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It is known that the oocyte has a limited capacity to acquire and metabolize glucose, and it must rely on cumulus cells (CCs) to take up glucose and produce pyruvate for use to produce ATP through oxidative phosphorylation. We therefore propose that miRNAs might regulate glucose metabolism (GM) in CCs and might be used as markers for oocyte quality assessment. Here, mouse CC models with impaired glycolysis or pentose phosphate pathway (PPP) were established, and miRNAs targeting the key enzymes in glycolysis/PPP were predicted using the miRNA target prediction databases. Expression of the predicted miRNAs was compared between CCs with normal and impaired glycolysis/PPP to identify candidate miRNAs. Function of the candidate miRNAs was validated by transfecting CCs or cumulus-oocyte-complexes (COCs) with miRNA inhibitors and observing effects on glucose metabolites of CCs and on competence of oocytes. The results validated that miR-23b-3p, let-7b-5p, 34b-5p and 145a-5p inhibited glycolysis, and miR-24-3p, 3078-3p,183-5p and 7001-5p inhibited PPP of CCs. Our observation using a more physiologically relevant model (intact cultured COCs) further validated the four glycolysis-targeting miRNAs we identified. Furthermore, miR-let-7b-5p, 34b-5p and 145a-5p may also inhibit PPP, as they decreased the production of glucose-6-phosphate. In conclusion, miRNAs play critical roles in GM of CCs and may be used as markers for oocyte quality assessment. Summary sentence: We identified and validated eight new miRNAs that inhibit glycolysis and/or pentose phosphate pathways in cumulus cells (CCs) suggesting that miRNAs play critical roles in glucose metabolism of CCs and may be used for oocyte quality markers.
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Células del Cúmulo , Glucosa , Glucólisis , MicroARNs , Animales , Células del Cúmulo/metabolismo , MicroARNs/metabolismo , MicroARNs/genética , Ratones , Glucosa/metabolismo , Femenino , Glucólisis/fisiología , Vía de Pentosa Fosfato , Oocitos/metabolismoRESUMEN
Plants typically activate distinct defense pathways against various pathogens. Heightened resistance to one pathogen often coincides with increased susceptibility to another pathogen. However, the underlying molecular basis of this antagonistic response remains unclear. Here, we demonstrate that mutants defective in the transcription factor ETHYLENE-INSENSITIVE 3-LIKE 2 (OsEIL2) exhibited enhanced resistance to the biotrophic bacterial pathogen Xanthomonas oryzae pv oryzae and to the hemibiotrophic fungal pathogen Magnaporthe oryzae, but enhanced susceptibility to the necrotrophic fungal pathogen Rhizoctonia solani. Furthermore, necrotroph-induced OsEIL2 binds to the promoter of OsWRKY67 with high affinity, leading to the upregulation of salicylic acid (SA)/jasmonic acid (JA) pathway genes and increased SA/JA levels, ultimately resulting in enhanced resistance. However, biotroph- and hemibiotroph-induced OsEIL2 targets OsERF083, resulting in the inhibition of SA/JA pathway genes and decreased SA/JA levels, ultimately leading to reduced resistance. Our findings unveil a previously uncharacterized defense mechanism wherein two distinct transcriptional regulatory modules differentially mediate immunity against pathogens with different lifestyles through the transcriptional reprogramming of phytohormone pathway genes.
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Ciclopentanos , Regulación de la Expresión Génica de las Plantas , Oryza , Oxilipinas , Enfermedades de las Plantas , Inmunidad de la Planta , Proteínas de Plantas , Rhizoctonia , Ácido Salicílico , Xanthomonas , Oxilipinas/metabolismo , Ácido Salicílico/metabolismo , Ciclopentanos/metabolismo , Oryza/microbiología , Oryza/genética , Oryza/inmunología , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/inmunología , Xanthomonas/fisiología , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Rhizoctonia/fisiología , Inmunidad de la Planta/efectos de los fármacos , Mutación/genética , Resistencia a la Enfermedad/genética , Regiones Promotoras Genéticas/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Unión Proteica/efectos de los fármacosRESUMEN
BACKGROUND: The morphology of tumor thrombus varies from person to person and it may affect surgical methods and tumor prognosis. However, studies on the morphology of tumor thrombus are limited. The purpose of our study was to evaluate the impact of tumor thrombus morphology on surgical complexity. METHODS: We retrospectively reviewed the clinical data of 229 patients with renal cell carcinoma combined with inferior vena cava (IVC) tumor thrombus who underwent surgical treatment at Peking University Third Hospital between January 2014 and December 2021. The patients were divided into floating morphology (107 patients) and filled morphology (122 patients) tumor thrombi groups. Chi-square and Mann-Whitney U tests were used for categorical and continuous variables, respectively. Postoperative complications were evaluated using the Clavien-Dindo surgical complication classification method. RESULTS: Patients with filled morphology tumor thrombus required more surgical techniques than those with floating morphology tumor thrombus, which was reflected in more open surgeries (P < 0.001), more IVC interruptions (Pâ<0.001), lesser use of the delayed occlusion of the proximal inferior vena cava (DOPI) technique (P < 0.001), and a greater need for cut-off of the short hepatic vein (P < 0.001) and liver dissociation (P = 0.001). Filled morphology significantly increased the difficulty of surgery in patients with renal cell carcinoma with tumor thrombus, reflected in longer operation time (P < 0.001), more surgical blood loss (Pâ<0.001), more intra-operative blood transfusion (P < 0.001), and longer postoperative hospital stay (P < 0.001). Filled morphology tumor thrombus also led to more postoperative complications (53% vs. 20%; P < 0.001). CONCLUSION: Compared with floating morphology thrombus, filled morphology thrombus significantly increased the difficulty of surgery in patients with renal cell carcinoma with IVC tumor thrombus.
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Carcinoma de Células Renales , Neoplasias Renales , Células Neoplásicas Circulantes , Vena Cava Inferior , Trombosis de la Vena , Humanos , Carcinoma de Células Renales/cirugía , Carcinoma de Células Renales/patología , Neoplasias Renales/cirugía , Neoplasias Renales/patología , Vena Cava Inferior/patología , Vena Cava Inferior/cirugía , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , China/epidemiología , Células Neoplásicas Circulantes/patología , Trombosis de la Vena/patología , Trombosis de la Vena/cirugía , Anciano , Nefrectomía/métodos , Complicaciones Posoperatorias/epidemiología , AdultoRESUMEN
Maize lethal necrosis (MLN) is a viral disease caused by host co-infection by maize chlorotic mottle virus (MCMV) and a potyvirus, such as sugarcane mosaic virus (SCMV). The disease is most effectively managed by growing MLN-resistant varieties. However, the relative importance of MCMV and potyvirus resistance in managing this synergistic disease is poorly characterized. In this study, we evaluated the effects of SCMV and/or MCMV resistance on disease, virus titers, and synergism and explored expression patterns of known potyvirus resistance genes TrxH and ABP1. MLN disease was significantly lower in both the MCMV-resistant and SCMV-resistant inbred lines compared with the susceptible control Oh28. Prior to 14 days postinoculation (dpi), MCMV titers in resistant lines N211 and KS23-6 were more than 100,000-fold lower than found in the susceptible Oh28. However, despite no visible symptoms, titer differences between MCMV-resistant and -susceptible lines were negligible by 14 dpi. In contrast, systemic SCMV titers in the potyvirus-resistant line, Pa405, ranged from 130,000-fold to 2 million-fold lower than susceptible Oh28 as disease progressed. Initial TrxH expression was up to 49,000-fold lower in Oh28 compared with other genotypes, whereas expression of ABP1 was up to 4.5-fold lower. Measures of virus synergy indicate that whereas MCMV resistance is effective in early infection, strong potyvirus resistance is critical for reducing synergist effects of co-infection on MCMV titer. These results emphasize the importance of both potyvirus resistance and MCMV resistance in an effective breeding program for MLN management.
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Coinfección , Potyvirus , Tombusviridae , Enfermedades de las Plantas , NecrosisRESUMEN
PURPOSE: We carried out the study aiming to explore and analyze the risk factors, the distribution of pathogenic bacteria, and their antibiotic-resistance characteristics influencing the occurrence of surgical site infection (SSI), to provide valuable assistance for reducing the incidence of SSI after traumatic fracture surgery. METHODS: A retrospective case-control study enrolling 3978 participants from January 2015 to December 2019 receiving surgical treatment for traumatic fractures was conducted at Tangdu Hospital of Air Force Medical University. Baseline data, demographic characteristics, lifestyles, variables related to surgical treatment, and pathogen culture were harvested and analyzed. Univariate analyses and multivariate logistic regression analyses were used to reveal the independent risk factors of SSI. A bacterial distribution histogram and drug-sensitive heat map were drawn to describe the pathogenic characteristics. RESULTS: Included 3978 patients 138 of them developed SSI with an incidence rate of 3.47% postoperatively. By logistic regression analysis, we found that variables such as gender (males) (odds ratio (OR) = 2.012, 95% confidence interval (CI): 1.235 - 3.278, p = 0.005), diabetes mellitus (OR = 5.848, 95% CI: 3.513 - 9.736, p < 0.001), hypoproteinemia (OR = 3.400, 95% CI: 1.280 - 9.031, p = 0.014), underlying disease (OR = 5.398, 95% CI: 2.343 - 12.438, p < 0.001), hormonotherapy (OR = 11.718, 95% CI: 6.269 - 21.903, p < 0.001), open fracture (OR = 29.377, 95% CI: 9.944 - 86.784, p < 0.001), and intraoperative transfusion (OR = 2.664, 95% CI: 1.572 - 4.515, p < 0.001) were independent risk factors for SSI, while, aged over 59 years (OR = 0.132, 95% CI: 0.059 - 0.296, p < 0.001), prophylactic antibiotics use (OR = 0.082, 95% CI: 0.042 - 0.164, p < 0.001) and vacuum sealing drainage use (OR = 0.036, 95% CI: 0.010 - 0.129, p < 0.001) were protective factors. Pathogens results showed that 301 strains of 38 species of bacteria were harvested, among which 178 (59.1%) strains were Gram-positive bacteria, and 123 (40.9%) strains were Gram-negative bacteria. Staphylococcus aureus (108, 60.7%) and Enterobacter cloacae (38, 30.9%) accounted for the largest proportion. The susceptibility of Gram-positive bacteria to Vancomycin and Linezolid was almost 100%. The susceptibility of Gram-negative bacteria to Imipenem, Amikacin, and Meropenem exceeded 73%. CONCLUSION: Orthopedic surgeons need to develop appropriate surgical plans based on the risk factors and protective factors associated with postoperative SSI to reduce its occurrence. Meanwhile, it is recommended to strengthen blood glucose control in the early stage of admission and for surgeons to be cautious and scientific when choosing antibiotic therapy in clinical practice.
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PURPOSE: To methodically assess the effectiveness of augmentative plating (AP) and exchange nailing (EN) in managing nonunion following intramedullary nailing for long bone fractures of the lower extremity. METHODS: PubMed, EMBASE, Web of Science, and the Cochrane Library were searched to gather clinical studies regarding the use of AP and EN techniques in the treatment of nonunion following intramedullary nailing of lower extremity long bones. The search was conducted up until May 2023. The original studies underwent an independent assessment of their quality, a process conducted utilizing the Newcastle-Ottawa scale. Data were retrieved from these studies, and meta-analysis was executed utilizing Review Manager 5.3. RESULTS: This meta-analysis included 8 studies involving 661 participants, with 305 in the AP group and 356 in the EN group. The results of the meta-analysis demonstrated that the AP group exhibited a higher rate of union (odds ratio: 8.61, 95% confidence intervals (CI): 4.12 - 17.99, p < 0.001), shorter union time (standardized mean difference (SMD): -1.08, 95 % CI: -1.79 - -0.37, p = 0.003), reduced duration of the surgical procedure (SMD: -0.56, 95 % CI: -0.93 - -0.19, p = 0.003), less bleeding (SMD: -1.5, 95 % CI: -2.81 - -0.18), p = 0.03), and a lower incidence of complications (relative risk: -0.17, 95 % CI: -0.27 - -0.06, p = 0.001). In the subgroup analysis, the time for union in the AP group in nonisthmal and isthmal nonunion of lower extremity long bones was shorter compared to the EN group (nonisthmal SMD: -1.94, 95 % CI: -3.28 - -0.61, p < 0.001; isthmal SMD: -1.08, 95 % CI: -1.64 - -0.52, p = 0.002). CONCLUSION: In the treatment of nonunion in diaphyseal fractures of the long bones in the lower extremity, the AP approach is superior to EN, both intraoperatively (with reduced duration of the surgical procedure and diminished blood loss) and postoperatively (with an elevated union rate, shorter union time, and lower incidence of complications). Specifically, in the management of nonunion of lower extremity long bones with non-isthmal and isthmal intramedullary nails, AP demonstrated shorter union time in comparison to EN.
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Cell-penetrating peptides (CPPs) are short (typically 5-30 amino acids), cationic, amphipathic, or hydrophobic peptides that facilitate the cellular uptake of diverse cargo molecules by eukaryotic cells via direct translocation or endocytosis across the plasma membrane. CPPs can deliver a variety of bioactive cargos, including proteins, peptides, nucleic acids, and small molecules into the cell. Once inside, the delivered cargo may function in the cytosol, nucleus, or other subcellular compartments. Numerous CPPs have been used for studies and drug delivery in mammalian systems. Although CPPs have many potential uses in plant research and agriculture, the application of CPPs in plants remains limited. Here we review the structures and mechanisms of CPPs and highlight their potential applications for sustainable agriculture.
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Exercise has shown to have beneficial effects on cognition in older adults. The purpose of this study was to investigate the cortical hemodynamic responses during the word-color Stroop test (WCST) prior and after acute walking and Tai Chi exercise by functional near-infrared spectroscopy (fNIRS). Twenty participants (9 males, mean age 62.8 ± 5.2), first underwent a baseline WCST test, after which they took three WCST tests in a randomized order, (a) after sitting rest (control), (b) after 6 minutes performing Tai Chi Quan, and (c) after a bout of 6 minutes brisk walking. During these four WCST tests cortical hemodynamic changes in the prefrontal area were monitored with fNIRS. Both brisk walking and Tai Chi enhanced hemodynamic activity during the Stroop incongruent tasks, leading to improved cognitive performance (quicker reaction time). Brisk walking induced a greater hemodynamic activity in the right dorsolateral prefrontal cortex (DLPFC) and ventrolateral prefrontal cortex (VLPFC) area, whereas Tai Chi induced a greater bilateral hemodynamic activity in the DLPFC and VLPFC areas. The present study provided empirical evidence of enhanced hemodynamic response in task- specific regions of the brain that can be achieved by a mere six minutes of brisk walking or Tai Chi in older adults.
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Taichi Chuan , Anciano , Humanos , Masculino , Persona de Mediana Edad , Encéfalo/fisiología , Cognición , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/fisiología , Espectroscopía Infrarroja Corta/métodos , Caminata , FemeninoRESUMEN
Information on long-term effects of postovulatory oocyte aging (POA) on offspring is limited. Whether POA affects offspring by causing oxidative stress (OS) and mitochondrial damage is unknown. Here, in vivo-aged (IVA) mouse oocytes were collected 9 h after ovulation, while in vitro-aged (ITA) oocytes were obtained by culturing freshly ovulated oocytes for 9 h in media with low, moderate, or high antioxidant potential. Oocytes were fertilized in vitro and blastocysts transferred to produce F1 offspring. F1 mice were mated with naturally bred mice to generate F2 offspring. Both IVA and the ITA groups in low antioxidant medium showed significantly increased anxiety-like behavior and impaired spatial and fear learning/memory and hippocampal expression of anxiolytic and learning/memory-beneficial genes in both male and female F1 offspring. Furthermore, the aging in both groups increased OS and impaired mitochondrial function in oocytes, blastocysts, and hippocampus of F1 offspring; however, it did not affect the behavior of F2 offspring. It is concluded that POA caused OS and damaged mitochondria in aged oocytes, leading to defects in anxiety-like behavior and learning/memory of F1 offspring. Thus, POA is a crucial factor that causes psychological problems in offspring, and antioxidant measures may be taken to ameliorate the detrimental effects of POA on offspring.
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Conducta Animal , Mitocondrias , Oocitos , Estrés Oxidativo , Animales , Oocitos/metabolismo , Mitocondrias/metabolismo , Femenino , Ratones , Masculino , Ovulación , Ansiedad/metabolismo , Ansiedad/patología , Antioxidantes/metabolismo , Hipocampo/metabolismo , Hipocampo/patología , Blastocisto/metabolismo , Senescencia Celular , MemoriaRESUMEN
F-box protein is a subunit of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex, which plays a critical role in regulating different pathways in plant immunity. In this study, we identified the rice (Oryza sativa) F-box protein OsFBX156, which targets the heat shock protein 70 (OsHSP71.1) to regulate resistance to the rice blast fungus Magnaporthe oryzae. Overexpression of OsFBX156 or knockout of OsHSP71.1 in rice resulted in the elevation of pathogenesis-related (PR) genes and an induction burst of reactive oxygen species (ROS) after flg22 and chitin treatments, thereby enhancing resistance to M. oryzae. Furthermore, OsFBX156 can promote the degradation of OsHSP71.1 through the 26S proteasome pathway. This study sheds lights on a novel mechanism wherein the F-box protein OsFBX156 targets OsHSP71.1 for degradation to promote ROS production and PR gene expression, thereby positively regulating rice innate immunity.
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Resistencia a la Enfermedad , Proteínas F-Box , Oryza , Enfermedades de las Plantas , Proteínas de Plantas , Ubiquitinación , Oryza/microbiología , Oryza/metabolismo , Oryza/genética , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/inmunología , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Resistencia a la Enfermedad/genética , Proteínas F-Box/metabolismo , Proteínas F-Box/genética , Especies Reactivas de Oxígeno/metabolismo , Regulación de la Expresión Génica de las Plantas , Complejo de la Endopetidasa Proteasomal/metabolismo , Proteolisis , Inmunidad de la Planta/genética , Ascomicetos/patogenicidadRESUMEN
Broad-spectrum disease resistance (BSR) is crucial for controlling plant diseases and relies on immune signals that are subject to transcriptional and post-translational regulation. How plants integrate and coordinate these signals remains unclear. We show here that the rice really interesting new gene (RING)-type E3 ubiquitin ligase OsRING113 targets APIP5, a negative regulator of plant immunity and programmed cell death (PCD), for 26S proteasomal degradation. The osring113 mutants in Nipponbare exhibited decreased BSR, while the overexpressing OsRING113 plants showed enhanced BSR against Magnaporthe oryzae (M. oryzae) and Xanthomonas oryzae pv. oryzae (Xoo). Furthermore, APIP5 directly suppressed the transcription of the Bowman-Birk trypsin inhibitor genes OsBBTI5 and AvrPiz-t-interacting protein 4 (APIP4). Overexpression of these two genes, which are partially required for APIP5-mediated PCD and disease resistance, conferred BSR. OsBBTI5 and APIP4 associated with and stabilized the pathogenesis-related protein OsPR1aL, which promotes M. oryzae resistance. Our results identify an immune module with integrated and coordinated hierarchical regulations that confer BSR in plants.
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Resistencia a la Enfermedad , Regulación de la Expresión Génica de las Plantas , Oryza , Enfermedades de las Plantas , Proteínas de Plantas , Inhibidores de Tripsina , Ubiquitina-Proteína Ligasas , Xanthomonas , Oryza/microbiología , Oryza/metabolismo , Oryza/genética , Resistencia a la Enfermedad/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/inmunología , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Xanthomonas/patogenicidad , Inhibidores de Tripsina/metabolismo , Inhibidores de Tripsina/farmacología , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Inmunidad de la Planta , Plantas Modificadas Genéticamente , MagnaportheRESUMEN
Proteins containing a ubiquitin regulatory X (UBX) domain are cofactors of Cell Division Cycle 48 (CDC48) and function in protein quality control. However, whether and how UBX-containing proteins participate in host-microbe interactions remain unclear. Here we show that MoNLE1, an effector from the fungal pathogen Magnaporthe oryzae, is a core virulence factor that suppresses rice immunity by specifically interfering with OsPUX8B.2. The UBX domain of OsPUX8B.2 is required for its binding to OsATG8 and OsCDC48-6 and controls its 26 S proteasome-dependent stability. OsPUX8B.2 and OsCDC48-6 positively regulate plant immunity against blast fungus, while the high-temperature tolerance heat-shock protein OsBHT, a putative cytoplasmic substrate of OsPUX8B.2-OsCDC48-6, negatively regulates defense against blast infection. MoNLE1 promotes the nuclear migration and degradation of OsPUX8B.2 and disturbs its association with OsBHT. Given the high conservation of MoNLE1 among fungal isolates, plants with broad and durable blast resistance might be generated by engineering intracellular proteins resistant to MoNLE1.
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Magnaporthe , Oryza , Interacciones Huésped-Patógeno , Inmunidad de la Planta/genética , Transporte Biológico , Plantas Modificadas Genéticamente/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Oryza/metabolismo , Enfermedades de las Plantas/microbiología , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismoRESUMEN
Although the antagonistic effects of host resistance against biotrophic and necrotrophic pathogens have been documented in various plants, the underlying mechanisms are unknown. Here, we investigated the antagonistic resistance mediated by the transcription factor ETHYLENE-INSENSITIVE3-LIKE 3 (OsEIL3) in rice. The Oseil3 mutant confers enhanced resistance to the necrotroph Rhizoctonia solani but greater susceptibility to the hemibiotroph Magnaporthe oryzae and biotroph Xanthomonas oryzae pv. oryzae. OsEIL3 directly activates OsERF040 transcription while repressing OsWRKY28 transcription. The infection of R. solani and M. oryzae or Xoo influences the extent of binding of OsEIL3 to OsWRKY28 and OsERF040 promoters, resulting in the repression or activation of both salicylic acid (SA)- and jasmonic acid (JA)-dependent pathways and enhanced susceptibility or resistance, respectively. These results demonstrate that the distinct effects of plant immunity to different pathogen types are determined by two transcription factor modules that control transcriptional reprogramming and the SA and JA pathways.
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Ciclopentanos , Regulación de la Expresión Génica de las Plantas , Oryza , Oxilipinas , Enfermedades de las Plantas , Inmunidad de la Planta , Proteínas de Plantas , Ácido Salicílico , Xanthomonas , Ciclopentanos/metabolismo , Oryza/microbiología , Oryza/genética , Oryza/inmunología , Oryza/metabolismo , Oxilipinas/metabolismo , Ácido Salicílico/metabolismo , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/inmunología , Xanthomonas/patogenicidad , Inmunidad de la Planta/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Rhizoctonia , Transducción de Señal , Resistencia a la Enfermedad/genética , Regiones Promotoras Genéticas/genética , Magnaporthe , Transcripción GenéticaRESUMEN
The ubiquitin-proteasome system (UPS) plays crucial roles in cellular processes including plant growth, development, and stress responses. In this study, we report that a pair of E3 ubiquitin ligases, AvrPiz-t-interaction protein 6 (APIP6) and IPA1-interaction protein 1 (IPI1), intricately target early flowering3 (ELF3) paralogous proteins to control rice immunity and flowering. APIP6 forms homo-oligomers or hetero-oligomers with IPI1. Both proteins interact with OsELF3-2, promoting its degradation to positively control resistance against the rice blast fungus (Magnaporthe oryzae). Intriguingly, overexpression of IPI1 in Nipponbare caused significantly late-flowering phenotypes similar to the oself3-1 mutant. Except for late flowering, oself3-1 enhances resistance against M. oryzae. IPI1 also interacts with and promotes the degradation of OsELF3-1, a paralog of OsELF3-2. Notably, IPI1 and APIP6 synergistically modulate OsELF3s degradation, finely tuning blast disease resistance by targeting OsELF3-2, while IPI1 controls both disease resistance and flowering by targeting OsELF3-1. This study unravels multiple functions for a pair of E3 ligases in rice.
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Adenosine deaminases acting on RNA 1(ADAR1), an RNA editing enzyme that converts adenosine to inosine by deamination in double-stranded RNAs, plays an important role in occurrence and progression of various types of cancer. Ferroptosis has emerged as a hot topic of cancer research in recent years. We have previously reported that ADAR1 promotes breast cancer progression by regulating miR-335-5p and METTL3. However, whether ADAR1 has effects on ferroptosis in breast cancer cells is largely unknown. In this study, we knocked down ADAR1 using CRISPR-Cas9 technology or over-expressed ADAR1 protein using plasmid expressing ADAR1 in MCF-7 and MDA-MB-231 breast cancer cell lines, then detected cell viability, and levels of ROS, MDA, GSH, Fe2+, GPX4 protein and miR-335-5p. We showed that the cell proliferation was inhibited, levels of ROS, MDA, Fe2+, and miR-335-5p were increased, while GSH and GPX4 levels were decreased after loss of ADAR1, compared to the control group. The opposite effects were observed after ADAR1 overexpression in the cells. Further, we demonstrated that ADAR1-controlled miR-335-5p targeted Sp1 transcription factor of GPX4, a known ferroptosis molecular marker, leading to inhibition of ferroptosis by ADAR1 in breast cancer cells. Moreover, RNA editing activity of ADAR1 is not essential for inducing ferroptosis. Collectively, loss of ADAR1 induces ferroptosis in breast cancer cells by regulating miR-335-5p/Sp1/GPX4 pathway. The findings may provide insights into the mechanism by which ADAR1 promotes breast cancer progression via inhibiting ferroptosis.