Molecular Biotechnology最新文献

{"title":"Effect of the Deubiquitinating Peptidase 7 (USP7) on Hepatitis B Virus (HBV) Replication and the Antiviral Efficacy of Entecavir (ETV).","authors":"Yue Liu, Shengfei Pei, Xue Wang, Xueying Li, Yifei Long, Shufeng Sun, Chunyan Meng, Fumin Feng","doi":"10.1007/s12033-024-01355-8","DOIUrl":"https://doi.org/10.1007/s12033-024-01355-8","url":null,"abstract":"<p><p>Hepatitis B is a viral infection of the liver caused by the hepatitis B virus (HBV). Entecavir (ETV) is considered the primary therapeutic option for HBV treatment, primarily functioning by inhibiting HBV replication. Ubiquitin-specific peptidase 7 (USP7), a deubiquitinating enzyme, plays a crucial role in regulating DNA repair mechanisms. This article aims to investigate the role of USP7 in HBV replication and its potential to enhance the antiviral efficacy of ETV, while exploring the underlying mechanisms involved. HBV infection is closely associated with the development of liver cancer. In this study, we selected the HepG2.2.15 cell line, which was stably HepG2 cell transfected with two complete HBV genomes. HepG2.2.15 supports HBV replication, assembly, and secretion. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB) assays were subsequently employed to measure USP7 mRNA and protein levels in both cell lines. The USP7 gene was silenced using small interfering RNA (siRNA), cells were transfected with siRNA-USP7 using Lipo6000™ Transfection Reagent, after which we assessed HBV replication, the levels of HBsAg, and HBeAg following 24, 48, and 72 h of culture in HepG2.2.15 cells. Afterwards, HepG2.2.15 cells were divided into several groups: control, USP7 gene silencing by siRNA group (siRNA-USP7), USP7 silencing negative control group (siRNA-NC), ETV drug treatment (ETV), ETV drug treatment combined with USP7 gene silencing by siRNA group (ETV + siRNA-USP7), and ETV therapy alongside a negative control for siRNA silencing (ETV + siRNA-NC). HBV replication, the levels of HBsAg, and HBeAg in the cell supernatant were assessed after 24, 48, and 72 h of culture. Additionally, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured to evaluate cellular damage. Furthermore, qRT-PCR and Western blot techniques were utilized to analyze p53 mRNA and protein levels as potential downstream mechanisms of USP7, along with assessing Bax and Bcl-2 mRNA and protein levels within the p53 signaling pathway. Lastly, we investigated the interaction between USP7 and p53 proteins through co-immunoprecipitation. USP7 protein and mRNA levels were up-regulated in the HepG2.2.15 cell line, and silencing of USP7 inhibited HBV replication. More importantly, HBV replication, HBsAg, and HBeAg levels in the ETV + siRNA-USP7 group were significantly reduced compared to the other groups (P < 0.05), indicating that silencing USP7 enhances the antiviral effect of ETV. Additionally, ALT and AST levels were significantly decreased (P < 0.05), suggesting a reduction in cellular damage. Furthermore, an interaction between USP7 and p53 was observed. Both mRNA and protein levels of p53, as well as its downstream factors Bax and Bcl-2 in the ETV + siRNA-USP7 group, were significantly down-regulated (P < 0.05), implying that USP7 is involved in regulating the p53 pathway. Decreasing of deubiquitinating peptidase 7 expr","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational Evaluation of Fusarium nygamai Compounds as AcrD Efflux Pump Protein Inhibitors of Salmonella Typhimurium.","authors":"Lennin Isaac Garrido-Palazuelos, José Roberto Aguirre-Sánchez, Maria Fernanda Sandoval-González, Mamuna Mukhtar, Omar Guerra-Meza, Haris Ahmed-Khan","doi":"10.1007/s12033-024-01329-w","DOIUrl":"https://doi.org/10.1007/s12033-024-01329-w","url":null,"abstract":"<p><p>In Salmonella Typhimurium, efflux pump proteins, such as AcrD actively expel drugs and hazardous chemicals from bacterial cells, resulting in treatment failure and the emergence of antibiotic-resistant variants. Focusing on AcrD may lead to the development of novel antimicrobials against multidrug-resistant bacteria. However, challenges persist in achieving high selectivity, low toxicity, and effective bacterial penetration. Natural products, particularly microbial secondary metabolites, possess distinct chemical structures that may target the efflux pump systems. The efflux pump inhibitor capabilities of Fusarium nygamai compounds in Salmonella have not been previously investigated. This study employed molecular docking and molecular dynamics simulations to evaluate 25 F. nygamai compounds as potential inhibitors of AcrD. Additionally, the pharmacological characteristics of these substances were examined. Molecular docking results revealed that 3,6-Dimethoxy-2,5-dinitrobenzonitrile, methyl (2-oxo-3-phenylquinoxalin-1(2H)-yl)acetate, and 7-Methyl-5-nitro-1,4-dihydro-quinoxaline-2,3-dione exhibited the highest binding energies with AcrD. Furthermore, molecular dynamics simulations indicated stable ligand-receptor complex variations over time. This study contributes to the efforts against antibiotic resistance and the improvement of Salmonella infection treatment outcomes globally by facilitating the development of novel therapeutic approaches and enhancing antibiotic efficacy.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apoptotic and Molecular Mechanisms of Carthamidin in Breast Cancer Therapy: An Integrated In Vitro and In Silico Study.","authors":"Selvakumari Palani, John Joseph, Priyadharshan Sridhar, Giridharan Bupesh, Konda Mani Saravanan, Rajkuberan Chandrasekaran","doi":"10.1007/s12033-024-01331-2","DOIUrl":"https://doi.org/10.1007/s12033-024-01331-2","url":null,"abstract":"<p><p>The current study examines the anticancer properties of the chemical carthamidin in breast cancer through in-vitro and in silico analysis. This study's results demonstrated that carthamidin strongly inhibited the proliferation of MCF 7 cells in vitro, as evidenced by an IC50 value of 128.65 µg/mL at 24 h, determined using the MTT test. Laser confocal microscopy utilizing AO/EB labeling validated apoptotic effects through upregulating pro-apoptotic cell markers. At the same time, the ROS assay demonstrated elevated ROS production in the treated cells. LDH leakage was corroborated by leakage analysis, revealing high LDH levels at 100 µg/mL. The cellular growth parameters were subsequently examined via flow cytometry, showing that the cell cycle was halted in the G0/G1 phase, with 82.9% of the cells residing there. The molecular docking research demonstrated that carthamidin displayed a significant binding affinity with Notch receptors - NOTCH 1-4 and p53, with binding scores ranging from - 5.027 to - 7.402 kcal/mol. The results suggest that carthamidin has therapeutic potential in inducing apoptosis and impairing cancer cells, warranting further investigation in breast cancer treatments.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling Key Genes Modulating Retinal Cell Survival and Autophagy in Glaucoma.","authors":"Yingmei Li, Jing Ma, Xin Li, Chao Huang","doi":"10.1007/s12033-024-01341-0","DOIUrl":"https://doi.org/10.1007/s12033-024-01341-0","url":null,"abstract":"<p><p>Glaucoma is a leading cause of irreversible blindness, with rising incidence globally. Effective treatment is challenging due to limited understanding of the disease mechanisms. Growth factor activity is crucial in glaucoma, with potential to reduce retinal ganglion cell (RGC) apoptosis and slow disease progression. This study aims to identify and analyze differentially expressed genes (DEGs) involved in growth factor activity to uncover new therapeutic targets. We analyzed the GSE9944 dataset from the Gene Expression Omnibus (GEO) to identify DEGs associated with glaucoma, resulting in 94 DEGs, including 29 down-regulated and 65 up-regulated genes. Functional enrichment and protein-protein interaction (PPI) network analyses were conducted using bioinformatics tools, highlighting the roles of Bone Morphogenetic Protein 1 (BMP1), Pleiotrophin (PTN), and f fibroblast Growth Factor 7 (FGF7). Aberrant expression vectors for these genes were transfected into RGCs derived from a glaucoma model to evaluate their impact on cell viability, apoptosis, and autophagy. Bioinformatics analysis of the GSE9944 dataset identified 94 DEGs, with 29 down-regulated and 65 up-regulated genes. Functional enrichment analysis revealed that these DEGs were involved in pathways related to growth factor activity, apoptosis, and autophagy, processes highly relevant to glaucoma pathogenesis. PPI network analysis identified BMP1, PTN, and FGF7 as central hub genes involved in extracellular matrix organization and growth factor signaling. In experimental validation using RGCs, we found that up-regulation of BMP1 significantly enhanced RGC viability and reduced apoptosis. Conversely, silencing PTN and FGF7 provided protective effects, enhancing RGC survival. Silencing BMP1 and upregulating PTN and FGF7 led to increased RGC apoptosis. Additionally, BMP1 was found to inhibit autophagy in RGCs, whereas PTN and FGF7 promoted autophagic activity, suggesting differential regulatory roles in glaucoma pathogenesis. Overall, BMP1, PTN, and FGF7 play critical roles in the regulation of RGC activity and autophagy in glaucoma, making them promising molecular targets for future therapeutic interventions.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intertwining of Cellular Osmotic Stress Handling Mechanisms and Heavy Metal Accumulation.","authors":"Rosina Sánchez-Thomas, Mariel Hernández-Garnica, Juan Carlos Granados-Rivas, Emma Saavedra, Ignacio Peñalosa-Castro, Sara Rodríguez-Enríquez, Rafael Moreno-Sánchez","doi":"10.1007/s12033-024-01351-y","DOIUrl":"https://doi.org/10.1007/s12033-024-01351-y","url":null,"abstract":"<p><p>Osmoregulation mechanisms are engaged in the detoxification and accumulation of heavy metals in plants, microalgae and other microorganisms. The present review paper analyzes osmotic resistance organisms and their heavy metal accumulation mechanisms closely related to osmoregulation. In prokaryotic and eukaryotic microorganisms, such as the green algae-like protist Euglena, osmotic and heavy metal stresses share similar cell responses and mechanisms. Likewise, some plants have developed specific mechanisms associated to water stress induced by salinity, flooding, or drought, which are also activated under heavy metal stress. Thus, synthesis of osmo-metabolites and strategies to maintain stable the intracellular water content under heavy metal exposure induce a state of apparent drought by blocking the water maintenance systems. Heavy metals affect the cellular redox state, triggering signaling pathways for intracellular water maintenance, which are mediated by the concentration of reactive oxygen species. Hence, cellular responses and mechanisms associated with osmotic stress, once fully elucidated, represent new opportunities to improve mechanistic strategies for bioremediation of heavy metal-polluted sites.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Note: Ethanol Extract of Anacyclus pyrethrum Root Ameliorates Cough-Variant Asthma Through the TLR4/NF-κB Pathway and Wnt/β-Catenin Pathway.","authors":"Jun Zheng, Hao Yang, Changjiang Liu, Rui Zhang, Nadire Yibulayimu, Xiaoyue Jin","doi":"10.1007/s12033-024-01350-z","DOIUrl":"10.1007/s12033-024-01350-z","url":null,"abstract":"","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: CRISPR-Cas9: Unraveling Genetic Secrets to Enhance Floral and Fruit Traits in Tomato.","authors":"S Bhoomika, Shubham Rajaram Salunkhe, A R Sakthi, T Saraswathi, S Manonmani, M Raveendran, M Sudha","doi":"10.1007/s12033-024-01336-x","DOIUrl":"https://doi.org/10.1007/s12033-024-01336-x","url":null,"abstract":"","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pivotal Role of miRNA-lncRNA Interactions in Human Diseases.","authors":"Farkhondeh Pooresmaeil, Sareh Azadi, Behnam Hasannejad-Asl, Shahla Takamoli, Azam Bolhassani","doi":"10.1007/s12033-024-01343-y","DOIUrl":"https://doi.org/10.1007/s12033-024-01343-y","url":null,"abstract":"<p><p>New technologies have shown that most of the genome comprises transcripts that cannot code for proteins and are referred to as non-coding RNAs (ncRNAs). Some ncRNAs, like long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), are of substantial interest because of their critical function in controlling genes and numerous biological activities. The expression levels and function of miRNAs and lncRNAs are rigorously monitored throughout developmental processes and the maintenance of physiological homeostasis. Due to their critical roles, any dysregulation or changes in their expression can significantly influence the pathogenesis of various human diseases. The interactions between miRNAs and lncRNAs have been found to influence gene expression in various ways. These interactions significantly influence the understanding of disease etiology, cellular processes, and potential therapeutic targets. Different experimental and in silico methods can be used to investigate miRNA-lncRNA interactions. By aiding the elucidation of miRNA-lncRNA interactions and deepening the understanding of post-transcriptional gene regulation, researchers can open a new window for designing hypotheses, conducting experiments, and discovering methods for diagnosing and treating complex human diseases. This review briefly summarizes miRNA and lncRNA functions, discusses their interaction mechanisms, and examines the experimental and computational methods used to study these interactions. Additionally, we highlight significant studies on lncRNA and miRNA interactions in various diseases from 2000 to 2024, using the academic research databases such as PubMed, Google Scholar, ScienceDirect, and Scopus.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiproliferative Activity and Molecular Docking Analyses of Sesquiterpene Lactones Obtained from Activity-Directed Isolation of Centaurea saligna (K.Koch) Wagenitz in Neoplastic Cells.","authors":"Aybeniz Yıldırım, Ali Şen, Bünyamin Göktaş, Harun Uslu, Özlem Bingöl Özakpınar, Leyla Bitiş","doi":"10.1007/s12033-024-01342-z","DOIUrl":"https://doi.org/10.1007/s12033-024-01342-z","url":null,"abstract":"<p><p>Secondary metabolites obtained from plants are among the most commonly encountered chemotherapeutics used in cancer treatment. Plants contain thousands of metabolites; therefore, it is important to reach the compound primarily responsible for activity by fractionating plant extracts through activity-guided isolation. The cytotoxic activities of C. saligna fractions, sub-fractions, and all pure compounds obtained from the plant were investigated in vitro using MCF-7 (human breast cancer), HeLa (human cervical cancer), and PC-3 (prostate cancer) cell lines. Eighteen compounds were isolated from C. saligna, comprising eight sesquiterpene lactones, three flavonoids, five lignans, and two phenolic compounds, with their structures elucidated through ¹H-NMR, ¹³C-NMR, and HMBC spectroscopic techniques. The molecular docking scores of the pure compounds obtained from these sub-fractions were determined using both AutoDock and AutoDock Vina programs. It has been proven that the affinities of linichlorin B and aguerin B for Bcl-2 are higher than those of other compounds, considering the calculated Ki values and placement scores. Notable activities of linichlorin B, cynaropicrin, and aguerin B (with IC₅₀ values of 13.67 μg/ml, 6.79 μg/ml, and 3.46 μg/ml, respectively) were detected in the PC-3 cell line; aguerin B demonstrated activity most comparable to the standard anticancer agent doxorubicin. Likewise, linichlorin B, aguerin B, and cynaropicrin demonstrated notable efficacy in the HeLa and MCF-7 cell lines, as reported by the American National Cancer Institute. Aguerin B, linichlorin B, and cynaropicrin are projected to serve as promising novel chemotherapeutic agents for cancer therapy.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Analysis of Gene Expression and Immune Cell Infiltration Reveals Dysregulated Genes and miRNAs in Acute Kidney Injury.","authors":"Jian-Nan Zhang, Rui Gong, Bai-Tao Lu, Yi-Qi Wang, Yang Chong, Xin-Tong Wang, Qi-Qi Lai, Yan-Hui Cao, Ming-Yan Zhao","doi":"10.1007/s12033-024-01344-x","DOIUrl":"https://doi.org/10.1007/s12033-024-01344-x","url":null,"abstract":"<p><p>Acute Kidney Injury (AKI) is a multifaceted condition characterised by rapid deterioration of renal function, often precipitated by diverse etiologies. A comprehensive understanding of the molecular underpinnings of AKI is pivotal for identifying potential diagnostic markers and therapeutic targets. This study utilised bioinformatics to elucidate gene expression and immune infiltration in AKI. Publicly available mRNA and miRNA datasets were harnessed to discern differentially expressed genes (DEGs) and miRNAs in AKI. The CIBERSORT algorithm was employed to quantify immune cell infiltration in AKI samples. Functional enrichment analyses were conducted to unravel the implicated biological processes. Furthermore, the expression of identified genes and miRNAs was validated by quantitative real-time PCR in an AKI model. Our study revealed significant dysregulation of three genes (Aspn, Clec2h, Tmigd1) and two miRNAs (mmu-miR-21a-3p, mmu-miR-223-3p) in AKI, each with p < 0.0001. These molecular markers are implicated in immune responses, tissue remodelling, and inflammation. We observed notable disturbances in specific immune cells, including activated and immature dendritic cells, M1 macrophages, and subsets of T cells (Treg, Th1, Th17). These alterations correlated significantly with AKI pathology, with dendritic cells and M1 macrophages showing p < 0.01, and T cell subsets demonstrating p < 0.05. These results highlight the intricate involvement of the immune system in AKI and indicate significant enrichment of pathways related to immune response, inflammation, and tissue remodelling, pointing to their pivotal roles in AKI pathophysiology. Our study underscored the significance of immune cell infiltration and dysregulated gene and miRNA expression in AKI. The identified genes (Clec2h, Aspn, and Tmigd1) and miRNAs (mmu-miR-21a-3p and mmu-miR-223-3p) offer potential diagnostic markers and therapeutic avenues for AKI. Subsequent investigations targeting these genes and miRNAs, along with the elucidated pathways, may augment the clinical management and outcomes for AKI patients.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}