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1.
Genome Med ; 16(1): 47, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566132

RESUMO

BACKGROUND: Aberrant DNA methylation is a major characteristic of cancer genomes. It remains unclear which biological processes determine epigenetic reprogramming and how these processes influence the variants in the cancer methylome, which can further impact cancer phenotypes. METHODS: We performed pairwise permutations of 381,900 loci in 569 paired DNA methylation profiles of cancer tissue and matched normal tissue from The Cancer Genome Atlas (TCGA) and defined conserved differentially methylated positions (DMPs) based on the resulting null distribution. Then, we derived independent methylation signatures from 2,465 cancer-only methylation profiles from the TCGA and 241 cell line-based methylation profiles from the Genomics of Drug Sensitivity in Cancer (GDSC) cohort using nonnegative matrix factorization (NMF). We correlated DNA methylation signatures with various clinical and biological features, including age, survival, cancer stage, tumor immune microenvironment factors, and immunotherapy response. We inferred the determinant genes of these methylation signatures by integrating genomic and transcriptomic data and evaluated the impact of these signatures on cancer phenotypes in independent bulk and single-cell RNA/methylome cohorts. RESULTS: We identified 7,364 differentially methylated positions (2,969 Hyper-DMPs and 4,395 Hypo-DMPs) in nine cancer types from the TCGA. We subsequently retrieved three highly conserved, independent methylation signatures (Hyper-MS1, Hypo-MS1, and Hypo-MS4) from cancer tissues and cell lines based on these Hyper and Hypo-DMPs. Our data suggested that Hypo-MS4 activity predicts poor survival and is associated with immunotherapy response and distant tumor metastasis, and Hypo-MS4 activity is related to TP53 mutation and FOXA1 binding specificity. In addition, we demonstrated a correlation between the activities of Hypo-MS4 in cancer cells and the fractions of regulatory CD4 + T cells with the expression levels of immunological genes in the tumor immune microenvironment. CONCLUSIONS: Our findings demonstrated that the methylation signatures of distinct biological processes are associated with immune activity in the cancer microenvironment and predict immunotherapy response.


Assuntos
Metilação de DNA , Neoplasias , Humanos , Epigênese Genética , Microambiente Tumoral/genética , Neoplasias/genética , Neoplasias/terapia , Perfilação da Expressão Gênica/métodos , Prognóstico , Imunoterapia
2.
Fish Shellfish Immunol ; 148: 109502, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38471627

RESUMO

ß-defensin of flounder plays an important role in immunomodulation by recruiting immune cells and has a potential vaccine adjuvant effect in addition to its bactericidal activity. In this study, adjuvant effects of ß-defensin on DNA vaccine OmpC against edwardsiellosis in flounder (Paralichthys olivaceus) were investigated. The bicistronic eukaryotic expression plasmid pBudCE4.1 plasmid vector with two independent coding regions was selected to construct DNA vaccine of p-OmpC which express only the gene for the outer membrane protein of Edwardsiella tarda and the vaccine of p-OmpC-ßdefensin which express both the outer membrane protein of the bacterium and ß-defensin of flounder. In vitro and in vivo studies have shown that the constructed plasmids can be expressed in flounder embryonic cell lines and injection sites of muscles. After vaccination by intramuscular injection, both p-OmpC and p-OmpC-ßdefensin groups showed significant upregulation of immune-response. Compared to the pBbudCE4.1 and the p-OmpC vaccinated groups, the p-OmpC-ßdefensin vaccinated group showed significantly more cell aggregation at the injection site and intense immune response. The proportion of sIgM+ cells, as well as the CD4-1+ and CD4-2+ cells in both spleen and kidney was significantly higher in the p-OmpC-ßdefensin vaccinated group at peak time point than in the control groups. The relative survival rate of the p-OmpC-ßdefensin vaccine was 74.17%, which was significantly higher than that of the p-OmpC vaccinated group 48.33%. The results in this study determined that ß-defensin enhances the responses in cellular and humoral immunity and evokes a high degree of protection against E. tarda, which is a promising candidate for vaccine adjuvant.


Assuntos
Infecções por Enterobacteriaceae , Doenças dos Peixes , Linguado , Vacinas de DNA , beta-Defensinas , Animais , beta-Defensinas/genética , Adjuvantes de Vacinas , Adjuvantes Imunológicos/farmacologia , Edwardsiella tarda , Vacinas Bacterianas , Infecções por Enterobacteriaceae/prevenção & controle , Infecções por Enterobacteriaceae/veterinária
3.
Ultrason Sonochem ; 105: 106860, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38554531

RESUMO

Harder kernels of barley are regarded as one of the factors that restrict water and enzyme movement within the endosperm during malting. A comprehensive study of two domestic varieties was performed for evaluating malting quality. Both ß-glucan and total protein content of the Chinese domestic barley (Ganpi-6 and Kenpi-14) were significantly higher than Copeland. Grain hardness of the Chinese domestic barley was higher and water uptake ratio was lower compared with the Copeland. During germination, the expression levels of NCED1, NCED2 (major key regulatory enzymes for abscisic acid biosynthesis genes) were higher, whereas gibberelic acid (GA) synthesis genes (GA20ox1, GA2ox3, GA3ox2) were lower in the Ganpi-6, Kenpi-14 compared with Copeland. These two domestic barley varieties also showed significantly lower limit dextrinase and ß-glucanase activity compared with Copeland. Ultrasound treatment improved the malting quality of Ganpi-6 by enhancing water uptake and GA synthesis gene expression increased. Therefore, these findings provided insights into the future direction on the utilization of ultrasonication for the applications towards the improvement of the harder barley variety.


Assuntos
Hordeum , Hordeum/genética , Hordeum/metabolismo , Água/química , Regulação da Expressão Gênica de Plantas , Germinação , Ondas Ultrassônicas , Giberelinas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
4.
Heliyon ; 9(12): e23093, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38144284

RESUMO

The volume fraction and rafting degree of the γ'-Ni3Al phase under stress and high temperature are the key characteristics of mechanical properties in Ni-based superalloys, the rafting and redissolution of γ' phase caused by the creep at high temperature damage the morphology and properties of Ni-based superalloys. The phase-field simulation is performed to study the rafting accompany with the redissolution of γ' phase under high temperature and loading stress in Ni-Al alloy, the driving force and kinetics evolution of the γ' rafting were revealed. During the rafting under continuous heating, the elastic energy in the vertical γ channel is different to that of the horizontal γ channel, this difference in elastic energy drives the elements diffusion directionally to form the γ' rafts morphology. With the increased tensile stress, the decrease of specific surface of the γ' phase slows down the redissolution, a higher volume fraction is reserved for the rafted γ' phase. With temperature increases, the interface of γ/γ' phase becomes more diffusional and wider under stress. The results give an insight on the rafting mechanism of γ' phase and the kinetics evolution in Ni-based superalloys under excess temperature.

5.
Adv Mater ; 35(51): e2304514, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37784226

RESUMO

Bacterial pneumonia is the leading cause of death worldwide among all infectious diseases. However, currently available vaccines against fatal bacterial lung infections, e.g., pneumonic plague, are accompanied by limitations, including insufficient antigen-adjuvant co-delivery and inadequate immune stimulation. Therefore, there is an urgent requirement to develop next-generation vaccines to improve the interaction between antigen and adjuvant, as well as enhance the effects of immune stimulation. This study develops a novel amino-decorated mesoporous manganese silicate nanoparticle (AMMSN) loaded with rF1-V10 (rF1-V10@AMMSN) to prevent pneumonic plague. These results suggest that subcutaneous immunization with rF1-V10@AMMSN in a prime-boost strategy induces robust production of rF1-V10-specific IgG antibodies with a geometric mean titer of 315,844 at day 42 post-primary immunization, which confers complete protection to mice against 50 × LD50 of Yersinia pestis (Y. pestis) challenge via the aerosolized intratracheal route. Mechanistically, rF1-V10@AMMSN can be taken up by dendritic cells (DCs) and promote DCs maturation through activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway and production of type I interferon. This process results in enhanced antigen presentation and promotes rF1-V10-mediated protection against Y. pestis infection. This manganese-based nanoparticle vaccine represents a valuable strategy for combating fatal bacterial pneumonia.


Assuntos
Vacina contra a Peste , Peste , Pneumonia Bacteriana , Vacinas , Camundongos , Animais , Peste/prevenção & controle , Nanovacinas , Manganês , Antígenos de Bactérias/genética , Pneumonia Bacteriana/prevenção & controle , Adjuvantes Imunológicos , Proteínas de Bactérias
6.
Huan Jing Ke Xue ; 44(10): 5718-5726, 2023 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-37827787

RESUMO

Phosphorus exerts a good stabilization effect on soil lead. In this study, the findings of 90 papers were summarized using the Meta-analysis method. These papers described the immobilization of soil lead using phosphorus from 1997 to 2022. The effects of phosphorus materials on the stabilization rate and speciation transformation of soil Pb and soil pH were quantitatively analyzed based on soil properties, stabilization process conditions, and types of phosphorus materials. The results revealed that the stronger the soil alkalinity (pH ≥ 7.5), the lower is the content of lead (≤ 500 mg·kg-1), and the higher the content of soil organic matter (>0.5%), the more conducive it is to the phosphorus-based stabilization of soil lead; the stabilization rates are 75.21%, 34.97% and 93.12%, respectively. In terms of stabilization process conditions, the higher the addition amount of phosphorus (≥ 10%), the higher is the water content (>50%)and longer is the curing time (≥ 30 days), and the higher the curing temperature (≥ 40℃), the more conducive it is to the stabilization of soil lead, and the stabilization rates are 80.65%, 84.98%, 79.39%, and 41.44%, respectively. According to the types of phosphorus, soluble phosphorus had a high stabilization rate of soil lead (96.24%). The conversion rate of exchangeable lead and carbonate-bound lead to residual lead was 95.93%. Soluble phosphorus was majorly acidic, reducing the soil pH by 7.27%, whereas insoluble phosphorus was majorly alkaline, increasing the soil pH by 3.63%. In conclusion, when the soil pH ≥ 7.5, soil lead content ≤ 500 mg·kg-1, soil organic matter content >0.5%, soluble phosphorus addition ≥ 10%, water content >50%, curing time ≥ 30 days, and curing temperature ≥ 40℃, phosphorus had a better effect on soil Pb stabilization. In the actual remediation process of lead-contaminated soil, to improve the lead stabilization rate, it is necessary to comprehensively consider the effects of soil properties, stabilization process conditions, phosphorus, and other factors.

7.
Vaccine ; 41(30): 4402-4413, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-37308364

RESUMO

Influenza A virus (IAV) is a deadly zoonotic pathogen that remains a burden to global health systems despite continuous vaccinations, indicating the need for an improved vaccine strategy. In this work, we constructed a new recombinant influenza vaccine using Bacillus subtilis spores expressing M2e-FP protein (RSM2eFP) and assessed its potency and efficacy in BALB/c mouse immunized via aerosolized intratracheal inoculation (i.t.) or intragastric (i.g.) administration. Immunization via i.t. route conferred 100 % protection against 20 × LD50 A/PR/8/34 (H1N1) virus compared with only 50 % via the i.g. route. Even when challenged with 40 × LD50 virus, the RSM2eFP vaccine immunized via i.t. provided 80 % protection. Consistently, i.t. inoculation of RSM2eFP spore vaccine induced a stronger lung mucosal immune response and a greater cellular immune response than i.g. administration, as indicated by the high production of IgG and SIgA. In addition, the RSM2eFP spore vaccine diminished the yield of infectious virus in the lung of mice immunized via i.t. These results suggest that i.t. immunization of the RSM2eFP spore vaccine may be a promising strategy for the development of mucosal vaccines against IAV infections.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A , Vacinas contra Influenza , Influenza Humana , Infecções por Orthomyxoviridae , Animais , Camundongos , Humanos , Influenza Humana/prevenção & controle , Bacillus subtilis/genética , Esporos Bacterianos/genética , Vacinas Sintéticas , Camundongos Endogâmicos BALB C , Anticorpos Antivirais
8.
Nanoscale Adv ; 5(11): 2873-2878, 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37260484

RESUMO

We present a novel method for preparing water-dispersed monolayer layered double hydroxide (LDH) nanosheets (m-LDH). By intercalating styrene-maleic anhydride copolymer (SMA) into LDH, we obtained m-LDH through a simple aging step that produced stable, translucent colloidal solutions. After drying, the resulting powder can be redispersed in water to recover the m-LDH monolayer structure. To our knowledge, this is the first report of immediate recovery of the m-LDH monolayer structure from dried powder after redispersion in water. Our method may have significant implications for preparing and utilizing m-LDH nanosheets in various applications.

9.
Nanomaterials (Basel) ; 13(3)2023 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-36770417

RESUMO

Irradiation-induced point defects and applied stress affect the concentration distribution and morphology evolution of the nanophase in Fe-Cr based alloys; the aggregation of point defects and the nanoscale precipitates can intensify the hardness and embrittlement of the alloy. The influence of normal strain on the coevolution of point defects and the Cr-enriched α' nanophase are studied in Fe-35 at.% Cr alloy by utilizing the multi-phase-field simulation. The clustering of point defects and the splitting of nanoscale particles are clearly presented under normal strain. The defects loop formed at the α/α' phase interface relaxes the coherent strain between the α/α' phases, reducing the elongation of the Cr-enriched α' phase under the normal strains. Furthermore, the point defects enhance the concentration clustering of the α' phase, and this is more obvious under the compressive strain at high temperature. The larger normal strain can induce the splitting of an α' nanoparticle with the nonequilibrium concentration in the early precipitation stage. The clustering and migration of point defects provide the diffusion channels of Cr atoms to accelerate the phase separation. The interaction of point defect with the solution atom clusters under normal strain provides an atomic scale view on the microstructure evolution under external stress.

10.
PLoS Pathog ; 16(12): e1009118, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33264360

RESUMO

There are 25 auxin response factors (ARFs) in the rice genome, which play critical roles in regulating myriad aspects of plant development, but their role (s) in host antiviral immune defense and the underneath mechanism remain largely unknown. By using the rice-rice dwarf virus (RDV) model system, here we report that auxin signaling enhances rice defense against RDV infection. In turn, RDV infection triggers increased auxin biosynthesis and accumulation in rice, and that treatment with exogenous auxin reduces OsIAA10 protein level, thereby unleashing a group of OsIAA10-interacting OsARFs to mediate downstream antiviral responses. Strikingly, our genetic data showed that loss-of-function mutants of osarf12 or osarf16 exhibit reduced resistance whereas osarf11 mutants display enhanced resistance to RDV. In turn, OsARF12 activates the down-stream OsWRKY13 expression through direct binding to its promoter, loss-of-function mutants of oswrky13 exhibit reduced resistance. These results demonstrated that OsARF 11, 12 and 16 differentially regulate rice antiviral defense. Together with our previous discovery that the viral P2 protein stabilizes OsIAA10 protein via thwarting its interaction with OsTIR1 to enhance viral infection and pathogenesis, our results reveal a novel auxin-IAA10-ARFs-mediated signaling mechanism employed by rice and RDV for defense and counter defense responses.


Assuntos
Ácidos Indolacéticos/imunologia , Oryza/imunologia , Oryza/virologia , Doenças das Plantas/imunologia , Imunidade Vegetal/imunologia , Reoviridae/imunologia , Regulação da Expressão Gênica de Plantas/imunologia , Interações Hospedeiro-Patógeno/imunologia , Doenças das Plantas/virologia , Proteínas de Plantas/imunologia
11.
Cell Host Microbe ; 28(1): 89-103.e8, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32504578

RESUMO

Small RNA-mediated RNA silencing is an important antiviral mechanism in higher plants. It has been shown that RNA silencing components can be upregulated by viral infection. However, the mechanisms underlying the upregulation remain largely unknown. Here, we show that jasmonate (JA) signaling transcriptionally activates Argonaute 18 (AGO18), a core RNA silencing component that promotes rice antiviral defense through sequestering miR168 and miR528, which repress key antiviral defense proteins. Mechanistically, the JA-responsive transcription factor JAMYB directly binds to the AGO18 promoter to activate AGO18 transcription. Rice stripe virus (RSV) coat protein (CP) triggers JA accumulation and upregulates JAMYB to initiate this host defense network. Our study reveals that regulatory crosstalk exists between the JA signaling and antiviral RNA silencing pathways and elucidates a molecular mechanism for CP-mediated viral resistance in monocot crops.


Assuntos
Proteínas Argonautas/fisiologia , Ciclopentanos/farmacologia , Oryza/fisiologia , Oxilipinas/farmacologia , Proteínas de Plantas/fisiologia , Interferência de RNA , Tenuivirus/patogenicidade , Antivirais/farmacologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Oryza/efeitos dos fármacos , Oryza/virologia , Doenças das Plantas/virologia , Imunidade Vegetal , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas , Fatores de Transcrição/fisiologia , Regulação para Cima
12.
Proc Natl Acad Sci U S A ; 117(16): 9112-9121, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32253321

RESUMO

Plant auxin response factor (ARF) transcription factors are an important class of key transcriptional modulators in auxin signaling. Despite the well-studied roles of ARF transcription factors in plant growth and development, it is largely unknown whether, and how, ARF transcription factors may be involved in plant resistance to pathogens. We show here that two fijiviruses (double-stranded RNA viruses) utilize their proteins to disturb the dimerization of OsARF17 and repress its transcriptional activation ability, while a tenuivirus (negative-sense single-stranded RNA virus) directly interferes with the DNA binding activity of OsARF17. These interactions impair OsARF17-mediated antiviral defense. OsARF17 also confers resistance to a cytorhabdovirus and was directly targeted by one of the viral proteins. Thus, OsARF17 is the common target of several very different viruses. This suggests that OsARF17 plays a crucial role in plant defense against different types of plant viruses, and that these viruses use independently evolved viral proteins to target this key component of auxin signaling and facilitate infection.


Assuntos
Regulação da Expressão Gênica de Plantas/imunologia , Oryza/imunologia , Proteínas de Plantas/metabolismo , Vírus de Plantas/imunologia , Vírus de RNA/imunologia , Fatores de Transcrição/metabolismo , Resistência à Doença/genética , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Ácidos Indolacéticos/metabolismo , Mutação , Oryza/genética , Oryza/virologia , Doenças das Plantas/genética , Doenças das Plantas/imunologia , Doenças das Plantas/virologia , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Vírus de Plantas/metabolismo , Plantas Geneticamente Modificadas , Multimerização Proteica/imunologia , Vírus de RNA/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transdução de Sinais/imunologia , Nicotiana/genética , Nicotiana/metabolismo , Nicotiana/virologia , Fatores de Transcrição/genética , Proteínas Virais/imunologia , Proteínas Virais/metabolismo
13.
J Mol Med (Berl) ; 96(11): 1189-1202, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30159587

RESUMO

NLRP3, a member of the nucleotide-binding oligomerization domain (NOD)-like receptor family, is involved in cardiac inflammation. However, the functional role of NLRP3 in cardiac remodeling is not clear. To investigate the roles of NLRP3 in pressure overload-induced cardiac remodeling, NLRP3 knockout and wild-type mice were subjected to aortic banding to induce cardiac remodeling. The data showed that NLRP3 expression was downregulated in the remodeling process. NLRP3 deficiency accelerated cardiac hypertrophy, fibrosis, and inflammation responses with deteriorating cardiac dysfunction in the pressure overload-induced cardiac remodeling mouse model. Neonatal rat cardiomyocytes were isolated and stimulated with phenylephrine (PE). We identified NLRP3 as a negative regulator of cardiomyocyte remodeling in PE-stimulated cardiomyocyte remodeling using adenovirus-NLRP3 and NLRP3 siRNA. Mechanistically, we found that the expression of Toll-like receptor (TLR) 4 was upregulated in NLRP3-deficient mouse hearts and PE-stimulated cardiomyocytes. NLRP3 knockout mice subjected to a TLR4 inhibitor revealed a relieved cardiac remodeling response with improved cardiac dysfunction. Our data suggested that NLRP3 could be a therapeutic target for cardiac remodeling and heart failure. KEY MESSAGES: NLRP3 expression was downregulated in the remodeling process. NLRP3 deficiency accelerated pressure overload-induced cardiac remodeling. NLRP3 acted as a negative regulator of cardiomyocyte remodeling via downregulating TLR4.


Assuntos
Proteína 3 que Contém Domínio de Pirina da Família NLR/fisiologia , Receptor 4 Toll-Like/fisiologia , Remodelação Ventricular/fisiologia , Animais , Pressão Sanguínea , Células Cultivadas , Fibroblastos/fisiologia , Masculino , Camundongos Knockout , Miócitos Cardíacos/fisiologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Ratos Sprague-Dawley
14.
Cell Physiol Biochem ; 46(5): 2165-2172, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29730652

RESUMO

BACKGROUND/AIMS: Abnormal fatty acid ß oxidation has been associated with obesity and type 2 diabetes. Resistin is an adipokine that has been considered as a potential factor in obesity-mediated insulin resistance and type 2 diabetes. However, the effect of resistin on fatty acid ß oxidation needs to be elucidated. METHODS: We detected the effects of resistin on the expression of fatty acid oxidation (FAO) transcriptional regulatory genes, the fatty acid transport gene, and mitochondrial ß-oxidation genes using real-time PCR. The rate of FAO was measured using 14C-palmitate. Immunofluorescence assay and western blot analysis were used to explore the underlying molecular mechanisms. RESULTS: Resistin leads to a reduction in expression of the FAO transcriptional regulatory genes ERRα and NOR1, the fatty acid transport gene CD36, and the mitochondrial ß-oxidation genes CPT1, MCAD, and ACO. Importantly, treatment with resistin led to a reduction in the rate of cellular fatty acid oxidation. In addition, treatment with resistin reduced phosphorylation of acetyl CoA carboxylase (ACC) (inhibitory). Mechanistically, resistin inhibited the activation of CREB, resulting in suppression of PGC-1α. Importantly, overexpressing PGC-1α can rescue the inhibitory effects of resistin on fatty acid ß oxidation. CONCLUSIONS: Activating the transcriptional activity of CREB using small molecular chemicals is a potential pharmacological strategy for preventing the inhibitory effects of resistin on fatty acid ß oxidation.


Assuntos
Regulação para Baixo , Ácidos Graxos/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Resistina/metabolismo , Animais , Linhagem Celular , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Camundongos , Oxirredução , Ativação Transcricional
15.
Nanoscale ; 10(16): 7377-7381, 2018 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-29664493

RESUMO

Energy density and mechanical strength are crucial for practical usage of flexible supercapacitors. Herein, we demonstrate a flexible supercapacitor using Ni(OH)2/CNTs hierarchical spheres with high specific capacity (854 C g-1) and tough PBI-KOH solid polymer electrolyte. The integrated device shows high specific energy (50.6 W h kg-1) and good flexibility under folding tests.

16.
ACS Appl Mater Interfaces ; 10(11): 9398-9406, 2018 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-29489331

RESUMO

In this work, Al-doped MnO2 (Al-MO) nanoparticles have been synthesized by a simple chemical method with the aim to enhance cycling stability. At room temperature and 50 °C, the specific capacitances of Al-MO are well-maintained after 10 000 cycles. Compared with pure MnO2 nanospheres (180.6 F g-1 at 1 A g-1), Al-MO also delivers an enhanced specific capacitance of 264.6 F g-1 at 1 A g-1. During the cycling test, Al-MO exhibited relatively stable structure initially and transformed to needlelike structures finally both at room temperature and high temperature. In order to reveal the morphology evolution process, in situ NMR under high magnetic field has been carried out to probe the dynamics of structural properties. The 23Na spectra and the SEM observation suggest that the morphology evolution may follow pulverization/reassembling process. The Na+ intercalation/deintercalation induced pulverization, leading to the formation of tiny MnO2 nanoparticles. After that, the pulverized tiny nanoparticles reassembled into new structures. In Al-MO electrodes, doping of Al3+ could slow down this structure evolution process, resulting in a better electrochemical stability. This work deepens the understanding on the structural changes in faradic reaction of pseudocapacitive materials. It is also important for the practical applications of MnO2-based supercapacitors.

17.
Biochem Biophys Res Commun ; 497(1): 292-297, 2018 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-29432738

RESUMO

Mitochondrial dysfunction is associated with ß-cell failure and insulin resistance in diabetes. Humanin is an endogenous cytoprotective peptide. In the current study, we aimed to define the effects of Humanin on mitochondrial biogenesis in pancreatic ß-cells. Our findings demonstrated that Humanin treatment significantly increased the expression of PGC-1α and its downstream target genes NRF1 and TFAM in MIN6 ß-cells. Notably, Humanin treatment significantly promoted mitochondrial biogenesis by increasing mitochondrial mass, elevating mtDNA/nDNA ratio, and stimulating the expression of cytochrome B, which were suppressed by the specific AMPK inhibitor compound C. Indeed, Humanin treatment caused the phosphorylation of AMPK, which was involved in the induction of PGC-1α, NRF1, and TFAM by Humanin. Importantly, our findings indicate that Humanin treatment led to a possible functional gain of the mitochondria by increasing ATP levels and respiratory rate. Our findings provided a new insight into the molecular mechanisms of action by which Humanin improves pancreatic ß-cell function via enhanced mitochondrial mass and performance.


Assuntos
Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/administração & dosagem , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/fisiologia , Biogênese de Organelas , Animais , Linhagem Celular , Células Secretoras de Insulina/citologia , Camundongos , Mitocôndrias/ultraestrutura , Resultado do Tratamento
18.
PLoS Pathog ; 13(10): e1006662, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28977024

RESUMO

MicroRNAs (miRNAs) are small regulatory RNAs processed from primary miRNA transcripts, and plant miRNAs play important roles in plant growth, development, and response to infection by microbes. Microbial infections broadly alter miRNA biogenesis, but the underlying mechanisms remain poorly understood. In this study, we report that the Rice stripe virus (RSV)-encoded nonstructural protein 3 (NS3) interacts with OsDRB1, an indispensable component of the rice (Oryza sativa) miRNA-processing complex. Moreover, the NS3-OsDRB1 interaction occurs at the sites required for OsDRB1 self-interaction, which is essential for miRNA biogenesis. Further analysis revealed that NS3 acts as a scaffold between OsDRB1 and pri-miRNAs to regulate their association and aids in vivo processing of pri-miRNAs. Genetic evidence in Arabidopsis showed that NS3 can partially substitute for the function of double-stranded RNA binding domain (dsRBD) of AtDRB1/AtHYL1 during miRNA biogenesis. As a result, NS3 induces the accumulation of several miRNAs, most of which target pivotal genes associated with development or pathogen resistance. In contrast, a mutant version of NS3 (mNS3), which still associated with OsDRB1 but has defects in pri-miRNA binding, reduces accumulation of these miRNAs. Transgenic rice lines expressing NS3 exhibited significantly higher susceptibility to RSV infection compared with non-transgenic wild-type plants, whereas the transgenic lines expressing mNS3 showed a less-sensitive response. Our findings revealed a previously unknown mechanism in which a viral protein hijacks OsDRB1, a key component of the processing complex, for miRNA biogenesis and enhances viral infection and pathogenesis in rice.


Assuntos
Regulação da Expressão Gênica de Plantas/genética , MicroRNAs/genética , Oryza/virologia , Proteínas de Ligação a RNA/metabolismo , Tenuivirus/genética , Proteínas Virais/metabolismo , Oryza/genética , Interferência de RNA/fisiologia , Proteínas de Ligação a RNA/genética
19.
PLoS Pathog ; 12(9): e1005847, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27606959

RESUMO

The phytohormone auxin plays critical roles in regulating myriads of plant growth and developmental processes. Microbe infection can disturb auxin signaling resulting in defects in these processes, but the underlying mechanisms are poorly understood. Auxin signaling begins with perception of auxin by a transient co-receptor complex consisting of an F-box transport inhibitor response 1/auxin signaling F-box (TIR1/AFB) protein and an auxin/indole-3-acetic acid (Aux/IAA) protein. Auxin binding to the co-receptor triggers ubiquitination and 26S proteasome degradation of the Aux/IAA proteins, leading to subsequent events, including expression of auxin-responsive genes. Here we report that Rice dwarf virus (RDV), a devastating pathogen of rice, causes disease symptoms including dwarfing, increased tiller number and short crown roots in infected rice as a result of reduced sensitivity to auxin signaling. The RDV capsid protein P2 binds OsIAA10, blocking the interaction between OsIAA10 and OsTIR1 and inhibiting 26S proteasome-mediated OsIAA10 degradation. Transgenic rice plants overexpressing wild-type or a dominant-negative (degradation-resistant) mutant of OsIAA10 phenocopy RDV symptoms are more susceptible to RDV infection; however, knockdown of OsIAA10 enhances the resistance of rice to RDV infection. Our findings reveal a previously unknown mechanism of viral protein reprogramming of a key step in auxin signaling initiation that enhances viral infection and pathogenesis.


Assuntos
Proteínas do Capsídeo/metabolismo , Ácidos Indolacéticos/metabolismo , Oryza/metabolismo , Doenças das Plantas/virologia , Proteínas de Plantas/metabolismo , Vírus de Plantas/metabolismo , Reoviridae/metabolismo , Transdução de Sinais , Proteínas do Capsídeo/genética , Oryza/genética , Oryza/virologia , Doenças das Plantas/genética , Proteínas de Plantas/genética , Vírus de Plantas/genética , Complexo de Endopeptidases do Proteassoma/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise , Reoviridae/genética
20.
ACS Appl Mater Interfaces ; 8(28): 18078-88, 2016 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-27347779

RESUMO

Long cyclic life is very important to the practical application of the pseudocapacitors. A systematic study has been carried out to reveal what key factors and how they affecting the cycling behaviors of manganese oxides. The specific capacitance degradation of MnOx is usually attributed to the so-called "dissolution" issue. Our results indicate that "dissoluted MnOx" is in the form of the "flotsam" derived from the detached active materials instead of Mn(2+) in the solution, which causes color change of electrolyte and the loss of specific capacitance. During the cycling, the morphology of manganese oxides transformed to flower-like flakes regardless of the starting structures. After that, it tends to form nanowires especially at elevated temperatures. According to the relative low electrochemical utility of nanowires, specific capacitance might decrease at this stage. These results put forward new questions on charge storage mechanism. Besides, electrochemical oxidation of MnOx leads to an increase in specific capacitance. The cycling behavior of MnOx is mainly determined by these three factors. Excitingly, a very stable cycling performance with no capacitance degradation over 40 000 cycles has been achieved in MnO2 hierarchical sphere-based electrodes. This study provides insightful understanding of the fundamental cycling behavior of MnOx-based electrodes and useful instructions for developing highly stable supercapacitors.

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