MedChemComm最新文献

{"title":"Effect of mono-guanidine-like derivatives on platelet aggregation and tumour cell induced platelet aggregation†","authors":"Nadhim Kamil Hante, Aaron P. Keogh, Yanni Huang, Tanya Kapoor, Harriet Bennett-Lenane, Eleanor Walsh, Isabel Rozas, Carlos Medina and Maria Jose Santos-Martinez","doi":"10.1039/D4MD00793J","DOIUrl":"10.1039/D4MD00793J","url":null,"abstract":"<p >Antiplatelet agents are the cornerstone for the treatment and prevention of cardiovascular diseases. However, they can induce severe side effects such as gastrointestinal bleeding. The main aim of this study is to determine the effect that novel guanidine-based derivatives exert on platelet aggregation. From a screening, in collaboration with the Psychoactive Drug Screening Project service of several compounds from our in-house library of α2-adrenoceptors' ligands, four compounds showed high to medium affinity towards α2C-adrenoceptors and H2 histamine receptors. Based on the structure of these compounds, another two in-house α2-adrenoceptors' ligands were also selected. The effect of the six compounds on platelet aggregation was investigated by light transmission aggregometry and optical microscopy. Flow cytometry was used to analyse their effect on platelet activation by measuring the expression of GPIIb/IIIa and P-selectin platelet receptors. Finally, the potential effect of those compounds on tumour cell-induced platelet aggregation was studied on three cancer cell lines from different origins using optical microscopy. We found that three of these compounds, with very good affinity towards H2 histamine receptors, significantly inhibited platelet aggregation, induced by both ADP and collagen, at the highest concentrations tested, and that tumour cell-induced platelet aggregation was also modulated by these derivatives. Our findings suggest that these aryl guanidine-like systems have an antiplatelet effect that could be also beneficial to reduce tumour cell–platelet interactions.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 4","pages":" 1695-1704"},"PeriodicalIF":3.597,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11865921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543123","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":"Antimicrobial triazinedione inhibitors of the translocase MraY–protein E interaction site: synergistic effects with bacitracin imply a new mechanism of action†","authors":"Julia A. Fairbairn, Rachel V. Kerr, Nika-Kare A. Pierre-White, Anthony Jacovides, Becca W. A. Baileeves, Phillip J. Stansfeld, Gerhard Bringmann, Andrew T. Merritt and Timothy D. H. Bugg","doi":"10.1039/D4MD00937A","DOIUrl":"10.1039/D4MD00937A","url":null,"abstract":"<p > <em>Escherichia coli</em> translocase MraY is the target for bacteriolytic protein E from bacteriophage ϕX174, interacting at a site close to Phe-288 on helix 9, on the extracellular face of the protein. A peptide motif Arg-Trp-x-x-Trp from protein E was used to design a set of triazinedione peptidomimetics, which inhibit particulate MraY (<strong>6d</strong> IC<small>₅₀</small> 48 μM), and show antimicrobial activity against Gram-negative and Gram-positive antibiotic-resistant clinical strains (<strong>7j</strong> MIC <em>Acinetobacter baumannii</em> 16 μg mL<small>⁻¹</small>, <em>Staphyloccoccus aureus</em> MRSA 2–4 μg mL<small>⁻¹</small>). Docking against a predicted structure for <em>E. coli</em> MraY revealed two possible binding sites close to helix 9, the binding site for protein E. Antimicrobial activity of analogue <strong>6j</strong> was found to be synergistic with bacitracin in <em>Micrococcus flavus</em>, consistent with a link between this inhibition site and undecaprenyl phosphate uptake. Alkaloid michellamine B, also predicted to bind in the cleft adjacent to helix 9, was also found to be synergistic with bacitracin. These data provide experimental evidence that the unusual hydrophobic cleft adjacent to helix 9 in MraY is involved in uptake of undecaprenyl phosphate, in addition to recently identified transporters UptA and PopT, and that this process can be targeted by small molecules as a novel antibacterial mechanism.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 4","pages":" 1641-1653"},"PeriodicalIF":3.597,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11812184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143410136","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":"Discovery of potent measles virus fusion inhibitor peptides via structure-guided derivatization†","authors":"Ziwei Gao, Jiei Sasaki, Tateki Suzuki, Tomoaki Suzuki, Yuki Miwa, Shinsuke Sando, Takao Hashiguchi and Jumpei Morimoto","doi":"10.1039/D4MD01006J","DOIUrl":"10.1039/D4MD01006J","url":null,"abstract":"<p >Fusion inhibitor peptide (FIP), a short peptide known as a measles virus (MeV) infection inhibitor, inhibits membrane fusion between the viral envelope of MeV and the host cell membrane. Therefore, FIP is potentially useful as a drug candidate for treating MeV infection, but improvement of inhibitory activity is desirable. In this study, we conducted a structure–activity relationship study of FIP and, based on the result and the previously reported crystal structure of the complex, we designed FIP derivatives. From a series of derivatives, we discovered an FIP derivative with a strong inhibitory activity (IC<small>₅₀</small> = 210 nM) derived from the enhanced binding affinity (<em>K</em><small>_D</small> = 6.6 nM) to the MeV fusion protein.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 4","pages":" 1619-1625"},"PeriodicalIF":3.597,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11799930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383214","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":"Aspirin vs. ibuprofen: unveiling the distinct cyclooxygenase-1/2 behaviour and dual efficacy of their synthesized analogues via molecular modeling and in vitro biological assessment†","authors":"Amandeep Kaur, Hafiz Muzzammel Rehman, Vipin Kumar Mishra, Gurmeet Kaur, Mandeep Kaur, Mohammad K. Okla, Masaud Shah and Manisha Bansal","doi":"10.1039/D4MD00751D","DOIUrl":"10.1039/D4MD00751D","url":null,"abstract":"<p >Dual inhibition of cyclooxygenase isozymes along with the platelet aggregation activities <em>via</em> the arachidonic acid pathway may offer a better anti-inflammatory agent with enhanced cardiac safety. Although the literature is more focused on COX-2 selectivity, sufficient or improved COX-1/COX-2 selectivity has garnered significant attention recently since it can ensure cardiovascular safety. Herein, in this regard, novel derivatives of non-steroidal anti-inflammatory drugs containing amide, thiourea, thiosemicarbazide, and triazole functionalities were synthesized and characterized. Calculations on the <em>in silico</em> drug-likeness and toxicological properties demonstrated the suitability of the compounds for oral administration. Meanwhile, the molecular docking results suggested two different mechanistic pathways for the anti-inflammatory and anti-platelet effects <em>via</em> COX-2 and COX-1 inhibition. Compounds <strong>3</strong> and <strong>12</strong> were shown to be the most efficient based on their excellent docking scores and favorable interactions, particularly with the selective side-pocket residues of COX-2 and main catalytic residues of COX-1. Furthermore, molecular dynamics simulation confirmed that compounds <strong>3</strong> and <strong>12</strong> exhibited good interactions at the active sites, having stable binding throughout 100 ns. Overall, two major findings were made in the current study. (i) Compound <strong>12</strong> bearing the triazole moiety proved to be the most effective cyclooxygenase inhibitor with IC<small>₅₀</small> values of 95.11 and 98.73 μM against COX-1 and COX-2 isozymes, respectively. It also maintained its anti-platelet activity (IC<small>₅₀</small> = 277.67 μM), confirming the dual functioning of compound <strong>12</strong>. (ii) Compound <strong>3</strong> purely behaved as an anti-platelet agent (IC<small>₅₀</small> = 261.0 μM) in contrast to aspirin with fare inhibitory effects against COX-2.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 5","pages":" 2027-2048"},"PeriodicalIF":3.597,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543005","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":"Expanding the chemical space for antiviral discovery: the potential of twistenediones†","authors":"Aida Jaafar, Daniel Guerra-González, Ana Pascual, Ana M. Ortuño, Carlos M. Cruz, Juan M. Cuerva, Paula Bueno, Victoria Castro, Urtzi Garaigorta, Pablo Gastaminza, Javier Adrio and María Ribagorda","doi":"10.1039/D4MD00891J","DOIUrl":"10.1039/D4MD00891J","url":null,"abstract":"<p >Despite significant progress in drug discovery, there remains an urgent need to identify new structures capable of targeting drug-resistant diseases, as well as novel pathogens, to address the growing challenges in global health. This work highlights the underexplored potential of twistane-like structures as promising candidates for drug development, particularly as antiviral agents. We provide the first comprehensive study of their antiviral activity, in particular against SARS-CoV-2. We report the synthesis of a family of chiral indolyl-twistenediones, with the separation and characterization of both enantiomers <em>via</em> chiral semipreparative HPLC. The absolute configurations were determined using experimental and theoretical ECD techniques, supported by DFT calculations. A detailed biological study of their antiviral activity against various pathogenic RNA viruses demonstrates selective efficacy against members of the <em>Coronaviridae</em> family, specifically targeting a post-entry step in the viral replication cycle. Further investigation revealed a remarkable chiral distinction in the antiviral activity between the two enantiomers, opening new avenues for research in the 3D space of chiral cage compounds.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 4","pages":" 1626-1632"},"PeriodicalIF":3.597,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11803301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383140","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":"Biocompatible glycolipid derived from bhilawanol as an antibiofilm agent and a promising platform for drug delivery†","authors":"Tohira Banoo, Abhijit Ghosh, Priyasha Mishra, Sanhita Roy and Subbiah Nagarajan","doi":"10.1039/D4MD00828F","DOIUrl":"10.1039/D4MD00828F","url":null,"abstract":"<p >Stimuli-responsive smart materials for biomedical applications have gained significant attention because of their potential for selectivity and sensitivity in biological systems. Even though ample stimuli-responsive materials are available, the use of traditional Ayurvedic compounds in the fabrication of pharmaceuticals is limited. Among various materials, gels are one of the essential classes because of their molecular-level tunability with little effort from the environment. In this study, we report a simple synthesis method for multifunctional glycolipids using a starting material derived from biologically significant natural molecules and carbohydrates in good yields. The synthesized glycolipids were prone to form a hydrogel by creating a 3D fibrous architecture. The mechanism of bottom-up assembly involving the molecular-level interaction was studied in detail using SEM, XRD, FTIR, and NMR spectroscopy. The stability, processability, and thixotropic behavior of the hydrogel were investigated through rheological measurements, and it was identified to be more suitable for biomedical applications. To evaluate the potential application of the self-assembled hydrogel in the field of medicine, we encapsulated a natural drug, curcumin, into a gel and studied its pH as a stimuli-responsive release profile. Interestingly, the encapsulated drug was released both in acidic and basic pH levels at a different rate, as identified using UV-vis spectroscopy. It is worth mentioning that the gelator used for fabricating smart soft materials displays significant potential in selectively compacting the biofilm formed by <em>Streptococcus pneumoniae</em>. We believe that the reported multifunctional hydrogel derived from bhilawanol-based glycolipid holds great promise in medicine.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 4","pages":" 1715-1728"},"PeriodicalIF":3.597,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11799929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383209","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":"A perspective on small molecules targeting the renin–angiotensin–aldosterone system and their utility in cardiovascular diseases: exploring the structural insights for rational drug discovery and development","authors":"Nisha Bansal, Deepika Kathuria, Arockia M. Babu, Sonia Dhiman, Sorabh Lakhanpal, K. Nagendra Prasad, Roshan Kumar, Yogita Tyagi, Bhupinder Kumar, Mahendra Pratap Singh and Abhay M. Gaidhane","doi":"10.1039/D4MD00720D","DOIUrl":"10.1039/D4MD00720D","url":null,"abstract":"<p >Renin–angiotensin–aldosterone system (RAAS) is crucial in cardiovascular homeostasis. Any disruption in this homeostasis often leads to numerous cardiovascular diseases (CVDs) and non-cardiovascular diseases. Small molecules that show ability toward mechanically modulating RAAS components have been developed to address this problem, thus providing opportunities for innovative drug discovery and development. This review is put forth to provide a comprehensive understanding not only on the signaling mechanisms of RAAS that lead to cardiovascular events but also on the use of small molecules targeting the modulation of RAAS components. Further, the detailed descriptions of the drugs affecting the RAAS and their pharmacodynamics, kinetics, and metabolism profiles are provided. This article also covers the limitations of the present therapeutic armory, followed by their mechanistic insights. A brief discussion is offered on the analysis of the chemical space parameters of the drugs affecting RAAS compared to other cardiovascular and renal categories of medications approved by the US FDA. This review provides structural insights and emphasizes the importance of integrating the current therapeutic regimen with pharmacological tactics to accelerate the development of new therapeutics targeting the RAAS components for improved and efficacious cardiovascular outcomes. Finally, chemical spacing parameters of RAAS modulators are provided, which will help in understanding their peculiarities in modulating the RAAS signaling through structural and functional analyses. Furthermore, this review will assist medicinal chemists working in this field in developing better drug regimens with improved selectivity and efficacy.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 4","pages":" 1550-1583"},"PeriodicalIF":3.597,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383202","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-Glycidyl d-tryptophan ether-based ointment with anti-infective, anti-inflammatory, and wound-healing properties†","authors":"Denial Mahata, Malabendu Jana, Suresh K. Mondal, Sounik Manna, Arundhuti Jana, Anirban Chakraborty, Ananta K. Ghosh, Ranadhir Chakraborty, Tapas K. Hazra and Santi M. Mandal","doi":"10.1039/D4MD00878B","DOIUrl":"10.1039/D4MD00878B","url":null,"abstract":"<p >Anti-infective hydrogel is an emerging and innovative material used as an antibacterial ointment or to coat medical devices. Here, we synthesized a novel derivative of <em>N</em>-glycidyl <small>D</small>-tryptophan ether using the <small>D</small>-isoform of tryptophan through a ring-opening polymerization reaction. The compound was characterized using gel permeation chromatography (GPC), HPLC, <small>¹</small>H NMR, <small>¹³</small>C NMR, MALDI-TOF-MS, and FTIR spectroscopy. The results demonstrated its antibacterial activity by inhibiting quorum sensing and subsequent biofilm formation. <em>In vivo</em> studies revealed the ability of the compound to promote wound healing by reducing inflammatory cytokine levels, such as tumor necrosis factor alpha, interleukin-1β, and IL-6. Moreover, the compound showed antioxidant activity by scavenging the DPPH radical due to the presence of polymeric hydroxyl acidic protons near the nitrogen. Since inflammation prompted ROS-initiated DNA strand breaks, it was also confirmed that the compound could reduce DNA strand break accumulation, as demonstrated through testing against bleomycin-induced DNA strand break accumulation. Therefore, the synthesized compound, which could be used as a base material for ointments, was found to be effective for antibacterial and wound healing actions by (a) inhibiting biofilm formation by bacteria, (b) reducing the expression of inflammatory cytokines, and (c) preventing the accumulation of DNA strand breaks through free-radical scavenging activity.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 4","pages":" 1729-1739"},"PeriodicalIF":3.597,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399958","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":"Development of benzofuran-derived sulfamates as dual aromatase-steroid sulfatase inhibitors (DASIs): design, synthesis and biological evaluation†","authors":"Ahmed G. Eissa, Francesca Gozzi, Oqab Aloqab, Charlotte E. Parrish, Nadira Mohamed, Irene Shiali, Harith Al-Baldawi, Paul A. Foster and Claire Simons","doi":"10.1039/D4MD00795F","DOIUrl":"10.1039/D4MD00795F","url":null,"abstract":"<p >Resistance of oestrogen receptor-positive (ER+) breast cancer, the most prevalent type of breast cancer accounting for ∼70% of all cases, to current therapies necessitates the study of alternative strategies. One promising strategy is the multi-targeting approach using dual aromatase-steroid sulfatase inhibitors (DASIs). Herein, we describe the development of DASIs using a common benzofuran pharmacophore. Triazole benzofuran sulfamates were found to have low nM aromatase (Arom) inhibitory activity but no steroid sulfatase (STS) inhibitory activity (IC<small>₅₀</small> &gt; 10 μM); by contrast, benzofuran ketone sulfamates demonstrated low nM STS inhibitory activity but no Arom inhibitory activity (IC<small>₅₀</small> &gt; 1 μM). The addition of a methyl group at the 3rd position of the benzofuran ring in the benzofuran ketone sulfamate <strong>19</strong> (R<small>¹</small> = CH<small>₃</small>) had a notable effect, resulting in dual aromatase and STS inhibitory activities with the 4-chloro derivative <strong>19b</strong> (Arom IC<small>₅₀</small> = 137 nM, STS IC<small>₅₀</small> = 48 nM) and 4-methoxy derivative <strong>19e</strong> (Arom IC<small>₅₀</small> = 35 nM, STS IC<small>₅₀</small> = 164 nM) optimal for dual inhibition. Arom/STS inhibition results combined with molecular dynamics studies provided a clear rationale for the activity observed.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 4","pages":" 1606-1618"},"PeriodicalIF":3.597,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256621","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":"Breaking the energy chain: importance of ATP synthase in Mycobacterium tuberculosis and its potential as a drug target","authors":"Summaya Perveen, Sunny Pal and Rashmi Sharma","doi":"10.1039/D4MD00829D","DOIUrl":"10.1039/D4MD00829D","url":null,"abstract":"<p >Unveiling novel pathways for drug discovery forms the foundation of a new era in the combat against tuberculosis. The discovery of a novel drug, bedaquiline, targeting mycobacterial ATP synthase highlighted the targetability of the energy metabolism pathway. The significant potency of bedaquiline against heterogeneous population of <em>Mycobacterium tuberculosis</em> marks ATP synthase as an important complex of the electron transport chain. This review focuses on the importance and unique characteristics of mycobacterial ATP synthase. Understanding these distinctions enables the targeting of ATP synthase subunits for drug discovery, without aiming at the mammalian counterpart. Furthermore, a brief comparison of the structural differences between mycobacterial and mitochondrial ATP synthase is discussed. Being a complex multi-subunit protein, ATP synthase offers multiple sites for potential inhibitors, including the a, c, ε, γ, and δ subunits. Inhibitors targeting these subunits are critically reviewed, providing insight into the design of better and more potent chemical entities with the potential for effective treatment regimens.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 4","pages":" 1476-1498"},"PeriodicalIF":3.597,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142954202","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}