Bioorganic Chemistry最新文献

{"title":"Steroid and bioactive molecule conjugates: Improving therapeutic approaches in disease management.","authors":"Anna Kawka, Hanna Koenig, Tomasz Pospieszny","doi":"10.1016/j.bioorg.2024.107933","DOIUrl":"https://doi.org/10.1016/j.bioorg.2024.107933","url":null,"abstract":"<p><p>Conjugates of steroids and other natural bioactive molecules (such as amino acids or carbohydrates) have proven promising compounds with diverse biological effects. This literature review summarises the importance of steroid conjugates in a broad spectrum of therapeutic applications. Steroid conjugates exhibit improved pharmacokinetic properties, improved target specificity, and reduced side effects compared to the parent compounds. This increases their clinical usefulness. Their versatility extends to drug delivery systems, enabling precise modulation of drug release kinetics and bioavailability. Moreover, steroid conjugates are vital in treating inflammatory and neurodegenerative diseases, hormonal disorders, cancer therapy, and combating microbial infections. The review presents the current state of research on steroid conjugates, highlighting the crucial role of steroid conjugates in modern medicine and their potential to revolutionise therapeutic paradigms and improve patient outcomes. Steroid compounds are excellent for developing agents with better bioavailability and are used as drug carriers or hydrogelators.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"107933"},"PeriodicalIF":4.5,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602249","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":"Structure-Based identification of a potent KDM7A inhibitor exerts anticancer activity through transcriptionally reducing MKRN1 in taxol- resistant and -sensitive triple-negative breast cancer cells.","authors":"Jin-Jin Shi, Yan-Jun Liu, Zhi-Guo Liu, Ru-Yi Chen, Ran Wang, Jing Yu, Chang-Yun Li, Guan-Jun Yang, Jiong Chen","doi":"10.1016/j.bioorg.2024.107945","DOIUrl":"https://doi.org/10.1016/j.bioorg.2024.107945","url":null,"abstract":"<p><p>KDM7A, a histone demethylase implicated in cancer proliferation, metastasis, and drug resistance, represents a crucial therapeutic target. Utilizing \"mcule.com\" for virtual screening of 100,000 compounds from the ZINC database, we identified 12 compounds with high affinity for KDM7A, with compound 4 emerging as the leading candidate for effectively inhibiting KDM7A's demethylase activity. Analysis of the GTRD database, the Breast Cancer Gene Expression Miner website, and recent studies highlighted MKRN1, a gene associated with cell proliferation and drug resistance, as a key intersecting factor. Compared to 2,4-pyridine dicarboxylic acid, compound 4 significantly reduced breast cancer stem cells and induced G1 phase cell cycle arrest. Mechanistically, compound 4 inhibited KDM7A's binding to H3K27me3, decreased MKRN1 transcription, and increased the levels of cell cycle regulators p16, p21, and p27, while reducing stem cell markers ALDH1A1, CD44, and CD133. These findings suggest that compound 4 could serve as a promising lead for selective KDM7A-targeting drugs. Additionally, this study is the first to demonstrate MKRN1 as a downstream gene of KDM7A, showing significant inhibitory effects in both taxol-resistant and drug-sensitive triple-negative breast cancer (TNBC) cells. This research offers new insights into the anticancer mechanisms of KDM7A inhibitors and underscores KDM7A's potential as a therapeutic target against TNBC.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"107945"},"PeriodicalIF":4.5,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602254","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":"Advances in drug discovery of flavivirus NS2B-NS3pro serine protease inhibitors for the treatment of Dengue, Zika, and West Nile viruses.","authors":"Emílio Emílio João, Juliana Romano Lopes, Bruna Fernanda Rodrigues Guedes, Paulo Ricardo da Silva Sanches, Chung Man Chin, Jean Leandro Dos Santos, Cauê Benito Scarim","doi":"10.1016/j.bioorg.2024.107914","DOIUrl":"https://doi.org/10.1016/j.bioorg.2024.107914","url":null,"abstract":"<p><p>Flaviviruses are vector-borne RNA viruses that seriously threaten global public health due to their high transmission index in humans, mainly in endemic areas. They spread infectious diseases that affect approximately 400 million people globally, primarily in developing countries struggling with persistent epidemic diseases. Viral infections manifest as hemorrhagic fever, encephalitis, congenital abnormalities, and fatalities. Despite nearly two decades of drug discovery campaigns, researchers have not identified promising lead compounds for clinical trials to treat or prevent flavivirus infections. Although scientists have made substantial progress through drug discovery approaches and vaccine development, resolving this complex issue might need some time. New therapeutic agents that can safely and effectively target key components of flaviviruses need to be identified. NS2B-NS3pro is an extensively studied pharmacological target among viral proteases. It plays a key role in the viral replication cycle by cleaving the polyprotein of flaviviruses and triggering the formation of structural and non-structural proteins. In this review, studies published from 2014 to 2023 were examined, and the specificity profile of compounds targeting NS2B-NS3 pro proteases for treating flavivirus infections was focused on. Additionally, the latest advancements in clinical trials were discussed. This article might provide information on the prospects of this promising pharmacological target.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"107914"},"PeriodicalIF":4.5,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637988","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":"Photochemical Metal-Free synthesis and biological Assessment of isocryptolepine analogues targeting estrogen receptor Alpha in breast cancer cells.","authors":"F B Bogdanov, R Yu Balakhonov, E S Volkov, I V Sonin, O E Andreeva, D V Sorokin, Yu A Piven, A M Scherbakov, V Z Shirinian","doi":"10.1016/j.bioorg.2024.107942","DOIUrl":"https://doi.org/10.1016/j.bioorg.2024.107942","url":null,"abstract":"<p><p>The aim of this study was to develop a new series of isocryptolepines and evaluate their antiproliferative and antiestrogenic activities on cancer cells. A series of isocryptolepine derivatives were synthesized using developed one-pot photochemical, metal-free protocol, employing readily available 2-arylindoles as starting compounds. The resulting isocryptolepines demonstrated (sub)micromolar inhibitory activity against selected breast cancer cell lines. The IC50 values ​​of lead compound 3c against hormone-dependent breast cancer types (MCF7 and T47D) were 0.3 μM and 0.12 μM, respectively, and significantly greater than 3 μM against estrogen receptor α (ERα)-deficient cell lines, MDA-MB-231 and HCC1954, respectively. To assess the antiestrogenic potency of compound 3c, MCF7 cells were transfected with a plasmid containing a luciferase reporter gene under the control of an estrogen-responsive element (ERE), creating the MCF7/ERE-LUC cell subline. In these cells, luciferase activity was induced by the natural ERα ligand, 17β-estradiol (E2). Compound 3c inhibited luciferase activity by 50 % at a concentration of 0.12 μM, highlighting its potent inhibitory effect on ERα. Molecular modeling further indicated that compound 3c could directly bind to ERα. Compound 3c induced apoptosis, as evidenced by PARP cleavage and downregulation of p-Bcl-2 and Bcl-2, and demonstrated synergistic effects in combination with the chemotherapeutic agent 5-fluorouracil. Compound 3c also showed selectivity towards hormone-dependent breast cancer cells, likely targeting ERα - a key driver in this cancer subtype. In summary, we report the development of a first-in-class antiestrogenic isocryptolepine with notable pro-apoptotic efficacy.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"107942"},"PeriodicalIF":4.5,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602169","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 potent hypoxia-inducible factor-1α (HIF-1α) degraders by proteolysis targeting chimera (PROTAC).","authors":"Yuying Li, Ruixue Zhu, Xuelian He, Yanjia Song, Ting Fan, Junhui Ma, Guangya Xiang, Xiang Ma","doi":"10.1016/j.bioorg.2024.107943","DOIUrl":"https://doi.org/10.1016/j.bioorg.2024.107943","url":null,"abstract":"<p><p>Under hypoxic conditions in tumor cells, HIF-1α is unable to bind to VHL E3 ligase due to the blocked hydroxylation reaction, resulting in impaired degradation and intracellular accumulation. Mounting evidences show a close association between HIF-1α overexpression and drug resistance, treatment failure, and increased mortality. To address HIF-1α overexpression, we innovatively introduced an E3 ligase ligand to the HIF-1α inhibitor IDF-11774 using the PROTACs strategy, aiming to reactivate the degradative pathway impeded under hypoxia, and thereby achieve the degradation of HIF-1α protein under hypoxia. Western blotting analyses demonstrated that most of our designed PROTACs effectively degraded HIF-1α. Among these, compounds C3 and V2 exhibited excellent anti-proliferation activity on MDA-MB-231 cells with IC₅₀ values of 48.98 μM and 7.54 μM, respectively. Both compounds induced protein degradation in a concentration-dependent manner, achieving degradation rates up to 80 %. Additionally, this degradation was inhibited by the proteasome inhibitor MG132. As a part of the ongoing effort to develop HIF-1 inhibitors, targeting the degradation of HIF-1α may offer an effective treatment strategy against solid tumors.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"107943"},"PeriodicalIF":4.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611347","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":"Exploring the selective incorporation of 15β-senecioyloxi-ent-kaurenoic acid methyl ester in Langmuir monolayers mimicking cell membranes.","authors":"Gustavo H O da Silva, Kevin F Dos Santos, Aline F Barcellos, Raquel M Ferreira de Sousa, Andre G Tempone, João Henrique G Lago, Luciano Caseli","doi":"10.1016/j.bioorg.2024.107941","DOIUrl":"https://doi.org/10.1016/j.bioorg.2024.107941","url":null,"abstract":"<p><p>A natural product isolated from Brazilian plant species Baccharis retusa (Asteraceae), 15β-senecioyloxi-ent-kaurenoic acid (1), demonstrated activity against trypomastigotes of the parasite Trypanosoma cruzi but it was inactive against intracellular forms. In the present work, compound 1a, a methyl ester derivative of 1, exhibited activity against intracellular amastigotes (EC₅₀ = 11.8 μM), similar to that determined by the standard drug benznidazol (EC₅₀ = 16.2 μM) and no toxicity against NCTC cells (CC₅₀ > 200 μM). Based on this selectivity, compound 1a was incorporated into Langmuir monolayers of three lipids, DPPC, DPPE, and DPPS, to characterize the interaction of the compound with each lipid as model for cell membranes. For that, we used tensiometry, surface potential measurements, and infrared spectroscopy. Our results showed that incorporating the drug into DPPC monolayers significantly altered the physicochemical properties, resulting in more condensed monolayers. In contrast, the incorporation of the drug into DPPE and DPPS monolayers led to their expansion. The effects on DPPC were more pronounced than on the other lipids, inducing a viscoelastic monolayer with lower alignment of the alkyl chains, as observed through surface potential measurements and infrared spectroscopy. These changes indicate a more cohesive DPPC monolayer upon drug incorporation, forming domains in a strip shape. We believe these results contribute to understanding the interaction between 1a and lipid interfaces, especially those involved in biological interactions with amastigotes of parasite T. cruzi.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"107941"},"PeriodicalIF":4.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611720","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":"The RIP3 activator C8 regulates the autophagy flux mediated by p62 and promotes the immunogenic form of cell death in human gastric cancer cells.","authors":"Xiaojie Liu, Yubin Jin, Mengli Zhang, Yanhe Jin, Jie Cao, Hangqi Dong, Xiangjing Fu, Cheng-Yun Jin","doi":"10.1016/j.bioorg.2024.107937","DOIUrl":"https://doi.org/10.1016/j.bioorg.2024.107937","url":null,"abstract":"<p><p>There has been growing interest in investigating anti-tumor drugs that not only kill cancer cells but also stimulate the immune system, among them, necroptosis is a classical immunogenic form of cell death. In our study, we discovered that by targeting RIP3, Jaspine B derivative C8 induces necroptosis and initiates cell death, and this effect can be reversed by knockout of RIP3. Furthermore, RIP3 initiates autophagy and binds to p62 to inhibit autophagic flux. Additionally, the autophagy process mediated by RIP3 activates the Nrf2 signaling pathway via the formation of the p62/Keap1 complex. Early autophagy inhibitors enhance necroptosis by impending the accumulation of p62 and restraining the activation of Nrf2, whereas late autophagy inhibitors partially prevent C8-induced necroptosis. Notably, the immunogenic form of cell death induced by C8 did not affect tumor immunity. Overall, C8 functions as a RIP3 activator to suppress the development of gastric cancer. Upon activation, RIP3 regulates p62-mediated autophagic flux and the Nrf2 signaling pathway through the RIP3/p62/Keap1 axis.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"107937"},"PeriodicalIF":4.5,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613408","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":"Functional interplay between short antimicrobial peptides and model lipid membranes.","authors":"Lorena Gratino, Marta Gogliettino, Marco Balestrieri, Alessandra Porritiello, Principia Dardano, Bruno Miranda, Rosa Luisa Ambrosio, Monica Ambrosio, Luigi Nicolais, Gianna Palmieri","doi":"10.1016/j.bioorg.2024.107939","DOIUrl":"https://doi.org/10.1016/j.bioorg.2024.107939","url":null,"abstract":"<p><p>Antimicrobial peptides (AMPs) are considered an attractive generation of novel antibiotics due to their advantageous properties such as a broad spectrum of antimicrobial activity against pathogens, low cytotoxicity, and drug resistance. Although they have common structural features and it has been widely demonstrated that bacterial membranes represent the main target of the peptide activity, the exact mechanism underlying the membrane perturbation by AMPs is not fully understood. Nevertheless, all the proposed modes of action implicate the preliminary interaction of AMPs with the negatively charged lipids in bacterial membranes. Recently, the structural and functional characterization of two AMPs, RiLK1 and RiLK3, was reported. Specifically, both peptides were revealed to be multitalented compounds capable of binding Gram-positive and Gram-negative liposome models with high affinity, but their mechanism of action remains elusive. In this paper, the effects of RiLK1 and RiLK3 on vesicles mimicking prokaryotic and eukaryotic cell membranes were further examined by using different approaches. Fluorescence and quenching assays either by acrylamide or lipophilic probes suggested that the peptides were mainly located at the interface of the negatively charged membranes that mimicked those of Salmonella Typhimurium and Staphylococcus aureus, possibly oriented in a parallel manner. Furthermore, RiLK1 and RiLK3 caused a significant leakage of carboxyfluorescein from bacterial liposomes, demonstrating that they can permeabilize the target membranes at high doses. Conversely, both peptides appear to behave like cell penetrating peptides (CPPs) at concentrations near their MIC values evaluated against the bacterial targets. Moreover, Dynamic Light Scattering provided further insights on the mechanisms of antimicrobial peptide against the bacterial liposomes. Conclusively, in vitro experiments indicated that RiLK1 and RiLK3 displayed potent bacteriostatic efficacy at low micromolar concentrations against an antibiotic-resistant ESKAPE pathogen, making them a valuable tool in preventing and treating infections caused by such bacteria.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"107939"},"PeriodicalIF":4.5,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, synthesis and FXR partial agonistic activity of anthranilic acid derivatives bearing aryloxy moiety as therapeutic agents for metabolic dysfunction-associated steatohepatitis.","authors":"Cong Chen, Xianghui Zhou, Wa Cheng, Xin Li, Bing Zhang, Jiaojiao Tu, Jieyun Meng, Yanfen Peng, Xiaoqun Duan, Qiming Yu, Xiangduan Tan","doi":"10.1016/j.bioorg.2024.107940","DOIUrl":"https://doi.org/10.1016/j.bioorg.2024.107940","url":null,"abstract":"<p><p>Farnesoid X receptor (FXR) is considered a promising therapeutic target for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). Increasing evidence suggests that targeting FXR with full agonists may lead to side effects. FXR partial agonists, which moderately activate FXR signaling, are emerging as a feasible approach to mitigate side effects and address MASH. Herein, a series of novel anthranilic acid derivatives bearing aryloxy moiety were designed and synthesized using a hybrid strategy from the previously identified FXR partial agonists DM175 and AIV-25. Particularly, compound 26 exhibited potent FXR partial agonistic activity in a dual-luciferase reporter gene assay with an EC₅₀ value of 0.09 ± 0.02 µM (75.13 % maximum efficacy relative to OCA). In the MASH mice model, compound 26 significantly ameliorated the pathological features of the liver, including steatosis, inflammation, and fibrosis. In addition, compound 26 displayed high selectivity, good oral bioavailability, high liver distribution, as well as an acceptable safety profile. Molecular simulation studies showed that compound 26 fitted well with the binding site of FXR. Collectively, these findings demonstrated that compound 26 might serve as a promising candidate targeting FXR for MASH treatment.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"107940"},"PeriodicalIF":4.5,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602189","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":"Multifrequency-STD NMR unveils the first Michaelis complex of an intramolecular trans-sialidase from Ruminococcus gnavus.","authors":"Serena Monaco, Louise E Tailford, Andrew Bell, Matthew Wallace, Nathalie Juge, Jesús Angulo","doi":"10.1016/j.bioorg.2024.107906","DOIUrl":"https://doi.org/10.1016/j.bioorg.2024.107906","url":null,"abstract":"<p><p>RgNanH is an intramolecular trans-sialidase expressed by the human gut symbiont Ruminococcus gnavus, to utilise intestinal sialylated mucin glycan epitopes. Its catalytic domain, belonging to glycoside hydrolase GH33 family, cleaves off terminal sialic acid residues from mucins, releasing 2,7-anhydro-Neu5Ac which is then used as metabolic substrate by R. gnavus to proliferate in the mucosal environment. RgNanH is one of the three intramolecular trans-sialidases (IT-sialidases) characterised to date, and the first from a gut commensal organism. Here, saturation transfer difference NMR (STD NMR) in combination with computational techniques (molecular docking and CORCEMA-ST) were used to elucidate the specificity, kinetics and relative affinity of RgNanH for sialoglycans and 2,7-anhydro-Neu5Ac. We propose the first 3D model for the Michaelis complex of an IT-sialidase. This confirms the sialic acid to be the main recognition element for the interaction in the enzymatic cleft and highlights the crucial role of Trp698 to make CH-π stacking with the galactose residue of the substrate 3'-sialyllactose. The same contact is shown not to be possible for 6'-sialyllactose, due to geometrical constrains of the α-2,6 linkage. Indeed 6'-sialyllactose is not a substrate, even though it is shown to bind to RgNanH by STD NMR. These findings corroborate the role of Trp698 for the α-2,3 specificity of IT-sialidases. In this structural study, the use of Differential Epitope Mapping STD NMR (DEEP-STD NMR) approach allowed the validation of the proposed 3D models in solution. These structural approaches are shown to be instrumental in shedding light on the molecular mechanisms underpinning enzymatic reactions in the absence of enzyme-substrate X-ray structures.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"107906"},"PeriodicalIF":4.5,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602215","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}