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In the ongoing arms race between rice and Magnaporthe oryzae, the pathogen employs effectors to evade the immune response, while the host develops resistance genes to recognise these effectors and confer resistance. In this study, we identified a novel Pik allele, Pik-W25, from wild rice WR25 through bulked-segregant analysis, creating the Pik-W25 NIL (Near-isogenic Lines) named G9. Pik-W25 conferred resistance to isolates expressing AvrPik-C/D/E alleles. CRISPR-Cas9 editing was used to generate transgenic lines with a loss of function in Pik-W25-1 and Pik-W25-2, resulting in loss of resistance in G9 to isolates expressing the three alleles, confirming that Pik-W25-induced immunity required both Pik-W25-1 and Pik-W25-2. Yeast two-hybrid (Y2H) and split luciferase complementation assays showed interactions between Pik-W25-1 and the three alleles, while Pik-W25-2 could not interact with AvrPik-C, -D, and -E alleles with Y2H assay, indicating Pik-W25-1 acts as an adaptor and Pik-W25-2 transduces the signal to trigger resistance. The Pik-W25 NIL exhibited enhanced field resistance to leaf and panicle blast without significant changes in morphology or development compared to the parent variety CO39, suggesting its potential for resistance breeding. These findings advance our knowledge of rice blast resistance mechanisms and offer valuable resources for effective and sustainable control strategies.
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BACKGROUND: We have innovatively developed a modified bikini direct anterior approach total hip arthroplasty (THA), endoscopy assisted minimal invasive direct anterior approach (Endo-DAA). The study compared aesthetic appearance of the scar, postoperative radiographic and functional outcomes, and complications of Endo-DAA with Bikini-DAA. METHODS: Patients who underwent primary THA using Endo-DAA or Bikini-DAA were included. The main innovation of Endo-DAA is the use of minimally invasive 5-7 cm proximal transverse incision and distal puncture with an endoscopy assisted split-type tool to complete the acetabular preparation and prosthesis implantation. Outcomes evaluated included evaluation of scar satisfaction, hip reconstruction including inclination, anteversion and leg-length discrepancy (LLD) and patient-reported outcomes including Harris Hip Scores (HHS) and Forgotten Joint Score (FJS). Follow-up time points included preoperative, 6 weeks, 6 months and 12 months. RESULTS: Finally, 195 hips in Endo-DAA and 207 hips in Bikini DAA completed the follow-up. The Endo-DAA group was superior to the Bikini-DAA group in the cosmetic aspects of scars. the cup anteversion angle of Endo-DAA group was significantly better than that in the Bikini-DAA group. The early HHS and FJS of the Endo-DAA group were superior to those of the Bikini-group. Operation time, blood loss, incision length, length of stay and duration to start no-assistive-device walking were also significantly better in the Endo-DAA group. Furthermore, the Bikini-DAA group had a higher incidence of complication. CONCLUSION: Compared with Bikini-incision, Endo-DAA improves patients' subjective satisfaction with scar aesthetics, accelerates rapid recovery of postoperative function, and reduces postoperative complications.
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Rice blast, caused by Pyricularia oryzae, is one of the most destructive rice diseases worldwide. Using resistant rice varieties is the most cost-effective way to control rice blast. Consequently, it is critical to monitor the distribution frequency of avirulence (Avr) genes in rice planting fields to facilitate the breeding of resistant rice varieties. In this study, we established a rapid recombinase polymerase amplification-lateral flow dipstick (RPA-LFD) detection system for the identification of AvrPik, Avr-Piz-t, and Avr-Pi9. The optimized reaction temperature and duration were 37°C and 20 min, indicating that the reaction system could be initiated by body temperature without relying on any precision instruments. Specificity analysis showed that the primer and probe combinations targeting the three Avr genes exhibited a remarkable specificity at genus-level detection. Under the optimized condition, the lower detected thresholds of AvrPik, Avr-Piz-t, and Avr-Pi9 were 10 fg/µl, 100 fg/µl, and 10 pg/µl, respectively. Notably, the detection sensitivity of the three Avr genes was much higher than that of PCR. In addition, we also successfully detected the presence of AvrPik, Avr-Piz-t, and Avr-Pi9 in the leaf and panicle blast lesions with the RPA-LFD detection system. In particular, the genomic DNA was extracted using the simpler PEG-NaOH rapid extraction method. In summary, we developed an RPA detection system for AvrPik, Avr-Pi9, and Avr-Piz-t, combined with the PEG-NaOH rapid DNA extraction method. The innovative approach achieved rapid, real-time, and accurate detection of the three Avr genes in the field, which is helpful to understand the distribution frequency of the three Avr genes in the field and provide theoretical reference for the scientific layout of resistant rice varieties.
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Ascomicetos , Oryza , Doenças das Plantas , Doenças das Plantas/microbiologia , Oryza/microbiologia , Ascomicetos/genética , Ascomicetos/patogenicidade , Técnicas de Amplificação de Ácido Nucleico/métodos , Virulência/genética , Genes Fúngicos/genéticaRESUMO
Surfactin is a cyclic hexalipopeptide compound, nonribosomal synthesized by representatives of the Bacillus subtilis species complex which includes B. subtilis group and its closely related species, such as B. subtilis subsp subtilis, B. subtilis subsp spizizenii, B. subtilis subsp inaquosorum, B. atrophaeus, B. amyloliquefaciens, B. velezensis (Steinke mSystems 6: e00057, 2021) It functions as a biosurfactant and signaling molecule and has antibacterial, antiviral, antitumor, and plant disease resistance properties. The Bacillus lipopeptides play an important role in agriculture, oil recovery, cosmetics, food processing and pharmaceuticals, but the natural yield of surfactin synthesized by Bacillus is low. This paper reviews the regulatory pathways and mechanisms that affect surfactin synthesis and release, highlighting the regulatory genes involved in the transcription of the srfAA-AD operon. The several ways to enhance surfactin production, such as governing expression of the genes involved in synthesis and regulation of surfactin synthesis and transport, removal of competitive pathways, optimization of media, and fermentation conditions were commented. This review will provide a theoretical platform for the systematic genetic modification of high-yielding strains of surfactin.
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Bacillus , Bacillus/genética , Bacillus/metabolismo , Bacillus subtilis/genética , Bacillus subtilis/metabolismo , Óperon , Fermentação , Lipopeptídeos , Peptídeos CíclicosRESUMO
Ras GTPase-activating proteins (Ras GAPs) act as negative regulators for Ras proteins and are involved in various signalling processes that influence cellular functions. Here, the function of four Ras GAPs, UvGap1 to UvGap4, was identified and analysed in Ustilaginoidea virens, the causal agent of rice false smut disease. Disruption of UvGAP1 or UvGAP2 resulted in reduced mycelial growth and an increased percentage of larger or dumbbell-shaped conidia. Notably, the mutant ΔUvgap1 completely lost its pathogenicity. Compared to the wild-type strain, the mutants ΔUvgap1, ΔUvgap2 and ΔUvgap3 exhibited reduced tolerance to H2 O2 oxidative stress. In particular, the ΔUvgap1 mutant was barely able to grow on the H2 O2 plate, and UvGAP1 was found to influence the expression level of genes involved in reactive oxygen species synthesis and scavenging. The intracellular cAMP level in the ΔUvgap1 mutant was elevated, as UvGap1 plays an important role in maintaining the intracellular cAMP level by affecting the expression of phosphodiesterases, which are linked to cAMP degradation in U. virens. In a yeast two-hybrid assay, UvRas1 and UvRasGef (Ras guanyl nucleotide exchange factor) physically interacted with UvGap1. UvRas2 was identified as an interacting partner of UvGap1 through a bimolecular fluorescence complementation assay and affinity capture-mass spectrometry analysis. Taken together, these findings suggest that the UvGAP1-mediated Ras pathway is essential for the development and pathogenicity of U. virens.
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Hypocreales , Oryza , Proteínas Ativadoras de GTPase/genética , Oryza/microbiologia , Proteínas Ativadoras de ras GTPase , Doenças das Plantas/microbiologiaRESUMO
The plant-growth-promoting rhizobacteria (PGPR) B. subtilis PTS-394 has been utilized as a biocontrol agent (in a wettable powder form) due to its excellent ability to suppress tomato soil-borne diseases caused by Fusarium oxysporum and Ralstonia solanacearum. In this study, we evaluated the biocontrol efficiency of Bacillus subtilis PTS-394 wettable powder on pepper root rot in pot experiments and field trials. B. subtilis PTS-394 and its lipopeptide crude extract possessed excellent inhibition activity against Fusarium solani, causing pepper root rot; in an antifungal activity test B. subtilis PTS-394 wettable powder exhibited a good ability to promote pepper seed germination and plant height. The experiments in pots and the field indicated that B. subtilis PTS-394 wettable powder had an excellent control effect at 100-fold dilution, and its biocontrol efficacy reached 69.63% and 74.43%, respectively. In this study, the biocontrol properties of B. subtilis PTS-394 wettable powder on pepper root rot were evaluated and its application method was established. It was concluded that B. subtilis PTS-394 wettable powder is a potential biocontrol agent with an excellent efficiency against pepper root rot.
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Members of the N-rich proteins (NRPs) gene family play important roles in the plant endoplasmic reticulum stress in response, which can be triggered by plant pathogens' infection. Previous studies of the NRP gene family have been limited to only a few plants, such as soybean and Arabidopsis thaliana. Thus, their evolutionary characteristics in the Oryza species and biological functions in rice defense against the pathogenic fungus Magnaporthe oryzae have remained unexplored. In the present study, we demonstrated that the NRP genes family may have originated in the early stages of plant evolution, and that they have been strongly conserved during the evolution of the Oryza species. Domain organization of NRPs was found to be highly conserved within but not between subgroups. OsNRP1, an NRP gene in the Oryza sativa japonica group, was specifically up-regulated during the early stages of rice-M. oryzae interactions-inhibited M. oryzae infection. Predicted protein-protein interaction networks and transcription-factor binding sites revealed a candidate interactor, bZIP50, which may be involved in OsNRP1-mediated rice resistance against M. oryzae infection. Taken together, our results established a basis for future studies of the NRP gene family and provided molecular insights into rice immune responses to M. oryzae.
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Arabidopsis , Magnaporthe , Oryza , Arabidopsis/microbiologia , Resistência à Doença/genética , Magnaporthe/fisiologia , Oryza/metabolismo , Doenças das Plantas/microbiologia , Mapas de Interação de ProteínasRESUMO
OBJECTIVES: The newly released eighth edition of the American Joint Committee on Cancer TNM staging system for lung cancer seeks to improve prognostic accuracy but lacks external validation for small cell lung cancer (SCLC). Moreover, previous studies posed a few questions concerning survival differences for patients with specific site N3 node involvement or single-site metastasis (SSM) in different distant organs. The aim of this study was to validate the eighth edition of the TNM classification for SCLC in an independent multi-institutional cohort from China and answer the questions raised by the previous research. METHODS: Patients with SCLC from four Chinese cancer centers between 2009 and 2019 were reclassified according to the seventh and eighth edition of the TNM classification. Survival was estimated using the Kaplan-Meier method. Comparisons between adjacent categories and stage groups were performed using Cox proportional hazard regression. R2 statistics were calculated to evaluate the discriminating performance of editions. RESULTS: Of 3384 enrolled cases, 3358 had clinical stage, 537 had pathological stage, and 511 had both. Progressive deterioration of survival was observed with advancing of TNM categories and stages both in the seventh and the eighth edition. The eighth edition stages had a higher R2 statistic than the seventh edition (0.207 versus 0.197). Newly defined categories M1b and M1c and stages IIIC, IVA and IVB in the eighth edition discriminated groups with significantly different prognosis. Patients with N3 contralateral supraclavicular nodes had a significantly worse prognosis than those without (p = 0.032). For patients with single-site metastasis, liver involvement showed a worse prognosis compared to brain involvement (p = 0.030). CONCLUSIONS: Our study provided an external validation of the eighth edition of the TNM classification for lung cancer in Chinese patients with SCLC, and confirmed its improved prognostic accuracy compared with the seventh edition. Patients with N3 and M1b might represent heterogeneous populations that warrant further research.
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Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Estudos de Coortes , Humanos , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/patologiaRESUMO
To address the shortcomings of the whale optimization algorithm (WOA) in terms of insufficient global search ability and slow convergence speed, a differential evolution chaotic whale optimization algorithm (DECWOA) is proposed in this paper. Firstly, the initial population is generated by introducing the Sine chaos theory at the beginning of the algorithm to increase the population diversity. Secondly, new adaptive inertia weights are introduced into the individual whale position update formula to lay the foundation for the global search and improve the optimization performance of the algorithm. Finally, the differential variance algorithm is fused to improve the global search speed and accuracy of the whale optimization algorithm. The impact of various improvement strategies on the performance of the algorithm is analyzed using different kinds of test functions that are randomly selected. The particle swarm optimization algorithm (PSO), butterfly optimization algorithm (BOA), WOA, chaotic feedback adaptive whale optimization algorithm (CFAWOA), and DECWOA algorithm are compared for the optimal search performance. Experimental simulations are performed using MATLAB software, and the results show that the improved whale optimization algorithm has a better global optimization-seeking capability. The improved whale optimization algorithm is applied to the distribution network fault location of IEEE-33 nodes, and the effectiveness and accuracy of the distribution network fault zone location based on the multistrategy improved whale optimization algorithm is verified.
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Algoritmos , Software , Coleta de DadosRESUMO
Magnaporthe oryzae causes rice blast disease and is responsible for major losses in rice production worldwide. Although numerous studies have focused on the interactions between Oryza sativa and M. oryzae, to date, the conserved mechanisms remain in part unclear. In this study, a comparative analysis of transcriptomes of O. sativa L. ssp. japonica cv. 'Nipponbare' interacting with three M. oryzae strains (248, 235, and 163) were performed to explore the conserved molecular mechanisms. Differentially expressed genes with similar expression patterns in the interactions between cultivar 'Nipponbare' and three M. oryzae strains were defined as Conserved Differentially Expressed Genes (CDEGs). These included 3,647 O. sativa CDEGs and 3,655 M. oryzae CDEGs. Four rice CDEGs (LOC_Os03g19270, LOC_Os07g36600, LOC_Os05g28740, and LOC_Os01g32780) encoding universal stress protein (USP) were induced within 24 h post-inoculation (hpi) by three M. oryzae strains. Meanwhile, overexpression of LOC_Os07g36600 resulted in enhanced rice resistance against M. oryzae. Furthermore, four rice genes coding light-harvesting chlorophyll a/b-binding (LHC) protein (LOC_Os02g52650, LOC_Os09g12540, LOC_Os11g13850, LOC_Os05g22730) were also identified as CDEGs and were induced at 48 hpi, which might contribute to blast resistance through reactive oxygen species (ROS) accumulation. MoCDIP4 is M. oryzae effector inducing rice cell death and were verified that include AA9 CAZy domain (namely GH61 domain). In this study, we found seven MoCDIP4-homologous genes coding proteins with signal peptides and AA9 CAZy domains, which were continuously up-regulated across all infection stages relative to uninoculated control. This study uncovered that genes are required for conserved mechanisms of rice-M. oryzae interaction, which includes rice genes encoding USP proteins and LHC proteins, as well as M. oryzae genes encoding AA9 proteins. This study will help us to understand how O. sativa responds to M. oryzae infections and the molecular mechanisms of M. oryzae pathogenicity.
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Autophagy is a conserved mechanism for nutrient and cytoplasmic components recycling in eukaryotic cell, in which E1-like enzyme Atg7 activates ubiquitin-like conjugation in the autophagy pathway. In plant pathogenic fungi Ustilaginoidea virens, UvAtg7, an ortholog of AAtg7 in baker's yeast was identified and functionally investigated. UvAtg7 was confirmed to be essential for autophagy, because the disruption of UvATG7 gene in U. virens completely blocked the fusion of autophagosome-like into vacuoles and catalytic degradation of GFP-UvAtg8 under N-starving condition. The fluorescent signal indicated UvAtg7 protein was dispersed in cytoplasma, but spatially coordinated with core autophagy protein UvAtg8 on occasion. Interestingly, disruption of UvATG7 in U. virens caused slightly reduction in mycelial growth, but resulted in a considerable decrease in virulence, conidia production in YT broth and chlamydospore formation on rice false smut balls. Moreover, the UvATG7 deletion mutants exhibited increased sensitivity to cell wall integrity stress caused by congo red and calcofluor white, meanwhile the UvATG7 deletion mutants showed decreased sensitivity to osmotic stress, cell membrane stress and reactiveoxygen stress caused by sorbitol, sodium dodecyl sulfate and H2O2, respectively. All of these defects in UvATG7 deletion mutants could be partially or completely restored by gene complementation. In general, our study indicates that UvAtg7 is essential in autophagy pathway and contributes to mycelial growth, virulence, asexual reproduction and cell stress response in U. virens.
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Hypocreales , Oryza , Ustilaginales , Proteínas Relacionadas à Autofagia/metabolismo , Peróxido de Hidrogênio/metabolismo , Hypocreales/metabolismo , Oryza/microbiologia , Doenças das Plantas/microbiologia , Reprodução Assexuada , VirulênciaRESUMO
Rice false smut (RFS), caused by Villosiclava virens, is an important fungal disease in panicles of rice. V. virens is a heterothallic ascomycete controlled by two opposite idiomorphs, MAT1-1 and MAT1-2. Previous study showed that sexual reproduction of V. virens plays an important role in the epidemic of RFS. In this study, we developed a loop-mediated isothermal amplification (LAMP) assay to detect the mating type of V. virens easily and rapidly by using specific primers based on the mating type genes MAT1-1-2 and MAT1-2-1, respectively. The LAMP assay used only a water/dry bath and could recognize the mating type of V. virens in just 45 min. The LAMP assay was so sensitive that it could detect small amounts of V. virens genomic DNA (as low as 2.0 pg of MAT1-1 and 200.0 pg of MAT1-2) and was 10 times more sensitive than PCR. In addition, we demonstrated the application of mating type via LAMP assay by assessing the genomic DNA of V. virens isolated from rice fields. The high efficiency and specificity of this LAMP assay suggest that it can be used as a rapid testing tool in mating type recognition of V. virens isolates in the field.
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Hypocreales , Oryza , Ustilaginales , Hypocreales/genética , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , Oryza/microbiologia , ReproduçãoRESUMO
Aneurysmal subarachnoid hemorrhage (aSAH) is a common disease causing vascular dementia. Survivors often suffer from cognitive impairment especially working memory deficit. Currently, lack of theoretical support limits the improvement of cognitive intervention or rehabilitation. It is unclear how the large-scale network differs and to what extent is the brain network affected? Our study aims to provide novel information about the topological characteristics of brain organization, especially "small-world" property. A total of 62 aSAH patients are enrolled in this study. They are divided into two groups according to the syndrome of working memory deficit. Their working memory function is evaluated by TMT-B and AVLT (Chinese version). Functional MRI scan is also performed for detecting resting-state cortical plasticity. We utilized ICA to extract functional sub-networks including working memory network from imaging data. And then we establish binarized network and calculate the small-worldness property as well as local and global efficiency of networks. aSAH group with working memory deficit shows no significant difference of clustering coefficient with control group. Our study discovered significant decrease of characteristic path length indicating an increase of overall routing efficiency. We reason that patients with working memory deficit have to recruit more neuronal resources and thus develops higher overall routing efficiency of local network. This study provides novel information about the neural alterations of aSAH patients with working memory deficit. It might contribute to the understanding of neural mechanism and the improvement of current intervention for vascular dementia.
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Ustilaginoidea virens, the causal agent of rice false smut disease, is an important plant pathogen that causes severe quantitative and qualitative losses in rice worldwide. UvSUN1 is the only member of Group-I SUN family proteins in U. virens. In this work, the role of UvSUN1 in different aspects of the U. virens biology was studied by phenotypic analysis of Uvsun1 knockout strains. We identified that UvSUN1 was expressed during both conidial germination and the infection of rice. Disruption of the Uvsun1 gene affected the hyphal growth, conidiation, morphology of hyphae and conidia, adhesion and virulence. We also found that UvSUN1 is involved in the production of toxic compounds, which are able to inhibit elongation of the germinated seeds. Moreover, RNA-seq data showed that knockout of Uvsun1 resulted in misregulation of a subset of genes involved in signal recognition and transduction system, glycometabolism, cell wall integrity, and secondary metabolism. Collectively, this study reveals that Uvsun1 is required for growth, cell wall integrity and pathogenicity of U. virens, thereby providing new insights into the function of SUN family proteins in the growth and pathogenesis of this pathogen.
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Pyricularia oryzae is a multi-host pathogen causing cereal disease, including the devastating rice blast. Panicle blast is a serious stage, leading to severe yield loss. Thirty-one isolates (average 4.1%) were collected from the rice panicle lesions at nine locations covering Jiangsu province from 2010 to 2017. These isolates were characterized as Pyricularia sp. jiangsuensis distinct from known Pyricularia species. The representative strain 18-2 can infect rice panicle, root and five kinds of grasses. Intriguingly, strain 18-2 can co-infect rice leaf with P. oryzae Guy11. The whole genome of P. sp. jiangsuensis 18-2 was sequenced. Nine effectors were distributed in translocation or inversion region, which may link to the rapid evolution of effectors. Twenty-one homologues of known blast-effectors were identified in strain 18-2, seven effectors including the homologues of SLP1, BAS2, BAS113, CDIP2/3, MoHEG16 and Avr-Pi54, were upregulated in the sample of inoculated panicle with strain 18-2 at 24 hpi compared with inoculation at 8 hpi. Our results provide evidences that P. sp. jiangsuensis represents an addition to the mycobiota of blast disease. This study advances our understanding of the pathogenicity of P. sp. jiangsuensis to hosts, which sheds new light on the adaptability in the co-evolution of pathogen and host.
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Magnaporthe , Oryza , Grão Comestível , Magnaporthe/genética , Doenças das Plantas , Poaceae , VirulênciaRESUMO
Hepatic injury induced by ischemia and reperfusion (HIRI) is a major clinical problem after liver resection or transplantation. The polarization of macrophages plays an important role in regulating the severity of hepatic ischemia/reperfusion injury. Recent evidence had indicated that the ischemia induces an acidic microenvironment by causing increased anaerobic glycolysis and accumulation of lactic acid. We hypothesize that the acidic microenvironment might cause the imbalance of intrahepatic immunity which aggravated HIRI. The hepatic ischemia/reperfusion injury model was established to investigate the effect of the acidic microenvironment to liver injury. Liposomes were used to deplete macrophages in vivo. Macrophages were cultured under low pH conditions to analyze the polarization of macrophages in vitro. Activation of the PPAR-γ signal was determined by Western blot. PPAR-γ agonist GW1929 was administrated to functionally test the role of PPAR-γ in regulating macrophage-mediated effects in the acidic microenvironment during HIRI. We demonstrate that acidic microenvironment aggravated HIRI while NaHCO3 reduced liver injury through neutralizing the acid, besides, liposome abolished the protective ability of NaHCO3 through depleting the macrophages. In vivo and vitro experiment showed that acidic microenvironment markedly promoted M1 polarization but inhibited M2 polarization of macrophage. Furthermore, the mechanistic study proved that the PPAR-γ signal was suppressed during the polarization of macrophages under pH = 6.5 culture media. The addition of PPAR-γ agonist GW1929 inhibited M1 polarization under acidic environment and reduced HIRI. Our results indicate that acidic microenvironment is a key regulator in HIRI which promoted M1 polarization of macrophages through regulating PPAR-γ. Conversely, PPAR-γ activation reduced liver injury, which provides a novel therapeutic concept to prevent HIRI.
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Fígado/lesões , Fígado/metabolismo , Macrófagos/metabolismo , PPAR gama/metabolismo , Traumatismo por Reperfusão/metabolismo , Animais , Benzofenonas/administração & dosagem , Células Cultivadas , Microambiente Celular/efeitos dos fármacos , Microambiente Celular/fisiologia , Modelos Animais de Doenças , Concentração de Íons de Hidrogênio , Imunidade Inata/efeitos dos fármacos , Células de Kupffer/efeitos dos fármacos , Células de Kupffer/imunologia , Células de Kupffer/metabolismo , Fígado/patologia , Macrófagos/classificação , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , PPAR gama/agonistas , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia , Índice de Gravidade de Doença , Transdução de Sinais , Bicarbonato de Sódio/farmacologia , Tirosina/administração & dosagem , Tirosina/análogos & derivadosRESUMO
Many pathogens infect hosts through specific organs, such as Ustilaginoidea virens, which infects rice panicles. Here, we show that a microbe-associated molecular pattern (MAMP), Ser-Thr-rich Glycosyl-phosphatidyl-inositol-anchored protein (SGP1) from U. virens, induces immune responses in rice leaves but not panicles. SGP1 is widely distributed among fungi and acts as a proteinaceous, thermostable elicitor of BAK1-dependent defense responses in N. benthamiana. Plants specifically recognize a 22 amino acid peptide (SGP1 N terminus peptide 22, SNP22) in its N-terminus that induces cell death, oxidative burst, and defense-related gene expression. Exposure to SNP22 enhances rice immunity signaling and resistance to infection by multiple fungal and bacterial pathogens. Interestingly, while SGP1 can activate immune responses in leaves, SGP1 is required for U. virens infection of rice panicles in vivo, showing it contributes to the virulence of a panicle adapted pathogen.
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Proteínas Fúngicas/imunologia , Hypocreales/patogenicidade , Oryza/imunologia , Doenças das Plantas/imunologia , Folhas de Planta/imunologia , Proteínas de Plantas/imunologia , Sequência de Aminoácidos , Morte Celular/genética , Morte Celular/imunologia , Proteínas Fúngicas/genética , Regulação da Expressão Gênica , Glicosilfosfatidilinositóis/química , Glicosilfosfatidilinositóis/metabolismo , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Hypocreales/genética , Hypocreales/crescimento & desenvolvimento , Hypocreales/imunologia , Inflorescência/genética , Inflorescência/imunologia , Inflorescência/microbiologia , Oryza/genética , Oryza/microbiologia , Moléculas com Motivos Associados a Patógenos/imunologia , Moléculas com Motivos Associados a Patógenos/metabolismo , Peptídeos/genética , Peptídeos/imunologia , Células Vegetais/imunologia , Células Vegetais/patologia , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Imunidade Vegetal/genética , Folhas de Planta/genética , Folhas de Planta/microbiologia , Proteínas de Plantas/genética , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Transdução de Sinais , VirulênciaRESUMO
Transcriptional deregulation initiated by oncogenic fusion proteins plays a vital role in leukemia. The prevailing view is that the oncogenic fusion protein promyelocytic leukemia/retinoic acid receptor-α (PML/RARα), generated by the chromosome translocation t(15;17), functions as a transcriptional repressor in acute promyelocytic leukemia (APL). Here, we provide rich evidence of how PML/RARα drives oncogenesis through both repressive and activating functions, particularly the importance of the newly identified activation role for the leukemogenesis of APL. The activating function of PML/RARα is achieved by recruiting both abundant P300 and HDAC1 and by the formation of super-enhancers. All-trans retinoic acid and arsenic trioxide, 2 widely used drugs in APL therapy, exert synergistic effects on controlling super-enhancer-associated PML/RARα-regulated targets in APL cells. We use a series of in vitro and in vivo experiments to demonstrate that PML/RARα-activated target gene GFI1 is necessary for the maintenance of APL cells and that PML/RARα, likely oligomerized, transactivates GFI1 through chromatin conformation at the super-enhancer region. Finally, we profile GFI1 targets and reveal the interplay between GFI1 and PML/RARα on chromatin in coregulating target genes. Our study provides genomic insight into the dual role of fusion transcription factors in transcriptional deregulation to drive leukemia development, highlighting the importance of globally dissecting regulatory circuits.
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Regulação Leucêmica da Expressão Gênica , Leucemia Promielocítica Aguda/genética , Proteínas de Fusão Oncogênica/genética , Proteína da Leucemia Promielocítica/genética , Receptor alfa de Ácido Retinoico/genética , Animais , Linhagem Celular Tumoral , Humanos , Camundongos Endogâmicos NOD , Camundongos SCID , Ativação Transcricional , Células Tumorais CultivadasRESUMO
Non-muscle myosin heavy chain 9 (MYH9) is one novel low frequency mutated gene identified in esophageal squamous cell carcinoma (ESCC) using next-generation sequencing. However, its clinical relevance, potential function and mechanisms remain elusive. Methods: Genomic sequencing datas from 104 esophageal squamous cell carcinoma (ESCC) cases were screened a series of low frequency mutant genes. MYH9 was selected to further analyze its clinical significance, function and PCR-array was performed to explore its potential mechanism. Results: MHY9 is a low frequency mutant gene with a mutation frequency of 2.88% in ESCC. Immunohistochemical analysis showed that MYH9 expression was significantly higher in ESCC tumor tissues, and the expression levels were associated with lymph node metastasis of ESCC patients. Moreover, we found that MYH9 knock-down led to inhibition of cell migration and invasion. PCR-array showed MYH9 knockdown led to a significant change of genes expression associated with angiogenesis and epithelial-to-mesenchymal transition (EMT). This observation is further confirmed in TCGA database of LUSC (lung squamous cell carcinoma), CESC (cervical squamous cell carcinomas) and HNSC (head and neck squamous cell carcinoma). Conclusions: Collectively, our study identifies a novel role and mechanism of MYH9, highlights a significance of MYH9 as a metastatic biomarker, and offers potential therapeutic targets for ESCC patients harboring MYH9 mutations.
Assuntos
Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Cadeias Pesadas de Miosina/genética , Neovascularização Patológica/genética , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Transição Epitelial-Mesenquimal/fisiologia , Neoplasias Esofágicas/irrigação sanguínea , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/irrigação sanguínea , Carcinoma de Células Escamosas do Esôfago/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Mutação , Cadeias Pesadas de Miosina/metabolismo , Neovascularização Patológica/patologia , PrognósticoRESUMO
Villosiclava virens is the prevalent causative pathogen of rice false smut, a destructive rice disease. Mating-type genes play a vital role in the evolution of mating systems in fungi. Some fungi have lost MAT1-1-3, one of the mating-type genes, during evolution, whereas others still retain MAT1-1-3. However, how MAT1-1-3 regulates the sexual development of heterothallic V. virens remains unknown. Here, we generated the MAT1-1-3 mutants, which exhibited defects in vegetative growth, stress response, pathogenicity, sclerotia formation and fruiting body maturation. An artificial outcrossing inoculation assay showed that the Δmat1-1-3 mutant was unable to produce sclerotia. Unexpectedly, the Δmat1-1-3 mutant could form immature fruiting bodies without mating on potato sucrose agar medium (PSA) compared with the wild-type strain, most likely by activating the truncated MAT1-2-1 transcription to regulate the sexual development. Moreover, RNA-seq data showed that knockout of MAT1-1-3 results in misregulation of a subset of genes involved in sexual development, MAPK signaling, cell wall integrity, autophagy, epigenetic modification, and transcriptional regulation. Collectively, this study reveals that MAT1-1-3 is required for asexual and sexual development, and pathogenicity of V. virens, thereby provides new insights into the function of mating-type genes in the fungi life cycle and infection process.