Chemical Biology & Drug Design最新文献

{"title":"Repurposing of FDA-Approved Drugs to Disrupt Iron Uptake in Mycobacterium abscessus: Targeting Salicylate Synthase as a Novel Approach","authors":"Giovanni Stelitano,&nbsp;Christian Bettoni,&nbsp;Matteo Mori,&nbsp;Mario Cocorullo,&nbsp;Andrea Tresoldi,&nbsp;Fiorella Meneghetti,&nbsp;Stefania Villa,&nbsp;Laurent R. Chiarelli","doi":"10.1111/cbdd.70162","DOIUrl":"https://doi.org/10.1111/cbdd.70162","url":null,"abstract":"<p>Non-tuberculous mycobacteria (NTM) are opportunistic pathogens that lead to severe, persistent infections, particularly in immunocompromised or vulnerable individuals. Infection rates are rising worldwide, highlighting NTM as an increasing threat to public health. There are currently no specific drugs, and the recommended regimens are usually ineffective. This scenario underlines the urgent need to develop new strategies to effectively combat these infections in a more innovative way. However, the development of new drugs can be a lengthy process, often taking more than a decade to identify even a single active compound. Among the new strategies that can expedite this process is the repurposing of approved drugs. In this work, we applied this approach to identify compounds inhibiting iron uptake in <i>Mycobacterium abscessus</i> (<i>Mab</i>). Specifically, we studied the targeting of salicylate synthase, an enzyme that plays a crucial role in the biosynthesis of mycobacterial siderophores necessary for iron acquisition. Performing an <i>in silico</i> virtual screening of three databases against the crystal structure of salicylate synthase, we identified 11 potential ligands. Then, in vitro assays on the recombinant enzyme highlighted three competitive inhibitors, namely fostamatinib, esomeprazole, and hydroxystilbamidine. These results confirm the potential of the repurposing approach and pave the way for further experimental validation and optimization of these inhibitors as promising compounds against NTM infections.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"106 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70162","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144716932","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":"Synthesis and Bioactivity Evaluation of Novel Sulfonamide-1,2,3-Triazole Hybrids: In Vitro and In Silico Studies","authors":"Mustafa Çeşme,&nbsp;Sultan Onur,&nbsp;Fatma Betül Özgeriş,&nbsp;Ferhan Tümer","doi":"10.1111/cbdd.70155","DOIUrl":"https://doi.org/10.1111/cbdd.70155","url":null,"abstract":"<p>Novel hybrid compounds, incorporating 4-iodosulfonamide and 1,2,3-triazole units, were synthesized and characterized using FT-IR, NMR, and elemental analysis. Their antioxidant (ABTS, DPPH, Cuprac), cholinesterase inhibition (AChE, BuChE), and anticancer (Caco-2, PC3) activities were evaluated. In DPPH assays, compounds 13, 6, and 11 showed superior antioxidant activity compared to α-tocopherol and BHT. Compound 6 exhibited the highest ABTS activity, while compound 9 excelled in Cuprac assays. For cholinesterase inhibition, compounds 8 and 13 outperformed Galantamine against AChE, and compound 9 showed the strongest BuChE inhibition. Antiproliferative studies revealed compound 13's effectiveness against PC3 and compound 9 against Caco-2. Comprehensive ADMET analysis indicated favorable pharmaceutical properties, including oral absorption via the BBB and GI tract. In silico molecular docking supported these findings, confirming the therapeutic potential of these hybrid structures.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"106 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70155","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705673","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":"2-Hydroxy-3-Methylanthraquinone Suppresses Hepatocellular Carcinoma Progression by Blocking Annexin A5-Mediated Phosphatidylinositol 3-Kinase/Protein Kinase B Signaling","authors":"Min Luo,&nbsp;Juanmei Mo,&nbsp;Chaoyuan Huang,&nbsp;Yan Mao,&nbsp;Hongzhi Wang,&nbsp;Xiaochen Wang","doi":"10.1111/cbdd.70161","DOIUrl":"https://doi.org/10.1111/cbdd.70161","url":null,"abstract":"<div>\u0000 \u0000 <p>Hepatocellular carcinoma (HCC), the most common subtype of primary liver cancer, remains a major cause of cancer-related mortality worldwide. Although 2-hydroxy-3-methylanthraquinone (HMA), a natural anthraquinone compound, has demonstrated antitumor activity in various malignancies, its specific role and underlying mechanisms in HCC are not fully understood. This study aimed to evaluate the antitumor effects and molecular mechanisms of HMA in HCC. Human HCC cell lines were treated with HMA, and cell proliferation and apoptosis were assessed using Cell Counting Kit-8 and flow cytometry assays, respectively. A heterotopic xenograft tumor model was established in nude mice to evaluate in vivo tumor growth and weight. Immunohistochemical staining for Ki67 and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed to assess tumor cell proliferation and apoptosis. Network pharmacology analysis was conducted to predict potential targets of HMA in HCC. Quantitative real-time polymerase chain reaction and Western blotting were used to evaluate mRNA and protein expression levels. Cell migration and invasion were assessed using wound healing and transwell assays. Our data revealed that HMA significantly suppressed cell proliferation, induced apoptosis, and inhibited migration and invasion in both HCC cells and tumor tissues. Mechanistically, HMA downregulated Annexin A5 (ANXA5) expression and inhibited activation of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway. Silencing of ANXA5 replicated the inhibitory effects of HMA and further enhanced its pro-apoptotic and anti-invasive activities. Conversely, overexpression of ANXA5 restored PI3K/AKT signaling activity and reversed the inhibitory effects of HMA on HepG2 cell proliferation, migration, and invasion. These reversal effects were abolished by treatment with LY294002, a selective PI3K inhibitor. In summary, HMA suppresses the progression of HCC by targeting ANXA5 and inhibiting the PI3K/AKT signaling pathway, highlighting its potential as a novel therapeutic agent for HCC.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"106 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688014","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":"Correction to “Improving Classical Scoring Functions Using Random Forest: The Non-Additivity of Free Energy Terms’ Contributions in Binding”","authors":"","doi":"10.1111/cbdd.70159","DOIUrl":"https://doi.org/10.1111/cbdd.70159","url":null,"abstract":"<p>Karim Afifi, Ahmed Farouk Al-Sadek. Improving classical scoring functions using random forest: The non-additivity of free energy terms’ contributions in binding. <i>Chemical Biology &amp; Drug Design</i>. 2018;92: 1429-1434. https://doi.org/10.1111/cbdd.13206</p><p>In the article, Ahmed Farouk Al-Sadek's affiliation has been incorrectly provided as “Central Lab for Agricultural Experts Systems, Ministry of Agriculture and Land Reclamation, Giza, Egypt.” However, it should be “Central Lab for Agricultural Experts Systems, Agricultural Research Center (ARC), Giza, Egypt.”</p><p>The author apologizes for this error.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"106 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70159","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681549","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":"Correction to “Synthesis and Activity Study of Gefitinib Derivatives Inducing Mitochondrial Apoptosis in HeLa Cells”","authors":"","doi":"10.1111/cbdd.70160","DOIUrl":"https://doi.org/10.1111/cbdd.70160","url":null,"abstract":"<p>Li, Y., Hou, X., Liu, S., Chen, Z., Wu, Q., He, B., Guo, J., Wang, L., Liu, C., Fei Mao, L. 2024. “Synthesis and Activity Study of Gefitinib Derivatives Inducing Mitochondrial Apoptosis in HeLa Cells.” <i>Chemical Biology and Drug Design</i> 104, no. 6: e70035.</p><p>The first affiliation was mistakenly listed as <b>Zhoukou Center Hospital</b>; however, the correct name should be <b>Zhoukou Central Hospital</b>.</p><p>The authors apologize for this error.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"106 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.70160","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681545","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":"Spalt-Like Transcription Factor 4 Mediates Fatty Acid Oxidation to Foster 5-Fluorouracil Resistance in Gastric Cancer Cells","authors":"Yong Zhu,&nbsp;Chuanmin Yi,&nbsp;Jin Zhao,&nbsp;Lei Wang,&nbsp;Tao Huang,&nbsp;Bo Xiang,&nbsp;Lvhai Zhang,&nbsp;Xiangfang He,&nbsp;Linke Wu","doi":"10.1111/cbdd.70158","DOIUrl":"https://doi.org/10.1111/cbdd.70158","url":null,"abstract":"<div>\u0000 \u0000 <p>Platinum-based and pyrimidine drugs are first-line treatments for gastric cancer (GC), but their efficacy is often affected by drug resistance. High spalt-like transcription factor 4 (SALL4) expression is associated with poor prognosis, but its role in 5-fluorouracil (5-FU) resistance is not yet clear. In this study, we investigated the effect of SALL4 on 5-FU resistance in GC cells by bioinformatics analysis, real-time quantitative reverse transcription polymerase chain reaction, cell counting kit-8, colony formation assay, and western blot. The results showed that SALL4 was highly expressed in GC and significantly correlated with the fatty acid oxidation (FAO) pathway. Knockdown of SALL4 resulted in a notable attenuation of cellular proliferative capacity and heightened susceptibility to 5-FU resistance in GC cells, while overexpression of SALL4 enhanced 5-FU resistance. Rescue assays confirmed that SALL4 fostered 5-FU resistance in GC cells by enhancing FAO. Our research confirmed that SALL4 promoted the resistance of GC cells to 5-FU by enhancing the FAO pathway. This suggests that drug development targeting SALL4 may help overcome chemotherapy resistance in GC.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"106 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688067","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":"New Thiadiazole-Benzenesulfonamide Hybrids as Dual B-Raf/VEGFR-2 Inhibitors With Promising Anti-Hepatic Cancer Activity","authors":"Aisha A. Alsfouk,&nbsp;Hazem Elkady,&nbsp;Saber M. Hassan,&nbsp;Walid E. Elgammal,&nbsp;Hazem A. Mahdy,&nbsp;Dalal Z. Husein,&nbsp;Fatma G. Amin,&nbsp;Mohamed Hagras,&nbsp;Eslam B. Elkaeed,&nbsp;Ahmed M. Metwaly,&nbsp;Ibrahim H. Eissa","doi":"10.1111/cbdd.70156","DOIUrl":"https://doi.org/10.1111/cbdd.70156","url":null,"abstract":"<div>\u0000 \u0000 <p>A new group of thiadiazole-benzenesulfonamide hybrids was designed, synthesized, and biologically evaluated as potential dual inhibitors targeting B-Raf and VEGFR-2 for cancer therapy. The cytotoxic activity of the synthesized derivatives was assessed against HepG2 and Huh7 liver cancer cell lines, where compound <b>7a</b> exhibited the most potent activity with IC₅₀ values of 17.89 μM and 25.07 μM, respectively. The kinase inhibition assay revealed that <b>7a</b> strongly inhibited both B-Raf (IC₅₀ = 0.11 μM) and VEGFR-2 (IC₅₀ = 0.15 μM), surpassing sorafenib in B-Raf inhibition. Further mechanistic studies revealed that <b>7a</b> induced G2/M phase arrest, with a significant increase in late apoptotic cells (57.08%) compared to the control group (0.15%), confirming its pro-apoptotic effect. The apoptotic pathway was further validated by caspase-3 activation, Bax upregulation, and Bcl-2 downregulation. Computational analyses verified the effective binding of compound <b>7a</b> to VEGFR-2. These analyses included molecular docking, molecular dynamic (MD) simulations, molecular mechanics with generalized Born and surface area solvation (MM-GBSA), protein-ligand interaction fingerprints (ProLIF), principal component analysis (PCAT), and free energy landscape (FEL) studies. Additionally, DFT studies indicated <b>7a</b>'s stability and reactivity. <i>In silico</i> ADMET predictions indicated that the derivatives had good absorption, were non-mutagenic, non-carcinogenic, and exhibited low toxicity risks compared to sorafenib. These findings suggest that the synthesized thiadiazole-benzenesulfonamide hybrids, particularly <b>7a</b>, represent promising dual BRAF/VEGFR-2 inhibitors with potent anti-cancer activity, warranting further optimization and preclinical evaluation.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"106 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666222","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":"New Pyrazole-Based Tetrazole Derivatives: Synthesis, Characterization, and Their Vasorelaxant and α-Amylase Inhibition Activities","authors":"Ahlam Oulous,&nbsp;Ikram Dib,&nbsp;Tarik Harit,&nbsp;Abdullah Yahya Abdullah Alzahrani,&nbsp;Mounir Cherfi,&nbsp;Nour Elhouda Daoudi,&nbsp;Abderrahim Ziyyat,&nbsp;Fouad Malek","doi":"10.1111/cbdd.70157","DOIUrl":"https://doi.org/10.1111/cbdd.70157","url":null,"abstract":"<div>\u0000 \u0000 <p>A series of new linear pyrazole-based tetrazole derivatives <b>1</b>–<b>10</b> were synthesized and characterized. The structures of the intermediate compounds were confirmed using ¹H and ¹³C NMR spectroscopy, as well as high-resolution mass spectrometry (HRMS). These derivatives were synthesized through a straightforward equimolar condensation between pyrazole and tetrazole precursors. The vasorelaxant activity of these compounds was assessed by determining their percentage inhibition, <i>E</i> (%), which ranged from 26% to 67%, with compound <b>4</b> exhibiting the highest activity. Additionally, their anti-diabetic potential was evaluated by determining the IC₅₀ values for α-amylase enzyme inhibition. Notably, compounds <b>2</b> and <b>6</b> demonstrated a comparable activity to the positive control acarbose. These experimental findings were further supported by molecular docking studies.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"106 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647671","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":"Multifaceted In Silico Screening Strategies Identifies Potent Inhibitors Facilitating Inhibition of ZNF726 Activity in Breast Cancer","authors":"Shreetama Bandyopadhayaya,&nbsp;Pooja Yadav,&nbsp;Monika Kumari,&nbsp;Sanjay Kumar Dey,&nbsp;Chandi C. Mandal","doi":"10.1111/cbdd.70144","DOIUrl":"https://doi.org/10.1111/cbdd.70144","url":null,"abstract":"<div>\u0000 \u0000 <p>Studies documented by our lab established ZNF726 to potently augment the tumorigenic behavior of breast cancer cells by increasing cellular cholesterol levels. Therefore, Zinc finger protein 726 (ZNF726) can be considered an attractive therapeutic target for the treatment of breast cancer. Based on these views, this study aimed to identify potent inhibitors targeting ZNF726 activity utilizing a structure-based molecular docking method. Virtual screening with the LOPAC library led to the identification of zoledronic acid monohydrate as a top-hit compound featuring good docking and MMGBSA scores. Further, zoledronic acid monohydrate was found to inhibit the proliferation potential of breast cancer cells. Ectopic expression of ZNF726 led to an increase in the cholesterol levels of breast cancer cells. Further, this study confirms that zoledronic acid tends to decrease the cholesterol content in ZNF726-overexpressed cells along with an inhibitory effect on breast cancer cell proliferation. Conclusively, these findings suggested that the cholesterol pathway and oncogenic ZNF726 form an interdependent relationship, and therefore, targeting the cholesterol pathway may prove to be a promising strategy to inhibit oncogenic ZNF726 expression in breast cancer. Additionally, this study also reveals nine phytochemicals that might target ZNF726 activity, identified through virtual screening by the IMPPAT library. Three phytochemicals (Swertiamacroside, Terflavin A, and N-(3-Carboxy-2,3-dihydroxypropyl)-4-((carboxymethyl)amino) threonine) out of the nine phytochemicals are still unknown for their anticancer role which needs further exploration. Briefly, this study draws attention toward finding potential therapeutics against the carcinogenic effects of ZNF726 by multiple in silico approaches.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"106 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144647241","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":"Structure-Based Bioisosterism Design, Synthesis, Antitumor and Toxicity Assessment of Novel Aplysinopsin Analogs","authors":"Bárbara Gonçalves Rivello,&nbsp;Julia Biz Willig,&nbsp;Jéssica Gotardi,&nbsp;Michele Resende Machado,&nbsp;Gloria Narjara Santos da Silva,&nbsp;Christian Dias Gomides,&nbsp;Gisele Augusto Rodrigues de Oliveira,&nbsp;Luciano Morais Lião,&nbsp;Diogo André Pilger,&nbsp;Ricardo Menegatti","doi":"10.1111/cbdd.70151","DOIUrl":"https://doi.org/10.1111/cbdd.70151","url":null,"abstract":"<div>\u0000 \u0000 <p>Eight new LQFM's Aplysinopsin analogs (<b>12a-h</b>) were synthesized and were evaluated for their anticancer profile on MCF-7 (breast cancer), SiHA and HeLa (cervical cancer). The compounds were obtained through the rational drug design strategy, bioisosterism, by changing the indole scaffold of Aplysinopsin by phenylpyrazole, a subunit extensively explored for designing potent and selective anticancer agents. The synthesis was performed in three simple steps, followed by structural elucidation through nuclear magnetic resonance, infrared spectroscopy, and mass spectrometry, and global yield ranged from 10% to 93%. Regarding the biological assay, the best result was achieved with <b>12g</b>, which showed antiproliferative activity against all cell lines evaluated, with IC₅₀ 59.22, 58.33, and 55.32 μM for MCF-7, SiHA and HeLa, respectively. The safety profile, in the Zebrafish-based model, showed the mortality rate for <b>12g</b> in concentration-time-dependent, from 87 μM, over 120 h. All Aplysinopsin analogs demonstrated drug-likeness in agreement to Lipinski and Veber rules. Although the moderate antiproliferative activity displayed by <b>12g</b>, our results include new Aplysinopsin analogs that may be promising lead compounds for further studies, since chemical structures related to this marine compound have provided satisfactory results as anticancer agents against a variety of human tumor cell lines.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"106 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598762","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}