Bioorganic & Medicinal Chemistry Letters最新文献

{"title":"Development and evaluation of biphenyl-based small-molecule radiotracers for PET imaging of PD-L1 in tumor","authors":"Nan Zhang ,&nbsp;Junyi Zhu ,&nbsp;Xin Hu ,&nbsp;Yuxuan Zhou ,&nbsp;Qianhui Wang ,&nbsp;Shuyue Cai ,&nbsp;Quan Xie ,&nbsp;Ling Qiu ,&nbsp;Gaochao Lv ,&nbsp;Jianguo Lin","doi":"10.1016/j.bmcl.2025.130187","DOIUrl":"10.1016/j.bmcl.2025.130187","url":null,"abstract":"<div><div>Accurate identification of programmed cell death ligand 1 (PD-L1) expression is crucial for anti-tumor immunotherapy. However, the heterogeneity of PD-L1 expression in tumors makes it challenging to detect by immunohistochemistry. In this study, we developed two novel PD-L1 small-molecule PET tracers, [¹⁸F]<strong>LGT-1</strong> and [¹⁸F]<strong>LGT-2</strong>, to enable the non-invasive and precise measurement of PD-L1 expression in tumors through PET imaging. The radiochemical yields for [¹⁸F]<strong>LGT-1</strong> and [¹⁸F]<strong>LGT-2</strong> were 12.54±2.73% and 10.54±2.21%, respectively, with both tracers exhibiting approximately 98% radiochemical purity and molar activities of 12.23±2.84 GBq/μmol and 11.41±1.47 GBq/μmol. Both tracers demonstrated good stability in PBS (pH 7.4) and mouse serum after 2 hours of incubation. In cellular uptake assays, [¹⁸F]<strong>LGT-1</strong> achieved a maximum uptake of 5.47±0.03 %AD at 4 hours, which could be significantly inhibited by the non-radioactive compound <strong>LGT-1</strong>. In contrast, [¹⁸F]<strong>LGT-2</strong> exhibited high non-specific uptake in tumor cells. PET imaging revealed that [¹⁸F]<strong>LGT-1</strong> quickly accumulated in tumors within 5 minutes, achieving an uptake of 1.48±0.15 %ID/mL, and maintained a stable level for 60 minutes, while [¹⁸F]<strong>LGT-2</strong> showed minimal tumor uptake. Additionally, [¹⁸F]<strong>LGT-1</strong> had significantly lower liver uptake compared to [¹⁸F]<strong>LGT-2</strong>. Despite the high uptake in non-target tissues for [¹⁸F]<strong>LGT-1</strong>, which complicates its application, this study provides new insights for developing novel PD-L1 small-molecule tracers, with further optimization of the tracers currently in progress.</div></div>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":"122 ","pages":"Article 130187"},"PeriodicalIF":2.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, screening and validation of cysteine-reactive fragments as chikungunya virus protease inhibitors","authors":"Junming He ,&nbsp;Henry Illingworth ,&nbsp;Sven Ullrich ,&nbsp;Pritha Ghosh ,&nbsp;Jennifer Ton ,&nbsp;Colin J. Jackson ,&nbsp;Christoph Nitsche","doi":"10.1016/j.bmcl.2025.130176","DOIUrl":"10.1016/j.bmcl.2025.130176","url":null,"abstract":"<div><div>Alphaviruses like the Chikungunya virus cause severe outbreaks; however, no specific treatments are available. Their viral replication depends on the nsP2 cysteine protease, a promising but underexplored target for drug discovery. In this study, we report a covalent fragment screening against Chikungunya virus nsP2 protease, resulting in the identification of three inhibitors that can serve as starting points for future drug development. Careful validation proved indispensable in eliminating false-positive hits from a Förster resonance energy transfer (FRET)-based inhibition assay, wherein interference was caused by the inner filter effect between the fluorescent substrate and coloured compounds. Jump-dilution experiments accompanied by reactivity studies with cysteine and the recombinant protein indicate covalent inhibition <em>via</em> thia-Michael addition. We further demonstrate cross-inhibition of the related alphavirus nsP2 protease from Sindbis virus. The study provides early insights into nsP2 inhibition by electrophilic fragments featuring non-promiscuous <em>N</em>-arylacrylamides, thus advancing the search for antivirals targeting Chikungunya and other alphaviruses of concern.</div></div>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":"122 ","pages":"Article 130176"},"PeriodicalIF":2.5,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent developments of benzimidazole based analogs as potential tubulin polymerization inhibitors: A critical review","authors":"Rajkumar Reddyrajula,&nbsp;Priya Varshini Kathirvel,&nbsp;Nagula Shankaraiah","doi":"10.1016/j.bmcl.2025.130167","DOIUrl":"10.1016/j.bmcl.2025.130167","url":null,"abstract":"<div><div>Microtubules, as dynamic regulators in many cellular processes, remain pivotal targets in cancer chemotherapy. Among the structural motifs explored, the benzimidazole scaffold has emerged as a privileged heterocyclic ring system in the development of potent therapeutic agents, owing to its versatility and pharmacological relevance. This review critically examines the synthesis, anticancer activity, structure-activity relationships (SAR), and tubulin polymerization inhibitory properties of diverse benzimidazole derivatives. In addition, various synthetic strategies and innovative approaches for generating benzimidazole based analogs with enhanced cytotoxic profiles are highlighted. Recent findings underscore the potential of benzimidazole derivatives as promising tubulin polymerization inhibitors, contributing significantly to the discovery of next-generation anticancer agents.</div></div>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":"122 ","pages":"Article 130167"},"PeriodicalIF":2.5,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research progress on critical viral protease inhibitors for coronaviruses and enteroviruses","authors":"Shulei Hu ,&nbsp;Qiuyu Zhong ,&nbsp;Xiong Xie ,&nbsp;Shurui Zhang ,&nbsp;Jinlin Wang ,&nbsp;Hong Liu ,&nbsp;Wenhao Dai","doi":"10.1016/j.bmcl.2025.130168","DOIUrl":"10.1016/j.bmcl.2025.130168","url":null,"abstract":"<div><div>Viral infectious diseases have been seriously affecting human life and health. SARS-CoV-2 was the pathogen that caused Coronavirus Disease 2019 (COVID-19), and the impact of COVID-19 is still existing. Enterovirus 71 (EV71) is the primary pathogen of hand, foot, and mouth disease (HFMD), and no effective direct-acting antiviral drugs targeting EV71 has been approved yet. Innate antiviral strategies play an important role in preventing virus infections depending on the powerful immune regulatory system of body, while viruses have evolved to exploit diverse methods to overcome immune response. Viral proteases, which are known in cleaving viral polyproteins, have also been found to modulate the innate immunity of host cells, thereby promoting viral proliferation. Herein, we reviewed the current development of SARS-CoV-2 3CL^pro, PL^pro, and EV71 3C^pro and 2A^pro, mainly including structure, function, modulation of immune response, and inhibitors of these four proteases, to further deepen the understanding of viral pathogenesis and provide a new perspective for subsequent corresponding drug development.</div></div>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":"122 ","pages":"Article 130168"},"PeriodicalIF":2.5,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potent synergistic effect of natural product-inspired Sinomenine derivatives with fluconazole against azole-resistant Candida albicans","authors":"Wei Liu ,&nbsp;Jiayao Du ,&nbsp;Zhenzhen Qin ,&nbsp;Mei Zhao ,&nbsp;Shuaibo Du ,&nbsp;Jianwu Xie ,&nbsp;Ya Zhang ,&nbsp;Mengzhou Wang ,&nbsp;Shengzheng Wang","doi":"10.1016/j.bmcl.2025.130159","DOIUrl":"10.1016/j.bmcl.2025.130159","url":null,"abstract":"<div><div><em>Candida albicans</em> (<em>C. albicans</em>) is the most common cause of invasive <em>Candida</em> infections worldwide. The acquired resistance of <em>C. albicans</em> to fluconazole, a first-line antifungal drug, has been frequently reported, posing significant challenges to treatment. Combination therapy has emerged as an effective strategy to combat drug resistance. In this study, we synthesized a series of sinomenine derivatives and evaluated in vitro synergistic activity against azole-resistant <em>C. albicans</em>. The results demonstrated that compound <strong>3ja</strong> exhibited a potent synergistic effect with fluconazole against azole-resistant <em>C. albicans</em>. Mechanism studies revealed that the combination of <strong>3ja</strong> and FLC significantly induced reactive oxygen species accumulation, disrupted membrane integrity, altered membrane sterols, and promoted apoptosis in <em>C. albicans</em>.</div></div>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":"121 ","pages":"Article 130159"},"PeriodicalIF":2.5,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, synthesis, and activity evaluation of C-8 arylated luteolin derivatives as influenza endonuclease inhibitors","authors":"Artem Tsalyy ,&nbsp;Michal Kráľ ,&nbsp;Róbert Reiberger ,&nbsp;Pavel Majer ,&nbsp;Jan Konvalinka ,&nbsp;Milan Kožíšek ,&nbsp;Aleš Machara","doi":"10.1016/j.bmcl.2025.130178","DOIUrl":"10.1016/j.bmcl.2025.130178","url":null,"abstract":"<div><div>The polymerase acidic (PA) subunit of the influenza virus, an endonuclease of the RNA-dependent RNA polymerase, represents a viable target for anti-influenza therapies, as evidenced by the efficacy of the FDA-approved drug Xofluza. A characteristic feature of endonuclease inhibitors is their ability to chelate Mg²⁺ or Mn²⁺ ions within the enzyme's catalytic site. Previously, our studies identified luteolin and its C-8-glucoside orientin as potent endonuclease inhibitors. This report details our subsequent investigation into the structural modifications of the phenyl moiety attached to the C-8 position of luteolin. The inhibitory potencies (IC₅₀ values) quantified with AlphaScreen technology indicated that substituting the C-8 glucose moiety of orientin resulted in compounds with comparable inhibitory potency. From a series of eighteen compounds, acid <strong>12</strong> with 3-carboxylphenyl moiety at the C-8 position was the most potent inhibitor with nanomolar potency.</div></div>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":"121 ","pages":"Article 130178"},"PeriodicalIF":2.5,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploration of quinoxaline triazoles as antimycobacterial agents: design, synthesis and biological evaluation","authors":"Boddupalli Venkata Siva Kumar ,&nbsp;Mahesh Kumar Talamadla ,&nbsp;Adinarayana Nandikolla ,&nbsp;Yogesh Mahadu Khetmalis ,&nbsp;Gauri Shetye ,&nbsp;Scott G. Franzblau ,&nbsp;Sankaranarayanan Murugesan ,&nbsp;Kondapalli Venkata Gowri Chandra Sekhar","doi":"10.1016/j.bmcl.2025.130177","DOIUrl":"10.1016/j.bmcl.2025.130177","url":null,"abstract":"<div><div>In this work, novel 2-substituted-3-((1-substituted-1H-1,2,3-triazol-4-yl) methoxy) quinoxaline analogues were designed, synthesized, and various analytical techniques, viz., ¹H NMR, ¹³C NMR, and Mass spectrometry, were deployed in the structure confirmation of the final compounds. Synthesized derivatives were evaluated for their antimycobacterial activity against <em>Mycobacterium tuberculosis</em> (<em>Mtb</em>) H37Rv. Target molecules mainly consist of methyl substituent in the second position of quinoxaline moiety (<strong>QM</strong> series) or phenyl substituent in the second position (<strong>QP</strong> series). Among the forty-two compounds synthesized and evaluated for anti-mycobacterial activity, the MIC values ranged between 5.58 μg/mL to &gt;100 μg/mL. Among <strong>QM</strong> series compounds, <strong>QM7,</strong> with MIC 5.58 μg /mL, was the most active compound. Among the <strong>QP</strong> series derivatives, the intermediate <strong>QP-Acy</strong> with MIC 23.39 μg /mL was the most promising. Most of the analogues tested in the <strong>QP</strong> series are less potent than the <strong>QM</strong> series. All the synthesized molecules showed good drug-likeness when evaluated using the SWISS ADME tool. <strong>QM7</strong> was evaluated for docking studies using the crystal structure of enoyl-acyl carrier (INH-A) enzyme PDB: <span><span>4TZK</span><svg><path></path></svg></span>, and it showed significant docking scores and interactions. MD simulations were carried out to assess the stability of the protein <strong>QM7</strong> complex. Single crystals were grown for <strong>QM1</strong>, <strong>QM6</strong>, and <strong>QPb</strong> from these forty-two compounds, and their structures were solved using OLEX. The corresponding CCDC numbers for these compounds are <strong>2,388,310</strong>, <strong>2,388,309</strong>, and <strong>2,388,291</strong>, respectively.</div></div>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":"121 ","pages":"Article 130177"},"PeriodicalIF":2.5,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of 9H-purine scaffold as novel CDK2 inhibitors: Design, synthesis, and biological evaluation","authors":"Yan Zhang ,&nbsp;Xiya Liu ,&nbsp;Ziming Li ,&nbsp;Xia Wang ,&nbsp;Chunlei Tang","doi":"10.1016/j.bmcl.2025.130166","DOIUrl":"10.1016/j.bmcl.2025.130166","url":null,"abstract":"<div><div>Cyclin-dependent kinase 2 (CDK2), a crucial regulator in multiple oncogenic signaling pathways, has emerged as a promising target for the development of innovative anticancer therapies and overcoming resistance to CDK4/6 inhibitors. In this study, three series of compounds were designed and synthesized, using the CDK2 inhibitor fadraciclib (CYC065) as the lead compound, with 9<em>H</em>-purine as the core structure. The design incorporated reported structure-activity relationship data and utilized computer-aided drug design techniques. Compounds in series <strong>1</strong> explored the binding mode between the ATP ribose binding site in CDK2 and C2 substituents, while compounds in series <strong>2</strong> and <strong>3</strong> validated the feasibility of modifying the specific binding region with different substituents and investigated the effects of filling the CDK2 hydrophobic pocket at the N9 position with alkyl substituents. Three compounds, <strong>1f</strong>, <strong>2e</strong>, and <strong>3a</strong>, demonstrated remarkable activity against CDK2-cyclin E2. Notably, <strong>3a</strong> exhibited the most potent effect, with a CDK2-cyclin E2 IC₅₀ value of 6.0 ± 0.1 nM, an MV4–11 IC₅₀ value of 489.2 ± 0.2 nM, and excellent selectivity for CDK2. This study evaluated the impact of substitutions at the 2, 6, and 9 positions of the purine ring on the activity of CDK2 small molecule inhibitors. The findings offer a theoretical foundation for future research, broadening the structural diversity and scope of CDK2 inhibitor studies.</div></div>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":"122 ","pages":"Article 130166"},"PeriodicalIF":2.5,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, synthesis, and activity evaluation of indole derivatives as potential stabilizers for p53 Y220C","authors":"Linquan Li ,&nbsp;Xi Gu ,&nbsp;Jingyi Meng ,&nbsp;Yiming Wen ,&nbsp;Jing Yi ,&nbsp;Fengqian Xu ,&nbsp;Li Zhang ,&nbsp;Sulin Zhang ,&nbsp;Zhili Zuo","doi":"10.1016/j.bmcl.2025.130161","DOIUrl":"10.1016/j.bmcl.2025.130161","url":null,"abstract":"<div><div>The p53 Y220C mutation is frequently observed in human cancers. This mutation renders the p53 Y220C unstable at physiological temperatures, leading to a loss of its normal function and promoting tumor development. In this study, a total of eight compounds were designed and synthesized based on the active compound <strong>C8</strong>. The protein thermal shift assay revealed that both <strong>C8-3b</strong> and <strong>C8–6</strong> exhibited similar activity of <strong>C8</strong>, with a ΔT_m value of +0.5 °C. Compounds <strong>C8-1a</strong>, <strong>C8-1b</strong>, and <strong>C8-2b</strong> were found to enhance the thermostability of p53 Y220C (ΔT_m: + 1.0 °C), the melting temperature exhibits an enhancement of 0.5 °C over the <strong>C8</strong>, indicating that these compounds possess the ability to stabilize p53 Y220C. The results of the cell viability assay revealed that <strong>C8-1b</strong> exhibited selective inhibitory effects on the proliferation of tumor cells harboring the p53 Y220C mutation. Furthermore, we utilized molecular docking and two-dimensional interaction analysis to elucidate the binding mode and key interactions of these compounds with p53 Y220C. Our study suggests that these compounds could potentially serve as lead compounds for enhancing the stability of p53 Y220C, thus providing a rational approach for designing small molecule stabilizers against p53 mutations.</div></div>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":"121 ","pages":"Article 130161"},"PeriodicalIF":2.5,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of Flavonol derivatives as porcine reproductive and respiratory syndrome virus inhibitors","authors":"Zhi-Zheng Wang ,&nbsp;Chen-Xu Xiao ,&nbsp;Wen-Li Huang ,&nbsp;Yang Hu ,&nbsp;Hui-Ting Zhang ,&nbsp;Zhang Liu ,&nbsp;Sheng-Hao Peng ,&nbsp;Zigong Wei","doi":"10.1016/j.bmcl.2025.130162","DOIUrl":"10.1016/j.bmcl.2025.130162","url":null,"abstract":"<div><div>Porcine reproductive and respiratory syndrome virus (PRRSV) causes serious threat to the global pig industry, and there was still no efficient treatment for porcine reproductive and respiratory syndrome (PRRS). Flavonol compounds were reported to show antiviral activity against a series of different virus. In this study, we designed a series of flavonol derivatives as promising lead structure for PRRSV inhibitors. A flavonol derivative database with diverse structures was first generated, and their anti-PRRSV activity were test. Among these compounds, compound <strong>4s</strong> showed promising anti-PRRSV activity with EC₅₀ values of 0.45 μM. In addition, it exhibited low cytotoxicity with CC₅₀ higher than 100 μM. We also found that compound <strong>4s</strong> inhibited PRRSV might be by repressing the activity of nsp4 protease. Molecular modeling study revealed that compound <strong>4s</strong> binding to nsp4 mainly relies on a salt bridge and hydrophobic interaction. Our results might provide a new way for the development of PRRSV inhibitors.</div></div>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":"121 ","pages":"Article 130162"},"PeriodicalIF":2.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}