Biomolecules & Therapeutics最新文献

{"title":"Tanshinone, a Natural NADPH Oxidase Inhibitor, Mitigates Testosterone-Induced Hair Loss.","authors":"Yeo Kyu Hur, Jin Yeong Chae, Min Hye Choi, Kkotnara Park, Da-Woon Bae, Soo-Bong Park, Sun-Shin Cha, Hye Eun Lee, In Hye Lee, Yun Soo Bae","doi":"10.4062/biomolther.2024.097","DOIUrl":"10.4062/biomolther.2024.097","url":null,"abstract":"<p><p>Previous studies have shown that testosterone activates the GPRC6A-Duox1 axis, resulting in the production of H₂O₂ which leads to the apoptosis of keratinocytes and ultimately hair loss. Here, we elucidated a molecular mechanism by which the non-genomic action of testosterone regulates cellular redox status in androgenetic alopecia (AGA). Building upon this molecular understanding, we conducted a high-throughput screening assay of Nox inhibitors from a natural compounds library. This screening identified diterpenoid compounds, specifically Tanshinone I, Tanshinone IIA, Tanshinone IIB, and Cryptotanshinone, derived from <i>Salviae Miltiorrhizae Radix</i>. The IC₅₀ values for Nox isozymes were found to be 2.6-12.9 μM for Tanshinone I, 1.9-7.2 μM for Tanshinone IIA, 5.2-11.9 μM for Tanshinone IIB, and 2.1-7.9 μM for Cryptotanshinone. Furthermore, 3D computational docking analysis confirmed the structural basis by which Tanshinone compounds inhibit Nox activity. These compounds were observed to substitute for NADPH at the π-π bond site between NADPH and FAD, leading to the suppression of Nox activity. Notably, Tanshinone I and Tanshinone IIA effectively inhibited Nox activity heightened by testosterone, consequently reducing the production of intracellular H₂O₂ and preventing cell apoptosis. In an animal study involving the application of testosterone to the back skin of 8-week-old C57BL/6J mice to inhibit hair growth, subsequent treatment with Tanshinone I or Tanshinone IIA alongside testosterone resulted in a substantial increase in hair follicle length compared to testosterone treatment alone. These findings underscore the potential efficacy of Tanshinone I and Tanshinone IIA as therapeutic agents for AGA by inhibiting Nox activity.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"210-220"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11704410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779278","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":"Epigenetic Regulation of Nuclear Factor Erythroid-2-Related Factor 2 in Colorectal Cancer Cells Resistant to Ionizing Radiation.","authors":"Kyoung Ah Kang, Jinny Park, Mei Jing Piao, Pincha Devage Sameera Madushan Fernando, Herath Mudiyanselage Udari Lakmini Herath, Herath Mudiyanselage Maheshika Madhuwanthi Senavirathna, Jung-Hwan Kim, Suk Ju Cho, Jin Won Hyun","doi":"10.4062/biomolther.2024.183","DOIUrl":"10.4062/biomolther.2024.183","url":null,"abstract":"<p><p>γ-Radiation resistance is a major obstacle to the success of radiotherapy in colorectal cancer. Antioxidant-related factors contribute to resistance to radiation therapy and, therefore, are targets for improving the therapeutic response. In this study, we evaluated the molecular mechanisms underlying γ-radiation resistance using the colorectal cancer cell line SNUC5 and γ-radiation-resistant variant SNUC5/RR, including analyses of the role of nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor that regulates antioxidant enzymes, and related epigenetic regulators. Reactive oxygen species (ROS) levels, antioxidant enzyme expression, NRF2 expression, and nuclear translocation were higher in SNUC5/RR cells irradiated with or without 8 Gy than in SNUC5 cells. The DNA demethylase ten-eleven translocation 1 (TET1) expression and TET1 binding to the <i>NRF2</i> promoter in SNUC5/RR cells were stronger than those in SNUC5 cells, indicating lower methylation of CpG islands in the <i>NRF2</i> promoter. TET1 knockdown in SNUC5/RR cells suppressed NRF2 expression significantly. Additionally, histone mixed-lineage leukemia (MLL), a histone methyltransferase, was upregulated, leading to increased trimethylation of histone H3 lysine 4, whereas enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, was downregulated, leading to decreased trimethylation of histone H3 lysine 27. Histone deacetylase (HDAC) and histone acetyltransferase (HAT) levels were lower and higher in SNUC5/RR cells than in SNUC5 cells, respectively. MLL and HAT knockdown in SNUC5/RR cells irradiated with or without 8 Gy decreased levels of NRF2 and heme-oxygenase 1, resulting in enhanced γ-radiation sensitivity. These findings support NRF2 as a target for improving the response to radiotherapy in patients with colorectal cancer.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"182-192"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11704403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876059","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":"The Dual Role of Survival Genes in Neurons and Cancer Cells: a Strategic Clinical Application of DX2 in Neurodegenerative Diseases and Cancer.","authors":"Kyunghwa Baek","doi":"10.4062/biomolther.2024.138","DOIUrl":"10.4062/biomolther.2024.138","url":null,"abstract":"<p><p>In cancer cells, survival genes contribute to uncontrolled growth and the survival of malignant cells, leading to tumor progression. Neurons are post-mitotic cells, fully differentiated and non-dividing after neurogenesis and survival genes are essential for cellular longevity and proper functioning of the nervous system. This review explores recent research findings regarding the role of survival genes, particularly DX2, in degenerative neuronal tissue cells and cancer cells. Survival gene DX2, an exon 2-deleted splice variant of AIMP2 (aminoacyl-tRNA synthetase-interacting multi-functional protein 2), was found to be overexpressed in various cancer types. The potential of DX2 inhibitors as an anti-cancer drug arises from its unique ability to interact with various oncoproteins, such as KRAS and HSP70. Meanwhile, AIMP2 has been reported as a multifunctional cell death-inducing gene, and survival gene DX2 directly and indirectly inhibits AIMP2-induced cell death. DX2 plays multifaceted survival roles in degenerating neurons via various signaling pathways, including PARP 1, TRAF2, and p53 pathways. It is noteworthy that genes that were previously classified as oncogenes, such as AKT and XBP1, are now being considered as curative transgenes for targeting neurodegenerative diseases. A strategic direction for clinical application of survival genes in neurodegenerative disease and in cancer is justified.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"75-85"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11704411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876071","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":"Combination of Cannabidiol with Taurine Synergistically Treated Periodontitis in Rats.","authors":"Se Woong Kim, Saroj Kumar Shrestha, Badmaarag-Altai Chuluunbaatar, Yunjo Soh","doi":"10.4062/biomolther.2024.104","DOIUrl":"10.4062/biomolther.2024.104","url":null,"abstract":"<p><p>The active component in cannabis, cannabidiol (CBD), was first isolated from the hemp plant in 1940. Chronic pain, inflammation, migraines, depression, and anxiety have long been treated with CBD. The fundamental mechanisms of CBD's effects on periodontal inflammation have yet to be fully understood. The amino sulfonic acid taurine is a substance that naturally exists in the body and is an inhibitory modulator of inflammation. This study examined the effects of CBD, taurine, and their combination on inflammatory cytokines and periodontitis <i>in vivo</i>. To assess the expression of inflammatory markers of iNOS, COX-2, TNF-α, and IL-1β, as well as TRAP count and resorbed pit areas, CBD and taurine were applied to RAW264.7 cells. The following groups of 45 Sprague-Dawley rats each were created: control (healthy), vehicle (induced periodontitis), low- and high-dose-CBD with taurine which were each treated for an additional 21 days. Rat teeth were obtained and subjected to histomorphometric studies. The combination of the two significantly decreased the expression of inflammatory markers TNF-α and IL-1β and the amount of TRAP+ cells and resorbed pit areas. Among rats with <i>P. gingivalis</i>-induced periodontitis, the alveolar bone resorption levels, periodontal pocket depth, and distance between cementoenamel junction (CEJ) and alveolar bone crest (ABC) were significantly reduced after treatment with CBD and taurine, suggesting that combining CBD with taurine could be a novel therapeutic agent against periodontal disease.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"203-209"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11704405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779220","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":"C-Peptide Ameliorates Particulate Matter 2.5-Induced Skin Cell Apoptosis by Inhibiting NADPH Oxidation.","authors":"Pincha Devage Sameera Madushan Fernando, Mei Jing Piao, Herath Mudiyanselage Udari Lakmini Herath, Kyoung Ah Kang, Kwon-Soo Ha, Sungwook Chae, Jin Won Hyun","doi":"10.4062/biomolther.2024.053","DOIUrl":"10.4062/biomolther.2024.053","url":null,"abstract":"<p><p>Connecting peptide (C-peptide), a byproduct of insulin biosynthesis, has diverse cellular and biological functions. Particulate matter 2.5 (PM_2.5) adversely affects human skin, leading to skin thickening, wrinkle formation, skin aging, and inflammation. This study aimed to investigate the protective effects of C-peptide against PM_2.5-induced damage to skin cells, focusing on oxidative stress as a key mechanism. C-peptide mitigated NADPH oxidation and intracellular reactive oxygen species (ROS) production induced by PM_2.5. It also suppressed PM_2.5-induced NADPH oxidase (NOX) activity and alleviated PM_2.5-induced NOX1 and NOX4 expression. C-peptide protected against PM_2.5-induced DNA damage, lipid peroxidation, and protein carbonylation. Additionally, C-peptide mitigated PM_2.5-induced apoptosis by inhibiting intracellular ROS production. In summary, our findings suggest that C-peptide mitigates PM_2.5-induced apoptosis in human HaCaT keratinocytes by inhibiting intracellular ROS production and NOX activity.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"221-230"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11704398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845759","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":"Emerging and Promising Keywords in Biomolecules and Therapeutics for 21st Century Diseases.","authors":"Hyun-Jeong Ko, Chang Hoon Lee","doi":"10.4062/biomolther.2024.007","DOIUrl":"10.4062/biomolther.2024.007","url":null,"abstract":"<p><p>Recent technological advancements and environmental changes are leading to an increase in various diseases such as obesity, fibrosis, metabolic disorders, and degenerative diseases associated with aging. Additionally, micro- and nanoplastics are emerging as as potential contributors to many of these conditions, posing a serious threat to human health. This special issue aims to explore new directions and opportunities for future drug development through recent review articles published in the issue, focusing on these key medical topics.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"33 1","pages":"1-4"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11704395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891888","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":"6-Gingerol Induced Apoptosis and Cell Cycle Arrest in Glioma Cells via MnSOD and ERK Phosphorylation Modulation.","authors":"Sher-Wei Lim, Wei-Chung Chen, Huey-Jiun Ko, Yu-Feng Su, Chieh-Hsin Wu, Fu-Long Huang, Chien-Feng Li, Cheng Yu Tsai","doi":"10.4062/biomolther.2024.084","DOIUrl":"10.4062/biomolther.2024.084","url":null,"abstract":"<p><p>6-gingerol, a bioactive compound from ginger, has demonstrated promising anticancer properties across various cancer models by inducing apoptosis and inhibiting cell proliferation and invasion. In this study, we explore its mechanisms against glioblastoma multiforme (GBM), a notably aggressive and treatment-resistant brain tumor. We found that 6-gingerol crosses the blood-brain barrier more effectively than curcumin, enhancing its potential as a therapeutic agent for brain tumors. Our experiments show that 6-gingerol reduces cell proliferation and triggers apoptosis in GBM cell lines by disrupting cellular energy homeostasis. This process involves an increase in mitochondrial reactive oxygen species (mtROS) and a decrease in mitochondrial membrane potential, primarily due to the downregulation of manganese superoxide dismutase (MnSOD). Additionally, 6-gingerol reduces ERK phosphorylation by inhibiting EGFR and RAF, leading to G1 phase cell cycle arrest. These findings indicate that 6-gingerol promotes cell death in GBM cells by modulating MnSOD and ROS levels and arresting the cell cycle through the ERFR-RAF-1/MEK/ERK signaling pathway, highlighting its potential as a therapeutic agent for GBM and setting the stage for future clinical research.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"129-142"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11704400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779217","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":"An Overview of Existing and Emerging Weight-Loss Drugs to Target Obesity-Related Complications: Insights from Clinical Trials.","authors":"Mi Kyung Kim, Hye Soon Kim","doi":"10.4062/biomolther.2024.228","DOIUrl":"10.4062/biomolther.2024.228","url":null,"abstract":"<p><p>Obesity requires treatment as it is associated with health problems such as type 2 diabetes, hypertension, dyslipidemia, cardiovascular diseases, and some cancers, which increase mortality rates. Achieving sufficient weight loss to reduce obesity-related diseases requires a variety of interventions, including comprehensive lifestyle modification of diet and exercise, change in behavior, anti-obesity medications, and surgery. To date, anti-obesity agents with various mechanisms of action have been developed, and mostly reduce energy intake, resulting in weight loss of about 5% to 10% compared to baseline. Recently developed drugs and those currently under development have been shown to reduce body weight by more than 10% and are expected to reduce obesity-related complications. This article summarizes existing and emerging anti-obesity medications, with a particular focus on those evaluated in clinical trials.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"5-17"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11704407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852256","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":"Low-Dose Perifosine, a Phase II Phospholipid Akt Inhibitor, Selectively Sensitizes Drug-Resistant ABCB1-Overexpressing Cancer Cells.","authors":"Jae Hyeon Park, Haeun Lee, Tian Zheng, Joo Kyung Shin, Sungpil Yoon, Hyung Sik Kim","doi":"10.4062/biomolther.2024.069","DOIUrl":"10.4062/biomolther.2024.069","url":null,"abstract":"<p><p>We identified drugs or mechanisms targeting ABCB1 (or P-glycoprotein; P-gp)-overexpressing drug-resistant cancer populations, given that these cells play a key role in tumor recurrence. Specifically, we searched for Akt inhibitors that could increase cytotoxicity in P-gp-overexpressing drug-resistant cancer cells. We performed cytotoxicity assays using five cell lines: 1. MCF-7/ADR, 2. KBV20C cancer cells (P-gp overexpression, vincristine [VIC] resistance, and GSK690693-resistance), 3. MCF-7, 4. normal HaCaT cells (non-P-gp-overexpressing, VIC-sensitive, and GSK690693-sensitive), and 5. MDA-MB-231 cancer cells (non-P-gp overexpression, relatively VIC-resistance, and GSK690693-sensitive). Herein, we found that low-dose perifosine markedly and selectively sensitizes both MCF-7/ADR and KBV20C drug-resistant cancer cells exhibiting P-gp overexpression. Compared with other Akt inhibitors (AZD5363, BKM120, and GSK690693), low-dose perifosine specifically sensitized P-gp-overexpressing resistant MCF-7/ADR cancer cells. Conversely, Akt inhibitors (other than perifosine) could enhance sensitization effects in drugsensitive MCF-7 and HaCaT cells. Considering that perifosine has both an alkyl-phospholipid structure and is an allosteric inhibitor for membrane-localizing Akt-targeting, we examined structurally and functionally similar Akt inhibitors (miltefosine and MK-2206). However, we found that these inhibitors were non-specific, suggesting that the specificity of perifosine in P-gp-overexpressing resistant cancer cells is unrelated to phospholipid localizing membranes or allosteric inhibition. Furthermore, we examined the molecular mechanism of low-dose perifosine in drug-resistant MCF-7/ADR cancer cells. MCF-7/ADR cells exhibited increased apoptosis via G2 arrest and autophagy induction. However, no increase in P-gp-inhibitory activity was observed in drug-resistant MCF-7/ADR cancer cells. Single low-dose perifosine treatment exerted a sensitization effect similar to co-treatment with VIC in P-gp-overexpressing drug-resistant MCF-7/ADR cancer cells, suggesting that single treatment with low-dose perifosine is a more powerful tool against P-gp-overexpressing drug-resistant cancer cells. These findings could contribute to its clinical use as a first-line treatment, explicitly targeting P-gp-overexpressing resistant cancer populations in heterogeneous tumor populations. Therefore, perifosine may be valuable in delaying or reducing cancer recurrence by targeting P-gp-overexpressing drug-resistant cancer cells.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"170-181"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11704409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779236","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":"The Emerging Threat of Micro- and Nanoplastics on the Maturation and Activity of Immune Cells.","authors":"Kang-Bin Dan, Ji Yoon Yoo, Hyeyoung Min","doi":"10.4062/biomolther.2024.195","DOIUrl":"10.4062/biomolther.2024.195","url":null,"abstract":"<p><p>With the increasing use of plastics worldwide, the amount of plastic waste being discarded has also risen. This plastic waste undergoes physical and chemical processes, breaking down into smaller particles known as microplastics (MPs) or nanoplastics (NPs). Advances in technology have enhanced our ability to detect these smaller particles, and it has been confirmed that plastics can be found in marine organisms as well as within the human body. However, research on the effects of MPs or NPs on living organisms has only recently been started, and our understanding remains limited. Studies on the immunological impacts are still ongoing, revealing that MPs and NPs can differentially affect various immune cells based on the material, size, and shape of the plastic particles. In this review, we aim to provide a comprehensive understanding of the effects of MPs and NPs on the immune system. We will also explore the methods for plastic removal through physicochemical, microbial, or biological means.</p>","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":" ","pages":"95-105"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11704408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811952","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}