Biomolecules & Therapeutics最新文献_第9页

Structure-Activity Relationship and Functional Evaluation of Cannabinoid Type-1 Receptor. 大麻素 1 型受体的结构-活性关系和功能评估。

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-07-01 Epub Date: 2024-06-07 DOI: 10.4062/biomolther.2023.205

Shujie Wang, Xinru Tian, Suresh Paudel, Sungho Ghil, Choon-Gon Jang, Kyeong-Man Kim

{"title":"Structure-Activity Relationship and Functional Evaluation of Cannabinoid Type-1 Receptor.","authors":"Shujie Wang, Xinru Tian, Suresh Paudel, Sungho Ghil, Choon-Gon Jang, Kyeong-Man Kim","doi":"10.4062/biomolther.2023.205","DOIUrl":"10.4062/biomolther.2023.205","url":null,"abstract":"The type-1 cannabinoid receptor (CB1R) is a potential therapeutic target in several pathological conditions, including neuropsychological disorders and neurodegenerative diseases. Owing to their structural diversity, it is not easy to derive general structure-activity relationships (SARs) for CB1R ligands. In this study, CB1R ligands were classified into six structural families, and the corresponding SAR was determined for their affinities for CB1R. In addition, we determined their functional activities for the activation of extracellular signal-regulated kinases (ERKs). Among derivatives of indol-3-yl-methanone, the highest ligand affinity was observed when a pentyl and a naphthalenyl group were attached to the N1 position of the indole ring and the carbon site of the methanone moiety, respectively. In the case of adamantane indazole-3-carboxamide derivatives, the presence of fluorine in the pentyl group, the substituent at the N1 position of the indazole ring, strongly increased the affinity for CB1R. For (naphthalen-1-yl) methanone derivatives, the presence of 4-alkoxynaphthalene in the methanone moiety was more beneficial for the affinity to CB1R than that of a heterocyclic ring. The functional activities of the tested compounds, evaluated through ERK assay, were correlated with their affinity for CB1R, suggesting their agonistic nature. In conclusion, this study provides valuable insight for designing novel ligands for CB1R, which can be used to control psychiatric disorders and drug abuse.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"442-450"},"PeriodicalIF":3.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11214964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141282949","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}

引用次数: 0

Extracellular Vesicles Derived from Adipose Stem Cells Alleviate Systemic Sclerosis by Inhibiting TGF-β Pathway. 脂肪干细胞衍生的细胞外小泡通过抑制 TGF-β 通路缓解系统性硬化症

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-07-01 Epub Date: 2024-06-05 DOI: 10.4062/biomolther.2023.191

Eunae Kim, Hark Kyun Kim, Jae Hoon Sul, Jeongmi Lee, Seung Hyun Baek, Yoonsuk Cho, Jihoon Han, Junsik Kim, Sunyoung Park, Jae Hyung Park, Yong Woo Cho, Dong-Gyu Jo

{"title":"Extracellular Vesicles Derived from Adipose Stem Cells Alleviate Systemic Sclerosis by Inhibiting TGF-β Pathway.","authors":"Eunae Kim, Hark Kyun Kim, Jae Hoon Sul, Jeongmi Lee, Seung Hyun Baek, Yoonsuk Cho, Jihoon Han, Junsik Kim, Sunyoung Park, Jae Hyung Park, Yong Woo Cho, Dong-Gyu Jo","doi":"10.4062/biomolther.2023.191","DOIUrl":"10.4062/biomolther.2023.191","url":null,"abstract":"Systemic sclerosis is an autoimmune disease characterized by inflammatory reactions and fibrosis. Myofibroblasts are considered therapeutic targets for preventing and reversing the pathogenesis of fibrosis in systemic sclerosis. Although the mechanisms that differentiate into myofibroblasts are diverse, transforming growth factor β (TGF-β) is known to be a key mediator of fibrosis in systemic sclerosis. This study investigated the effects of extracellular vesicles derived from human adipose stem cells (ASC-EVs) in an in vivo systemic sclerosis model and in vitro TGF-β1-induced dermal fibroblasts. The therapeutic effects of ASC-EVs on the in vivo systemic sclerosis model were evaluated based on dermal thickness and the number of α-smooth muscle actin (α-SMA)-expressing cells using hematoxylin and eosin staining and immunohistochemistry. Administration of ASC-EVs decreased both the dermal thickness and α-SMA expressing cell number as well as the mRNA levels of fibrotic genes, such as Acta2, Ccn2, Col1a1 and Comp. Additionally, we discovered that ASC-EVs can decrease the expression of α-SMA and CTGF and suppress the TGF-β pathway by inhibiting the activation of SMAD2 in dermal fibroblasts induced by TGF-β1. Finally, TGF-β1-induced dermal fibroblasts underwent selective death through ASC-EVs treatment. These results indicate that ASC-EVs could provide a therapeutic approach for preventing and reversing systemic sclerosis.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"432-441"},"PeriodicalIF":3.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11214968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247357","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}

引用次数: 0

Structural Insights into the Interaction of Terpenoids with Streptomyces avermitilis CYP107P2. 萜类化合物与 Streptomyces avermitilis CYP107P2 相互作用的结构见解。

IF 3 3区医学

Biomolecules & Therapeutics Pub Date : 2024-07-01 Epub Date: 2024-06-05 DOI: 10.4062/biomolther.2024.045

Eunseo Jeong, Vitchan Kim, Changmin Kim, Yoo-Bin Lee, Donghak Kim

{"title":"Structural Insights into the Interaction of Terpenoids with Streptomyces avermitilis CYP107P2.","authors":"Eunseo Jeong, Vitchan Kim, Changmin Kim, Yoo-Bin Lee, Donghak Kim","doi":"10.4062/biomolther.2024.045","DOIUrl":"10.4062/biomolther.2024.045","url":null,"abstract":"Streptomyces avermitilis genome includes 33 genes encoding monooxygenation-catalyzing cytochrome P450 enzymes. We investigated the structure of CYP107P2 and its interactions with terpenoid compounds. The recombinant CYP107P2 protein was expressed in Escherichia coli and the purified enzyme exhibited a typical P450 spectrum upon CO-binding in its reduced state. Type-I substrate-binding spectral titrations were observed with various terpenoid compounds, including α-pinene, β-pinene, α-terpinyl acetate, and (+)-3-carene. The calculated binding affinities (Kd) ranged from 15.9 to 50.8 μM. The X-ray crystal structure of CYP107P2 was determined at 1.99 Å resolution, with a well-conserved overall P450 folding conformation. The terpenoid compound docking models illustrated that the structural interaction between monoterpenes and CYP107P2, with the distance between heme and terpenes ranging from 3.4 to 5.4 Å, indicates potential substrate binding for P450 enzyme. This study suggests that CYP107P2 is a Streptomyces P450 enzyme capable of catalyzing terpenes as substrates, signifying noteworthy advancements in comprehending a novel P450 enzyme's involvement in terpene reactions.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"474-480"},"PeriodicalIF":3.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11214959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247364","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}

引用次数: 0

Erratum to "Bispecific Antibody-Bound T Cells as a Novel Anticancer Immunotherapy" [Biomol. Ther. 30 (2022) 418-426]. 双特异性抗体结合 T 细胞作为一种新型抗癌免疫疗法》的勘误 [Biomol.

IF 3.7 3区医学

Biomolecules & Therapeutics Pub Date : 2024-05-01 DOI: 10.4062/biomolther.2024.003

Jaewon Cho, Nara Tae, Jae-Hee Ahn, Sun-Young Chang, Hyun-Jeong Ko, Dae Hee Kim

引用次数: 0

Erratum to "Potential Role of Dietary Salmon Nasal Cartilage Proteoglycan on UVB-Induced Photoaged Skin" [Biomol. Ther. 32 (2024) 249-260]. 膳食鲑鱼鼻软骨蛋白多糖对紫外线诱导的光老化皮肤的潜在作用》的勘误 [Biomol.

IF 3.7 3区医学

Biomolecules & Therapeutics Pub Date : 2024-05-01 DOI: 10.4062/biomolther.2024.004

Hae Ran Lee, Seong-Min Hong, Kyohee Cho, Seon Hyeok Kim, Eunji Ko, Eunyoo Lee, Hyun Jin Kim, Se Yeong Jeon, Seon Gil Do, Sun Yeou Kim

引用次数: 0

Lysophosphatidic Acid Receptor 1 Plays a Pathogenic Role in Permanent Brain Ischemic Stroke by Modulating Neuroinflammatory Responses. 溶血磷脂酸受体 1 通过调节神经炎症反应在永久性脑缺血中风中发挥致病作用

IF 3.7 3区医学

Biomolecules & Therapeutics Pub Date : 2024-04-17 DOI: 10.4062/biomolther.2024.052

Supriya Tiwari, Nikita Basnet, Ji Woong Choi

{"title":"Lysophosphatidic Acid Receptor 1 Plays a Pathogenic Role in Permanent Brain Ischemic Stroke by Modulating Neuroinflammatory Responses.","authors":"Supriya Tiwari, Nikita Basnet, Ji Woong Choi","doi":"10.4062/biomolther.2024.052","DOIUrl":"https://doi.org/10.4062/biomolther.2024.052","url":null,"abstract":"Lysophosphatidic acid receptor 1 (LPA1) plays a critical role in brain injury following a transient brain ischemic stroke. However, its role in permanent brain ischemic stroke remains unknown. To address this, we investigated whether LPA1 could contribute to brain injury of mice challenged by permanent middle cerebral artery occlusion (pMCAO). A selective LPA1 antagonist (AM152) was used as a pharmacological tool for this investigation. When AM152 was given to pMCAO-challenged mice one hour after occlusion, pMCAO-induced brain damage such as brain infarction, functional neurological deficits, apoptosis, and blood-brain barrier disruption was significantly attenuated. Histological analyses demonstrated that AM152 administration attenuated microglial activation and proliferation in injured brain after pMCAO challenge. AM152 administration also attenuated abnormal neuroinflammatory responses by decreasing expression levels of pro-inflammatory cytokines while increasing expression levels of anti-inflammatory cytokines in the injured brain. As underlying effector pathways, NF-κB, MAPKs (ERK1/2, p38, and JNKs), and PI3K/Akt were found to be involved in LPA1-dependent pathogenesis. Collectively, these results demonstrate that LPA1 can contribute to brain injury by permanent ischemic stroke, along with relevant pathogenic events in an injured brain.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"184 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140613610","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}

引用次数: 0

Morroniside Protects C2C12 Myoblasts from Oxidative Damage Caused by ROS-Mediated Mitochondrial Damage and Induction of Endoplasmic Reticulum Stress. 莫罗尼苷能保护 C2C12 肌细胞免受 ROS 介导的线粒体损伤和内质网应激引起的氧化损伤。

IF 3.7 3区医学

Biomolecules & Therapeutics Pub Date : 2024-04-11 DOI: 10.4062/biomolther.2024.012

Hyun Hwangbo, Cheol Park, EunJin Bang, Hyuk Soon Kim, Sung-Jin Bae, Eunjeong Kim, Youngmi Jung, Sun-Hee Leem, Young Rok Seo, Su Hyun Hong, Gi-Young Kim, Jin Won Hyun, Yung Hyun Choi

{"title":"Morroniside Protects C2C12 Myoblasts from Oxidative Damage Caused by ROS-Mediated Mitochondrial Damage and Induction of Endoplasmic Reticulum Stress.","authors":"Hyun Hwangbo, Cheol Park, EunJin Bang, Hyuk Soon Kim, Sung-Jin Bae, Eunjeong Kim, Youngmi Jung, Sun-Hee Leem, Young Rok Seo, Su Hyun Hong, Gi-Young Kim, Jin Won Hyun, Yung Hyun Choi","doi":"10.4062/biomolther.2024.012","DOIUrl":"https://doi.org/10.4062/biomolther.2024.012","url":null,"abstract":"Oxidative stress contributes to the onset of chronic diseases in various organs, including muscles. Morroniside, a type of iridoid glycoside contained in Cornus officinalis, is reported to have advantages as a natural compound that prevents various diseases. However, the question of whether this phytochemical exerts any inhibitory effect against oxidative stress in muscle cells has not been well reported. Therefore, the current study aimed to evaluate whether morroniside can protect against oxidative damage induced by hydrogen peroxide (H2O2) in murine C2C12 myoblasts. Our results demonstrate that morroniside pretreatment was able to inhibit cytotoxicity while suppressing H2O2-induced DNA damage and apoptosis. Morroniside also significantly improved the antioxidant capacity in H2O2-challenged C2C12 cells by blocking the production of cellular reactive oxygen species and mitochondrial superoxide and increasing glutathione production. In addition, H2O2-induced mitochondrial damage and endoplasmic reticulum (ER) stress were effectively attenuated by morroniside pretreatment, inhibiting cytoplasmic leakage of cytochrome c and expression of ER stress-related proteins. Furthermore, morroniside neutralized H2O2-mediated calcium (Ca2+) overload in mitochondria and mitigated the expression of calpains, cytosolic Ca2+-dependent proteases. Collectively, these findings demonstrate that morroniside protected against mitochondrial impairment and Ca2+-mediated ER stress by minimizing oxidative stress, thereby inhibiting H2O2-induced cytotoxicity in C2C12 myoblasts.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"55 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140602951","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}

引用次数: 0

Tumor Stroma as a Therapeutic Target for Pancreatic Ductal Adenocarcinoma. 将肿瘤基质作为胰腺导管腺癌的治疗靶点

IF 3.7 3区医学

Biomolecules & Therapeutics Pub Date : 2024-04-10 DOI: 10.4062/biomolther.2024.029

Dae Ui Lee, Beom Seok Han, Kyung Hee Jung, Soon-Sun Hong

{"title":"Tumor Stroma as a Therapeutic Target for Pancreatic Ductal Adenocarcinoma.","authors":"Dae Ui Lee, Beom Seok Han, Kyung Hee Jung, Soon-Sun Hong","doi":"10.4062/biomolther.2024.029","DOIUrl":"https://doi.org/10.4062/biomolther.2024.029","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis owing to its desmoplastic stroma. Therefore, therapeutic strategies targeting this tumor stroma should be developed. In this study, we describe the heterogeneity of cancer-associated fibroblasts (CAFs) and their diverse roles in the progression, immune evasion, and resistance to treatment of PDAC. We subclassified the spatial distribution and functional activity of CAFs to highlight their effects on prognosis and drug delivery. Extracellular matrix components such as collagen and hyaluronan are described for their roles in tumor behavior and treatment outcomes, implying their potential as therapeutic targets. We also discussed the roles of extracellular matrix (ECM) including matrix metalloproteinases and tissue inhibitors in PDAC progression. Finally, we explored the role of the adaptive and innate immune systems in shaping the PDAC microenvironment and potential therapeutic strategies, with a focus on immune cell subsets, cytokines, and immunosuppressive mechanisms. These insights provide a comprehensive understanding of PDAC and pave the way for the development of prognostic markers and therapeutic interventions.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"27 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140570195","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}

引用次数: 0

Novel Potential Therapeutic Targets in Autosomal Dominant Polycystic Kidney Disease from the Perspective of Cell Polarity and Fibrosis. 从细胞极性和纤维化的角度看常染色体显性多囊肾病的潜在新治疗靶点

IF 3.7 3区医学

Biomolecules & Therapeutics Pub Date : 2024-04-09 DOI: 10.4062/biomolther.2023.207

Yejin Ahn, Jong Hoon Park

{"title":"Novel Potential Therapeutic Targets in Autosomal Dominant Polycystic Kidney Disease from the Perspective of Cell Polarity and Fibrosis.","authors":"Yejin Ahn, Jong Hoon Park","doi":"10.4062/biomolther.2023.207","DOIUrl":"https://doi.org/10.4062/biomolther.2023.207","url":null,"abstract":"Autosomal dominant polycystic kidney disease (ADPKD), a congenital genetic disorder, is a notable contributor to the prevalence of chronic kidney disease worldwide. Despite the absence of a complete cure, ongoing research aims for early diagnosis and treatment. Although agents such as tolvaptan and mTOR inhibitors have been utilized, their effectiveness in managing the disease during its initial phase has certain limitations. This review aimed to explore new targets for the early diagnosis and treatment of ADPKD, considering ongoing developments. We particularly focus on cell polarity, which is a key factor that influences the process and pace of cyst formation. In addition, we aimed to identify agents or treatments that can prevent or impede the progression of renal fibrosis, ultimately slowing its trajectory toward end-stage renal disease. Recent advances in slowing ADPKD progression have been examined, and potential therapeutic approaches targeting multiple pathways have been introduced. This comprehensive review discusses innovative strategies to address the challenges of ADPKD and provides valuable insights into potential avenues for its prevention and treatment.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"37 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140570202","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}

引用次数: 0

Metabolomic Profiles in Patients with Cervical Cancer Undergoing Cisplatin and Radiation Therapy. 接受顺铂和放射治疗的宫颈癌患者的代谢组学特征

IF 3.7 3区医学

Biomolecules & Therapeutics Pub Date : 2024-04-09 DOI: 10.4062/biomolther.2023.159

Seo-Yeon Choi, Suin Kim, Ji-Young Jeon, Min-Gul Kim, Sun-Young Lee, Kwang-Hee Shin

{"title":"Metabolomic Profiles in Patients with Cervical Cancer Undergoing Cisplatin and Radiation Therapy.","authors":"Seo-Yeon Choi, Suin Kim, Ji-Young Jeon, Min-Gul Kim, Sun-Young Lee, Kwang-Hee Shin","doi":"10.4062/biomolther.2023.159","DOIUrl":"https://doi.org/10.4062/biomolther.2023.159","url":null,"abstract":"This study was aimed to evaluate endogenous metabolic changes before and after cisplatin and radiation therapy in patients with cervical cancer via untargeted metabolomic analysis using plasma samples. A total of 13 cervical cancer patients were enrolled in this study. Plasma samples were collected from each patient on two occasions: approximately one week before therapy (P1) and after completion of cisplatin and radiation therapy (P2). Of the 13 patients, 12 patients received both cisplatin and radiation therapy, whereas one patient received radiation therapy alone. The samples were analyzed using the Ultimate 3000 coupled with Q ExactiveTM Focus Hybrid Quadrupole-OrbitrapTM mass spectrometry (Thermo Fisher Scientific, Waltham, MA, USA). Chromatographic separation utilized a Kinetex C18 column 2.1×100 mm (2.6 μm) (Phenomenex, Torrance, CA, USA), and the temperature was maintained at 40°C. Following P2, there were statistically significant increases in the concentrations of indoxyl sulfate, phenylacetylglutamine, Lysophosphatidyethanolamine (LysoPE) (18:1), and indole-3-acetic acid compared with the concentrations observed at P1. Specifically, in the human papillomavirus (HPV) noninfection group, indoxyl sulfate, LysoPE (18:1), and phenylacetylglutamine showed statistically significant increases at P2 compared with P1. No significant changes in metabolite concentrations were observed in the HPV infection group. Indoxyl sulfate, LysoPE (18:1), phenylacetylglutamine, and indole-3-acetic acid were significantly increased following cisplatin and radiation therapy.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"202 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140570213","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}

引用次数: 0