Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 115
Filtrar
1.
Small ; 20(37): e2311967, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38712482

RESUMO

Intracellular bacteria pose a great challenge to antimicrobial therapy due to various physiological barriers at both cellular and bacterial levels, which impede drug penetration and intracellular targeting, thereby fostering antibiotic resistance and yielding suboptimal treatment outcomes. Herein, a cascade-target bacterial-responsive drug delivery nanosystem, MM@SPE NPs, comprising a macrophage membrane (MM) shell and a core of SPE NPs. SPE NPs consist of phenylboronic acid-grafted dendritic mesoporous silica nanoparticles (SP NPs) encapsulated with epigallocatechin-3-gallate (EGCG), a non-antibiotic antibacterial component, via pH-sensitive boronic ester bonds are introduced. Upon administration, MM@SPE NPs actively home in on infected macrophages due to the homologous targeting properties of the MM shell, which is subsequently disrupted during cellular endocytosis. Within the cellular environment, SPE NPs expose and spontaneously accumulate around intracellular bacteria through their bacteria-targeting phenylboronic acid groups. The acidic bacterial microenvironment further triggers the breakage of boronic ester bonds between SP NPs and EGCG, allowing the bacterial-responsive release of EGCG for localized intracellular antibacterial effects. The efficacy of MM@SPE NPs in precisely eliminating intracellular bacteria is validated in two rat models of intracellular bacterial infections. This cascade-targeting responsive system offers new solutions for treating intracellular bacterial infections while minimizing the risk of drug resistance.


Assuntos
Nanopartículas , Animais , Nanopartículas/química , Antibacterianos/farmacologia , Antibacterianos/química , Infecções Bacterianas/tratamento farmacológico , Catequina/análogos & derivados , Catequina/farmacologia , Catequina/química , Ácidos Borônicos/química , Ácidos Borônicos/farmacologia , Macrófagos/microbiologia , Macrófagos/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Bactérias/efeitos dos fármacos , Camundongos , Dióxido de Silício/química , Ratos , Células RAW 264.7 , Humanos
2.
Langmuir ; 40(26): 13458-13466, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38887034

RESUMO

Single-atom catalysts (SACs) are attractive in one-carbon (C1) chemistry because of their high atom efficiency. However, it is a great challenge for understanding the dynamic roles of SACs under operating conditions. Here, isolated Pt atoms trapped on defective CeO2 surface are investigated by experiments, especially operando techniques, which offers basic understanding of the nature and dynamic evolution of the Pt-CeO2 interface in dry reforming of methane (DRM). The Pt-Olattice configuration is highly active for CH4 dissociation at the expense of the Olattice atoms, which in turn promotes the H-assisted dissociation of CO2. The transformation of Pt atoms between positive and metallic states is driven by the DRM reaction, which is essential for rendering highly efficient catalysis. The dynamic evolution of Pt atoms favors to eliminate the reactive intermediates, such as carbonates and formates. The dynamic nature of the Pt-CeO2 interface in the DRM reaction shows a similar picture to the Yin and Yang transformation in ancient Chinese Tai Ji wisdom.

3.
Inorg Chem ; 63(28): 13079-13085, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38958051

RESUMO

The synthesis of a specific product via the Fischer-Tropsch synthesis remains challenging due to the uncontrollable coupling of CHx on active sites. Isoparaffins, essential high-quality petroleum additives for improving octane numbers, are primarily derived from petroleum or natural gas. With petroleum reserves dwindling and the associated low selectivity, the direct conversion of syngas to isoparaffins has emerged as a promising alternative. This study presents a tandem catalyst comprising CoxMn1-xO and zeolites for catalyzing the direct conversion of syngas to C4-C5 isoparaffins. The relay catalyst exhibited an impressive selectivity of 55.6% toward the desired products while maintaining a low CO2 selectivity of approximately 20%. Notably, the selectivity of isobutane reached 43.5%, exceeding predictions based on the Anderson-Schulz-Flory distribution. Syngas undergoes conversion into olefins on CoxMn1-xO nanocomposites, diffuses into microporous zeolites, and interacts with Brønsted acids to produce isoparaffins. The stability of the relay catalyst relied significantly on the pore characteristics and acidic density of the zeolites.

4.
Angew Chem Int Ed Engl ; 63(46): e202412777, 2024 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-39113321

RESUMO

Unlike many studies that regulate transport and separation behaviour of photogenerated charge carriers through controlling the chemical composite, our work demonstrates this goal can be achieved through simply tuning the molecular π-π packing from short-range to long-range within hydrogen-bonded organic frameworks (HOFs) without altering the building blocks or network topology. Further investigations reveal that the long-range π-π stacking significantly promotes electron delocalization and enhances electron density, thereby effectively suppressing electron-hole recombination and augmenting the charge transfer rate. Simultaneously, acting as a porous substrate, it boosts electron density of Pd nanoparticle loaded on its surfaces, resulting in remarkable CO2 photoreduction catalytic activity (CO generation rate: 48.1 µmol/g/h) without the need for hole scavengers. Our study provide insight into regulating the charge carrier behaviours in molecular assemblies based on hydrogen bonds, offering a new clue for efficient photocatalyst design.

5.
Small ; : e2304944, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38085165

RESUMO

The rational design of hybrid nanocrystals structures facilitates electronic and energetic communication between different component, which can optimize their specific performance. In this study, an efficient approach for building intricate ZnO@h-CoO nanocomposites and their derivatives is presented, based on a lattice-match/mismatch mechanism. Due to the ultra-low lattice mismatch between ZnO and hexagonal CoO (as low as 0.18%), the h-CoO layer enables epitaxial growth on the ZnO templates, and ZnO can also grow epitaxially outside the CoO layer with ease. Similarly, the thickness of the epitaxial layer and the number of alternating layers can be adjusted arbitrarily. In contrast to h-CoO, the growth of cubic crystalline oxides (such as MnO) on ZnO results in the formation of nanoparticles due to a large mismatch index (following the Volmer-Weber models). Interestingly, when h-CoO is introduced as a further component into the MnO/ZnO composite, the cubic crystalline particles on the surface of the ZnO do not disturb the epitaxial growth of the h-CoO, allowing for the formation of nanocomposites with more components. Furthermore, additional units can be added to the nanocomposite further based on the lattice-match/mismatch mechanism, which is analogous to the building nano-bricks.

6.
PLoS Pathog ; 17(9): e1009954, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34543352

RESUMO

Topoisomerases are essential for the replication of herpesviruses but the mechanisms by which the viruses hijack the cellular enzymes are largely unknown. We found that topoisomerase-II (TOP2) is a substrate of the Epstein-Barr virus (EBV) ubiquitin deconjugase BPLF1. BPLF1 co-immunoprecipitated and deubiquitinated TOP2, and stabilized SUMOylated TOP2 trapped in cleavage complexes (TOP2ccs), which halted the DNA damage response to TOP2-induced double strand DNA breaks and promoted cell survival. Induction of the productive virus cycle in epithelial and lymphoid cell lines carrying recombinant EBV encoding the active enzyme was accompanied by TOP2 deubiquitination, accumulation of TOP2ccs and resistance to Etoposide toxicity. The protective effect of BPLF1 was dependent on the expression of tyrosyl-DNA phosphodiesterase 2 (TDP2) that releases DNA-trapped TOP2 and promotes error-free DNA repair. These findings highlight a previously unrecognized function of BPLF1 in supporting a non-proteolytic pathway for TOP2ccs debulking that favors cell survival and virus production.


Assuntos
DNA Topoisomerases Tipo II/metabolismo , Infecções por Vírus Epstein-Barr/metabolismo , Proteínas Virais Reguladoras e Acessórias/metabolismo , Células HEK293 , Células HeLa , Humanos
7.
Metab Eng ; 80: 25-32, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37689258

RESUMO

Optically pure D-amino acids are key chemicals with various applications. Although the production of specific D-amino acids has been achieved by chemical synthesis or with in vitro enzyme catalysts, it is challenging to convert a simple carbon source into D-amino acids with high efficiency. Here, we design an artificial metabolic pathway by engineering bacteria to heterologously express racemase and N-acetyltransferase to produce N-acetyl-D-amino acids from L-amino acids. This new platform allows the cytotoxicity of D-amino acids to be avoided. The universal potential of this acetylation protection strategy for effectively synthesizing optically pure D-amino acids is demonstrated by testing sixteen amino acid targets. Furthermore, we combine pathway optimization and metabolic engineering in Escherichia coli and achieve practically useful efficiency with four specific examples, including N-acetyl-D-valine, N-acetyl-D-serine, N-acetyl-D-phenylalanine and N-acetyl-D-phenylglycine, with titers reaching 5.65 g/L, 5.25 g/L, 8.025 g/L and 130 mg/L, respectively. This work opens up opportunities for synthesizing D-amino acids directly from simple carbon sources, avoiding costly and unsustainable conventional approaches.


Assuntos
Aminoácidos , Escherichia coli , Aminoácidos/genética , Acetilação , Escherichia coli/metabolismo , Fenilalanina , Engenharia Metabólica , Carbono/metabolismo
8.
Plant Cell ; 32(4): 1124-1135, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32051213

RESUMO

Autophagy plays an important role in plant-pathogen interactions. Several pathogens including viruses induce autophagy in plants, but the underpinning mechanism remains largely unclear. Furthermore, in virus-plant interactions, viral factor(s) that induce autophagy have yet to be identified. Here, we report that the ßC1 protein of Cotton leaf curl Multan betasatellite (CLCuMuB) interacts with cytosolic glyceraldehyde-3-phosphate dehydrogenase (GAPC), a negative autophagic regulator, to induce autophagy in Nicotiana benthamiana CLCuMuB ßC1 bound to GAPCs and disrupted the interaction between GAPCs and autophagy-related protein 3 (ATG3). A mutant ßC1 protein (ßC13A) in which I45, Y48, and I53 were all substituted with Ala (A), had a dramatically reduced binding capacity with GAPCs, failed to disrupt the GAPCs-ATG3 interactions and failed to induce autophagy. Furthermore, mutant virus carrying ßC13A showed increased symptoms and viral DNA accumulation associated with decreased autophagy in plants. These results suggest that CLCuMuB ßC1 activates autophagy by disrupting GAPCs-ATG3 interactions.


Assuntos
Proteínas Relacionadas à Autofagia/metabolismo , Autofagia , Begomovirus/metabolismo , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Nicotiana/metabolismo , Nicotiana/virologia , Proteínas de Plantas/metabolismo , Proteínas Virais/metabolismo , Ligação Proteica , Nicotiana/ultraestrutura , Vacúolos/metabolismo , Vacúolos/ultraestrutura
9.
Environ Res ; 237(Pt 1): 116927, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37604225

RESUMO

Archaea and bacteria are distributed throughout the sediment; however, our understanding of their biodiversity patterns, community composition, and interactions is primarily limited to the surface horizons (0-20 cm). In this research, sediment samples were collected from three vertical sediment profiles (depths of 0-295 cm) in the Three Gorges Reservoir (TGR), one of the largest reservoirs in the world. Through 16S rRNA sequencing, it was shown that sediment microbial diversity did not significantly vary across the sediment. Nevertheless, a decline in the similarity of archaeal and bacterial communities over distance along sediment vertical profiles was noted. Nonmetric multidimensional scaling (NMDS) analysis revealed that archaeal and bacterial communities could be clearly separated into two groups, located in the upper sediments (0-135 cm) and deep sediments (155-295 cm). Meanwhile, at the fine-scale of the vertical section, noteworthy variations were observed in the relative abundance of prominent archaea (e.g., Euryarchaeota) and bacteria (e.g., Proteobacteria). The linear discriminant analysis effect size (LEfSe) demonstrated that twenty-four bacterial and twenty-six archaeal biomarker microbes exist in the upper and deep sediment layers. Each layer exhibited distinctive microbial divisions, suggesting that microbes with diverse biological functions are capable of thriving and propagating along the sediment profile. Co-occurrence network analysis further indicated that the microbial network in the upper sediments was more complex than that in the deep sediments. Additionally, the newly discovered anaerobic methanotrophic archaeon Candidatus Methanoperedens was identified as the most abundant keystone archaeal taxon in both sediment layers, highlighting the significance of methane oxidation in material cycling within the TGR ecosystem. In summary, our study examined the biodiversity and coexistence patterns of benthic microbial communities throughout the vertical sediment profile, providing detailed insights into the vertical geography of archaeal and bacterial communities in typical deep-water reservoir ecosystems.

10.
Sensors (Basel) ; 23(21)2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37960609

RESUMO

Dynamic characteristics play a crucial role in evaluating the performance of weight sensors and are essential for achieving fast and accurate weight measurements. This study focuses on a weight sensor based on optical coherence displacement. Using finite element analysis, the sensor was numerically simulated. Frequency domain and time domain dynamic response characteristics were explored through harmonic response analysis and transient dynamic analysis. The superior dynamic performance and reduced conditioning time of the non-contact optical coherence-based displacement weight sensor were confirmed via a negative step response experiment that compared the proposed sensing method to strain sensing. Moreover, dynamic performance metrics for the optical coherence displacement-type weight sensor were determined. Ultimately, the sensor's dynamic performance was enhanced using the pole-zero placement method, decreasing the overshoot to 4.72% and reducing the response time to 0.0132 s. These enhancements broaden the sensor's operational bandwidth and amplify its dynamic response capabilities.

11.
J Environ Sci (China) ; 134: 117-125, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37673527

RESUMO

Formaldehyde (HCHO) and carbon monoxide (CO) are both common air pollutants and hazardous to human body. It is imperative to develop the catalyst that is able to efficiently remove these pollutants. In this work, we activated Pt-MnO2 under different conditions for highly active oxidation of HCHO and CO, and the catalyst activated under CO displayed superior performance. A suite of complementary characterizations revealed that the catalyst activated with CO created the highly dispersed Pt nanoparticles to maintain a more positively charged state of Pt, which appropriately weakens the Mn-O bonding strength in the adjacent region of Pt for efficient supply of active oxygen during the reaction. Compared with other catalysts activated under different conditions, the CO-activated Pt-MnO2 displays much higher activity for oxidation of HCHO and CO. This research contributes to elucidating the mechanism for regulating the oxidation activity of Pt-based catalyst.


Assuntos
Poluentes Atmosféricos , Oxigênio , Humanos , Compostos de Manganês , Óxidos , Espécies Reativas de Oxigênio
12.
Am J Physiol Cell Physiol ; 322(4): C605-C613, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35196165

RESUMO

Heparan sulfate (HS) is a linear polysaccharide attached to a core protein, forming heparan sulfate proteoglycans (HSPGs) that are ubiquitously expressed on the surface of almost all mammalian cells and the extracellular matrix. HS orchestrates the binding of various signal molecules to their receptors, thus regulating many biological processes, including homeostasis, metabolism, and various pathological processes. Due to its wide distribution and negatively charged properties, HS is exploited by many viruses as a cofactor to attach to host cells. Therefore, inhibition of the interaction between virus and HS is proposed as a promising approach to mitigate viral infection, including SARS-CoV-2. In this review, we summarize the interaction manners of HS with viruses with focus on significant pathogenic RNA viruses, including alphaviruses, flaviviruses, and coronaviruses. We also provide an overview of the challenges we may face when using HS mimetics as antivirals for clinical treatment. More studies are needed to provide a further understanding of the interplay between HS and viruses both in vitro and in vivo, which will favor the development of specific antiviral inhibitors.


Assuntos
COVID-19 , Animais , Proteoglicanas de Heparan Sulfato/química , Proteoglicanas de Heparan Sulfato/metabolismo , Heparitina Sulfato/metabolismo , Mamíferos/metabolismo , Proteínas , SARS-CoV-2
13.
PLoS Pathog ; 16(4): e1008475, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32339200

RESUMO

The nucleotide-binding, leucine-rich repeat-containing (NLR) class of immune receptors of plants and animals recognize pathogen-encoded proteins and trigger host defenses. Although animal NLRs form oligomers upon pathogen recognition to activate downstream signaling, the mechanisms of plant NLR activation remain largely elusive. Tm-22 is a plasma membrane (PM)-localized coiled coil (CC)-type NLR and confers resistance to Tobacco mosaic virus (TMV) by recognizing its viral movement protein (MP). In this study, we found that Tm-22 self-associates upon recognition of MP. The CC domain of Tm-22 is the signaling domain and its function requires PM localization and self-association. The nucleotide-binding (NB-ARC) domain is important for Tm-22 self-interaction and regulates activation of the CC domain through its nucleotide-binding and self-association. (d)ATP binding may alter the NB-ARC conformation to release its suppression of Tm-22 CC domain-mediated cell death. Our findings provide the first example of signaling domain for PM-localized NLR and insight into PM-localized NLR activation.


Assuntos
Proteínas NLR/metabolismo , Nicotiana/metabolismo , Nicotiana/virologia , Doenças das Plantas/imunologia , Proteínas de Plantas/metabolismo , Receptores Imunológicos/metabolismo , Membrana Celular/metabolismo , Resistência à Doença , Proteínas NLR/imunologia , Doenças das Plantas/virologia , Imunidade Vegetal , Proteínas de Plantas/imunologia , Ligação Proteica , Domínios Proteicos , Receptores Imunológicos/imunologia , Transdução de Sinais , Nicotiana/imunologia , Vírus do Mosaico do Tabaco/metabolismo , Vírus do Mosaico do Tabaco/patogenicidade
14.
New Phytol ; 236(4): 1358-1374, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35978547

RESUMO

Autophagy is an essential degradation pathway that assists eukaryote survival under multiple stress conditions. Autophagosomes engulfing cargoes accomplish degradation only when they have matured through fusing with lysosomes or vacuoles. However, the molecular machinery mediating autophagosome maturation in plants remains unknown. Using the combined approaches of mass spectrometry, biochemistry, reverse genetics and microscopy, we uncover that UVRAG, a subunit of the class III phosphatidylinositol 3-kinase complexes in Nicotiana benthamiana, plays an essential role in autophagsome maturation via ATG14-assisted recruitment to autophagosomes and by facilitating RAB7 activation. An interaction between N. benthamiana UVRAG and ATG14 was observed in vitro and in vivo, which strikingly differed from their mutually exclusive appearance in different PI3KC3 complexes in yeast and mammals. This interaction increased the localisation of UVRAG on autophagosomes and enabled the convergence of autophagic and late endosomal structures, where they contributed to fusions between these two types of organelles by recruiting the essential membrane fusion factors RAB7 GTPase and the homotypic fusion and protein sorting (HOPS) complex. In addition, we uncovered a joint contribution of ATG14 and UVRAG to geminiviral infection, beyond autophagy. Our study provides insights into the mechanisms of autophagosome maturation in plants and expands the understanding of organisations and roles of the PI3KC3 complexes.


Assuntos
Autofagossomos , Geminiviridae , Animais , Autofagossomos/metabolismo , Geminiviridae/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Autofagia/fisiologia , Classe III de Fosfatidilinositol 3-Quinases/metabolismo , GTP Fosfo-Hidrolases/metabolismo , Mamíferos
15.
Environ Sci Technol ; 56(23): 17331-17340, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36354790

RESUMO

While utilization of transitional metals as a promoter has been extensively studied to enhance the activity of Pt-based catalysts for the oxidation of formaldehyde (HCHO), there is still a lack of well elucidated property-function relationship for the rational selection of a promoter in catalyst design. Herein, we modified a Pt/CeO2 catalyst with two transitional metal dopants (i.e., Mn and Cu) that showed negligible influence on the physical structure of the Pt-CeO2 matrix but distinct effects on the activity of the catalyst. Complementary characterizations combined with density functional theory modeling revealed that the transitional metal dopants significantly modified the electronic structure of the catalyst and shifted the d-band of Pt to higher energy with different extents, which may tune the bonding strength of HCHO/intermediates with the Pt-CeO2 interface domain. The catalyst with moderate bonding strength (i.e., Pt-Mn/CeO2) displayed the highest reactivity under the ambient condition, while Pt-Cu/CeO2 with the highest bonding strength showed a dramatically decreased activity. No correlation was observed between the abundancy of the active oxygen and catalytic activity, likely due to the oxygen supply having a much higher rate than the rate-determining step. This work contributes to the elucidation about the property-function relationship of a transitional metal dopant in Pt-based catalysts for the oxidation of HCHO.

16.
Phys Chem Chem Phys ; 24(18): 11104-11111, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35474371

RESUMO

Co@C is a novel class of catalysts with many structural advantages, such as highly dispersed active species, developed pore structure, and special encapsulated structure. Although considerable progress has been made in the development of new Co@C materials, research on the formation mechanism of these materials is lacking. Herein, the overall microcosmic structure of the Co@C catalyst was investigated by systematic characterization. Subsequently, a pseudo in situ method was employed to explore the detailed structure of the Co@C catalyst pyrolyzed at different temperatures. The special carbon environment of materials is essential for synthesizing materials during pyrolysis at high temperatures. Co ions were reduced to Co0 by the surrounding carbon atoms at a high temperature. In return, the surrounding carbon atoms were catalyzed by Co0 particles to form carbon nanotubes. However, with the obstruction of amorphous carbon atoms that are not in contact with Co0, the paths through which the carbon nanotubes move forward formed the porous structure of the catalyst, as well as the graphitic encapsulated structure. Further, the effects of pretreatment conditions on the structure and properties of the Co@C catalyst were studied systematically.

17.
PLoS Pathog ; 15(8): e1007980, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31461506

RESUMO

Almost one third of herpesvirus proteins are expressed with late kinetics. Many of these late proteins serve crucial structural functions such as formation of virus particles, attachment to host cells and internalization. Recently, we and others identified a group of Epstein-Barr virus early proteins that form a pre-initiation complex (vPIC) dedicated to transcription of late genes. Currently, there is a fundamental gap in understanding the role of post-translational modifications in regulating assembly and function of the complex. Here, we used mass spectrometry to map potential phosphorylation sites in BGLF3, a core component of the vPIC module that connects the BcRF1 viral TATA box binding protein to other components of the complex. We identified threonine 42 (T42) in BGLF3 as a phosphoacceptor residue. T42 is conserved in BGLF3 orthologs encoded by other gamma herpesviruses. Abolishing phosphorylation at T42 markedly reduced expression of vPIC-dependent late genes and disrupted production of new virus particles, but had no effect on early gene expression, viral DNA replication, or expression of vPIC-independent late genes. We complemented failure of BGLF3(T42A) to activate late gene expression by ectopic expression of other components of vPIC. Only BFRF2 and BVLF1 were sufficient to suppress the defect in late gene expression associated with BGLF3(T42A). These results were corroborated by the ability of wild type BGLF3 but not BGLF3(T42A) to form a trimeric complex with BFRF2 and BVLF1. Our findings suggest that phosphorylation of BGLF3 at threonine 42 serves as a new checkpoint for subsequent formation of BFRF2:BGLF3:BVLF1; a trimeric subcomplex essential for transcription of late genes. Our findings provide evidence that post-translational modifications regulate the function of the vPIC nanomachine that initiates synthesis of late transcripts in herpesviruses.


Assuntos
Replicação do DNA , Regulação Viral da Expressão Gênica , Herpesvirus Humano 4/genética , Treonina/metabolismo , Transcrição Gênica , Proteínas Virais/genética , Proteínas Virais/metabolismo , Sequência de Aminoácidos , DNA Viral/genética , Células HEK293 , Humanos , Mutação , Fosforilação , Ligação Proteica , Homologia de Sequência , Treonina/química , Treonina/genética , Proteínas Virais/química , Replicação Viral
18.
Plant Cell ; 30(7): 1582-1595, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29848767

RESUMO

Autophagy is a conserved defense strategy against viral infection. However, little is known about the counterdefense strategies of plant viruses involving interference with autophagy. Here, we show that γb protein from Barley stripe mosaic virus (BSMV), a positive single-stranded RNA virus, directly interacts with AUTOPHAGY PROTEIN7 (ATG7). BSMV infection suppresses autophagy, and overexpression of γb protein is sufficient to inhibit autophagy. Furthermore, silencing of autophagy-related gene ATG5 and ATG7 in Nicotiana benthamiana plants enhanced BSMV accumulation and viral symptoms, indicating that autophagy plays an antiviral role in BSMV infection. Molecular analyses indicated that γb interferes with the interaction of ATG7 with ATG8 in a competitive manner, whereas a single point mutation in γb, Tyr29Ala (Y29A), made this protein deficient in the interaction with ATG7, which was correlated with the abolishment of autophagy inhibition. Consistently, the mutant BSMVY29A virus showed reduced symptom severity and viral accumulation. Taken together, our findings reveal that BSMV γb protein subverts autophagy-mediated antiviral defense by disrupting the ATG7-ATG8 interaction to promote plant RNA virus infection, and they provide evidence that ATG7 is a target of pathogen effectors that functions in the ongoing arms race of plant defense and viral counterdefense.


Assuntos
Vírus de Plantas/metabolismo , Vírus de Plantas/patogenicidade , Proteínas de Plantas/metabolismo , Vírus de Plantas/genética , Ligação Proteica , RNA Viral/genética , Nicotiana/metabolismo , Nicotiana/virologia
19.
BMC Med Inform Decis Mak ; 21(1): 245, 2021 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-34419027

RESUMO

BACKGROUND: To enhance teleconsultation management, demands can be classified into different patterns, and the service of each pattern demand can be improved. METHODS: For the effective teleconsultation classification, a novel ensemble hierarchical clustering method is proposed in this study. In the proposed method, individual clustering results are first obtained by different hierarchical clustering methods, and then ensembled by one-hot encoding, the calculation and division of cosine similarity, and network graph representation. In the built network graph about the high cosine similarity, the connected demand series can be categorized into one pattern. For verification, 43 teleconsultation demand series are used as sample data, and the efficiency and quality of teleconsultation services are respectively analyzed before and after the demand classification. RESULTS: The teleconsultation demands are classified into three categories, erratic, lumpy, and slow. Under the fixed strategies, the service analysis after demand classification reveals the deficiencies of teleconsultation services, but analysis before demand classification can't. CONCLUSION: The proposed ensemble hierarchical clustering method can effectively category teleconsultation demands, and the effective demand categorization can enhance teleconsultation management.


Assuntos
Consulta Remota , Análise por Conglomerados , Humanos
20.
Microb Cell Fact ; 19(1): 202, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33138821

RESUMO

BACKGROUND: In industrial fermentation, pH fluctuation resulted from microbial metabolism influences the strain performance and the final production. The common way to control pH is adding acid or alkali after probe detection, which is not a fine-tuned method and often leads to increased costs and complex downstream processing. Here, we constructed an intelligent pH-sensing and controlling genetic circuits called "Genetic pH Shooting (GPS)" to realize microbial self-regulation of pH. RESULTS: In order to achieve the self-regulation of pH, GPS circuits consisting of pH-sensing promoters and acid-/alkali-producing genes were designed and constructed. Designed pH-sensing promoters in the GPS can respond to high or low pHs and generate acidic or alkaline substances, achieving endogenously self-responsive pH adjustments. Base shooting circuit (BSC) and acid shooting circuit (ASC) were constructed and enabled better cell growth under alkaline or acidic conditions, respectively. Furthermore, the genetic circuits including GPS, BSC and ASC were applied to lycopene production with a higher yield without an artificial pH regulation compared with the control under pH values ranging from 5.0 to 9.0. In scale-up fermentations, the lycopene titer in the engineered strain harboring GPS was increased by 137.3% and ammonia usage decreased by 35.6%. CONCLUSIONS: The pH self-regulation achieved through the GPS circuits is helpful to construct intelligent microbial cell factories and reduce the production costs, which would be much useful in industrial applications.


Assuntos
Escherichia coli/genética , Escherichia coli/metabolismo , Regulação Bacteriana da Expressão Gênica , Redes Reguladoras de Genes , Engenharia Metabólica/métodos , Ácidos , Álcalis , Concentração de Íons de Hidrogênio , Regiões Promotoras Genéticas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA