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1.
EMBO J ; 42(20): e113743, 2023 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-37661833

RESUMO

Mitochondria play essential roles in cancer cell adaptation to hypoxia, but the underlying mechanisms remain elusive. Through mitochondrial proteomic profiling, we here find that the prolyl hydroxylase EglN1 (PHD2) accumulates on mitochondria under hypoxia. EglN1 substrate-binding region in the ß2ß3 loop is responsible for its mitochondrial translocation and contributes to breast tumor growth. Furthermore, we identify AMP-activated protein kinase alpha (AMPKα) as an EglN1 substrate on mitochondria. The EglN1-AMPKα interaction is essential for their mutual mitochondrial translocation. After EglN1 prolyl-hydroxylates AMPKα under normoxia, they rapidly dissociate following prolyl-hydroxylation, leading to their immediate release from mitochondria. In contrast, hypoxia results in constant EglN1-AMPKα interaction and their accumulation on mitochondria, leading to the formation of a Ca2+ /calmodulin-dependent protein kinase 2 (CaMKK2)-EglN1-AMPKα complex to activate AMPKα phosphorylation, ensuring metabolic homeostasis and breast tumor growth. Our findings identify EglN1 as an oxygen-sensitive metabolic checkpoint signaling hypoxic stress to mitochondria through its ß2ß3 loop region, suggesting a potential therapeutic target for breast cancer.


Assuntos
Proteínas Quinases Ativadas por AMP , Neoplasias da Mama , Feminino , Humanos , Proteínas Quinases Ativadas por AMP/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Hipóxia , Prolina Dioxigenases do Fator Induzível por Hipóxia/genética , Prolina Dioxigenases do Fator Induzível por Hipóxia/metabolismo , Mitocôndrias/metabolismo , Proteômica
2.
Nat Immunol ; 16(5): 525-33, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25848866

RESUMO

Innate immunological signals induced by pathogen- and/or damage-associated molecular patterns are essential for adaptive immune responses, but it is unclear if the brain has a role in this process. Here we found that while the abundance of tumor-necrosis factor (TNF) quickly increased in the brain of mice following bacterial infection, intra-brain delivery of TNF mimicked bacterial infection to rapidly increase the number of peripheral lymphocytes, especially in the spleen and fat. Studies of various mouse models revealed that hypothalamic responses to TNF were accountable for this increase in peripheral lymphocytes in response to bacterial infection. Finally, we found that hypothalamic induction of lipolysis mediated the brain's action in promoting this increase in the peripheral adaptive immune response. Thus, the brain-fat axis is important for rapid linkage of innate immunity to adaptive immunity.


Assuntos
Tecido Adiposo/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Hipotálamo/imunologia , Listeriose/imunologia , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Fator de Necrose Tumoral alfa/administração & dosagem , Imunidade Adaptativa , Animais , Linfócitos T CD4-Positivos/microbiologia , Linfócitos T CD8-Positivos/microbiologia , Contagem de Células , Células Cultivadas , Ácidos Graxos/sangue , Hipotálamo/microbiologia , Imunidade Inata , Lipólise/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/líquido cefalorraquidiano
3.
Plant J ; 114(6): 1405-1424, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36948889

RESUMO

Protein lysine acetylation is an important post-translational modification mechanism involved in cellular regulation in eukaryotes. Calmodulin (CaM) is a ubiquitous Ca2+ sensor in eukaryotes and is crucial for plant immunity, but it is so far unclear whether acetylation is involved in CaM-mediated plant immunity. Here, we found that GhCaM7 is acetylated upon Verticillium dahliae (V. dahliae) infection and a positive regulator of V. dahliae resistance. Overexpressing GhCaM7 in cotton and Arabidopsis enhances V. dahliae resistance and knocking-down GhCaM7 makes cotton more susceptible to V. dahliae. Transgenic Arabidopsis plants overexpressing GhCaM7 with mutation at the acetylation site are more susceptible to V. dahliae than transgenics overexpressing the wild-type GhCaM7, implying the importance of the acetylated GhCaM7 in response to V. dahliae infection. Yeast two-hybrid, bimolecular fluorescent complementation, luciferase complementation imaging, and coimmunoprecipitation assays demonstrated interaction between GhCaM7 and an osmotin protein GhOSM34 that was shown to have a positive role in V. dahliae resistance. GhCaM7 and GhOSM34 are co-localized in the cell membrane. Upon V. dahliae infection, the Ca2+ content reduces almost instantly in plants with downregulated GhCaM7 or GhOSM34. Down regulating GhOSM34 enhances accumulation of Na+ and increases cell osmotic pressure. Comparative transcriptomic analyses between cotton plants with an increased or reduced expression level of GhCaM7 and wild-type plants indicate the involvement of jasmonic acid signaling pathways and reactive oxygen species in GhCaM7-enabled disease resistance. Together, these results demonstrate the involvement of CaM protein in the interaction between cotton and V. dahliae, and more importantly, the involvement of the acetylated CaM in the interaction.


Assuntos
Arabidopsis , Ascomicetos , Verticillium , Gossypium/genética , Gossypium/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Plantas/metabolismo , Acetilação , Verticillium/fisiologia , Resistência à Doença/genética , Ascomicetos/genética , Calmodulina/genética , Calmodulina/metabolismo , Processamento de Proteína Pós-Traducional , Plantas Geneticamente Modificadas/metabolismo , Doenças das Plantas , Regulação da Expressão Gênica de Plantas
4.
BMC Genomics ; 25(1): 11, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38166605

RESUMO

Genomic dissection of genetic effects on desirable traits and the subsequent use of genomic selection hold great promise for accelerating the rate of genetic improvement of forest tree species. In this study, a total of 661 offspring trees from 66 open-pollinated families of Japanese larch (Larix kaempferi (Lam.) Carrière) were sampled at a test site. The contributions of additive and non-additive effects (dominance, imprinting and epistasis) were evaluated for nine valuable traits related to growth, wood physical and chemical properties, and competitive ability using three pedigree-based and four Genomics-based Best Linear Unbiased Predictions (GBLUP) models and used to determine the genetic model. The predictive ability (PA) of two genomic prediction methods, GBLUP and Reproducing Kernel Hilbert Spaces (RKHS), was compared. The traits could be classified into two types based on different quantitative genetic architectures: for type I, including wood chemical properties and Pilodyn penetration, additive effect is the main source of variation (38.20-67.46%); for type II, including growth, competitive ability and acoustic velocity, epistasis plays a significant role (50.76-91.26%). Dominance and imprinting showed low to moderate contributions (< 36.26%). GBLUP was more suitable for traits of type I (PAs = 0.37-0.39 vs. 0.14-0.25), and RKHS was more suitable for traits of type II (PAs = 0.23-0.37 vs. 0.07-0.23). Non-additive effects make no meaningful contribution to the enhancement of PA of GBLUP method for all traits. These findings enhance our current understanding of the architecture of quantitative traits and lay the foundation for the development of genomic selection strategies in Japanese larch.


Assuntos
Larix , Larix/genética , Genótipo , Japão , Genoma , Genômica/métodos , Fenótipo , Modelos Genéticos , Polimorfismo de Nucleotídeo Único
5.
Small ; : e2400912, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38530048

RESUMO

Gels show great promise for applications in wearable electronics, biomedical devices, and energy storage systems due to their exceptional stretchability and adjustable electrical conductivity. However, the challenge lies in integrating multiple functions like elasticity, instantaneous self-healing, and a wide operating temperature range into a single gel. To address this issue, a hybrid hydrogen bonding strategy to construct gel with these desirable properties is proposed. The intricate network of hybrid strong weak hydrogen bonds within the polymer matrix enables these ionohydrogel to exhibit remarkable instantaneous self-healing, stretching up to five times their original length within seconds. Leveraging these properties, the incorporation of ionic liquids, water, and zinc salts into hybrid hydrogen bond crosslinked network enables conductivity and redox reaction, making it a versatile ionic skin for real-time monitoring of human movements and respiratory. Moreover, the ionohydrogel can be used as electrolyte in the assembly of a zinc-ion battery, ensuring a reliable power supply for wearable electronics, even in extreme conditions (-20 °C and extreme deformations). This ionohydrogel electrolyte simplifies the diverse structural requirements of gels to meet the needs of various electronic applications, offering a new approach for multi-functional electronics.

6.
Chemistry ; : e202401011, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38757219

RESUMO

The room temperature metal-free cascade electrophilic addition/cyclization/oxidation reactions of (3-phenoxyprop-1-yn-1-yl)benzenes to divergently synthesize various brominated benzopyran derivatives (3-bromo-2H-chromenes, 3-bromo-2H-chromen-2-ols and 3-bromo coumarins) by tuning the amount of Br2 and H2O have been developed. The method exhibited high selectivity, mild reaction conditions, broad substrate scope, high efficiency, and the applicability for derivatization of the brominated products. The importance of the strategies provides a great advantage for selective synthesis of brominated benzopyran derivatives.

7.
BMC Cancer ; 24(1): 150, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38291351

RESUMO

BACKGROUND: The existing staging system cannot meet the needs of accurate survival prediction. Accurate survival prediction for locally advanced cervical cancer (LACC) patients who have undergone concurrent radiochemotherapy (CCRT) can improve their treatment management. Thus, this present study aimed to develop and validate radiomics models based on pretreatment 18Fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)-computed tomography (CT) images to accurately predict the prognosis in patients. METHODS: The data from 190 consecutive patients with LACC who underwent pretreatment 18F-FDG PET-CT and CCRT at two cancer hospitals were retrospectively analyzed; 176 patients from the same hospital were randomly divided into training (n = 117) and internal validation (n = 50) cohorts. Clinical features were selected from the training cohort using univariate and multivariate Cox proportional hazards models; radiomic features were extracted from PET and CT images and filtered using least absolute shrinkage and selection operator and Cox proportional hazard regression. Three prediction models and a nomogram were then constructed using the previously selected clinical, CT and PET radiomics features. The external validation cohort that was used to validate the models included 23 patients with LACC from another cancer hospital. The predictive performance of the constructed models was evaluated using receiver operator characteristic curves, Kaplan Meier curves, and a nomogram. RESULTS: In total, one clinical, one PET radiomics, and three CT radiomics features were significantly associated with progression-free survival in the training cohort. Across all three cohorts, the combined model displayed better efficacy and clinical utility than any of these parameters alone in predicting 3-year progression-free survival (area under curve: 0.661, 0.718, and 0.775; C-index: 0.698, 0.724, and 0.705, respectively) and 5-year progression-free survival (area under curve: 0.661, 0.711, and 0.767; C-index, 0.698, 0.722, and 0.676, respectively). On subsequent construction of a nomogram, the calibration curve demonstrated good agreement between actually observed and nomogram-predicted values. CONCLUSIONS: In this study, a clinico-radiomics prediction model was developed and successfully validated using an independent external validation cohort. The nomogram incorporating radiomics and clinical features could be a useful clinical tool for the early and accurate assessment of long-term prognosis in patients with LACC patients who undergo concurrent chemoradiotherapy.


Assuntos
Nomogramas , Neoplasias do Colo do Útero , Feminino , Humanos , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Intervalo Livre de Progressão , Radiômica , Estudos Retrospectivos , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/terapia
8.
FASEB J ; 37(4): e22852, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36906289

RESUMO

Polydatin (PD), a natural product derived from Polygonum cuspidatum, has anti-inflammatory and antioxidant effects and has significant benefits in treating allergic diseases. However, its role and mechanism in allergic rhinitis (AR) have not been fully elucidated. Herein, we investigated the effect and mechanism of PD in AR. AR model was established in mice with OVA. Human nasal epithelial cells (HNEpCs) were stimulated with IL-13. HNEpCs were also treated with an inhibitor of mitochondrial division or transfected with siRNA. The levels of IgE and cellular inflammatory factors were examined by enzyme linked immunosorbent assay and flow cytometry. The expressions of PINK1, Parkin, P62, LC3B, NLRP3 inflammasome proteins, and apoptosis proteins in nasal tissues and HNEpCs were measured by Western blot. We found that PD suppressed OVA-induced epithelial thickening and eosinophil accumulation in the nasal mucosa, reduced IL-4 production in NALF, and regulated Th1/Th2 balance. In addition, mitophagy was induced in AR mice after OVA challenge and in HNEpCs after IL-13 stimulation. Meanwhile, PD enhanced PINK1-Parkin-mediated mitophagy but decreased mitochondrial reactive oxygen species (mtROS) production, NLRP3 inflammasome activation, and apoptosis. However, PD-induced mitophagy was abrogated after PINK1 knockdown or Mdivi-1 treatment, indicating a key role of the PINK1-Parkin in PD-induced mitophagy. Moreover, mitochondrial damage, mtROS production, NLRP3 inflammasome activation, and HNEpCs apoptosis under IL-13 exposure were more severe after PINK1 knockdown or Mdivi-1 treatment. Conclusively, PD may exert protective effects on AR by promoting PINK1-Parkin-mediated mitophagy, which further suppresses apoptosis and tissue damage in AR through decreasing mtROS production and NLRP3 inflammasome activation.


Assuntos
Mitofagia , Rinite Alérgica , Camundongos , Humanos , Animais , Espécies Reativas de Oxigênio/metabolismo , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Interleucina-13 , Ubiquitina-Proteína Ligases/metabolismo , Proteínas Quinases/metabolismo
9.
J Org Chem ; 89(6): 3809-3820, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38395778

RESUMO

The La(OTf)3-catalyzed [3+2] cycloaddition reactions for the synthesis of benzo[d]oxazoles/benzofurans via quinones and 1,2-di-tert-butyl-3-(cyanimino)diaziridine (1,3-di-tert-butyl-2-cyanoguanidine)/vinyl azides have been explored. A series of 5-hydroxybenzofuran-4-carboxylic acid derivatives and 5-hydroxybenzo[d]oxazole-4-carboxylic acid derivatives were conveniently obtained with high yields and good stereoselectivities, which could be used for further transformations to valuable compounds.

10.
Org Biomol Chem ; 22(18): 3732-3739, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38651493

RESUMO

Microwave irradiation (MW) and ionic liquids (ILs) are two of the most promising relatively greener synthetic approaches to preparing value-added chemicals. Herein, a series of 2-acylbenzothiazole derivatives were synthesized for the first time from commercially available α-bromoacetophenones and disulfane-diyl-dianilines through the cooperation of ionic liquids and microwave irradiation under metal- and extra-additives-free conditions. A plausible mechanism involving the successive IL-induced enolation has been proposed.

11.
Nature ; 560(7719): E33, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29950723

RESUMO

The microarray data generated and analysed in this Article have been uploaded to the Gene Expression Omnibus (GEO) under accession number GSE113383 . Accordingly, the 'Data availability' section of the Methods of the original Article has been rephrased online.

12.
Appl Microbiol Biotechnol ; 108(1): 371, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38861165

RESUMO

Understanding the extent of heritability of a plant-associated microbiome (phytobiome) is critically important for exploitation of phytobiomes in agriculture. Two crosses were made between pairs of cotton cultivars (Z2 and J11, L1 and Z49) with differential resistance to Verticillium wilt. F2 plants were grown in a field, together with the four parents to study the heritability of cotton rhizosphere microbiome. Amplicon sequencing was used to profile bacterial and fungal communities in the rhizosphere. F2 offspring plants of both crosses had higher average alpha diversity indices than the two parents; parents differed significantly from F2 offspring in Bray-Curtis beta diversity indices as well. Two types of data were used to study the heritability of rhizosphere microbiome: principal components (PCs) and individual top microbial operational taxonomic units (OTUs). For the L1 × Z49 cross, the variance among the F2 progeny genotypes (namely, genetic variance, VT) was significantly greater than the random variability (VE) for 12 and 34 out of top 100 fungal and bacterial PCs, respectively. For the Z2 × J11 cross, the corresponding values were 10 and 20 PCs. For 29 fungal OTUs and 10 bacterial OTUs out of the most abundant 100 OTUs, genetic variance (VT) was significantly greater than VE for the L1 × Z49 cross; the corresponding values for the Z2 × J11 cross were 24 and one. The estimated heritability was mostly in the range of 40% to 60%. These results suggested the existence of genetic control of polygenic nature for specific components of rhizosphere microbiome in cotton. KEY POINTS: • F2 offspring cotton plants differed significantly from parents in rhizosphere microbial diversity. • Specific rhizosphere components are likely to be genetically controlled by plants. • Common PCs and specific microbial groups are significant genetic components between the two crosses.


Assuntos
Bactérias , Fungos , Gossypium , Microbiota , Rizosfera , Microbiologia do Solo , Gossypium/microbiologia , Gossypium/genética , Microbiota/genética , Fungos/genética , Fungos/classificação , Fungos/isolamento & purificação , Bactérias/genética , Bactérias/classificação , Bactérias/isolamento & purificação , Doenças das Plantas/microbiologia , Raízes de Plantas/microbiologia , Raízes de Plantas/genética , Variação Genética , Verticillium/genética , Genótipo
13.
J Chem Phys ; 160(18)2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38726929

RESUMO

The time-dependent quantum transportation through a metal/polymer/metal system is theoretically investigated on the basis of a Su-Schrieffer-Heeger model combined with the hierarchical equations of motion formalism. Using a non-adiabatic dynamical method, the evolution of the electron subspace and lattice atoms with time can be obtained. It is found that the calculated transient currents vary with time and reach stable values after a response time under the bias voltages. However, the stable current as the system reaches its dynamical steady state exhibits a discrepancy between two sweep directions of the bias voltage, which results in pronounced electrical hysteresis loops in the current-voltage curve. By analyzing the evolution of instantaneous energy eigenstates, the occupation number of the instantaneous eigenstates, and the lattice of the polymer, we show that the formation of excitons and the delay of their annihilation are responsible for the hysteretic current-voltage characteristics, where electron-phonon interactions play the key factor. Furthermore, the hysteresis width and amplitude can also be modulated by the strength of the electron-phonon coupling, level-width broadening function, and temperature. We hope these results about past condition-dependent switching performance at a sweep voltage can provide further insight into some of the basic issues of interest in hysteresis processes in conducting polymers.

14.
J Nurs Scholarsh ; 56(4): 585-598, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38691056

RESUMO

BACKGROUND: Cancer screening is a pivotal method for reducing mortality from disease, but the screening coverage is still lower than expected. Telehealth interventions demonstrated significant benefits in cancer care, yet there is currently no consensus on their impact on facilitating cancer screening or on the most effective remote technology. DESIGN: A network meta-analysis was conducted to detect the impact of telehealth interventions on cancer screening and to identify the most effective teletechnologies. METHODS: Six English databases were searched from inception until July 2023 to yield relevant randomized controlled trials (RCTs). Two individual authors completed the literature selection, data extraction, and methodological evaluations using the Cochrane Risk of Bias tool. Traditional pairwise analysis and network meta-analysis were performed to identify the overall effects and compare different teletechnologies. RESULTS: Thirty-four eligible RCTs involving 131,644 participants were enrolled. Overall, telehealth interventions showed statistically significant effects on the improvement of cancer screening. Subgroup analyses revealed that telehealth interventions were most effective for breast and cervical cancer screening, and rural populations also experienced benefits, but there was no improvement in screening for older adults. The network meta-analysis indicated that mobile applications, video plus telephone, and text message plus telephone were associated with more obvious improvements in screening than other teletechnologies. CONCLUSION: Our study identified that telehealth interventions were effective for the completion of cancer screening and clarified the exact impact of telehealth on different cancer types, ages, and rural populations. Mobile applications, video plus telephone, and text message plus telephone are the three forms of teletechnologies most likely to improve cancer screening. More well-designed RCTs involving direct comparisons of different teletechnologies are needed in the future. CLINICAL RELEVANCE: Telehealth interventions should be encouraged to facilitate cancer screening, and the selection of the optimal teletechnology based on the characteristics of the population is also necessary.


Assuntos
Detecção Precoce de Câncer , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Telemedicina , Humanos , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/estatística & dados numéricos , Programas de Rastreamento/estatística & dados numéricos , Programas de Rastreamento/métodos , Neoplasias/diagnóstico
15.
J Clin Nurs ; 33(6): 2030-2049, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38454556

RESUMO

AIMS AND OBJECTIVES: To assess the effectiveness of different nonpharmacological treatments for severe radiation-induced oral mucositis in patients with head and neck cancer. BACKGROUND: Radiation-induced oral mucositis is highly prevalent in patients with head and neck cancer. Current medications for radiation-induced oral mucositis are limited in effectiveness and susceptible to side effects, and while there is an increasing adoption of nonpharmacological interventions, the optimal one remains unclear. DESIGN: Systematic review and network meta-analysis based on the PRISMA-NMA guidelines. METHODS: Six databases were searched. Two authors independently performed the literature screening, data extraction and methodological quality assessment of the included studies. Traditional pairwise meta-analysis was performed by R Studio. A network meta-analysis was then conducted to assess the effects of nonpharmacological interventions for severe radiation-induced oral mucositis in patients with head and neck cancer. RESULTS: Fifty-two studies involving seven types of nonpharmacological interventions were enrolled. The network meta-analysis indicated that natural plant-based therapies might be the most effective, health education interventions might be the second most effective, and honey might be the third most effective interventions for reducing the incidence of severe radiation-induced oral mucositis. For reducing the incidence of severe oral mucositis-related pain, the pairwise meta-analysis showed that only natural plant-based therapies and health education interventions were effective. CONCLUSIONS: Nonpharmacological interventions are effective in the management of severe radiation-induced oral mucositis among patients with head and neck cancer. RELEVANCE TO CLINICAL PRACTICE: Nonpharmacological interventions are a category of safe and effective adjunctive therapies that should be encouraged in clinical practice. TRIAL REGISTRATION DETAILS: CRD42023400745.


Assuntos
Neoplasias de Cabeça e Pescoço , Lesões por Radiação , Estomatite , Humanos , Neoplasias de Cabeça e Pescoço/radioterapia , Metanálise em Rede , Lesões por Radiação/terapia , Lesões por Radiação/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Estomatite/etiologia
16.
Curr Genet ; 69(1): 25-40, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36416932

RESUMO

The ergosterol biosynthesis pathway plays an important role in model pathogenic bacteria Saccharomyces cerevisiae, but little is known about the biosynthesis of ergosterol in the pathogenic fungus Verticillium dahliae. In this study, we identified the VdERG2 gene encoding sterol C-8 isomerase from V. dahliae and investigated its function in virulence by generating gene deletion mutants (ΔVdERG2) and complemented mutants (C-ΔVdERG2). Knockout of VdERG2 reduced ergosterol content. The conidial germination rate and conidial yield of ΔVdERG2 significantly decreased and abnormal conidia were produced. In spite of VdERG2 did not affect the utilization of carbon sources by V. dahliae, but the melanin production of ΔVdERG2 was decreased in cellulose and pectin were used as the sole carbon sources. Furthermore, the ΔVdERG2 mutants produced less microsclerotia and melanin with a significant decrease in the expression of microsclerotia and melanin-related genes VaflM, Vayg1, VDH1, VdLAC, VdSCD and VT4HR. In addition, mutants ΔVdERG2 were very sensitive to congo red (CR), sodium dodecyl sulfate (SDS) and hydrogen peroxide (H2O2) stresses, indicating that VdERG2 was involved in the cell wall and oxidative stress response. The absence of VdERG2 weakened the penetration ability of mycelium on cellophane and affected the growth of mycelium. Although ΔVdERG2 could infect cotton, its pathogenicity was significantly impaired. These phenotypic defects in ΔVdERG2 could be complemented by the reintroduction of a full-length VdERG2 gene. In summary, as a single conservative secretory protein, VdERG2 played a crucial role in ergosterol biosynthesis, nutritional differentiation and virulence in V. dahliae.


Assuntos
Ascomicetos , Verticillium , Virulência/genética , Melaninas , Peróxido de Hidrogênio/farmacologia , Peróxido de Hidrogênio/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Ascomicetos/metabolismo , Doenças das Plantas/microbiologia
17.
Nature ; 548(7665): 52-57, 2017 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-28746310

RESUMO

It has been proposed that the hypothalamus helps to control ageing, but the mechanisms responsible remain unclear. Here we develop several mouse models in which hypothalamic stem/progenitor cells that co-express Sox2 and Bmi1 are ablated, as we observed that ageing in mice started with a substantial loss of these hypothalamic cells. Each mouse model consistently displayed acceleration of ageing-like physiological changes or a shortened lifespan. Conversely, ageing retardation and lifespan extension were achieved in mid-aged mice that were locally implanted with healthy hypothalamic stem/progenitor cells that had been genetically engineered to survive in the ageing-related hypothalamic inflammatory microenvironment. Mechanistically, hypothalamic stem/progenitor cells contributed greatly to exosomal microRNAs (miRNAs) in the cerebrospinal fluid, and these exosomal miRNAs declined during ageing, whereas central treatment with healthy hypothalamic stem/progenitor cell-secreted exosomes led to the slowing of ageing. In conclusion, ageing speed is substantially controlled by hypothalamic stem cells, partially through the release of exosomal miRNAs.


Assuntos
Envelhecimento/genética , Envelhecimento/fisiologia , Exossomos/genética , Hipotálamo/citologia , Hipotálamo/fisiologia , Longevidade/fisiologia , MicroRNAs/genética , Células-Tronco Neurais/fisiologia , Envelhecimento/líquido cefalorraquidiano , Envelhecimento/patologia , Animais , Microambiente Celular , Exossomos/metabolismo , Hipotálamo/patologia , Proteínas I-kappa B/genética , Proteínas I-kappa B/metabolismo , Inflamação , Longevidade/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/líquido cefalorraquidiano , MicroRNAs/metabolismo , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/transplante , Complexo Repressor Polycomb 1/deficiência , Proteínas Proto-Oncogênicas/deficiência , Fatores de Transcrição SOXB1/deficiência , Fatores de Tempo
18.
BMC Pulm Med ; 23(1): 50, 2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36726128

RESUMO

BACKGROUND: Asthma is characterized by chronic inflammation and airway remodeling. However, limited study is conducted on the gene expression profiles of ovalbumin (OVA) induced asthma in mice. Here, we explored the gene expression profiles in lung tissues from mice with OVA-induced asthma using microarray and bioinformatics analysis. METHODS: For establishment of OVA-induced asthma model, mice first received intraperitoneal sensitization with OVA on day 0, 7 and 14, followed by atomizing inhalation of OVA 3 times a week for 8 weeks. The lung tissues were collected and subjected to microarray analysis, bioinformatics analysis and expression validation. RESULTS: Microarray data of lung tissues suggested that 3754 lncRNAs and 2976 mRNAs were differentially expressed in lung tissues between control and asthmatic mice, including 1647 up-regulated and 2106 down-regulated lncRNAs, and 1201 up-regulated and 1766 down-regulated mRNAs. GO analysis displayed that the up-regulated genes were enriched in inflammatory response, leukocyte migration involved in inflammatory response, and Notch signaling pathway. KEGG pathway analysis indicated that the enriched pathway terms of the up-regulated gene included Toll-like receptor signaling pathway and Th17 cell differentiation signaling pathway. Additionally, based on the previously published literatures on asthma and inflammation, we screened out down-regulated genes, such as Smg7, Sumo2, and Stat5a, and up-regulated genes, such as Myl9, Fos and Tlr4. According to the mRNA-lncRNA co-expression network, we selected lncRNAs associated with above genes, including the down-regulated lncRNAs of NONMMUT032848, NONMMUT008873, NONMMUT009478, and NONMMUT006807, and the up-regulated lncRNAs of NONMMUT052633, NONMMUT05340 and NONMMUT042325. The expression changes of the above genes were validated in lung tissues by real-time quantitaive PCR and Western blot. CONCLUSIONS: Overall, we performed gene microarray on lung samples from OVA-induced asthmatic mice and summarized core mRNAs and their related lncRNAs. This study may provide evidence for further research on the therapeutic targets of asthma.


Assuntos
Asma , RNA Longo não Codificante , Camundongos , Animais , Ovalbumina/efeitos adversos , Transcriptoma , RNA Longo não Codificante/metabolismo , Asma/induzido quimicamente , Asma/genética , Asma/tratamento farmacológico , Pulmão/metabolismo , Inflamação , Camundongos Endogâmicos BALB C , Modelos Animais de Doenças
19.
Plant Dis ; 107(6): 1680-1689, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36471458

RESUMO

Rusty root rot is the most destructive soilborne disease of ginseng caused by pathogenic Ilyonectria spp., predominantly Ilyonectria robusta, in China. However, there remains no effective strategy to control the disease. Current control of the disease requires that soil and ginseng seeds and seedlings infected with I. robusta are avoided during planting. Therefore, rapid and accurate detection of I. robusta would be indispensable in disease control programs. A one-step polymerase chain reaction (PCR) and quantitative real-time PCR (qPCR) assay was developed to detect I. robusta in ginseng seeds, roots, and soil. The species-specific primers HIS H3-F and HIS H3-R, designed based on a partial histone gene sequence of I. robusta, yielded a 268-bp product using the optimized PCR and qPCR protocol. DNA of I. robusta was detected by qPCR in all diseased soil and ginseng roots and seeds resulting from artificial inoculation and sampled from natural fields. I. robusta was detected at an abundance of 1.42 fg/µl at 12 h postinoculation and 191.31 fg/µl at 7 days postinoculation in ginseng roots that showed disease symptoms. In naturally infected soil sampled from ginseng fields, pathogen abundances ranging from 13.23 to 503.39 fg/µl were detected, which were 2.04 to 11.01 times higher than those in ginseng roots. The pathogen was first detected and was more abundant on the surface of the ginseng seed coat compared with that in the seed kernel. This study provides a high-efficiency detection technique for early diagnosis of I. robusta and real-time disease prevention and control strategies.


Assuntos
Basidiomycota , Hypocreales , Panax , Reação em Cadeia da Polimerase em Tempo Real , Solo
20.
J Clin Nurs ; 32(13-14): 3887-3897, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36101490

RESUMO

AIMS AND OBJECTIVES: To detect the mediating effect of resilience on the relationship between perceived social support and burnout in Chinese palliative nurses. BACKGROUND: Palliative nurses are a group that is vulnerable to burnout. Perceived social support may contribute to decreasing palliative nurses' burnout and facilitating their personal resilience, and resilience may be associated with lower levels of burnout. However, these relationships were unclear in the Chinese context. DESIGN: A cross-sectional design. METHODS: The STROBE guideline was performed to report this study. A mixed sampling method including convenience sampling and stratified sampling was used to recruit participants, and a total of 319 palliative nurses completed the Nursing Burnout Scale, the Perceived Social Support Scale and the Connor-Davidson Resilience Scale from May 2021 to September 2021. Influencing factors were primarily identified using independent-sample t tests and one-way ANOVA. Bootstrap method was used to detect the mediating effect of resilience. RESULTS: The level of burnout in palliative nurses (23.4 ± 7.68) was higher than that of general nurses in China. Education level, health condition and monthly income were influencing factors of burnout. Resilience was detected as a mediator in the relationships between perceived social support and dimensions of burnout. CONCLUSIONS: Chinese palliative nurses experience a relatively high level of burnout, which may be influenced by several sociodemographic variables. Resilience could mediate the effect of perceived social support on the dimensions of burnout. Problem-oriented and palliative-tailored strategies should be developed to further address burnout in Chinese palliative nurses. RELEVANCE TO CLINICAL PRACTICE: Nurse managers and policy makers should support nurse ongoing education, adopt health-promoting interventions and optimise salary systems. In addition, perceived social support resources and resilience training programmes are also warranted. PATIENT OR PUBLIC CONTRIBUTION: All participants were invited to complete the informed consent form and paper questionnaires. Human resource managers helped us collect some subjective data through the personnel management system. Nurse managers of palliative units conducted regular staff meetings to promote the data collection process.


Assuntos
Esgotamento Profissional , Enfermeiras e Enfermeiros , Humanos , Estudos Transversais , Inquéritos e Questionários , Apoio Social , Satisfação no Emprego
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