Bioorganic & Medicinal Chemistry最新文献

{"title":"Dual inhibitors of butyrylcholinesterase and histone deacetylase 6 for the treatment of Alzheimer’s disease: design, synthesis, and biological evaluation","authors":"Bingbing Lv ,&nbsp;Zhenqi Wang ,&nbsp;Qinjie Wang ,&nbsp;Zhaoxin Xu ,&nbsp;Jixiong Tang ,&nbsp;Yuqiong Pei ,&nbsp;Yaoyao Bian ,&nbsp;Haopeng Sun ,&nbsp;Yao Chen","doi":"10.1016/j.bmc.2025.118219","DOIUrl":"10.1016/j.bmc.2025.118219","url":null,"abstract":"<div><div>To address the multifactorial pathology of Alzheimer’s disease (AD), eighteen butyrylcholinesterase (BChE) and histone deacetylase 6 (HDAC6) dual inhibitors were designed, synthesized, and biologically evaluated. Through structure–activity relationship studies, compound <strong>17</strong> emerged as the most potent candidate, with IC₅₀ value of 0.3 nM for human BChE and 56.7 nM for HDAC6. This compound demonstrated favorable safety profiles, drug-like properties, and significant neuroprotective effects <em>in vitro</em>. In a mouse model of scopolamine-induced cognitive impairment, <strong>17</strong> (10 mg/kg) exhibited excellent safety and markedly improved cognitive deficits. These findings highlight compound <strong>17</strong> as a promising BChE/HDAC6 dual inhibitor, supporting its further development as a potential therapeutic agent for AD.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"127 ","pages":"Article 118219"},"PeriodicalIF":3.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143927400","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":"Synthesis and biological evaluation of 68Ga-DOTA-AngII as a radiotracer for PET/MR imaging of hepatocellular carcinoma","authors":"Ke-Xin Sun ,&nbsp;Zhen-Peng Yu ,&nbsp;Jia-Lun Luo ,&nbsp;Zhi-Qiang Yu ,&nbsp;Hong Zhu ,&nbsp;Tao Wu ,&nbsp;Peng-Fei Dai ,&nbsp;Hongwei Si","doi":"10.1016/j.bmc.2025.118221","DOIUrl":"10.1016/j.bmc.2025.118221","url":null,"abstract":"<div><div>The precise diagnosis of HCC is confronted with severe challenges due to the tumor heterogeneity and insidious symptoms of hepatocellular carcinoma (HCC), and meanwhile the limitations of positron emission tomography (PET) with traditional 2-deoxy-2-[fluorine-18] fluoro-<span>d</span>-glucose (¹⁸F-FDG) tracer. Given that angiotensin II type 1 receptor (AT1R) is significantly upregulated in HCC and closely related to its progression, we have developed a novel ⁶⁸Ga-radiolabeled compound, ⁶⁸Ga-DOTA-AngII (⁶⁸Ga-DOTA-GGDRVYIHPF), and evaluated its HCC detection capability. ⁶⁸Ga-DOTA-AngII demonstrated acceptable stability in both human plasma and phosphate buffered saline. In vivo imaging and in vitro biodistribution analysis in tumor-bearing mice showed that ⁶⁸Ga-DOTA-AngII demonstrate a high tumor uptake, and the tumor tissue exhibited rapid uptake. In brief, this radiotracer possesses a promising potency for imaging the expression of AT1R for further clinical application.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"125 ","pages":"Article 118221"},"PeriodicalIF":3.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143895774","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":"Synthesis and in vivo biological characterization of six carbon-11 sigma-1 receptor radiotracers in rodent and nonhuman primate","authors":"Anil Kumar Soda ,&nbsp;Tianyu Huang ,&nbsp;Wenjuan Zhou ,&nbsp;Hong Chen ,&nbsp;Hao Jiang ,&nbsp;Sandip B. Jadhav ,&nbsp;Zhimin Xing ,&nbsp;Yanbo Yu ,&nbsp;Linlin Tian ,&nbsp;Dean F. Wong ,&nbsp;Joel S. Perlmutter ,&nbsp;Ruiqing Ni ,&nbsp;Tammie L.S. Benzinger ,&nbsp;Zhude Tu","doi":"10.1016/j.bmc.2025.118218","DOIUrl":"10.1016/j.bmc.2025.118218","url":null,"abstract":"<div><div>Six enantiomers of three racemic sigma-1 receptor (<em>σ</em>₁R) ligands were resolved, and absolute configuration was determined. Their high σ₁R potency and selectivity were determined through <em>in vitro</em> binding assays, further validated by molecular docking analysis. Central Nervous System Multiparameter Optimization algorithm (CNS MPO) predicts efficient brain penetration for these enantiomers. Six C-11 radiotracers were radiosynthesized successfully, <em>ex vivo</em> biodistribution in rats showed that (−)-[¹¹C]<strong>7</strong> had high brain uptake of ∼4.8-fold for 5 min versus 60 min. Mouse brain PET imaging studies showed (−)-[¹¹C]<strong>7</strong> and (−)-[¹¹C]<strong>16</strong> have <em>in vivo</em> binding specificity for <em>σ</em>₁R. Macaque PET scans showed high brain uptake for all six radiotracers, with (−)-[¹¹C]<strong>7</strong> peaked at ∼45 min (SUV 2.5), possessing the best washout kinetics and highest cerebellum-to-white matter ratio (∼3.1), in agreement with <em>in vitro</em> or <em>ex vivo</em> measures of <em>σ</em>₁R expression. Radiometabolite analysis showed that no newly formed radiometabolite was observed post-injection of (−)-[¹¹C]<strong>7</strong>. Our data suggest that further evaluation is warranted to determine that (−)-[¹¹C]<strong>7</strong> is a suitable PET radiotracer for imaging <em>σ</em>₁R in the brain of animal and human.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"126 ","pages":"Article 118218"},"PeriodicalIF":3.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143918489","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":"Synthesis of USP5-IN-1 derivatives as novel USP5 inhibitors with potent activity against cholangiocarcinoma cells","authors":"Xuetao Hu ,&nbsp;Zanzhe Yu ,&nbsp;Haoran Zhu ,&nbsp;Haolin Cui ,&nbsp;Fengling Ning ,&nbsp;Junhao Dai ,&nbsp;Jie Zhang ,&nbsp;Yan Li ,&nbsp;Xuemei Zhang","doi":"10.1016/j.bmc.2025.118213","DOIUrl":"10.1016/j.bmc.2025.118213","url":null,"abstract":"<div><div>USP5 is a crucial deubiquitinase involved in regulating various pathophysiological processes, including DNA damage repair, immune responses, pathological pain, and, most notably, oncogenesis. Despite the considerable clinical potential of USP5-targeted inhibitors, their development remains in the early stages. <strong>USP5-IN-1</strong> (also known as compound 64<strong>)</strong> stands out from other USP5 inhibitors due to its reported high selectivity for USP5 and its specific co-crystal structure with the USP5 ZnF-UBD (PDB: 7MS7). However, the activity of <strong>USP5-IN-1</strong> has only been validated in vitro through the inhibition of USP5-catalyzed cleavage of a di-ubiquitin substrate, with its cell membrane penetration ability and intracellular activity still unverified. In this study, we structurally modified <strong>USP5-IN-1</strong> to enhance its cell membrane penetration and inhibitory activity against USP5, and synthesized fifteen <strong>USP5-IN-1</strong> derivatives (compounds <strong>1a-1j</strong>, <strong>2a-2d</strong>, and <strong>3a</strong>). Compared to <strong>USP5-IN-1</strong>, compounds <strong>1a</strong> and <strong>1h</strong> exhibited enhanced inhibitory effects on USP5 deubiquitinase activity, as well as on the proliferation and metastasis of cholangiocarcinoma cells. Mechanistically, <strong>1a</strong> and <strong>1h</strong> significantly inhibited the mTORC1 and Erk1/2 pathways in HCCC9810 cells, without affecting the activation of PKCα, β-catenin or FAK, a pattern consistent with the effects of direct USP5 knockdown. Furthermore, both of the compounds, along with USP5 knockdown, significantly induced cell cycle arrest, apoptosis and ferroptosis. In-silico studies revealed that compounds <strong>1a</strong> and <strong>1h</strong> had significantly lower binding free energies and larger octanol–water partition coefficients than <strong>USP5-IN-1</strong>, indicating stronger affinity for USP5 and improved cell membrane penetration. We believe compounds <strong>1a</strong> and <strong>1h</strong> are promising USP5 inhibitors and merit further investigation.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"126 ","pages":"Article 118213"},"PeriodicalIF":3.3,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143908303","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":"Development of indole derivatives as inhibitors targeting STING-dependent inflammation","authors":"Peng Zhou,&nbsp;Gen Yang,&nbsp;Yan Wang,&nbsp;Yaya Peng,&nbsp;Lingyun Xu,&nbsp;Tao Jiang,&nbsp;Jinliang Ma,&nbsp;Wenpei Dong,&nbsp;Chang-Po Chen","doi":"10.1016/j.bmc.2025.118216","DOIUrl":"10.1016/j.bmc.2025.118216","url":null,"abstract":"<div><div>Constant activation of stimulator of interferon genes (STING), resulting from aberrant metabolism or mutations in <em>STING1</em>, can initiate inflammatory damage or autoimmune disease. STING antagonists have the potential to be used as therapeutics for inflammatory and autoimmune diseases. Based on the structures of the covalent STING inhibitor <strong>H151</strong> and <strong>C178</strong>, we designed, synthesized, and evaluated a novel series of indole derivatives for STING inhibition. Several compounds exhibited efficacious STING inhibitory activity. One of these novel chemical entities, <strong>4dc</strong>, was more potent than <strong>H151</strong>, with IC₅₀ values of 0.14 μM in RAW-Lucia^TM ISG cells and 0.39 μM in THP1-Dual™ cells. The compound effectively relieved the symptoms of renal injury in a cisplatin-induced acute kidney injury mouse model. Compound <strong>4dc</strong> represents a new chemotype of STING inhibitor that deserves further investigation as anti-inflammatory agent.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"126 ","pages":"Article 118216"},"PeriodicalIF":3.3,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143908301","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":"Development of a PSMA and EphA2 dual-receptor-activated fluorescent probe for wash-free prostate cancer cell imaging","authors":"Xingcan Pan ,&nbsp;Xiao Wang ,&nbsp;Yijing Zhang ,&nbsp;Xing Yang","doi":"10.1016/j.bmc.2025.118217","DOIUrl":"10.1016/j.bmc.2025.118217","url":null,"abstract":"<div><div>Prostate cancer (PCa) remains a leading cause of cancer-related mortality in men, underscoring the need for improved diagnostic tools. In this study, a novel dual-receptor-activated fluorescence probe (<strong>9</strong>) designed to simultaneously bind to prostate-specific membrane antigen (PSMA) and erythropoietin-producing hepatocellular receptor type A2 (EphA2), two key biomarkers in PCa, was developed and applied for wash-free cell imaging. The probe was synthesized by conjugating both PSMA- and EphA2-targeting ligands with a sulfonated benzothiazole environment-sensitive dye. <strong>9</strong> demonstrated good binding affinity (<em>K</em>_d = 34 nM for PSMA, 9.70 nM for EphA2) with significant fluorescence activation upon receptor binding (14.1-fold for PSMA; 8.6-fold for EphA2). Cell studies demonstrated <strong>9</strong> showed negligible cytotoxicity and good targeting specificity, which could enable convenient monitoring of the dynamic biological processes in PCa, such as ligand-receptor interactions. The study may also provide insights into the design and applications of multiple-receptor-activated fluorescence probes.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"125 ","pages":"Article 118217"},"PeriodicalIF":3.3,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143890619","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 3-phenyl-[1,2,4]triazolo[4,3-a]pyridine derivatives as potent smoothened inhibitors against colorectal carcinoma","authors":"Fengqiu Guo ,&nbsp;Yangcheng Ai ,&nbsp;Yongxin Chen ,&nbsp;Guowu Wu ,&nbsp;Huanxian Wu ,&nbsp;Jingyun lin ,&nbsp;Ying Jiang ,&nbsp;Jiajie Zhang ,&nbsp;Tingting Zhang","doi":"10.1016/j.bmc.2025.118214","DOIUrl":"10.1016/j.bmc.2025.118214","url":null,"abstract":"<div><div>Smoothened (SMO) in Hedgehog (Hh) signaling pathway is intricately associated with the genesis of colorectal carcinoma (CRC), but SMO inhibitor Vismodegib lacks of therapeutic benefits. Based on the principles of preserving critical interactions and ring substitution, a series of 3-phenyl-[1,2,4]triazolo[4,3-<em>a</em>]pyridine derivatives were designed and synthesized. Among them, compound <strong>A11</strong> exhibited significant inhibitory activity against SMO^WT (IC₅₀ = 0.27 ± 0.06 µM) and SMO^D473H (IC₅₀ = 0.84 ± 0.12 µM), respectively, while displayed negligible toxicity towards normal cells. Furthermore, <strong>A11</strong> demonstrated superior antiproliferative activity against CRC cells compared to Vismodegib. In additions, <strong>A11</strong> competitively bound to SMO and inhibit its downstream signaling pathways. Molecular modeling studies suggested that the triazolopyridine ring of <strong>A11</strong> may contribute to the important interaction for binding to SMO. In sum, these results suggest that <strong>A11</strong> deserves further investigation as a SMO inhibitor for CRC treatment.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"125 ","pages":"Article 118214"},"PeriodicalIF":3.3,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143895773","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 of potent and proteolytically stable double biaryl-stapled GLP-1R/GIPR peptide dual agonists","authors":"Yifang Yang ,&nbsp;Qing Lin","doi":"10.1016/j.bmc.2025.118215","DOIUrl":"10.1016/j.bmc.2025.118215","url":null,"abstract":"<div><div>The successful treatment of type 2 diabetes and obesity with tirzepatide highlights the dual agonists of glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic peptide receptor (GIPR) as a powerful new generation of anti-diabetic drugs. However, tirzepatide and other GLP-1R/GIPR dual agonists currently in clinical development are linear peptides susceptible to proteolytic cleavage, thus preventing their uses as oral drugs. Previously, we reported the design of the proteolytically stable GLP-1R/GIPR peptide dual agonists via sidechain biaryl stapling. Although the stapled peptides exhibit improved proteolytic stability, they are still not sufficiently stable for oral delivery. Here, we report on the design and synthesis of more stable GLP-1R/GIPR dual agonists through a combined use of double biaryl stapling and α-methylation. One of the double-stapled and α-methylated peptides, DA23-Bpy^10,17Bpy^21,28, showed more potent and balanced dual agonist activities than tirzepatide, a half-life of 30 min in simulated intestinal fluid, and equal glucose lowering activity compared to semaglutide in oral glucose tolerance test in rodents. These potent and proteolytically stable double biaryl-stapled analogs should provide valuable lead peptides for developing oral GLP-1R/GIPR dual agonist drugs to treat diabetes and obesity.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"125 ","pages":"Article 118215"},"PeriodicalIF":3.3,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143890623","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":"Saturation transfer difference (STD)-NMR spectroscopy in drug discovery: A comprehensive review on identified potential hits based on natural and synthetic scaffolds against therapeutic drug targets","authors":"Salar Hafez-Ghoran ,&nbsp;Uzma Salar","doi":"10.1016/j.bmc.2025.118212","DOIUrl":"10.1016/j.bmc.2025.118212","url":null,"abstract":"<div><div>Among the various multiple nuclear magnetic resonance (NMR) approaches available, saturation transfer difference (STD) NMR spectroscopy has proven to be highly effective in identifying potential binders (ligands). Researchers increasingly recognize the integration of STD-NMR data with ligand-receptor docking studies as a reliable approach for elucidating binding modes at an atomic level. Beyond drug discovery, STD-NMR provides significant contributions to fundamental biological interactions. This review compiles natural and synthetic molecules identified as potential binders through STD-NMR spectroscopy for specific targets associated with chronic diseases, including cancers, neurological disorders, infectious diseases, and others. In cancer research, STD-NMR has helped identify ligands targeting B-cell lymphoma 2, fucosyltransferase 2, ubiquitin ligase, RNA-binding protein HuR, microtubules, cadherins, and urease. Similarly, various synthetic and natural scaffolds have been identified as modulators of enzymes and proteins implicated in neurological disorders, such as acetylcholinesterase, butyrylcholinesterase, amyloid beta, and α1A- and α1B-adrenoceptors. This review also highlights potential identified hits for validated and emerging drug targets in infectious and other diseases.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"125 ","pages":"Article 118212"},"PeriodicalIF":3.3,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143895772","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 tetracyclic 1,2,4-triazoline-fused dibenzo[b,f][1,4]oxazepine as a potent anti-colorectal cancer agent with good efficacy and low toxicity","authors":"Qiwen Shi ,&nbsp;Tao Zhou ,&nbsp;Yuqi Zhou ,&nbsp;Zhi-Hao Wang ,&nbsp;Yao-Jie Xue ,&nbsp;Ya-Jing Chen","doi":"10.1016/j.bmc.2025.118203","DOIUrl":"10.1016/j.bmc.2025.118203","url":null,"abstract":"<div><div>A series of tetracyclic 1,2,4-triazoline-fused dibenzo[<em>b,f</em>][1,4]oxazepines were evaluated as novel anti-tumor agents. MTT assay conducted in four human cancer cell lines (SW620, A549, MCF-7, HepG2) showed that 1,2,4-triazoline-fused dibenzo[<em>b,f</em>][1,4]oxazepine decorated by a methyl group on the benzene ring of 1,2,4-triazoline moiety exhibited a superior antiproliferative activity against SW620 cells with a IC₅₀ value of 0.86 μM. The above compound was thus chosen for further investigation on its anti-colorectal cancer (CRC) effect, and displayed inhibitory effects on the proliferation of HCT116 and CT26 cells with IC₅₀ values of 0.96 μM and 1.71 μM, respectively. Furthermore, this compound could effectively suppress colony formation and induce cell cycle arrest and apoptosis in SW620 cells. Western blot analysis demonstrated that it exerted the anti-tumor activity through blocking the PI3K-AKT signaling pathway. Next, we examined its <em>in vivo</em> anti-tumor activity by establishing a subcutaneous CT26 xenograft model, and found that it significantly reduced the tumor sizes with limited toxicity. Collectively, these findings suggest that this compound could be utilized as a promising candidate against CRC.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"125 ","pages":"Article 118203"},"PeriodicalIF":3.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859596","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}