RSC medicinal chemistry最新文献

{"title":"Novel PROTAC probes targeting KDM3 degradation to eliminate colorectal cancer stem cells through inhibition of Wnt/β-catenin signaling†","authors":"Shadid U. Zaman, Piyusha P. Pagare, Hongguang Ma, Rosalie G. Hoyle, Yan Zhang and Jiong Li","doi":"10.1039/D4MD00122B","DOIUrl":"10.1039/D4MD00122B","url":null,"abstract":"<p >It has been demonstrated that the KDM3 family of histone demethylases (KDM3A and KDM3B) epigenetically control the functional properties of colorectal cancer stem cells (CSCs) through Wnt/β-catenin signaling. Meanwhile, a broad-spectrum histone demethylase inhibitor, IOX1, suppresses Wnt-induced colorectal tumorigenesis predominantly through inhibiting the enzymatic activity of KDM3. In this work, several cereblon (CRBN)-recruiting PROTACs with various linker lengths were designed and synthesized using IOX1 as a warhead to target KDM3 proteins for degradation. Two of the synthesized PROTACs demonstrated favorable degradation profile and selectivity towards KDM3A and KDM3B. Compound <strong>4</strong> demonstrated favorable <em>in vitro</em> metabolic profile in liver enzymes as well as no hERG-associated cardiotoxicity. Compound <strong>4</strong> also showed dramatic ability in suppressing oncogenic Wnt signaling to eliminate colorectal CSCs and inhibit tumor growth, with around 10- to 35-fold increased potency over IOX1. In summary, this study suggests that PROTACs provide a unique molecular tool for the development of novel small molecules from the IOX1 skeleton for selective degradation of KDM3 to eliminate colorectal CSCs <em>via</em> suppressing oncogenic Wnt signaling.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 11","pages":" 3746-3758"},"PeriodicalIF":4.1,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/md/d4md00122b?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252003","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":"Rational design and in vitro testing of new urease inhibitors to prevent urinary catheter blockage†","authors":"Rachel A. Heylen, Nicola Cusick, Tom White, Emily J. Owen, Bethany L. Patenall, Martin Alm, Peter Thomsen, Maisem Laabei and A. Toby A. Jenkins","doi":"10.1039/D4MD00378K","DOIUrl":"10.1039/D4MD00378K","url":null,"abstract":"<p >Catheter associated urinary tract infections (CAUTI) caused by urease-positive organisms can lead to catheter blockage: urease metabolizes urea in urine to ammonia causing an increase in pH and hence precipitation of struvite and apatite salts into the catheter lumen and bladder leading to blockage. Acetohydroxamic acid (AHA) is the only urease inhibitor currently approved for patient use, however, it is rarely used owing to its side effects. Here, we report the identification and development of new urease inhibitors discovered using a rational <em>in silico</em> drug design approach. A series of compounds were designed, the compounds were screened and filtered to identify three compounds which were tested in <em>in vitro</em> urease activity assays. <em>N</em>,<em>N</em>′-Bis(3-pyridinylmethyl)thiourea (Bis-TU) outperformed AHA in activity assays and was tested in an <em>in vitro</em> bladder model, where it significantly extended the lifetime of the catheter compared to AHA. Bis-TU was delivered <em>via</em> a diffusible balloon catheter directly to the site of activity, thus demonstrating localized drug delivery. This cost-effective drug design approach allowed the identification of a potent urease inhibitor, which could be improved through iterative repeats of the method, and the process of design could be utilized to target other diseases.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 10","pages":" 3597-3608"},"PeriodicalIF":4.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/md/d4md00378k?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222183","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":"Inhibition of monoamine oxidases by heterocyclic derived conjugated dienones: synthesis and <i>in vitro</i> and <i>in silico</i> investigations.","authors":"Sunil Kumar, Bishnu Prasad Pandey, Mohamed A Abdelgawad, Mohammed M Ghoneim, Rania B Bakr, Hoon Kim, Bijo Mathew","doi":"10.1039/d4md00608a","DOIUrl":"10.1039/d4md00608a","url":null,"abstract":"<p><p>A total of 18 heterocyclic derived conjugated dienones (CD1-CD18) were evaluated for their potential monoamine oxidase (MAO)-A/-B inhibitory activity. Among the analyzed molecules, CD11 and CD14 showed notable inhibitory potentials against MAO-B, with half-maximal inhibitory concentration (IC₅₀) values of 0.063 ± 0.001 μM and 0.036 ± 0.008 μM, respectively. In contrast, CD1, CD2 and CD3 showed comparable inhibitory activities toward MAO-A, with IC₅₀ values of 3.45 ± 0.07, 3.23 ± 0.24, and 3.15 ± 0.10 μM, respectively. Derivatives of thiophene (CD13-CD17) exhibited selectivity indices greater than 250 for MAO-B. Both lead compounds exhibited similar potencies to safinamide and were more potent than pargyline. According to kinetic analysis, CD11 and CD14 exhibited competitive inhibition of MAO-B activity, with <i>K</i> _i values of 12.67 ± 3.85 nM and 4.5 ± 0.62 nM, respectively. Furthermore, the reversibility test results indicated that the inhibitions were reversible. Molecular docking and molecular dynamics simulation studies can provide insights into the probable binding interactions of CD11 and CD14 with MAO-B. CD11 demonstrated a bipartite contact with Tyr326 and Phe343, whereas CD14 showed contact with Pro102 and Tyr435 <i>via</i> aromatic hydrogen bonds. These results indicated that both compounds have high-affinity binding interactions ( -10.13 and -9.90 kcal mol^-1, respectively) at the active site of MAO-B. Furthermore, we used SwissADME to estimate ADME, and both lead compounds demonstrated blood-brain barrier penetration. The study results indicated that all the compounds evaluated demonstrated potent inhibition of MAO-B activity, which was comparable to the efficacy of reference medications. It is necessary to do further investigations on the lead molecules to see whether they may be used to treat different neurodegenerative illnesses.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473772","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":"Stereochemical optimization of N,2-substituted cycloalkylamines as norepinephrine reuptake inhibitors†","authors":"Majlen A. Dilweg, Tamara A. M. Mocking, Pantelis Maragkoudakis, Gerard J. P. van Westen, Laura H. Heitman, Adriaan P. IJzerman, Willem Jespers and Daan van der Es","doi":"10.1039/D4MD00521J","DOIUrl":"10.1039/D4MD00521J","url":null,"abstract":"<p >The norepinephrine transporter (NET), encoded by the SLC6A2 gene, is one of three key monoamine neurotransmitter transporters. Inhibition of NET-mediated reuptake of norepinephrine by monoamine reuptake inhibitors has been the main therapeutic strategy to treat disorders such as depression, ADHD and Parkinson's disease. Nevertheless, lack of efficacy as well as risk of adverse effects are still common for these treatments underscoring the necessity to improve drug discovery efforts for this target. In this study, we developed new inhibitors based on 4-((2-(3,4-dichlorophenyl)cyclopentyl)amino)butan-1-ol (<strong>8</strong>), a potent NET inhibitor, which emerged from earlier virtual screening efforts using a predictive proteochemometric model. Hence, we optimized the <em>N</em>,2-substituted cycloalkylamine scaffold in three regions to design twenty new derivatives. To establish structure–activity relationships for these NET inhibitors, all novel compounds were tested utilizing an impedance-based ‘transporter activity through receptor activation’ assay. Moreover, all stereoisomers of the most potent compound (<strong>27</strong>) were synthesized and evaluated for their inhibitory potencies. Initial screening indicated that modifications in the cyclopentylamine moiety and phenyl substitutions decreased NET inhibition compared to <strong>8</strong>, emphasizing the importance of the five-membered ring, secondary amine and dichloro-substitution pattern in NET binding. Substituting the original butylalcohol at the <em>R</em><small>²</small> position with a rigid cyclohexanol yielded lead compound <strong>27</strong>, with potency similar to reference inhibitor nisoxetine. Pharmacological characterization of all eight stereoisomers of <strong>27</strong> revealed varying inhibitory potencies, favoring a <em>trans</em>-orientation of the <em>N</em>,2-substituted cyclopentyl moiety. Molecular docking highlighted key interactions and the impact of a hydrophilic region in the binding pocket. This study presents a novel set of moderate to highly potent NET inhibitors, elucidating the influence of molecular orientation in the NET binding pocket and offering valuable insights into drug discovery efforts for monoamine transport-related treatments.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 12","pages":" 4068-4079"},"PeriodicalIF":4.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142353068","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":"Exploring apoptotic induction of malabaricone A in triple-negative breast cancer cells: an acylphenol phyto-entity isolated from the fruit rind of Myristica malabarica Lam.†","authors":"Pothiyil S. Vimalkumar, Neethu Sivadas, Vishnu Priya Murali, Daisy R. Sherin, Madhukrishnan Murali, Anuja Gracy Joseph, Kokkuvayil Vasu Radhakrishnan and Kaustabh Kumar Maiti","doi":"10.1039/D4MD00391H","DOIUrl":"10.1039/D4MD00391H","url":null,"abstract":"<p > <em>Myristica malabarica</em> Lam., commonly known as Malabar nutmeg or false nutmeg, is used in traditional medicine and as a spice. Our exploration focuses on malabaricones, a distinct group of secondary metabolites isolated from the fruit rind of <em>M. malabarica</em>. We investigated the selective cytotoxicity of malabaricones against the triple-negative breast cancer (TNBC) cell line. In particular, malabaricone A (Mal-A) displays heightened toxicity towards TNBC cells (MDA-MB-231), with an IC<small>₅₀</small> of 8.81 ± 0.03 μM. <em>In vitro</em> fluorimetric assays confirmed the apoptotic capability of Mal-A and its capacity to induce nuclear fragmentation. Additionally, ultrasensitive surface-enhanced Raman spectroscopy confirms DNA fragmentation during cellular apoptosis. Cell cycle analysis indicates arrest during the sub-G<small>₀</small> phase by downregulating key regulatory proteins involved in cell cycle progression. Increased expression levels of caspase 3, 9, and 8 suggest involvement of both extrinsic and intrinsic apoptotic pathways. Finally, assessment of protein expression patterns within apoptotic pathways reveals upregulation of key apoptotic proteins like Fas/FasL, TNF/TNFR1, and p53, coupled with downregulation of several inhibitors of apoptosis proteins such as XIAP, cIAP-2, and Livin. These findings are further verified with <em>in silico</em> molecular docking. Mal-A reveals a strong affinity towards apoptotic proteins, including TNF, Fas, HTRA, Smac, and XIAP, with docking scores ranging from −5.1 to −7.2 kcal mol<small>⁻¹</small>. Subsequently, molecular dynamics simulation confirms the binding stability. This conclusive <em>in vitro</em> evaluation validates Mal-A as a potent phyto-entity against TNBC. To the best of our knowledge, this study represents the first comprehensive anticancer evaluation of Mal-A in TNBC cells.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 10","pages":" 3558-3575"},"PeriodicalIF":4.1,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222188","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 biological evaluation of novel thiazole derivatives as PI3K/mTOR dual inhibitors†","authors":"Samar I. Faggal, Yara El-Dash, Amr Sonousi, Amr M. Abdou and Rasha A. Hassan","doi":"10.1039/D4MD00462K","DOIUrl":"10.1039/D4MD00462K","url":null,"abstract":"<p >The development of anticancer drugs targeting both PI3K and mTOR pathways is recognized as a promising cancer therapeutic approach. In the current study, we designed and synthesized seventeen new thiazole compounds to investigate their effect on both PI3K and mTOR as well as their anti-apoptotic activity. All the synthesized thiazoles were investigated for their antiproliferative activity on a panel of 60 different cancer cell lines at the National Cancer Institute. Compounds <strong>3b</strong> and <strong>3e</strong> were selected for further investigation at five dose concentrations due to their effective growth inhibiting activity. Compounds <strong>3b</strong> and <strong>3e</strong> were further evaluated for their <em>in vitro</em> inhibitory activities against PI3Kα and mTOR compared to alpelisib and dactolisib, respectively as reference drugs. The inhibitory effect of compound <strong>3b</strong> on PI3Kα was similar to alpelisib, but it showed weaker inhibitory activity on mTOR compared to dactolisib. Moreover, compound <strong>3b</strong> exhibited significantly higher inhibitory activity compared to compound <strong>3e</strong> against both PI3Kα and mTOR. The cell cycle analysis showed that compounds <strong>3b</strong> and <strong>3e</strong> induced G0–G1 phase cell cycle arrest in the leukemia HL-60(TB) cell line. Meanwhile, they significantly increased the total apoptotic activity which was supported by an increase in the level of caspase-3 in leukemia HL-60(TB) cell lines. Molecular docking experiments provided additional explanation for these results by demonstrating the ability of these derivatives to form a network of key interactions, known to be essential for PI3Kα/mTOR inhibitors. All these experimental results suggested that <strong>3b</strong> and <strong>3e</strong> are potential PI3Kα/mTOR dual inhibitors and could be considered promising lead compounds for the development of anticancer agents.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 12","pages":" 4111-4125"},"PeriodicalIF":4.1,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142353063","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":"Outstanding Reviewers for RSC Medicinal Chemistry in 2023","authors":"","doi":"10.1039/D4MD90031F","DOIUrl":"10.1039/D4MD90031F","url":null,"abstract":"<p >We would like to take this opportunity to thank all of <em>RSC Medicinal Chemistry</em>'s reviewers for helping to preserve quality and integrity in chemical science literature. We would also particularly like to highlight the Outstanding Reviewers for <em>RSC Medicinal Chemistry</em> in 2023.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 9","pages":" 2973-2973"},"PeriodicalIF":4.1,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154865","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":"Outstanding Reviewers for <i>RSC Medicinal Chemistry</i> in 2023.","authors":"","doi":"10.1039/d4md90031f","DOIUrl":"https://doi.org/10.1039/d4md90031f","url":null,"abstract":"<p><p>We would like to take this opportunity to thank all of <i>RSC Medicinal Chemistry</i>'s reviewers for helping to preserve quality and integrity in chemical science literature. We would also particularly like to highlight the Outstanding Reviewers for <i>RSC Medicinal Chemistry</i> in 2023.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":"15 9","pages":"2973"},"PeriodicalIF":4.1,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392972","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":"Prediction of synergistic gemcitabine-based combination treatment through a novel tumor stemness biomarker NANOG in pancreatic cancer","authors":"Jiongjia Cheng, Ting Zhu, Shaoxian Liu, Jiayu Zhou, Xiaofeng Wang and Guangxiang Liu","doi":"10.1039/D4MD00165F","DOIUrl":"10.1039/D4MD00165F","url":null,"abstract":"<p >Gemcitabine remains a first-class chemotherapeutic drug for pancreatic cancer. However, due to the rapid development of gemcitabine resistance in pancreatic cancer, gemcitabine alone or in combination with other anti-cancer drugs only showed limited effect in the clinic. It is extremely challenging to effectively and efficiently determine the optimal drug regimens. Thus, identification of appropriate prediction biomarkers is critical for the rational design of gemcitabine-based therapeutic options. Herein, a pancreatic cancer stem cell (PCSC) model exhibiting chemoresistance to gemcitabine was used to test the activity of clinical cancer drugs in the presence or absence of gemcitabine. As determined by combinatorial treatment, several types of drugs resensitized gemcitabine-resistant PCSCs to gemcitabine, with sorafenib (EGFR inhibitor)/gemcitabine and sunitinib (TBK1 inhibitors)/gemcitabine drug combinations being the most preferred treatments for PCSCs. Following the validation of the PCSC model by an antibody array test of 15-gene expression of stemness biomarkers, NANOG showed markedly different expression in PCSCs compared to the parental cells. From comprehensive analysis of stem cell index <em>versus</em> combination index, a stemness-related correlation model was successfully constructed to demonstrate the correlation between NANOG expression and synergism. Cancer cell stemness was ascertained to be highly relevant to NANOG overexpression that can be abrogated by synergized gemcitabine-drug combinations. Therefore, NANOG works as a therapeutic biomarker for predicating efficient combinatorial treatment of gemcitabine in pancreatic cancer.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 11","pages":" 3853-3861"},"PeriodicalIF":4.1,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252005","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":"Asymmetric imidazole-4,5-dicarboxamide derivatives as SARS-CoV-2 main protease inhibitors: design, synthesis and biological evaluation†","authors":"Phuong Nguyen Hoai Huynh, Phatcharin Khamplong, Minh-Hoang Phan, Thanh-Phuc Nguyen, Phuong Ngoc Lan Vu, Quang-Vinh Tang, Phumin Chamsodsai, Supaphorn Seetaha, Truong Lam Tuong, Thien Y. Vu, Duc-Duy Vo, Kiattawee Choowongkomon and Cam-Van T. Vo","doi":"10.1039/D4MD00414K","DOIUrl":"10.1039/D4MD00414K","url":null,"abstract":"<p >The SARS-CoV-2 main protease, a vital enzyme for virus replication, is a potential target for developing drugs in COVID-19 treatment. Until now, three SARS-CoV-2 main protease inhibitors have been approved for COVID-19 treatment. This study explored the inhibitory potency of asymmetric imidazole-4,5-dicarboxamide derivatives against the SARS-CoV-2 main protease. Fourteen derivatives were designed based on the structure of the SARS-CoV-2 main protease active site, the hydrolysis mechanism, and the experience gained from the reported inhibitor structures. They were synthesized through a four-step procedure from benzimidazole and 2-methylbenzimidazole. SARS-CoV-2 main protease inhibition was evaluated <em>in vitro</em> by fluorogenic assay with lopinavir, ritonavir, and ebselen as positive references. <em>N</em>-(4-Chlorophenyl)-2-methyl-4-(morpholine-4-carbonyl)-1<em>H</em>-imidazole-5-carboxamide (<strong>5a2</strong>) exhibited the highest potency against the SARS-CoV-2 main protease with an IC<small>₅₀</small> of 4.79 ± 1.37 μM relative to ebselen with an IC<small>₅₀</small> of 0.04 ± 0.013 μM. Enzyme kinetic and molecular docking studies were carried out to clarify the inhibitory mechanism and to prove that the compound interacts at the active site. We also performed cytotoxicity assay to confirm that these compounds are not toxic to human cells.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" 11","pages":" 3880-3888"},"PeriodicalIF":4.1,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142353061","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}