Fangfang Jiao, Pinkai Wang, Derong Zeng, Yiqiong Bao, Yan Zhang, Jun Tao, Jingjing Guo
{"title":"Identification of Potential PBP2a Inhibitors Against Methicillin-Resistant Staphylococcus aureus via Drug Repurposing and Combination Therapy","authors":"Fangfang Jiao, Pinkai Wang, Derong Zeng, Yiqiong Bao, Yan Zhang, Jun Tao, Jingjing Guo","doi":"10.1111/cbdd.70088","DOIUrl":"https://doi.org/10.1111/cbdd.70088","url":null,"abstract":"<div>\u0000 \u0000 <p>Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) achieves high-level resistance against β-lactam antibiotics through the expression of penicillin-binding protein 2a (PBP2a), which features a closed active site that impedes antibiotic binding. Herein, we implemented a strategy that combines drug repurposing with synergistic therapy to identify potential inhibitors targeting PBP2a's allosteric site from an FDA-approved drug database. Initially, retrospective verifications were conducted, employing different Glide docking methods (HTVS, SP, and XP) and two representative PBP2a structures. The combination of Glide SP and one representative PBP2a conformation showed the highest efficacy in identifying active compounds. The optimized parameters were then utilized to screen FDA-approved drugs, and 15 compounds were shortlisted for potential combination therapy with cefazolin, an ineffective cephalosporin against MRSA. Through biological assays—checkerboard, time-kill assays, and live/dead bacterial staining—we discovered that four compounds exhibited robust bactericidal activity (FICI < 0.5) compared to both untreated control and monotherapy with cefazolin alone. Scanning electron microscopy (SEM) confirmed that while cefazolin alone did not cause visible damage to MRSA cells, the combination treatment markedly induced cell lysis. Additional MM-GBSA studies underscored the strong binding affinity of mitoxantrone to the allosteric site. These findings introduce a combination therapy approach that potentially restores MRSA's susceptibility to β-lactam antibiotics.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Targeting Blood-Stage Malaria: Design, Synthesis, Characterization, In Vitro, and In Silico Evaluation of Pyrrolidinodiazenyl Chalcones","authors":"Ahammed Ameen Thottasseri, Vinoth Rajendran, Deepthi Ramesh, Anju Agnes Tom, Roshiny Roy Thomas, Sreetama Ray, Gopika Gopan, Maheswaran Mani, Tharanikkarasu Kannan","doi":"10.1111/cbdd.70081","DOIUrl":"https://doi.org/10.1111/cbdd.70081","url":null,"abstract":"<div>\u0000 \u0000 <p>Malaria is a pervasive and deadly threat to the global population, and the resources available to treat this disease are limited. There is widespread clinical resistance to the most commonly prescribed antimalarial drugs. To address this issue, we synthesized a range of 4′-pyrrolidinodiazenyl chalcones using a covalent bitherapy approach to study their potential antimalarial properties. We examined the structure–activity relationships of these compounds, which could explain their antimalarial activities. The in vitro blood stage antimalarial activity of the compounds was evaluated against the mixed-blood stage culture (ring, trophozoites and schizonts) of <i>Plasmodium falciparum</i> 3D7, and the 50% inhibitory concentrations (IC<sub>50</sub>s) ranged from 3.3 to 22.2 μg/mL after 48 h of exposure. Compounds <b>11</b>, <b>19</b>, and <b>22</b> displayed pronounced IC<sub>50</sub> values of 7.6 μg/mL, 6.4 μg/mL, and 3.3 μg/mL, respectively. The in vitro cytotoxicity of the active compounds was evaluated on human-derived Mo7e cells and murine-derived BA/F3 cells. Compounds <b>11</b> and <b>19</b> were found to be noncytotoxic (> 40 μg/mL), whereas compound <b>22</b> displayed cytotoxicity at higher concentrations. Moreover, these compounds exerted negligible hemolytic effects on human RBCs at their active concentrations. Molecular docking of these compounds revealed good hydrophobic and hydrogen bonding interactions with the binding sites of <i>Plasmodium falciparum</i>-dihydrofolate reductase, providing a rationale for their antimalarial activity, which is consistent with the in vitro results.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qingxin Liu, Aoqi Luo, Hongwei Jin, Xinxin Si, Ming Li
{"title":"Machine Learning-Based Discovery of a Novel Noncovalent MurA Inhibitor as an Antibacterial Agent","authors":"Qingxin Liu, Aoqi Luo, Hongwei Jin, Xinxin Si, Ming Li","doi":"10.1111/cbdd.70084","DOIUrl":"https://doi.org/10.1111/cbdd.70084","url":null,"abstract":"<div>\u0000 \u0000 <p>The bacterial cell wall is crucial for maintaining the integrity of bacterial cells. UDP-N-acetylglucosamine 1-carboxyethylene transferase (MurA) is an important enzyme involved in bacterial cell wall synthesis. Therefore, it is an important target for antibacterial drug research. Although many MurA inhibitors have been discovered, only fosfomycin is still used as a MurA inhibitor in clinical practice. Owing to the long-term use of fosfomycin, the emergence of fosfomycin resistance is worrisome. Therefore, it is still necessary to discover new MurA inhibitors with different types of action than fosfomycin. In this study, we used AutoMolDesigner to construct a machine learning model combined with molecular docking to screen for noncovalent MurA inhibitors. We subsequently conducted the MurA inhibition activity assay and identified compound <b>L16</b> (N-(3-(benzo[d]oxazol-2-yl)-4-hydroxyphenyl) carbamoyl-4-methylbenzamide) as a moderately active MurA inhibitor (IC<sub>50</sub> = 26.63 ± 1.60 μM). The compound was structurally different from other known MurA inhibitors. We used molecular dynamics simulation to reveal possible interactions between the compound and MurA. In addition, we also found that compound <b>L16</b> was nontoxic to human liver cancer cells (HepG2) (IC<sub>50</sub> > 100 μM). In conclusion, through virtual screening and in vitro biological evaluation, we identified a novel structural type of MurA inhibitor which may become a candidate drug for inhibiting bacterial cell wall synthesis.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pei Chen, Jin Yang, Lin Chen, Chenhuan Liu, Zhihao Li, Xiaoming Long, Jinbang Wu, Bo Wu, Jianjun Wu
{"title":"Moscatilin Induces Ferroptosis in Clear Cell Renal Cell Carcinoma via the JAK–STAT Signaling Pathway","authors":"Pei Chen, Jin Yang, Lin Chen, Chenhuan Liu, Zhihao Li, Xiaoming Long, Jinbang Wu, Bo Wu, Jianjun Wu","doi":"10.1111/cbdd.70071","DOIUrl":"https://doi.org/10.1111/cbdd.70071","url":null,"abstract":"<div>\u0000 \u0000 <p>Moscatilin, a biphenyl compound derived from <i>Dendrobium nobile</i>, exhibits significant anti-tumor activity. However, the specific role of moscatilin in clear cell renal cell carcinoma (ccRCC) and its underlying molecular mechanisms have not been fully studied. This study aims to fill this gap by demonstrating through a series of experiments that moscatilin can effectively inhibit the proliferation and migration of ccRCC and induce its apoptosis process. More importantly, we found that moscatilin can also trigger ferroptosis in ccRCC, a process accompanied by significant increases in Fe<sup>2+</sup>, MDA (a lipid peroxidation product), and ROS (reactive oxygen species) levels, as well as decreases in mitochondrial membrane potential and GSH (glutathione) levels. These changes strongly suggest a key role for moscatilin in inducing ferroptosis. To further explore its underlying mechanism, we speculate that moscatilin may inhibit the phosphorylation level of the JAK–STAT signaling pathway, thereby blocking the function of the key protein SLC7A11 in the ferroptosis signaling pathway, which promotes the occurrence of ferroptosis. This discovery not only reveals a new mechanism of moscatilin in the treatment of ccRCC but also provides new ideas for the development of related drugs in the future. In summary, based on the important discovery that moscatilin can induce ferroptosis in ccRCC, we have reason to believe that moscatilin has the potential to become a new type of drug for the treatment of ccRCC.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ailanthone Restrains Osteosarcoma Growth and Metastasis by Decreasing the Expression of Regulator of G Protein Signaling 4 and Twist Family BHLH Transcription Factor 1","authors":"Qiang Tan, Hongzhan Liu, Qiaojing Shi","doi":"10.1111/cbdd.70075","DOIUrl":"https://doi.org/10.1111/cbdd.70075","url":null,"abstract":"<div>\u0000 \u0000 <p>Traditional Chinese medicine Ailanthone (AIL) has been confirmed to possess antimalarial, anti-inflammatory, and anticancer effects. Here, this study aimed to excavate the biological role and mechanism of AIL on osteosarcoma (OS) progression. Levels of Regulator of G protein signaling 4 (RGS4) and Twist Family BHLH Transcription Factor 1 (TWIST1) were detected by qRT-PCR and western blotting. In vitro and tumor formation experiments were conducted for functional analysis. The protein interaction between RGS4 and TWIST1 was verified by using a Co-immunoprecipitation assay. AIL impeded the proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) progression, but induced apoptosis in OS cells. RGS4 was highly expressed in OS tissues and cells and was decreased by AIL in cells. RGS4 silencing suppressed the growth and metastasis of OS cells, and RGS4 overexpression reversed the anticancer action of AIL in OS cells. Mechanistically, RGS4 interacted with TWIST1 and positively regulated its expression. TWIST1 was highly expressed in OS tissues and cells and could be reduced by AIL in cells. Moreover, TWIST1 overexpression abolished RGS4 silencing-triggered growth and metastasis inhibition in OS cells. Importantly, AIL impeded OS growth and metastasis in vivo by regulating RGS4 and TWIST1. Ailanthone restrained OS growth and metastasis by decreasing RGS4 and TWIST1 expression.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tanshinone IIA Reverses Osteogenic Differentiation of Bone Marrow Mesenchymal Stromal Cells Impaired by Glucocorticoids via the ERK1/2-CREB Signaling Pathway","authors":"Xiaodong Li, Xinyue Yang, Zelin Liu, Hongpeng Liu, Hang Lv, Xue Li, Xilin Xu, Yiwei Shen","doi":"10.1111/cbdd.70069","DOIUrl":"https://doi.org/10.1111/cbdd.70069","url":null,"abstract":"<div>\u0000 \u0000 <p>Glucocorticoids-induced osteoporosis poses a critical health issue due to its detrimental impact on bone marrow mesenchymal stem cells (BMSCs); Tanshinone IIA (TSA) emerges as a promising therapeutic intervention, demonstrating its capacity to reverse osteogenic differentiation impairment. The aim is to determine whether TSA enhances the osteogenic differentiation of BMSCs damaged by dexamethasone (DEX) through the ERK1/2 –CREB signaling pathway. BMSCs were treated with varying concentrations of DEX (0.1–30 μM) and TSA (0.04–5 μM) for 18 or 36 h. Cell viability was assessed using the MTT assay. Osteogenic differentiation was evaluated through Alizarin Red S staining and quantified by qRT-PCR for osteogenic markers such as Runx2 and ALP. Apoptosis was measured by Annexin V-FITC/PI staining and TUNEL/DAPI co-staining. The ERK1/2-CREB signaling pathway was examined using Western blot and immunofluorescence. TSA at 5 μM significantly bolstered BMSCs viability and osteogenic differentiation, reversing the deleterious effects of 30 μM DEX. TSA pre-treatment decreased apoptosis and ROS levels, and importantly, it enhanced the ERK1/2-CREB signaling pathway, as evidenced by increased phosphorylation of ERK1/2 and CREB. The ERK1/2 inhibitor PD98059 and siCREB abrogated TSA's protective effects, highlighting the pathway's significance. These findings indicate that TSA, through the ERK1/2-CREB axis, provides a protective strategy against DEX-induced impairment in BMSCs. TSA's modulation of the ERK1/2 –CREB pathway reverses DEX-induced osteogenic inhibition and apoptosis in BMSCs, suggesting its therapeutic efficacy against glucocorticoid-induced bone disorders.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Fused and Substituted Piperazines as Anticancer Agents: A Review","authors":"Saumya Singh, Rajnish Kumar, Shrishti Tripathi, Salahuddin, Avijit Mazumder, Nardev Singh","doi":"10.1111/cbdd.70077","DOIUrl":"https://doi.org/10.1111/cbdd.70077","url":null,"abstract":"<div>\u0000 \u0000 <p>Cancer is an abnormal and uncontrolled proliferation of normal cells. The availability of safer anticancer drugs with exceptional selectivity for healthy cells and great efficacy against various cancer forms continues to be a significant obstacle. The piperazine moiety is used as the building block of several molecules and is reported to have the ability to inhibit the cell cycle (G1/S phase), inhibit angiogenesis, and interact with DNA. Piperazine also has a flexible binding feature that allows it to interact with a variety of biological targets, which makes it effective against cancers. As there is a continuous need to obtain an anticancer drug with improved efficacy and fewer side effects, the piperazine derivatives attract the attention of researchers. This review highlights the recently reported methods of synthesis of fused/substituted piperazines, structure–activity relationship, and interactions with targets/receptors as anticancer agents. Thus, the presented review will help medicinal chemists in designing anticancer molecules with piperazines.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Identification of Potent Leucine-Rich Repeat Kinase 2 Inhibitors by Virtual Screening and Biological Evaluation","authors":"Hualiang Shen, Guoqi Yu, Tao Cai, Kai Hu, Tianbo Shang, Yanjuan Luo, Jiawei Zhu, Xiaoxue Bai, Yicheng Xiong, Meiyang Xi, Runpu Shen","doi":"10.1111/cbdd.70082","DOIUrl":"https://doi.org/10.1111/cbdd.70082","url":null,"abstract":"<div>\u0000 \u0000 <p>Parkinson's disease (PD) is the second most common neurodegenerative disease but has limited medications. Targeting leucine-rich repeat kinase 2 (LRRK2) has been identified as a potential strategy for the treatment of PD. The development of LRRK2 inhibitors has attracted much interest, and various compounds have been reported with significant improvement in preclinical and clinical models. Currently, no LRRK2 inhibitor has been approved for PD intervention. Herein, we reported a virtual screening (VS) workflow combining molecular docking and molecular dynamics (MD) simulations to achieve eight compounds for further enzymatic assay. The results indicated a potent LRRK2 inhibitor <b>2</b> with IC<sub>50</sub> values of 2.396 and 5.996 μM against LRRK2 and LRRK2 G2019S, respectively, implying the reliability of this VS approach. Combined with predicted favorable drug-like properties, this hit can be used as a starting point for further structural optimization, probably offering insight into targeting LRRK2 for PD treatment in the future.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bing He, Hong-zhou Tan, Cheng-bo Liu, Hong Wu, Li-qin He
{"title":"Synthesis and Antitumor Evaluation of a Novel Class of Chalcone Mannich Base Derivatives","authors":"Bing He, Hong-zhou Tan, Cheng-bo Liu, Hong Wu, Li-qin He","doi":"10.1111/cbdd.70079","DOIUrl":"https://doi.org/10.1111/cbdd.70079","url":null,"abstract":"<div>\u0000 \u0000 <p>A novel class of chalcone Mannich base derivatives <b>I</b><sub><b>1-9</b></sub> and <b>II</b><sub><b>1-11</b></sub> was synthesized, which exhibited significant antiproliferation activities in five different cancer cells. The activities of most compounds were superior to those of the positive control drug 5-FU. Moreover, compared with the intermediate chalcone, their water solubility was also significantly enhanced. Among them, the most prospective compound <b>I</b><sub><b>4</b></sub> (IC<sub>50</sub> = 3.09–5.08 μM for the tested cancer cells) can effectively inhibit the proliferation of A549/DDP cells (IC<sub>50</sub> = 4.69 μM). Further mechanistic studies revealed that it can induce apoptosis of A549 and A549/DDP cells by arresting the G2/M phase of the cell cycle. Although the selectivity of compound <b>I</b><sub><b>4</b></sub> between tumor cells and normal cells was not obvious, it might be a promising lead compound for lung cancer and is worthy of further investigation.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Protocatechuic Acid Alleviates Inflammation and Oxidative Stress in Acute Respiratory Distress Syndrome by Promoting Unconventional Prefoldin RPB5 Interactor 1-Mediated Mitophagy","authors":"Xianyong Li, Quankuan Gu, Jiaxi Xu, Bowen Liu, Peiyao Luo, Mingyan Zhao","doi":"10.1111/cbdd.70072","DOIUrl":"https://doi.org/10.1111/cbdd.70072","url":null,"abstract":"<div>\u0000 \u0000 <p>Protocatechuic acid (PCA) is a type of polyphenol with diverse biological activities, including antioxidant and anti-inflammatory properties. This study aimed to explore the function of PCA in acute respiratory distress syndrome (ARDS) and delve into its functional mechanism. Lipopolysaccharides were applied to stimulate human pulmonary microvascular endothelial cells (HPMECs) or C57BL/6 mice to generate ARDS models in vitro and in vivo. PCA treatment (300 μM for cells and 20 or 30 mg/kg for mice) reduced proinflammatory cytokine production and oxidative stress in HPMECs or mouse models, and it reduced cell apoptosis while alleviating alveolar septum thickening. Chromobox 4 (CBX4) was identified as a target protein of PCA, and it was found to activate the transcription of unconventional prefoldin RPB5 interactor 1 (URI1) by recruiting histone acetyltransferase general control nondepressible 5 (GCN5) to its promoter region. CBX4 and URI1 levels were reduced by LPS but restored by PCA. Knockdown of either CBX4 or URI1 negated the ameliorating effects of PCA on LPS-induced inflammation and oxidative stress and diminished the promoting roles of PCA in promoting mitochondrial biogenesis and mitophagy. This study suggests that PCA holds promise in alleviating inflammation and oxidative stress in ARDS by promoting CBX4/URI1-mediated mitophagy.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"105 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}