Bioorganic Chemistry最新文献

{"title":"Design and optimization of selective and potent LSD1 inhibitors with tranylcypromine-pyrimidine scaffold for the treatment of acute myeloid leukemia","authors":"Ming-Jie Huang ,&nbsp;Jian Song ,&nbsp;Meiqi Jia ,&nbsp;Sai-Yang Zhang ,&nbsp;Lihua Huang","doi":"10.1016/j.bioorg.2026.109588","DOIUrl":"10.1016/j.bioorg.2026.109588","url":null,"abstract":"<div><div>Lysine-specific demethylase 1 (LSD1), a key epigenetic regulator mediating histone modification, has been a potential therapeutic target for acute myeloid leukemia (AML) due to its critical role in disease pathogenesis. In this work, we designed and synthesized novel LSD1 inhibitors with the scaffold of tranylcypromine-pyrimidine. The representative compound <strong>7a</strong> was a highly effective LSD1 inhibitor (IC₅₀ = 7.87 nM) with excellent selectivity over MAO-A and MAO-B (&gt;127-fold over MAO-A and &gt; 1270-fold over MAO-B). Meanwhile, compound <strong>7a</strong> also showed effective inhibitory activity against MV-4-11 with IC₅₀ values of 0.36 μM. Mechanistic studies demonstrated that <strong>7a</strong> could directly targeted LSD1, thereby promoting a significant increase of H3K4me1/2 histone methylation levels in MV-4-11 cells. <strong>7a</strong> induced apoptosis while upregulating the differentiation marker CD86 and downregulating the stem cell-associated proteins SOX2 and CD44. Collectively, these findings establish compound <strong>7a</strong>, a tranylcypromine-pyrimidine derivative, provides the structural foundation for the development of LSD1 inhibitors for the treatment of AML.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"173 ","pages":"Article 109588"},"PeriodicalIF":4.7,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146147292","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":"Effects of Cytochrome P450 enzymes and drug–drug interaction on donafenib metabolism: in vivo, in vitro and in silico","authors":"Yuxin Shen ,&nbsp;Jun Wu ,&nbsp;Lu Cao ,&nbsp;Shiqi Jiang ,&nbsp;Yan Chen ,&nbsp;Ren-ai Xu ,&nbsp;Ling Ji","doi":"10.1016/j.bioorg.2026.109523","DOIUrl":"10.1016/j.bioorg.2026.109523","url":null,"abstract":"<div><div>This study systematically elucidated the metabolic characteristics of the hepatocellular carcinoma (HCC) therapeutic drug donafenib and its drug–drug interaction (DDI) with the antiviral agent arbidol. <em>In vitro</em> phenotyping assays using chemical inhibitors and recombinant CYP enzymes identified CYP3A4 as the primary enzyme catalyzing donafenib N-oxide formation. This was further confirmed by <em>in vivo</em> pharmacokinetic experiments in Cyp3a1/2 knockout rats, where AUC_(0-t), AUC_(0-∞) and t_1/2 of donafenib were increased compared with wild-type rats. Additionally, the study was the first to report the effects of 8 CYP3A4 variants (CYP3A4.39-.46) on donafenib metabolism. Among these, 7 variants (except CYP3A4.42) had reduced metabolic catalytic activity compared to wild-type CYP3A4.1, and the intrinsic clearance (CL_int) was 8.60%–97.89% of that of CYP3A4.1. Subsequently, the potential mechanism of enzymatic activity changes was investigated through molecular docking. Finally, the study found that arbidol significantly inhibited donafenib metabolism, where the half-maximum inhibitory concentration (IC₅₀) value of arbidol was 3.16 ± 0.09 μM in rat liver microsome (RLM) and 36.38 ± 1.23 μM in human liver microsome (HLM), respectively. Animal studies have shown that the pharmacokinetics of donafenib were significantly altered following co-administration of arbidol in Sprague-Dawley rats. The results indicated that the AUC_(0-t), AUC_(0-∞) and C_max of donafenib were increased by 1.19-, 1.05- and 0.54-fold, respectively. Moreover, T_max was prolonged by 68.42%, while CL_z/F was decreased by 53.85%. These results provided critical references for clinical dosage adjustment, facilitating personalized treatment and reducing the risk of adverse reactions.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"173 ","pages":"Article 109523"},"PeriodicalIF":4.7,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172536","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":"Eupalinolide B prevents cerebral ischemia-reperfusion injury via the PI3K/Akt/GSK3β(Ser9) signaling pathway","authors":"Man Li ,&nbsp;Yuxin Jiang ,&nbsp;Yongkang Xue,&nbsp;Yuanqi Duan,&nbsp;Yanan Liu,&nbsp;Xianghao Xin,&nbsp;Xiaoyu Wei,&nbsp;Zhengyu Hu,&nbsp;Pengcheng Yang,&nbsp;Shengbao Diao,&nbsp;Wei Zhou,&nbsp;Jinfeng Sun,&nbsp;Gao Li","doi":"10.1016/j.bioorg.2026.109635","DOIUrl":"10.1016/j.bioorg.2026.109635","url":null,"abstract":"<div><div>Ischemic stroke (IS) is the leading cause of prevalence and mortality in China and a major global public health problem. Eupalinolide B (EB) stands as the main biologically active constituent extracted from <em>Eupatorium lindleyanum</em>, exhibits diverse pharmacological activities, with particular emphasis on its neuroprotective potential in neurodegenerative disorders. Nevertheless, the precise therapeutic outcomes and the specific molecular pathways mediating the protective effects of EB against cerebral ischemia-reperfusion injury (CIRI) are still not fully elucidated. This study systematically explores the potential therapeutic targets and regulatory networks of EB in CIRI treatment through an integrative approach combining network pharmacology analysis with <em>in vitro</em> oxygen-glucose deprivation/reoxygenation (OGD/R) modeling in PC12 cells and <em>in vivo</em> middle cerebral artery occlusion/reperfusion (MCAO/R) modeling in mice. Our findings demonstrate that EB modulates a network composed of 54 core therapeutic targets, including apoptosis regulators (Bcl-2) and components of the PI3K/Akt signaling cascade. <em>In vitro</em> experiments indicate that EB significantly improves the viability of PC12 cells induced by OGD/R, while attenuating intracellular reactive oxygen species (ROS) accumulation and restoring mitochondrial membrane potential. Complementary <em>in vivo</em> studies reveal that the administration of EB activates the PI3K/Akt/GSK3β(Ser9) signaling pathway in MCAO/R mice, leading to reduced neurological deficits, decreased cerebral infarction area, and a mitigation of neuronal pathological changes. Collectively, these findings indicate that EB inhibits neuronal apoptosis by activating the PI3K/Akt/GSK3β(Ser9) signaling pathway, thereby exerting a preventive effect against CIRI. This provides robust experimental evidence for the potential of EB as a new anti-IS therapy.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"173 ","pages":"Article 109635"},"PeriodicalIF":4.7,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146256721","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":"Rational β-turn engineering of a disulfide-free β-hairpin-like antimicrobial peptide W2PG with enhanced stability, selectivity, and in vivo efficacy","authors":"Meng Liu,&nbsp;Peng Jiang,&nbsp;Binghui Ruan,&nbsp;Yunfei Cui,&nbsp;Junjie Zhang,&nbsp;Yuxiu Ye,&nbsp;Dongting Zhangsun,&nbsp;Sulan Luo,&nbsp;Yong Wu","doi":"10.1016/j.bioorg.2026.109612","DOIUrl":"10.1016/j.bioorg.2026.109612","url":null,"abstract":"<div><div>Antimicrobial resistance (AMR) is an increasing global concern, while the development of new antibiotics remains limited. Antimicrobial peptides (AMPs) offer an alternative due to their broad-spectrum and membrane-targeting features, but their translation is restricted by instability and cytotoxicity. Here, we describe a β-turn engineering strategy that incorporates a Pro-Gly motif and aromatic residues to create a short, disulfide-free β-hairpin-like AMP (W2PG). W2PG showed broad-spectrum activity (MIC 4–8 μM) with low hemolysis and cytotoxicity, along with improved protease and serum stability. It caused concentration-dependent membrane permeabilization and depolarization, consistent with molecular dynamics simulations indicating aromatic-assisted anchoring and stable insertion. In murine infection models, W2PG achieved efficacy comparable to polymyxin B without observable organ toxicity. These results suggest that β-turn-guided design can balance stability, selectivity, and activity, providing a useful scaffold for peptide antibiotic development.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"173 ","pages":"Article 109612"},"PeriodicalIF":4.7,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172537","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":"Z226407860 attenuates HDM-induced airway epithelial injury and ROS accumulation via RBX1 inhibition","authors":"Ling Feng ,&nbsp;Li Li ,&nbsp;Yale Sun ,&nbsp;Yuan Yin ,&nbsp;Yuan Zhong ,&nbsp;Yuan Ma","doi":"10.1016/j.bioorg.2026.109646","DOIUrl":"10.1016/j.bioorg.2026.109646","url":null,"abstract":"<div><div>Asthma is characterized by airway inflammation and epithelial barrier dysfunction, yet the underlying molecular mechanisms remain incompletely understood. Here, we identify RING-box protein 1 (RBX1) as a critical regulator of airway epithelial injury, whose expression is markedly elevated in asthma. Mechanistically, RBX1 expression correlates with increased reactive oxygen species (ROS) levels and epithelial barrier disruption, potentially involving its downstream target NOD-like receptor family pyrin domain containing 1 (NLRP1). Furthermore, we demonstrate that Z226407860, a novel small molecule, effectively suppresses RBX1 expression, mitigates ROS accumulation, and restores epithelial barrier integrity in house dust mite (HDM)-stimulated bronchial epithelial cells, without inducing cytotoxicity. Collectively, these findings reveal that RBX1 drives oxidative stress and epithelial injury in asthma and demonstrate that pharmacological inhibition of RBX1 with Z226407860 offers a potential therapeutic strategy to restore airway epithelial homeostasis.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"173 ","pages":"Article 109646"},"PeriodicalIF":4.7,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146217984","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":"Neuroprotective effects of pepsin-hydrolyzed ovotransferrin on H2O2-induced oxidative damage in SH-SY5Y neuronal cells","authors":"Hyeong-Jin Kim ,&nbsp;Seung-Woo Yu ,&nbsp;Kee-Tae Kim ,&nbsp;Dong-Uk Ahn ,&nbsp;Na-Kyoung Lee ,&nbsp;Hyun-Dong Paik","doi":"10.1016/j.bioorg.2026.109613","DOIUrl":"10.1016/j.bioorg.2026.109613","url":null,"abstract":"<div><div>Neurodegenerative diseases are considered critical disorders due to the absence of effective treatments and serious damage to brain function. Ovotransferrin, an egg white protein, and its hydrolysate obtained using proteolytic enzymes have been reported to have beneficial effects on various bioactive functions. Therefore, the purpose of this study was to investigate the neuroprotective effects of enzymatically hydrolyzed ovotransferrin in SH-SY5Y cells exposed to oxidative stress. Hydrolyzed ovotransferrin showed higher antioxidative activities than pure ovotransferrin. Furthermore, 0.5 mg/mL of pepsin-derived ovotransferrin hydrolysate (OHPE) exhibited the highest cell viability (81.89%), and OHPE effectively reduced cellular ROS accumulation (72%) and decreased total apoptosis rate (46.41%). These anti-apoptotic and antioxidative effects were influenced by the regulation of the mRNA and protein expression of Bax, Bcl-2, caspase-9, caspase-3, Nrf2, and HO-1. Additionally, nine peptides comprising OHPE were identified by LC-MS/MS and compared with the sequences reported in DFBP to explore their potential as antioxidants. These results indicate that OHPE can be used as a nature-derived compound to prevent neurodegenerative diseases by inhibiting ROS interactions and regulating protein expression in neuronal cells.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"173 ","pages":"Article 109613"},"PeriodicalIF":4.7,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146147293","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":"Research advances in the antimicrobial activity of natural product-antimicrobial peptide (AMP) mimic conjugates","authors":"Ayue Kang ,&nbsp;Yue Tian ,&nbsp;Yan Wang ,&nbsp;Xinhui Li ,&nbsp;Shengnan Xu ,&nbsp;Ruige Yang ,&nbsp;Longhua Yang ,&nbsp;Yong Guo","doi":"10.1016/j.bioorg.2026.109618","DOIUrl":"10.1016/j.bioorg.2026.109618","url":null,"abstract":"<div><div>The global crisis of antimicrobial resistance (AMR) has become a leading cause of death worldwide. With the traditional antibiotic pipeline increasingly depleted and the evolution of drug-resistant bacteria outpacing the development of new therapeutics—Particularly against challenges like methicillin-resistant <em>Staphylococcus aureus</em> (MRSA)—The development of novel antimicrobials is urgently needed. Antimicrobial peptides (AMPs), key effector molecules of innate immunity, are considered promising candidates owing to their membrane-targeting mechanisms and low potential for inducing resistance. However, their clinical translation has been hampered by poor druggability, including issues of cytotoxicity and hemolytic activity. Meanwhile, natural products represent a valuable source of privileged scaffolds with inherent antimicrobial activity or biocompatibility. The combination of natural products with AMP mimics offers a highly promising strategy for combating drug-resistant bacterial infections. This review summarizes recent advances in natural product-AMP mimic conjugates, discusses the development of their antibacterial activity and structure-activity relationships (SARs), and elucidates the mechanisms of action of some representative conjugates. Overall, this review provides new insights and strategic approaches for the rational development of antimicrobials based on natural products and AMPs</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"173 ","pages":"Article 109618"},"PeriodicalIF":4.7,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146147294","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":"Bispecific aptamer LYTAC for PCSK9 degradation: a promising strategy for cholesterol regulation","authors":"Shuaishuai Cui ,&nbsp;Mingjie Li ,&nbsp;Xiangjun Li ,&nbsp;Yujian He ,&nbsp;Li Wu","doi":"10.1016/j.bioorg.2026.109648","DOIUrl":"10.1016/j.bioorg.2026.109648","url":null,"abstract":"<div><div>PCSK9 is a key regulator of LDLR turnover and an established therapeutic target for CVD. Here, we report the development of a bispecific DNA aptamer-based lysosome-targeting chimera (PCSK9-LYTAC) that promotes extracellular degradation of PCSK9 via IGFIIR-mediated lysosomal trafficking. This dual-aptamer construct simultaneously blocks the PCSK9–LDLR interaction and directs PCSK9 toward lysosomal degradation. In HepG2 cells, PCSK9-LYTAC efficiently undergoes lysosomal localization and significantly restores LDL uptake (∼22% recovery), outperforming the corresponding monovalent PCSK9 aptamer. Mechanistically, this functional rescue is associated with enhanced LDLR availability at the cell surface following PCSK9 degradation. Collectively, these results demonstrate the feasibility of aptamer-based LYTACs as a non-antibody, modular strategy for regulating extracellular protein homeostasis and highlight their potential for therapeutic intervention in dyslipidemia and CVD.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"173 ","pages":"Article 109648"},"PeriodicalIF":4.7,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146218065","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 new non-macrocyclic TRK inhibitors based on conformational flexibility and scaffold hopping to overcome clinical acquired resistance","authors":"Zhong-Rui Liu ,&nbsp;Zi-Long Li ,&nbsp;Hong-Chuang Xu ,&nbsp;Xiu-Qin Yang,&nbsp;Neng-Fang She,&nbsp;Long-Can Mei,&nbsp;Wei Huang","doi":"10.1016/j.bioorg.2026.109603","DOIUrl":"10.1016/j.bioorg.2026.109603","url":null,"abstract":"<div><div>Targeted tropomyosin receptor kinase (TRK) inhibitors represent a therapeutic approach for cancers with NTRK gene fusions. However, the therapeutic efficacy of first-generation inhibitors is limited by the emergence of acquired drug resistance. Through the application of scaffold-hopping and conformational-flexibility design strategies, we identified a series of novel non-macrocyclic inhibitors, which showed enhanced activity against the TRKA^G595R and TRKA^G667C. The best TRK inhibitor <strong>5c</strong> had IC₅₀ values of 0.75 and 0.96 nM against TRKA^G595R and TRKA^G667C, showing better potency than drugs larotrectinib (approximately 87- and 46-fold improvement) and selitrectinib (approximately 10- and 13-fold improvement). <strong>5c</strong> also strongly suppressed the proliferation of Ba/F3 cells transfected with TRKA^{WT/595R 667C} with IC₅₀ values of 3 − 41 nM. More importantly, <strong>5c</strong> demonstrated favorable <em>in vivo</em> pharmacokinetic properties and antitumor efficacy (tumor growth inhibition (TGI) of 91% at 30 mg/kg and 115% at 60 mg/kg with 4 of 6 partial regression) in a BaF3-TMP3-TRKA^G667C xenograft mouse model, which is greatly superior to that of selitrectinib (TGI of 2% at 30 mg/kg). Compound <strong>5c</strong> exhibits significant potential to overcome clinical acquired multiple resistance to TRK inhibitors.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"172 ","pages":"Article 109603"},"PeriodicalIF":4.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146155592","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":"Mechanistic enzyme-oriented investigation of benzimidazole derivatives associated with kidney dysfunction: synthesis, molecular docking and in vivo toxicological evaluation","authors":"Sha Liu ,&nbsp;Wenna Song ,&nbsp;Qingliang Hu ,&nbsp;Yibing Liang ,&nbsp;Lifen Wang ,&nbsp;Yebing Liu ,&nbsp;Xinpan Chen ,&nbsp;Liyan Wang ,&nbsp;Dai Deng ,&nbsp;Aihua Zhang ,&nbsp;Yiming Guang ,&nbsp;Xueqi Wang ,&nbsp;Yongli Han ,&nbsp;Hongdong Huang","doi":"10.1016/j.bioorg.2026.109554","DOIUrl":"10.1016/j.bioorg.2026.109554","url":null,"abstract":"<div><div>A series of benzimidazole–oxadiazole–based Schiff base derivatives (1−10) was synthesized and evaluated as potential angiotensin-converting enzyme (ACE) inhibitors. The compounds were characterized using standard spectroscopic techniques and assessed for ACE inhibitory activity through in vitro enzyme assays, with ramipril used as the reference inhibitor. Several derivatives demonstrated significant inhibition, with analogue 8, bearing a trifluoromethyl (CF₃) substituent, exhibiting superior potency compared to ramipril. Molecular docking studies revealed favorable hydrogen bonding and hydrophobic interactions of the active compounds within the ACE catalytic pocket, supporting the observed inhibitory trends. Density functional theory (DFT) calculations provided insight into electronic features associated with enhanced activity, while in silico ADMET analysis suggested acceptable drug-likeness profiles. Furthermore, in vivo toxicity evaluation in rats indicated no observable adverse effects at the tested doses. Overall, the study identifies these benzimidazole–oxadiazole Schiff bases as promising ACE inhibitory scaffolds for further pharmacological optimization.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"172 ","pages":"Article 109554"},"PeriodicalIF":4.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098616","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}