Yang Tian, Yanzhuo Liu, Jianyu Liu, Jing Luo, Jingwen Zhang, Xiong Zhang, Hengkang He, Yixi Xiao, Jianhui Zhang, Tao Yang
{"title":"Identification of a novel compound containing benzyloxy terminal structure as a selective TYK2 inhibitor for the treatment of inflammatory diseases","authors":"Yang Tian, Yanzhuo Liu, Jianyu Liu, Jing Luo, Jingwen Zhang, Xiong Zhang, Hengkang He, Yixi Xiao, Jianhui Zhang, Tao Yang","doi":"10.1016/j.ejmech.2025.118211","DOIUrl":"https://doi.org/10.1016/j.ejmech.2025.118211","url":null,"abstract":"In this study, we described three series of <em>N</em>-phenylpyrimidin-2-amine derivatives as selective TYK2 inhibitors. Systematic exploration of the structure-activity relationship through the introduction of an O-linker and the flexible benzyl substituent based on the reported non-selective JAKs inhibitor <strong>yt52</strong> led to the discovery of the optimized derivative compound <strong>29i</strong>. Compound <strong>29i</strong> showed a potency on TYK2 with an IC<sub>50</sub> value of 18 nM and exhibited more than >70-fold selectivity over JAK1/2/3 isoforms. Kinase panel screening, WB assays, and human peripheral blood mononuclear cell assays further validated the selectivity of compound <strong>29i</strong>. Compound <strong>29i</strong> demonstrated pharmacokinetic properties with an oral bioavailability of 42.7 %. Moreover, in models of inflammatory disease (allergic rhinitis) and autoimmune disease (alopecia areata), compound <strong>29i</strong> demonstrated comparable therapeutic effects to market drugs. Taken together, these findings establish that compound <strong>29i</strong> is a selective TYK2 inhibitor with compelling potential for clinical development.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"103 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145229298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andres Valdivia, Joshua L. Zhu, Vanessa Hernandez, Purav P. Vagadia, Natalia Masnica, Ana Maria Isac, Qin Changyuan, Hao Huang, Salvatore Condello, Sandra Orsulic, Gary E. Schiltz, Daniela Matei
{"title":"Novel PROTACs targeting tissue transglutaminase (TG2) suppress tumorigenicity of ovarian cancer cells","authors":"Andres Valdivia, Joshua L. Zhu, Vanessa Hernandez, Purav P. Vagadia, Natalia Masnica, Ana Maria Isac, Qin Changyuan, Hao Huang, Salvatore Condello, Sandra Orsulic, Gary E. Schiltz, Daniela Matei","doi":"10.1016/j.ejmech.2025.118228","DOIUrl":"https://doi.org/10.1016/j.ejmech.2025.118228","url":null,"abstract":"Tissue transglutaminase (TG2), a multifunctional enzyme involved in protein crosslinking through transamidation, fibronectin–integrin interactions and GTP hydrolysis, is upregulated in cancer. Due to its diverse functions, TG2 has been a challenging therapeutic target. Here, we investigate the use of PROteolysis TArgeting Chimeras (PROTACs) to degrade TG2 and inhibit its tumor-promoting functions in ovarian cancer models. We describe a novel family of VHL based PROTACs using a ligand that binds to the TG2 fibronectin interacting domain and a thiol ether PEG linker. Three structurally related PROTACs—P374, P404, and P405—induced significant proteasome dependent TG2 degradation at 24 hours (p < 0.05), with stable effects at 48 hours. These compounds also potently inhibited cell adhesion and migration (p < 0.005), outside-in signaling, and blocked TG2 enzymatic activity (p < 0.001). An unbiased evaluation using reverse phase protein array of P374-treated cells revealed 136 differentially expressed proteins, including protein networks related to cell adhesion and involved in extracellular matrix (ECM) interactions. P374 and P405 reduced omental colonization in vivo and P374 inhibited intraperitoneal tumor dissemination and growth. Visium HD based spatial profiling of human ovarian tumors identified TG2 as a highly enriched protein at the tumors invasive edge and the interface with the ECM. Together, our findings put forward novel TG2-targeting PROTACs which effectively degrade TG2, impair its functions, and block <em>in-vivo</em> tumor dissemination. These results highlight the potential development of TG2 degraders towards therapeutic targeting in ovarian cancer.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"108 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maximiliano Colobbio, Ramiro Teixeira, Gerardo Duarte, Mauricio Silvera, Jenny Carolina Saldaña, Magdalena Nieves, Andrea Medeiros, Marcelo Alberto Comini, Laura Domínguez, María Elisa Melian, Beatríz Munguía, Juan Carlos Ramos, Eduardo Manta
{"title":"Fenbendazole–Amino Acid Derivatives as Novel Anthelmintic Candidates: Synthesis, Activity Against Haemonchus contortus, and In Silico Profiling.","authors":"Maximiliano Colobbio, Ramiro Teixeira, Gerardo Duarte, Mauricio Silvera, Jenny Carolina Saldaña, Magdalena Nieves, Andrea Medeiros, Marcelo Alberto Comini, Laura Domínguez, María Elisa Melian, Beatríz Munguía, Juan Carlos Ramos, Eduardo Manta","doi":"10.1016/j.ejmech.2025.118247","DOIUrl":"https://doi.org/10.1016/j.ejmech.2025.118247","url":null,"abstract":"We report the synthesis and biological evaluation of fifteen fenbendazole–amino acid derivatives from a δ-valerolactam-based scaffold. These compounds were designed to enhance anthelmintic efficacy while reducing mammalian cytotoxicity. Their activity was assessed against <em>Haemonchus contortus</em> at both the exsheathed third-stage larval (xL3) and adult stages. Several derivatives showed early anthelmintic activity (24 h) and low cytotoxicity towards murine macrophages. <em>In silico</em> analysis indicated a correlation between MLOGP–TPSA profiles and biological performance, suggesting improved cuticular diffusion. Compared with albendazole and fenbendazole, active compounds exhibited lower toxicity and occupied distinct regions in the physicochemical property space. These results support the potential of these new compounds as selective scaffolds for developing next-generation anthelmintics.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"108 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"1-(3,4-Diaminophenyl)-1H-pyrrole-2-carboxylic acids as potent apo-IDO1 inhibitors exhibiting efficacy in syngeneic tumor mouse models","authors":"Yi Zou, Shushan Ge, Haiqing Zhong, Yingbo Zheng, Xuewei Ma, Wenbin Liu, Fang Wang, Wenjie Guo, Wen Liu, Qiang Xu, Yisheng Lai","doi":"10.1016/j.ejmech.2025.118222","DOIUrl":"https://doi.org/10.1016/j.ejmech.2025.118222","url":null,"abstract":"Indolamine 2,3-dioxygenase 1 (IDO1)-mediated kynurenine pathway has been identified as an important immune escape mechanism in cancer, and pharmacological inhibition of IDO1 is regarded as a potential strategy for cancer treatment. Herein, we describe the identification of novel 1<em>H</em>-pyrrole-2-carboxylic acid-based IDO1 inhibitors targeting its apo form with picomolar potency in the HeLa cell-based assay. Among them, compound <strong>45</strong> showed the strongest inhibitory activity against IDO1 with an IC<sub>50</sub> value of 10 pM. Notably, oral administration of <strong>45</strong> at 10 mg/kg significantly suppressed tumor growth by activating antitumor immunity without significant toxicity in a CT26 syngeneic mouse model. Furthermore, the tumor burden could similarly be decreased in an LLC syngeneic mouse model treated with <strong>45</strong>, indicating the potential of <strong>45</strong> for the treatment of distinct tumor types. Collectively, these data suggest that compound <strong>45</strong> may be used as a promising lead compound for further investigation.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"157 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ekaterina Levashova, Luca Bischof, Alexander Bunev, Alexander Sapegin, Olga Grygor’eva, Andrey Kudinov, Sebastian Ebeling, Ilya Tatarinov, Dmitry Dar’in, Grigory Kantin, Marcus D. Hartmann, Stanislav Kalinin
{"title":"EXTENDING THE CHEMICAL SPACE OF GLUTARIMIDE-BASED CEREBLON LIGANDS THROUGH AN EFFICIENT Rh(II)-CATALYZED X-H INSERTION REACTION","authors":"Ekaterina Levashova, Luca Bischof, Alexander Bunev, Alexander Sapegin, Olga Grygor’eva, Andrey Kudinov, Sebastian Ebeling, Ilya Tatarinov, Dmitry Dar’in, Grigory Kantin, Marcus D. Hartmann, Stanislav Kalinin","doi":"10.1016/j.ejmech.2025.118235","DOIUrl":"https://doi.org/10.1016/j.ejmech.2025.118235","url":null,"abstract":"In this work we present an easy, one-step synthetic protocol to explore a large chemical space of glutarimide-based cereblon (CRBN) ligands for targeted protein degradation. It is built upon our recently suggested approach to generating structurally diverse series of alpha-substituted glutarimide derivatives through an efficient Rh(II)-catalyzed X-H insertion reaction of 3-diazopiperidine-2,6-dione, with moderate to high yields. In total, 25 glutarimide derivatives incorporating variable side chains were synthesized and evaluated <em>in vitro</em>. All ligands showed a favorable lipophilicity, and several were able to outperform the binding affinity of thalidomide as a reference. In addition, most compounds showed low intrinsic cytotoxicity in myeloma cell lines and human peripheral blood mononuclear cells, and did not recruit canonical neosubstrates. A cellular thermal shift assay further demonstrated that the most potent analogues stabilize CRBN in live cells, confirming their on-target engagement. The development of the series was accompanied by a crystallographic study, which rationalizes the observed improvements in binding affinity and neosubstrate selectivity, and can support further development towards molecular glue activity and PROTACs design.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"7 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiao Chen, Kefan Liao, Jiawei Yuan, Jianchao Zhang, Hai Rao
{"title":"Mighty mini-PROTACs: an emerging class of degraders","authors":"Xiao Chen, Kefan Liao, Jiawei Yuan, Jianchao Zhang, Hai Rao","doi":"10.1016/j.ejmech.2025.118202","DOIUrl":"https://doi.org/10.1016/j.ejmech.2025.118202","url":null,"abstract":"Proteolysis-targeting chimera (PROTAC) is an emerging therapeutic strategy that rewires the ubiquitin-proteasome system to destroy pathogenic proteins. Despite tremendous progress, PROTACs still face significant challenges in their development and clinical application. The historically first and simplest degradation signal is a single amino acid, leading to the N-end rule proteolytic pathway, but its PROTAC adaptation has been under-explored. Here, we examine the feasibility of the N-end rule pathway in addressing some major issues in the field and introduce the resulting mini-PROTACs bearing small, diverse, and interchangeable degrons. Such an approach potentially helps overcome resistance issues associated with existing ubiquitin ligases as well as helps enhance drug-like properties. Finally, we discuss the advantages and limitations of mini-PROTACs compared to other classical PROTACs, which will facilitate their clinical applications.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"4 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yanmei Hu , Yuyang Wu , Haicui Liu , Shiji Cheng , Feiyan Wen , Li Wan
{"title":"QS-21: Structural insights, immunological mechanisms, and prospects for rational design of safer vaccine adjuvants","authors":"Yanmei Hu , Yuyang Wu , Haicui Liu , Shiji Cheng , Feiyan Wen , Li Wan","doi":"10.1016/j.ejmech.2025.118223","DOIUrl":"10.1016/j.ejmech.2025.118223","url":null,"abstract":"<div><div>QS-21, a refined adjuvant based on saponins, is isolated from the bark of the soap-bark tree (<em>Quillaja saponaria</em>). It has garnered significant interest in the creation of next-generation vaccine adjuvants due to its robust ability to elicit Th1-type and Th2-type immunological responses. Despite its successful incorporation into licensed vaccines such as Shingrix® (herpes zoster) and Mosquirix® (malaria), the widespread application of QS-21 remains constrained by several limitations, including limited natural availability, chemical instability, dose-dependent toxicity, and an incompletely elucidated mechanism of action. This review provides a comprehensive overview of the natural sources, molecular structure, clinical applications, and immunological mechanisms of QS-21, based on research conducted both <em>in vivo</em> and <em>in vitro</em>. It also presents new developments in QS-21's structure-activity relationship (SAR), highlighting the possibility of creating less hazardous and more stable analogs through chemical synthesis and biosynthetic engineering. These strategies offer promising avenues for the rational design of novel adjuvants to support the development of more effective and safer vaccines.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"301 ","pages":"Article 118223"},"PeriodicalIF":5.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145209552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ping-Fan Zhang, Yi-Sheng Li, Cheng Wang, Yu-Hui Gao, Jing-Ying Liu, Hong-En Zhang, Lei Shi, Li-Ping Sun
{"title":"Recent Advances and Strategies in BET Bromodomain Inhibition for Drug Discovery","authors":"Ping-Fan Zhang, Yi-Sheng Li, Cheng Wang, Yu-Hui Gao, Jing-Ying Liu, Hong-En Zhang, Lei Shi, Li-Ping Sun","doi":"10.1016/j.ejmech.2025.118230","DOIUrl":"https://doi.org/10.1016/j.ejmech.2025.118230","url":null,"abstract":"BET proteins, which function as epigenetic readers to modulate gene expression and drive cancer progression, have emerged as promising targets for novel epigenetic anticancer therapies. Although preclinical models and initial clinical trials have demonstrated the anticancer potential of BET inhibitors, Pan-BET inhibitors often exhibit unsatisfied tolerability, dose-limiting toxicities, and limited efficacy as monotherapies. Recent studies highlight that selective BET inhibitors targeting individual bromodomains (BET-BD1 or BET-BD2) offer distinct advantages over pan-inhibitors, including reduced toxicity profiles. Notably, certain selective BET inhibitors demonstrate comparable or superior therapeutic efficacy in treating inflammatory diseases and cancers compared to pan-inhibitors. Consequently, the development of domain-selective BET inhibitors has become a focal point in medicinal chemistry research. This review summarizes the structural and functional characteristics of BET proteins, elucidates the differential binding preferences and biological roles of BD1 and BD2 domains, and systematically outlines recent advancements over the past five years in BD1- and BD2-selective BET inhibitors. Furthermore, it provides a detailed overview of dual-target inhibitors and degraders. Finally, perspectives on future research directions for BET-targeted therapeutics are discussed.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"214 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145209550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yan Liu, Jin Li, Yucheng Ma, Wenfang Gao, Yuanlong Li, Jiangnan Zhang, Baozhu Luo, Jing Sui, Tao Yang, Yuan Ju, Youfu Luo
{"title":"Discovery of potent ClpX modulators with pronounced antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA)","authors":"Yan Liu, Jin Li, Yucheng Ma, Wenfang Gao, Yuanlong Li, Jiangnan Zhang, Baozhu Luo, Jing Sui, Tao Yang, Yuan Ju, Youfu Luo","doi":"10.1016/j.ejmech.2025.118207","DOIUrl":"https://doi.org/10.1016/j.ejmech.2025.118207","url":null,"abstract":"The high morbidity and mortality rates associated with invasive methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) infections underscore the pressing need to develop novel antibiotics. ClpX, functioning as a cochaperone protein of ClpP, has been identified as a crucial target in combating MRSA. In this study, we screened an in-house library and identified a small molecule compound, <strong>PFK-158</strong>, with high affinity for <em>Staphylococcus aureus</em> ClpX (<em>K</em><sub>d</sub> = 4.1 μM). Simultaneously, <strong>PFK-158</strong> displayed potent activity against MRSA (MIC = 2 μg/mL, MBC = 8 μg/mL). Further optimization resulted in a novel α, β-unsaturated ketone bearing a quinolinyl group and a 2-bromophenyl substituent with comparable binding affinity for <em>Staphylococcus aureus</em> ClpX (<em>K</em><sub>d</sub> = 3.6 μM), and it showed enhanced antibacterial activity against MRSA and lower propensity for inducing resistance. Significantly, the novel α, β-unsaturated ketone bearing a quinolinyl group and a 2-bromophenyl substituent demonstrated favorable <em>in vivo</em> safety, oral bioavailability (F = 37.9 %), and promising therapeutic effects in a MRSA-infected skin abscess model. Overall, our findings presented a novel <em>Sa</em>ClpX modulator with the potential to combat Staphylococcus infections, and suggested a promising strategy for the further development of specific <em>Staphylococcus aureus</em> ClpX modulators.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"101 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Design, Synthesis, Anticancer Evaluation, and In Silico Studies of 2-Thiopyrimidine-5-Carbonitrile Derivatives as Potent Thymidylate Synthase Inhibitors","authors":"Aashish Jaitak, Kailash Jangid, Rajveer Singh, Vikramdeep Monga","doi":"10.1016/j.ejmech.2025.118205","DOIUrl":"https://doi.org/10.1016/j.ejmech.2025.118205","url":null,"abstract":"Thymidylate Synthase (TS) is a validated therapeutic target against cancer. The research examined whether the anticancer effects of lead compound <strong>4d</strong> surpassed the action of 5-fluorouracil (5-FU) while monitoring its impact on MCF-7 breast cancer cells under 2D and 3D experimental conditions. The treatment of MCF-7 cells with <strong>4d</strong> at 1 μM and 5 μM concentrations and 5-FU at 1 μM level allowed researchers to measure cytotoxicity, apoptosis, and cell cycle arrest activities. Further, ROS production and TS expression levels, including migration dynamics and 3D spheroid structure integrity, were also examined. The cell viability declined dramatically when exposing cells to compound <strong>4d,</strong> which causes cell cycle blockage at G<sub>2</sub>/M phase and elevated ROS levels while reducing the TS expression. Severe, destructive effects on cell movement and spheroid organization led to dose-dependent death of cells. The compound <strong>4d</strong> demonstrated effects that matched the results obtained from using 5-FU. The potential of TS-targeted therapeutic candidate status for breast cancer treatment seems promising because compound <strong>4d</strong> demonstrates strong anticancer effects through multiple pathways.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"113 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145195389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}