RESUMO
Bacterial wilt, caused by Ralstonia solanacearum, one of the most destructive phytopathogens, leads to significant annual crop yield losses. Type III effectors (T3Es) mainly contribute to the virulence of R. solanacearum, usually by targeting immune-related proteins. Here, we clarified the effect of a novel E3 ubiquitin ligase (NEL) T3E, RipAW, from R. solanacearum on pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and further explored its action mechanism. In the susceptible host Arabidopsis thaliana, we monitored the expression of PTI marker genes, flg22-induced ROS burst, and callose deposition in RipAW- and RipAWC177A-transgenic plants. Our results demonstrated that RipAW suppressed host PTI in an NEL-dependent manner. By Split-Luciferase Complementation, Bimolecular Fluorescent Complimentary, and Co-Immunoprecipitation assays, we further showed that RipAW associated with three crucial components of the immune receptor complex, namely FLS2, XLG2, and BIK1. Furthermore, RipAW elevated the ubiquitination levels of FLS2, XLG2, and BIK1, accelerating their degradation via the 26S proteasome pathway. Additionally, co-expression of FLS2, XLG2, or BIK1 with RipAW partially but significantly restored the RipAW-suppressed ROS burst, confirming the involvement of the immune receptor complex in RipAW-regulated PTI. Overall, our results indicate that RipAW impairs host PTI by disrupting the immune receptor complex. Our findings provide new insights into the virulence mechanism of R. solanacearum.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Ralstonia solanacearum , Complexo Antígeno-Anticorpo , Reconhecimento da Imunidade Inata , Espécies Reativas de Oxigênio , Imunoprecipitação , Receptores Imunológicos , Proteínas Serina-Treonina Quinases , Proteínas de Arabidopsis/genéticaRESUMO
RING-finger-type ubiquitin E3 ligase Constitutively Photomorphogenic 1 (COP1) and floral integrators such as FLOWERING LOCUS T (FT), TWIN SISTER OF FT (TSF) and SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 (SOC1) have been identified as regulators of stomatal movement. However, little is known about their roles and relationship in dark-induced stomatal closure. Here, we demonstrated that COP1 is required for dark-induced stomatal closure using cop1 mutant. The cop1 mutant closed stomata in response to exogenous nitric oxide (NO) but not hydrogen peroxide (H2O2), and H2O2 but not NO accumulated in cop1 in darkness, further indicating that COP1 acts downstream of H2O2 and upstream of NO in dark-induced stomatal closure. Expression of FT, TSF and SOC1 in wild-type (WT) plants decreased significantly with dark duration time, but this process was blocked in cop1. Furthermore, ft, tsf, and soc1 mutants accumulated NO and closed stomata faster than WT plants in response to darkness. Altogether, our results indicate that COP1 transduces H2O2 signaling, promotes NO accumulation in guard cells by suppressing FT, TSF and SOC1 expression, and consequently leads to stomatal closure in darkness. These findings add new insights into the mechanisms of dark-induced stomatal closure.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Óxido Nítrico/metabolismo , Estômatos de Plantas/metabolismo , Peróxido de Hidrogênio/farmacologia , Peróxido de Hidrogênio/metabolismo , Regulação da Expressão Gênica de Plantas , Proteína de Ligação a Fosfatidiletanolamina/genéticaRESUMO
Bacterial infection is a common wound complication that can significantly delay healing. Classical local therapies for infected wounds are expensive and are frequently ineffective. One alternative therapy is photodynamic therapy (PDT). We conducted a systematic review to clarify whether PDT is useful for bacteria-infected wounds in animal models. PubMed and Medline were searched for articles on PDT in infected skin wounds in animals. The language was limited to English. Nineteen articles met the inclusion criteria. The overall study methodological quality was moderate, with a low-moderate risk of bias. The animal models were mice and rats. The wounds were excisional, burn, and abrasion wounds. Wound size ranged from 6 mm in diameter to 1.5 × 1.5 cm2 . Most studies inoculated the wounds with Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus. Eleven and 17 studies showed that the PDT of infected wounds significantly decreased wound size and bacterial counts, respectively. Six, four, and two studies examined the effect of PDT on infected wound-cytokine levels, wound-healing time, and body weight, respectively. Most indicated that PDT had beneficial effects on these variables. PDT accelerated bacteria-infected wound healing in animals by promoting wound closure and killing bacteria.
Assuntos
Antibacterianos/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Fotoquimioterapia/métodos , Lesões dos Tecidos Moles/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Infecção dos Ferimentos/tratamento farmacológico , Animais , Modelos Animais de Doenças , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/microbiologia , Infecção dos Ferimentos/microbiologiaRESUMO
Background: Endometriosis (EM) is a prevalent gynecological disorder frequently associated with irregular menstruation and infertility. Programmed cell death (PCD) is pivotal in the pathophysiological mechanisms underlying EM. Despite this, the precise pathogenesis of EM remains poorly understood, leading to diagnostic delays. Consequently, identifying biomarkers associated with PCD is critical for advancing the diagnosis and treatment of EM. Methods: This study used datasets from the Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs) following preprocessing. By cross-referencing these DEGs with genes associated with PCD, differentially expressed PCD-related genes (DPGs) were identified. Enrichment analyses for KEGG and GO pathways were conducted on these DPGs. Additionally, Mendelian randomization and machine learning techniques were applied to identify biomarkers strongly associated with EM. Results: The study identified three pivotal biomarkers: TNFSF12, AP3M1, and PDK2, and established a diagnostic model for EM based on these genes. The results revealed a marked upregulation of TNFSF12 and PDK2 in EM samples, coupled with a significant downregulation of AP3M1. Single-cell analysis further underscored the potential of TNFSF12, AP3M1, and PDK2 as biomarkers for EM. Additionally, molecular docking studies demonstrated that these genes exhibit significant binding affinities with drugs currently utilized in clinical practice. Conclusion: This study systematically elucidated the molecular characteristics of PCD in EM and identified TNFSF12, AP3M1, and PDK2 as key biomarkers. These findings provide new directions for the early diagnosis and personalized treatment of EM.
Assuntos
Biomarcadores , Endometriose , Aprendizado de Máquina , Análise da Randomização Mendeliana , Humanos , Endometriose/genética , Endometriose/diagnóstico , Endometriose/metabolismo , Feminino , Biomarcadores/metabolismo , Apoptose/genética , Perfilação da Expressão Gênica , Simulação de Acoplamento Molecular , Piruvato Desidrogenase Quinase de Transferência de Acetil/genética , Piruvato Desidrogenase Quinase de Transferência de Acetil/metabolismoRESUMO
Background: Emerging evidence suggests the potential relationship between vitamin D deficiency and risk of cognitive impairment or dementia. To what extent the excess risk of dementia conferred by vitamin D deficiency is less clear. Objective: We summarized the current evidence from several aspects and further quantified these associations. Methods: We collected relevant prospective cohort studies by searching PubMed, Embase and Cochrane up to July 2023. The pooled relative risks (RR) were evaluated by random-effects models. Dose-response analyses were conducted by the method of two-stage generalized least squares regression. Results: Of 9,267 identified literatures, 23 were eligible for inclusion in the meta-analyses, among which 9 and 4 literatures were included in the dose-response analyses for the risk of dementia and Alzheimer's disease (AD). Vitamin D deficiency exhibited a 1.42 times risk for dementia (95% confidence interval (CI)â=â1.21-1.65) and a 1.57-fold excess risk for AD (95% CIâ=â1.15-2.14). And vitamin D deficiency was associated with 34% elevated risk with cognitive impairment (95% CIâ=â1.19-1.52). Additionally, vitamin D was non-linearly related to the risk of dementia (pnonlinearityâ=â0.0000) and AD (pnonlinearityâ=â0.0042). The approximate 77.5-100ânmol/L 25-hydroxyvitamin D [25(OH)D] was optimal for reducing dementia risk. And the AD risk seemed to be decreased when the 25(OH)D level >40.1ânmol/L. Conclusions: Vitamin D deficiency was a risk factor for dementia, AD, and cognitive impairment. The nonlinear relationships may further provide the optimum dose of 25(OH)D for dementia prevention.
Assuntos
Disfunção Cognitiva , Demência , Deficiência de Vitamina D , Vitamina D , Humanos , Vitamina D/sangue , Disfunção Cognitiva/sangue , Disfunção Cognitiva/epidemiologia , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia , Demência/epidemiologia , Demência/sangue , Estudos Prospectivos , Fatores de Risco , Doença de Alzheimer/sangue , Doença de Alzheimer/epidemiologiaRESUMO
A new calixpyridinium-based light-responsive host-guest recognition motif was found in this work. This host-guest recognition motif was further discovered to be applied as a selective turn-on fluorescent sensor for lysine over other natural amino acids.