Chemical Biology & Drug Design最新文献

{"title":"Puerarin Decreases the Expression of FUS-Dependent MAPK4 to Inhibit the Development of Triple-Negative Breast Cancer","authors":"Jian Guo,&nbsp;Huiheng Qu,&nbsp;Zhigang Huang,&nbsp;Yu Xue","doi":"10.1111/cbdd.14617","DOIUrl":"10.1111/cbdd.14617","url":null,"abstract":"<div>\u0000 \u0000 <p>Puerarin has been reported to have anticancer properties; however, its mechanism in regulating triple-negative breast cancer (TNBC) remains unclear. Cell function was assessed using a cell counting kit-8 assay, 5-ethynyl-2′-deoxyuridine assay, flow cytometry, and transwell assay. Additionally, the glucose assay kit, lactate assay kit, and ADP/ATP ratio assay kit were used to analyze glucose metabolism. mRNA and protein expression levels were analyzed using qRT-PCR and western blotting assays, respectively. The relationship between FUS RNA binding protein (FUS) and mitogen-activated protein kinase 4 (MAPK4) was determined using an RNA immunoprecipitation assay. TNBC cell malignancy in vitro was validated using a xenograft mouse model assay. Puerarin treatment or MAPK4 knockdown effectively inhibited TNBC cell proliferation, invasion, and glucose metabolism, and induced cell apoptosis. Additionally, puerarin treatment downregulated MAPK4 and FUS expression. Conversely, MAPK4 overexpression attenuated the effects of puerarin in TNBC cells. FUS stabilized MAPK4 mRNA expression in TNBC cells. Furthermore, puerarin decreased MAPK4 expression by downregulating FUS in TNBC cells. Finally, puerarin inhibited tumor formation in vivo. Puerarin inhibited TNBC development by decreasing the expression of FUS-dependent MAPK4, indicating that puerarin may serve as a promising therapeutic agent to hind TNBC.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121336","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":"Dietary Natural Flavonoids: Intervention for MAO-B Against Parkinson's Disease","authors":"Ashini Singh,&nbsp;Suman Sinha,&nbsp;Niraj Kumar Singh","doi":"10.1111/cbdd.14619","DOIUrl":"10.1111/cbdd.14619","url":null,"abstract":"<div>\u0000 \u0000 <p>Parkinson's disease (PD) stands as the second most common neurological disorder after Alzheimer's disease, primarily affecting the elderly population and significantly compromising their quality of life. The precise etiology of PD remains elusive, but recent research has shed light on potential factors, including the formation of α-synuclein aggregates, oxidative stress, neurotransmitter imbalances, and dopaminergic neurodegeneration in the substantia nigra pars compacta (SNpc) region of the brain, culminating in motor symptoms such as bradykinesia, akinesia, tremors, and rigidity. Monoamine oxidase (MAO) is an essential enzyme, comprising two isoforms, MAO-A and MAO-B, responsible for the oxidation of monoamines such as dopamine. Increased MAO-B activity is responsible for decreased dopamine levels in the SNpc region of mid brain which is remarkably associated with the pathogenesis of PD-like manifestations. Inhibitors of MAO-B enhance striatal neuronal responses to dopamine, making them valuable in treating PD, which involves dopamine deficiency. Clinically approved MAO-B inhibitors such as selegiline, L-deprenyl, pargyline, and rasagiline are employed in the management of neurodegenerative conditions associated with PD. Current therapeutic interventions including MAO-B inhibitors for PD predominantly aim to alleviate these motor symptoms but often come with a host of side effects that can be particularly challenging for the patients. While effective, they have limitations, prompting a search for alternative treatments, there is a growing interest in exploring natural products notably flavonoids as potential sources of novel MAO-B inhibitors. In line with that, the present review focuses on natural flavonoids of plant origin that hold promise as potential candidates for the development of novel MAO-B inhibitors. The discussion encompasses both in vitro and in vivo studies, shedding light on their potential therapeutic applications. Furthermore, this review underscores the significance of exploring natural products as valuable reservoirs of MAO-B inhibitors, offering new avenues for drug development and addressing the pressing need for improved treatments in PD-like pathological conditions. The authors of this review majorly explore the neuroprotective potential of natural flavonoids exhibiting notable MAO-B inhibitory activity and additionally multi-targeted approaches in the treatment of PD with clinical evidence and challenges faced in current therapeutic approaches.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121335","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":"Prediction of Drug-Induced Liver Injury: From Molecular Physicochemical Properties and Scaffold Architectures to Machine Learning Approaches","authors":"Yulong Zhao,&nbsp;Zhoudong Zhang,&nbsp;Xiaotian Kong,&nbsp;Kai Wang,&nbsp;Yaxuan Wang,&nbsp;Jie Jia,&nbsp;Huanqiu Li,&nbsp;Sheng Tian","doi":"10.1111/cbdd.14607","DOIUrl":"10.1111/cbdd.14607","url":null,"abstract":"<div>\u0000 \u0000 <p>The process of developing new drugs is widely acknowledged as being time-intensive and requiring substantial financial investment. Despite ongoing efforts to reduce time and expenses in drug development, ensuring medication safety remains an urgent problem. One of the major problems involved in drug development is hepatotoxicity, specifically known as drug-induced liver injury (DILI). The popularity of new drugs often poses a significant barrier during development and frequently leads to their recall after launch. In silico methods have many advantages compared with traditional in vivo and in vitro assays. To establish a more precise and reliable prediction model, it is necessary to utilize an extensive and high-quality database consisting of information on drug molecule properties and structural patterns. In addition, we should also carefully select appropriate molecular descriptors that can be used to accurately depict compound characteristics. The aim of this study was to conduct a comprehensive investigation into the prediction of DILI. First, we conducted a comparative analysis of the physicochemical properties of extensively well-prepared DILI-positive and DILI-negative compounds. Then, we used classic substructure dissection methods to identify structural pattern differences between these two different types of chemical molecules. These findings indicate that it is not feasible to establish property or substructure-based rules for distinguishing between DILI-positive and DILI-negative compounds. Finally, we developed quantitative classification models for predicting DILI using the naïve Bayes classifier (NBC) and recursive partitioning (RP) machine learning techniques. The optimal DILI prediction model was obtained using NBC, which combines 21 physicochemical properties, the <i>VolSurf</i> descriptors and the LCFP_10 fingerprint set. This model achieved a global accuracy (GA) of 0.855 and an area under the curve (AUC) of 0.704 for the training set, while the corresponding values were 0.619 and 0.674 for the test set, respectively. Moreover, indicative substructural fragments favorable or unfavorable for DILI were identified from the best naïve Bayesian classification model. These findings may help prioritize lead compounds in the early stage of drug development pipelines.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047652","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":"Thymoquinone reversed doxorubicin resistance in U87 glioblastoma cells via targeting PI3K/Akt/mTOR signaling","authors":"Mohammad Shimia,&nbsp;Monireh Amini,&nbsp;Armin Ostovar Ravari,&nbsp;Peyman Tabnak,&nbsp;Amir Valizadeh,&nbsp;Mohammad Ghaheri,&nbsp;Bahman Yousefi","doi":"10.1111/cbdd.14587","DOIUrl":"10.1111/cbdd.14587","url":null,"abstract":"<p>Natural compounds such as thymoquinone (TQ) have recently gained increasing attention in treating glioblastoma (GBM). However, the effects of TQ in reversing drug resistance are not completely understood. Therefore, we aimed to examine TQ impacts on GBM cells with doxorubicin (DOX) resistance and the involvement of the PI3K/Akt/mTOR pathway. GBM cancer U87 and U87/DOX (resistant cells) cells were exposed to DOX and TQ, and cell proliferation was assessed by the MTT assay. ELISA was applied to evaluate cell apoptosis. The expression of apoptotic mediators such as Caspase-3, Bax, Bcl-2 and PI3K, Akt, mTOR, P-gp, and PTEN was assessed via qRT-PCR and western blot. We found that a combination of TQ and DOX suppressed dose-dependent cell growth capacity in cells and increased the cytotoxic effects of DOX in resistant cells. In addition, TQ treatment increased DOX-mediated apoptosis in U87/DOX cell lines via modulating the pro- and anti-apoptotic markers. A combination of TQ and DOX upregulated PTEN and downregulated PI3K, Akt, and mTOR, suppressing this signal transduction in resistant cells. In conclusion, we showed TQ potentiated doxorubicin-mediated antiproliferative and pro apoptotic function DOX-resistant glioblastoma cells, which is mediated by targeting and suppressing PI3K/Akt/mTOR signal transduction.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142038017","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":"Alantolactone facilitates ferroptosis in non-small cell lung cancer through promoting FTH1 ubiquitination and degradation","authors":"Yijiao Huang,&nbsp;Pei Xiang,&nbsp;Yuanyuan Chen,&nbsp;Qi Pan,&nbsp;Kemiao Yuan","doi":"10.1111/cbdd.14560","DOIUrl":"10.1111/cbdd.14560","url":null,"abstract":"<p>Alantolactone (ALT), a natural sesquiterpene lactone from <i>Inula helenium L</i>., demonstrates potent antitumor activity in various human cancers, notably non-small cell lung cancer (NSCLC). Despite its recognized efficacy, the precise mechanisms of action remain elusive. Our study aimed to elucidate ALT's impact on NSCLC. Our findings suggested that ALT triggered apoptosis both in vitro and in vivo, underscoring its anticancer potential. Interestingly, the ferroptosis inhibitor (Fer-1), rather than necrostatin-1 (Nec-1) or Z-VAD-FMK, rescued ALT-induced cell death, implicating ferroptosis as pivotal. Subsequent analyses revealed ferroptosis as the primary mechanism underlying ALT-induced NSCLC cell death, supported by markers including ROS accumulation, MDA elevation, GSH depletion, Fe²⁺ generation, and GPX4 reduction. Through DARTS/MS proteomics, we identified FTH1 as the target of ALT-induced ferroptosis. Immunoblotting confirmed ALT's inhibition of FTH1 protein expression and accelerated its degradation in NSCLC cells. Immunoprecipitation assays demonstrated increased FTH1 ubiquitination induced by ALT. Additionally, ALT induced ferroptosis and facilitated Fe²⁺ accumulation via FTH1 ubiquitination. Importantly, ALT displayed potent antitumor effects in a subcutaneous xenograft model in BALB/c-nu/nu nude mice by enhancing ferroptosis. In summary, ALT induced ferroptosis by promoting intracellular Fe²⁺ accumulation through accelerated FTH1 degradation, highlighting its potential as an antitumor agent targeting ferroptosis.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142038016","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 Quinoline (Quinolinone) Derivatives as NADPH Oxidase (NOX) Inhibitors","authors":"Lei Zhang,&nbsp;Xinliang Yang,&nbsp;Rui Yi,&nbsp;Siming Wu,&nbsp;Qianbin Li,&nbsp;Gaoyun Hu,&nbsp;Zhuo Chen","doi":"10.1111/cbdd.14610","DOIUrl":"10.1111/cbdd.14610","url":null,"abstract":"<div>\u0000 \u0000 <p>NADPH oxidases (NOXs) are the sole enzyme in the human body that can directly produce reactive oxygen species. Recent studies have shown that NOXs is a very promising target for the treatment of diabetic nephropathy (DN). Here, a series of quinoline(quinolinone) derivatives have been designed based on pharmacophore strategy, synthesized and evaluated. Among them, 19d exhibits potent antiproliferative and NOXs inhibitory activities, and is worthy for further investigation.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142006106","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":"Benzimidazole–Oxadiazole Hybrids—Development in Medicinal Chemistry: An Overview","authors":"Raveendra Madhukar Bhat,&nbsp;Venkatraman Hegde,&nbsp;Srinivasa Budagumpi,&nbsp;Vinayak Adimule,&nbsp;Rangappa S. Keri","doi":"10.1111/cbdd.14609","DOIUrl":"10.1111/cbdd.14609","url":null,"abstract":"<div>\u0000 \u0000 <p>To increase the success rate of drug discovery, one practical strategy is to begin molecular hybridisation. The presence of two or more pharmacophores in a single unit leads to a pharmacological potency greater than the sum of each individual moiety's potency. Heterocyclic compounds are very widely distributed in nature and are essential for life activities. Benzimidazole and oxadiazole are privileged structures in medicinal chemistry and are widely used in drug discovery and development due to their vast biological properties. The drug-like properties (like pharmacokinetics and pharmacodynamics) of the individual scaffolds can be improved by benzimidazole–oxadiazole chimeric molecules via a molecular hybridisation approach. Benzimidazole and oxadiazole cores can either be fused or incorporated using either functional groups/bonds. Over the last few decades, drug discovery scientists have predicted that these moieties could be interconnected to yield a novel or modified hybrid compound. Benzimidazole and oxadiazole hybrids were identified as the most potent anticancer, antimicrobial, anti-inflammatory, antioxidant, anticonvulsant, antidepressant, antihypertensive and antitubercular agents. In this context, the present review describes the biological properties of benzimidazole–oxadiazole (1,3,4 and 1,2,4) hybrids, their possible structure–activity relationship and the mechanism of action studies presented. This review article is intended to stimulate fresh ideas in the search for rational designs of more active and less toxic benzimidazole–oxadiazole hybrid prospective therapeutic candidates, as well as more effective diagnostic agents and pathologic probes.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001533","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":"Baicalein Enhances Radiosensitivity in Colorectal Cancer via JAK2/STAT3 Pathway Inhibition","authors":"Qingqing Yu,&nbsp;Rongjun Tang,&nbsp;Weixing Mo,&nbsp;Linfang Zhao,&nbsp;Lingdi Li","doi":"10.1111/cbdd.14611","DOIUrl":"https://doi.org/10.1111/cbdd.14611","url":null,"abstract":"<p>Radiation resistance is a crucial factor influencing therapeutic outcomes in colorectal cancer (CRC). Baicalein (BE), primarily derived from <i>Scutellaria baicalensis</i>, has demonstrated anti-CRC properties. However, the impact of BE on the radiosensitivity of CRC remains unclear. This study aimed to evaluate the radiosensitization effects of BE and elucidate its mechanism in CRC radiotherapy. We established an in vitro radioresistant cell model (CT26-R) using parental CRC cells (CT26) subjected to ionizing radiation (IR). CT26-R cells were pretreated with or without BE, followed by transfection with pcDNA-NC and pcDNA-JAK2. The proliferation of CT26-R cells treated with BE and IR was assessed using a colony formation assay. A CRC animal model was developed in BALB/c mice via CT26-R cell transplantation. The radiosensitizing effect of BE on CRC was evaluated in vivo. TUNEL assay was conducted to detect apoptosis in tumor tissue. The expression levels of p-STAT3, JAK2, PD-L1, and SOCS3 in vitro and in vivo were measured by western blotting. Our results demonstrated that BE significantly increased radiosensitivity in vitro and in vivo and enhanced apoptosis in tumor tissues. Additionally, BE significantly downregulated the expression of p-STAT3, JAK2, and PD-L1, and significantly upregulated SOCS3 expression. These in vivo effects were reversed by pcDNA-JAK2. In summary, our data suggest that BE enhances CRC radiosensitivity by inhibiting the JAK2/STAT3 pathway.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.14611","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141994045","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 Jasminoidin Reduces Ischemic Stroke Injury by Regulating Microglia Polarization via PASK-EEF1A1 Axis","authors":"","doi":"10.1111/cbdd.14608","DOIUrl":"10.1111/cbdd.14608","url":null,"abstract":"<p>Wu, J., S. Mao, X. Wu, Y. Zhao, W. Zhang, and F. Zhu. 2024. “Jasminoidin Reduces Ischemic Stroke Injury by Regulating Microglia Polarization via PASK-EEF1A1 Axis.” Chemical Biology &amp; Drug Design, 103: e14354. http://doi.org/10.1111/cbdd.14354</p><p>We apologize for this error.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.14608","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141989790","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":"Exploring the Mechanism of Myrrh in the Treatment of Breast Cancer Based on Network Pharmacology and Cell Experiments","authors":"Wu Tao,&nbsp;Yu Xufeng,&nbsp;Chen Xianmei,&nbsp;Qu Mengrou,&nbsp;Wang Jieqiong,&nbsp;Qiao Mingqi","doi":"10.1111/cbdd.14604","DOIUrl":"10.1111/cbdd.14604","url":null,"abstract":"<div>\u0000 \u0000 <p>This study aimed to investigate the mechanism of action of myrrh in breast cancer (BC) treatment and identify its effective constituents. Data on the compounds and targets of myrrh were collected from the TCMSP, PubChem, and Swiss Target Prediction databases. BC-related targets were obtained from the Genecard database. A protein–protein interaction (PPI) analysis, gene ontology (GO) enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted on the intersecting targets of the disease and drug. The key targets of myrrh in BC treatment were identified based on the PPI network. The active constituents of myrrh were determined through reverse-screening using the top 20 KEGG pathways. Macromolecular docking studies, molecular dynamic (MD) simulations, and cell assays were utilized to validate the active constituents and critical targets. Network pharmacology indicated that VEGFA, TP53, ESR1, EGFR, and AKT1 are key targets of myrrh. Pelargonidin chloride, Quercetin, and Naringenin were identified as the active constituents of myrrh. Macromolecular docking showed that Quercetin and Naringenin have strong docking capabilities with ESR1. The results of MD simulation experiments align with those of molecular docking experiments. Cell and western blot assays demonstrated that Quercetin and Naringenin could inhibit MCF-7 cells and significantly reduce the expression of ESR1 protein. The findings reveal the active constituents, key targets, and molecular mechanisms of myrrh in BC treatment, providing scientific evidence that supports the role of myrrh in BC therapy. Furthermore, the results suggest that network pharmacology predictions require experimental validation for reliability.</p>\u0000 </div>","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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141989791","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}