Bioorganic & Medicinal Chemistry最新文献

{"title":"Machine learning-driven QSAR modeling combined with molecular dynamics suggests high-affinity CD33-targeting peptides for leukemia therapy","authors":"Mohammad Pirouzbakht ,&nbsp;Saeed Zanganeh ,&nbsp;Ali Afgar ,&nbsp;Roohollah Mirzaee Khalilabadi ,&nbsp;Alireza Farsinejad ,&nbsp;Mohamad Javad Mirzaei-Parsa","doi":"10.1016/j.bmc.2025.118332","DOIUrl":"10.1016/j.bmc.2025.118332","url":null,"abstract":"<div><div>Despite advances in antibody-based therapies for leukemia, significant limitations persist, including immunogenicity, toxicity, and resistance development. To address these challenges, we pursued an innovative peptide-based targeting strategy against CD33, a well-validated surface marker in leukemia. This study establishes a comprehensive pipeline integrating computational design with experimental validation to develop novel CD33-targeting peptides with optimal therapeutic properties.</div><div>Our methodology combined machine learning-based QSAR modeling (achieving R² = 0.93) with molecular docking and 100-ns molecular dynamics simulations to predict and validate peptide-CD33 interactions. From this pipeline, we identified two lead peptides A3K2L2 (AKAKLAL-NH₂) and K4I3 (KKKKIII-NH₂), demonstrating exceptional binding affinities (−146.11 and − 108.08 kcal/mol, respectively) and complex stability (RMSD 0.25–0.35 nm).</div><div>Experimental characterization revealed these peptides form stable reverse β-sheet structures and self-assembling nanostructures while maintaining remarkable selectivity, showing potent cytotoxicity against K-562 cells (IC₅₀ 60–90 μM) with minimal effects on normal PBMCs. Additional safety profiling confirmed low hemolytic activity (&lt;5 %) and favorable induction of cancer cell death through combined apoptotic and necrotic pathways.</div><div>These findings represent a significant advancement in targeted leukemia therapy, offering peptide-based alternatives that overcome key limitations of current antibody treatments. Our integrated design platform provides a generalizable framework for developing receptor-specific anticancer peptides, with particular promise for hematological malignancies where target specificity is paramount.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"129 ","pages":"Article 118332"},"PeriodicalIF":3.3,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of pH on the cytotoxic activity of organic acids against breast cancer cells","authors":"Sungmun Lee","doi":"10.1016/j.bmc.2025.118330","DOIUrl":"10.1016/j.bmc.2025.118330","url":null,"abstract":"<div><div>Breast cancer is the most prevalent cancer among women worldwide. Unlike normal cells, breast cancer cells exhibit a reversed pH gradient characterized by a lower extracellular pH (pH_e, ∼6.7–7.1) and a higher intracellular pH (pH_i, ∼7.4). Modulation of extracellular pH can influence the growth and viability of these cells. In this study, we examined the effects of ten organic acids on MDA-MB-231 metastatic breast cancer cells. Among ten organic acids, dicarboxylic acids (succinic acid (SA), fumaric acid (FA), and tartaric acid (TA)) and tricarboxylic acid (citric acid (CA)) exhibited significantly higher cytotoxicity compared to the others including monocarboxylic acid. Further analysis revealed that their cytotoxic effects were primarily induced by acidic pH associated with the number of <img>COOH in their chemical structures. These acids also impacted cell viability, density, and morphology in both 2D cultures and 3D spheroid models. The results of this research can aid in the development of innovative anticancer drugs treating breast cancer.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"129 ","pages":"Article 118330"},"PeriodicalIF":3.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144711665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"(R)-6-[N-(3-(4-chlorophenyl) propyl] derivative of (R)-roscovitine inhibits lung carcinoma progression via cyclin-dependent kinase suppression","authors":"Jie Guo ,&nbsp;Jianshe Chen ,&nbsp;Weijie Li ,&nbsp;Jinwen Yang ,&nbsp;Abdul Basit ,&nbsp;Siwei Zhang ,&nbsp;Siyuan Wang","doi":"10.1016/j.bmc.2025.118331","DOIUrl":"10.1016/j.bmc.2025.118331","url":null,"abstract":"<div><div>Cyclin-dependent kinases (CDKs) are crucial regulators of cell cycle checkpoints, capable of phosphorylating proteins and thereby governing essential cellular functions such as differentiation, proliferation, and apoptosis. Although various CDK inhibitors (CDKIs), including (<em>R</em>)-roscovitine, also known as seliciclib, have demonstrated promising outcomes in preclinical models, their clinical translation has been limited. This study aimed to design and synthesize (<em>R</em>)-roscovitine derivatives with improved pharmacological profiles. A series of compounds (<strong>4a</strong>–<strong>4q</strong>) was synthesized, structurally validated and evaluated against cancerous cells, including lung carcinoma (A549), triple-negative breast cancer (MDA-MB-231), and malignant melanoma (A375) cells and normal human epithelial (BEAS-2B) and embryonic lung fibroblasts (MRC-5) cells. Furthermore, the compound was assessed for its inhibitory potential against a broad panel of CDKs. Among these, the (<em>R</em>)-6-[<em>N</em>-(3-(4-chlorophenyl) propyl)] analogue (<strong>4 g</strong>) showed the highest inhibition of CDK2 and CDK13, along with potent antiproliferative activity (IC₅₀ = 0.61 ± 0.06 μM) against A549 cells compared to (<em>R</em>)-roscovitine (13.30 ± 1.05 μM). Similarly, Compound <strong>4 g</strong> showed an IC₅₀ value of 1.437 ± 0.17 μM and 1.280 ± 0.37 μM in BEAS-2B and MRC-5 cells, which is 2 to 2.35 folds of the IC₅₀ value in A549 cells. Compound <strong>4 g</strong> significantly (<em>p</em> &lt; 0.0001) induced S-phase cell cycle arrest and suppressed cellular migration and invasion of A549 cells. <em>In silico</em> docking studies revealed a strong and stable interaction with CDK13, with a binding affinity of −8.0 kcal/mol. Compound <strong>4 g</strong> demonstrates promising anticancer potential, likely mediated by CDK inhibition with comparatively lower toxicity toward normal cells, however, it requires further toxicological assessment and preclinical studies.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"129 ","pages":"Article 118331"},"PeriodicalIF":3.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144686419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Indazole partial agonists targeting peripheral cannabinoid receptors","authors":"George Amato,&nbsp;Lucas Laudermilk,&nbsp;Vineetha Vasukuttan,&nbsp;Elaine A. Gay,&nbsp;Ann M. Decker,&nbsp;Rodney Snyder,&nbsp;Yun Lan Yue,&nbsp;Scott Runyon,&nbsp;Rangan Maitra","doi":"10.1016/j.bmc.2025.118327","DOIUrl":"10.1016/j.bmc.2025.118327","url":null,"abstract":"<div><div>Considerable efforts have been made to produce full agonists of cannabinoid receptors (CBRs), but there has been limited reports on partial agonists and the associated structure activity relationship (SAR) studies. Partial agonists of peripheral CBRs may have unique pharmacological profiles that provide prolonged efficacy through delayed or limited development of tolerance, absent or limited psychiatric effects, and good therapeutic index. Some potential therapeutic applications include inflammatory diseases, gastrointestinal (GI) disorders and pain. In this report, we show the SAR developed in the conversion of indazole full agonists to peripheral partial agonists. Compound <strong>45</strong> is a partial agonist of CBRs with 50% Effective Concentration (EC₅₀) of ∼150 nM at human (h)CB1 and 35 nM at hCB2 along with % Maximum Efficacy (E_max) of ∼32 at hCB1 and ∼17 at hCB2 respectively. This compound demonstrated peripheral selectivity and oral absorption in mouse pharmacokinetic (PK) studies with a half-life of ∼7.3 h in plasma and &lt;10% brain penetrance.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"129 ","pages":"Article 118327"},"PeriodicalIF":3.3,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144711756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural insights for peptide and small molecules based drug discovery targeting the KEAP1 Kelch domain: A review","authors":"Suman Sinha ,&nbsp;Ram Kumar ,&nbsp;Niraj Kumar Singh ,&nbsp;M. Arockia Babu","doi":"10.1016/j.bmc.2025.118329","DOIUrl":"10.1016/j.bmc.2025.118329","url":null,"abstract":"<div><div>The KEAP1-Nrf2 pathway plays a pivotal role in redox homeostasis and cellular stress. Abnormal regulation of this pathway results in neurodegenerative diseases, including Alzheimer's Disease and Parkinson's Disease, cancer and diabetes. Targeting the KEAP1 Kelch domain presents a promising therapeutic strategy to regulate Nrf2 activity. Structural insights acquired from macromolecular crystallography have enabled the development of potent inhibitors disrupting the KEAP1-Nrf2 interaction. This article focuses exclusively on compiling studies of the 112 KEAP1 structures co-crystallized with peptides and small molecule ligands over the last 20 years, investigating interactions that govern inhibitory potency. After a thorough review, small molecule ligands have been classified according to their chemical structures, including naphthalene, isoquinoline, benzotriazole, pyrazole, and azabicyclic, along with their biological efficacies to investigate the decisive interactions at the orthosteric site. Among all the reported PDB records of KEAP1, hydrogen bonding, cation–π, π–π stacking, and salt-bridge interactions predominantly contribute to stabilizing protein-ligand complexes. These insights will pave the way for the design and development of selective peptide and small molecule-based ligands for regulating the KEAP1-Nrf2 pathway, providing breakthroughs for the management of various diseases.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"129 ","pages":"Article 118329"},"PeriodicalIF":3.3,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent research progress of β-carbolines as privileged scaffold in the discovery of anticancer agent (2019–2024)","authors":"Fuqiang Yu ,&nbsp;Shutang Li ,&nbsp;Baohu Li ,&nbsp;Peng Zhan ,&nbsp;Xujie Wang ,&nbsp;Jinfei Yang","doi":"10.1016/j.bmc.2025.118325","DOIUrl":"10.1016/j.bmc.2025.118325","url":null,"abstract":"<div><div>Cancer remains a formidable global health challenge, driving the need for targeted therapeutic agents to improve clinical outcomes. Natural and synthetic β-carboline alkaloids, characterized by their indole-based heterocyclic structures, have emerged as privileged scaffolds in oncology drug development due to their multimodal antitumor mechanisms. This review systematically evaluates recent advancements in β-carboline derivatives research, with emphasis on structural modification strategies, structure-activity relationships, and mechanistic elucidation of tumor suppression pathways. Through multidimensional evaluation and analysis, we propose actionable directions for the development of β-carboline derivatives with enhanced pharmacological profiles for treating various cancers.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"129 ","pages":"Article 118325"},"PeriodicalIF":3.3,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144679096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery, synthesis and SAR of 3-aryl pyrazolidines, novel dual orexin receptor antagonists for the treatment of sleep disorders","authors":"Jean-Philippe Surivet,&nbsp;Melanie Kessler,&nbsp;Catherine Vaillant,&nbsp;Jean-Christophe Gauvin,&nbsp;Manon Kiry,&nbsp;Jonathan Gill,&nbsp;Christopher Kohl","doi":"10.1016/j.bmc.2025.118326","DOIUrl":"10.1016/j.bmc.2025.118326","url":null,"abstract":"<div><div>We report a facet of the drug discovery program aimed at identifying dual orexin receptor antagonists (DORAs) suitable for treating sleep disorders requiring a fast onset of action (&lt;30 min) and a short duration of the hypnotic effect (2–4 h). Starting from the previously disclosed orexin antagonist (+)-<strong>6</strong>, we designed a novel and potent DORA, the 3-aryl pyrazolidine (+)-<strong>7</strong>. With the objective of identifying 3-aryl pyrazolidine DORAs that could back-up our preclinical candidate IDOR-1117-1680 DORA <strong>5</strong>, we established structure-activity relationships (SAR) of the three motives substituting the pyrazolidine core of (+)-<strong>7</strong>. These investigations afforded DORA (+)-<strong>27</strong>, whose dog pharmacokinetic (PK) parameters were not supportive of further <em>in vivo</em> studies. Additional investigations afforded DORA (+)-<strong>33</strong>, a 3-aryl pyrazolidine demonstrating improved dog PK parameters and achieving <em>in silico</em> fast and short-action pharmacological requirements. DORA (+)-<strong>33</strong> demonstrated <em>in vivo</em> efficacy in a rat sleep model but it time-dependently inhibited CYP3A4 so its advancement to further <em>in vivo</em> studies was halted.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"129 ","pages":"Article 118326"},"PeriodicalIF":3.3,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144696511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 evaluation of new dihydropyrimidine derivatives as HBV capsid protein inhibitors","authors":"Xiaodan Qiu ,&nbsp;Shengnan Zhao ,&nbsp;Ya Wang ,&nbsp;Kun Xiao ,&nbsp;Yitong Liu ,&nbsp;Yuhuan Li ,&nbsp;Shuo Wu ,&nbsp;Qingguo Meng ,&nbsp;Guangzhi Shan","doi":"10.1016/j.bmc.2025.118320","DOIUrl":"10.1016/j.bmc.2025.118320","url":null,"abstract":"<div><div>The assembly of the capsid is a critical phase in the lifecycle of the hepatitis B virus (HBV). Capsid protein assembly inhibitors can specifically target HBV capsid formation, thereby disrupting its assembly and exerting antiviral effects. In this study, a total of 40 dihydropyrimidine derivatives across four series were synthesized by the modification of solvent-exposed region. The results indicated that compound I-3e exhibited potent anti-HBV activity (EC₅₀ = 0.033 ± 0.012 μM). Mechanistic studies revealed that this compound can dose-dependently inhibit levels of both HBc proteins and capsid proteins. Surface plasmon resonance and molecular docking confirmed the interactions between I-3e and the target protein. Furthermore, predictions regarding the properties of I-3e suggested it aligns well with Lipinski's five rules and is anticipated to possess pharmacokinetic characteristics similar to those of GLS4. This research lays a foundation for discovering effective HBV capsid protein assembly inhibitors.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"129 ","pages":"Article 118320"},"PeriodicalIF":3.3,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144679097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of a potent C20-oxime pachysandra alkaloid analogue promising for treatment of hepatocellular carcinoma","authors":"Chen-Liang Zhao ,&nbsp;Wen-Wen Zhang ,&nbsp;Jin-Feng Zhao ,&nbsp;Jiang-Hai Ye ,&nbsp;Peng Wei ,&nbsp;Juan Zou ,&nbsp;Kang He","doi":"10.1016/j.bmc.2025.118324","DOIUrl":"10.1016/j.bmc.2025.118324","url":null,"abstract":"<div><div>The Miao medicine “Sanliangyin” is derived from the root of the <em>Sarcococca ruscifolia</em> (genus Sarcococca, family Buxaceae), which has been commonly used in Miao regions to treat malignant tumors. Previous research by our group has identified pachysandra alkaloids as the primary active ingredients in this plant, which exhibited anti-tumor properties. However, the low structural diversity and moderate activity of the isolated alkaloids hampered their clinical application. One of the effective strategies to address these challenges is the introduction of bioactive pharmacophores, leading to the development of natural product-pharmacophore hybrids (NPPH) with enhanced drug properties. To the best of our knowledge, oxime groups that introduced into natural products usually have enhanced the anti-cancer activity. Therefore, to develop more potent pachysandra alkaloid analogues with low toxicity, we synthesized a series of derivatives (<strong>7a</strong>-<strong>7</strong> <strong>g</strong>) to increase their structure diversity by introducing various anilines at C-3 and oxime at C-20 positions of epiandrosterone. Using the CCK-8 assay, we found that the IC₅₀ values of the pachysandra alkaloid derivatives against HepG2 liver cancer cells ranged from 0.127 to 1.536 μM. Further evaluation on THP-1 cells showed that, at a concentration of 12.50 μM, the cytotoxicity of the seven compounds ranged from 46.06 % to 100.00 %. Based on cell viability and cytotoxicity assay, we found that compound <strong>7a</strong> exhibited the strongest activity against liver cancer cells while showing the lowest toxicity. Network pharmacology and molecular dynamics simulation studies revealed that compound <strong>7a</strong> had a strong correlation and good binding affinity with the JAK2/STAT3 signaling pathway. Further mechanism studies have shown that compound <strong>7a</strong> could inhibit migration, induce mitochondrion-mediated apoptosis, thereby suppressing cell proliferation in HepG2 cells through regulation of Bcl-2 family proteins and the JAK2/STAT3 signaling pathway.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"129 ","pages":"Article 118324"},"PeriodicalIF":3.3,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144679099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of cytochrome bd oxidase in Mycobacterium tuberculosis by benzothiazole amides","authors":"Rohit Kumar ,&nbsp;Arnab Roy ,&nbsp;Nitin P. Kalia ,&nbsp;Deepak K. Sharma","doi":"10.1016/j.bmc.2025.118323","DOIUrl":"10.1016/j.bmc.2025.118323","url":null,"abstract":"<div><div>Cytochrome <em>bd</em> (Cyt-<em>bd</em>) oxidase, a key enzyme in the <em>Mtb</em> respiratory chain, is particularly crucial for ATP synthesis when the primary cytochrome <em>bc</em>_<em>1</em><em>:aa</em>_<em>3</em> (Cyt-<em>bc</em>_<em>1</em><em>:aa</em>_<em>3</em>) complex is compromised. There are several reported inhibitors of the Cyt-<em>bd</em> oxidase, predominantly featuring quinoline and quinazoline scaffolds. This study explores benzothiazole amides as potential inhibitors of Cyt-bd oxidase for their ability to deplete ATP in the presence of the Cyt-<em>bc</em>_<em>1</em><em>:aa</em>_<em>3</em> inhibitor Q203. These compounds demonstrated significant bactericidal activity against both replicating and non-replicating <em>Mtb</em> strains in this combined approach. Methylene blue assays confirmed their ability to inhibit oxygen consumption, validating their Cyt-<em>bd</em> inhibitory mechanism. Moreover, cytotoxicity studies indicated low toxicity and high selectivity for bacterial cells over mammalian cells. Molecular docking studies elucidated favourable binding interactions with the Cyt-<em>bd</em> protein, while <em>in silico</em> ADME profiling suggested promising pharmacokinetic properties. These results highlight the potential of benzothiazole amides as promising candidates for anti-TB drug development, specifically targeting the Cyt-<em>bd</em> oxidase. Future research will focus on further optimising these compounds and conducting preclinical evaluations to realize their clinical potential as adjuncts in TB therapy.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"129 ","pages":"Article 118323"},"PeriodicalIF":3.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144696510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}