RNA BiologyPub Date : 2025-12-01Epub Date: 2025-01-29DOI: 10.1080/15476286.2025.2453963
Karolin Wellner, Josefine Gnauck, Dorian Bernier, Stephan H Bernhart, Heike Betat, Mario Mörl
{"title":"Two complementing <i>in vivo</i> selection systems based on CCA-trimming exonucleases as a tool to monitor, select and evaluate enzymatic features of tRNA nucleotidyltransferases.","authors":"Karolin Wellner, Josefine Gnauck, Dorian Bernier, Stephan H Bernhart, Heike Betat, Mario Mörl","doi":"10.1080/15476286.2025.2453963","DOIUrl":"10.1080/15476286.2025.2453963","url":null,"abstract":"<p><p>tRNA nucleotidyltransferase represents a ubiquitous and essential activity that adds the indispensable CCA triplet to the 3'-end of tRNAs. To fulfill this function, the enzyme contains a set of highly conserved motifs whose coordinated interplay is crucial for the sequence-specific CCA polymerization. In the human enzyme, alterations within these regions have been shown to lead to the manifestation of disease. Recently, we developed an <i>in vivo</i> screening system that allows for the selection and analysis of tRNA nucleotidyltransferase variants by challenging terminal AMP incorporation into tRNA during induced RNase T-catalyzed CCA-decay. Here, we extend this method for screening of full CCA-end repair by utilizing the CCA-trimming activity of exonuclease LCCR4. To demonstrate the combined potential of these two <i>in vivo</i> selection systems, we applied a semi-rational library design to investigate the mode of operation of catalytically important motifs in the human CCA-adding enzyme. This approach revealed unexpected requirements for amino acid composition in two motifs and gives new insights into the mechanism of CCA addition. The data show the potential of these RNase-based screening systems, as they allow the detection of enzyme variations that would not have been identified by a conventional rational approach. Furthermore, the combination of both RNase T and LCCR4 systems can be used to investigate and dissect the effects of pathogenic mutations on C- and A-addition.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":"1-14"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VirulencePub Date : 2025-12-01Epub Date: 2025-02-08DOI: 10.1080/21505594.2025.2462092
Fangzheng Guo, Yamin Song, Sihang Dong, Jing Wei, Baiqing Li, Tao Xu, Hongtao Wang
{"title":"Characterization and anti-tuberculosis effects of γδ T cells expanded and activated by <i>Mycobacterium tuberculosis</i> heat-resistant antigen.","authors":"Fangzheng Guo, Yamin Song, Sihang Dong, Jing Wei, Baiqing Li, Tao Xu, Hongtao Wang","doi":"10.1080/21505594.2025.2462092","DOIUrl":"https://doi.org/10.1080/21505594.2025.2462092","url":null,"abstract":"<p><p>Tuberculosis (TB) is a chronic infectious disease caused by <i>Mycobacterium tuberculosis</i> (Mtb) that poses a severe threat to human health. A variety of highly immunogenic tuberculosis proteins have been used as targets in vaccine development to mitigate the spread of TB. Although Th1-type immunity has long been considered a crucial part of resistance to Mtb, γδ T cells, the predominant source of IL-17, are not negligible in controlling the early stages of TB infection. In addition to classical phosphoantigens, <i>Mycobacterium tuberculosis</i> heat-resistant antigens (HAg), a complex containing 564 proteins obtained from live tuberculosis bacteria after heat treatment at 121 °C for 20 min, have been confirmed to be highly effective γδ T cell stimulators as well. Several studies have demonstrated that HAg-activated γδ T cells can participate in TB immunity by secreting multiple cytokines against Mtb or by interacting with other innate immune cells. In this review, we present a possible mechanism of HAg stimulation of γδ T cells and the role of HAg-activated γδ T cells in anti-TB immunity. We also highlight the limitations of studies on HAg activation of γδ T cells and suggest further research directions on the relationship between HAg and γδ T cells.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2462092"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Protection acquired upon intraperitoneal group a <i>Streptococcus</i> immunization is independent of concurrent adaptive immune responses but relies on macrophages and IFN-γ.","authors":"Shiva Emami, Elsa Westerlund, Thiago Rojas Converso, Bengt Johansson-Lindbom, Jenny J Persson","doi":"10.1080/21505594.2025.2457957","DOIUrl":"https://doi.org/10.1080/21505594.2025.2457957","url":null,"abstract":"<p><p>Group A <i>Streptococcus</i> (GAS; <i>Streptococcus pyogenes</i>) is an important bacterial pathogen causing over 700 million superficial infections and around 500.000 deaths due to invasive disease or severe post-infection sequelae yearly. In spite of this major impact on society, there is currently no vaccine available against this bacterium. GAS strains can be separated into >250 distinct <i>emm</i> (M)-types, and protective immunity against GAS is believed to in part be dependent on type-specific antibodies. Here, we analyse the nature of protective immunity generated against GAS in a model of intraperitoneal immunization in mice. We demonstrate that multiple immunizations are required for the ability to survive a subsequent lethal challenge, and although significant levels of GAS-specific antibodies are produced, these are redundant for protection. Instead, our data show that the immunization-dependent protection in this model is induced in the absence of B and T cells and is accompanied by the induction of an altered acute cytokine profile upon subsequent infection, noticeable e.g. by the absence of classical pro-inflammatory cytokines and increased IFN-γ production. Further, the ability of immunized mice to survive a lethal infection is dependent on macrophages and the macrophage-activating cytokine IFN-γ. To our knowledge these findings are the first to suggest that GAS may have the ability to induce forms of trained innate immunity. Taken together, the current study proposes a novel role for the innate immune system in response to GAS infections that potentially could be leveraged for future development of effective vaccines.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2457957"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Importance of pesticide and additional food in pest-predator system: a theoretical study.","authors":"K Durga Prasad, B S R V Prasad, Kritish De","doi":"10.1080/17513758.2024.2444263","DOIUrl":"https://doi.org/10.1080/17513758.2024.2444263","url":null,"abstract":"<p><p>Integrated pest management (IPM) combines chemical and biological control to maintain pest populations below economic thresholds. The impact of providing additional food for predators on pest-predator dynamics, along- side pesticide use, in the IPM context remains unstudied. To address this issue, in this work a theoretical model was developed using differential equations, assuming Holling type II functional response for the predator, with additional food sources included. Strategies for controlling pest populations were derived by analyzing Hopf bifurcation occurring in the system using dynamical system theory. The study revealed that the quality and quantity of additional food supplied to predators play a crucial role in the system's dynamics. Pesticides, combined with the introduction of predators supported by high-quality supplementary food, enable a quick elimination of pests from the system more effectively. This observation highlights the role of IPM in optimizing pest management strategies with minimal pesticide application and supporting the environment.</p>","PeriodicalId":48809,"journal":{"name":"Journal of Biological Dynamics","volume":"19 1","pages":"2444263"},"PeriodicalIF":1.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
RNA BiologyPub Date : 2025-12-01Epub Date: 2025-01-05DOI: 10.1080/15476286.2024.2448387
Lei Chen, Xia Gao, Xiangshen Liu, Ye Zhu, Dong Wang
{"title":"Translational regulation of PKD1 by evolutionarily conserved upstream open reading frames.","authors":"Lei Chen, Xia Gao, Xiangshen Liu, Ye Zhu, Dong Wang","doi":"10.1080/15476286.2024.2448387","DOIUrl":"https://doi.org/10.1080/15476286.2024.2448387","url":null,"abstract":"<p><p>Mutations in <i>PKD1</i> coding sequence and abnormal PKD1 expression levels contribute to the development of autosomal-dominant polycystic kidney disease, the most common genetic disorder. Regulation of PKD1 expression by factors located in the promoter and 3´ UTR have been extensively studied. Less is known about its regulation by 5´ UTR elements. In this study, we investigated the effects of uORFs and uORF-affecting variants by combining bioinformatic analyses, luciferase reporter assays, RT-qPCR and immunoblotting experiments. Our analyses demonstrate that <i>PKD1</i> mRNA contains two evolutionarily conserved translation-inhibitory uORFs. uORF1 is translatable, and uORF2 is likely not translatable. The 5´ UTR and uORFs do not modulate downstream protein output under endoplasmic reticulum stress and oxidative stress conditions. Some of uORF-perturbing variants in the SNP database are predicted to affect gene translation. Luciferase reporter assays and RT-qPCR results reveal that rs2092942382 and rs1596636969 increase, while rs2092942900 decreases main gene translation without affecting transcription. Antisense oligos targeting the uORFs reduce luciferase protein levels without altering luciferase mRNA levels. Our results establish <i>PKD1</i> as a novel target of uORF-mediated translational regulation and mutations that perturb uORFs may dysregulate PKD1 protein level.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":"22 1","pages":"1-12"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EpigeneticsPub Date : 2025-12-01Epub Date: 2025-01-28DOI: 10.1080/15592294.2025.2456418
Shafiq Shaikh, Xia Zhao, Ryan T Wagner, Xiaoyu Pan, Ryan A Hlady, Liguo Wang, Thai H Ho, Keith D Robertson
{"title":"Deciphering the interplay between SETD2 mediated H3K36me3 and RNA N6-methyladenosine in clear cell renal cell carcinoma (ccRCC).","authors":"Shafiq Shaikh, Xia Zhao, Ryan T Wagner, Xiaoyu Pan, Ryan A Hlady, Liguo Wang, Thai H Ho, Keith D Robertson","doi":"10.1080/15592294.2025.2456418","DOIUrl":"10.1080/15592294.2025.2456418","url":null,"abstract":"<p><p>RNA N6-methyladenosine (m6A) plays diverse roles in RNA metabolism and its deregulation contributes to tumor initiation and progression. Clear cell renal cell carcinoma (ccRCC) is characterized by near ubiquitous loss of <i>VHL</i> followed by mutations in epigenetic regulators <i>PBRM1</i>, <i>SETD2</i>, and <i>BAP1</i>. Mutations in <i>SETD2</i>, a histone H3 lysine 36 trimethylase (H3K36me3), are associated with reduced survival, greater metastatic propensity, and metabolic reprogramming. While m6A and H3K36me3 deregulation are separately implicated in renal tumorigenesis, H3K36me3 may participate directly in m6A targeting, but the m6A-H3K36me3 interplay has not been investigated in the context of ccRCC. Using RCC-relevant SETD2 isogenic knockout and rescue cell line models, we demonstrate a dynamic redistribution of m6A in the SETD2 depleted transcriptome, with a subset of transcripts involved in metabolic reprogramming demonstrating SETD2 dependent m6A and expression level changes. Using a panel of six histone modifications we show that m6A redistributes to regions enriched in gained active enhancers upon <i>SETD2</i> inactivation. Finally, we demonstrate a reversal of transcriptomic programs involved in SETD2 loss mediated metabolic reprogramming, and reduced cell viability through pharmacologic inhibition or genetic ablation of m6A writer METTL3 specific to SETD2 deficient cells. Thus, targeting m6A may represent a novel therapeutic vulnerability in <i>SETD2</i> mutant ccRCC.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2456418"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clinical analysis and risk factors associated with poor prognosis in nontuberculous mycobacterial infection.","authors":"Jinjing Chai, Sujie Zhang, Chong Ma, Qimin Mei, Tao Liu, Jihai Liu, Yecheng Liu, Huadong Zhu","doi":"10.1080/21505594.2025.2459313","DOIUrl":"10.1080/21505594.2025.2459313","url":null,"abstract":"<p><p>Recently, the incidence and prevalence of NTM have been increasing nationwide in many countries. This study aimed to identify risk factors associated with the prognosis and mortality of non-HIV nontuberculous mycobacterial disease patients. This retrospective study was conducted at Peking Union Medical College Hospital. The electronic medical records in the hospital's database from January 2013 to December 2022 were retrospectively reviewed. Relevant data, including clinical characteristics, laboratory findings, microbiological tests, treatments, and outcomes were collected and subjected to statistical analyses. The search identified 745 patients diagnosed with NTM infection, of whom 147 met the inclusion criteria. NTM pulmonary disease was the most commonly observed (<i>n</i> = 93; 63.3%), followed by disseminated infection (<i>n</i> = 43; 29.3%). The most frequent NTM species was <i>Mycobacterium avium</i> complex (55.8%), followed by <i>Mycobacterium abscessus</i> (21.2%). The incidence of <i>Aspergillus</i> and <i>Pseudomonas aeruginosa</i> infection was significantly higher in the NTM pulmonary disease group than in the disseminated NTM group. Cumulative mortality in the total patients was 24.49% at 5 years. High Charlson Comorbidity Index (CCI), high neutrophil-to-lymphocyte-ratio (NLR), haematological disease, and disseminated infection were identified as independent predictors of unfavourable outcomes. The area under the curve (AUC) values for NLR and neutrophil-to-monocyte-plus-lymphocyte-ratio (NMLR) were 0.751 and 0.763 with optimal cut-off values of 9.50 and 3.83, respectively, for prediction of mortality in patients with NTM disease.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2459313"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effect of COVID-19 infection on thyroid function status and clinical indexes among hypothyroid outpatients.","authors":"Bingxin Li, Xiaoyun Feng, Yihan Zhang, Yunhong Huang, Mingyu Gu, Haiyan Sun, Wenqian Ren, Qin Zhen, Tingting Shen, Ling Pan, Tingting Fan, Qin Qin, Fang Liu, Yongde Peng, Yufan Wang, Huanbai Xu","doi":"10.1080/21505594.2024.2441397","DOIUrl":"https://doi.org/10.1080/21505594.2024.2441397","url":null,"abstract":"<p><p>The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly, leading to an Omicron outbreak in Shanghai in mid-December after adjustments to the Coronavirus Disease 2019 (COVID-19) control strategy. To investigate the impact of COVID-19 infection among hypothyroid patients, we gathered data on the hypothyroid outpatients with COVID-19 infection during this time at the Thyroid Disease Center (TDC) of Shanghai Central Hospital. Patients were divided into two groups based on whether their hypothyroidism was caused by Hashimoto's Thyroiditis (HT): the HT and the non-HT group. We assessed the differences between pre-infection and clinical follow-up at one month (day (D) 30) and three months (D90) after COVID-19 infection. In HT group, thyroid-stimulating hormone (TSH) levels decreased significantly compared to pre-infection levels (<i>p</i> = 0.013), while free triiodothyronine (FT3) levels increased at D90 compared to both D30 post-infection and pre-infection levels (<i>p</i> < 0.001 and <i>p</i> = 0.005). Hemoglobin levels also increased after COVID-19 infection (<i>p</i> = 0.033). For non-HT patients, FT3 levels increased at D30 compared to pre-infection levels (<i>p</i> = 0.017). Moreover, inactivated SARS-CoV-2 vaccination can preserve thyroid function stability in patients with hypothyroidism.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2441397"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FlyPub Date : 2025-12-01Epub Date: 2024-12-24DOI: 10.1080/19336934.2024.2438473
Girish Deshpande, Subhradip Das, Adheena Elsa Roy, Girish S Ratnaparkhi
{"title":"A face-off between Smaug and Caspar modulates primordial germ cell count and identity in <i>Drosophila</i> embryos.","authors":"Girish Deshpande, Subhradip Das, Adheena Elsa Roy, Girish S Ratnaparkhi","doi":"10.1080/19336934.2024.2438473","DOIUrl":"https://doi.org/10.1080/19336934.2024.2438473","url":null,"abstract":"<p><p>Proper formation and specification of Primordial Germ Cells (PGCs) is of special significance as they gradually transform into Germline Stem Cells (GSCs) that are ultimately responsible for generating the gametes. Intriguingly, not only the PGCs constitute the only immortal cell type but several specific determinants also underlying PGC specification such as Vasa, Nanos and Germ-cell-less are conserved through evolution. In <i>Drosophila melanogaster</i>, PGC formation and specification depends on two independent factors, the maternally deposited specialized cytoplasm (or germ plasm) enriched in germline determinants, and the mechanisms that execute the even partitioning of these determinants between the daughter cells. Prior work has shown that Oskar protein is necessary and sufficient to assemble the functional germ plasm, whereas centrosomes associated with the nuclei that invade the germ plasm are responsible for its equitable distribution. Our recent data suggests that Caspar, the <i>Drosophila</i> orthologue of human Fas-associated factor-1 (FAF1) is a novel regulator that modulates both mechanisms that underlie the determination of PGC fate. Consistently, early blastoderm embryos derived from females compromised for <i>caspar</i> display reduced levels of Oskar and defective centrosomes.</p>","PeriodicalId":12128,"journal":{"name":"Fly","volume":"19 1","pages":"2438473"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881623","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}
FlyPub Date : 2025-12-01Epub Date: 2024-12-20DOI: 10.1080/19336934.2024.2439111
Stewart Leigh, Michael G Ritchie
{"title":"A history of studies of reproductive isolation between <i>Drosophila pseudoobscura</i> and <i>D. persimilis</i>.","authors":"Stewart Leigh, Michael G Ritchie","doi":"10.1080/19336934.2024.2439111","DOIUrl":"https://doi.org/10.1080/19336934.2024.2439111","url":null,"abstract":"<p><p><i>Drosophila pseudoobscura</i> and <i>D. persimilis</i> are a sister species pair that have been used as a model for studies of reproductive isolation and speciation for almost 100 years owing to their close evolutionary history, well characterized genetic differences, and overlapping geographic distribution. There are extensive analyses of both pre- and post-zygotic isolation, including studies of courtship divergence, conspecific sperm precedence (CSP) and how reinforcement by natural selection may or may not act to strengthen isolation in sympatry. Post-zygotic analyses explore the underlying mechanics of reproductive isolation; how inversions may give rise to initial speciation events and misexpression of key genes typically found within inversion regions render hybrid offspring unfit or inviable. We aim here to present a history of studies of reproductive isolation between this species pair, looking at how the field has developed over the last century and identifying the open questions and gaps within the literature.</p>","PeriodicalId":12128,"journal":{"name":"Fly","volume":"19 1","pages":"2439111"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871919","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}