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Although RNA structures play important roles in regulating gene expression, the mechanism and function of mRNA folding in plant bacterial pathogens remain elusive. Therefore, we perform dimethyl sulfate sequencing (DMS-seq) on the Pseudomonas syringae under nutrition-rich and -deficient conditions, revealing that the mRNA structure changes substantially in the minimal medium (MM) that tunes global translation efficiency (TE), thereby inducing virulence. This process is led by the increased expression of hfq, which is directly activated by transcription regulators RpoS and CysB. The co-occurrence of Hfq and RpoS in diverse bacteria and the deep conservation of Hfq Y25 is critical for RNA-mediated regulation and implicates the wider biological importance of mRNA structure and feedback loops in the control of global gene expression.
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BACKGROUND: In China, CRC incidence is escalating. The main hurdles are heterogeneity and drug resistance. This research delves into cellular senescence in CRC, aiming to devise a prognostic model and pinpoint mechanisms impacting drug resistance. METHODS: Mendelian randomization (MR) analysis confirmed the association between CRC and cellular aging. The Cancer Genome Atlas (TCGA)-CRC data served as the training set, with GSE38832 and GSE39582 as validation sets. Various bioinformatics methods were employed to construct and validate a risk model. CRC cells with NADPH Oxidase 4 (NOX4) knockout were generated using CRISPR-Cas9 technology. Protein blotting and colony formation assays elucidated the role of NOX4 in CRC cell aging and drug resistance. RESULTS: A prognostic model, derived from dataset analysis, uncovered a link between high-risk groups and cancer progression. Notable differences in the tumor microenvironment were observed between risk groups. Finally, NOX4 was found to be linked with aging and drug resistance in CRC. CONCLUSION: This research presents a novel senescence-based CRC prognosis model. It identifies NOX4's role in CRC drug resistance, suggesting it is a potential treatment target.
Assuntos
Senescência Celular , Neoplasias Colorretais , Resistencia a Medicamentos Antineoplásicos , NADPH Oxidase 4 , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genética , NADPH Oxidase 4/metabolismo , NADPH Oxidase 4/genética , Prognóstico , Microambiente Tumoral , Linhagem Celular Tumoral , Masculino , FemininoRESUMO
Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder characterized by aberrant amyloid precursor protein (APP) cleavage, pathological aggregations of beta-amyloid (Aß) that make up Aß plaques and hyperphosphorylation of Tau that makes up neurofibrillary tangles (NFTs). Although progress has been made in research on AD, the fundamental causes of this disease have not been fully elucidated. Recent studies have shown that vascular dysfunction especially the loss of pericytes plays a significant role in the onset of AD. Pericytes play a variety of important roles in the nervous system including the regulation of the cerebral blood flow (CBF), the formation and maintenance of the blood-brain barrier (BBB), angiogenesis, and the clearance of toxic substances from the brain. Pericytes participate in the transport of Aß through various receptors, and Aß acts on pericytes to cause them to constrict, detach, and die. The loss of pericytes elevates the levels of Aß1-40 and Aß1-42 by disrupting the integrity of the BBB and reducing the clearance of soluble Aß from the brain interstitial fluid. The aggravated deposition of Aß further exacerbates pericyte dysfunction, forming a vicious cycle. The combined influence of these factors eventually results in the loss of neurons and cognitive decline. Further exploration of the interactions between pericytes and Aß is beneficial for understanding AD and could lead to the identification of new therapeutic targets for the prevention and treatment of AD. In this review, we explore the characterization of pericytes, interactions between pericytes and other cells in the neurovascular unit (NVU), and the physiological functions of pericytes and dysfunctions in AD. This review discusses the interactions between pericytes and Aß, as well as current and further strategies for preventing or treating AD targeting pericytes.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Barreira Hematoencefálica , Pericitos , Pericitos/metabolismo , Doença de Alzheimer/metabolismo , Humanos , Peptídeos beta-Amiloides/metabolismo , Barreira Hematoencefálica/metabolismo , Animais , Encéfalo/metabolismoRESUMO
Colorectal cancer (CRC) is one of the most common malignant tumors with complex molecular regulatory mechanisms. Alternative splicing (AS), a fundamental regulatory process of gene expression, plays an important role in the occurrence and development of CRC. This study analyzed AS Percent Spliced In (PSI) values from 49 pairs of CRC and normal samples in the TCGA SpliceSeq database. Using Lasso and SVM, AS features that can differentiate colorectal cancer from normal were screened. Univariate COX regression analysis identified prognosis-related AS events. A risk model was constructed and validated using machine learning, Kaplan-Meier analysis, and Decision Curve Analysis. The regulatory effect of protein arginine methyltransferase 5 (PRMT5) on poly(RC) binding protein 1 (PCBP1) was verified by immunoprecipitation experiments, and the effect of PCBP1 on the AS of Obscurin (OBSCN) was verified by PCR. Five AS events, including HNF4A.59461.AP and HNF4A.59462.AP, were identified, which can distinguish CRC from normal tissue. A machine learning model using 21 key AS events accurately predicted CRC prognosis. High-risk patients had significantly shorter survival times. PRMT5 was found to regulate PCBP1 function and then influence OBSCN AS, which may drive CRC progression. The study concluded that some AS events is significantly different in CRC and normal tissues, and some of these AS events are related to the prognosis of CRC. In addition, PRMT family-driven arginine modifications play an important role in CRC-specific AS events.
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Processamento Alternativo , Neoplasias Colorretais , Humanos , Processamento Alternativo/genética , Arginina , Estimativa de Kaplan-Meier , Metiltransferases , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Proteína-Arginina N-Metiltransferases/genéticaRESUMO
Raffinose synthase (Rafs) is an important enzyme in the synthesis pathway of raffinose from sucrose and galactinol in higher plants and is involved in the regulation of seed development and plant responses to abiotic stresses. In this study, we analyzed the Rafs families and profiled their alternative splicing patterns at the genome-wide scale from 10 grass species representing crops and grasses. A total of 73 Rafs genes were identified from grass species such as rice, maize, foxtail millet, and switchgrass. These Rafs genes were assigned to six groups based the phylogenetic analysis. We compared the gene structures, protein domains, and expression patterns of Rafs genes, and also unraveled the alternative transcripts of them. In addition, different conserved sequences were observed at these putative splice sites among grass species. The subcellular localization of PvRafs5 suggested that the Rafs gene was expressed in the cytoplasm or cell membrane. Our findings provide comprehensive knowledge of the Rafs families in terms of genes and proteins, which will facilitate further functional characterization in grass species in response to abiotic stress.
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Processamento Alternativo , Setaria (Planta) , Humanos , Filogenia , Galactosiltransferases/genética , Galactosiltransferases/metabolismo , Estresse Fisiológico/genética , Setaria (Planta)/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
Soil salinity has become one of the major factors that threaten tall fescue growth and turf quality. Plants recruit diverse microorganisms in the rhizosphere to cope with salinity stress. In this study, 15 plant growth-promoting rhizobacteria (PGPR) were isolated from the salt-treated rhizosphere of tall fescue and were annotated to 10 genera, including Agrobacterium, Fictibacillus, Rhizobium, Bhargavaea, Microbacterium, Paenarthrobacter, Pseudarthrobacter, Bacillus, Halomonas, and Paracoccus. All strains could produce indole-3-acetic acid (IAA). Additionally, eight strains exhibited the ability to solubilize phosphate and potassium. Most strains could grow on the medium containing 600 mM NaCl, such as Bacillus zanthoxyli and Bacillus altitudinis. Furthermore, Bacillus zanthoxyli and Bacillus altitudinis were inoculated with tall fescue seeds and seedlings to determine their growth-promoting effect. The results showed that Bacillus altitudinis and mixed culture significantly increased the germination rate of tall fescue seeds. Bacillus zanthoxyli can significantly increase the tillers number and leaf width of seedlings under salt conditions. Through the synergistic effect of FaSOS1, FaHKT1, and FaHAK1 genes, Bacillus zanthoxyli helps to expel the excess Na+ from aboveground parts and absorb more K+ in roots to maintain ion homeostasis in tall fescue. Unexpectedly, we found that Bacillus altitudinis displayed an inapparent growth-promoting effect on seedlings under salt stress. Interestingly, the mixed culture of the two strains was also able to alleviate, to some extent, the effects of salt stress on tall fescue. This study provides a preliminary understanding of tall fescue rhizobacteria and highlights the role of Bacillus zanthoxyli in tall fescue growth and salt tolerance.
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Bacillus , Festuca , Lolium , Rizosfera , Estresse Salino , Desenvolvimento Vegetal , Plântula , Raízes de PlantasRESUMO
Hydrogen sulfide (H2S), as a gaseous messenger molecule, plays critical roles in signal transduction and biological modulation. In the present study, the roles of H2S in regulating chlorophyll (Chl) and carotenoid (Car) contents to improve photosynthesis in tall fescue were investigated under low-light (LL) stress. Compared to control conditions, LL stress significantly reduced total biomass, net photosynthetic rate (Pn), maximal quantum yield of photosystem II (PSII) photochemistry (Fv/Fm), and the contents of Chl and Car. Under exogenous sodium hydrosulfide (NaHS, H2S donor) application, these parameters were enhanced, ultimately increasing photosynthesis. Moreover, exogenous H2S up-regulated the expression of chlorophyll biosynthesis genes while down-regulated chlorophyll degradation genes, resulting in increases in chlorophyll precursors. Components of carotenoids and expression of genes encoding biosynthesis and degradation enzymes varied similarly. Additionally, application exogenous H2S up-regulated expression of FaDES1 and FaDCD. Thus, it enhanced L-cysteine desulfhydrase 1 (DES1, EC 4.4.1.1) and D-cysteine desulfhydrase (DCD, EC 4.4.1.15) activities leading to elevated endogenous H2S. However, these responses were reversed by treatment with hypotaurine (HT, H2S scavenger). These results suggested that H2S is involved in regulating photosynthesis to improve LL tolerance via modulating Chl and Car metabolisms in tall fescue.