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The development of vaccines, which induce effective immune responses while ensuring safety and affordability, remains a substantial challenge. In this study, we proposed a vaccine model of a restructured "head-to-tail" dimer to efficiently stimulate B cell response. We also demonstrate the feasibility of using this model to develop a paramyxovirus vaccine through a low-cost rice endosperm expression system. Crystal structure and small-angle X-ray scattering data showed that the restructured hemagglutinin-neuraminidase (HN) formed tetramers with fully exposed quadruple receptor binding domains and neutralizing epitopes. In comparison with the original HN antigen and three traditional commercial whole virus vaccines, the restructured HN facilitated critical epitope exposure and initiated a faster and more potent immune response. Two-dose immunization with 0.5 µg of the restructured antigen (equivalent to one-127th of a rice grain) and one-dose with 5 µg completely protected chickens against a lethal challenge of the virus. These results demonstrate that the restructured HN from transgenic rice seeds is safe, effective, low-dose useful, and inexpensive. We provide a plant platform and a simple restructured model for highly effective vaccine development.
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Oryza , Paramyxovirinae , Vacunas Virales , Animales , Pollos , Virus de la Enfermedad de Newcastle , Oryza/genética , Diseño Universal , Epítopos , Anticuerpos AntiviralesRESUMEN
Polymersomes, composed of amphiphilic block copolymers, are self-assembled vesicles that have gained attention as potential drug delivery systems due to their good biocompatibility, stability, and versatility. Various experimental techniques have been employed to characterize the self-assembly behaviors and properties of polymersomes. However, they have limitations in revealing molecular details and underlying mechanisms. Computational modeling techniques have emerged as powerful tools to complement experimental studies and enabled researchers to examine drug delivery mechanisms at molecular resolution. This review aims to provide a comprehensive overview of the state of the art in the field of polymersome-based drug delivery systems, with an emphasis on insights gained from both experimental and computational studies. Specifically, we focus on polymersome morphologies, self-assembly kinetics, fusion and fission, behaviors in flow, as well as drug encapsulation and release mechanisms. Furthermore, we also identify existing challenges and limitations in this rapidly evolving field and suggest possible directions for future research.
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Sistemas de Liberación de Medicamentos , Polímeros , Preparaciones Farmacéuticas , Sistemas de Liberación de Medicamentos/métodosRESUMEN
Aspergillus flavus infects important crops and produces carcinogenic aflatoxins, posing a serious threat to food safety and human health. Biochemical analysis and RNA-seq were performed to investigate the effects and mechanisms of piperitone on A. flavus growth and aflatoxin B1 biosynthesis. Piperitone significantly inhibited the growth of A. flavus, AFB1 production, and its pathogenicity on peanuts and corn flour. Differentially expressed genes (DEGs) associated with the synthesis of chitin, glucan, and ergosterol were markedly down-regulated, and the ergosterol content was reduced, resulting in a disruption in the integrity of the cell wall and cell membrane. Moreover, antioxidant genes were down-regulated, the correspondingly activities of antioxidant enzymes such as catalase, peroxidase, and superoxide dismutase were reduced, and levels of superoxide anion and hydrogen peroxide were increased, leading to a burst of reactive oxygen species (ROS). Accompanied by ROS accumulation, DNA fragmentation and cell autophagy were observed, and 16 aflatoxin cluster genes were down-regulated. Overall, piperitone disrupts the integrity of the cell wall and cell membrane, triggers the accumulation of ROS, causes DNA fragmentation and cell autophagy, ultimately leading to defective growth and impaired AFB1 biosynthesis.
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Aflatoxina B1 , Antifúngicos , Aspergillus flavus , Especies Reactivas de Oxígeno , Zea mays , Aspergillus flavus/efectos de los fármacos , Aspergillus flavus/genética , Aspergillus flavus/crecimiento & desarrollo , Aspergillus flavus/metabolismo , Zea mays/microbiología , Antifúngicos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Arachis/microbiología , Pared Celular/efectos de los fármacos , Pared Celular/metabolismoRESUMEN
Pestiviruses, including classical swine fever virus, remain a concern for global animal health and are responsible for major economic losses of livestock worldwide. Despite high levels of vaccination, currently available commercial vaccines are limited by safety concerns, moderate efficacy, and required high doses. The development of new vaccines is therefore essential. Vaccine efforts should focus on optimizing antigen presentation to enhance immune responses. Here, we describe a simple herringbone-dimer strategy for efficient vaccine design, using the classical swine fever virus E2 expressed in a rice endosperm as an example. The expression of rE2 protein was identified, with the rE2 antigen accumulating to 480 mg/kg. Immunological assays in mice, rabbits, and pigs showed high antigenicity of rE2. Two immunizations with 284 ng of the rE2 vaccine or one shot with 5.12 µg provided effective protection in pigs without interference from pre-existing antibodies. Crystal structure and small-angle X-ray scattering results confirmed the stable herringbone dimeric conformation, which had two fully exposed duplex receptor binding domains. Our results demonstrated that rice endosperm is a promising platform for precise vaccine design, and this strategy can be universally applied to other Flaviviridae virus vaccines.
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Virus de la Fiebre Porcina Clásica , Peste Porcina Clásica , Oryza , Vacunas Virales , Animales , Porcinos , Conejos , Ratones , Peste Porcina Clásica/prevención & control , Anticuerpos Antivirales , Proteínas del Envoltorio Viral , InmunidadRESUMEN
Task-irrelevant threatening faces (e.g., fearful) are difficult to filter from visual working memory (VWM), but the difficulty in filtering non-threatening negative faces (e.g., sad) is not known. Depressive symptoms could also potentially affect the ability to filter different emotional faces. We tested the filtering of task-irrelevant sad and fearful faces by depressed and control participants performing a color-change detection task. The VWM storage of distractors was indicated by contralateral delay activity, a specific event-related potential index for the number of objects stored in VWM during the maintenance phase. The control group did not store sad face distractors, but they automatically stored fearful face distractors, suggesting that threatening faces are specifically difficult to filter from VWM in non-depressed individuals. By contrast, depressed participants showed no additional consumption of VWM resources for either the distractor condition or the non-distractor condition, possibly suggesting that neither fearful nor sad face distractors were maintained in VWM. Our control group results confirm previous findings of a threat-related filtering difficulty in the normal population while also suggesting that task-irrelevant non-threatening negative faces do not automatically load into VWM. The novel finding of the lack of negative distractors within VWM storage in participants with depressive symptoms may reflect a decreased overall responsiveness to negative facial stimuli. Future studies should investigate the mechanisms underlying distractor filtering in depressed populations.
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Miedo , Memoria a Corto Plazo , Humanos , Emociones , Potenciales EvocadosRESUMEN
The succinate dehydrogenase inhibitor (SDHI) fungicide boscalid is an excellent broad-spectrum fungicide but has not been registered in China to control Penicillium digitatum, the causal agent of green mold of citrus. The present study evaluated the risk and molecular mechanisms for boscalid resistance in P. digitatum. Resistance induction with four arbitrarily selected sensitive isolates of P. digitatum by ultraviolet (UV) irradiation on conidia plated on boscalid-amended potato dextrose agar (PDA) and consecutive growing on boscalid-amended PDA produced five highly resistant isolates with EC50 values greater than 1000 µg/mL and two resistant isolates with EC50 lower than 200 µg/mL. Boscalid resistance of the five mutants with EC50 values above 1000 µg/mL was stable after successive transfers on PDA for 16 generations. However, for the other two mutants with EC50 lower than 200 µg/mL, the EC50 values decreased significantly after successive transfers. There was significant cross-resistance between boscalid and carboxin (r = 0.925, P < 0.001), but no significant cross-resistance was detected between boscalid and fludioxonil (r = 0.533ï¼P = 0.095) or between boscalid and prochloraz (r = -0.543ï¼P = 0.088). The seven resistant mutants varied greatly in the mycelia growth, sporulation, pathogenicity, and sensitivities to exogenous stresses including NaCl, salicylhydroxamic acid (SHAM), and H2O2. Alignment of the deduced amino acid sequence showed that there was no point mutation in the target enzyme succinate dehydrogenase (Sdh) subunits SdhA, SdhC, or SdhD in each of the seven resistant mutants, and the mutation of a conserved histidine residue to tyrosine (H243Y) in the subunit SdhB (i.e., ironsulfur protein) occurred in only three highly resistant isolates. Molecular docking indicated that mutation H243Y could not prevent the binding of boscalid into the quinone-binding site of SDH in the presence of the heme moiety. However, for SDH without the heme moiety, boscalid could bind into a deeper site with a much higher affinity, and the mutation H243Y spatially blocked the docking of boscalid into the deeper site. This may be the molecular mechanism for boscalid resistance caused by SdhB-H243Y mutation.
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Fungicidas Industriales , Succinato Deshidrogenasa , Compuestos de Bifenilo , Farmacorresistencia Fúngica/genética , Fungicidas Industriales/farmacología , Hemo/metabolismo , Peróxido de Hidrógeno/metabolismo , Simulación del Acoplamiento Molecular , Niacinamida/análogos & derivados , Penicillium , Succinato Deshidrogenasa/genética , Succinato Deshidrogenasa/metabolismoRESUMEN
The solubility of glimepiride (GM) was improved from 1.6 µg/mL to 22.0 mg/mL when GM and meglumine (MU) complexes were prepared. Therefore, transdermal hydrogels of GM Carbopol (GM-CP) and GM hydroxypropyl methylcellulose pullulan (GM-HPMC-Pu) were prepared successfully utilizing the improved drug solubility by GM-MU. Based on a single factor experiment and response surface methodology, two kinds of hydrogel formulations were optimized by drug release studies in vitro. The optimized GM-CP hydrogel was composed of GM, a mixture of azone and oleic acid (1:1, 2.6%, v/v) and carbopol 940 (1%, w/v). The GM-HPMC-Pu hydrogel was developed using GM, HPMC (3.5%, w/v), Pu (1.5%, w/v), glycerol (5%, v/v), azone (2.9%, v/v) and oleic acid (2.6%, v/v). The study of hydrogels in vivo was performed using rabbits. The results indicated that the drug could sustain release from GM-CP or GM-HPMC-Pu hydrogel and maintain the high plasma concentration for 48 h. Compared with commercial GM tablets, the relative bioavailability of GM-CP and GM-HPMC-Pu hydrogel reached 48% and 133%, respectively. Moreover, the drug release in vitro could well predict its absorption in vivo. There was a good correlation (R2≥0.966) in GM hydrogel between the drug release in vitro and transdermal absorption in vivo. Therefore, a novel GM hydrogel dosage form may be considered to design.
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Hidrogeles , Ácido Oléico , Animales , Conejos , Administración Cutánea , Compuestos de SulfonilureaRESUMEN
Visual attention and visual working memory (VWM) are two major cognitive functions in humans, and they have much in common. A growing body of research has investigated the effect of emotional information on visual attention and VWM. Interestingly, contradictory findings have supported both a negative bias and a positive bias toward emotional faces (e.g., angry faces or happy faces) in the attention and VWM fields. We found that the classical paradigms-that is, the visual search paradigm in attention and the change detection paradigm in VWM-are considerably similar. The settings of these paradigms could therefore be responsible for the contradictory results. In this paper, we compare previous controversial results from behavioral and neuroscience studies using these two paradigms. We suggest three possible contributing factors that have significant impacts on the contradictory conclusions regarding different emotional bias effects; these factors are stimulus choice, experimental setting, and cognitive process. We also propose new research directions and guidelines for future studies.
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Atención/fisiología , Emociones , Expresión Facial , Memoria a Corto Plazo/fisiología , Modelos Neurológicos , Ira , Electroencefalografía , Felicidad , Humanos , Imagen por Resonancia Magnética , FotograbarRESUMEN
Describing the mechanisms of zinc (Zn) accumulation in plants is essential to counteract the effects of excessive Zn uptake in crops grown in contaminated soils. Increasing evidence suggests that there is a positive correlation between nitrate supply and Zn accumulation in plants. However, the role of the primary nitrate transporter NRT1.1 in Zn accumulation in plants remains unknown. In this study, a Zn stress-induced increase in nitrate uptake and an increase in NRT1.1 protein levels in wild-type (Col-0) Arabidopsis plants were measured using microelectrode ion flux and green fluorescent protein (GFP)/ß-glucuronidase (GUS) staining, respectively. Both agar and hydroponic cultures showed that mutants lacking the NRT1.1 function in nrt1.1 and chl1-5 (chlorate resistant 1) exhibited lower Zn levels in the roots and shoots of Zn-stressed plants than the wild-type. A lack of NRT1.1 activity also alleviated Zn-induced photosynthetic damage and growth inhibition in plants. Further, we used a rotation system with synchronous or asynchronous uptakes of nitrate and Zn to demonstrate differences in Zn levels between the Col-0 and nrt1.1/chl1-5 mutants. Significantly lower difference in Zn levels were noted in the nitrate/Zn asynchronous treatment than in the nitrate/Zn synchronous treatment. From these results, it can be concluded that NRT1.1 modulates Zn accumulation in plants via a nitrate-dependent pathway.
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Proteínas de Transporte de Anión/metabolismo , Arabidopsis/metabolismo , Zinc/metabolismo , Arabidopsis/efectos de los fármacos , Proteínas de Arabidopsis/metabolismo , Transporte Biológico , Transporte Iónico , Transportadores de Nitrato , Nitratos , Proteínas de Plantas/metabolismo , Raíces de Plantas/metabolismo , Compuestos de ZincRESUMEN
Hormetic effects of fungicides on phytopathogens are of great importance for proper application of fungicides. The aim of the present study was to investigate the stimulatory effects of the fungicide boscalid on mycelial growth and virulence of the devastating plant pathogen Sclerotinia sclerotiorum. Boscalid in potato dextrose agar (PDA) at a dosage range from 0.0005 to 0.002 µg/ml exerted statistically significant (P ≤ 0.015) stimulations on mycelial growth of S. sclerotiorum, and the maximum stimulation magnitudes were 5.55 ± 0.73% (mean ± SD) for the four isolates tested. Boscalid in PDA at 0.02 µg/ml inhibited mycelial growth of isolates HLJ3H and HLJ4H by 15.0 and 8.9%, respectively. However, after the growth-inhibited mycelia were inoculated on rapeseed leaves, isolates HLJ3H and HLJ4H exhibited virulence stimulations of 8.7 and 17.8%, respectively, indicating that hormesis may be masked by inhibitions. Boscalid sprayed at 0.0001 to 0.1 µg/ml on detached rapeseed leaves had significant (P ≤ 0.041) stimulations on virulence of S. sclerotiorum, and the maximum stimulation magnitudes were 17.90 ± 5.94% (mean ± SD) for the four isolates tested. Experiments on 12 isolates with different levels of virulence showed there was a negative correlation (R = -0.663, P = 0.019) between the maximum virulence stimulation magnitude and virulence of S. sclerotiorum in the absence of fungicide. Boscalid at stimulatory concentrations had no significant effect on the expression levels of three virulence-associated genes that encode cutinase (SsCut), polygalacturonase (SsPG1), and oxaloacetate acetylhydrolase (SsOah1). The molecular mechanisms for hormetic effects of boscalid on S. sclerotiorum remain to be studied in the future.
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Ascomicetos , Fungicidas Industriales , Compuestos de Bifenilo , Hormesis , Niacinamida/análogos & derivados , VirulenciaRESUMEN
Contamination of vegetable plants with cadmium (Cd) has become a serious issue in recent years. In the present study, pakchoi (Brassica chinensis L.) grown in Cd-contaminated soil inoculated with abscisic acid (ABA)-generating bacteria, Azospirillum brasilense and Bacillus subtilis, showed 28%-281% and 26%-255% greater biomass, and 40%-79% and 43%-77% lower Cd concentrations, respectively, than those of the controlbacteria-free plants. These treatments also alleviated the Cd-induced photosynthesis inhibition and oxidative damage (indicated by malondialdehyde [MDA], H2O2, and O2⢠-). Furthermore, the application of bacteria also remarkably improved the levels of antioxidant-related compounds (total phenolics, total flavonoids, ascorbate, and 2,2-diphenyl-1-picrylhydrazyl [DPPH] activity) and nutritional quality (soluble sugar and soluble protein) in the Cd-supplied plants. Based on these results, we conclude that the application of ABA-generating bacteria might be an alternative strategy for improving the biomass production and quality of vegetable plants grown in Cd-contaminated soil.
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Ácido Abscísico/biosíntesis , Brassica/metabolismo , Cadmio/análisis , Contaminantes del Suelo/análisis , Antioxidantes/metabolismo , Azospirillum brasilense/metabolismo , Bacillus subtilis/metabolismo , Brassica/microbiología , Cadmio/metabolismo , Cadmio/toxicidad , Contaminación Ambiental , Peróxido de Hidrógeno/metabolismo , Malondialdehído/metabolismo , Suelo/química , Microbiología del Suelo , Contaminantes del Suelo/metabolismo , Contaminantes del Suelo/toxicidad , Verduras/crecimiento & desarrollo , Verduras/metabolismo , Verduras/microbiologíaRESUMEN
Previous studies showed that dimethachlone has significant hormetic effects on phytopathogenic fungus Sclerotinia sclerotiorum. The present study investigated hormetic effects of mixtures of dimethachlone and prochloraz on mycelial growth and virulence of two dimethachlone-resistant isolates of S. sclerotiorum. The stimulatory dimethachlone dosage range was around 1 to 100 µg/ml in potato dextrose agar (PDA) medium for mycelial growth of the two isolates, and dimethachlone at 10 and 50 µg/ml had the maximum percent stimulations of 80.6 and 19.3% for isolates JMS14 and HLJ4, respectively. Prochloraz at 0.0003 and 0.002 µg/ml had the maximum percent stimulations of 9.3 and 11.1% for isolates JMS14 and HLJ4, respectively. However, dimethachlone and prochloraz mixed at their respective stimulatory concentrations had the maximum percent stimulations of 48.1 and 9.3% for isolates JMS14 and HLJ4, respectively. After the mycelia with increased and inhibited growth on fungicide-amended PDA were subcultured on PDA without fungicide, mycelial growth for the second generation increased compared with the nontreated control. After the mycelia grown on fungicide-amended PDA were inoculated on rapeseed leaves, the amplitude of virulence stimulation was much greater than that of mycelial growth on PDA amended with fungicide, and the inhibited mycelia also showed substantially increased virulence on leaves. The mixture of dimethachlone at 100 µg/ml and prochloraz at 0.03 µg/ml in PDA inhibited mycelial growth of isolate JMS14 by 59.4%; however, after the inhibited mycelia were inoculated on rapeseed leaves, virulence was stimulated by 69.0%. Spraying sublethal doses of dimethachlone and prochloraz on rapeseed leaves also exhibited significant stimulatory effects on virulence. For isolate JMS14, the stimulatory concentration ranges for dimethachlone and prochloraz were around 1 to 600 µg/ml and 0.0003 to 0.18 µg/ml, respectively. The fitted curve of virulence stimulation for the mixture of dimethachlone and prochloraz shifted to the left on the x axis, denoting dose-additive interactions between the two fungicides with regard to virulence stimulation. Spraying dimethachlone alone at 10 to 50 µg/ml had significant stimulations on virulence, whereas prochloraz alone at 10 to 50 µg/ml had significant inhibitory effects on virulence, and the mixture of dimethachlone and prochloraz at the concentration ratio of 1:1 had greater inhibitory effects than prochloraz alone, indicating dose-additive interactions for the inhibitory effects. Dimethachlone and prochloraz and their mixtures increased tolerance of mycelia to hydrogen peroxide. Dimethachlone significantly increased, whereas prochloraz reduced mycelial cell membrane permeability, and the mixture of the two fungicides had effect-additive interactions with respect to effects on cell membrane permeability. These studies will advance our understanding of hormesis of fungicide mixtures.
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Ascomicetos , Clorobencenos , Hormesis , Imidazoles , Succinimidas , Ascomicetos/efectos de los fármacos , Clorobencenos/farmacología , Fungicidas Industriales/farmacología , Succinimidas/farmacologíaRESUMEN
Emotional information is critical for our social life, in which attentional bias is now a focus in the study on attention. However, the attentional bias processing mechanism of emotional faces still arouses huge controversy. Using similar experimental paradigms and stimuli, the published studies have yielded contradictory results. Some studies suggest that angry faces could automatically stimulate attention, that is, there is an anger superiority effect. On the contrary, lines of growing evidence support the existence of a happiness superiority effect, suggesting that the superiority effect is shown in happy faces rather than angry faces. In the present paper, the behavioral and neuroscience studies of anger and happiness superiority effects are combined. It is found that there are three major reasons for the debate over the two types of effects, which include the choice of stimulus materials, the difference of paradigm setting, and the different stages of emotional processing. By comparatively integrating the previous published results, we highlight that the future studies should further control the experimental materials and procedures, and investigate the processing mechanism of anger and happiness superiority effects by combining cognitive neurobiology means to resolve the disputes.
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Ira , Sesgo Atencional , Expresión Facial , Felicidad , HumanosRESUMEN
The ergosterol biosynthesis inhibitor prochloraz is a broad-spectrum fungicide and has been registered in China since 2007 for control of the economically important necrotrophic pathogen Sclerotinia sclerotiorum. In this study, relative baseline sensitivity and toxic actions of prochloraz on S. sclerotiorum were investigated. The mean EC50 values (effective concentrations causing 50% mycelial growth inhibition) for isolates collected in 2008 (n = 73) and 2014 (n = 76) were 0.0463 and 0.0434 µg/ml, respectively. There was no significant difference (P = 0.348) in EC50 values between the two years. Both frequency distributions of EC50 values for 2008 and 2014 were unimodal. The curative efficacy of prochloraz was significantly higher (P < 0.05) than that of the reference fungicide carbendazim. Prochloraz in potato dextrose agar (PDA) at concentrations from 0.01 to 0.36 µg/ml had no significant (P = 0.574) effects on the weight of sclerotia, but the number of sclerotia per plate increased for treatments with prochloraz at 0.15 and 0.36 µg/ml. Light microscopic observations showed that prochloraz in PDA at 0.03 µg/ml increased the number of hyphal offshoots. Observations with a transmission electron microscope showed that the cell wall of the prochloraz-treated hyphae became thicker and darker than the nontreated control. Prochloraz at 0.01 and 0.04 µg/ml significantly (P < 0.001) reduced rather than increased cell membrane permeability. Prochloraz significantly (P = 0.041) increased the mannan content in the cell wall of S. sclerotiorum. The observed mycelial growth inhibitions for the mixtures of prochloraz at 0.03 µg/ml and Congo red at a dose range from 0.05 to 0.4% (w/v) were lower than the expected inhibitions, indicating prochloraz might reduce the content of chitin in S. sclerotiorum. These results demonstrate that prochloraz has significant effects on the morphology and components of the cell wall of S. sclerotiorum and thus will advance our understanding of the toxic actions of prochloraz on phytopathogenic fungi.
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Ascomicetos/efectos de los fármacos , Fungicidas Industriales/farmacología , Imidazoles/farmacología , Enfermedades de las Plantas/microbiología , Ascomicetos/crecimiento & desarrollo , Ascomicetos/ultraestructura , Permeabilidad de la Membrana Celular/efectos de los fármacos , Pared Celular/efectos de los fármacos , Pared Celular/ultraestructura , Hifa/efectos de los fármacos , Hifa/crecimiento & desarrollo , Hifa/ultraestructuraRESUMEN
External distractions often occur when information must be retained in visual working memory (VWM)-a crucial element in cognitive processing and everyday activities. However, the distraction effects can differ if they occur during the encoding rather than the delay stages. Previous research on these effects used simple stimuli (e.g., color and orientation) rather than considering distractions caused by real-world stimuli on VWM. In the present study, participants performed a facial VWM task under different distraction conditions across the encoding and delay stages to elucidate the mechanisms of distraction resistance in the context of complex real-world stimuli. VWM performance was significantly impaired by delay-stage but not encoding-stage distractors (Experiment 1). In addition, the delay distraction effect arose primarily due to the absence of distractor process at the encoding stage rather than the presence of a distractor during the delay stage (Experiment 2). Finally, the impairment in the delay-distraction condition was not due to the abrupt appearance of distractors (Experiment 3). Taken together, these findings indicate that the processing mechanisms previously established for resisting distractions in VWM using simple stimuli can be extended to more complex real-world stimuli, such as faces.
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Atención , Reconocimiento Facial , Memoria a Corto Plazo , Humanos , Memoria a Corto Plazo/fisiología , Atención/fisiología , Masculino , Femenino , Adulto Joven , Reconocimiento Facial/fisiología , Tiempo de Reacción , Adulto , Reconocimiento Visual de Modelos/fisiología , OrientaciónRESUMEN
Embryonic stem cells (ESCs), with abilities of infinite proliferation (self-renewal) and to differentiate into distinct cell types (pluripotency), show attenuated inflammatory response against cytokines or pathogens, which is recognized as a unique characteristic of ESCs compared with somatic cells. However, the underlying molecular mechanisms remain unclear, and whether the attenuated inflammatory state is involved in ESC differentiation is completely unknown. Our recent study demonstrated that macroautophagy/autophagy-related protein ATG5 inhibits the inflammatory response of mouse ESCs (MmESCs) by promoting the degradation of BTRC/ß-TrCP1 and further the downregulation of NFKB/NF-κB signaling. In addition, maintenance of an attenuated inflammation status in MmESCs is required for their differentiation. In conclusion, ATG5 is a key regulator for the regulation of inflammatory response and differentiation of MmESCs.
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Proteína 5 Relacionada con la Autofagia , Autofagia , Diferenciación Celular , Inflamación , Células Madre Embrionarias de Ratones , Animales , Ratones , Inflamación/patología , Células Madre Embrionarias de Ratones/metabolismo , Células Madre Embrionarias de Ratones/citología , Proteína 5 Relacionada con la Autofagia/metabolismo , Proteína 5 Relacionada con la Autofagia/genética , Transducción de Señal , FN-kappa B/metabolismoRESUMEN
Attenuated inflammatory response is a property of embryonic stem cells (ESCs). However, the underlying mechanisms are unclear. Moreover, whether the attenuated inflammatory status is involved in ESC differentiation is also unknown. Here, we found that autophagy-related protein ATG5 is essential for both attenuated inflammatory response and differentiation of mouse ESCs and that attenuation of inflammatory signaling is required for mouse ESC differentiation. Mechanistically, ATG5 recruits FBXW7 to promote ubiquitination and proteasome-mediated degradation of ß-TrCP1, resulting in the inhibition of nuclear factor κB (NF-κB) signaling and inflammatory response. Moreover, differentiation defects observed in ATG5-depleted mouse ESCs are due to ß-TrCP1 accumulation and hyperactivation of NF-κB signaling, as loss of ß-TrCP1 and inhibition of NF-κB signaling rescued the differentiation defects. Therefore, this study reveals a previously uncharacterized mechanism maintaining the attenuated inflammatory response in mouse ESCs and further expands the understanding of the biological roles of ATG5.
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Proteína 5 Relacionada con la Autofagia , Células Madre Embrionarias de Ratones , Animales , Ratones , Diferenciación Celular/fisiología , Células Madre Embrionarias , Células Madre Embrionarias de Ratones/metabolismo , FN-kappa B/metabolismo , Transducción de Señal/fisiología , Proteína 5 Relacionada con la Autofagia/metabolismoRESUMEN
It has been shown that the perceiver's mood affects the perception of emotional faces, but it is not known how mood affects preattentive brain responses to emotional facial expressions. To examine the question, we experimentally induced sad and neutral mood in healthy adults before presenting them with task-irrelevant pictures of faces while an electroencephalography was recorded. Sad, happy, and neutral faces were presented to the participants in an ignore oddball condition. Differential responses (emotional - neutral) for the P1, N170, and P2 amplitudes were extracted and compared between neutral and sad mood conditions. Emotional facial expressions modulated all the components, and an interaction effect of expression by mood was found for P1: an emotional modulation to happy faces, which was found in neutral mood condition, disappeared in sad mood condition. For N170 and P2, we found larger response amplitudes for both emotional faces, regardless of the mood. The results add to the previous behavioral findings showing that mood already affects low-level cortical feature encoding of task-irrelevant faces.
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Emociones , Potenciales Evocados , Adulto , Humanos , Potenciales Evocados/fisiología , Emociones/fisiología , Electroencefalografía/métodos , Encéfalo , Felicidad , Expresión FacialRESUMEN
BACKGROUND: Pain can have a significant impact on an individual's life, as it has both cognitive and affective consequences. However, our understanding of how pain affects social cognition is limited. Previous studies have shown that pain, as an alarm stimulus, can disrupt cognitive processing when focal attention is required, but whether pain also affects task-irrelevant perceptual processing remains unclear. METHODS: We examined the effect of laboratory-induced pain on event-related potentials (ERPs) to neutral, sad and happy faces before, during and after a cold pressor pain. ERPs reflecting different stages of visual processing (P1, N170 and P2) were analysed. RESULTS: Pain decreased the P1 amplitude for happy faces and increased the N170 amplitude for happy and sad faces compared to the pre-pain phase. The effect of pain on N170 was also observed in the post-pain phase. The P2 component was not affected by pain. CONCLUSIONS: Our results suggest that pain alters both featural (P1) and structural face-sensitive (N170) visual encoding of emotional faces, even when the faces are irrelevant to the task. While the effect of pain on initial feature encoding seemed to be disruptive and specific to happy faces, later processing stages showed long-lasting and increased activity for both sad and happy emotional faces. SIGNIFICANCE: The observed alterations in face perception due to pain may have consequences for real-life interactions, as fast and automatic encoding of facial emotions is important for social interactions.
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Electroencefalografía , Expresión Facial , Electroencefalografía/métodos , Emociones/fisiología , Encéfalo , Potenciales Evocados/fisiologíaRESUMEN
Reclaimed water from municipal wastewater has great potential in mitigating the water resource crisis, while the inevitable residue of organic micropollutants (OMPs) challenges the safety of reclaimed water reuse. Limited information was available regarding the overall adverse effects of mixed OMPs in reclaimed water, especially the endocrine-disrupting effects on living organisms. Herein, chemical monitoring in two municipal wastewater treatment plants showed that 31 of 32 candidate OMPs including polycyclic aromatic hydrocarbons (PAHs), phenols, pharmaceuticals and personal care products (PPCPs) were detected in reclaimed water, with a concentration ranging from ng/L to µg/L. Then, based on the risk quotient value, phenol, bisphenol A, tetracycline, and carbamazepine were ranked as high ecological risks. Most PAHs and PPCPs were quantified as medium and low risks, respectively. More importantly, using aquatic vertebrate zebrafish as an in vivo model, the endocrine-disrupting potentials of OMP mixtures were comprehensively characterized. We found that a realistic exposure to reclaimed water induced estrogen-like endocrine disruption and hyperthyroidism in zebrafish, abnormal expression of genes along the hypothalamus-pituitary-thyroid (-gonad) axes, reproductive impairment, and transgenerational toxicity. Based on the chemical analyses, risk quotient calculations, and biotoxicity characterization, this study contributed to understanding the ecological risks of reclaimed water and developing the control standards for OMPs. In addition, application of the zebrafish model in this study also highlighted the significance of in vivo biotoxicity test in water quality evaluation.