MedChemComm最新文献

{"title":"Thiochromenes and thiochromanes: a comprehensive review of their diverse biological activities and structure–activity relationship (SAR) insights","authors":"Jatin, Solai Murugappan, Shivani Kirad, Chandu Ala, Pranali Vijaykumar Kuthe, Chandra Sekhar Venkata Gowri Kondapalli and Murugesan Sankaranarayanan","doi":"10.1039/D4MD00995A","DOIUrl":"10.1039/D4MD00995A","url":null,"abstract":"<p >Thiochromene and thiochromane scaffolds, sulfur containing heterocycles, have gained significant attention in medicinal chemistry due to their diverse pharmacological activities. This review provides a comprehensive analysis of their antibacterial, antifungal, antiviral, anti-parasitic, and anticancer properties, emphasizing their therapeutic potential. SAR studies highlight key molecular modifications such as electron withdrawing substituents, sulfur oxidation, and tailored ring substitutions that enhance bioactivity, potency, and target specificity. Mechanistic insights reveal their ability to inhibit microbial enzymes, disrupt cellular pathways, and modulate key biological targets. By summarizing recent advancements, this review underscores the potential of thiochromene and thiochromane based therapeutics and encourages further research to address existing limitations and enhance their drug development prospects.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 5","pages":" 1941-1968"},"PeriodicalIF":3.597,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711140","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":"Development, biological evaluation, and molecular modelling of novel isocytosine and guanidine derivatives as BACE1 inhibitors using a fragment growing strategy†","authors":"Asmaa M. Atta, Nouran Rihan, Ahmad M. Abdelwaly, Mohamed S. Nafie, Mohamed S. Elgawish, Samia M. Moustafa, Mohamed A. Helal and Khaled M. Darwish","doi":"10.1039/D4MD00698D","DOIUrl":"10.1039/D4MD00698D","url":null,"abstract":"<p >Alzheimer's disease (AD) is a neurodegenerative condition characterized by significant synaptic loss and neuronal death in brain regions critical for cognitive functions. The disease is characterized by the formation of amyloid plaques, which are extracellular constructs consisting mainly of aggregated Aβ42. The latter is a peptide formed by the proteolytic cleavage of β-amyloid precursor protein (APP) by two enzymes, β- and γ-secretase. Therefore, inhibition of the aspartic protease β-secretase (BACE1) is considered a promising therapeutic approach for the treatment and prevention of Alzheimer's disease. Unfortunately, a limited number of β-secretase inhibitors have reached human trials and eventually failed due to inconclusive therapeutic and/or safety profiles. In this study, we developed drug-like molecules with a β-secretase inhibitory activity using a fragment growing strategy on isocytosine and acyl guanidine warheads. Our approach is based on optimizing the hydrophobic part of the molecules to obtain a conformationally restrained scaffold complementary to the hydrophobic pockets within the enzyme active site. We developed 32 compounds with promising <em>in vitro</em> inhibitory activity against BACE1 down to sub-micromolar IC<small>₅₀</small>. Docking simulation studies were performed to understand the mode of binding of the prepared compounds. We demonstrated that compounds with superior activities, such as <strong>16b</strong> and <strong>16g</strong>, are able to provide the best balance between the steric shape and position of the polar substituent for achieving preferential anchoring into the S1, S3, S1′, and S2′ sub-pockets. Further, <em>in vivo</em> characterization of selected drug-like candidates of the benzimidazole series AMK-IV, namely <strong>16a</strong> and <strong>16k</strong>, demonstrated their ability to reduce oxidation stress and their safety within brain and liver tissues.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 5","pages":" 2202-2230"},"PeriodicalIF":3.597,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650241","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 evaluation of acetylcholine-antitumor lipid hybrids led to identification of a potential anticancer agent disrupting the CDK4/6-Rb pathway in lung cancer†","authors":"Ahmed H. E. Hassan, Eun Seo Bae, Youngdo Jeong, Chae Won Ock, Selwan M. El-Sayed, Minji Kim, Mohamed F. Radwan, Tarek S. Ibrahim, Jun-Young Cho, Boyoung Y. Park, Jaehoon Sim, Sang Kook Lee and Yong Sup Lee","doi":"10.1039/D4MD01007H","DOIUrl":"10.1039/D4MD01007H","url":null,"abstract":"<p >Hybridization of acetylcholine with antitumor lipids (ATLs) was explored to achieve novel potential anticancer agents. The combination with a 2-stearoxyphenyl moiety substantially enhanced the anticancer activity of the acetylcholine hybrids. Compounds <strong>6</strong>, <strong>8</strong>, <strong>9</strong> and <strong>10</strong> exhibited pronounced anticancer activities higher than edelfosine and stPEPC and NSC43067. Compounds <strong>6</strong>, <strong>8</strong>, <strong>9</strong> and <strong>10</strong> also showed broad-spectrum anticancer activity against diverse cancer cells including lung, ovarian, renal, prostate, leukaemia, colon, CNS, melanoma, and breast cancer cells. Compounds <strong>6</strong> and <strong>8</strong> were potent compounds eliciting single digit low micromolar GI<small>₅₀</small> values. Compound <strong>6</strong> was the most potent against non-small cell lung cancer, ovarian cancer, renal cancer, and prostate cancer. Meanwhile, compound <strong>8</strong> was the most potent against leukaemia, colon cancer, CNS cancer, melanoma, and breast cancer. Exploration of the mechanism of action of compound <strong>6</strong> in A549 non-small cell lung cancer cells showed that it triggers cell cycle arrest in the G<small>₀</small>/G<small>₁</small> phase <em>via</em> disruption of the CDK4/6-Rb pathway and induces apoptosis <em>via</em> the activation of caspases, upregulation of BAX and cleavage of PARP. Overall, the results present acetylcholine-ATL hybrids <strong>6</strong> and <strong>8</strong> as potential anticancer agents for possible further development.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 5","pages":" 2281-2296"},"PeriodicalIF":3.597,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11931566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711111","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":"Nitroreductase-activatable photosensitizers for selective antimicrobial photodynamic therapy†","authors":"Matthew T. Tung, Tianyi Ma, Ivonne Rebeca Lopez-Miranda, Joshua N. Milstein and Andrew A. Beharry","doi":"10.1039/D4MD00890A","DOIUrl":"10.1039/D4MD00890A","url":null,"abstract":"<p >Antimicrobial photodynamic therapy (aPDT) utilizes light, oxygen and a photosensitizer (PS) to enact cell death <em>via</em> the production of reactive oxygen species (ROS). This mechanism of cell death, <em>via</em> oxidative stress, has allowed aPDT to be effective against antibiotic-resistant bacterial strains, with the development of resistance being minimal as no specific pathway is targeted. While promising, as ambient light can activate PSs, damage to mammalian tissues can occur, leading to drug-induced photosensitivity. To mitigate this, we developed a nitroreductase-activatable PS containing a quenching group that inhibits fluorescence and ROS. Upon reaction with nitroreductase, the quenching group can be liberated, restoring fluorescence and ROS production. As nitroreductase is not present in healthy mammalian tissues but expressed in many bacteria, photosensitivity of mammalian cells can be reduced. Herein, the synthesis and photophysical characterization of the nitroreductase-activatable PS, <strong>DB2</strong>, is described. <strong>DB2</strong> was quenched compared to the free PS, <strong>DB1</strong>, and activation both <em>in vitro</em> by purified nitroreductase and in the gram-positive bacterial strain, <em>Bacillus subtilis</em>, was confirmed by fluorescence recovery. Cell viability studies in <em>B. subtilis</em> showed low dark toxicity and an IC<small>₅₀</small> of 0.16 μM under 10-minute irradiation (530 nm, 42 mW cm<small>⁻²</small>). Minimal toxicity was observed under the same conditions in mammalian cell cultures demonstrating the potential of <strong>DB2</strong> to mitigate photosensitivity and provide a promising approach for aPDT.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 5","pages":" 2133-2141"},"PeriodicalIF":3.597,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586543","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":"Development of p300-targeting degraders with enhanced selectivity and onset of degradation†","authors":"Graham P. Marsh, Mark S. Cooper, Sean Goggins, Stephen J. Reynolds, Dean F. Wheeler, Joel O. Cresser-Brown, Robert E. Arnold, Emily G. Babcock, Gareth Hughes, Darko Bosnakovski, Michael Kyba, Samuel Ojeda, Drew A. Harrison, Christopher J. Ott and Hannah J. Maple","doi":"10.1039/D4MD00969J","DOIUrl":"10.1039/D4MD00969J","url":null,"abstract":"<p >p300 and CBP are paralogous epigenetic regulators that are considered promising therapeutic targets for cancer treatment. Small molecule p300/CBP inhibitors have so far been unable to differentiate between these closely related proteins, yet selectivity is desirable in order to probe their distinct cellular functions. Additionally, in multiple cancers, loss-of-function <em>CREBBP</em> mutations set up a paralog dependent synthetic lethality with p300, that could be exploited with a selective therapeutic agent. To address this, we developed p300-targeting heterobifunctional degraders that recruit p300 through its HAT domain using the potent spiro-hydantoin-based inhibitor, iP300w. Lead degrader, BT-O2C, demonstrates improved selectivity and a faster onset of action compared to a recently disclosed A 485-based degrader in HAP1 cells and is cytotoxic in CIC::DUX4 sarcoma (CDS) cell lines (IC<small>₅₀</small> = 152–221 nM), significantly reducing expression of CDS target genes (ETV1, ETV4, ETV5). Taken together, our results demonstrate that BT-O2C represents a useful tool degrader for further exploration of p300 degradation as a therapeutic strategy.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 5","pages":" 2049-2060"},"PeriodicalIF":3.597,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650271","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":"Betaine–salicylic acid cocrystal for enhanced skincare and acne treatment†","authors":"Zhenyuan Wang, Mi Wang, Qingsheng Tao, Yufei Li, Hao Wang, Mei Zhang, Xueli Liu and Jiaheng Zhang","doi":"10.1039/D5MD00001G","DOIUrl":"10.1039/D5MD00001G","url":null,"abstract":"<p >Salicylic acid (SA) is a natural lipophilic active ingredient commonly used in cosmetics and skin disease treatments, offering benefits such as exfoliation, anti-inflammation effects, antibacterial properties, oil control, and acne alleviation. However, its poor water solubility, low bioavailability, and potential side effects, such as allergies, irritation, and dryness, hinder its widespread application. In this study, we prepared a betaine–salicylic acid (BeSA) cocrystal and systematically characterized its crystal structure, biological activity, and clinical efficacy. The results showed that BeSA has significantly lower irritancy and cytotoxicity than SA, but exhibits excellent anti-inflammatory and antioxidant properties as well as high moisturizing and anti-acne efficacy, making it a potential alternative to SA. Further, quantum chemical calculations and molecular docking simulations were conducted to investigate the intrinsic mechanisms underlying the excellent bioactivity of BeSA cocrystals. This study introduces an innovative solution for safer and more effective skincare formulations based on SA and offers theoretical guidance regarding material engineering and further material optimization, which has crucial implications for both industry and academia.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 4","pages":" 1705-1714"},"PeriodicalIF":3.597,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543024","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":"Application of a bivalent “click” approach to target tyrosyl-DNA phosphodiesterase 1 (TDP1)†","authors":"Xue Zhi Zhao, Wenjie Wang, Md Rasel Al Mahmud, Keli Agama, Yves Pommier and Terrence R. Burke","doi":"10.1039/D4MD00824C","DOIUrl":"10.1039/D4MD00824C","url":null,"abstract":"<p >Although inhibiting the DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1) synergizes with topoisomerase type I (TOP1) inhibitors in anticancer therapy, development of TDP1 inhibitors has been highly challenging. This may be due to the open and shallow nature of the TDP1 catalytic site and the necessity of competing with a large and highly extended substrate. The toolbox available to chemical biologists for studying TDP1 could be significantly enhanced by introducing the ability to selectively eliminate TDP1 using protein degraders. Our current work starts from phenyl imidazopyridine-based TDP1 inhibitors previously developed from small molecule microarrays (SMMs). Using crystal structures of lead inhibitors bound to TDP1, we designed and synthesized a series of bivalent proteolysis-targeting chimeras (PROTACs). The focus of our current work is to explore synthetic approaches that permit installation of E3 ligase-targeting functionality, while retaining the TDP1 binding. We employed copper-catalyzed azide–alkyne cycloaddition (CuAAC) “click” reactions to assemble PROTAC constituents with 1,2,3-triazole-containing linkers. With the addition of the relatively large parts of the linkers and E3-targeting moieties, we retained the ability to inhibit TDP1. The successful development of TDP1-directed PROTACS would yield a new therapeutic class that could potentially enhance the efficacy and selectivity of TOP1 inhibitors including those used as payloads in antibody drug conjugates (ADCs).</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 5","pages":" 1969-1985"},"PeriodicalIF":3.597,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483535","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":"Design, synthesis and biological evaluation of 2H-[1,4]oxazino-[2,3-f]quinazolin derivatives as potential EGFR inhibitors for non-small cell lung cancer†","authors":"Linchang Huang, Ying Zhang, Peng Liu, Lihong Lan, Lifang Yang, Bo Wang, Tingting Cao, Liming Hu and Xuemei Qin","doi":"10.1039/D4MD01016G","DOIUrl":"10.1039/D4MD01016G","url":null,"abstract":"<p >Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have emerged as the first-line treatment for patients with EGFR-mutant non-small cell lung cancer (NSCLC). A series of 2<em>H</em>-[1,4]oxazino[2,3-<em>f</em>]quinazolin derivatives were synthesized and evaluated as irreversible EGFR-TKIs for the treatment of NSCLC. Most of the synthesized compounds demonstrated strong inhibitory activity against the EGFR kinase and the tested cancer cells. Notably, compound <strong>4a</strong> exhibited considerable inhibitory effects against the EGFR kinase and the EGFR<small>^L858R/T790M</small> mutant NCI-H1975 cancer cells. Compound <strong>4a</strong> was found to suppress cell proliferation, colony formation, cell invasion, and migration, while also inducing G0/G1 phase arrest of the cell cycle in NCI-H1975 cells. Compound <strong>4a</strong> was docked into the active pocket of the EGFR mutant to ascertain the probable binding conformation. Overall, compound <strong>4a</strong> was identified as a promising irreversible EGFR-TKI for the treatment of NSCLC.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 5","pages":" 2231-2239"},"PeriodicalIF":3.597,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650268","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":"Pyrazolo[3,4-d]pyrimidine-based neplanocin analogues identified as potential de novo pharmacophores for dual-target HBV inhibition†","authors":"Mohan Kasula, Masaaki Toyama, Ramakrishnamraju Samunuri, Ashok Kumar Jha, Mika Okamoto, Masanori Baba and Ashoke Sharon","doi":"10.1039/D4MD00932K","DOIUrl":"10.1039/D4MD00932K","url":null,"abstract":"<p >The discovery of selective and potent inhibitors through <em>de novo</em> pathways is essential to combat drug resistance in chronic hepatitis B (CHB) infections. Recent studies have highlighted that neplanocin A (NepA) derivatives are biologically selective inhibitors of the hepatitis B virus (HBV). In this study, we designed, synthesized, and evaluated various pyrazolo[3,4-<em>d</em>]pyrimidine-based NepA analogues (<strong>4a–h</strong>) for their anti-HBV activity. Notably, analogue <strong>4g</strong> demonstrated significant activity against HBV replication, with EC<small>₅₀</small> (HBV DNA) = 0.96 μM, CC<small>₅₀</small> &gt; 100 μM and EC<small>₅₀</small> (HBsAg) = 0.82 μM, showing selective inhibition of HBsAg secretion. The SAR analysis concluded that replacing the polar 4-NH<small>₂</small> group with –CH<small>₃</small> also acted as a weak H-bonding donor, and the presence of 3-iodo was found to be desirable for the activity/toxicity profile. The nucleoside analogues exhibited a distinct mechanism of action compared to existing nucleoside analogues for the selective inhibition of HBsAg secretion. Based on these findings, compound <strong>4g</strong> represents a promising lead molecule for the development of new anti-HBV agents with unique mechanisms of action.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 4","pages":" 1740-1745"},"PeriodicalIF":3.597,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483611","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":"Transmembrane protease serine 2 (TMPRSS2) inhibitors screened from an Fv-antibody library for preventing SARS-CoV-2 infection","authors":"Jaeyong Jung, Jeong Soo Sung, Soonil Kwon, Hyung Eun Bae, Min-Jung Kang, Joachim Jose, Misu Lee and Jae-Chul Pyun","doi":"10.1039/D4MD00992D","DOIUrl":"10.1039/D4MD00992D","url":null,"abstract":"<p >Fv-antibodies targeting the transmembrane protease serine 2 (TMPRSS2) were screened from an Fv-antibody library for inhibiting SARS-CoV-2 infection. Fv-antibodies were derived from the variable region of heavy-chain immunoglobulin G (IgG), which consisted of three complementarity-determining regions (CDRs) and frame regions (FRs). The Fv-antibody library was prepared through site-directed mutagenesis of CDR3 region. The proteolytic cleavage site (S2′ site) of TMPRSS2 on the spike protein (SP) of SARS-CoV-2 was used as a screening probe for the library. Two Fv-antibodies were screened and subsequently expressed as soluble recombinant proteins. The binding affinities of the expressed Fv-antibodies were estimated using a surface plasmon resonance (SPR) biosensor. The two expressed Fv-antibodies specifically bound to the active site of TMPRSS2 which interacts with S2′ site in the proprotein convertase (PPC) region. The neutralizing activities of the two expressed Fv-antibodies were demonstrated using a cell-based infection assay with pseudo-viruses that expressed the SP of four types of SARS-CoV-2 variants: Wu-1 (D614), Delta (B.1.617.2), Omicron (BA.2), and Omicron (BA.4/5). Additionally, a docking simulation was performed to analyze the interaction between the screened Fv-antibodies and the active sites of TMPRSS2.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 4","pages":" 1758-1765"},"PeriodicalIF":3.597,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483624","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}