Chemical Biology & Drug Design最新文献

{"title":"In silico optimization of analogs derived pro-adrenomedullin peptide to evaluate antimicrobial potential","authors":"Raquel M. Quigua-Orozco,&nbsp;Isadora E. P. Andrade,&nbsp;Karen G. N. Oshiro,&nbsp;Samilla B. Rezende,&nbsp;Alexandre Duarte O. Santos,&nbsp;Julia A. L. Pereira,&nbsp;Viviane G. da Silva,&nbsp;Danieli F. Buccini,&nbsp;William F. Porto,&nbsp;Maria L. R. Macedo,&nbsp;Marlon H. Cardoso,&nbsp;Octávio L. Franco","doi":"10.1111/cbdd.14588","DOIUrl":"10.1111/cbdd.14588","url":null,"abstract":"<p>Diverse computational approaches have been widely used to assist in designing antimicrobial peptides with enhanced activities. This tactic has also been used to address the need for new treatment alternatives to combat resistant bacterial infections. Herein, we have designed eight variants from a natural peptide, pro-adrenomedullin N-terminal 20 peptide (PAMP), using an in silico pattern insertion approach, the Joker algorithm. All the variants show an α-helical conformation, but with differences in the helix percentages according to circular dichroism (CD) results. We found that the C-terminal portion of PAMP may be relevant for its antimicrobial activities, as revealed by the molecular dynamics, CD, and antibacterial results. The analogs showed variable antibacterial potential, but most were not cytotoxic. Nevertheless, PAMP2 exhibited the most potent activities against human and animal-isolated bacteria, showing cytotoxicity only at a substantially higher concentration than its minimal inhibitory concentration (MIC). Our results suggest that the enhanced activity in the profile of PAMP2 may be related to their particular physicochemical properties, along with the adoption of an amphipathic α-helical arrangement with the conserved C-terminus portion. Finally, the peptides designed in this study can constitute scaffolds for the design of improved sequences.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763251","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":"Peptide derived from plant defensins: A promising 68Ga radiolabelled agent for diagnostic of infection foci in PET","authors":"Jessica Osorio,&nbsp;Roberto Castro Rosas,&nbsp;Mariana Barraco Vega,&nbsp;Ana Laura Reyes,&nbsp;Andrea Paolino,&nbsp;Florencia Menéndez,&nbsp;Mauricio Vega-Teijido,&nbsp;Eduardo Savio,&nbsp;Javier Giglio,&nbsp;Gianna Cecchetto,&nbsp;Mariella Terán","doi":"10.1111/cbdd.14578","DOIUrl":"10.1111/cbdd.14578","url":null,"abstract":"<p>The development of new radiopharmaceuticals for the detection of hidden infection foci has great relevance for early detection and the selection of the correct treatment, particularly in immunosuppressed patients. In that sense, the labelling of antimicrobial peptides (AMPs) that are capable of binding specifically to the pathogenic microorganism which causes the infection, should provide a sufficiently specific agent, able to distinguish an infection from a sterile inflammation. Defensins are particularly interesting molecules with antimicrobial activity, the EcgDf1 defensin was identified from the genome of a Uruguayan native plant, <i>Erythrina crista</i>-<i>galli</i>, the ‘Ceibo’ tree. Our group has previously reported a synthetic biologically active short analogue EcgDf21 (ERFTGGHCRGFRRRCFCTKHC) successfully labelled with ^99mTc. Herein we present a shorter analogue which also preserves the γ-core domain, as a pharmacophore for a potential infection detection agent. This peptide was derivatized with the bifunctional chelating agent 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) through a lysine linker in the amino-terminal group (NOTA-KGHCRGFRRRC) and radiolabelled with ⁶⁸Ga ([⁶⁸Ga]Ga-NOTA-K-EcgDf1₍₁₀₎). The [⁶⁸Ga]Ga-NOTA-K-EcgDf1₍₁₀₎ labelling procedure rendered a product with high radiochemical purity and stability in the labelling milieu. The Log P value indicated that the complex has a hydrophilic behaviour, confirmed by the biodistribution profile. The [⁶⁸Ga]Ga-NOTA-K-EcgDf1₍₁₀₎ complex demonstrated specific binding to cultures of <i>Candida albicans</i> and <i>Aspergillus niger</i>. Its biodistribution showed renal elimination and low accumulation in the rest of the body. It was possible to successfully differentiate sterile inflammation from infection by PET images in nude mice with a target/non-target ratio of 3.3 for <i>C</i>. <i>albicans</i> and 3.7 for <i>A. niger</i>, respectively.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141753554","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":"Pterostilbene exerts anti-lung squamous cell carcinoma function by suppressing the level of KANK3","authors":"Hua He,&nbsp;Tian Li","doi":"10.1111/cbdd.14597","DOIUrl":"10.1111/cbdd.14597","url":null,"abstract":"<p>Early detection of lung squamous cell carcinoma (LUSC) has a significant impact on clinical outcomes, and pterostilbene (PT) is a natural compound with promising anti-oncogenic activities. This study aimed to identify potential LUSC biomarkers through a series of bioinformatic analyses and clinical verification and explored the interaction between PT and selected biomarkers during the treatment of LUSC. The analysis of the expression profile of the clinical samples of LUSC was performed to identify dysexpressed genes (DEGs) and validated by IHC. The role of KANK3 in the anti-LUSC effects of PT was assessed with a series of in vitro and in vivo assays. 4335 DEGs were identified, including 1851 upregulated genes and 2484 downregulated genes. Survival analysis showed that KANK3 was significantly higher in patients with LUSC with an advanced tumor stage. In in vitro assays, PT suppressed cell viability, induced apoptosis, and inhibited migration and invasion in LUSC cell lines, which was associated with downregulation of KANK3. After the reinduction of the KANK3 level in LUSC cells, the anti-LUSC function of PT was impaired. In mice model, reinduction of KANK3 increased tumor growth and metastasis even under the treatment of PT. The findings outlined in the current study indicated that PT exerted anti-LUSC function in a KANK3 inhibition-dependent manner.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141753582","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":"Transition metal complexes of hydrazones as potential antimicrobial and anticancer agents: A short review","authors":"Izabela Czyżewska,&nbsp;Liliana Mazur,&nbsp;Łukasz Popiołek","doi":"10.1111/cbdd.14590","DOIUrl":"10.1111/cbdd.14590","url":null,"abstract":"<p>Hydrazones display an interesting profile of biological activities, which includes mainly antimicrobial and antiproliferative properties. Hydrazones also play an important role in the synthesis of heterocyclic rings and in coordination chemistry. Currently, the synthesis of complexes of hydrazones with transition metals is quite frequently reported in the scientific literature. The interest in this topic is largely due to diverse biological activities of the metal complexes of hydrazones that in some cases are much more effective than hydrazones themselves. This review focuses on the complexes of hydrazones with transition metals which display antibacterial, antitubercular, antifungal and anticancer activities. In the following subchapters devoted to a given activity, an attempt has been made to present the most active complexes of hydrazones, their trends in their activity and application in medicinal chemistry. The paper presents the literature data from 2009 to 2023. This review constitutes a useful guide for the researchers who intend to synthesize and investigate complexes of hydrazones in terms of their antimicrobial and anticancer activities.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749968","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":"A series of quinazolin-4(3H)-one-morpholine hybrids as anti-lung-cancer agents: Synthesis, molecular docking, molecular dynamics, ADME prediction and biological activity studies","authors":"Feyzi Sinan Tokalı,&nbsp;Halil Şenol,&nbsp;Şeyma Ateşoğlu,&nbsp;Fahri Akbaş","doi":"10.1111/cbdd.14599","DOIUrl":"10.1111/cbdd.14599","url":null,"abstract":"<p>In this study, we synthesized 15 novel quinazoline-morpholinobenzylideneamino hybrid compounds from methyl anthranilate and we assessed their cytotoxicity via in vitro assays against A549 and BEAS-2B cell lines. Molecular docking studies were conducted to evaluate the protein-ligand interactions and inhibition mechanisms on nine different molecular targets, while molecular dynamics (MD) simulations were carried out to assess the stability of the best docked ligand–protein complexes. Additionally, ADME prediction was carried out to determine physicochemical parameters and drug likeness. According to the cytotoxicity assays, compound <b>1</b> (IC₅₀ = 2.83 μM) was found to be the most active inhibitor against A549 cells. While the selectivity index (SI) of compound <b>1</b> is 29, the SI of the reference drugs paclitaxel and sorafenib, used in this study, are 2.40 and 4.92, respectively. Among the hybrid compounds, <b>1</b> has the best docking scores against VEGFR1 (−11.744 kcal/mol), VEGFR2 (−12.407 kcal/mol) and EGFR (−10.359 kcal/mol). During MD simulations, compound <b>1</b> consistently exhibited strong hydrogen bond interactions with the active sites of VEGFR1 and 2, and these interactions were maintained for more than 90% of the simulation time. Additionally, the RMSD and RMSF values of the ligand–protein complexes exhibited high stability at their minimum levels around 1–2 Å. In conclusion, these findings suggest that compound <b>1</b> may be a potent and selective inhibitor candidate for lung cancer treatment and inhibition of VEGFR2, especially.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749967","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":"MW-19, a dihydropyrazole derivative, induces human triple-negative breast cancer cell apoptosis by targeting apoptosis-related pathways","authors":"Nanting Zou,&nbsp;Runfang Wu,&nbsp;Zhao Wu,&nbsp;Chunfei Zhang,&nbsp;Haohong Zhang,&nbsp;Qingyan Mo,&nbsp;Mingqian Ju,&nbsp;Xinan Shi,&nbsp;Zewei Mao,&nbsp;Chunping Wan","doi":"10.1111/cbdd.14589","DOIUrl":"10.1111/cbdd.14589","url":null,"abstract":"<p>Previous studies have indicated that heterocyclic substituted dihydropyrazole derivatives, particularly MW-19, potentially exert anticancer activity in vitro; however, the underlying mechanism remains unknown. The present study was designed to investigate the mechanisms underlying MW-19 activity in triple-negative breast cancer cells. A sulforhodamine B assay was performed to evaluate cell proliferation inhibition rates, and the antitumor effect of MW-19 was evaluated in mice with HCC-1806 xenografts. Apoptosis was analyzed by Hoechst 33342 and annexin V/propidium iodide staining. Expression of pro- and antiapoptotic proteins and mRNA were analyzed by western blotting and reverse transcription-quantitative (RT-q) PCR, respectively. We found that MW-19 significantly inhibited HCC-1806 cell proliferation in a dose- and time-dependent manner, and significantly inhibited MDA-MB-231 cell migration. Importantly, oral administration of MW-19 significantly inhibited HCC-1806 tumor growth in BALB/c-nu/nu mice. Moreover, MW-19 treatment induced marked apoptosis and G2/M arrest in the sensitive cell line, HCC-1806. RT-qPCR analysis showed that levels of proapoptotic genes (Bax, caspase-3, caspase-7, and Fas) were considerably increased in the MW-19 group relative to the control group, while those of antiapoptotic factors (Bcl-2, C-MYC) were dramatically decreased. Consistently, Bax, caspase-3, and caspase-7 were significantly induced after MW-19 treatment, while levels of phosphorylated (p-)AKT, p-PI3K, p-ERK, and the antiapoptotic protein, Bcl-2, were clearly diminished, and the P38 MAPK signaling pathway was activated. Furthermore, P38 pharmacological inhibitors abrogated MW-19-induced apoptosis. Together, our findings indicate that MW-19 exerts antitumor effects by targeting PI3K/AKT and ERK/P38 signaling pathways.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141731697","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":"Nanoemulsion based lipid nanoparticles for effective demethylcantharidin delivery to cure liver cancer","authors":"Zijun Yan,&nbsp;Ting Yu,&nbsp;Xiaoping Wu,&nbsp;Mengyue Deng,&nbsp;Panpan Wei,&nbsp;Ning Su,&nbsp;Yuzhen Ding,&nbsp;Die Xia,&nbsp;Yuehui Zhang,&nbsp;Liangming Zhang,&nbsp;Tong Chen","doi":"10.1111/cbdd.14580","DOIUrl":"10.1111/cbdd.14580","url":null,"abstract":"<p>Demethylcantharidin (DEM) is a widely used antitumor drug; however, its poor tumor targeting and serious organotoxicity limit its application. The aim of this study was to develop a new drug delivery system for efficient delivery of DEM. Nanoemulsion based lipid nanoparticles containing demethylcantharidin (DNLNs) were prepared by loading nanoemulsions into lipid nanoparticles. The cells proliferation, apoptosis, cycle, and uptake were investigated by Cell counting kit-8 (CCK-8), flow cytometry, and in situ fluorescence assays, respectively. Then, we established the H22 tumor-bearing mouse model to evaluate the antitumor efficacy of DNLNs and further studied its organ toxicity and distribution. DNLNs significantly inhibited the proliferation and promoted apoptosis of H22 cells, and H22 cells could take up more DNLNs. Compared with DEM, DNLNs had certain tumor-targeting properties, and the tumor inhibition rate increased by 23.24%. Moreover, DNLNs can increase white blood cell count and reduce organ toxicity. This study paves the way for nanoemulsion-based lipid nanoparticle (NLNs)-efficient DEM delivery to treat liver cancer.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141731698","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":"Investigating potential mechanisms of vitamin D against thyroid cancer via network pharmacology and experimental validation","authors":"Bin Liu,&nbsp;Bowen Hou,&nbsp;Yu Zhao,&nbsp;Fengyi Gao,&nbsp;Xiaoyin Dong,&nbsp;Jiageng He","doi":"10.1111/cbdd.14586","DOIUrl":"10.1111/cbdd.14586","url":null,"abstract":"<p>Thyroid cancer (TC) is one of the most common endocrine malignancies worldwide. Increasing evidence suggests that vitamin D (VD) has potential benefits in the treatment of TC. However, evidence regarding the targets and molecular mechanisms of VD in TC remains limited. In this study, we conducted network pharmacology, molecular docking, and experimental evaluation to explore the target genes, biological functions, and signaling pathways involved in this process. Network analysis revealed 77 potential target genes of VD against TC, and four hub target genes were identified: ESR1, KIT, CCND1, and PGR. Furthermore, we identified the biological processes (BP) and signaling pathways involving these potential target genes, and then determined the possible interaction between the hub targets and VD through molecular docking. Finally, through in vitro experiments, we found that VD effectively inhibits the proliferation of TC cells and downregulates the expression of the ESR1 gene. In conclusion, the effects of VD against TC involve multiple biological targets, BP, and signaling pathways. These findings provide scientific evidence for the application of VD in the treatment of TC.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141629576","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":"Integrative analysis of ex vivo studies and microarray reveals the novel inhibitor effects of trehalose on the pathogenesis of pterygium","authors":"Yasin Durkal,&nbsp;Kubilay İnci,&nbsp;Onur Tokgun,&nbsp;Ugur Yilmaz,&nbsp;Banu Candan Yılmaz","doi":"10.1111/cbdd.14571","DOIUrl":"10.1111/cbdd.14571","url":null,"abstract":"<p>Pterygium is a frequent eye surface condition that is characterized by a high rate of proliferation, fibrovascular development, cellular migration, corneal infiltration, and angiogenesis. We investigated that ex vivo primary pterygium and conjunctival cell cultures were generated to analyze the effect of trehalose on cellular proliferation. After trehalose treatment, we performed microarray analysis to evaluate changes in the mRNA profile. We analyzed gene ontology (GO) and KEGG pathways to identify hub genes that changed expression levels after treatment and were associated with pterygium development. We selected three genes to verify their expression levels using qRT–PCR. The study also evaluated the impact of trehalose treatment on cell migration through a wound-healing assay. Our results suggested that pterygium cell proliferation was inhibited in a dose-dependent manner by trehalose. 2354 DEG were identified in pterygium and conjunctiva cells treated with trehalose compared to untreated groups. Functional enrichment analysis showed that differentially expressed mRNAs are involved in proliferation, vasculature development, and cell migration. We identified ten hub genes including upregulated (<i>RANBP3L, SLC5A3, RERG, ANKRD1, DHCR7, RAB27B, GPRC5B, MSMO1, ASPN, DRAM1</i>) and downregulated (<i>TNC, PTGS2, GREM2, NPTX1, NR4A1, HMOX1, CXCL12, IL6, MYH2, TXNIP</i>). Microarray analysis and functional investigations suggest that trehalose affects the pathogenesis of pterygium by modifying the expression of genes involved in crucial pathways related to cell function.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.14571","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141629575","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":"Therapeutic potential and recent progression of BTK inhibitors against rheumatoid arthritis","authors":"Swati Paliwal,&nbsp;Sandhya Bawa,&nbsp;Nishtha Shalmali,&nbsp;Rajiv K. Tonk","doi":"10.1111/cbdd.14582","DOIUrl":"10.1111/cbdd.14582","url":null,"abstract":"<p>Rheumatoid arthritis (RA) is a complex chronic inflammatory illness that affects the entire physiology of human body. It has become one of the top causes of disability worldwide. The development and progression of RA involves a complex interplay between an individual's genetic background and various environmental factors. In order to effectively manage RA, a multidisciplinary approach is required, as this disease is complicated and its pathophysiological mechanism is not fully understood yet. In majority of arthritis patients, the presence of abnormal B cells and autoantibodies, primarily anti-citrullinated peptide antibodies and rheumatoid factor affects the progression of RA. Therefore, drugs targeting B cells have now become a hot topic in the treatment of RA which is quite evident from the recent trends seen in the discovery of various B cell receptors (BCRs) targeting agents. Bruton's tyrosine kinase (BTK) is one of these recent targets which play a role in the upstream phase of BCR signalling. BTK is an important enzyme that regulates the survival, proliferation, activation and differentiation of B-lineage cells by preventing BCR activation, FC-receptor signalling and osteoclast development. Several BTK inhibitors have been found to be effective against RA during the in vitro and in vivo studies conducted using diverse animal models. This review focuses on BTK inhibition mechanism and its possible impact on immune-mediated disease, along with the types of RA currently being investigated, preclinical and clinical studies and future prospective.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141629580","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}