Xian-Jia Li , Ke-Xin Huang , Ke-Xin Wang , Ru Liu , Dong-Chao Wang , Yu-Ru Liang , Er-Jun Hao , Yang Wang , Hai-Ming Guo
{"title":"Design, synthesis, and antitumor activity of novel thioheterocyclic nucleoside derivatives by suppressing the c-MYC pathway","authors":"Xian-Jia Li , Ke-Xin Huang , Ke-Xin Wang , Ru Liu , Dong-Chao Wang , Yu-Ru Liang , Er-Jun Hao , Yang Wang , Hai-Ming Guo","doi":"10.1016/j.apsb.2025.05.008","DOIUrl":"10.1016/j.apsb.2025.05.008","url":null,"abstract":"<div><div>Eightly-four novel thioheterocyclic nucleoside derivatives were designed, synthesized, and evaluated for antitumor activity <em>in vitro</em> and <em>in vivo</em>. Most of the compounds inhibited the growth of HCT116 and HeLa cancer cells <em>in vitro</em>, among them <strong>33a</strong> and <strong>36b</strong> exhibited potent activity against HCT116 cells (IC<sub>50</sub> = 0.27 and 0.49 μmol/L, respectively). Both compounds <strong>33a</strong> and <strong>36b</strong> inhibited cell metastasis, arrested the cell cycle in the G<sub>2</sub>/M phase, and induced apoptosis <em>in vitro</em>. Mechanistic studies revealed that <strong>33a</strong> and <strong>36b</strong> increased ROS levels, led to DNA damage, ER stress, and mitochondrial dysfunction, and inhibited autophagy in HCT116 cells. Biological information analysis, RNA-sequencing, Gene Set Enrichment Analysis (GSEA), drug affinity responsive target stability (DARTS) assay, cellular thermal shift assay (CETSA), and SPR experiments identified that compounds <strong>33a</strong> and <strong>36b</strong> showed antitumor activity by suppressing the c-MYC pathway. <em>c-MYC</em> silencing assays indicated that c-MYC proteins participated in <strong>33a</strong>-mediated anticancer activities in HCT116 cells. More importantly, compound <strong>33a</strong> presented favorable pharmacokinetic properties in mice (<em>T</em><sub>1/2</sub> = 6.8 h) and showed significant antitumor efficacy <em>in vivo</em> without obvious toxicity, showing promising potential for further clinical development.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 7","pages":"Pages 3685-3707"},"PeriodicalIF":14.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572182","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":"Traditional Chinese medicine in the early prevention of colorectal cancer from the perspective of tumor microenvironment","authors":"Huan Tang, Jigang Wang","doi":"10.1016/j.apsb.2025.06.020","DOIUrl":"10.1016/j.apsb.2025.06.020","url":null,"abstract":"","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 7","pages":"Pages 3829-3830"},"PeriodicalIF":14.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572771","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}
Ting Wen , Yanping Fu , Xiangting Yi , Ying Sun , Wanchen Zhao , Chaonan Shi , Ziyao Chang , Beibei Yang , Shuling Li , Chao Lu , Tingting Peng , Chuanbin Wu , Xin Pan , Guilan Quan
{"title":"Autonomous drug delivery and scar microenvironment remodeling using micromotor-driven microneedles for hypertrophic scars therapy","authors":"Ting Wen , Yanping Fu , Xiangting Yi , Ying Sun , Wanchen Zhao , Chaonan Shi , Ziyao Chang , Beibei Yang , Shuling Li , Chao Lu , Tingting Peng , Chuanbin Wu , Xin Pan , Guilan Quan","doi":"10.1016/j.apsb.2025.05.017","DOIUrl":"10.1016/j.apsb.2025.05.017","url":null,"abstract":"<div><div>Hypertrophic scar is a fibrous hyperplastic disorder that arises from skin injuries. The current therapeutic modalities are constrained by the dense and rigid scar tissue which impedes effective drug delivery. Additionally, insufficient autophagic activity in fibroblasts hinders their apoptosis, leading to excessive matrix deposition. Here, we developed an active microneedle (MN) system to overcome these challenges by integrating micromotor-driven drug delivery with autophagy regulation to remodel the scar microenvironment. Specifically, sodium bicarbonate and citric acid were introduced into the MNs as a built-in engine to generate CO<sub>2</sub> bubbles, thereby enabling enhanced lateral and vertical drug diffusion into dense scar tissue. The system concurrently encapsulated curcumin (Cur), an autophagy activator, and triamcinolone acetonide (TA), synergistically inducing fibroblast apoptosis by upregulating autophagic activity. <em>In vitro</em> studies demonstrated that active MNs achieved efficient drug penetration within isolated scar tissue. The rabbit hypertrophic scar model revealed that TA-Cur MNs significantly reduced the scar elevation index, suppressed collagen I and transforming growth factor-<em>β</em>1 (TGF-<em>β</em>1) expression, and elevated LC3 protein levels. These findings highlight the potential of the active MN system as an efficacious platform for autonomous augmented drug delivery and autophagy-targeted therapy in fibrotic disorder treatments.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 7","pages":"Pages 3738-3755"},"PeriodicalIF":14.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572185","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}
Jialing Cheng , Zhiyang Chen , Demin Lin , Yanfang Yang , Yanjing Bai , Lingshuang Wang , Jie Li , Yuchen Wang , Hongliang Wang , Youbai Chen , Jun Ye , Yuling Liu
{"title":"A high clinically translatable strategy to anti-aging using hyaluronic acid and silk fibroin co-crosslinked hydrogels as dermal regenerative fillers","authors":"Jialing Cheng , Zhiyang Chen , Demin Lin , Yanfang Yang , Yanjing Bai , Lingshuang Wang , Jie Li , Yuchen Wang , Hongliang Wang , Youbai Chen , Jun Ye , Yuling Liu","doi":"10.1016/j.apsb.2025.04.020","DOIUrl":"10.1016/j.apsb.2025.04.020","url":null,"abstract":"<div><div>An ideal dermal filler should integrate filling, repair, and anti-aging effects, with immediate tissue augmentation, slow degradation, and progressive stimulation of collagen regeneration. However, commonly used hyaluronic acid (HA) hydrogels, while effective for rapid filling, suffer from limited duration of support, weak cell adhesion, and an inability to promote collagen regeneration. Silk fibroin (SF), a natural protein from silkworm cocoons, is known for its excellent cell adhesion and collagen-stimulating abilities. However, its limited gelation capability restricts its potential application as a standalone injectable hydrogel. Based on a complementary strategy, this study combines the rapid gelling properties of HA with the collagen regenerative properties of SF to create a co-crosslinked HA-SF hydrogel. The composite hydrogel merges HA's rapid filling effect with SF's strong tissue adhesion and collagen-stimulating abilities. The formulation, physicochemical properties, degradation, biocompatibility, and filling effects of the HA-SF hydrogel were systematically investigated. HA-SF hydrogel exhibits excellent mechanical properties and ensures long-term support while maintaining injectability. Interestingly, after intradermal injection in the UVB-induced photoaging model, HA-SF hydrogel not only enhances hydrogel–cell interaction but also continues to stimulate collagen regeneration, especially type III collagen. This dual action achieves the biological effects of repair and anti-aging while maintaining the filling effect. Proteomic analysis confirms that repair and anti-aging effects are enhanced by the regulation of skin fibroblasts and modulation of amino acid and lipid metabolism. This composite hydrogel holds strong promise for clinical applications, offering a safer, long-lasting, and more natural injectable filler that combines filling, repair, and anti-aging into one system.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 7","pages":"Pages 3767-3787"},"PeriodicalIF":14.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572188","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}
Lijun Cai , Meimei Yin , Shuangzhou Peng , Fen Lin , Liangliang Lai , Xindao Zhang , Lei Xie , Chuanying Wang , Huiying Zhou , Yunfeng Zhan , Gulimiran Alitongbieke , Baohuan Lian , Zhibin Su , Tenghui Liu , Yuqi Zhou , Zongxi Li , Xiaohui Chen , Qi Zhao , Ting Deng , Lulu Chen , Xiao-Kun Zhang
{"title":"RXRα modulates hepatic stellate cell activation and liver fibrosis by targeting CaMKKβ–AMPKα axis","authors":"Lijun Cai , Meimei Yin , Shuangzhou Peng , Fen Lin , Liangliang Lai , Xindao Zhang , Lei Xie , Chuanying Wang , Huiying Zhou , Yunfeng Zhan , Gulimiran Alitongbieke , Baohuan Lian , Zhibin Su , Tenghui Liu , Yuqi Zhou , Zongxi Li , Xiaohui Chen , Qi Zhao , Ting Deng , Lulu Chen , Xiao-Kun Zhang","doi":"10.1016/j.apsb.2025.05.023","DOIUrl":"10.1016/j.apsb.2025.05.023","url":null,"abstract":"<div><div>Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXR<em>α</em>), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXR<em>α</em> exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase <em>β</em> (CaMKK<em>β</em>)-mediated activation of AMP-activated protein kinase-alpha (AMPK<em>α</em>). In addition, we demonstrate that K-80003, which binds RXR<em>α</em> by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl<sub>4</sub> and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPK<em>α</em> activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPK<em>α</em> by inducing RXR<em>α</em> to form condensates with CaMKK<em>β</em> and AMPK<em>α via</em> a two-phase process. The formation of RXR<em>α</em> condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKK<em>β</em>. Our results reveal a crucial role of RXR<em>α</em> in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXR<em>α</em> modulators hold promise as therapeutic agents for fibrosis-related diseases.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 7","pages":"Pages 3611-3631"},"PeriodicalIF":14.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572781","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}
Hui Chen , Hanqi Zhang , Chao Niu , Bianlin Wang , Biao Gao , Zhijun Liu , Guangmin Yao , Haji Akber Aisa
{"title":"Anacyphrethines A and B as potent analgesics: Multiple ion channel inhibitors with an unprecedented chemical architecture","authors":"Hui Chen , Hanqi Zhang , Chao Niu , Bianlin Wang , Biao Gao , Zhijun Liu , Guangmin Yao , Haji Akber Aisa","doi":"10.1016/j.apsb.2025.04.032","DOIUrl":"10.1016/j.apsb.2025.04.032","url":null,"abstract":"<div><div>Multi-target analgesics with minimal side effects and high efficacy are a key research focus in addressing the global pain crisis. Using a molecular networking approach, five pairs of potent analgesic alkaloid enantiomers were isolated from the roots of <em>Anacyclus pyrethrum</em> (<em>A</em>. <em>pyrethrum</em>). Their structures were elucidated by comprehensive spectroscopic data analysis, including LR-HSQMBC and <sup>1</sup>H–<sup>15</sup>N HMBC, quantum <sup>13</sup>C NMR DP4+ and ECD calculations, and single-crystal X-ray diffraction analysis. Anacyphrethines A (<strong>1</strong>) and B (<strong>2</strong>) are highly conjugated and polymethylated 6/6/6/6/5/7/5/5-fused octacyclic tetraazabic alkaloids possessing an unprecedented 8,14,18,24-tetraaza-octacyclo[16.8.2.1<sup>1,23</sup>.0<sup>4,28</sup>.0<sup>5,17</sup>.0<sup>9,16</sup>.0<sup>11,15</sup>.0<sup>21,27</sup>] nonacosane motif. Their biosynthetic pathways are proposed involving key aldol, hydroamination, and Schiff base reactions. All isolates showed potent analgesic effects <em>in vivo</em>. Even at a lower dose of 0.2 mg/kg, (±)-<strong>1</strong> and (+)-<strong>1</strong> still exhibited more potent analgesic activities than morphine. Interestingly, the racemic mixture (±)-<strong>1</strong> showed stronger analgesic effect than either pure enantiomer alone at higher doses of 5 and 1 mg/kg; while, (±)-<strong>1</strong> showed significant analgesic activities comparable to (+)-<strong>1</strong> at lower doses of 0.2 and 0.04 mg/kg. (+)-<strong>1</strong> had stronger analgesic effect than (−)-<strong>1</strong> at five tested does. Further tests on 44 analgesic-related targets demonstrated that (+)-<strong>1</strong> showed significant inhibitory effects against many ion channels such as TRPM8, Kv1.2, Kv1.3, and Ca<sub>v</sub>2.1 with IC<sub>50</sub> values of 1.10 ± 0.26, 4.20 ± 0.07, 2.20 ± 0.24, and 10.40 ± 0.69 μmol/L, respectively, while (−)-<strong>1</strong> primarily inhibited TRPC6, Kv1.2, and Kv1.3 ion channels with IC<sub>50</sub> values of 0.81 ± 0.05, 0.91 ± 0.04, and 1.50 ± 0.13 μmol/L, respectively, without affecting the opioid receptors, suggesting their non-opioid analgesic potentials. The molecular dockings provided structural guidance to develop potent non-opioid analgesics.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 7","pages":"Pages 3725-3737"},"PeriodicalIF":14.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572184","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}
Xiaohui Zhang , Xinyu Tang , Ting Gao , Yuanfang Guo , Guangping Lu , Qingbo Liu , Jiahao Li , Jie Wang , Mingrui Liu , Dongmei Zhang , Yufeng Tang , Junlian Gu
{"title":"Melatonin receptor 1a alleviates sleep fragmentation-aggravated testicular injury in T2DM by suppression of TAB1/TAK1 complex through FGFR1","authors":"Xiaohui Zhang , Xinyu Tang , Ting Gao , Yuanfang Guo , Guangping Lu , Qingbo Liu , Jiahao Li , Jie Wang , Mingrui Liu , Dongmei Zhang , Yufeng Tang , Junlian Gu","doi":"10.1016/j.apsb.2025.05.018","DOIUrl":"10.1016/j.apsb.2025.05.018","url":null,"abstract":"<div><div>A major obstacle in type 2 diabetes mellitus (T2DM) is sleep fragmentation (SF), which negatively affects testicular function. However, the underlying mechanisms remain to be elucidated. In this study, we demonstrate that SF induces testicular damage through a mechanism involving lipid metabolism, specifically mediated by melatonin (MEL) receptor 1a (MT1). T2DM mice with SF intervention displayed several deleterious phenotypes such as apoptosis, deregulated lipid metabolism, and impaired testicular function. Unexpectedly, sleep recovery (SR) for 2 consecutive weeks could not completely abrogate SF's detrimental effects on lipid deposition and testicular function. Interestingly, MEL and MT1 agonist 2-iodomelatonin (2IM) effectively improved lipid homeostasis, highlighting MEL/2IM as a promising therapeutic drug for SF-trigged testicular damage. Mechanistically, MEL and 2IM activated FGFR1 and sequentially restrained the crosstalk and physical interaction between TAB1 and TAK1, which ultimately suppressed the phosphorylation of TAK1 to block lipid deposition and cell apoptosis caused by SF. The ameliorating effect of MEL/2IM was overtly nullified in <em>Fgfr1</em> knockout (<em>Fgfr1-KO</em><sup><em>+/–</em></sup>) diabetic mice. Meanwhile, testicular-specific overexpression of <em>Tak1</em> abolished the protective effect of FGF1<sup>mut</sup> on diabetic mouse testis. Our findings offer valuable insights into the molecular mechanisms underlying the testicular pathogenesis associated with SF and propose a novel therapeutic approach for addressing male infertility in T2DM.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 7","pages":"Pages 3591-3610"},"PeriodicalIF":14.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572778","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}
Yajun Wang , Xueni Zhang , Mengli Qing , Wen Dang , Xuemei Bai , Yingjie Wang , Di Zhou , Lingjuan Zhu , Degang Qing , Juan Zhang , Gang Chen , Ning Li
{"title":"Trends in intestinal aging: From underlying mechanisms to therapeutic strategies","authors":"Yajun Wang , Xueni Zhang , Mengli Qing , Wen Dang , Xuemei Bai , Yingjie Wang , Di Zhou , Lingjuan Zhu , Degang Qing , Juan Zhang , Gang Chen , Ning Li","doi":"10.1016/j.apsb.2025.05.011","DOIUrl":"10.1016/j.apsb.2025.05.011","url":null,"abstract":"<div><div>Intestinal aging is central to systemic aging, characterized by a progressive decline in intestinal structure and function. The core mechanisms involve dysregulation of epithelial cell renewal and gut microbiota dysbiosis. In addition to previous results in model organisms like <em>Drosophila melanogaster</em>, recent studies have shown that in mammalian models, aging causes increased intestinal permeability and intestinal-derived systemic inflammation, thereby affecting longevity. Therefore, anti-intestinal aging can be an important strategy for reducing frailty and promoting longevity. There are three key gaps remaining in the study of intestinal aging: (1) overemphasis on aging-related diseases rather than the primary aging mechanisms; (2) lack of specific drugs or treatments to prevent or treat intestinal aging; (3) limited aging-specific dysbiosis research. In this review, the basic structures and renewal mechanisms of intestinal epithelium, and mechanisms and potential therapies for intestinal aging are discussed to advance understanding of the causes, consequences, and treatments of age-related intestinal dysfunction.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 7","pages":"Pages 3372-3403"},"PeriodicalIF":14.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572730","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}
Yufei Hui , Xue Jiao , Li Yang , Dejin Lu , Yanbo Han , Wen Yang , Yanli Cao , Yuxi Miao , Shiqiang Gong , Minjie Wei
{"title":"Indoleamine-2,3-dioxygenase: An important controller in maintaining mesenchymal stem cell-mediated immunomodulatory homeostasis","authors":"Yufei Hui , Xue Jiao , Li Yang , Dejin Lu , Yanbo Han , Wen Yang , Yanli Cao , Yuxi Miao , Shiqiang Gong , Minjie Wei","doi":"10.1016/j.apsb.2025.04.022","DOIUrl":"10.1016/j.apsb.2025.04.022","url":null,"abstract":"<div><div>Mesenchymal stem cells (MSCs) have been widely used in the treatment of various autoimmune and inflammation-related diseases due to their potent immunomodulatory properties. Several studies have demonstrated that MSC-mediated immunomodulation is complex and bidirectional, with the <em>in vivo</em> microenvironment influencing the direction of this modulation. Indoleamine-2,3-dioxygenase (IDO), an immunosuppressive factor, has been identified as a key “switch” in the immunomodulatory role of MSCs. In this review, we explore how IDO functions as a critical regulator of MSC immunoregulatory plasticity. We delve into the mechanisms by which changes in IDO expression affect the function of various immune cells, summarize relevant research and clinical advances regarding the role of IDO expression in MSC-based therapies for various diseases, and discuss potential therapeutic strategies that target IDO to enhance the stability of MSC therapeutic effects. This provides a theoretical foundation for optimizing MSCs as safer and more effective clinical therapeutic agents.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 7","pages":"Pages 3404-3418"},"PeriodicalIF":14.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572731","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}