{"title":"Design and synthesis of pyridine-based benzamides as potent HDAC3 inhibitors as an armament against breast cancer with in vivo validation","authors":"Ambati Himaja , Ganesh Routholla , Tarun Patel , Suvankar Banerjee , Darakhshan Begum , Sanjeev Regula , Sravani Pulya , Swati Biswas , Nilanjan Adhikari , Balaram Ghosh","doi":"10.1016/j.ejmech.2025.117636","DOIUrl":"10.1016/j.ejmech.2025.117636","url":null,"abstract":"<div><div>Some novel benzamide derivatives with modified linker group were designed and synthesized as promising HDAC3-selective inhibitors. These compounds exerted promising antiproliferative potential compared to reference molecule CI994 while tested against several cancer cell lines. Notably, all these molecules exhibited nontoxicity towards normal human cell lines. The most promising molecule in series <strong>7c</strong> exhibited ∼47-fold HDAC3 selectivity over HDAC2 isoform. Compound <strong>7c</strong> induced apoptosis and cell cycle arrest in the G2/M phase in the 4T1 cell line. Moreover, compound <strong>7c</strong> yielded a good <em>in vivo</em> pharmacokinetic profile. Notably, compound <strong>7c</strong> markedly reduced tumor growth in the 4T1-Luc breast cancer xenograft model in female Balb/c mice. Compound <strong>7c</strong> also upregulated apoptotic proteins namely caspase-3, caspase-7, and cytochrome <em>c</em>, and downregulated Bcl-2. The antitumor potential of compound <strong>7c</strong> was further justified by the downregulation of EGFR and Ki-67 through Western blot analysis. Nevertheless, the HDAC3 inhibitory potency of compound <strong>7c</strong> depicted strong and stable binding interaction at the HDAC3 active site. These findings validated that compound <strong>7c</strong> is a promising HDAC3 inhibitor that can be further investigated for clinical translation to achieve emerging breast cancer therapeutics.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"291 ","pages":"Article 117636"},"PeriodicalIF":6.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846904","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}
Chunlin Ren , Qiding Xu , Qiusi Luo , Xue Qiao , Taotao Ding , Wumei Wang , Xiaodong Zeng , Cheng Chen , Yuling Xiao , Xuechuan Hong
{"title":"Benzothiazole amide analogues as antagonists of TRPC 6 channels: A therapeutic approach for kidney fibrosis","authors":"Chunlin Ren , Qiding Xu , Qiusi Luo , Xue Qiao , Taotao Ding , Wumei Wang , Xiaodong Zeng , Cheng Chen , Yuling Xiao , Xuechuan Hong","doi":"10.1016/j.ejmech.2025.117628","DOIUrl":"10.1016/j.ejmech.2025.117628","url":null,"abstract":"<div><div>Transient receptor potential canonical 6 (TRPC6) channels, which function as receptor-operated, non-selective cation channels, are widely expressed in the kidney, lungs, and brain. Within these organs, they play crucial roles in regulating diverse physiological processes and contribute to the pathogenesis of various disorders. The resolution of the cryo-electron microscopy structure of TRPC6 has significantly advanced our understanding of its molecular mechanisms, thereby providing a robust platform for structure-based drug design. Building upon compound <strong>1S</strong> as a lead, we developed and synthesized a series of benzothiazole derivatives, ultimately identifying compound <strong>X26</strong> as a potent TRPC6 antagonist with an IC<sub>50</sub> of 0.97 μM. <em>In vitro</em> administration of <strong>X26</strong> significantly suppressed TGF-β1–induced myofibroblast differentiation in HK-2 cells, as evidenced by a reduced expression of α-SMA, collagen I, and fibronectin. Furthermore, in a unilateral ureteral obstruction (UUO)–induced kidney fibrosis mouse model, treatment with <strong>X26</strong> resulted in a substantial reduction in serum urea nitrogen, serum creatinine, and urinary protein levels, as well as a decrease in renal collagen deposition. These findings establish <strong>X26</strong> as a promising lead for the development of TRPC6 antagonists and therapeutic interventions for kidney fibrosis.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"291 ","pages":"Article 117628"},"PeriodicalIF":6.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143842006","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}
Yali Sang , Weifang Huang , Jiacheng Lin , Liu Yang , Yuge Zhou , Chang Yu , Xuehua Sun , Hong Yu , Xiaoni Kong
{"title":"Fluorinated sulfonamide-flavonoid derivatives as novel Keap1-Nrf2 inhibitors: Potent induction of cytoprotective gene HO-1 in vivo","authors":"Yali Sang , Weifang Huang , Jiacheng Lin , Liu Yang , Yuge Zhou , Chang Yu , Xuehua Sun , Hong Yu , Xiaoni Kong","doi":"10.1016/j.ejmech.2025.117650","DOIUrl":"10.1016/j.ejmech.2025.117650","url":null,"abstract":"<div><div>Nuclear factor-erythroid 2 related factor 2 (Nrf2) is a key regulator in cellular defense against oxidative stress. While flavonoids have been identified as Nrf2 activators by inhibiting Keap1-Nrf2 protein-protein interaction (PPI), their limited bioactivity presents significant challenges for therapeutic applications. To compensate for this shortcoming, 28 sulfonamide-flavonoid analogues targeting the Keap1-Nrf2 PPI were synthesized by a fragment-based approach. Among these, SG16, which incorporates a fluorine atom, exhibited potent Nrf2-activated capacity and notable anti-inflammatory properties. In AML12 hepatocytes, SG16 significantly enhanced the expression of antioxidant genes by promoting Nrf2 nuclear translocation. In an acute liver injury (ALI) mouse model, SG16 treatment led to a substantial, hundredfold upregulation of the cytoprotective gene HO-1 mRNA. Meanwhile, a dose-dependent decline in ALT, AST, and inflammatory cytokine levels was observed, reflecting improved liver function. Histopathological evaluations, including hematoxylin and eosin (HE) staining, TUNEL, myeloperoxidase (MPO) activity assessment, and F4/80 macrophage marker analysis, consistently demonstrated substantial attenuation of liver tissue damage following SG16 treatment. Moreover, Co-IP assays combined with experiments in Nrf2 knockout mice suggested that the novel sulfonamide-containing flavonoids are a promising class of Nrf2-targeted therapeutic candidates, warranting further exploration for oxidative stress-related disorders.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"291 ","pages":"Article 117650"},"PeriodicalIF":6.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846906","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":"Discovery of fluorescent and theranostic probes for glycogen synthase kinase-3β in living cells and brain tissues: Detection and imaging in models of Alzheimer's disease","authors":"Yu Chen , Hanyue Dong , Xiaoling Huang, Lulu Jiang, Zixing Jiang, Lanqing Li, Jinhui Hu, Wen-Hua Chen","doi":"10.1016/j.ejmech.2025.117639","DOIUrl":"10.1016/j.ejmech.2025.117639","url":null,"abstract":"<div><div>Alzheimer's disease (AD) represents a progressive neurodegenerative disorder marked by complex pathologies. Glycogen synthase kinase-3<em>β</em> (GSK-3<em>β</em>) plays a pivotal role in AD pathogenesis, influencing key pathological processes such as hyperphosphorylation of tau and production of amyloid-beta. However, current methods for detecting GSK-3<em>β</em> in living cells and tissues are limited in sensitivity and real-time tracking. Herein, we reported a series of environment-sensitive fluorescent probes to detect GSK-3<em>β</em> in both living cells and brain slices. These probes exhibit fluorescence upon the binding of GSK-3<em>β</em>, providing high sensitivity and selectivity with minimal background interference. Compound <strong>10c</strong> was further validated in an AD mouse model with elevated expression of GSK-3<em>β</em>, showing clear imaging in hippocampal regions. Compared to immunofluorescence, compound <strong>10c</strong> demonstrated a lower background and faster labeling. In addition, this compound showed neuroprotective effects, supporting its potential as a theranostic tool in AD. These findings provide new tools for investigating the role of GSK-3<em>β</em> in AD and advancing targeted therapies.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"291 ","pages":"Article 117639"},"PeriodicalIF":6.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846909","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}
Qiu-Ge Liu , Ji Wu , Zi-Yue Wang , Bing-Bing Chen , Yi-Fei Du , Jin-Bo Niu , Jian Song , Sai-Yang Zhang
{"title":"ALK-based dual inhibitors: Focus on recent development for non-small cell lung cancer therapy","authors":"Qiu-Ge Liu , Ji Wu , Zi-Yue Wang , Bing-Bing Chen , Yi-Fei Du , Jin-Bo Niu , Jian Song , Sai-Yang Zhang","doi":"10.1016/j.ejmech.2025.117646","DOIUrl":"10.1016/j.ejmech.2025.117646","url":null,"abstract":"<div><div>As a prevalent oncogenic driver gene in non-small cell lung cancer (NSCLC), ALK represents a crucial and efficacious therapeutic target. To date, seven ALK inhibitors have been approved for ALK fusion-positive NSCLC, with several others undergoing clinical trials. These therapies demonstrate significant efficacy in ALK fusion-positive NSCLC patients. However, acquired resistance mechanisms, including ALK kinase domain mutations, ALK gene amplification, and bypass pathway activation, significantly compromise the efficacy of targeted therapy in ALK fusion-positive NSCLC. Therefore, the discovery of novel ALK inhibitors and the development of related treatment strategies remain critical. Compared to the combination therapy strategy based on ALK inhibitors, dual-target inhibitors (targeting two distinct pathways within a single molecule) may reduce systemic toxicity and mitigate resistance mechanisms in cancer treatment. Notably, recent years have witnessed remarkable progress in dual-target ALK inhibitor development for NSCLC. Consequently, this review aims to summarize the advancements achieved through dual ALK-based inhibitors in NSCLC therapy, analyze their rational design and structure-activity relationships, and provide perspectives for overcoming resistance through next-generation inhibitors and innovative therapeutic approaches.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"291 ","pages":"Article 117646"},"PeriodicalIF":6.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846988","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":"Anticancer potential of synthetic costunolide and dehydrocostus lactone derivatives: A systematic review","authors":"Mumen F.A. Amer , Dima Hattab , Athirah Bakhtiar","doi":"10.1016/j.ejmech.2025.117648","DOIUrl":"10.1016/j.ejmech.2025.117648","url":null,"abstract":"<div><h3>Background</h3><div>Costunolide (Cos) and dehydrocostus lactone (DhC) are naturally occurring sesquiterpene lactones with potent anticancer properties. Despite their promising bioactivity, limitations such as poor solubility, metabolic instability, and off-target toxicity restrict their clinical application. To overcome these challenges, synthetic derivatives have been developed to enhance cytotoxicity, selectivity, and pharmacokinetics.</div></div><div><h3>Method</h3><div>ology: Following Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines, a systematic literature was conducted across PubMed, SciFinder, ScienceDirect, Scopus, and Wiley Online Library. Thirteen studies published between 2006 and 2024 met the inclusion criteria, focusing on the anticancer properties of synthetic Cos and DhC derivatives.</div></div><div><h3>Results</h3><div>Synthetic modifications, particularly amino and triazole conjugations, improved tumor selectivity and water solubility, while maintaining or enhancing cytotoxic potency. The most effective derivatives induced apoptosid, cell cycle arrest, and oxidative stress in various cancer cell lines. However, pharmacokinetic data remain limited, and only one study included <em>in vivo</em> evaluation.</div></div><div><h3>Conclusion</h3><div>Synthetic derivatives of Cos and DhC exhibit enhanced anticancer potential and improved pharmacokinetic properties, making them promising candidates for drug potential. However, further <em>in vivo</em> studies and clinical trials are necessary to validate their therapeutic efficacy and safety.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"291 ","pages":"Article 117648"},"PeriodicalIF":6.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143842009","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}
Zhiteng Luo , Haipeng Qiu , Xiaoying Peng , Qingyun Tan , Bingyi Chen , Qiong Gu , Hongwei Liu , Huihao Zhou
{"title":"Development of potent inhibitors targeting bacterial prolyl-tRNA synthetase through fluorine scanning-directed activity tuning","authors":"Zhiteng Luo , Haipeng Qiu , Xiaoying Peng , Qingyun Tan , Bingyi Chen , Qiong Gu , Hongwei Liu , Huihao Zhou","doi":"10.1016/j.ejmech.2025.117647","DOIUrl":"10.1016/j.ejmech.2025.117647","url":null,"abstract":"<div><div>As essential enzymes encoded by single genes, aminoacyl-tRNA synthetases (aaRSs) have long been considered promising drug targets for combating microbial infections. In this study, we developed a novel class of amino acid-ATP dual-site inhibitors of prolyl-tRNA synthetase (ProRS) through the structural simplification of the intermediate product prolyl adenylate and its non-hydrolyzable mimic. The co-crystal structures of the compound <strong>PAA-5</strong> bound to both <em>Pseudomonas aeruginosa</em> and human cytoplasmic ProRSs (<em>Pa</em>ProRS and <em>Hs</em>Prors) were solved to high resolution. Utilizing the structural information gained, a fluorine scanning (F-scanning) strategy was applied to <strong>PAA-5</strong>, and the biochemical and biophysical assays demonstrated that fluorine substitutions at specific positions of <strong>PAA-5</strong> selectively enhanced its activity against bacterial ProRS. The dual-fluorinated derivative <strong>PAA-38</strong> exhibited the highest antibacterial potency, with a <em>K</em><sub>d</sub> value of 0.399 ± 0.074 nM and an IC<sub>50</sub> value of 4.97 ± 0.98 nM against <em>Pa</em>ProRS and an MIC value of 4–8 μg mL<sup>−1</sup> against tested bacterial strains. Our study provides a novel lead compound for the development of aaRS-based antibiotics and highlights F-scanning as a powerful strategy for lead optimization, particularly in pinpointing the subtle fluorophilic environments within the protein pocket to achieve better activity and selectivity.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"291 ","pages":"Article 117647"},"PeriodicalIF":6.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143842024","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}
Min Jiang , Shaowei Ma , Ying Xuan , Kuanbing Chen
{"title":"Synthetic approaches and clinical application of KRAS inhibitors for cancer therapy","authors":"Min Jiang , Shaowei Ma , Ying Xuan , Kuanbing Chen","doi":"10.1016/j.ejmech.2025.117626","DOIUrl":"10.1016/j.ejmech.2025.117626","url":null,"abstract":"<div><div>Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations are among the most common oncogenic alterations in various cancers, including pancreatic, colorectal, and non-small cell lung cancer (NSCLC). Targeting KRAS has long been considered a difficult challenge due to its high affinity for guanosine triphosphate (GTP) and the lack of a druggable binding site. However, recent advancements in small-molecule inhibitor design have led to the development of targeted therapies aimed at KRAS mutations, particularly the KRAS<sup>G12C</sup> mutation. Inhibitors such as Sotorasib and Adagrasib have shown promise in preclinical and clinical studies by irreversibly binding to the mutant KRAS protein, locking it in an inactive state and disrupting downstream signaling pathways critical for tumor growth and survival. These inhibitors have demonstrated clinical efficacy in treating patients with KRAS<sup>G12C</sup>-mutated cancers, leading to tumor regression, prolonged progression-free survival, and improved patient outcomes. This review discusses the synthetic strategies employed to develop these KRAS inhibitor and also examines the clinical application of these inhibitors, highlighting the challenges and successes encountered during clinical trials. Ultimately, KRAS inhibitors represent a breakthrough in cancer therapy, offering a promising new treatment option for patients with KRAS-driven tumors.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"291 ","pages":"Article 117626"},"PeriodicalIF":6.0,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143837498","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":"STING inhibitors and degraders: Potential therapeutic agents in inflammatory diseases","authors":"Kerong Wu , Yiwen Xu , Peizhao Liu , Kexin Chen , Yun Zhao","doi":"10.1016/j.ejmech.2025.117632","DOIUrl":"10.1016/j.ejmech.2025.117632","url":null,"abstract":"<div><div>The regulation of the STING (stimulator of interferon genes) pathway represents a promising target for a range of inflammatory diseases. This review provides an overview of the structure of STING and discusses the mechanisms by which the cyclic GMP-AMP synthase (cGAS)-STING pathway is associated with various autoinflammatory and autoimmune diseases. We explore how targeting STING inhibition or degradation can alleviate excessive inflammatory signaling and improve efficacy. Emerging strategies include inhibiting STING expression by covalently binding compounds or using ligands that target the binding pocket. In addition, selective degradation of STING via the ubiquitin-proteasome system or the lysosomal pathway shows promise. In addition, we explore the implications of modulating the cGAS-STING pathway in the context of various inflammatory diseases. Finally, we summarize the chemical properties of recently developed STING compounds and their potential clinical applications. By comprehensively reviewing the current understanding of the role of STING in inflammation and the therapeutic potential of targeting STING, we aim to identify new avenues of intervention that could improve outcomes for patients with inflammatory diseases. This review highlights the important role of STING in the regulation of inflammation and its potential as a target for innovative therapeutic strategies.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"291 ","pages":"Article 117632"},"PeriodicalIF":6.0,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143837495","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}
Xuan Zhang , Dinesh Thummuri , Wanyi Hu , Xingui Liu , Peiyi Zhang , Shuo Zhou , Daohong Zhou , Guangrong Zheng
{"title":"Discovery of XZ338, a highly potent BCL-XL degrader","authors":"Xuan Zhang , Dinesh Thummuri , Wanyi Hu , Xingui Liu , Peiyi Zhang , Shuo Zhou , Daohong Zhou , Guangrong Zheng","doi":"10.1016/j.ejmech.2025.117624","DOIUrl":"10.1016/j.ejmech.2025.117624","url":null,"abstract":"<div><div>BCL-X<sub>L</sub> is a crucial anti-apoptotic protein involved in tumorigenesis and resistance to cancer chemotherapy. Transitioning from conventional inhibitors to PROTAC degraders has shown promising potential, particularly in minimizing the on-target thrombocytopenia linked to BCL-X<sub>L</sub> inhibition. However, reported BCL-X<sub>L</sub> degraders were mostly derived from BCL-X<sub>L</sub>/BCL-2 dual inhibitor ABT-263, which also inhibits or degrades BCL-2 and can potentially cause neutropenia when combined with conventional chemotherapy as seen with ABT-263 in the clinic. The goal of the present study is to develop a highly specific BCL-X<sub>L</sub> degrader without BCL-2 inhibition/degradation. In this study, XZ338, a highly potent and selective BCL-X<sub>L</sub> degrader derived from BCL-X<sub>L</sub> specific inhibitor A-1331852, was generated. XZ338 is 70-fold more potent than ABT-263 against MOLT-4 T-ALL cells, with over 89-fold selectivity for MOLT-4 cells over human platelets.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"291 ","pages":"Article 117624"},"PeriodicalIF":6.0,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828727","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}