Chemical Biology & Drug Design最新文献

{"title":"Plumbagin's Antiproliferative Mechanism in Human Cancer Cells: A Copper-Dependent Cytotoxic Approach","authors":"Mohamed El Oirdi","doi":"10.1111/cbdd.14606","DOIUrl":"10.1111/cbdd.14606","url":null,"abstract":"<p>Cancer is a serious global health problem, causing the loss of millions of lives each year. Plumbagin, a compound derived from the medicinal plant <i>Plumbago zeylanica</i>, has shown promise in stopping the growth of tumor cells both in laboratory settings and in living organisms. Many plant-based compounds exert their effects through copper's ability to produce reactive oxygen species (ROS). This study aimed to understand how plumbagin, dependent on copper, induces cell death (apoptosis) in human cancer cells through various experiments. The results demonstrate that plumbagin hinders the growth of pancreatic cancer cells PNAC-1 and MIA PaCa-2 by utilizing the copper naturally present in the cells. Unlike metal chelators that remove iron and zinc (desferrioxamine mesylate and histidine), a specific copper chelator called neocuproine lessens the cell death caused by plumbagin. When ROS scavengers are used, plumbagin-induced apoptosis is inhibited, indicating that ROS plays a role in initiating cell death. The study also proves that plumbagin prevents copper from leaving cancer cells by suppressing the expression of specific genes (<i>CTR1</i> and <i>ATP7A</i>). It is confirmed that plumbagin targets the nuclear copper, leading to signals that promote oxidative stress and, ultimately, cell death. These findings provide valuable insights into the potential of plumbagin as a substance to combat cancer, highlighting the importance of understanding how copper behaves within cancer cells.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.14606","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141989792","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":"Promotion Effect of Catalpol on Angiogenesis and Potential Mechanisms: A Research Based on Network Pharmacology","authors":"Jin-rong Ni,&nbsp;Qun-hu Zhang,&nbsp;Jie-lin Deng,&nbsp;Hai-hu Wang,&nbsp;Yong-chi Duan,&nbsp;Cheng-ji Zhang,&nbsp;Lue-tao Jiang","doi":"10.1111/cbdd.14602","DOIUrl":"10.1111/cbdd.14602","url":null,"abstract":"<div>\u0000 \u0000 <p>Catalpol, a natural iridoid glycoside, has potential therapeutic benefits, including anti-inflammatory and neuroprotective effects. Investigating catalpol's role in angiogenesis is critical for understanding its potential therapeutic applications, particularly in diseases where modulating angiogenesis is beneficial. This study investigates catalpol's influence on angiogenesis and its mechanisms, combining network pharmacology and in vitro experiments. The target genes corresponding to the catalpol were analyzed by SwissTargetPrediction. Then angiogenesis-related targets were acquired from databases like GeneCards. Subsequently, the Database for Annotation, Visualization and Integrated Discovery was employed for Gene Ontology and pathway analysis, while Cytoscape visualized protein interactions. The effect of catalpol on viability and angiogenesis of HUVECs was further examined using Cell Counting Kit-8 and angiogenesis assays. RT-qPCR and western blot were applied to check the expression of angiogenesis-related proteins. Totally, 312 target genes of catalpol and 823 angiogenesis-related targets were obtained with 56 common targets leading to PPI network analysis, highlighting hub genes (AKT1, EGFR, STAT3, MAPK3, and CASP3). These hub genes were mainly enriched in lipid and atherosclerosis pathway and EGFR-related pathway. The in vitro experimental results showed that catalpol achieved a concentration-dependent increase in HUVECs viability. Catalpol also promoted the migration and angiogenesis of HUVECs and up-regulated the expression of EGFR. EGFR knockdown inhibited the effect of catalpol on HUVECs. Catalpol promotes angiogenesis in HUVECs by upregulating EGFR and angiogenesis-related proteins, indicating its potential therapeutic application in vascular-related diseases.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972463","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":"An integrated network pharmacology and molecular docking approach to reveal the role of Arctigenin against Cutibacterium acnes-induced skin inflammation by targeting the CYP19A1","authors":"Xiaoyan Lu,&nbsp;Yanzhong Han,&nbsp;Yongkang Zhang,&nbsp;Rui Li,&nbsp;Jiaoyan Xu,&nbsp;Jian Yang,&nbsp;Jingchun Yao,&nbsp;Zhihai Lv","doi":"10.1111/cbdd.14598","DOIUrl":"10.1111/cbdd.14598","url":null,"abstract":"<p>Acne caused by inflammation of hair follicles and sebaceous glands is a common chronic skin disease. Arctigenin (ATG) is an extract of Arctium lappa L., which has significant anti-inflammatory effects. However, the effect and mechanism of ATG in cutaneous inflammation mediated by <i>Cutibacterium acnes</i> (<i>C</i>. <i>acnes</i>) has not been fully evaluated. The purpose of this study was to explore the effect and potential mechanism of ATG in the treatment of acne through network pharmacology and experimental confirmation. An acne model was established by injected live <i>C. acnes</i> into living mice and treated with ATG. Our data showed that ATG effectively improved acne induced by live <i>C. acnes</i>, which was confirmed by determining ear swelling rate, estradiol concentration and hematoxylin and eosin (H&amp;E) staining. In addition, ATG inhibited the NLRP3 inflammasome signaling pathway in mice ear tissues and reduced the secretion of pro-inflammatory cytokines IL-1β to relieve inflammation. The results of network pharmacology and molecular docking confirmed that ATG can regulate 17β-Estradiol (E2) levels through targeted to CYP19A1, and finally inhibited skin inflammation. Taken together, our results confirmed that ATG regulated E2 secretion by targeting CYP19A1, thereby inhibiting the NLRP3 inflammasome signaling pathway and improving inflammation levels in acne mice. This study provides a basis for the feasibility of ATG in treating acne in clinical practice.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and evaluation of di-heterocyclic benzazole compounds as potential antibacterial and anti-biofilm agents against Staphylococcus aureus","authors":"Mine Buga Aktekin,&nbsp;Zehra Oksuz,&nbsp;Burcin Turkmenoglu,&nbsp;Erman Salih Istifli,&nbsp;Mehmet Kuzucu,&nbsp;Oztekin Algul","doi":"10.1111/cbdd.14601","DOIUrl":"10.1111/cbdd.14601","url":null,"abstract":"<p>Cumulative escalation in antibiotic-resistant pathogens necessitates the quest for novel antimicrobial agents, as current options continue to diminish bacterial resistance. Herein, we report the synthesis of di-heterocyclic benzazole structures (<b>12–19</b>) and their in vitro evaluation for some biological activities. Compounds <b>16</b> and <b>17</b> demonstrated potent antibacterial activity (MIC = 7.81 μg/mL) against <i>Staphylococcus aureus</i>, along with significant anti-biofilm activity. Noteworthy is the capability of Compound <b>17</b> to inhibit biofilm formation by at least 50% at sub-MIC (3.90 μg/mL) concentration. Furthermore, both compounds exhibited the potential to inhibit preformed biofilm by at least 50% at the MIC concentration (7.81 μg/mL). Additionally, Compounds <b>16</b> and <b>17</b> were examined for cytotoxic effects in HFF-1 cells, using the MTT method, and screened for binding interactions within the active site of <i>S. aureus</i> DNA gyrase using in silico molecular docking technique, employing AutoDock 4.2.6 and Schrödinger Glidse programs. Overall, our findings highlight Compounds <b>16</b> and <b>17</b> as promising scaffolds warranting further optimization for the development of effective antibacterial and anti-biofilm agents.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.14601","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861940","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":"Structural modification of 2-phenylquinoline-4-carboxylic acid containing SIRT3 inhibitors for the cancer differentiation therapy","authors":"Yanmei Du,&nbsp;Xiaojing Wang,&nbsp;Lihui Zhang,&nbsp;Hongyu Qin,&nbsp;Guangzhao Xu,&nbsp;Fahui Li,&nbsp;Chunyan Fang,&nbsp;Honggang Li,&nbsp;Lei Zhang","doi":"10.1111/cbdd.14595","DOIUrl":"10.1111/cbdd.14595","url":null,"abstract":"<p>Inhibition of SIRT3 exhibited potency in triggering leukemic cell differentiation. In discovery of potent SIRT3 inhibitors for cancer differentiation therapy, structural modification was performed on the previously developed lead compound <b>P6</b>. A total of 33 compounds were designed and synthesized. In the enzyme inhibitory assay, several molecules <b>S18</b>, <b>S26</b>, <b>S27</b> and <b>T5</b> showed potent SIRT3 inhibitory activity with IC₅₀ value of 0.53, 1.86, 5.06, and 2.88 μM, respectively. Moreover, the tested compounds exhibited SIRT3 inhibitory selectivity over SIRT1 and SIRT2. Compounds <b>S27</b> and <b>T5</b> were potent in inhibition the growth of MM1.S and RPMI-8226 cells in the in vitro antiproliferative test. Significantly, representative compounds, especially <b>S27</b> and <b>T5</b>, promoted differentiation of tested MM cells in the cellular morphological evaluation, accompanied by increasing the expression of differentiation antigen CD49e and human immunoglobulin light chain lambda and kappa. Additionally, molecule <b>S18</b> without antiproliferative potency itself, showed significant inhibitory activity against growth factor IL-6 induced RPMI-8226 cell proliferation. Collectively, potent SIRT3 selective inhibitors with MM cell differentiation potency were developed for further discovery of anticancer drugs.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861939","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 “Nanoemulsion Based Lipid Nanoparticles for Effective Demethylcantharidin Delivery to Cure Liver Cancer”","authors":"","doi":"10.1111/cbdd.14603","DOIUrl":"10.1111/cbdd.14603","url":null,"abstract":"<p>Z. Yan, T. Yu, X. Wu, et al., “Nanoemulsion Based Lipid Nanoparticles for Effective Demethylcantharidin Delivery to Cure Liver Cancer,” <i>Chemical Biology &amp; Drug Design</i> 104, no. 1 (2024), e14580, https://doi.org/10.1111/cbdd.14580.</p><p>In Paragraph 6 of the “3.1 | Preparation and characterization of DNLNs” section, the text “the zeta potential of DNLNs was −8.21 ± 2.12 mV” was incorrect. This should have read “the zeta potential of DNLNs was −4.87 ± 0.31 mV.”</p><p>We apologize for this error.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.14603","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141857394","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":"Sodium copper chlorophyllin-loaded chitosan nanoparticle-based photodynamic therapy for B16 melanoma cancer cells","authors":"Vinod Ravasaheb Shinde,&nbsp;Sajmina Khatun,&nbsp;Ajinkya Madhukar Thanekar,&nbsp;Basu Bhattacharjee,&nbsp;Aravind Kumar Rengan","doi":"10.1111/cbdd.14594","DOIUrl":"10.1111/cbdd.14594","url":null,"abstract":"<p>Melanoma is one of the most aggressive and fatal skin cancers owing to its ability to metastasize and develop resistance to chemotherapy. Photodynamic therapy (PDT) is a minimally noninvasive treatment modality comprising photosensitizers (PSs), light sources, and endogenous molecular oxygen that exert a localized cytotoxic effect on cancer cells. The current study explores the therapeutic potential of sodium copper chlorophyllin-loaded chitosan nanoparticles (CH-SCC NPs) along with handheld laser-based PDT on B16 cancer cells. A modified chlorophyll derivative identified as sodium copper chlorophyllin (SCC) is a dietary supplement that has anticancer properties. Herein, we have synthesized CH-SCC NPs using the ionic gelation method to enhance the PS's bioavailability and efficiency. Chitosan nanoparticles exhibited high biocompatibility in a normal cell line L929, zebrafish, and chick embryos, and were successfully employed to deliver the SCC to cancer cells. CH-SCC NPs showed an enhanced PDT effect that killed approximately 80%–85% of B16 cells. CH-SCC NPs in combination with a handheld portable laser source showed significant therapeutic potential against the B16 skin cancer cell line. The experimental findings further strengthen our device-repurposing strategy, which suggests that SCC nanoformulations along with handheld laser can be a suitable treatment for skin cancer even in remote areas where power source and treatment cost can be a limitation.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141790266","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":"Quercetin and taxifolin inhibits TMPRSS2 activity and its interaction with EGFR in paclitaxel-resistant breast cancer cells: An in silico and in vitro study","authors":"Durga Bhavani Kundrapu,&nbsp;Amajala Krishna Chaitanya,&nbsp;Kothapalli Manaswi,&nbsp;Seema Kumari,&nbsp;RamaRao Malla","doi":"10.1111/cbdd.14600","DOIUrl":"10.1111/cbdd.14600","url":null,"abstract":"<p>Transmembrane protease/serine (TMPRSS2), a type II transmembrane serine protease, plays a crucial role in different stages of cancer. Recent studies have reported that the triggering epidermal growth factor receptor (EGFR) activation through protease action promotes metastasis. However, there are no reports on the interaction of TMPRSS2 with EGFR, especially in triple-negative triple negative (TNBC). The current study investigates the unexplored interaction between TMPRSS2 and EGFR, which are key partners mediating metastasis. This interaction is explored for potential targeting using quercetin (QUE) and taxifolin (TAX). TMPRSS2 expression patterns in breast cancer (BC) tissues and subtypes have been predicted, with the prognostic significance assessed using the GENT2.0 database. Validation of TMPRSS2 expression was performed in normal and TNBC tissues, including drug-resistant cell lines, utilizing GEO datasets. TMPRSS2 was further validated as a predictive biomarker for FDA-approved chemotherapeutics through transcriptomic data from BC patients. The study demonstrated the association of TMPRSS2 with EGFR through in silico analysis and validates the findings in TNBC cohorts using the TIMER2.0 web server and the TCGA dataset through C-Bioportal. Molecular docking and molecular dynamic simulation studies identified QUE and TAX as best leads targeting TMPRSS2. They inhibited cell-free TMPRSS2 activity like clinical inhibitor of TMPRSS2, Camostat mesylate. In cell-based assays focused on paclitaxel-resistant TNBC (TNBC/PR), QUE and TAX demonstrated potent inhibitory activity against extracellular and membrane-bound TMPRSS2, with low IC₅₀ values. Furthermore, ELISA and cell-based AlphaLISA assays demonstrated that QUE and TAX inhibit the interaction of TMPRSS2 with EGFR. Additionally, QUE and TAX exhibited significant inhibition of proliferation and cell cycle accompanied by notable alterations in the morphology of TNBC/PR cells. This study provides valuable insights into potential of QUE and TAX targeting TMPRSS2 overexpressing TNBC.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141794262","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":"Discovering novel derivatives of STAT3 and HDAC inhibitors with anti-tumor activity","authors":"Yu Yang,&nbsp;Yamin Pu,&nbsp;Xiaoli Huang,&nbsp;Mengya Liao,&nbsp;Yiwen Zhang","doi":"10.1111/cbdd.14593","DOIUrl":"10.1111/cbdd.14593","url":null,"abstract":"<p>In modern cancer therapy, blockage of more than one target is a standard approach, and there are already many dual-target drugs that can achieve multiple inhibition through a single molecule. Herein, we designed and synthesized a series of novel derivatives with signal transducer and activator of transcription 3 (STAT3) and histone deacetylase (HDAC) inhibitory activity through strategy of combining pharmacophore based on the STAT3 inhibitor E28 and HDAC inhibitor MS-275. Among them, compound <b>24</b> (IC₅₀ = 8.22 ± 0.27 μM) showed better anti-tumor activity than the clinical Class I HDAC inhibitor MS-275 (IC₅₀ = 14.65 ± 0.24 μM) in MCF-7 breast cancer cells. Furthermore, the dual inhibition to HDAC and STAT3 of compound <b>24</b> was validated by western blot analysis. The study provides new tool compounds for further exploration of STAT3–HDAC pathway inhibitor achieved with a single molecule.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763240","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":"Evaluation of doxorubicin and β-lapachone analogs as anticancer agents, a biological and computational study","authors":"Itzel Mercado-Sánchez,&nbsp;Julio López,&nbsp;Rogelio Chávez-Rocha,&nbsp;Ismael Vargas-Rodríguez,&nbsp;Adán Bazán-Jiménez,&nbsp;Mariana Segovia-Mendoza,&nbsp;Heriberto Prado-Garcia,&nbsp;Miguel A. Vázquez,&nbsp;Rocío García-Becerra,&nbsp;Marco A. Garcia-Revilla","doi":"10.1111/cbdd.14596","DOIUrl":"10.1111/cbdd.14596","url":null,"abstract":"<p>We have conducted an experimental and computational evaluation of new doxorubicin (<b>4a</b>–<b>c</b>) and β-lapachone (<b>5a</b>–<b>c</b>) analogs. These novel anticancer analogs were previously synthesized, but had not been tested or characterized until now. We have evaluated their antiproliferative and DNA cleavage inhibition properties using breast (MCF-7 and MDA-MB-231) and prostate (PC3) cancer cell lines. Additionally, cell cycle analysis was performed using flow cytometry. Computational studies, including molecular docking, pharmacokinetic properties, and an analysis of DFT and QTAIM chemical descriptors, were performed to gain insights into the electronic structure and elucidate the molecular binding of the new β-lapachone and doxorubicin analogs with a DNA sequence and Topoisomerase II (Topo II)α. Our results show that <b>4a</b> analog displays the highest antiproliferative activity in cancer cell lines by inducing cell death. We observed that stacking interactions and hydrogen bonding are essential to stabilize the molecule-DNA-Topo IIα complex. Moreover, <b>4a</b> and <b>5a</b> analogs inhibited Topo's DNA cleavage activity. Pharmacodynamic results indicated that studied molecules have favorable adsorption and permeability properties. The calculated chemical descriptors indicate that electron accumulation in quinone rings is relevant to the reactivity and biological activity. Based on our results, <b>4a</b> is a strong candidate for becoming an anticancer drug.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763241","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}