RESUMEN
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). SARS-CoV-2 relies on cellular RNA-binding proteins (RBPs) to replicate and spread, although which RBPs control its life cycle remains largely unknown. Here, we employ a multi-omic approach to identify systematically and comprehensively the cellular and viral RBPs that are involved in SARS-CoV-2 infection. We reveal that SARS-CoV-2 infection profoundly remodels the cellular RNA-bound proteome, which includes wide-ranging effects on RNA metabolic pathways, non-canonical RBPs, and antiviral factors. Moreover, we apply a new method to identify the proteins that directly interact with viral RNA, uncovering dozens of cellular RBPs and six viral proteins. Among them are several components of the tRNA ligase complex, which we show regulate SARS-CoV-2 infection. Furthermore, we discover that available drugs targeting host RBPs that interact with SARS-CoV-2 RNA inhibit infection. Collectively, our results uncover a new universe of host-virus interactions with potential for new antiviral therapies against COVID-19.
Asunto(s)
COVID-19/metabolismo , Proteoma/metabolismo , ARN Viral/metabolismo , Proteínas de Unión al ARN/metabolismo , SARS-CoV-2/fisiología , Proteínas Virales/metabolismo , Replicación Viral/fisiología , Células A549 , COVID-19/genética , Humanos , Proteoma/genética , ARN Viral/genética , Proteínas de Unión al ARN/genética , Proteínas Virales/genéticaRESUMEN
Intervention mapping (IM) is a framework for formulating theory-and evidence-based health education projects with participatory approaches from ecological perspectives.The intervention program designed via IM plays a role in reducing the exposure of cancer risk factors,increasing cancer prevention behaviors,and promoting early cancer screening and rehabilitation of cancer patients.This study summarizes the characteristics,implementation steps,and application status of IM in tertiary prevention of cancer,aiming to provide reference for the application of IM in the health education projects for cancer in China.
Asunto(s)
Neoplasias , Humanos , Prevención Terciaria , Neoplasias/prevención & control , China , Factores de RiesgoRESUMEN
Adaptive intervention(AI)is a methodology which dynamically evaluates adaptive variables at decision points and timely adjusts and develops tailored strategies to meet individual needs.The study reviewed the origin and development and elaborated the core elements(including intervention outcomes,intervention options,decision points,tailoring variables,and decision rules)and the classification of AI.Based on the literature,the key points of the design and implementation of AI were prospected,which can provide evidence for the research and development of health behavior intervention.
RESUMEN
Oncodriver genes are usually identified when mutations recur in multiple tumours. Different drivers often converge in the activation or repression of key cancer-relevant pathways. However, as many pathways contain multiple members of the same gene family, individual mutations might be overlooked, as each family member would necessarily have a lower mutation frequency and thus not identified as significant in any one-gene-at-a-time analysis. Here, we looked for mutated, functional sequence positions in gene families that were mutually exclusive (in patients) with another gene in the same pathway, which identified both known and new candidate oncodrivers. For instance, many inactivating mutations in multiple G-protein (particularly Gi/o) coupled receptors, are mutually exclusive with Gαs oncogenic activating mutations, both of which ultimately enhance cAMP signalling. By integrating transcriptomics and interaction data, we show that the Gs pathway is upregulated in multiple cancer types, even those lacking known GNAS activating mutations. This suggests that cancer cells may develop alternative strategies to activate adenylate cyclase signalling in multiple cancer types. Our study provides a mechanistic interpretation for several rare somatic mutations in multi-gene oncodrivers, and offers possible explanations for known and potential off-label cancer treatments, suggesting new therapeutic opportunities.
Asunto(s)
Mutación , Neoplasias/genética , Oncogenes/genética , Receptores Acoplados a Proteínas G/genética , Cromograninas/genética , Biología Computacional , Epistasis Genética , Subunidades alfa de la Proteína de Unión al GTP Gs/genética , Frecuencia de los Genes , Redes Reguladoras de Genes/fisiología , Genes Supresores de Tumor , Células HEK293 , Humanos , Modelos Moleculares , Familia de Multigenes/genética , Mutación/fisiología , Neoplasias/mortalidad , Neoplasias/patología , Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/metabolismo , Transducción de Señal/genética , Análisis de Supervivencia , Factores de Transcripción/genéticaRESUMEN
Intervention mapping (IM) is a framework for formulating theory-and evidence-based health education projects with participatory approaches from ecological perspectives.The intervention program designed via IM plays a role in reducing the exposure of cancer risk factors,increasing cancer prevention behaviors,and promoting early cancer screening and rehabilitation of cancer patients.This study summarizes the characteristics,implementation steps,and application status of IM in tertiary prevention of cancer,aiming to provide reference for the application of IM in the health education projects for cancer in China.
Asunto(s)
Humanos , Prevención Terciaria , Neoplasias/prevención & control , China , Factores de RiesgoRESUMEN
Adaptive intervention(AI)is a methodology which dynamically evaluates adaptive variables at decision points and timely adjusts and develops tailored strategies to meet individual needs.The study reviewed the origin and development and elaborated the core elements(including intervention outcomes,intervention options,decision points,tailoring variables,and decision rules)and the classification of AI.Based on the literature,the key points of the design and implementation of AI were prospected,which can provide evidence for the research and development of health behavior intervention.
RESUMEN
Objective In this paper, HPLC-DAD-ELSD technique was used to establish the chromatography fingerprint of Ilex kudingcha. Methods Shimadzu C18 column (250 mm × 4.6 mm, 5 μm) was used. Acetonitrile-water as the mobile phase; The flow speed was 1.0 mL/min. The detection wavelength was 210 nm and the column temperature was 35 ℃. Results The chromatography fingerprint of Ilex kudingcha from 10 different origins was established. In the chromatography fingerprint with HPLC-DAD of Ilex kudingcha, 18 common peaks were damarcated and the similarities of Ilex kudingcha were between 0.911-0.970, and the chromatography fingerprint with HPLC-ELSD of Ilex kudingcha, 11 common peaks were damarcated and the similarities of Ilex kudingcha were between 0.914-0.962. Chlorogenic acid, kaempferol-3-O-β-D-rhamnoside, isorhamnetin-3-O-β- D-rhamnoside, kudinoside C, kudinoside A, kudinoside E, kudinoside D were confired by LC-MS and binding control. Conclusion The method of precision, reproducibility, stability is accurate, which can be used as the evaluation of the quality of Ilex kudingcha.