Bioorganic & Medicinal Chemistry最新文献

{"title":"Carbonic anhydrases: Moiety appended derivatives, medicinal and pharmacological implications","authors":"Aashish Jaitak,&nbsp;Khushi Kumari,&nbsp;Sanjay Kounder,&nbsp;Vikramdeep Monga","doi":"10.1016/j.bmc.2024.117933","DOIUrl":"10.1016/j.bmc.2024.117933","url":null,"abstract":"<div><div>In the realm of enzymology, Carbonic anhydrase (CA) emerges as a pivotal protagonist orchestrating the rapid conversion of carbon dioxide and water into bicarbonate ions and hydrogen ions, respectively. Carbonic anhydrase inhibitors (CAIs) are the class of drugs that target various isoforms of the enzyme, and these inhibitors play a crucial role in the treatment and management of multiple diseases such as cancer, glaucoma, high altitude sickness, rheumatoid arthritis, obesity, epilepsy, and sleep apnea. Several structural classes of CAIs developed till date possess unique architects of the pharmacophoric requirements around the central core moiety for the selective targeting of various isoforms of the CA. Recent advancements in drug design and development, along with technologies that aid in structure determination, have led to the development of several isoform-selective inhibitors of CA enzymes. However, their clinical development was hampered by the lack of desired therapeutic efficacy, isoform selectivity and safety profile. This review covers the most recent approaches used by different researchers concerned with the development of isoform-selective carbonic anhydrase inhibitors belonging to distinct structural classes like sulphonamides, carbazoles, selenols, coumarin, organotelluride, topiramate, thiophene, triazole, uracil-modified benzylic amines, and thiourea etc. In addition, their structure–activity relationships, biological evaluation, and <em>in silico</em> studies inlcuding the forthcoming avenues of advancements have been discussed. This review serves as a valuable resource for developing potent and efficacious CAIs with remarkable therapeutic implications; offering insights into their potency, specificity, and potential clinical applications.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"114 ","pages":"Article 117933"},"PeriodicalIF":3.3,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2-Arylhydrazinylidene-3-oxo-3-polyfluoroalkylpropanoic acids as selective and effective carboxylesterase inhibitors with powerful antioxidant potential","authors":"Yanina V. Burgart ,&nbsp;Galina F. Makhaeva ,&nbsp;Olga G. Khudina ,&nbsp;Olga P. Krasnykh ,&nbsp;Nadezhda V. Kovaleva ,&nbsp;Natalia A. Elkina ,&nbsp;Natalia P. Boltneva ,&nbsp;Elena V. Rudakova ,&nbsp;Sofya V. Lushchekina ,&nbsp;Evgeny V. Shchegolkov ,&nbsp;Galina A. Triandafilova ,&nbsp;Ksenia O. Malysheva ,&nbsp;Olga G. Serebryakova ,&nbsp;Sophia S. Borisevich ,&nbsp;Margarita G. Ilyina ,&nbsp;Ekaterina F. Zhilina ,&nbsp;Victor I. Saloutin ,&nbsp;Valery N. Charushin ,&nbsp;Rudy J. Richardson","doi":"10.1016/j.bmc.2024.117938","DOIUrl":"10.1016/j.bmc.2024.117938","url":null,"abstract":"<div><div>A series of 2-arylhydrazinylidene-3-oxo acids (AHOAs) was prepared by dealkylation of alkyl-2-arylhydrazinylidene-3-oxo-3-alkanoates with AlBr₃. Using X-Ray, NMR spectroscopy, and quantum mechanical calculations (QM), the existence of AHOAs in a thermodynamically favorable Z-form stabilized by two intramolecular H-bonds was established. All AHOAs had acceptable ADME parameters. The esterase profile study showed that polyfluoroalkyl-AHOAs were effective and selective carboxylesterase (CES) inhibitors, while they were inactive against acetyl- and butyrylcholinesterase. In agreement with molecular docking, the most effective CES inhibitors (IC₅₀ as low as 42 nM) were compounds bearing long polyfluoroalkyl substituents. The acids were also active against hCES1 and hCES2, and CF₃-containing acids possessed selectivity against hCES2. Non-fluorinated acids did not inhibit CES, but they exhibited potent antioxidant capability. AHOAs having unsubstituted phenyl or electron-donating groups in the arylhydrazinylidene moiety displayed high primary antioxidant activity in the ABTS, FRAP, and ORAC tests, which did not depend on the substituent in the acyl fragment in the ABTS and ORAC assays. The radical-scavenging mechanism of AHOAs was investigated using QM calculations, showing a preference for cleavage of N<img>H rather than O<img>H bonds. For the lead antioxidants, 4-methoxysubstituted AHOAs, protective effects on erythrocyte membranes in AAPH-induced oxidative stress conditions were shown, including membrane stabilizing activity, inhibition of AAPH-induced lipid peroxidation of erythrocyte membranes, and Fe(II)-chelating ability. Thus, a new class of potent and selective CES inhibitors with powerful antioxidant potential has been developed as promising co-drugs capable of regulating the metabolism of esterified drugs and scavenging reactive radicals that form during Phase I biotransformation.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"115 ","pages":"Article 117938"},"PeriodicalIF":3.3,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rational design, synthesis, and biophysical characterization of a peptidic MDM2-MDM4 interaction inhibitor","authors":"Marco Ballarotto ,&nbsp;Elisa Bianconi ,&nbsp;Sonia Valentini ,&nbsp;Andrea Temperini ,&nbsp;Fabiola Moretti ,&nbsp;Antonio Macchiarulo","doi":"10.1016/j.bmc.2024.117937","DOIUrl":"10.1016/j.bmc.2024.117937","url":null,"abstract":"<div><div>In recent years, the restoration of p53 physiological functions has become an attractive therapeutic approach to develop novel and efficacious cancer therapies. Among other mechanisms, the oncosuppressor protein p53 is functionally regulated by MDM2 through its E3 ligase function. MDM2 promotes p53 ubiquitination and degradation following homodimerization or heterodimerization with MDM4. Recently, we discovered Pep3 (<strong>1</strong>, Pellegrino <em>et al.</em>, 2015), a novel peptidic inhibitor of MDM2 dimerization able to restore p53 oncosuppressive functions both <em>in vitro</em> and <em>in vivo</em>. In this work, we were able to identify the key interactions between peptide <strong>1</strong> and MDM2 RING domain and to design peptide <strong>2</strong>, a truncated version of <strong>1</strong> that is still able to bind MDM2. Integrating both computational and biophysical techniques, we show that peptide <strong>2</strong> maintains the conserved peptide <strong>1</strong>-MDM2 interactions and is still able to bind to full-length MDM2.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"113 ","pages":"Article 117937"},"PeriodicalIF":3.3,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design of a potent and selective dual JAK1/TYK2 inhibitor","authors":"Oscar Mammoliti ,&nbsp;Christel Menet ,&nbsp;Céline Cottereaux ,&nbsp;Javier Blanc ,&nbsp;Ann De Blieck ,&nbsp;Ghjuvanni Coti ,&nbsp;Raphaël Geney ,&nbsp;Line Oste ,&nbsp;Koen Ostyn ,&nbsp;Adeline Palisse ,&nbsp;Evelyne Quinton ,&nbsp;Benoit Schmitt ,&nbsp;Monica Borgonovi ,&nbsp;Isabelle Parent ,&nbsp;Catherine Jagerschmidt ,&nbsp;Steve De Vos ,&nbsp;Béatrice Vayssiere ,&nbsp;Miriam López-Ramos ,&nbsp;Kenji Shoji ,&nbsp;Reginald Brys ,&nbsp;Caroline Joannesse","doi":"10.1016/j.bmc.2024.117932","DOIUrl":"10.1016/j.bmc.2024.117932","url":null,"abstract":"<div><div>Janus kinase (JAK) inhibitors have gathered interest as treatments for several inflammatory and autoimmune diseases. The four first marketed inhibitors target JAK1, with varying selectivity towards other JAK family members, but none inhibit tyrosine kinase-2 (TYK2) at clinically relevant doses. TYK2 is required for the signaling of the interleukin (IL)-12 and IL-23 cytokines, which are key to the polarization of T_H1 and T_H17 cells, respectively; two cell subtypes that play major roles in inflammatory diseases. Herein, we report our effort towards the optimization of a potent and selective dual JAK1/TYK2 inhibitor series starting from a HTS hit. Structural information revealed vectors required to improve both JAK1 and TYK2 potency as well as selectivity towards JAK2. The potent inhibition of both JAK1 (3.5 nM) and TYK2 (5.7 nM) in biochemical assays by our optimized lead compound, as well as its notable selectivity against JAK2, were confirmed in cellular and whole blood assays. Inhibition of TYK2 by the lead compound was demonstrated by dose-dependent efficacy in an IL-23-induced psoriasis-like inflammation mouse model.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"114 ","pages":"Article 117932"},"PeriodicalIF":3.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A methamphetamine vaccine using short monoamine and diamine peptide linkers and poly-mannose","authors":"Md Kamal Hossain ,&nbsp;Majid Davidson ,&nbsp;Jack Feehan ,&nbsp;John M Matsoukas ,&nbsp;Kulmira Nurgali ,&nbsp;Vasso Apostolopoulos","doi":"10.1016/j.bmc.2024.117930","DOIUrl":"10.1016/j.bmc.2024.117930","url":null,"abstract":"<div><p>Methamphetamine (METH) substance use disorder is a long-standing and ever-growing public health concern. Efforts to develop successful immunotherapies are ongoing with vaccines that generate strong antibody responses are an area of significant research interest. Herein, we describe the development of a METH Hapten conjugate vaccine comprised of either two short-length peptides as linkers and mannan as an immunogenic delivery carrier. Initially, Hapten 1 (with a monoamine linker) and Hapten 2 (with a diamine linker) were synthesised. Each step of the Hapten synthesis were characterized by LC-MS and purified by Flash Chromatography and the identity of the purified Haptens were confirmed by ¹H NMR. Haptens were conjugated with mannan (a polymannose), and conjugation efficiency was confirmed by LC-MS, TLC, ¹H NMR, and 2,4 DNPH tests. The immunogenic potential of the two conjugated vaccines were assessed in mice with a 3-dose regimen. Concentrations of anti-METH antibodies were measured by enzyme-linked immunosorbent assay. All the analytical techniques confirmed the identity of Hapten 1 and 2 during the synthetic phase. Similarly, all the analytical approaches confirmed the conjugation between the Haptens and mannan. Mouse immunogenicity studies confirmed that both vaccine candidates were immunogenic and the vaccine with the monoamine linker plus adjuvants induced the highest antibody response after the second booster.</p></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"113 ","pages":"Article 117930"},"PeriodicalIF":3.3,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0968089624003444/pdfft?md5=147a11aefdf9620c7b11a6c2c2573a34&pid=1-s2.0-S0968089624003444-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142274718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing molecular probes for imaging of human epidermal growth factor receptor (HER) family","authors":"Na Li ,&nbsp;Shengxi Chen ,&nbsp;Xiaoqing Cai","doi":"10.1016/j.bmc.2024.117931","DOIUrl":"10.1016/j.bmc.2024.117931","url":null,"abstract":"<div><div>The human epidermal growth factor receptor (HER) family plays a critical role in the development, migration, and invasion of various cancers. Currently, the FDA has approved numerous targeting therapies for the HER family consist of small molecule drugs, monoclonal antibodies and antibody-drug conjugates. To facilitate precision therapy using currently approved targeted agents, early detection and quantification of each HER receptor are essential for assessment, treatment, and prognostic purposes. This study provides a comprehensive review of the latest advancements in detection and quantification of HER receptors, including traditional biopsies, liquid biopsies, and non-invasive detection methods. Although traditional histological methods, such as immunohistochemistry (IHC) and fluorescence <em>in situ</em> hybridization (FISH), have yielded valuable insights, advancements in real-time and non-invasive detection technologies necessitate improved methods for the dynamic evaluation of HER status. This article also reviews several emerging real-time techniques for detecting and quantifying HER status in circulating tumor cells (CTCs) extracted from blood samples, as well as <em>in vivo</em> assessments using positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging. This review emphasizes the importance of continuous innovation in the application of HER receptor imaging technologies, with the goal of enhancing treatment outcomes and prognoses for cancer patients.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"113 ","pages":"Article 117931"},"PeriodicalIF":3.3,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research progress of BRD4 in head and neck squamous cell carcinoma: Therapeutic application of novel strategies and mechanisms","authors":"Jiao Tang ,&nbsp;Huaqiu Chen ,&nbsp;Hengrui Fan ,&nbsp;Tao Chen ,&nbsp;Chunlan Pu ,&nbsp;Yuanbiao Guo","doi":"10.1016/j.bmc.2024.117929","DOIUrl":"10.1016/j.bmc.2024.117929","url":null,"abstract":"<div><div>Bromodomain-containing protein 4 (BRD4) belongs to the bromodomain and extra-terminal domain (BET) protein family, which plays a crucial role in recognizing acetylated lysine residues in chromatin. The abnormal expression of BRD4 contributes to the development of various human malignant tumors, including head and neck squamous cell carcinoma (HNSCC). Recent studies have shown that BRD4 inhibition can effectively prevent the proliferation and growth of HNSCC. However, the specific role and mechanism of BRD4 in HNSCC are not yet fully clarified. This article will briefly summarize the critical role of BRD4 in the pathogenesis of HNSCC and discuss the potential clinical applications of targeting BRD4 in HNSCC therapy. We further inquiry the challenges and opportunities for HNSCC therapies based on BRD4 inhibition, including BRD4 inhibitor combination with conventional chemotherapy, radiotherapy, and immunotherapy, as well as new strategies of BRD4-targeting drugs and BRD4 proteolysis-targeting chimeras (PROTACs). Moreover, we will also offer outlook on the associated challenges and future directions of targeting BRD4 for the treatment of patients with HNSCC.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"113 ","pages":"Article 117929"},"PeriodicalIF":3.3,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142312225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 biological evaluation of novel diphenylamine analogues as NLRP3 inflammasome inhibitors","authors":"Tongtong Kang ,&nbsp;Simin Sun ,&nbsp;Huimin Wang ,&nbsp;Jinyu Liu ,&nbsp;Xiaoyang Li ,&nbsp;Yuqi Jiang","doi":"10.1016/j.bmc.2024.117927","DOIUrl":"10.1016/j.bmc.2024.117927","url":null,"abstract":"<div><div>The aberrant activation of the NLRP3 inflammasome has been implicated in the pathogenesis of numerous inflammation-related diseases. Development of NLRP3 inflammasome inhibitors is expected to provide a new strategy for the treatment of these diseases. Herein, a novel series of diphenylamine derivatives were designed based on the lead compounds <strong>H20</strong> and <strong>H28</strong>, and the preliminary structure–activity relationship was studied. The representative compound <strong>19</strong> displayed significantly higher inhibitory activity against NLRP3 inflammasome compared to lead compounds <strong>H20</strong> and <strong>H28</strong>, with an IC₅₀ of 0.34 μM. Mechanistic studies indicated that compound <strong>19</strong> directly targets the NLRP3 protein (<em>K</em>_D: 0.45 μM), blocking the assembly and activation of the NLRP3 inflammasome, leading to anti-inflammatory effects and inhibition of cellular pyroptosis. Our findings indicated that compound <strong>19</strong> is a promising NLRP3 inhibitor and could potentially serve as a lead compound for further optimization.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"113 ","pages":"Article 117927"},"PeriodicalIF":3.3,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142312226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of phenanthridine derivatives by a water-compatible gold-catalyzed hydroamination","authors":"Yixuan Lin ,&nbsp;Riichi Hashimoto ,&nbsp;Tsung-Che Chang ,&nbsp;Katsunori Tanaka","doi":"10.1016/j.bmc.2024.117928","DOIUrl":"10.1016/j.bmc.2024.117928","url":null,"abstract":"<div><p>Since transition-metal-catalyzed reactions are one of the most powerful and direct approaches for the synthesis of organic molecules, translating them to biological systems for biomedical applications is an emerging field. The manipulation of transition metal reactions in biological settings for uncaging prodrugs and synthesizing bioactive drugs has been widely studied. To expand the toolbox of transition-metal-mediated prodrug strategy, this work introduces the 2′-alkynl-biphenylamine precursors for the synthesis of phenanthridine derivatives using a water-compatible gold-catalyzed hydroamination under mild conditions. Moreover, the structure–reactivity relationship revealed that the nucleophilicity of the amine group in the precursor was critical for facilitating the gold-catalyzed synthesis of phenanthridine derivatives. The research shows the potential to be used for phenanthridine-based prodrug designs in an aqueous solution.</p></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"113 ","pages":"Article 117928"},"PeriodicalIF":3.3,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142238569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A review on synthetic inhibitors of dual-specific tyrosine phosphorylation-regulated kinase 1A (DYRK1A) for the treatment of Alzheimer’s disease (AD)","authors":"Pinky Gehlot ,&nbsp;Rekha Pathak ,&nbsp;Sunil Kumar ,&nbsp;Naveen Kumar Choudhary ,&nbsp;Vivek Kumar Vyas","doi":"10.1016/j.bmc.2024.117925","DOIUrl":"10.1016/j.bmc.2024.117925","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is a complex disorder that is influenced by a number of variables, such as age, gender, environmental factors, disease, lifestyle, infections, and many more. The main characteristic of AD is the formation of amyloid plaque and neurofibrillary tangles (NFT), which are caused by various reasons such as inflammation, impairment of neurotransmitters, hyperphosphorylation of tau protein, generation of toxic amyloid beta (Aβ) 40/42, oxidative stress, etc. Protein kinases located in chromosome 21, namely dual-specific tyrosine phosphorylation-regulated kinase 1A (DYRK1A), play an essential role in the pathogenesis of AD. DYRK1A stimulates the Aβ peptide aggregation and phosphorylation of tau protein to generate the NFT formation that causes neurodegeneration. Thus, DYRK1A is associated with AD, and inhibition of DYRK1A has the potential to treat AD. In this review, we discussed the pathophysiology of AD, various factors responsible for AD, and the role of DYRK1A in AD. We have also discussed the latest therapeutic potential of DYRK1A inhibitors for neurogenerative disease, along with their structure–activity relationship (SAR) studies. This article provides valuable information for guiding the future discovery of novel and target-specific DYRK1A inhibitors over other kinases and their structural optimization to treat AD.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"113 ","pages":"Article 117925"},"PeriodicalIF":3.3,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}