Medicinal Chemistry Research最新文献

{"title":"Structure-based discovery of acridone alkaloids as disruptors of the HEG1-KRIT1 protein-protein interaction in cerebral cavernous malformation signaling.","authors":"Emadeldin M Kamel, May Bin-Jumah, Haifa E Alfassam, Raghad A Alotaibi, Ahmed A Allam, Fahad M Alshabrmi, Faris F Aba Alkhayl, Al Mokhtar Lamsabhi","doi":"10.1007/s00044-026-03627-1","DOIUrl":"https://doi.org/10.1007/s00044-026-03627-1","url":null,"abstract":"<p><p>The HEG1-KRIT1 interaction is essential for endothelial cerebral cavernous malformation complex localization and signaling, making this interface a relevant target for chemical disruption. This study aimed to identify acridone alkaloids capable of inhibiting HEG1 binding to KRIT1 through integrated virtual screening, molecular simulations, binding-energy analysis, drug-likeness prediction, and experimental validation. Screening of 2,449 acridone alkaloids prioritized five candidates: 5-hydroxynoracronycine, acronycine, arborinine, glycocitrine I, and rutacridone. Computational analyses showed stable binding within the HEG1-recognition pocket of KRIT1 and predicted interface weakening, with rutacridone and 5-hydroxynoracronycine producing the strongest destabilizing effects. A bead-based flow-cytometry competition assay confirmed concentration-dependent inhibition, with half-maximal inhibitory concentration values of 2.21 ± 0.31 µM for rutacridone, 2.30 ± 0.30 µM for arborinine, and 2.90 ± 0.35 µM for 5-hydroxynoracronycine. These findings identify rutacridone, arborinine, and 5-hydroxynoracronycine as promising acridone-based starting points for developing HEG1-KRIT1 interaction disruptors. The image explains the difference between normal and disrupted HEG1-KRIT1 protein interactions affecting CCM signaling. On the left, the homeostatic HEG1-KRIT1 complex forms at the endothelial cell membrane, where HEG1 and VE-cadherin proteins connect with KRIT1 (FERM domain) and CCM2 and CCM3 proteins. This complex activates a signaling cascade through MEKK3, MEK5, ERK5, MEF2, and KLF2/4, resulting in regulated CCM signaling. On the right, a small-molecule protein-protein interaction disruptor blocks the binding between HEG1 and KRIT1, shown by a red cross. This disruption prevents the normal complex formation, leading to dysregulated CCM signaling and an altered KLF2/4 transcriptional response. A predicted binding model illustrates the small molecule at the HEG1-KRIT1 interface, with HEG1 cytoplasmic tail and KRIT1 FERM domain labeled.</p>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178653","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":"Coumarin scaffolds in breast cancer research: derivatives, hybrids, and therapeutic potential.","authors":"Shagufta, Irshad Ahmad, Isha Khan, Maimonah Al Zubaidi, Aayat Aladhamy","doi":"10.1007/s00044-026-03629-z","DOIUrl":"https://doi.org/10.1007/s00044-026-03629-z","url":null,"abstract":"<p><p>Breast cancer remains one of the most common cancers worldwide and continues to present major therapeutic challenges due to tumor diversity, drug resistance, and recurrence. These issues highlight the need for new treatments with better selectivity and multitarget effects. Coumarins, a class of naturally occurring benzopyran-2-one derivatives, have attracted significant interest in medicinal chemistry because of their structural flexibility, favorable drug-like properties, and broad range of biological activities. The coumarin scaffold offers several chemically accessible sites for extensive structural modification, facilitating the development of derivatives and hybrid molecules with improved pharmacological profiles. This review covers recent advances in developing coumarin-based derivatives and hybrid compounds as potential agents for breast cancer treatment. Overall, coumarin scaffolds remain promising platforms for designing multitarget anticancer agents and continue to offer valuable opportunities for creating new therapeutic strategies against breast cancer. This diagram presents coumarin as a central chemical structure with two categories of related compounds: derivatives and hybrid molecules. Derivatives are associated with potent anticancer activity, structural diversity, and multiple mechanisms. Hybrid molecules are linked to molecular hybridization, enhanced efficacy, and broad therapeutic potential. Both categories are connected to an effect on breast cancer cells.</p>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178676","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":"Special issue of Medicinal Chemistry Research in honor of Dr. Kenneth A. Jacobson","authors":"Carola Gallo-Rodriguez,&nbsp;Juan Bautista Rodriguez,&nbsp;Pnina Fishman","doi":"10.1007/s00044-026-03630-6","DOIUrl":"10.1007/s00044-026-03630-6","url":null,"abstract":"","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"35 10","pages":"1819 - 1820"},"PeriodicalIF":3.5,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00044-026-03630-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bicyclononane-2,8-bis(trifluoromethyl)quinoline hybrids: synthesis, antiplasmodial and antitrypanosomal activity.","authors":"Johanna Dolensky, Werner Seebacher, Eva-Maria Pferschy-Wenzig, Miriam Zehentner, Robert Saf, Pascal Mäser, Monica Cal, Robert Weis","doi":"10.1007/s00044-026-03628-0","DOIUrl":"https://doi.org/10.1007/s00044-026-03628-0","url":null,"abstract":"<p><p>With the aim to design dual-acting antiprotozoals, a set of hybrid-molecules was prepared. Amino-substituted 2-aza- and 3-azabicyclo[3.2.2]nonanes with antiplasmodial and antitrypanosomal activity were linked via aminoalkyl linkers to the 2,8-bis(trifluoromethyl)quinoline scaffold of mefloquine. All newly synthesized compounds were characterized by IR spectroscopy, NMR spectroscopy, and HRMS. Their antiplasmodial activities were examined in vitro against the NF54 strain of Plasmodium falciparum and their antitrypanosomal activity against the STIB900 strain of Trypanosoma brucei rhodesiense. Most of the compounds showed antiprotozoal activity in submicromolar concentration. Structure-activity relationships concerning the linker length as well as the amino substituent and ring position of the nitrogen in the bicyclic ring system were discussed. The most promising of the newly synthesized compounds was a 2-azabicyclononane with an aminopropyl linker and a 4-methylpiperazinyl substituent at a bridgehead atom. It showed excellent antiplasmodial and antitrypanosomal activity (IC₅₀ ≤ 0.065 µM). Two chemical compounds labeled 8d and 9c are shown with their molecular structures and activity data. Compound 8d has a half-maximal inhibitory concentration (IC50) of 0.050 micromolar against P.f NF54, 0.065 micromolar against T. b. r., and 2.860 micromolar cytotoxicity in L6 cells. Compound 9c has an IC50 of 0.051 micromolar against P.f. NF54, 0.537 micromolar against T. b. r., and 1.845 micromolar cytotoxicity in L6 cells. The structures share a common core with variations in the nitrogen-containing ring and side chains.</p>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102576","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":"From danger to resolution: targeting purinergic signaling in CNS diseases","authors":"Camille Degryse,&nbsp;Kirti Gupta,&nbsp;Luc Buée,&nbsp;Thierry Burnouf,&nbsp;David Blum,&nbsp;Ming-Li Chou","doi":"10.1007/s00044-026-03583-w","DOIUrl":"10.1007/s00044-026-03583-w","url":null,"abstract":"<div><p>The central nervous system (CNS) is a dynamic immunological environment, where specialized interfaces, immune reservoirs, and metabolic clearance pathways, such as the glymphatic system, orchestrate immune surveillance and homeostasis. Within this intricate network, purinergic signaling, mediated by nucleotides like ATP and adenosine, emerges as a critical regulator of immune responses, inflammation resolution, and tissue repair. Adenosine, drives immunosuppression and immune exhaustion, shaping the balance between neuroprotection and neurodegeneration. Purinergic signaling influences a diverse array of cells, including platelets, neutrophils, dendritic cells, lymphocytes, macrophages/microglia, astrocytes, oligodendrocytes as well as neurons, each contributing uniquely to CNS immune dynamics. Dysregulation of this signaling network is implicated in major neurodegenerative and neurological diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), stroke, and traumatic brain injury (TBI). Recent advances in therapeutic strategies targeting purinergic receptors, such as A_2AR and P2X₇, have demonstrated promising clinical potential, offering new avenues for immunomodulation and neuroprotection. This review synthesizes current understanding of purinergic signaling in CNS immunity, explores its role in disease pathogenesis, and discusses innovative therapeutic approaches. By framing purinergic signaling as a tunable “rheostat”, we highlight its potential to shift the CNS from danger to resolution, paving the way for precision immunotherapies in neurological disorders.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"35 10","pages":"2007 - 2027"},"PeriodicalIF":3.5,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00044-026-03583-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vepdegestrant: the first FDA-approved oral PROTAC and a milestone in targeted protein degradation.","authors":"Jeffrey Yang, Longqin Hu","doi":"10.1007/s00044-026-03622-6","DOIUrl":"https://doi.org/10.1007/s00044-026-03622-6","url":null,"abstract":"<p><p>Vepdegestrant (ARV-471, Veppanu) represents an important milestone in targeted protein degradation (TPD) as the first FDA-approved heterobifunctional proteolysis-targeting chimera (PROTAC). Designed to selectively degrade estrogen receptor α (ERα) through recruitment of the cereblon E3 ubiquitin ligase, vepdegestrant provides an event-driven approach to targeting ERα, including clinically relevant estrogen receptor-1 (ESR1)-mutated forms associated with endocrine therapy resistance. Its oral bioavailability and pharmacological properties enabled clinical development in patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer. In clinical studies, vepdegestrant improved progression-free survival compared with fulvestrant in this patient population, supporting the therapeutic potential of PROTAC-mediated protein degradation. The approval of vepdegestrant provides clinical and regulatory validation of the PROTAC modality and offers important medicinal chemistry lessons for the design and development of next-generation degraders.</p>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102533","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":"Baxdrostat (Baxfendy^®), a first-in-class aldosterone synthase inhibitor approved for adults with uncontrolled hypertension.","authors":"Ahmed R Ali, Longqin Hu","doi":"10.1007/s00044-026-03620-8","DOIUrl":"https://doi.org/10.1007/s00044-026-03620-8","url":null,"abstract":"<p><p>Despite the availability of multiple antihypertensive therapies, many patients remain unable to achieve adequate blood pressure control. Excess aldosterone is a key contributor to resistant and uncontrolled hypertension. Baxdrostat (Baxfendy^®), a first-in-class selective aldosterone synthase (CYP11B2) inhibitor, was approved on May 15, 2026, for use in adults with inadequately controlled hypertension receiving other antihypertensive medications. Unlike mineralocorticoid receptor antagonists, baxdrostat reduces aldosterone biosynthesis while preserving cortisol production, offering a distinct mechanism of action. In phase 3 clinical trials, once-daily baxdrostat (1-2 mg) produced placebo-adjusted reductions of ~ 9-10 mmHg in seated systolic blood pressure. Hyperkalemia was generally manageable, with no clinically meaningful cortisol suppression observed. These findings support baxdrostat as a promising new option for patients with difficult-to-control hypertension.</p>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079410","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":"Design and biological evaluation of sulfonamide-chalcone hybrids with in vitro tumor-selective cytotoxicity against oral squamous cell carcinoma: SAR, QSAR, and in silico ADME studies.","authors":"Gulsen Ozli, Hiroshi Sakagami, M Fatih Polat, Cavit Kazaz, Kota Kurosaki, Yoshihiro Uesawa, Kaito Inden, Halise Inci Gul","doi":"10.1007/s00044-026-03624-4","DOIUrl":"https://doi.org/10.1007/s00044-026-03624-4","url":null,"abstract":"<p><p>Multidrug resistance and off-target toxicity remain major challenges in the treatment of oral squamous cell carcinoma (OSCC). In this study, sulfonamide-chalcone hybrids were designed by combining the chalcone scaffold with a benzenesulfonamide moiety to explore tumor-selective cytotoxicity and structure-activity relationships. Thirty-two N-(4-(3-(aryl)prop-2-enoyl)phenyl)benzenesulfonamide derivatives, including 17 previously unreported compounds, were synthesized via base-catalyzed Claisen-Schmidt condensation and characterized by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry. Cytotoxicity was evaluated against the human OSCC cell lines Ca9-22 and HSC-2 and non-malignant human gingival fibroblasts and human pulp cells. Compounds 5, 13, 21, 30, and 32 showed the most favorable activity/selectivity profiles, with 50% cytotoxic concentration values of 1.6-2.2 µM against Ca9-22 cells and tumor-selectivity index values of 14.6-21.1. Structure-activity relationship analysis indicated that meta- and para-substitution patterns generally favored tumor-selective cytotoxicity, whereas bulky ortho-substituents reduced activity. Descriptor-based quantitative structure-activity relationship analysis suggested associations between cytotoxicity and molecular shape, polarizability, electronic properties, polarity, and surface descriptors. In silico studies indicated variable gastrointestinal absorption among the selected lead compounds, while none were predicted to permeate the blood-brain barrier. The selected leads also complied with Lipinski's Rule of Five. Overall, these findings suggest that sulfonamide-chalcone hybrids represent potentially useful tumor-selective cytotoxic scaffolds for further OSCC-focused optimization.</p>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079393","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":"Optimization of a bis-imine scaffold as a glyoxalase I inhibitor: synthesis, SAR, and docking studies.","authors":"Buthina A Al-Oudat, Farah B Al-Omari, Suaad A Audat, Nizar A Al-Shar'i, Qosay A Al-Balas","doi":"10.1007/s00044-026-03626-2","DOIUrl":"https://doi.org/10.1007/s00044-026-03626-2","url":null,"abstract":"<p><p>Glyoxalase I (Glo-I) enzyme is a validated anticancer target due to its role in methylglyoxal detoxification and its association with tumor progression and drug resistance. Inhibition of Glo-I promotes the accumulation of toxic metabolites and can trigger apoptosis in cancer cells. Building on our previously reported bis-imine Glo-I inhibitor N3 (IC₅₀ = 0.89 ± 0.06 µM), which contains two pyrogallol moieties linked via para-positioned imines on a central benzene linker, the present study introduces a focused scaffold-optimization strategy aimed at defining the structural elements required for stronger Glo-I inhibition. Structural simplification of N3, through removal of the central benzene linker, generated compound 8a, a simplified bis-imine analogue with two-fold improved potency (IC₅₀ = 0.46 ± 0.10 µM). This enhancement was attributed to preserved hydrogen bonding capacity and improved Zn²⁺ chelation within Glo-I active site. A comprehensive structure-activity relationship (SAR) investigation of compound 8a and its analogues demonstrated that the number, position, and free phenolic character of the hydroxyl groups are critical determinants of activity, mainly by supporting hydrogen bonding and bidentate Zn²⁺ coordination. Masking the hydroxyl groups abolished activity, whereas selected alternative chelating groups preserved moderate inhibition, highlighting the importance and flexibility of metal-binding interactions. Importantly, replacement of the bis-imine with amide-imine linker, or reduction to mono-imine analogues, reduced potency, confirming that the bis-imine linker is a key pharmacophoric feature for optimal Glo-I inhibition. Molecular docking further rationalized these findings by identifying the essential interactions with Zn²⁺, polar residues at the active site entrance, and the hydrophobic pocket. Overall, this study provides a clear innovative-driven SAR model for bis-imine-based Glo-I inhibitors and identified compound 8a as an optimized lead for the future design of anticancer candidates targeting Glo-I enzyme.Clinical trial number: not applicable. The image presents a chemical structure at the top, connected by arrows to three groups of related chemical structures labeled 8a-p, 11a-f, and 14a-c. The top structure includes two benzene rings each with hydroxyl groups, linked by a diazene group and a phenyl ring. The three groups below show variations of this structure with different substituents labeled as R. The top right includes a molecular surface model showing a ligand bound within a protein pocket, illustrating the interaction between the molecule and the protein.</p>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073145","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":"Glypican-3-targeted bioconjugates for hepatocellular carcinoma: design, engineering, and translational applications.","authors":"Yi Liu, Jiaying Zhu, Haolei Yu, Chenyu Wang, Yue You, Zixuan Hong, Chenbo Zhang, Chenpengyu Zhang, Zhihao Zhang","doi":"10.1007/s00044-026-03625-3","DOIUrl":"https://doi.org/10.1007/s00044-026-03625-3","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is among the most prevalent malignancies and remains a leading cause of cancer-related mortality worldwide. Because early-stage HCC often has a silent clinical course and current surveillance strategies remain imperfect, many patients with HCC are diagnosed at an intermediate or advanced stage. In addition, the high rates of recurrence and metastasis contribute to the persistently poor overall prognosis. Glypican-3 (GPC3) is minimally expressed in normal adult liver tissue, but is frequently upregulated in HCC. However, several major barriers remain, including intratumoral expression heterogeneity, the challenge of achieving stable delivery under conditions of high intrahepatic background, and the lack of robust clinical evidence supporting combined diagnostic and therapeutic strategies. In this review, we summarize the biological basis of GPC3 and recent advances in its application in HCC, with particular emphasis on the development of multiple targeting platforms, including peptides, single-chain variable fragments (scFvs), nanobodies, and full-length antibodies. Our translational decision framework evaluates these platforms not only by absolute tumor uptake but also by tumor-to-liver (T/L) ratio, tumor retention, organ dosimetry, conjugation homogeneity, and manufacturability. Looking ahead, GPC3 molecular imaging may support patient selection, treatment planning, and the evidence-based optimization of combination strategies. GPC3-targeting bioconjugate platforms include four types: GPC3-binding peptide, anti-GPC3 nanobody, anti-GPC3 single-chain variable fragment, and anti-GPC3 monoclonal antibody. These platforms integrate with other diagnostics and therapeutic modalities such as PET/CT imaging, radioligand therapy, immune checkpoint inhibitors targeting PD-1/PD-L1, tyrosine kinase inhibitors including sorafenib and lenvatinib, and chemotherapy or immunotherapy.</p>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073098","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}