme <em>in vitro</em> comparable to Cortistatin A (IV). Furthermore, compounds <strong>4e</strong> and <strong>4f</strong> CS-PEG nanoparticles significantly downregulated the CDK8, β-catenin, c-MYC, and HIF-1α genes as well as the protein expression levels of PI3K and AKT, and also upregulated the levels of P53 gene and MDA in A549 cells, thereby triggering ROS-mediated apoptosis and suppressing angiogenesis, invasion, and cell growth. Additionally, the molecular docking study confirmed that compounds <strong>4e</strong> and <strong>4f</strong> had a strong binding affinity to the active site of CDK8, consistent with their results and antiproliferative activity on A549 lung cancer cells.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 2","pages":" 932-950"},"PeriodicalIF":3.597,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145805346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On the history, synthesis, and medicinal use of cantharidin, LB-100, and their analogs†","authors":"Kevin A. Scott, Adam McCluskey, Jon T. Njardarson and Wei Wang","doi":"10.1039/D5MD00917K","DOIUrl":"10.1039/D5MD00917K","url":null,"abstract":"<p >Cantharidin, a defensive toxin produced by blister beetles, has fascinated chemists, physicians, and historians for centuries. From its notorious use as the aphrodisiac “Spanish fly” to its modern FDA approval as YCANTH™ for molluscum contagiosum, this small yet complex molecule has inspired both infamy and innovation. Over the past hundred years, some of the most eminent synthetic chemists, including Professors Diels, Alder, Ziegler, Schenck, Stork, and Dauben, have tackled the formidable challenges of cantharidin synthesis, establishing benchmarks in organic chemistry. Parallel biological studies revealed cantharidin and its analogs as potent inhibitors of serine/threonine protein phosphatases, particularly PP1, PP2A, and PP5, with wide-ranging implications in oncology, immunology, and chemical biology. Derivatives such as norcantharidin and LB-100 have broadened therapeutic horizons, the latter reaching clinical trials as a novel anticancer agent and immune checkpoint potentiator. Despite inconsistencies in the literature, ranging from pharmacological selectivity to reproducibility of assay data, recent advances in structural biology, computational modeling, and medicinal chemistry have opened new opportunities to refine potency, selectivity, and stability of cantharidin-derived therapeutic molecules. This review critically examines the historical, chemical, and biomedical landscape of cantharidin and its derivatives, clarifies longstanding ambiguities, and highlights future opportunities to develop phosphatase-targeting therapies for cancer, autoimmune, and inflammatory disease.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 2","pages":" 743-767"},"PeriodicalIF":3.597,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12772682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145918370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sterically hindered catechol-derived Schiff bases: design, synthesis, SAR analysis and mechanisms of the antioxidant activity","authors":"Maxim Gvozdev, Iveta Turomsha, Nikolai Osipovich, Roman Sverdlov and Natalia Loginova","doi":"10.1039/D5MD00969C","DOIUrl":"10.1039/D5MD00969C","url":null,"abstract":"<p >Sterically hindered phenols represent a fascinating class of redox-active compounds with unique radical regulatory properties. In this comprehensive study, we explored the <em>in vitro</em> antioxidant activity of 24 novel sterically hindered catechol-derived Schiff bases through a multi-technique approach. Using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical scavenging assays alongside ferric ion reducing antioxidant power (FRAP) and copper reducing antioxidant capacity (CUPRAC) reduction potential tests, complemented by cyclic voltammetry and density functional theory (DFT) calculations with the B3LYP/UB3LYP functional and 6-311++G(d,p) basis set, we have revealed remarkable structure–activity relationships that challenge the conventional understanding of antioxidant mechanisms. Our findings suggest that antioxidant behavior is highly dependent on the structure of a Schiff base and reaction conditions, with the compound dynamically switching between hydrogen atom transfer (HAT) and electron transfer (ET) pathways. Intriguingly, thiol-derived antioxidants demonstrated exceptional activity in DPPH and ABTS assays, while their potency surprisingly decreased under acidic FRAP conditions. Electron-donating groups consistently enhanced antioxidant activity, whereas strong electron-withdrawing groups significantly compromised radical scavenging and metal reducing capacity. Mechanistic studies have revealed that Hammett constants effectively predict antioxidant behavior in the DPPH radical scavenging assay in aprotic solvents, whereas in polar media, we have observed the coexistence of HAT and single electron transfer–proton transfer (SET–PT) pathways. The ABTS assay predominantly followed the sequential proton loss electron transfer (SPLET) mechanism, while the results of FRAP and CUPRAC assays aligned best with SET–PT descriptors. Most notably, we identified the formation of <em>ortho</em>-quinones, disulfides, and complex adducts as key transformation products, providing unprecedented insights into the multifaceted antioxidant mechanisms of these promising compounds and opening new prospects for rational design of antioxidant agents.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 2","pages":" 898-911"},"PeriodicalIF":3.597,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146012124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N-Cyano sulfoximine-mediated thiazole ligation with N-terminal cysteine under mild aqueous conditions","authors":"Eunsil Kim, Ji Young Hyun, Ji Ho Song, Hwan Jung Lim and Seong Jun Park","doi":"10.1039/D5MD00948K","DOIUrl":"10.1039/D5MD00948K","url":null,"abstract":"<p >An <em>N</em>-terminal cysteine-selective click reaction employing <em>N</em>-cyano sulfoximines enables rapid thiazole formation under mild conditions. These three-dimensional, hydrophilic scaffolds offer high selectivity, tunable reactivity, and improved drug-like properties. The platform holds promise for bioorthogonal conjugation and ligand design in drug discovery applications.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 2","pages":" 1031-1036"},"PeriodicalIF":3.597,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12777572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145934929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small molecule-mediated spatial targeting of mitochondria and the Golgi apparatus in cancer cells","authors":"Phanindra Kumar, Asima Sahu, Tripti Mishra and Sudipta Basu","doi":"10.1039/D5MD00758E","DOIUrl":"10.1039/D5MD00758E","url":null,"abstract":"<p >Cancer remains one of the most dynamic and complex diseases, driven by intricate interplay and cross-talk among various sub-cellular organelles. Among these, mitochondria and the Golgi apparatus (GA) have garnered significant attention due to their critical roles in diverse biological processes—many of which, when dysregulated, contribute to cancer development and progression. Despite this, the mechanistic understanding of mitochondria–GA cross-talk and their location–function relationships remains limited, largely due to the lack of chemical tools for spatial organelle-specific targeting. To bridge this gap, we designed and synthesized a concise library of protonated 3-methoxy-pyrrole-based small molecules featuring a positive charge. Screening this library in HeLa (cervical) and HCT-116 (colon) cancer cells identified a lead molecule, <strong>7f</strong>, which self-assembled into nanoparticles and selectively localized to the mitochondria in HeLa cells, followed by mitochondrial impairment and generation of reactive oxygen species (ROS) leading to the induction of apoptosis by downregulating Bcl-2 and Cas-3 and upregulating BAX. Interestingly, a neutral phenylsulfonamide derivative (compound <strong>9</strong>) of <strong>7f</strong> rapidly localized to the GA within 30 minutes, triggered autophagy through the upregulation of Beclin and LC3-II/I and exhibited cytotoxicity when combined with the autophagy inhibitor chloroquine. These findings highlighted how subtle structural modifications can govern organelle-specific localization. We anticipate that these 3-methoxy-pyrrole-based small molecules represent promising chemical biology tools to dissect the spatial and functional dynamics of mitochondria–GA interplay, with potential implications for targeted cancer therapeutics.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 2","pages":" 1200-1206"},"PeriodicalIF":3.597,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146012176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, synthesis, and structural elucidation of ethyl 2-amino-5-oxo-4-aryl-4H-pyrano[3,2-c]quinoline-3-carboxylates as dual EGFR/HER-2 inhibitors endowed with antiproliferative activity","authors":"Lamya H. Al-Wahaibi, Hesham A. Abou-Zied, Aliaa M. Mohassab, Hazem M. Fathy, Abdullah Yahya Abdullah Alzahrani and Bahaa G. M. Youssif","doi":"10.1039/D5MD00868A","DOIUrl":"10.1039/D5MD00868A","url":null,"abstract":"<p >A new series of quinoline-3-carboxylate derivatives <strong>3a–k</strong> were developed as prospective dual inhibitors of EGFR and HER-2. Structural elucidation was accomplished <em>via</em><small>¹</small>H NMR, <small>¹³</small>C NMR, DEPT NMR, elemental analysis and mass spectrometry. The synthesized compounds were evaluated for antiproliferative activity against breast (MCF-7) and colon (HT-29) cancer cell lines. Compounds <strong>3a</strong> and <strong>3f</strong> had the highest antiproliferative efficacy, especially against HT-29 colon cancer cells (IC<small>₅₀</small> = 23 and 25 nM, respectively), surpassing erlotinib (IC<small>₅₀</small> = 30 nM). Kinase inhibition experiments further validated the dual action of <strong>3a</strong> and <strong>3f</strong>, yielding IC<small>₅₀</small> values of 68 nM and 30 nM against EGFR and HER-2, respectively, for <strong>3a</strong> and IC<small>₅₀</small> values of 71 and 33 nM against the same two kinases for <strong>3f</strong>. Compounds <strong>3a</strong> and <strong>3f</strong> induced apoptosis by the activation of caspases 3, 8, and 9, alongside the overexpression of Bax and the downregulation of Bcl-2. <em>In silico</em> molecular docking studies were performed to investigate the binding interactions of the most active compound, <strong>3a</strong>, with EGFR and HER-2 kinase domains. The compound showed strong binding affinities, forming critical hydrogen bonds and hydrophobic interactions with key active-site residues. Additionally, SwissADME analysis of <strong>3a</strong> revealed full compliance with major drug-likeness filters, highlighting its potential as an orally available, dual EGFR/HER-2 inhibitor with favorable pharmacokinetic properties.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 12","pages":" 6319-6332"},"PeriodicalIF":3.597,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145701834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, antibacterial activity, and mechanistic characterization of novel 9-substituted berberine derivatives","authors":"Jiaying Tong, Huamao Yang, Yeying He, Kejie Chen, Chaoyue Chen, Haoyi Han and Chenping Li","doi":"10.1039/D5MD00825E","DOIUrl":"10.1039/D5MD00825E","url":null,"abstract":"<p >Natural products serve as valuable sources for developing antibacterial agents. In this study, 35 berberine derivatives were synthesized, and preliminary screening revealed that most compounds effectively inhibited the growth of Methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) and <em>Pseudomonas aeruginosa</em>. Notably, <strong>B12</strong>-loaded HAMA/PEGDA hydrogels exhibited a sustained-release profile that ensured prolonged local exposure and produced significant antibacterial effects in an MRSA-infected wound mouse model. Furthermore, <strong>B12</strong> showed potent antibacterial and therapeutic effects in a <em>P. aeruginosa</em>-induced bacterial pneumonia-associated acute lung injury model. Mechanistically, <strong>B12</strong> reduced bacterial loads in skin and lung tissues, suppressed pro-inflammatory cytokine expression, and promoted tissue repair. Acute toxicity assessment further confirmed its <em>in vivo</em> safety. Additional mechanistic analyses demonstrated that <strong>B12</strong> disrupted bacterial cell membrane integrity, altered cell morphology, and increased membrane permeability. Collectively, these findings support <strong>B12</strong> as a promising candidate for antibacterial drug development.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 2","pages":" 951-964"},"PeriodicalIF":3.597,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145828235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent developments in the discovery of indole-based scaffolds as promising targeted cancer therapeutics","authors":"Prasanna A. Yakkala, Venkatesh Erram, Sajeli A. Begum and Ahmed Kamal","doi":"10.1039/D5MD00849B","DOIUrl":"10.1039/D5MD00849B","url":null,"abstract":"<p >Cancer remains the leading cause of mortality worldwide, driving the need for new and more effective therapeutics. Indole-based scaffolds have emerged as highly versatile structural frameworks in drug discovery in view of their structural diversity and ability to modulate multiple biological targets, including kinases, enzymes, and receptors. These compounds exhibit broad anticancer potential by inducing apoptosis, disrupting cell cycle progression, and inhibiting angiogenesis and metastasis. Recent studies have highlighted small-molecule indoles, bis-indoles, and oxindole-based scaffolds, including spirooxindoles, 3-alkenyl oxindoles, 3-iminooxindoles, 4, 5, 6, and 7-azaindole and isoindoline derivatives, as promising inhibitors of key cancer pathways, particularly through multi-kinase modulation. However, challenges such as drug resistance, off-target effects, and poor bioavailability must be addressed to fully realize their clinical potential. This review discusses recent progress in the development of indole-related compounds, focusing on their structural features, mechanisms of action, and therapeutic relevance in targeted cancer therapy.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 2","pages":" 846-897"},"PeriodicalIF":3.597,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery and optimization of pyrrolopyrimidines as highly potent, selective and brain-penetrant LRRK2 inhibitors","authors":"Jeffrey M. Axten, Xiao Ding, Luigi Piero Stasi, Baowei Zhao, Yingxia Sang, Ming-Hsun Ho, Lizhen Wang, Minhua Zhang, Xianjun Guo, Chengfang Tan, Xu Feng, Colin Edge, Klara Valko, Yi Li, Kelly Dong, Xiaoming Guan, Nico Zinn, F. David Tattersall, Feng Ren, Dai-Shi Su and Alastair D. Reith","doi":"10.1039/D5MD00856E","DOIUrl":"10.1039/D5MD00856E","url":null,"abstract":"<p >Leucine-rich repeat kinase 2 (LRRK2) is a promising therapeutic target for Parkinson's disease. We report herein the discovery of pyrrolopyrimidine analogs as potent and selective LRRK2 kinase inhibitors. Elucidation of the structure–activity relationship (SAR) of the kinase-inhibitor-focused screening lead compound <strong>1</strong> led to the development of compound <strong>39</strong> (GSK3357679) that shows excellent cellular potency, oral bioavailability, brain-penetration, and excellent PK/PD correlation in animal studies. The SAR optimization of the biological and pharmacokinetic profiles of the compounds are described. The pharmacodynamic characteristics for extended oral dosing studies in rodents are also presented.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 1","pages":" 676-685"},"PeriodicalIF":3.597,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145757565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}