Pharmacology & Therapeutics最新文献

{"title":"Neuroimmune modulators derived from natural products: Mechanisms and potential therapies","authors":"Wan-Di Feng,&nbsp;Dong-Ni Liu,&nbsp;Yu-Fu Shang,&nbsp;Wen-Fang Zhang,&nbsp;Shuang Xu,&nbsp;Dan-Hong Feng,&nbsp;Yue-Hua Wang","doi":"10.1016/j.pharmthera.2025.108830","DOIUrl":"10.1016/j.pharmthera.2025.108830","url":null,"abstract":"<div><div>Neuroimmunology is a multidisciplinary field that investigates the interactions between the nervous and immune systems. Neuroimmune interactions persist throughout the entire lifespan, and their dysregulation can lead to the onset and development of multiple diseases. Despite significant progress over the past decades in elucidating the interaction between neuroscience and immunology, the exact mechanism underlying neuroimmune crosstalk has not yet been fully elucidated. In recent years, natural products have emerged as a promising avenue for the therapeutic implications of neuroimmune diseases. Naturally derived anti-neuroimmune disease agents, such as polyphenols, flavonoids, alkaloids, and saponins, have been extensively studied for their potential neuroimmune modulatory effects. This comprehensive review delves into the specific molecular mechanisms of bidirectional neuro-immune interactions, with particular emphasis on the role of neuro-immune units. The review synthesizes a substantial body of evidence from in vitro and in vivo experiments as well as clinical studies, highlighting the therapeutic potential of various natural products in intervening in neuroimmune disorders.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"269 ","pages":"Article 108830"},"PeriodicalIF":12.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in target identification technology of natural products","authors":"Ting-Ting Liu ,&nbsp;Ke-Wu Zeng","doi":"10.1016/j.pharmthera.2025.108833","DOIUrl":"10.1016/j.pharmthera.2025.108833","url":null,"abstract":"<div><div>Natural products, characterized by their structural diversity, broad spectrum of biological activities, and safe yet effective therapeutic potential, have become pivotal resources in drug research and development. However, the target proteins of many natural products remain unidentified, a significant challenge that impedes their development into viable drug candidates. Therefore, the target identification is crucial for elucidating the pharmacological mechanisms of natural products and facilitating their therapeutic applications. In this review, we present a comprehensive overview of recent advancements in methodologies for target identification of natural products. Additionally, we predict future developments in new technologies for target discovery. Collectively, this review establishes a methodological framework for uncovering the cellular targets and pharmacological mechanisms of natural products, thereby advancing the development of innovative natural product-based drugs.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"269 ","pages":"Article 108833"},"PeriodicalIF":12.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The anti-inflammatory effects of saponins from natural herbs","authors":"Qinpin Zheng ,&nbsp;Tian Wang ,&nbsp;Sensen Wang ,&nbsp;Zhuoxi Chen ,&nbsp;Xue Jia ,&nbsp;Hui Yang ,&nbsp;Huijin Chen ,&nbsp;Xin Sun ,&nbsp;Kejun Wang ,&nbsp;Leiming Zhang ,&nbsp;Fenghua Fu","doi":"10.1016/j.pharmthera.2025.108827","DOIUrl":"10.1016/j.pharmthera.2025.108827","url":null,"abstract":"<div><div>Inflammation is a protective mechanism that also starts the healing process. However, inflammatory reaction may cause severe tissue damage. The increased influx of phagocytic leukocytes may produce excessive amount of reactive oxygen species, which leads to additional cell injury. Inflammatory response activates the leukocytes and thus induces tissue damage and prolongs inflammation. The inflammation-induced activation of the complement system may also contribute to cell injury. Non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids are chief agents for treating inflammation associated with the diseases. However, the unwanted side effects of NSAIDs (<em>e.g.</em>, gastrointestinal disturbances, skin reactions, adverse renal effects, cardiovascular side effects) and glucocorticoids (<em>e.g.</em>, suppression of immune system, Cushing's syndrome, osteoporosis, hyperglycemia) limit their use in patients. Natural herbs are important sources of anti-inflammatory drugs. The ingredients extracted from natural herbs display anti-inflammatory effects to work through multiple pathways with lower risk of adverse reaction. At present, the main anti-inflammatory natural agents include saponins, flavonoids, alkaloids, polysaccharides, and so on. The present article will review the anti-inflammatory effects of saponins including escin, ginsenosides, glycyrrhizin, astragaloside, Panax notoginseng saponins, saikosaponin, platycodin, timosaponin, ophiopogonin D, dioscin, senegenin.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"269 ","pages":"Article 108827"},"PeriodicalIF":12.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of macrophages in asthma-related fibrosis and remodelling","authors":"Xin Yuan Yang ,&nbsp;Fuguang Li ,&nbsp;Guojun Zhang ,&nbsp;Paul S. Foster ,&nbsp;Ming Yang","doi":"10.1016/j.pharmthera.2025.108820","DOIUrl":"10.1016/j.pharmthera.2025.108820","url":null,"abstract":"<div><div>Airway remodelling significantly contributes to the progressive loss of lung function and heightened symptom severity in chronic asthma. Additionally, it often persists and demonstrates reduced responsiveness to the mainstay treatments. The excessive deposition of collagen and extracellular matrix proteins leads to subepithelial fibrosis and airway remodelling, resulting in increased stiffness and decreased elasticity in the airway. Studies have emphasized the crucial role of subepithelial fibrosis in the pathogenesis of asthma. Fibrotic processes eventually cause airway narrowing, reduced lung function, and exacerbation of asthma symptoms. Macrophages play a crucial role in this process by producing pro-fibrotic cytokines, growth factors, and enzymes such as matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Additionally, identification of novel genetic markers has provided evidence for a strong genetic component in fibrosis within macrophage regulated fibrosis. Although macrophages contribute to the progression of airway remodelling and subepithelial fibrosis, interventions targeting macrophage-driven fibrotic changes have not yet been developed. This review synthesizes research on the intricate pathways through which macrophages contribute to subepithelial fibrosis in chronic asthma and its' pathological features. Understanding the interplay between macrophages, fibrosis, and asthma pathogenesis is essential for developing effective therapeutic strategies to manage severe asthma and improve patient outcomes.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"269 ","pages":"Article 108820"},"PeriodicalIF":12.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The (neuro)inflammatory system in anxiety disorders and PTSD: Potential treatment targets","authors":"Anupam Sah,&nbsp;Nicolas Singewald","doi":"10.1016/j.pharmthera.2025.108825","DOIUrl":"10.1016/j.pharmthera.2025.108825","url":null,"abstract":"<div><div>Targeting the immune system has recently garnered attention in the treatment of stress- associated psychiatric disorders resistant to existing pharmacotherapeutics. While such approaches have been studied in considerable detail in depression, the role of (neuro)inflammation in anxiety-related disorders, or in anxiety as an important transdiagnostic symptom, is much less clear. In this review we first critically review clinical and in part preclinical evidence of central and peripheral immune dysregulation in anxiety disorders and post-traumatic stress disorder (PTSD) and briefly discuss proposed mechanisms of how inflammation can affect anxiety-related symptoms. We then give an overview of existing and potential future targets in inflammation-associated signal transduction pathways and discuss effects of different immune-modulatory drugs in anxiety-related disorders. Finally, we discuss key gaps in current clinical trials such as the lack of prospective studies involving anxiety patient stratification strategies based on inflammatory biomarkers. Overall, although evidence is rather limited so far, there is data to indicate that increased (neuro)inflammation is present in subgroups of anxiety disorder patients. Although exact identification of such immune subtypes of anxiety disorders and PTSD is still challenging, these patients will likely particularly benefit from therapeutic targeting of aspects of the inflammatory system. Different anti-inflammatory treatment approaches (microglia-directed treatments, pro-inflammatory cytokine inhibitors, COX-inhibitors, phytochemicals and a number of novel anti-inflammatory agents) have indeed shown some efficacy even in non-stratified anxiety patient groups and appear promising as novel alternative or complimentary therapeutic options in specific (“inflammatory”) subtypes of anxiety disorder and PTSD patients.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"269 ","pages":"Article 108825"},"PeriodicalIF":12.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GLP-1 receptor agonists, are we witnessing the emergence of a paradigm shift for neuro-cardio-metabolic disorders?","authors":"Abdelilah Arredouani","doi":"10.1016/j.pharmthera.2025.108824","DOIUrl":"10.1016/j.pharmthera.2025.108824","url":null,"abstract":"<div><div>Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as groundbreaking therapeutic agents in managing a spectrum of metabolic disorders, demonstrating remarkable efficacy across multiple organ systems and disease states. These compounds are not only well-established in the treatment of type 2 diabetes (T2D) and obesity—conditions for which they have received widespread approval—but also exhibit promising potential in addressing cardiovascular disease (CVD) and Metabolic dysfunction-associated steatotic liver disease (MASLD).</div><div>Recent investigations have begun to illuminate the utility of GLP-1RAs in the management of type 1 diabetes (T1D), as well as neurodegenerative disorders such as Alzheimer's and Parkinson's disease and various behavioral disorders. A plethora of clinical trials have consistently validated the capacity of GLP-1RAs to improve glycemic control, promote weight loss, and mitigate cardiovascular risk factors in individuals with T2D and obesity. While their application in T1D remains limited due to safety concerns—particularly regarding the risks of hypoglycemia and hyperglycemic ketoacidosis—emerging data suggest that GLP-1RAs may offer hepatoprotective benefits, potentially reducing liver fat content and decelerating the progression of MASLD.</div><div>The neuroprotective attributes of GLP-1 RAs have garnered significant interest, with research indicating their potential to alleviate cognitive decline associated with neurodegenerative diseases. Furthermore, preliminary findings highlight the role of GLP-1 RAs in addressing behavioral disorders, emphasizing their extensive therapeutic promise.</div><div>This comprehensive review synthesizes the current evidence supporting the diverse therapeutic applications of GLP-1RAs, positioning them as “magic drug” therapies for metabolic and neurological disorders. As ongoing research continues to explore innovative applications and combinations of GLP-1RAs, the landscape of disease management in metabolic and neurological contexts is poised for transformative advancements. This review will also critically assess safety considerations and underscore the need for personalized treatment strategies to optimize patient outcomes in these complex and often comorbid conditions.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"269 ","pages":"Article 108824"},"PeriodicalIF":12.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"G protein-coupled estrogen receptor biased signaling in health and disease","authors":"Aisha Bushi ,&nbsp;Yixuan Ma ,&nbsp;Joseph Adu-Amankwaah ,&nbsp;Rong Wang ,&nbsp;Fen Cui ,&nbsp;Rui Xiao ,&nbsp;Jinming Zhao ,&nbsp;Jinxiang Yuan ,&nbsp;Rubin Tan","doi":"10.1016/j.pharmthera.2025.108822","DOIUrl":"10.1016/j.pharmthera.2025.108822","url":null,"abstract":"<div><div>G protein-coupled estrogen receptor (GPER) is now recognized for its pivotal role in cellular signaling, influencing diverse physiological processes and disease states. Unlike classical estrogen receptors, GPER exhibits biased signaling, wherein ligand binding triggers selective pathways over others, significantly impacting cellular responses. This review explores the nuanced mechanisms of biased signaling mediated by GPER, underscoring its relevance in cardiovascular health, neurological function, immune modulation, and oncogenic processes. Despite its critical implications, biased signaling through GPER remains underexplored compared to traditional signaling paradigms. We explore recent progress in understanding GPER signaling specificity and its potential therapeutic implications across various diseases. Future research directions aim to uncover the molecular basis of biased signaling, develop selective ligands, and translate these insights into personalized therapeutic approaches. Exploiting the therapeutic potential of GPER biased signaling represents a promising frontier in precision medicine, offering innovative strategies to address unmet medical needs.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"269 ","pages":"Article 108822"},"PeriodicalIF":12.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The tumor suppressor role and epigenetic regulation of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in cancer and tumor microenvironment (TME)","authors":"SubbaRao V. Tulimilli ,&nbsp;Medha Karnik ,&nbsp;Anjali Devi S. Bettadapura ,&nbsp;Olga A. Sukocheva ,&nbsp;Edmund Tse ,&nbsp;Gowthamarajan Kuppusamy ,&nbsp;Suma M. Natraj ,&nbsp;SubbaRao V. Madhunapantula","doi":"10.1016/j.pharmthera.2025.108826","DOIUrl":"10.1016/j.pharmthera.2025.108826","url":null,"abstract":"<div><div>Oxidative stress and inflammation may initiate carcinogenesis and facilitate metastasis <em>via</em> activation of pro-inflammatory signaling network. The side product of arachidonic acid processing by cyclooxygenase-2 (COX-2), the prostaglandin E2 (PGE2), plays a key role in various metabolic disorders and during inflammation-mediated tumorigenesis. It has been demonstrated that PGE2 increases the proliferation, migration, invasion, metastasis, and resistance of cancer cells to apoptosis and other forms of programmed cell death. The expression level of PGE2 metabolizing enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is often decreased in various malignancies. However, the role of 15-PGDH and PGE2 in the regulation of carcinogenesis remains controversial. Numerous cancer cell lines and mouse models have demonstrated the role of 15-PGDH as a tumor suppressor. Downregulation of 15-PGDH increased cancer cell proliferation, migration, anchorage independent growth, colony formation while overexpression reversed these effects, by inducing apoptosis and cell cycle arrest <em>in vitro</em> and <em>in vivo</em>. The expression of 15-PGDH is regulated by various mechanisms, including (a) epigenetic alterations (methylation of promoter region, histone deacetylases, microRNAs (miR-21, miR-26a/b, miR-106b-5p, miR-146b-3p, miR-155, miR-218-5p, and miR-620)); and (b) dysregulated oxidative stress and associated mediators (elevated levels of growth factors and proinflammatory cytokines (such as IL1β and TNFα)). Several transcription factors, such as HNF3β, β-catenin, Snail, Slug, can bind to 15-PGDH promoter region and downregulate the enzyme expression. In contrast, the expression of 15-PGDH can be upregulated by several anti-inflammatory cytokines and anti-cancer agents, such as IL10 and vitamin D. The functional activity of 15-PGDH protein can be modulated by signaling effectors and oxidative stress, including increased production of reactive oxygen species (ROS). However, the role of oxidative stress regulator protein, <em>i.e.</em>, nuclear factor erythroid 2-related factor 2 (Nrf2), in the control of 15-PGDH expression remains unclear. This article provides insights and comprehensive overview of the tumor suppressor role of 15-PGDH in various cancers. Epigenetic and post-translational mechanisms regulating 15-PGDH expression and the role of novel ROS-Nrf2–15-PGDH axis were discussed and accented as potential drug targets.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"268 ","pages":"Article 108826"},"PeriodicalIF":12.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarker identification in bipolar disorder","authors":"Francesca Martella ,&nbsp;Andrea Caporali ,&nbsp;Monica Macellaro ,&nbsp;Rita Cafaro ,&nbsp;Francesco De Pasquale ,&nbsp;Bernardo Dell'Osso ,&nbsp;Claudio D'Addario","doi":"10.1016/j.pharmthera.2025.108823","DOIUrl":"10.1016/j.pharmthera.2025.108823","url":null,"abstract":"<div><div>Bipolar disorder (BD) is a severe psychiatric condition whose pathophysiology is complex and multifactorial. Genetic, environmental and social risk factors play a role in its development as well as in its progressive course. Research is currently focusing on the identification of the biological basis underlying these processes in order to suggest novel biomarkers capable to predict BD etiopathogenesis and staging. Staging has been recognized as of great value for the treatment and management of many illnesses and might also be suitable for mental health issues, particularly in disorders like BD, which progress from an initial mild phase to a more severe and thus difficult-to-treat situation. Thus, it would be of great help the characterization of to suggest better treatment requirements and improve prognosis across the different stages of the illness. Here, we summarize current research on the biological hypotheses of BD and the biomarkers associated with its progression, reviewing clinical studies available in the literature.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"268 ","pages":"Article 108823"},"PeriodicalIF":12.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143444735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biased signaling by human follicle-stimulating hormone variants","authors":"Alfredo Ulloa-Aguirre ,&nbsp;Teresa Zariñán ,&nbsp;James A. Dias ,&nbsp;T. Rajendra Kumar ,&nbsp;George R. Bousfield","doi":"10.1016/j.pharmthera.2025.108821","DOIUrl":"10.1016/j.pharmthera.2025.108821","url":null,"abstract":"<div><div>Follicle-stimulating hormone (FSH) or follitropin plays a fundamental role in several mammalian species, including humans. This gonadotropin is produced by the anterior pituitary gland and has as its main targets the granulosa cells of the ovary and the Sertoli cells of the testis. Structurally, FSH is composed of two non-convalently linked subunits, the α- and β-subunit, as well as highly heterogenous oligosaccharide structures, which play a key role in determining a number of physiological and biological features of the hormone. Glycosylation in FSH and the other members belonging to the glycoprotein hormone family, is essential for many functions of the gonadotropin, including subunit assembly and stability, secretion, circulatory half-life and biological activity. Carbohydrate heterogeneity in FSH comes in two forms, <em>microheterogeneity,</em> which results from variations in the carbohydrate structural complexity in those oligosaccharides attached to the α- or β-subunit of the hormone and <em>macroheterogeneity</em>, which results from the absence of carbohydrate chain at FSHβ Asn-glycosylation sites. A number of <em>in vitro</em> and <em>in vivo</em> studies have conclusively demonstrated differential, unique and even opposing effects provoked by variations in the carbohydrate structures of FSH, including circulatory survival, binding to and activation of its cognate receptor in the gonads, intracellular signaling, and activation/inhibition of a number of FSH-regulated genes essential for follicle development. Herein, we review the effects of the FSH oligosaccharides on several functions of FSH, and how variations in these structures have been shown to lead to functional selectivity of the hormone.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"268 ","pages":"Article 108821"},"PeriodicalIF":12.0,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}