{"title":"99mTc-Labeled Quinolone-Based Novel Skeletal Tracers for Tumor Visualization through Fibroblast Activation Protein","authors":"Yang Luo, Pengjun Zhang, Zihan Wu, Lenan Zou, Xuedong Bai, Xue Li, Wenhui Gan, Faying Wang, Zhihao Han, Qiao Lin, Feng Wang, Yueqing Gu","doi":"10.1021/acs.jmedchem.5c00132","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.5c00132","url":null,"abstract":"Fibroblast activation protein (FAP) has emerged as a prominent target for tumor diagnosis. Quinoline-based FAP PET tracers demonstrated clinical feasibility. However, there is a relative scarcity of clinical studies on <sup>99m</sup>Tc-labeled FAP SPECT tracers. The existing quinoline-derived <sup>99m</sup>Tc-FAPI tracer exhibits relatively low tumor uptake and suboptimal pharmacokinetic properties, which restrict its clinical application. Consequently, it is necessary to alter the pharmacophores to improve its druggability. In this study, a novel quinolone-based pharmacophore was developed by utilizing scaffold hopping and conformational constrained strategies. Serial screening and preclinical evaluations were conducted. The <sup>99m</sup>Tc-FAPI-YQ3 showed extremely high tumor uptake and excellent pharmacokinetic properties. Additionally, <sup>99m</sup>Tc-FAPI-YQ3 demonstrated reliable safety characteristics and clinical efficacy on four different oncology patients. In conclusion, <sup>99m</sup>Tc-FAPI-YQ3 was a promising radiotracer for FAP-targeted cancer diagnosis, shedding light on substantially advancing SPECT molecular imaging.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":"55 1","pages":""},"PeriodicalIF":7.3,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143627433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jianzhang Yang, Yu Chang, Kaijie Zhou, Weixue Huang, Jean Ching-Yi Tien, Pujuan Zhang, Wenyan Liu, Licheng Zhou, Yang Zhou, Xiaomei Ren, Rahul Mannan, Somnath Mahapatra, Yuping Zhang, Rudana Hamadeh, Grafton Ervine, Zhen Wang, George Xiaoju Wang, Arul M. Chinnaiyan, Ke Ding
{"title":"Discovery of YJZ5118: A Potent and Highly Selective Irreversible CDK12/13 Inhibitor with Synergistic Effects in Combination with Akt Inhibition","authors":"Jianzhang Yang, Yu Chang, Kaijie Zhou, Weixue Huang, Jean Ching-Yi Tien, Pujuan Zhang, Wenyan Liu, Licheng Zhou, Yang Zhou, Xiaomei Ren, Rahul Mannan, Somnath Mahapatra, Yuping Zhang, Rudana Hamadeh, Grafton Ervine, Zhen Wang, George Xiaoju Wang, Arul M. Chinnaiyan, Ke Ding","doi":"10.1021/acs.jmedchem.5c00127","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.5c00127","url":null,"abstract":"Cyclin-dependent kinases 12 and 13 (CDK12/13) have emerged as promising therapeutic targets for castration-resistant prostate cancer (CRPC) and other human cancers. Despite the development of several CDK12/13 inhibitors, challenges remain in achieving an optimal balance of potency, selectivity and pharmacokinetic properties. Here, we report the discovery of <b>YJZ5118</b>, a novel, potent and highly selective covalent inhibitor of CDK12/13 with reasonable pharmacokinetic profiles. <b>YJZ5118</b> effectively inhibited CDK12 and CDK13 with IC<sub>50</sub> values of 39.5 and 26.4 nM, respectively, while demonstrating high selectivity over other CDKs. Mass spectrometry analysis, cocrystal structure determination, and pulldown-proteomic experiments confirmed the compound’s covalent binding mode with CDK12/13. Functionally, <b>YJZ5118</b> efficiently suppressed the transcription of DNA damage response genes, induced DNA damage, and triggered apoptosis. Moreover, the compound significantly inhibited the proliferation of multiple tumor cell lines, particularly prostate cancer cells. Notably, <b>YJZ5118</b> exhibited synergistic effects with Akt inhibitors both in vitro and in vivo.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":"275 1","pages":""},"PeriodicalIF":7.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Quan Wang, Lili Yang, Xiaoyu Xing, Wenjie Liang, Renzhi Wu, Chen Xiong, Meng Wu, Cheng Zhong, Haoke Zhang, Shixuan Wang, Fan Xia, Xiaoding Lou, Dugang Chen* and Jun Dai*,
{"title":"Regio-isomerization Optimization Strategy for Photosensitizers: Achieving Ultrahigh Type I Reactive Oxygen Species Generation to Enhance Cancer Photoimmunotherapy","authors":"Quan Wang, Lili Yang, Xiaoyu Xing, Wenjie Liang, Renzhi Wu, Chen Xiong, Meng Wu, Cheng Zhong, Haoke Zhang, Shixuan Wang, Fan Xia, Xiaoding Lou, Dugang Chen* and Jun Dai*, ","doi":"10.1021/acs.jmedchem.4c0291610.1021/acs.jmedchem.4c02916","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.4c02916https://doi.org/10.1021/acs.jmedchem.4c02916","url":null,"abstract":"<p >Phototherapy, renowned for its noninvasiveness, is widely employed in tumor treatment. However, the tumor microenvironment is usually hypoxic, with insufficient reactive oxygen species (ROS) production, severely limiting its application. Herein, we introduce a regio-isomerization optimization strategy and have synthesized four regio-isomeric photosensitizers featuring a donor–acceptor (D–A) configuration by tactically varying the linkage sites between D and A. Among them, TAF-3 with excellent photostability has an ultrahigh type I ROS production efficiency (4.79 times that of methylene blue) and a photothermal conversion efficiency of 41.7%. TAF-3 improves the conjugation degree; produces an appropriate intramolecular charge transfer effect, which enhances its optical properties and phototherapeutic efficiency; and promotes a stronger immune cell death effect, reducing postoperative melanoma recurrence by 60%. Overall, the optical attributes of D–A type photosensitizers can be tailored through the precision modulation of regio-isomerization, offering a promising avenue for the advancement of clinical photosensitizers suitable for phototherapy.</p>","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":"68 6","pages":"6431–6449 6431–6449"},"PeriodicalIF":6.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143703779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Small-Molecule Modulators Targeting Coactivator-Associated Arginine Methyltransferase 1 (CARM1) as Therapeutic Agents for Cancer Treatment: Current Medicinal Chemistry Insights and Emerging Opportunities.","authors":"Shuqing Li, Wanyi Pan, Chengpeng Tao, Zhihao Hu, Binbin Cheng, Jianjun Chen, Xiaopeng Peng","doi":"10.1021/acs.jmedchem.4c02106","DOIUrl":"10.1021/acs.jmedchem.4c02106","url":null,"abstract":"<p><p>Overexpression of coactivator associated arginine methyltransferase 1 (CARM1) is associated with various diseases including cancer. Therefore, CARM1 has emerged as an attractive therapeutic target and a drug response biomarker for anticancer drug discovery. However, the development of conventional CARM1 inhibitors has been hampered by their limited clinical efficacy, acquired resistance, and inability to inhibit nonenzymatic functions of CARM1. To overcome these challenges, new strategies such as isoform-selective inhibitors, dual-acting inhibitors, targeted protein degradation technology (e.g., PROTACs), and even activators, are essential to enhance the anticancer activity of CARM1 modulators. In this perspective, we first summarize the structure and biofunctions of CARM1 and its association with cancer. Next, we focus on the recent advances in CARM1 modulators, including isoform-selective CARM1 inhibitors, dual-target inhibitors, PROTAC degraders, and activators, from the perspectives of rational design, pharmacodynamics, pharmacokinetics, and clinical status. Finally, we discuss the challenges and future directions for CARM1-based drug discovery.</p>","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":" ","pages":"5024-5054"},"PeriodicalIF":6.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Morena Miciaccia, Olga Maria Baldelli, Cosimo G Fortuna, Gianfranco Cavallaro, Domenico Armenise, Anselma Liturri, Savina Ferorelli, Denise P Muñoz, Alessandro Bonifazi, Francesca Rizzo, Antonella Cormio, Silvana Filieri, Giuseppe Micalizzi, Paola Dugo, Luigi Mondello, Anna Maria Sardanelli, Francesco Bruni, Paola Loguercio Polosa, Maria Grazia Perrone, Antonio Scilimati
{"title":"ONC201-Derived Tetrahydropyridopyrimidindiones as Powerful ClpP Protease Activators to Tackle Diffuse Midline Glioma.","authors":"Morena Miciaccia, Olga Maria Baldelli, Cosimo G Fortuna, Gianfranco Cavallaro, Domenico Armenise, Anselma Liturri, Savina Ferorelli, Denise P Muñoz, Alessandro Bonifazi, Francesca Rizzo, Antonella Cormio, Silvana Filieri, Giuseppe Micalizzi, Paola Dugo, Luigi Mondello, Anna Maria Sardanelli, Francesco Bruni, Paola Loguercio Polosa, Maria Grazia Perrone, Antonio Scilimati","doi":"10.1021/acs.jmedchem.4c01723","DOIUrl":"10.1021/acs.jmedchem.4c01723","url":null,"abstract":"<p><p>Pediatric diffuse intrinsic pontine glioma (DIPG), classified under diffuse midline glioma, is a deadly tumor, with no effective treatments. The human mitochondrial protease <i>h</i>ClpP is a potential DIPG therapeutic target, and this study describes the synthesis of two new series of tetrahydropyridopyrimidindiones (THPPDs) as <i>h</i>ClpP activators. Among the tested compounds, we have identified <b>36</b> (THX6) that shows a strong <i>h</i>ClpP activation (EC<sub>50</sub> = 1.18 μM) and good cytotoxicity in <b>ONC201</b>-resistant cells (IC<sub>50</sub> = 0.13 μM). Studying the oxidation mechanisms on cell membranes, the treatment of DIPG cells with <b>36</b> (THX6) causes a change in levels of fatty acids (PUFAs, MUFAs, and SFAs) compared to untreated cells and dysregulates the level of proteins involved in oxidative phosphorylation, biogenesis, and mitophagy that lead to a global collapse of mitochondrial integrity and function suggesting this as the mechanism through which <b>36</b> (THX6) accomplishes its antitumor activity in DIPG cell lines.</p>","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":" ","pages":"5190-5210"},"PeriodicalIF":6.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jun Jiang, Gang Chen, Weiqin Zhang, Si Qin, Man Li, Shiyi Zhong, Ying Yang, Liuxin Yang, Muqing Shao, Kai Wang*, Qin Li, Chen Jiang, Jingfang Yang, Fang Wang, Shuang Qiu* and Xiang Li*,
{"title":"Pseudonatural Flavonols as Novel Copper Ionophores for NAFLD Intervention via Synergistic Copper Delivery and Flavonoid Activity","authors":"Jun Jiang, Gang Chen, Weiqin Zhang, Si Qin, Man Li, Shiyi Zhong, Ying Yang, Liuxin Yang, Muqing Shao, Kai Wang*, Qin Li, Chen Jiang, Jingfang Yang, Fang Wang, Shuang Qiu* and Xiang Li*, ","doi":"10.1021/acs.jmedchem.4c0292710.1021/acs.jmedchem.4c02927","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.4c02927https://doi.org/10.1021/acs.jmedchem.4c02927","url":null,"abstract":"<p >Copper plays crucial roles in fundamental life processes, including proliferation, metabolism, and survival. Copper deficiency is associated with multiple diseases, such as nonalcoholic fatty liver disease (NAFLD) and Wilson’s disease. Therapeutic programs targeting copper supply are prospectively employed for disease intervention. Herein, we developed biofriendly copper ionophores (<b>HQFs</b>) by constructing pseudonatural flavonols, which possess flavonoid bioactivity and enhanced copper transport properties. In cell models and mice, we found that <b>HQF</b>-mediated copper delivery synergistically, safely, and efficiently intervened in the development of fatty liver. Mechanistically, NAFLD remission involves fatty acid metabolism, anti-inflammatory processes, and pentose phosphate pathway (PPP) enhancement. Our work is the first to propose the utilization of synergistic copper loading and flavonoid activity for NAFLD intervention, which may inform the clinical management of liver disease.</p>","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":"68 6","pages":"6450–6461 6450–6461"},"PeriodicalIF":6.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143703776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhen-Meng Zhang, Si-Yu Zhao, Wen-Qian Liu, Xiao Wu, Jie Tang, Yu-Jie Li, Xi-Bing Hu, Ying-Bo Zhou, Li-Xuan Dai, Mei-Yan Huang, Ping Lan, Ping-Hua Sun, Jun Xu*, Jun Liu* and Jun-Xia Zheng*,
{"title":"Hybrid Molecules of Benzothiazole and Hydroxamic Acid as Dual-Acting Biofilm Inhibitors with Antibacterial Synergistic Effect against Pseudomonas aeruginosa Infections","authors":"Zhen-Meng Zhang, Si-Yu Zhao, Wen-Qian Liu, Xiao Wu, Jie Tang, Yu-Jie Li, Xi-Bing Hu, Ying-Bo Zhou, Li-Xuan Dai, Mei-Yan Huang, Ping Lan, Ping-Hua Sun, Jun Xu*, Jun Liu* and Jun-Xia Zheng*, ","doi":"10.1021/acs.jmedchem.4c0251710.1021/acs.jmedchem.4c02517","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.4c02517https://doi.org/10.1021/acs.jmedchem.4c02517","url":null,"abstract":"<p >The ubiquitous opportunistic pathogen <i>Pseudomonas aeruginosa</i> (<i>P. aeruginosa</i>) causes biofilm-associated drug-resistant infections that often lead to treatment failure. Targeting the bacterium’s quorum sensing (QS) and iron homeostasis presents a promising strategy to combat biofilm formation. This study synthesized benzothiazole-conjugated hydroxamic acid derivatives as dual-acting biofilm inhibitors, and compound <b>JH21</b> was identified as the hit compound with potent submicromolar biofilm inhibitory activity (IC<sub>50</sub> = 0.4 μM). Further mechanistic studies demonstrated not only that the production of virulence was decreased through mainly inhibiting QS system but also that <b>JH21</b> competed for iron with the high-affinity siderophore pyoverdine, inducing iron deficiency and inhibiting biofilm. Moreover, <b>JH21</b> significantly enhanced the efficacy of tobramycin and ciprofloxacin by 200- and 1000-fold, respectively, in a mouse wound infection model. These results emphasized the feasibility of dual-acting biofilm inhibitors against resistant <i>P. aeruginosa</i> infections and the potential of <b>JH21</b> as a novel antibacterial synergist.</p>","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":"68 6","pages":"6210–6232 6210–6232"},"PeriodicalIF":6.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143703777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhen-Meng Zhang, Si-Yu Zhao, Wen-Qian Liu, Xiao Wu, Jie Tang, Yu-Jie Li, Xi-Bing Hu, Ying-Bo Zhou, Li-Xuan Dai, Mei-Yan Huang, Ping Lan, Ping-Hua Sun, Jun Xu, Jun Liu, Jun-Xia Zheng
{"title":"Hybrid Molecules of Benzothiazole and Hydroxamic Acid as Dual-Acting Biofilm Inhibitors with Antibacterial Synergistic Effect against Pseudomonas aeruginosa Infections","authors":"Zhen-Meng Zhang, Si-Yu Zhao, Wen-Qian Liu, Xiao Wu, Jie Tang, Yu-Jie Li, Xi-Bing Hu, Ying-Bo Zhou, Li-Xuan Dai, Mei-Yan Huang, Ping Lan, Ping-Hua Sun, Jun Xu, Jun Liu, Jun-Xia Zheng","doi":"10.1021/acs.jmedchem.4c02517","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.4c02517","url":null,"abstract":"The ubiquitous opportunistic pathogen <i>Pseudomonas aeruginosa</i> (<i>P. aeruginosa</i>) causes biofilm-associated drug-resistant infections that often lead to treatment failure. Targeting the bacterium’s quorum sensing (QS) and iron homeostasis presents a promising strategy to combat biofilm formation. This study synthesized benzothiazole-conjugated hydroxamic acid derivatives as dual-acting biofilm inhibitors, and compound <b>JH21</b> was identified as the hit compound with potent submicromolar biofilm inhibitory activity (IC<sub>50</sub> = 0.4 μM). Further mechanistic studies demonstrated not only that the production of virulence was decreased through mainly inhibiting QS system but also that <b>JH21</b> competed for iron with the high-affinity siderophore pyoverdine, inducing iron deficiency and inhibiting biofilm. Moreover, <b>JH21</b> significantly enhanced the efficacy of tobramycin and ciprofloxacin by 200- and 1000-fold, respectively, in a mouse wound infection model. These results emphasized the feasibility of dual-acting biofilm inhibitors against resistant <i>P. aeruginosa</i> infections and the potential of <b>JH21</b> as a novel antibacterial synergist.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":"15 1","pages":""},"PeriodicalIF":7.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143608308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Quan Wang, Lili Yang, Xiaoyu Xing, Wenjie Liang, Renzhi Wu, Chen Xiong, Meng Wu, Cheng Zhong, Haoke Zhang, Shixuan Wang, Fan Xia, Xiaoding Lou, Dugang Chen, Jun Dai
{"title":"Regio-isomerization Optimization Strategy for Photosensitizers: Achieving Ultrahigh Type I Reactive Oxygen Species Generation to Enhance Cancer Photoimmunotherapy","authors":"Quan Wang, Lili Yang, Xiaoyu Xing, Wenjie Liang, Renzhi Wu, Chen Xiong, Meng Wu, Cheng Zhong, Haoke Zhang, Shixuan Wang, Fan Xia, Xiaoding Lou, Dugang Chen, Jun Dai","doi":"10.1021/acs.jmedchem.4c02916","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.4c02916","url":null,"abstract":"Phototherapy, renowned for its noninvasiveness, is widely employed in tumor treatment. However, the tumor microenvironment is usually hypoxic, with insufficient reactive oxygen species (ROS) production, severely limiting its application. Herein, we introduce a regio-isomerization optimization strategy and have synthesized four regio-isomeric photosensitizers featuring a donor–acceptor (D–A) configuration by tactically varying the linkage sites between D and A. Among them, TAF-3 with excellent photostability has an ultrahigh type I ROS production efficiency (4.79 times that of methylene blue) and a photothermal conversion efficiency of 41.7%. TAF-3 improves the conjugation degree; produces an appropriate intramolecular charge transfer effect, which enhances its optical properties and phototherapeutic efficiency; and promotes a stronger immune cell death effect, reducing postoperative melanoma recurrence by 60%. Overall, the optical attributes of D–A type photosensitizers can be tailored through the precision modulation of regio-isomerization, offering a promising avenue for the advancement of clinical photosensitizers suitable for phototherapy.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":"10 1","pages":""},"PeriodicalIF":7.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143618961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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