Archives of Pharmacal Research最新文献

{"title":"Interplay between YAP/TAZ and metabolic dysfunction-associated steatotic liver disease progression","authors":"Na Young Lee,&nbsp;Myeung Gi Choi,&nbsp;Eui Jin Lee,&nbsp;Ja Hyun Koo","doi":"10.1007/s12272-024-01501-5","DOIUrl":"10.1007/s12272-024-01501-5","url":null,"abstract":"<div><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming an increasingly pressing global health challenge, with increasing mortality rates showing an upward trend. Two million deaths occur annually from cirrhosis and liver cancer together each year. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), key effectors of the Hippo signaling pathway, critically regulate tissue homeostasis and disease progression in the liver. While initial studies have shown that YAP expression is normally restricted to cholangiocytes in healthy livers, the activation of YAP/TAZ is observed in other hepatic cells during chronic liver disease. The disease-driven dysregulation of YAP/TAZ appears to be a critical element in the MASLD progression, contributing to hepatocyte dysfunction, inflammation, and fibrosis. In this study, we focused on the complex roles of YAP/TAZ in MASLD and explored how the YAP/TAZ dysregulation of YAP/TAZ drives steatosis, inflammation, fibrosis, and cirrhosis. Finally, the cell-type-specific functions of YAP/TAZ in different types of hepatic cells, such as hepatocytes, hepatic stellate cells, hepatic macrophages, and biliary epithelial cells are discussed, highlighting the multifaceted impact of YAP/TAZ on liver physiology and pathology.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"47 6","pages":"558 - 570"},"PeriodicalIF":6.9,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11217110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141316670","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":"Antibacterial properties of natural products from marine fungi reported between 2012 and 2023: a review","authors":"Ping Wang,&nbsp;Xiaomei Huang,&nbsp;Chenyuan Jiang,&nbsp;Rushuang Yang,&nbsp;Jialing Wu,&nbsp;Yinghui Liu,&nbsp;Shuangshuang Feng,&nbsp;Tingting Wang","doi":"10.1007/s12272-024-01500-6","DOIUrl":"10.1007/s12272-024-01500-6","url":null,"abstract":"<div><p>The oceans are rich in diverse microorganisms, animals, and plants. This vast biological complexity is a major source of unique secondary metabolites. In particular, marine fungi are a promising source of compounds with unique structures and potent antibacterial properties. Over the last decade, substantial progress has been made to identify these valuable antibacterial agents. This review summarizes the chemical structures and antibacterial activities of 223 compounds identified between 2012 and 2023. These compounds, effective against various bacteria including drug-resistant strains such as methicillin-resistant <i>Staphylococcus aureus</i>, exhibit strong potential as antibacterial therapeutics. The review also highlights the relevant challenges in transitioning from drug discovery to product commercialization. Emerging technologies such as metagenomics and synthetic biology are proposed as viable solutions. This paper sets the stage for further research on antibacterial compounds derived from marine fungi and advocates a multidisciplinary approach to combat drug-resistant bacteria.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"47 6","pages":"505 - 537"},"PeriodicalIF":6.9,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293095","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":"Exploring molecular mechanisms, therapeutic strategies, and clinical manifestations of Huntington’s disease","authors":"Alaa Shafie,&nbsp;Amal Adnan Ashour,&nbsp;Saleha Anwar,&nbsp;Farah Anjum,&nbsp;Md. Imtaiyaz Hassan","doi":"10.1007/s12272-024-01499-w","DOIUrl":"10.1007/s12272-024-01499-w","url":null,"abstract":"<div><p>Huntington’s disease (HD) is a paradigm of a genetic neurodegenerative disorder characterized by the expansion of CAG repeats in the <i>HTT</i> gene. This extensive review investigates the molecular complexities of HD by highlighting the pathogenic mechanisms initiated by the mutant huntingtin protein. Adverse outcomes of HD include mitochondrial dysfunction, compromised protein clearance, and disruption of intracellular signaling, consequently contributing to the gradual deterioration of neurons. Numerous therapeutic strategies, particularly precision medicine, are currently used for HD management. Antisense oligonucleotides, such as Tominersen, play a leading role in targeting and modulating the expression of mutant huntingtin. Despite the promise of these therapies, challenges persist, particularly in improving delivery systems and the necessity for long-term safety assessments. Considering the future landscape, the review delineates promising directions for HD research and treatment. Innovations such as Clustered regularly interspaced short palindromic repeats associated system therapies <b>(</b>CRISPR)-based genome editing and emerging neuroprotective approaches present unprecedented opportunities for intervention. Collaborative interdisciplinary endeavors and a more insightful understanding of HD pathogenesis are on the verge of reshaping the therapeutic landscape. As we navigate the intricate landscape of HD, this review serves as a guide for unraveling the intricacies of this disease and progressing toward transformative treatments.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"47 6","pages":"571 - 595"},"PeriodicalIF":6.9,"publicationDate":"2024-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065283","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":"Phytochemical and pharmacological properties of the genus Tamarix: a comprehensive review","authors":"Fangjie Li,&nbsp;Wenli Xie,&nbsp;Xianrui Ding,&nbsp;Kuo Xu,&nbsp;Xianjun Fu","doi":"10.1007/s12272-024-01498-x","DOIUrl":"10.1007/s12272-024-01498-x","url":null,"abstract":"<div><p>The genus <i>Tamarix</i> in the Tamaricaceae family consists of more than 100 species of halophyte plants worldwide that are mainly used to improve saline-alkali land and for coastal windbreaks, sand fixation, and afforestation in arid areas. A considerable number of species in this genus are also used as traditional medicines to treat various human diseases, especially in Asian and African countries. This review presents a comprehensive summary of 655 naturally occurring compounds derived from the genus <i>Tamarix</i>, categorized into flavonoids (18.0%), phenols (13.9%), tannins (9.3%), terpenoids (10.5%), essential oils (31.0%), and others (17.3%). The investigation revealed that the crude extracts and phytochemicals of this genus exhibited significant therapeutic potential, including anti-inflammatory, anti-Alzheimer, anticancer, antidiabetic, antibacterial, and antifungal activities. Six species of <i>Tamarix</i> have anticancer effects by causing cancer cell death, inducing autophagy, and stopping cell division. Seven species from the same genus have the potential for treating diabetes by inhibiting α-glycosidase activity, suppressing human islet amyloid polypeptide, regulating blood glucose levels, and modulating autophagy or inflammation. The focus on antibacterial and antidiabetic effects is due to the presence of volatile oil and flavonoid components. Extensive research has been conducted on the biological activity of 30 constituents, including 15 flavonoids, 5 phenols, 3 terpenoids, 1 tannin, and 6 others. Therefore, future research should thoroughly study the mechanisms of action of these and similar compounds. This is the most comprehensive review of the phytochemistry and pharmacological properties of <i>Tamarix</i> species, with a critical assessment of the current state of knowledge.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"47 5","pages":"410 - 441"},"PeriodicalIF":6.9,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943971","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":"Potential of natural products in inflammation: biological activities, structure–activity relationships, and mechanistic targets","authors":"Yajing Guo,&nbsp;Xuling Peng,&nbsp;Fanfei Liu,&nbsp;Qi Zhang,&nbsp;Liqin Ding,&nbsp;Gen Li,&nbsp;Feng Qiu","doi":"10.1007/s12272-024-01496-z","DOIUrl":"10.1007/s12272-024-01496-z","url":null,"abstract":"<div><p>A balance between the development and suppression of inflammation can always be found in the body. When this balance is disturbed, a strong inflammatory response can damage the body. It sometimes is necessary to use drugs with a significant anti-inflammatory effect, such as nonsteroidal anti-inflammatory drugs and steroid hormones, to control inflammation in the body. However, the existing anti-inflammatory drugs have many adverse effects, which can be deadly in severe cases, making research into new safer and more effective anti-inflammatory drugs necessary. Currently, numerous types of natural products with anti-inflammatory activity and distinct structural features are available, and these natural products have great potential for the development of novel anti-inflammatory drugs. This review summarizes 260 natural products and their derivatives with anti-inflammatory activities in the last two decades, classified by their active ingredients, and focuses on their structure–activity relationships in anti-inflammation to lay the foundation for subsequent new drug development. We also elucidate the mechanisms and pathways of natural products that exert anti-inflammatory effects via network pharmacology predictions, providing direction for identifying subsequent targets of anti-inflammatory natural products.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"47 5","pages":"377 - 409"},"PeriodicalIF":6.9,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140911371","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":"Continuous TNF-α exposure in mammary epithelial cells promotes cancer phenotype acquisition via EGFR/TNFR2 activation","authors":"Jin-Hee Lee,&nbsp;Steffanus Pranoto Hallis,&nbsp;Mi-Kyoung Kwak","doi":"10.1007/s12272-024-01497-y","DOIUrl":"10.1007/s12272-024-01497-y","url":null,"abstract":"<div><p>Tumor necrosis factor alpha (TNF-α), an abundant inflammatory cytokine in the tumor microenvironment (TME), is linked to breast cancer growth and metastasis. In this study, we established MCF10A cell lines incubated with TNF-α to investigate the effects of continuous TNF-α exposure on the phenotypic change of normal mammary epithelial cells. The established MCF10A-LE cell line, through long-term exposure to TNF-α, displayed cancer-like features, including increased proliferation, migration, and sustained survival signaling even in the absence of TNF-α stimulation. Unlike the short-term exposed cell line MCF10A-SE, MCF10A-LE exhibited elevated levels of epidermal growth factor receptor (EGFR) and subsequent TNF receptor 2 (TNFR2), and silencing of <i>EGFR</i> or <i>TNFR2</i> suppressed the cancer-like phenotype of MCF10A-LE. Notably, we demonstrated that the elevated levels of NAD(P)H oxidase 4 (NOX4) and the resulting increase in reactive oxygen species (ROS) were associated with EGFR/TNFR2 elevation in MCF10A-LE. Furthermore, mammosphere-forming capacity and the expression of cancer stem cell (CSC) markers increased in MCF10A-LE. Silencing of <i>EGFR</i> reversed these effects, indicating the acquisition of CSC-like properties via EGFR signaling. In conclusion, our results reveal that continuous TNF-α exposure activates the EGFR/TNFR2 signaling pathway via the NOX4/ROS axis, promoting neoplastic changes in mammary epithelial cells within the inflammatory TME.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"47 5","pages":"465 - 480"},"PeriodicalIF":6.9,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140907907","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":"PBPK modeling to predict the pharmacokinetics of venlafaxine and its active metabolite in different CYP2D6 genotypes and drug–drug interactions with clarithromycin and paroxetine","authors":"Chang-Keun Cho,&nbsp;Pureum Kang,&nbsp;Choon-Gon Jang,&nbsp;Seok-Yong Lee,&nbsp;Yun Jeong Lee,&nbsp;Jung-Woo Bae,&nbsp;Chang-Ik Choi","doi":"10.1007/s12272-024-01495-0","DOIUrl":"10.1007/s12272-024-01495-0","url":null,"abstract":"<div><p>Venlafaxine, a serotonin-norepinephrine reuptake inhibitor (SNRI), is indicated for the treatment of major depressive disorder, social anxiety disorder, generalized anxiety disorder, and panic disorder. Venlafaxine is metabolized to the active metabolite desvenlafaxine mainly by CYP2D6. Genetic polymorphism of <i>CYP2D6</i> and coadministration with other medications can significantly affect the pharmacokinetics and/or pharmacodynamics of venlafaxine and its active metabolite. This study aimed to establish the PBPK models of venlafaxine and its active metabolite related to <i>CYP2D6</i> genetic polymorphism and to predict drug–drug interactions (DDIs) with clarithromycin and paroxetine in different <i>CYP2D6</i> genotypes. Clinical pharmacogenomic data for venlafaxine and desvenlafaxine were collected to build the PBPK model. Physicochemical and absorption, distribution, metabolism, and excretion (ADME) characteristics of respective compounds were obtained from previously reported data, predicted by the PK-Sim^® software, or optimized to capture the plasma concentration–time profiles. Model evaluation was performed by comparing the predicted pharmacokinetic parameters and plasma concentration–time profiles to the observed data. Predicted plasma concentration–time profiles of venlafaxine and its active metabolite were visually similar to the observed profiles and all predicted AUC and C_max values for respective compounds were included in the twofold error range of observed values in non-genotyped populations and different <i>CYP2D6</i> genotypes. When clarithromycin or clarithromycin plus paroxetine was concomitantly administered, predicted plasma concentration–time profiles of venlafaxine properly captured the observed profiles in two different <i>CYP2D6</i> genotypes and all predicted DDI ratios for AUC and C_max were included within the acceptance range. Consequently, the present model successfully captured the pharmacokinetic alterations of venlafaxine and its active metabolite according to <i>CYP2D6</i> genetic polymorphism as well as the DDIs between venlafaxine and two CYP inhibitors. The present model can be used to predict the pharmacokinetics of venlafaxine and its active metabolite considering different races, ages, coadministered drugs, and CYP2D6 activity of individuals and it can contribute to individualized pharmacotherapy of venlafaxine.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"47 5","pages":"481 - 504"},"PeriodicalIF":6.9,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140655933","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":"Combination therapy involving HSP90 inhibitors for combating cancer: an overview of clinical and preclinical progress","authors":"Yajun Liu,&nbsp;Chenyao Li,&nbsp;Hongwei Liu,&nbsp;Shutao Tan","doi":"10.1007/s12272-024-01494-1","DOIUrl":"10.1007/s12272-024-01494-1","url":null,"abstract":"<div><p>The molecular chaperone heat shock protein 90 (HSP90) regulates multiple crucial signalling pathways in cancer by driving the maturation of key signalling components, thereby playing a crucial role in tumorigenesis and drug resistance in cancer. Inhibition of HSP90 results in metastable conformational collapse of its client proteins and their proteasomal degradation. Considerable efforts have been devoted to the development of small-molecule inhibitors targeting HSP90, and more than 20 inhibitors have been evaluated in clinical trials for cancer therapy. However, owing to disadvantages such as organ toxicity and drug resistance, only one HSP90 inhibitor has been approved for use in clinical settings. In recent years, HSP90 inhibitors used in combination with other anti-cancer therapies have shown remarkable potential in the treatment of cancer. HSP90 inhibitors work synergistically with various anti-cancer therapies, including chemotherapy, targeted therapy, radiation therapy and immunotherapy. HSP90 inhibitors can improve the pharmacological effects of the above-mentioned therapies and reduce treatment resistance. This review provides an overview of the use of combination therapy with HSP90 inhibitors and other anti-cancer therapies in clinical and preclinical studies reported in the past decade and summarises design strategies and prospects for these combination therapies. Altogether, this review provides a theoretical basis for further research and application of these combination therapies in the treatment of cancer.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"47 5","pages":"442 - 464"},"PeriodicalIF":6.9,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140611385","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":"Advances in sarcopenia: mechanisms, therapeutic targets, and intervention strategies","authors":"Youle Zheng,&nbsp;Jin Feng,&nbsp;Yixin Yu,&nbsp;Min Ling,&nbsp;Xu Wang","doi":"10.1007/s12272-024-01493-2","DOIUrl":"10.1007/s12272-024-01493-2","url":null,"abstract":"<div><p>Sarcopenia is a multifactorial condition characterized by loss of muscle mass. It poses significant health risks in older adults worldwide. Both pharmacological and non-pharmacological approaches are reported to address this disease. Certain dietary patterns, such as adequate energy intake and essential amino acids, have shown positive outcomes in preserving muscle function. Various medications, including myostatin inhibitors, growth hormones, and activin type II receptor inhibitors, have been evaluated for their effectiveness in managing sarcopenia. However, it is important to consider the variable efficacy and potential side effects associated with these treatments. There are currently no drugs approved by the Food and Drug Administration for sarcopenia. The ongoing research aims to develop more effective strategies in the future. Our review of research on disease mechanisms and drug development will be a valuable contribution to future research endeavors.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"47 4","pages":"301 - 324"},"PeriodicalIF":6.9,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140572465","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":"TNF receptor 2 knockout mouse had reduced lung cancer growth and schizophrenia-like behavior through a decrease in TrkB-dependent BDNF level","authors":"In Jun Yeo,&nbsp;Ji Eun Yu,&nbsp;Sung-Hyun Kim,&nbsp;Dae Hwan Kim,&nbsp;Miran Jo,&nbsp;Dong Ju Son,&nbsp;Jaesuk Yun,&nbsp;Sang-Bae Han,&nbsp;Jin Tae Hong","doi":"10.1007/s12272-024-01487-0","DOIUrl":"10.1007/s12272-024-01487-0","url":null,"abstract":"<div><p>The relationship between schizophrenia (SCZ) and cancer development remains controversial. Based on the disease-gene association platform, it has been revealed that tumor necrosis factor receptor (TNFR) could be an important mediatory factor in both cancer and SCZ development. TNF-α also increases the expression of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) in the development of SCZ and tumor, but the role of TNFR in mediating the association between the two diseases remains unclear. We studied the vital roles of TNFR2 in the progression of tumor and SCZ-like behavior using A549 lung cancer cell xenografted TNFR2 knockout mice. TNFR2 knockout mice showed significantly decreased tumor size and weight as well as schizophrenia-like behaviors compared to wild-type mice. Consistent with the reduced tumor growth and SCZ-like behaviors, the levels of TrkB and BDNF expression were significantly decreased in the lung tumor tissues and pre-frontal cortex of TNFR2 knockout mice. However, intravenous injection of BDNF (160 μg/kg) to TNFR2 knockout mice for 4 weeks increased tumor growth and SCZ-like behaviors as well as TrkB expression. In in vitro study, significantly decreased cell growth and expression of TrkB and BDNF by siTNFR2 transfection were found in A549 lung cancer cells. However, the addition of BDNF (100 ng/ml) into TNFR2 siRNA transfected A549 lung cancer cells recovered cell growth and the expression of TrkB. These results suggest that TNFR2 could be an important factor in mediating the comorbidity between lung tumor growth and SCZ development through increased TrkB-dependent BDNF levels.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"47 4","pages":"341 - 359"},"PeriodicalIF":6.9,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-024-01487-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140572464","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}