RESUMEN
Microsporidia are intracellular eukaryotic pathogens that pose a substantial threat to immunocompromised hosts. The way these pathogens manipulate host cells during infection remains poorly understood. Using a proximity biotinylation strategy we established that microsporidian EnP1 is a nucleus-targeted effector that modifies the host cell environment. EnP1's translocation to the host nucleus is meditated by nuclear localization signals (NLSs). In the nucleus, EnP1 interacts with host histone H2B. This interaction disrupts H2B monoubiquitination (H2Bub), subsequently impacting p53 expression. Crucially, this inhibition of p53 weakens its control over the downstream target gene SLC7A11, enhancing the host cell's resilience against ferroptosis during microsporidian infection. This favorable condition promotes the proliferation of microsporidia within the host cell. These findings shed light on the molecular mechanisms by which microsporidia modify their host cells to facilitate their survival.
Asunto(s)
Ferroptosis , Histonas , Microsporidios , Ubiquitinación , Microsporidios/metabolismo , Microsporidios/genética , Histonas/metabolismo , Humanos , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Interacciones Huésped-Patógeno , Animales , Núcleo Celular/metabolismo , Sistema de Transporte de Aminoácidos y+/metabolismo , Sistema de Transporte de Aminoácidos y+/genética , Microsporidiosis/metabolismoRESUMEN
Microsporidia are prolific producers of effector molecules, encompassing both proteins and nonproteinaceous effectors, such as toxins, small RNAs, and small peptides. These secreted effectors play a pivotal role in the pathogenicity of microsporidia, enabling them to subvert the host's innate immunity and co-opt metabolic pathways to fuel their own growth and proliferation. However, the genomes of microsporidia, despite falling within the size range of bacteria, exhibit significant reductions in both structural and physiological features, thereby affecting the repertoire of secretory effectors to varying extents. This review focuses on recent advances in understanding how microsporidia modulate host cells through the secretion of effectors, highlighting current challenges and proposed solutions in deciphering the complexities of microsporidial secretory effectors.
RESUMEN
Ameson portunus is an intracellular pathogen that infects marine crabs Portunus trituberculatus and Scylla paramamosain, causing significant economic losses. However, research into this important parasite has been limited due to the absence of an in vitro culture system. To address this challenge, we developed an in vitro cultivation model of A. portunus using RK13 cell line in this study. The fluorescent labeling assay indicated a high infection rate (â¼60 %) on the first day post-infection and quantitative PCR (qPCR) detection demonstrated successful infection as early as six hours post-inoculation. Fluorescence in situ hybridization (FISH) and qPCR were used for the detection of A. portunus infected cells. The FISH probe we designed allowed detection of A. portunus in infected cells and qPCR assay provided accurate quantification of A. portunus in the samples. Transmission electron microscopy (TEM) images revealed that A. portunus could complete its entire life cycle and produce mature spores in RK13 cells. Additionally, we have identified novel life cycle characteristics during the development of A. portunus in RK 13 cells using TEM. These findings contribute to our understanding of new life cycle pathways of A. portunus. The establishment of an in vitro culture model for A. portunus is critical as it provides a valuable tool for understanding the molecular and immunological events that occur during infection. Furthermore, it will facilitate the development of effective treatment strategies for this intracellular pathogen.
Asunto(s)
Braquiuros , Microsporidios , Animales , Microsporidios/fisiología , Microsporidios/genética , Braquiuros/parasitología , Braquiuros/microbiología , Línea Celular , Hibridación Fluorescente in SituRESUMEN
Developing high-performance electrocatalysts for oxygen evolution reaction (OER) is of importance for improving the overall efficiency of water splitting. Herein, the CoFe/(CoxFe1-x)3Mo3C heterojunction is purposely designed as an OER catalyst, which displays a low overpotential of 293 mV for affording a current density of 10 mA cm-2 and a small Tafel slope of 48 mV/dec. Various characterization results demonstrate that the significant work-function difference between CoFe and (CoxFe1-x)3Mo3C can induce interfacial charge redistribution, which results in the formation of Co and Fe sites with a high-spin state, thus stimulating the surface phase reconstruction of CoFe/(CoxFe1-x)3Mo3C to corresponding active oxyhydroxide. Meanwhile, the electrochemical leaching of Mo ions from the initial structure can contribute to the formation of defective sites, further benefiting OH- adsorption and surface oxidation. Moreover, the remaining CoFe can accelerate electron migration during the electrocatalytic process. This study presents new insights into constructing efficient OER electrocatalysts with an optimized spin-state configuration via interfacial engineering.
RESUMEN
Exploiting precious-metal-free and high-activity oxygen evolution reaction (OER) electrocatalysts has been in great demands toward many energy storage and conversion processes, for example, carbon dioxide reduction, metal-air batteries, and water splitting. In this study, the simple solid-state method is employed for coupling Ni (electron donors) with lower-Fermi-level MoO2 or WOx (electron acceptors) into donor-acceptor ensembles with well-designed interfaces as robust electrocatalysts for OER. The resulting Ni/MoO2 and Ni/WOx electrocatalysts exhibit smaller overpotentials of 287 and 333 mV at 10 mA cm-2 as well as smaller Tafel slopes of 51 and 65 mV/dec, respectively, with respect to the single Ni, MoO2, WOx, and even the benchmark RuO2 in 1 M KOH. Specially, on account of a higher Fermi level of Ni in comparison with MoO2 and WOx, their strong electronic interaction results in directional interfacial electron transfer and increases the hole density over Ni, dramatically enriching the population of high-valence Ni3+ active sites and decreasing the Fermi level of Ni. The existence of Ni3+ can strengthen the chemisorption of OH-, and the downshift of the Ni Fermi level can significantly expedite migration of electrons toward the surface of catalysts during OER, thus synergistically boosting the OER catalytic performance. Furthermore, the inner Ni/MoO2 and Ni/WOx heterostructures and the electrochemically induced surface layers of oxides/hydroxides collectively boost the OER kinetics. This study highlights the importance of designing highly efficient OER electrocatalysts with high-valence active species (Ni3+) and better matched energy levels induced by the work function difference through interfacial engineering.
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Three triphenylamine-based polyaminal networks (TMPs) with monodispersed ultramicropore (about 0.54â¯nm) and abundant doped-nitrogen (up to 42.88â¯wt%) are successfully prepared through the direct polycondensation of triphenylamine-based aldehydes with melamine. The synergistic effects of uniform ultramicropore and rich CO2-philic polar sites endow TMPs with exceptional CO2 sorption capacity and selectivity over N2 and CH4. For example, the CO2 uptakes of TMPs can reach 15.7â¯wt% (273â¯K) and 11.2â¯wt% (298â¯K) at 1â¯bar. Especially, at a low pressure of 0.15â¯bar, TMP-3 simultaneously exhibits excellent CO2 sorption capacity of 4.16â¯wt% (â¼1â¯mmolâ¯g-1, 298â¯K), high adsorption selectivities of CO2/N2 (61.9, 298â¯K) and CO2/CH4 (7.8, 298â¯K) and good cycle reusability, which are superior to most of the microporous polymers. In addition, the porous properties of TMPs could be effectively tuned by varying the amount of substitution formyl. This facile preparation method and excellent CO2 adsorption properties enable TMPs to possess promising application potential in CO2 capture and separation from low-concentration gas mixtures.
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In this paper, we described a temperature responsive nano-system that can regulate activity of enzyme with different temperature. Temperature responsive polymer poly(N-isopropylacrylamide) (PNIPAAm), with low critical solution temperature of 32°C, was synthesized with thiol modification. PNIPAAm and thrombin aptamer were co-functionalized on the surface of gold nanoparticles for effective regulation of thrombin activity with different temperature. On the one hand, we studied the thermal responsive properties of this inhibitor via UV-visible spectroscopy. On the other hand, we investigated the regulation of thrombin activity by this platform with different temperature. The PNIPAAm chains could extend and shrink with different temperature, which suggested that PNIPAAm on the surface of gold nanoparticles could regulate interaction between thrombin and aptamer according to temperature changing. At 25°C, PNIPAAm was hydrophilic extended state, which blocked the interaction between thrombin and aptamer on the surface of gold nanoparticles, therefore thrombin activity had no change. On the contrary, at 37°C, PNIPAAm transformed from hydrophilic extended state to hydrophobic shrank state, allowing the aptamer to capture thrombin, inhibiting the activity of thrombin. More interestingly, this regulation was reverse to normal condition, where 37°C was always the optimum reaction temperature for most of human enzymes. This system we prepared was opposite, which was capable of inhibiting the thrombin activity at 37°C. Furthermore, this was the first report of regulation of thrombin activity using this temperature responsive platform.
Asunto(s)
Resinas Acrílicas/química , Resinas Acrílicas/farmacología , Nanopartículas del Metal , Temperatura , Trombina/metabolismo , Activación Enzimática/efectos de los fármacos , Oro/química , HumanosRESUMEN
In this study, four engineered Saccharomyces cerevisiae carrying xylanase, ß-xylosidase and xylose reductase genes by different transcriptional regulations were constructed to directly convert xylan to xylitol. According to the results, the high-copy number plasmid required a rigid selection for promoter characteristics, on the contrast, the selection of promoters could be more flexible for low-copy number plasmid. For cell growth and xylitol production, glucose and galactose were found more efficient than other sugars. The semi-aerobic condition and feeding of co-substrates were taken to improve the yield of xylitol. It was found that the strain containing high-copy number plasmid had the highest xylitol yield, but it was sensitive to the change of fermentation. However, the strain carrying low-copy number plasmid was more adaptable to different processes. By optimization of the transcriptional regulation and fermentation processes, the xylitol concentration could be increased of 1.7 folds and the yield was 0.71 g xylitol/g xylan.