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Epithelial-derived cytokines, especially type 2 alarmins (TSLP, IL-25, and IL-33), have emerged as critical mediators of type 2 inflammation. IL-33 attracts more interest for its strong association with allergic asthma, especially in childhood asthma. However, the age-dependent role of IL-33 to the development of allergic asthma remains elusive. Here, using OVA-induced allergic asthma model in neonatal and adult mice, we report that IL-33 is the most important alarmin in neonatal lung both at steady state or inflammation. The deficiency of IL-33/ST2 abrogated the development of allergic asthma only in neonates, whereas in adults the effect was limited. Interestingly, the deficiency of IL-33/ST2 equally dampened the ILC2 responses in both neonatal and adult models. However, the effect of IL-33/ST2 deficiency on Th2 responses is age-dependent, which is only blocked in neonates. Furthermore, IL-33/ST2 signaling is dispensable for OVA sensitization. Following OVA challenge in adults, the deficiency of IL-33/ST2 results in compensational more TSLP, which in turn recruits and activates lung DCs and boosts Th2 responses. The enriched γδ T17 cells in IL-33/ST2 deficient neonatal lung suppress the expression of type 2 alarmins, CCL20 and GM-CSF via IL-17A, thus might confer the inhibition of allergic asthma. Finally, on the basis of IL-33 deficiency, the additive protective effects of TSLP blocking is much more pronounced than IL-25 blocking in adults. Our studies demonstrate that the role of IL-33 for ILC2 and Th2 responses varies among ages in OVA models and indicate that the factor of age should be considered for intervention of asthma.
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S-Adenosylmethionine (SAM) is a crucial metabolic intermediate playing irreplaceable roles in organismal activities. However, the synthesis of SAM by methionine adenosyltransferase (MAT) is hindered by low conversion due to severe product inhibition. Herein structure-guided semirational engineering was conducted on MAT from Escherichia coli (EcMAT) to mitigate the product inhibitory effect. Compared with the wild-type EcMAT, the best variant E56Q/Q105R exhibited an 8.13-fold increase in half maximal inhibitory concentration and a 4.46-fold increase in conversion (150 mM ATP and l-methionine), leading to a SAM titer of 47.02 g/L. Another variant, E56N/Q105R, showed superior thermostability with an impressive 85.30-fold increase in half-life (50 °C) value. Furthermore, molecular dynamics (MD) simulation results demonstrate that the alleviation in product inhibitory effect could be attributed to facilitated product release. This study offers molecular insights into the mitigated product inhibition, and provides valuable guidance for engineering MAT toward enhanced catalytic performance.
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Escherichia coli , Metionina Adenosiltransferase , S-Adenosilmetionina , Metionina Adenosiltransferase/genética , Metionina Adenosiltransferase/metabolismo , Metionina Adenosiltransferase/química , S-Adenosilmetionina/metabolismo , S-Adenosilmetionina/química , Escherichia coli/genética , Escherichia coli/metabolismo , Engenharia de Proteínas , Cinética , Simulação de Dinâmica Molecular , Estabilidade Enzimática , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/químicaRESUMO
Even though lead halide perovskite has been demonstrated as a promising optoelectronic material for next-generation display applications, achieving high-efficiency and stable pure-red (620~635 nm) emission to cover the full visible wavelength is still challenging. Here, we report perovskite light-emitting diodes emitting pure-red light at 628 nm achieving high external quantum efficiencies of 26.04%. The performance is attributed to successful synthesizing strongly confined CsPbI3 quantum dots with good stability. The strong binding 2-naphthalene sulfonic acid ligands are introduced after nucleation to suppress Ostwald ripening, meanwhile, ammonium hexafluorophosphate exchanges long chain ligands and avoids regrowth by strong binding during the purification process. Both ligands enhance the charge transport ability of CsPbI3 quantum dots. The state-of-the-art synthesis of pure red CsPbI3 quantum dots achieves 94% high quantum efficiency, which can maintain over 80% after 50 days, providing a method for synthesizing stable strong confined perovskite quantum dots.
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Since oxidative stress is often associated with neurodegenerative diseases, antioxidants are likely to confer protection against neurodegeneration. Despite an increasing number of food-derived peptides being identified as antioxidants, their antineurodegenerative potentials remain largely unexplored. Here, a sea cucumber peptide preparation - the peptide-rich fraction of <3 kDa (UF<3K) obtained by ultrafiltration from Apostichopus japonicus protein hydrolyzate - was found to protect PC12 cells and Caenorhabditis elegans from neurodegeneration by reducing oxidative stress and apoptosis, demonstrating its in vitro and in vivo neuroprotective effects. As many food-originated peptides are cryptides (cryptic peptides - short amino acid sequences encrypted in parent proteins) released in quantities by protein hydrolysis, UF<3K was subjected to sequencing analysis. As expected, a large repertoire of peptides were identified in UF<3K, establishing a sea cucumber cryptome (1238 peptides in total). Then 134 peptides were randomly selected from the cryptome (>10%) and analyzed for their antioxidant activities using a number of in silico bioinformatic programs as well as in vivo experimental assays in C. elegans. From these results, a novel antioxidant peptide - HoloPep#362 (FETLMPLWGNK) - was shown to not only inhibit aggregation of neurodegeneration-associated polygluatmine proteins but also ameliorate behavioral deficits in proteotoxicity nematodes. Proteomic analysis revealed an increased expression of several lysosomal proteases by HoloPep#362, suggesting proteostasis maintenance as a mechanism for its antineurodegenerative action. These findings provide an insight into the health-promoting potential of sea cucumber peptides as neuroprotective nutraceuticals and also into the importance of training in silico peptide bioactivity prediction programs with in vivo experimental data.
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Antioxidantes , Caenorhabditis elegans , Fármacos Neuroprotetores , Estresse Oxidativo , Peptídeos , Pepinos-do-Mar , Animais , Caenorhabditis elegans/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/química , Peptídeos/farmacologia , Peptídeos/química , Pepinos-do-Mar/química , Estresse Oxidativo/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Células PC12 , Ratos , Doenças Neurodegenerativas/tratamento farmacológico , Simulação por ComputadorRESUMO
Although the SNARC effect in the processing of most magnitude stimuli and sequence stimuli has been reported for the past 30 years, it remains unclear whether this effect is caused by the spatial representation or polarity encoding of stimuli. In the present study, we designed five experiments using a four-way classification task to evaluate the ability of spatial representation theory and polarity encoding theory to explain the SNARC effect in the processing of number and sequence stimuli. In all five experiments in the present study, stimuli (Experiments 1 and 4: four different Arabic numbers, Experiment 2: sequence stimuli, Experiment 3: ordinal sequences relevant to working memory, Experiment 5: Chinese characters without any implicit spatial information) were centrally presented. Participants were asked to respond to specific number or sequence stimuli by pressing the A, S, K, and L keys in consistent trials (or the L, K, S, and A keys in inconsistent trials). The results showed that (1) the SNARC effect occurred in the processing of number and sequence stimuli both when only one specific number was mapped to one specific key (Experiments 1, 2 and 3) and when two numbers were mapped to one specific key (Experiment 4). (2) There was not a SNARC effect when the numbers were replaced with Chinese characters without any implicit spatial information (Experiment 5). The results of these five experiments imply that the SNARC effect in the processing of magnitude stimuli, including numbers and sequences, originates from the spatial representation of stimuli, supporting spatial representation theory.
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Percepção Espacial , Humanos , Masculino , Feminino , Adulto Jovem , Percepção Espacial/fisiologia , Adulto , Memória de Curto Prazo/fisiologia , Tempo de Reação/fisiologia , Reconhecimento Visual de Modelos/fisiologiaRESUMO
The substantial expense associated with catalysts significantly hampers the progress of electrolytic water-based hydrogen production technology. There is an urgent need to find non-precious metal catalysts that are both cost-effective and highly efficient. Here, the porous Ni2P-FePx nanomaterials were successfully prepared by hydrothermal method, nickel foam as the base, iron nitrate solution as the caustic agent and iron source, and finally phosphating at low temperature. The obtained porous Ni2P-FePx nanosheets showed excellent catalytic activity under alkaline PH = 14, and an overpotential of merely 241 mV was required to achieve a current density of 50 mA cm-2. The morphology of the nanosheet can still be flawlessly presented on the screen after 50 h of working at high current density.
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BACKGROUND: The protozoan parasite Toxoplasma gondii encodes dozens of phosphatases, among which a plant-like phosphatase absent from mammalian genomes named PPKL, which is involved in regulating brassinosteroid signaling in Arabidopsis, was identified in the genome. Among the Apicomplexa parasites, T. gondii is an important and representative pathogen in humans and animals. PPKL was previously identified to modulate the apical integrity and morphology of the ookinetes and parasite motility and transmission in another important parasite, Plasmodium falciparum. However, the exact function of PPKL in the asexual stages of T. gondii remains unknown. METHODS: The plant auxin-inducible degron (AID) system was applied to dissect the phenotypes of PPKL in T. gondii. We first analyzed the phenotypes of the AID parasites at an induction time of 24 h, by staining of different organelles using their corresponding markers. These analyses were further conducted for the parasites grown in auxin for 6 and 12 h using a quantitative approach and for the type II strain ME49 of AID parasites. To further understand the phenotypes, the potential protein interactions were analyzed using a proximity biotin labeling approach. The essential role of PPKL in parasite replication was revealed. RESULTS: PPKL is localized in the apical region and nucleus and partially distributed in the cytoplasm of the parasite. The phenotyping of PPKL showed its essentiality for parasite replication and morphology. Further dissections demonstrate that PPKL is required for the maturation of daughter parasites in the mother cells, resulting in multiple nuclei in a single parasite. The phenotype of the daughter parasites and parasite morphology were observed in another type of T. gondii strain ME49. The substantial defect in parasite replication and morphology could be rescued by genetic complementation, thus supporting its essential function for PPKL in the formation of parasites. The protein interaction analysis showed the potential interaction of PPKL with diverse proteins, thus explaining the importance of PPKL in the parasite. CONCLUSIONS: PPKL plays an important role in the formation of daughter parasites, revealing its subtle involvement in the proper maturation of the daughter parasites during division. Our detailed analysis also demonstrated that depletion of PPKL resulted in elongated tubulin fibers in the parasites. The important roles in the parasites are potentially attributed to the protein interaction mediated by kelch domains on the protein. Taken together, these findings contribute to our understanding of a key phosphatase involved in parasite replication, suggesting the potential of this phosphatase as a pharmaceutic target.
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Parasitos , Toxoplasma , Humanos , Animais , Toxoplasma/fisiologia , Proteínas de Plantas/metabolismo , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Fosfoproteínas Fosfatases/metabolismo , Ácidos Indolacéticos/metabolismo , MamíferosRESUMO
This study investigated whether the interference between two tasks in dual-task processing stems from bottleneck limitations or insufficient cognitive resources due to resource sharing. Experiment 1 used tone discrimination as Task 1 and word or pseudoword classification as Task 2 to evaluate the effect of automatic versus controlled processing on dual-task interference under different SOA conditions. Experiment 2 reversed the task order. The results showed that dual-task interference persisted regardless of task type or order. Neither experiment found evidence that automatic tasks could eliminate interference. This suggests that resource limitations, rather than bottlenecks, may better explain dual-task costs. Specifically, when tasks compete for limited resources, the processing efficiency of both tasks is significantly reduced. Future research should explore how cognitive resources are dynamically allocated between tasks to better account for dual-task interference effects.
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Atenção , Tempo de Reação , Humanos , Masculino , Feminino , Adulto Jovem , Discriminação da Altura Tonal , Automatismo/psicologia , Reversão de Aprendizagem , Função Executiva/fisiologia , Semântica , AdultoRESUMO
Motivation: The human microbiome, found throughout various body parts, plays a crucial role in health dynamics and disease development. Recent research has highlighted microbiome disparities between patients with different diseases and healthy individuals, suggesting the microbiome's potential in recognizing health states. Traditionally, microbiome-based status classification relies on pre-trained machine learning (ML) models. However, most ML methods overlook microbial relationships, limiting model performance. Results: To address this gap, we propose PM-CNN (Phylogenetic Multi-path Convolutional Neural Network), a novel phylogeny-based neural network model for multi-status classification and disease detection using microbiome data. PM-CNN organizes microbes based on their phylogenetic relationships and extracts features using a multi-path convolutional neural network. An ensemble learning method then fuses these features to make accurate classification decisions. We applied PM-CNN to human microbiome data for status and disease detection, demonstrating its significant superiority over existing ML models. These results provide a robust foundation for microbiome-based state recognition and disease prediction in future research and applications. Availability and implementation: PM-CNN software is available at https://github.com/qdu-bioinfo/PM_CNN.
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Introduction: To explore the predictive effect of effort-reward imbalance on students' learning engagement and to elucidate the underlying mechanism, 796 students were selected for a survey. Methods: The participants were required to complete four scales: the Effort-reward Imbalance Scale, the Learning Engagement Scale, the Learned Helplessness Questionnaire, and the Perceived Social Support Scale. Results: (1) Students' effort-reward imbalance significantly and negatively predicts their learning engagement; (2) Learned helplessness serves as a mediator in the relationship between students' effort-reward imbalance and learning engagement; (3) Social support plays a moderating role in the association between effort-reward imbalance and learned helplessness. High levels of social support can buffer the impact of an effort-reward imbalance on learned helplessness, and the protective effect of social support is more obvious when the effort-reward imbalance is low. Discussion: The present study revealed how an effort-reward imbalance affects learning engagement among students through the dimensions of learned helplessness and perceived social support. The constructed model not only further clarifies the mechanism underlying the relationship between effort-reward imbalance and learning engagement but also holds significant implications for guiding students' education.
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Liver disease, a major health concern worldwide, is a serious and progressive disorder. Herein, we not only established a mouse model of DEN+CCl4-induced primary liver disease but also collected clinical human samples to investigate longitudinal alterations in the gut mycobiome. As liver disease advanced, gut integrity was disrupted, and the mycobiota was disturbed in the mouse models. The metabolites associated with hepatocellular carcinoma (HCC) differed from those associated with the cirrhotic phase as follows: levels of stercobilin and aflatoxin B1 dialcohol were reduced, while levels of triterpenoids, bafilomycin A1, and DHEA were increased in the HCC group. The abundance of the phylum Chytridiomycota increased as the chronic liver disease progressed and was then replaced by the phylum Ascomycota in HCC. Based on the results from clinical human samples, the genus Candida (Ascomycota) (in humans) and the genus Kazachstania (Ascomycota) (in mice) occupied a dominant position in the HCC group, while other fungi were depleted. The increased abundance of C. albicans and depletion of S. cerevisiae may be hallmarks of the progression of liver cirrhosis to early HCC. Moreover, the administration of C. albicans and S. cerevisiae in the LC-HCC progression could accelerate or retard the progression of HCC. Therefore, gut fungi have the potential to serve as a noninvasive clinical biomarker and even a treatment method.
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Biomarcadores , Carcinoma Hepatocelular , Progressão da Doença , Microbioma Gastrointestinal , Neoplasias Hepáticas , Animais , Humanos , Camundongos , Biomarcadores/metabolismo , Neoplasias Hepáticas/microbiologia , Neoplasias Hepáticas/metabolismo , Carcinoma Hepatocelular/microbiologia , Carcinoma Hepatocelular/metabolismo , Masculino , Cirrose Hepática/microbiologia , Cirrose Hepática/metabolismo , Modelos Animais de Doenças , Ascomicetos , Camundongos Endogâmicos C57BL , Hepatopatias/microbiologia , Hepatopatias/metabolismo , Fungos/classificação , Fungos/metabolismo , Candida albicans/metabolismoRESUMO
Artificial intelligence technology will be increasingly applied in the oil and gas industry. The rapid development of artificial intelligence technology can solve problems such as high environmental sensitivity and complex production processes in the oil and gas industry. In recent years, emerging technologies represented by artificial intelligence have developed rapidly, assisting petroleum enterprises in digital transformation and intelligent upgrading. This article elaborates on the development trend of artificial intelligence technology. Based on the business scenarios and characteristics of the oil and gas industry, the application status of artificial intelligence technology in domestic and foreign petroleum technology service enterprises was summarized and analyzed. The application scenarios of artificial intelligence technology in the fields of dynamic analysis of oil and gas reservoirs, intelligent historical fitting, numerical simulation proxy models, and production plan optimization were analyzed with emphasis. Based on the problems and challenges faced in the development process of oil and gas reservoirs, it is proposed that petroleum enterprises should attach importance to the "three modernizations" innovation of data standardization, oil and gas field intelligence, and platform collaboration, in order to achieve more refined intelligent analysis and management of oil and gas reservoirs and quickly develop more targeted oil and gas reservoir development plans to assist in the intelligent transformation of oil and gas reservoir development. On this basis, prospects for future artificial intelligence technology are proposed, pointing out that the development of artificial intelligence technology will be faster and faster, and there will be higher demand for artificial intelligence technology in the construction of digital oil and gas fields in China in the future. The research results have important reference value for the development of the oil and gas industry.
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We report a novel strategy for reversible modulation of the supramolecular chirality based on guest-facilitated heteroleptic assembly of helical anionocages. Two triple-stranded helical anionocages including a chiral cage 1 (A2 L1 3 ) and a crown ether functionalized achiral cage 2 (A2 L2 3 ) were synthesized by anion coordination of bis-monourea-based ligands and PhPO3 2- . Both cages exhibited favorable binding with tetraethylammonium TEA+ and cobaltocenium Cob+ (endo-guest, bound in the cavity). Additionally, cage 2 could reversibly release and recapture the guests through binding the exo-guest potassium ions (K+ ) in the crown ethers and subsequent removal of the K+ by [2,2,2]-cryptand. The circular dichroism (CD) spectrum of cage 1 was not significantly affected by guest encapsulation or mixing with the "empty" cage 2. However, in the presence of both cage 2 and an endo-guest/exo-guest, the Cotton effects were reversed at 391â nm and significantly enhanced at 310â nm. This observation was attributed to the guest-facilitated formation of heteroleptic cages that enabled effective chirality transfer from the chiral to the achiral ligands. The CD changes induced by K+ could be fully reversed by removing it with [2,2,2]-cryptand. Sequential addition and removal of K+ allowed reversible modulation of the chirality for at least 10â cycles without significant attenuation.
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A major goal of healthy aging is to prevent declining resilience and increasing frailty, which are associated with many chronic diseases and deterioration of stress response. Here, we propose a loss-or-gain survival model, represented by the ratio of cumulative stress span to life span, to quantify stress resilience at organismal level. As a proof of concept, this is demonstrated by reduced survival resilience in Caenorhabditis elegans exposed to exogenous oxidative stress induced by paraquat or with endogenous proteotoxic stress caused by polyglutamine or amyloid-ß aggregation. Based on this, we reveal that a hidden peptide ("cryptide")-AbaPep#07 (SETYELRK)-derived from abalone hemocyanin not only enhances survival resilience against paraquat-induced oxidative stress but also rescues proteotoxicity-mediated behavioral deficits in C. elegans, indicating its capacity against stress and neurodegeneration. Interestingly, AbaPep#07 is also found to increase cost-free longevity and age-related physical fitness in nematodes. We then demonstrate that AbaPep#07 can promote nuclear localization of SKN-1/Nrf, but not DAF-16/FOXO, transcription factor. In contrast to its effects in wild-type nematodes, AbaPep#07 cannot increase oxidative stress survival and physical motility in loss-of-function skn-1 mutant, suggesting an SKN-1/Nrf-dependent fashion of these effects. Further investigation reveals that AbaPep#07 can induce transcriptional activation of immune defense, lipid metabolism, and metabolic detoxification pathways, including many SKN-1/Nrf target genes. Together, our findings demonstrate that AbaPep#07 is able to boost stress resilience and reduce behavioral frailty via SKN-1/Nrf-governed transcriptional reprogramming, and provide an insight into the health-promoting potential of antioxidant cryptides as geroprotectors in aging and associated conditions.
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Proteínas de Caenorhabditis elegans , Fragilidade , Resiliência Psicológica , Animais , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Ligação a DNA/metabolismo , Longevidade/genética , Reprogramação Metabólica , Estresse Oxidativo/genética , Paraquat/toxicidade , Peptídeos/metabolismoRESUMO
Haemonchus contortus is a gastrointestinal parasite that adversely impacts small ruminants, resulting in a notable reduction in animal productivity. In the current investigation, we developed a nanovaccine by encapsulating the recombinant protein rHcES-15, sourced from the excretory/secretory products of H. contortus, within biodegradable poly (D, L-lactide-co-glycolide) (PLGA) nanoparticles (NPs). The development of this nanovaccine involved the formulation of PLGA NPs using a modified double emulsion solvent evaporation technique. Scanning electron microscopy (SEM)verified the successful encapsulation of rHcES-15 within PLGA NPs, exhibiting a size range of 350-400 nm. The encapsulation efficiency (EE) of the antigen in the nanovaccine was determined to be 72%. A total of forty experimental mice were allocated into five groups, with the nanovaccine administered on day 0 and the mice euthanized at the end of the 14-day trial. The stimulation index (SI) from the mice subjected to the nanovaccine indicated heightened lymphocyte proliferation (*** p < 0.001) and a noteworthy increase in anti-inflammatory cytokines (IL-4, IL-10, and IL-17). Additionally, the percentages of T-cells (CD4+, CD8+) and dendritic cell phenotypes (CD83+, CD86+) were significantly elevated (** p < 0.01, *** p < 0.001) in mice inoculated with the nanovaccine compared to control groups and the rHcES-15 group. Correspondingly, higher levels of antigen-specific serum immunoglobulins (IgG1, IgG2a, IgM) were observed in response to the nanovaccine in comparison to both the antigenic (rHcES-15) and control groups (* p < 0.05, ** p < 0.01). In conclusion, the data strongly supports the proposal that the encapsulation of rHcES-15 within PLGA NPs effectively triggers immune cells in vivo, ultimately enhancing the antigen-specific adaptive immune responses against H. contortus. This finding underscores the promising potential of the nanovaccine, justifying further investigations to definitively ascertain its efficacy.
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BACKGROUND: The protozoan parasite Toxoplasma gondii encodes a dozen Rab proteins, which are parts of the small GTPase superfamily and regulate intracellular membrane trafficking. Our previous study showed that depletion of Rab1B caused severe defects regarding parasite growth and morphological structure, yet early defects of endocytic trafficking and vesicle sorting to the rhoptry in T. gondii are not expected to have a strong effect. To understand this discrepancy, we performed an integrated analysis at the level of transcriptomics and metabolomics. METHODS: In the study, tetracycline-inducible TATi/Ty-Rab1B parasite line treated with ATc at three different time points (0, 18 and 24 h) was used. We first observed the morphological changes caused by Rab1B depletion via transmission electron technology. Then, high-throughput transcriptome along with non-targeted metabolomics were performed to analyze the RNA expression and metabolite changes in the Rab1B-depleted parasite. The essential nature of Rab1B in the parasite was revealed by the integrated omics approach. RESULTS: Transmission electron micrographs showed a strong disorganization of endo-membranes in the Rab1B-depleted parasites. Our deep analysis of transcriptome and metabolome identified 2181 and 2374 differentially expressed genes (DEGs) and 30 and 83 differentially expressed metabolites (DEMs) at 18 and 24 h of induction in the tetracycline-inducible parasite line, respectively. These DEGs included key genes associated with crucial organelles that contain the rhoptry, microneme, endoplasmic reticulum and Golgi apparatus. The analysis of qRT-PCR verified some of the key DEGs identified by RNA-Seq, supporting that the key vesicular regulator Rab1B was involved in biogenesis of multiple parasite organelles. Functional enrichment analyses revealed pathways related to central carbon metabolisms and lipid metabolisms, such as the TCA cycle, glycerophospholipid metabolism and fatty acid biosynthesis and elongation. Further correlation analysis of the major DEMs and DEGs supported the role of Rab1B in biogenesis of fatty acids (e.g. myrisoleic acid and oleic acid) (R > 0.95 and P < 0.05), which was consistent with the scavenging role in biotin via the endocytic process. CONCLUSIONS: Rab1B played an important role in parasite growth and morphology, which was supported by the replication assay and transmission electron microscopy observation. Our multi-omics analyses provided detailed insights into the overall impact on the parasite upon depletion of the protein. These analyses reinforced the role of Rab1B in the endocytic process, which has an impact on fatty acid biogenesis and the TCA cycle. Taken together, these findings contribute to our understanding of a key vesicular regulator, Rab1B, on parasite metabolism and morphological formation in T. gondii.
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Parasitos , Toxoplasma , Animais , Toxoplasma/genética , Toxoplasma/metabolismo , Transcriptoma , Perfilação da Expressão Gênica , Parasitos/genética , Ácidos Graxos/metabolismo , Tetraciclinas/metabolismo , Proteínas de Protozoários/genéticaRESUMO
Gut microbiota are closely related to lipopolysaccharide (LPS)-induced acute lung injury (ALI). Akkermansia muciniphila (A. muciniphila) maintains the intestinal barrier function and regulates the balance of reduced glutathione/oxidized glutathione. However, it may be useful as a treatment strategy for LPS-induced lung injury. Our study aimed to explore whether A. muciniphila could improve lung injury by affecting the gut microbiota. The administration of A. muciniphila effectively attenuated lung injury tissue damage and significantly decreased the oxidative stress and inflammatory reaction induced by LPS, with lower levels of myeloperoxidase (MDA), enhanced superoxide dismutase (SOD) activity, decreased pro-inflammatory cytokine levels, and reduced macrophage and neutrophil infiltration. Moreover, A. muciniphila maintained the intestinal barrier function, reshaped the disordered microbial community, and promoted the secretion of short-chain fatty acids (SCFAs). A. muciniphila significantly downregulated the expression of TLR2, MyD88 and NF-kappa B (P < 0.05). Butyrate supplementation demonstrated a significant improvement in the inflammatory response (P < 0.05) and mitigation of histopathological damage in mice with ALI, thereby restoring the intestinal butyric acid concentration. In conclusion, our findings indicate that A. muciniphila inhibits the accumulation of inflammatory cytokines and attenuates the activation of the TLR2/Myd88/NF-κB pathway due to exerting anti-inflammatory effects through butyrate. This study provides an experimental foundation for the potential application of A. muciniphila and butyrate in the prevention and treatment of ALI.
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Lesão Pulmonar Aguda , Microbioma Gastrointestinal , Animais , Camundongos , Lipopolissacarídeos/efeitos adversos , Fator 88 de Diferenciação Mieloide/metabolismo , Receptor 2 Toll-Like/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , NF-kappa B/genética , NF-kappa B/metabolismo , Citocinas/metabolismo , Ácidos Graxos Voláteis/farmacologia , Ácido Butírico/farmacologia , PulmãoRESUMO
Previous studies of illusory conjunction (IC) mainly focused on alphabetic languages, while researchers have poorly understood the IC mechanism of Chinese words as an ideographic writing system. In the present study, we aimed to investigate the dynamic changes of IC effects for Chinese words under different stimulus exposure times and spatial arrangements. We conducted two experiments with a 3 (Condition: IC, non-IC-same, non-IC-different) × 3 (Exposure time: 38 ms, 88 ms, 138 ms) within-subject design. The results showed that in the IC condition, the two characters recombined regardless of exposure time as long as they could form an orthographically correct new word, demonstrating the universality of IC. In non-IC conditions, increasing exposure time decreased response time and significantly reduced error rate, indicating that attention played a decisive role in perceptual processing. The spatial arrangement had no impact on IC production. These findings support the feature confirmation account model, suggesting that attention modulates IC through top-down feature confirmation processes. These data expand an understanding of IC mechanisms, validate the role of attention in feature confirmation, and elucidate the inimitable mechanism of the Chinese word IC influenced by both low-level visual processing and high-level cognitive control.
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Ilusões , Humanos , Percepção Visual/fisiologia , Idioma , Atenção/fisiologia , Tempo de Reação , Reconhecimento Visual de ModelosRESUMO
Perovskite nanocrystals for light-emitting diodes are often synthesized by uncontrollable metathesis reactions, suffering from low product yield, nonuniform growth, and poor stability. Herein, by controlling the nucleation kinetics with high dissociation constant (Ka or Kb) acids or bases, homogenous one-route nucleation of perovskite nanocrystals is achieved as the cluster intermediates are eliminated. The stable, shape uniform, and narrow size distribution green nanocrystals are synthesized. The perovskite nanocrystal film exhibites excellent stability in 80% humidity air with only a 10% photoluminescence intensity drop after 16 h. Efficient and stable electroluminescence is demonstrated with an FWHM of 16 nm at 517 nm. The green devices shows a peak EQE of 24.13% with a lifetime T50 of 54 min at 10 000 cd m-2 .
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Glia and neurons face different challenges in aging and may engage different mechanisms to maintain their morphology and functionality. Here, we report that adult-onset downregulation of a Drosophila gene CG32529/GLAD led to shortened lifespan and age-dependent brain degeneration. This regulation exhibited cell type and subtype-specificity, involving mainly surface glia (comprising the BBB) and cortex glia (wrapping neuronal soma) in flies. In accordance, pan-glial knockdown of GLAD disrupted BBB integrity and the glial meshwork. GLAD expression in fly heads decreased with age, and the RNA-seq analysis revealed that the most affected transcriptional changes by RNAi-GLAD were associated with upregulation of immune-related genes. Furthermore, we conducted a series of lifespan rescue experiments and the results indicated that the profound upregulation of immune and related pathways was not the consequence but cause of the degenerative phenotypes of the RNAi-GLAD flies. Finally, we showed that GLAD encoded a heterochromatin-associating protein that bound to the promoters of an array of immune-related genes and kept them silenced during the cell cycle. Together, our findings demonstrate a previously unappreciated role of heterochromatic gene silencing in repressing immunity in fly glia, which is required for maintaining BBB and brain integrity as well as normal lifespan.