Central nervous system agents in medicinal chemistry最新文献

{"title":"Lead Identification Through <i>In Silico</i> Studies: Targeting Acetylcholinesterase Enzyme Against Alzheimer's Disease.","authors":"Dhairiya Agarwal, Sumit Kumar, Ramesh Ambatwar, Neeru Bhanwala, Lokesh Chandrakar, Gopal L Khatik","doi":"10.2174/0118715249268585240107184956","DOIUrl":"10.2174/0118715249268585240107184956","url":null,"abstract":"<p><strong>Aims: </strong>In this work, we aimed to acquire the best potential small molecule for Alzheimer's disease (AD) treatment using different models in Biovia Discovery Studio to identify new potential inhibitors of acetylcholinesterase (AChE) <i>via in silico</i> studies.</p><p><strong>Background: </strong>The prevalence of cognitive impairment-related neurodegenerative disorders, such as AD, has been observed to escalate rapidly. However, we still know little about the underlying functions, outcome predictors, or intervention targets causing AD.</p><p><strong>Objectives: </strong>The objective of the study was to optimize and identify the lead compound to target AChE against Alzheimer's disease.</p><p><strong>Methods: </strong>Different <i>in silico</i> studies were employed, including the pharmacophore model, virtual screening, molecular docking, <i>de novo</i> evolution model, and molecular dynamics.</p><p><strong>Results: </strong>The pharmacophoric features of AChE inhibitors were determined by ligand-based pharmacophore models and 3D QSAR pharmacophore generation. Further validation of the best pharmacophore model was done using the cost analysis method, Fischer's randomization method, and test set. The molecules that harmonized the best pharmacophore model with the estimated activity < 1 nM and ADMET parameters were filtered, and 12 molecules were subjected to molecular docking studies to obtain binding energy. 3vsp_EK8_1 secured the highest binding energy of 65.60 kcal/mol. Further optimization led to a 3v_Evo_4 molecule with a better binding energy of 70.17 kcal/mol. The molecule 3v_evo_4 was subjected to 100 ns molecular simulation compared to donepezil, which showed better stability at the binding site.</p><p><strong>Conclusion: </strong>A lead compound, 3v_Evo_4 molecule, was identified to inhibit AChE, and it could be further studied to develop as a drug with better efficacy than the existing available drugs for treating AD.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139577140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glutamate Receptors and C-ABL Inhibitors: A New Therapeutic Approach for Parkinson's Disease.","authors":"Priya P Shejul, Gaurav M Doshi","doi":"10.2174/0118715249268627231206115942","DOIUrl":"10.2174/0118715249268627231206115942","url":null,"abstract":"<p><p>Parkinson's disease (PD) is the second-most prevalent central nervous system (CNS) neurodegenerative condition. Over the past few decades, suppression of BCR-Abelson tyrosine kinase (c-Abl), which serves as a marker of -synuclein aggregation and oxidative stress, has shown promise as a potential therapy target in PD. c-Abl inhibition has the potential to provide neuroprotection against PD, as shown by experimental results and the first-in-human trial, which supports the strategy in bigger clinical trials. Furthermore, glutamate receptors have also been proposed as potential therapeutic targets for the treatment of PD since they facilitate and regulate synaptic neurotransmission throughout the basal ganglia motor system. It has been noticed that pharmacological manipulation of the receptors can change normal as well as abnormal neurotransmission in the Parkinsonian brain. The review study contributes to a comprehensive understanding of the approach toward the role of c-Abl and glutamate receptors in Parkinson's disease by highlighting the significance and urgent necessity to investigate new pharmacotherapeutic targets. The article covers an extensive insight into the concept of targeting, pathophysiology, and c-Abl interaction with α-synuclein, parkin, and cyclin-dependent kinase 5 (Cdk5). Furthermore, the concepts of Nmethyl- D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPA) receptor, and glutamate receptors are discussed briefly. Conclusion: This review article focuses on in-depth literature findings supported by an evidence-based discussion on pre-clinical trials and clinical trials related to c-Abl and glutamate receptors that act as potential therapeutic targets for PD.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139565323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sulfonamide Derivatives: Recent Compounds with Potent Anti-alzheimer's Disease Activity.","authors":"Melford Chuka Egbujor","doi":"10.2174/0118715249278489231128042135","DOIUrl":"10.2174/0118715249278489231128042135","url":null,"abstract":"<p><p>Facile synthetic procedures and broad spectrum of biological activities are special attributes of sulfonamides. Sulfonamide derivatives have demonstrated potential as a class of compounds for the treatment of Alzheimer's disease (AD). Recent sulfonamide derivatives have been reported as prospective anti-AD agents, with a focus on analogues that significantly inhibit the function of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes and exhibit remarkable antioxidant and anti-inflammatory properties, all of which are critical for the treatment of AD. Sulfonamide- mediated activation of nuclear factor erythroid 2-related factor 2 (NRF2), a key regulator of the endogenous antioxidant response, has also been suggested as a potential therapeutic approach in AD. Additionally, it has been discovered that a number of sulfonamide derivatives show selectivity for the β- and γ-secretase enzymes and a significant reduction of amyloid B (Aβ) aggregation, which have been implicated in AD. The comparative molecular docking of benzenesulfonamide and donepezil, an AD reference drug showed comparable anti-AD activities. These suggest that sulfonamide derivatives may represent a new class of drugs for the treatment of AD. Thus, the current review will focus on recent studies on the chemical synthesis and evaluation of the anti-AD properties, molecular docking, pharmacological profile, and structure-activity relationship (SAR) of sulfonamide derivatives, as well as their potential anti-AD mechanisms of action. This paper offers a thorough assessment of the state of the art in this field of study and emphasizes the potential of sulfonamide derivatives synthesized during the 2012-2023 period as a new class of compounds for the treatment of AD.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139565346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Pathway, Epidemiological Data and Treatment Strategies of Fungal Infection (Mycoses): A Comprehensive Review.","authors":"Namrata Singh, Vibha Kumari, Karan Agrawal, Mayank Kulshreshtha","doi":"10.2174/0118715249274215231205062701","DOIUrl":"10.2174/0118715249274215231205062701","url":null,"abstract":"<p><p>The recent increase in fungal infections is a health crisis. This surge is directly tied to the increase in immunocompromised people caused by changes in medical practice, such as the use of harsh chemotherapy and immunosuppressive medicines. Immunosuppressive disorders such as HIV have exacerbated the situation dramatically. Subcutaneous or superficial fungal infections can harm the skin, keratinous tissues, and mucous membranes. This category includes some of the most common skin disorders that impact millions of people worldwide. Despite the fact that they are seldom fatal, they can have a catastrophic impact on a person's quality of life and, in rare situations, spread to other people or become obtrusive. The majority of fungal infections under the skin and on the surface are simply and quickly cured. An opportunistic organism that preys on a weak host or a natural intruder can both result in systemic fungal infections. Furthermore, it might be exceedingly lethal and dangerous to one's life. Dimorphic fungi may pose a hazard to healthy populations that are not exposed to endemic fungi. Increased surveillance, the availability of quick, noninvasive diagnostic tests, monitoring the emergence of antifungal medication resistance, and research on the pathophysiology, prevention, and management of fungal infections are just a few potential solutions to these new health problems. The goal of this review is to summarize the data available for fungal infections and the different therapies which are involved in their treatment. Additionally, it also summarizes the molecular and scientific data of the plants which contain anti-fungal activity. Data are acquired using Google, PubMed, Scholar, and other online sources.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139673888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing Blood-brain Barrier Function in the Context of Pain Management.","authors":"Farshad Hassanzadeh Kiabi, Saeed Gharooee Ahangar, Siavash Beiranvand","doi":"10.2174/0118715249283159240316091312","DOIUrl":"10.2174/0118715249283159240316091312","url":null,"abstract":"<p><p>One essential component of the neurovascular system is known as the blood-brain barrier (BBB). This highly effective biological barrier plays a pivotal role in regulating the brain's internal microenvironment and carefully controlling the passage of various chemicals into and out of the brain. Notably, it serves as a safeguard for the brain, particularly when it comes to the selective transportation of drugs like opioids and non-steroidal anti-inflammatory medications (NSAIDs), which are commonly used in the management of chronic pain. It's important to note that during the development of chronic pain, the activation of microglia and astrocytes can potentially disrupt or damage the integrity of the BBB. In this comprehensive review, we aim to delve into the intricate interplay between the blood-brain barrier and the transportation of pain-relieving drugs, shedding light on the challenges and mechanisms involved in this process.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140178237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Therapeutic Potential of Phytoconstituents for Addressing Neurodegenerative Disorders.","authors":"Sweta Kamboj, Prerna Sharma, Rohit Kamboj, Shikha Kamboj, Hariom, Girija, Kumar Guarve, Rohit Dutt, Inderjeet Verma, Kamal Dua, Nidhi Rani","doi":"10.2174/0118715249273015231225091339","DOIUrl":"10.2174/0118715249273015231225091339","url":null,"abstract":"<p><p>Neurodegenerative disorder is a serious condition that is caused by abnormal or no neurological function. Neurodegenerative disease is a major growing cause of mortality and morbidity worldwide, especially in the elderly. After World War Ⅱ, eugenics term was exterminated from medicines. Neurodegenerative disease is a genetically inherited disease. Lifestyle changes, environmental factors, and genetic modification, together or alone, are involved in the occurrence of this disorder. The major examples of neurodegenerative disorders are Alzheimer's and Parkinson's disease, in which apoptosis and necrosis are the two major death pathways for neurons. It has been determined from various studies that the etiology of the neurodegenerative disease involves the role of oxidative stress and anti-oxidant defence system, which are prime factors associated with the activation of signal transduction pathway that is responsible for the formation of synuclein in the brain and manifestation of toxic reactions in the form of functional abnormality, which ultimately leads to the dysfunction of neuronal pathway or cell. There has not been much success in the discovery of effective therapy to treat neurodegenerative diseases because the main cause of abnormal functioning or death of neurons is not well known. However, the use of natural products that are derived from plants has effective therapeutic potential against neurodegenerative disease. The natural compounds with medicinal properties to prevent neurological dysfunction are curcumin, wolfberry, ginseng, and Withania somnifera. The selection and use of natural compounds are based on their strong anti-inflammatory and anti-oxidant properties against neurodegenerative disease. Herbal products have active constituents that play an important role in the prevention of communication errors between neurons and neurotransmitters and their respective receptors in the brain, which influence their function. Considering this, natural products have great potential against neurodegenerative diseases. This article reviews the natural compounds used to treat neurodegenerative diseases and their mechanisms of action.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139543765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Ocimene in Decreasing α-Synuclein Aggregation using Rotenone-induced Rat Model.","authors":"Ankul Singh Suresh, Aarita Sood, Chitra Vellapandian","doi":"10.2174/0118715249283425240212111523","DOIUrl":"10.2174/0118715249283425240212111523","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease is defined by the loss of dopaminergic neurons in the midbrain of substantia nigra associated with Lewy bodies. The precise mechanism is not yet entirely understood.</p><p><strong>Objective: </strong>The study aims to determine whether ocimene has antiparkinsonian activity by reducing α-Synuclein aggregation levels in the brains of rotenone-induced rat models.</p><p><strong>Methods: </strong>36 male rats were used for six groups, with six animals in each group. Vehicle, control (rotenone, 2.5 mg/kg, i.p), standard (L-Dopa, 10 mg/kg, i.p), Test drug of low dose (66.66 mg/kg, i.p), medium dose (100 mg/kg, i.p), and high dose (200 mg/kg, i.p) were administered to the rats. The open field, actophotometer, hanging wire, and catalepsy tests were used to assess the rat's motor performance. The expressions of biomarkers such as AchE, D2 Receptor, and α- Synuclein were evaluated, and their level of expression in the brain samples was checked using ELISA. Histopathological analysis was also carried out to determine the degree of neuron degeneration in the brain samples.</p><p><strong>Results: </strong>The open field test showed significant anxiety levels, whereas test groups showed fewer anxiety levels but increased motor activity. The biochemical tests revealed that rotenonetreated rats had higher levels of AchE, but ocimene-treated rats had a significant decrease in AchE levels. The test drug-treated rats also expressed high levels of D2 receptors. In ocimenetreated rats, α-Synuclein aggregation was reduced, however, in rotenone-treated rats' brain samples, higher clumps of α-Synuclein were observed.</p><p><strong>Conclusion: </strong>Ocimene has neuroprotective properties. As a result, this essential oil might be helpful as a therapeutic treatment for Parkinson's disease.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139975018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Therapeutic Potential of Alkaloids in Alzheimer's Disease Management.","authors":"Randhir Singh, Nidhi Rani, Rajwinder Kaur, Geeta Chahal, Praveen Kumar, Gagandeep Kaur","doi":"10.2174/0118715249269092231109181638","DOIUrl":"10.2174/0118715249269092231109181638","url":null,"abstract":"<p><strong>Background: </strong>Alkaloids are important phytoconstituents obtained from various plant sources. The study's primary goal is to assess the anti-Alzheimer potential of alkaloids using a molecular docking study. Alzheimer's disease (AD) is considered a gradual decline in memory, reasoning, decision-making, orientation to one's physical surroundings, and language.</p><p><strong>Materials and methods: </strong>The main target i.e. acetylcholinesterase proteins was selected for the molecular docking study.</p><p><strong>Results: </strong>The structures of various alkaloids were drawn using Chem Draw Software, PDB was retrieved from the RCSB PDB database, and molecular docking study was performed on Molergo Virtual Docker. The potential alkaloids were identified with anti-Alzheimer potency.</p><p><strong>Conclusion: </strong>Reserpine, vinblastine, ergotamine, and tubocurarine were found to exhibit potential anti-Alzheimer potency.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139428058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GABA-transaminase: A Key Player and Potential Therapeutic Target for Neurological Disorders.","authors":"Sania Grover, Raj Kumar Narang, Shamsher Singh","doi":"10.2174/0118715249267700231116053516","DOIUrl":"10.2174/0118715249267700231116053516","url":null,"abstract":"<p><p>Neurological disorders such as epilepsy, autism, Huntington's disease, multiple sclerosis, and Alzheimer's disease alter brain functions like cognition, mood, movements, and language, severely compromising the well-being of persons, suffering from their negative effects. The neurotransmitters (GABA, glutamate, norepinephrine, dopamine) are found to be involved in neuronal signaling and neurotransmission. GABA, a \"commanding neurotransmitter\" is directly or indirectly associated with various neurological disorders. GABA is metabolized to succinic semialdehyde by a mitochondrial gamma-aminobutyric acid-transaminase (GABA-T) enzyme. Therefore, the alterations in the GABA performance in the distinct regions of the brain <i>via</i> GABA-T overstimulation or inhibition would play a vital role in the pathogenesis of various neurological disorders. This review emphasizes the leading participation of GABA-T in neurological disorders like Huntington's disease, epilepsy, autism, Alzheimer's disease, and multiple sclerosis. In Huntington's disease, epilepsy, and multiple sclerosis, the surfeited performance of GABA-T results in diminished levels of GABA, whereas in autism, the subsidence of GABA-T activity causes the elevation in GABA contents, which is responsible for behavioral changes in these disorders. Therefore, GABA-T inhibitors (in Huntington's disease, epilepsy, and multiple sclerosis) or agonists (in autism) can be used therapeutically. In the context of Alzheimer's disease, some researchers favor the stimulation of GABA-T activity whereas some disagree with it. Therefore, the activity of GABA-T concerning Alzheimer's disease is still unclear. In this way, studies of GABA-T enzymatic activity in contrast to neurological disorders could be undertaken to understand and be considered a therapeutic target for several GABA-ergic CNS diseases.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139514402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current Concepts in the Molecular Mechanisms and Management of Diabetic Neuropathy by Pharmacotherapeutics and Natural Compounds.","authors":"Shivam, Asheesh Kumar Gupta, Sushil Kumar","doi":"10.2174/0118715249278438240325072758","DOIUrl":"10.2174/0118715249278438240325072758","url":null,"abstract":"<p><p>One of the most crippling effects of diabetes mellitus is diabetic neuropathy, which can cause discomfort, loss of movement, and even amputation. Diabetic neuropathy manifests in a variety of ways, ranging from pain to death. Diagnosing diabetic neuropathy can be challenging since it often goes unnoticed for many years following the onset of diabetes. In addition to oxidative stress in neurons, hyperglycemia activates a number of metabolic pathways that are important sources of damage and possible targets for treatment in diabetic neuropathy. Downstream metabolic cascades caused by prolonged hyperglycemia include activation of protein kinase C, increased production of advanced glycation end products, excessive release of cytokines, increased oxidative stress, and injury to peripheral nerves. Despite the fact that these metabolic anomalies are considered the main cause of diabetes-related microvascular issues, the diverse mechanistic processes of neuropathy are characterized by organ-specific histological and biochemical features. Although the symptoms of diabetic neuropathy can be treated, there are few options to correct the underlying problem. Diabetic neuropathy exerts a tremendous financial, psychological, and physical burden on society, emphasizing the need for efficient and focused treatment. The major goal of this review is to shed light on the multiple mechanisms and pathways that contribute to the onset of diabetic neuropathy and to provide readers with a comprehensive understanding of emerging therapeutic strategies to postpone or reverse various forms of diabetic neuropathy. The article discusses available medications and provides the latest guidelines for the treatment of pain and distal symmetric polyneuropathy, including diabetic autonomic neuropathy, which may help the patients control pain well and assess alternatives for treatment that might be more successful in preventing or delaying the course of a disease.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140320125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}