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1.
Immunity ; 56(7): 1515-1532.e9, 2023 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-37437538

RESUMO

The nervous system is critical for intestinal homeostasis and function, but questions remain regarding its impact on gut immune defense. By screening the major neurotransmitters of C. elegans, we found that γ-aminobutyric acid (GABA) deficiency enhanced susceptibility to pathogenic Pseudomonas aeruginosa PA14 infection. GABAergic signaling between enteric neurons and intestinal smooth muscle promoted gut defense in a PMK-1/p38-dependent, but IIS/DAF-16- and DBL-1/TGF-ß-independent, pathway. Transcriptomic profiling revealed that the neuropeptide, FLP-6, acted downstream of enteric GABAergic signaling. Further data determined that FLP-6 was expressed and secreted by intestinal smooth muscle cells and functioned as a paracrine molecule on the intestinal epithelium. FLP-6 suppressed the transcription factors ZIP-10 and KLF-1 that worked in parallel and converged to the PMK-1/p38 pathway in the intestinal epithelia for innate immunity and gut defense. Collectively, these findings uncover an enteric neuron-muscle-epithelium axis that may be evolutionarily conserved in higher organisms.


Assuntos
Caenorhabditis elegans , Neurônios , Animais , Músculo Liso , Transdução de Sinais , Imunidade Inata
2.
Nature ; 595(7868): 596-599, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34234347

RESUMO

Biomolecular condensates have emerged as an important subcellular organizing principle1. Replication of many viruses, including human respiratory syncytial virus (RSV), occurs in virus-induced compartments called inclusion bodies (IBs) or viroplasm2,3. IBs of negative-strand RNA viruses were recently shown to be biomolecular condensates that form through phase separation4,5. Here we report that the steroidal alkaloid cyclopamine and its chemical analogue A3E inhibit RSV replication by disorganizing and hardening IB condensates. The actions of cyclopamine and A3E were blocked by a point mutation in the RSV transcription factor M2-1. IB disorganization occurred within minutes, which suggests that these molecules directly act on the liquid properties of the IBs. A3E and cyclopamine inhibit RSV in the lungs of infected mice and are condensate-targeting drug-like small molecules that have in vivo activity. Our data show that condensate-hardening drugs may enable the pharmacological modulation of not only many previously undruggable targets in viral replication but also transcription factors at cancer-driving super-enhancers6.


Assuntos
Condensados Biomoleculares/virologia , Vírus Sincicial Respiratório Humano/efeitos dos fármacos , Alcaloides de Veratrum/farmacologia , Replicação Viral/efeitos dos fármacos , Animais , Antivirais/farmacologia , Linhagem Celular , Feminino , Humanos , Corpos de Inclusão , Pulmão/virologia , Camundongos , Camundongos Endogâmicos BALB C , Vírus Sincicial Respiratório Humano/fisiologia , Fatores de Transcrição , Proteínas Virais
3.
Fish Shellfish Immunol ; 145: 109322, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38128679

RESUMO

Nocardia seriolae is a severe bacterial pathogen that has seriously affected the development of aquaculture industry. Largemouth bass (Micropterus salmoides) is a commercially significant freshwater fish that suffers a variety of environmental threats, including bacterial pathogens. However, the immune responses and metabolic alterations of largemouth bass to N. seriolae infection remain largely unclear. We discovered that N. seriolae caused pathological alterations in largemouth bass and shifted the transcript of immune-related and apoptotic genes in head kidney after infection. To answer the aforementioned question, a combined transcriptome and metabolome analysis was employed to explore the alterations in genes, metabolites, and metabolic pathways in largemouth bass following bacterial infection. A total of 3579 genes and 1929 metabolites are significant differentially changed in the head kidney post infection. In response to N. seriolae infection, host modifies the PI3K-Akt signaling pathway, TCA cycle, glycolysis, and amino acid metabolism. The integrated analysis of transcriptome and metabolome suggested that with the arginine metabolism pathway as the core, multiple biomarkers (arg gene, arginine) are involved in the antibacterial and immune functions of largemouth bass. Thus, we hypothesized that arginine plays a crucial role in the immune responses of largemouth bass against N. seriolae infection, and increasing arginine levels suitably is beneficial for the host against bacterial infection. Our results shed light on the regulatory mechanism of largemouth bass resistance to N. seriolae infection and contributed to the development of more effective N. seriolae resistance strategies.


Assuntos
Infecções Bacterianas , Bass , Nocardiose , Nocardia , Animais , Transcriptoma , Fosfatidilinositol 3-Quinases/genética , Metaboloma , Arginina
4.
Proc Natl Acad Sci U S A ; 118(20)2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-33972423

RESUMO

GABAergic neurotransmission constitutes a major inhibitory signaling mechanism that plays crucial roles in central nervous system physiology and immune cell immunomodulation. However, its roles in innate immunity remain unclear. Here, we report that deficiency in the GABAergic neuromuscular junctions (NMJs) of Caenorhabditis elegans results in enhanced resistance to pathogens, whereas pathogen infection enhances the strength of GABAergic transmission. GABAergic synapses control innate immunity in a manner dependent on the FOXO/DAF-16 but not the p38/PMK-1 pathway. Our data reveal that the insulin-like peptide INS-31 level was dramatically decreased in the GABAergic NMJ GABAAR-deficient unc-49 mutant compared with wild-type animals. C. elegans with ins-31 knockdown or loss of function exhibited enhanced resistance to Pseudomonas aeruginosa PA14 exposure. INS-31 may act downstream of GABAergic NMJs and in body wall muscle to control intestinal innate immunity in a cell-nonautonomous manner. Our results reveal a signaling axis of synapse-muscular insulin-intestinal innate immunity in vivo.


Assuntos
Proteínas de Caenorhabditis elegans/imunologia , Caenorhabditis elegans/imunologia , Imunidade Inata/imunologia , Insulina/imunologia , Intestinos/imunologia , Receptores de GABA-A/imunologia , Sinapses/imunologia , Adulto , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/microbiologia , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/fisiologia , Neurônios GABAérgicos/imunologia , Neurônios GABAérgicos/metabolismo , Neurônios GABAérgicos/microbiologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata/genética , Insulina/metabolismo , Intestinos/microbiologia , Intestinos/fisiologia , Mutação , Junção Neuromuscular/imunologia , Junção Neuromuscular/microbiologia , Junção Neuromuscular/fisiologia , Pseudomonas aeruginosa/imunologia , Pseudomonas aeruginosa/fisiologia , Receptores de GABA-A/genética , Receptores de GABA-A/fisiologia , Transdução de Sinais/imunologia , Sinapses/microbiologia , Sinapses/fisiologia , Transmissão Sináptica/genética , Transmissão Sináptica/imunologia , Transmissão Sináptica/fisiologia
5.
J Environ Manage ; 352: 120053, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38211429

RESUMO

The combination of chemical phosphorus (P) inactivation and submerged macrophyte transplantation has been widely used in lake restoration as it yields stronger effects than when applying either method alone. However, the dose effect of chemical materials on P inactivation when used in combination with submerged macrophytes and the influences of the chemicals used on the submerged macrophytes growth remain largely unknown. In this study, we investigated P inactivation in both the water column and the sediment, and the responses of submerged macrophytes to Lanthanum modified bentonite (LMB) in an outdoor mesocosm experiment where Vallisneria denseserrulata were transplanted into all mesocosms and LMB was added at four dosage levels, respectively: control (LMB-free), low dosage (570 g m-2), middle dosage (1140 g m-2), and high dosage (2280 g m-2). The results showed that the combination of LMB dosage and V. denseserrulata reduced TP in the water column by 32%-38% compared to V. denseserrulata alone, while no significant difference was observed among the three LMB treatments. Porewater soluble reactive P, two-dimensional diffusive gradient in thin films (DGT)-labile P concentrations, and P transformation in the 0-1 cm sediment layer exhibited similar trends along the LMB dosage gradient. Besides, LMB inhibited plant growth and reduced the uptake of mineral elements (i.e., calcium, manganese, iron, and magnesium) in a dosage-dependent manner with LMB. LMB may reduce plant growth by creating a P deficiency risk for new ramets and by interfering with the uptake of mineral elements. Considering both the dose effect of LMB on P inactivation and negative effect on macrophyte growth, we suggest a "small dosage, frequent application" method for LMB application to be used in lake restoration aiming to recover submerged macrophytes and clear water conditions.


Assuntos
Fósforo , Poluentes Químicos da Água , Bentonita , Lantânio , Poluentes Químicos da Água/análise , Lagos , Água
6.
Neuroimage ; 281: 120369, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37690592

RESUMO

Individuals exhibit considerable variability in their capacity to learn and retain new information, including novel vocabulary. Prior research has established the importance of vigilance and electroencephalogram (EEG) alpha rhythm in the learning process. However, the interplay between vigilant attention, EEG alpha oscillations, and an individual's word learning ability (WLA) remains elusive. To address this knowledge gap, here we conducted two experiments with a total of 140 young and middle-aged adults who underwent resting EEG recordings prior to completing a paired-associate word learning task and a psychomotor vigilance test (PVT). The results of both experiments consistently revealed significant positive correlations between WLA and resting EEG alpha oscillations in the occipital and frontal regions. Furthermore, the association between resting EEG alpha oscillations and WLA was mediated by vigilant attention, as measured by the PVT. These findings provide compelling evidence supporting the crucial role of vigilant attention in linking EEG alpha oscillations to an individual's learning ability.

7.
Opt Express ; 31(19): 30495-30504, 2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37710590

RESUMO

We have designed a metal-semiconductor-metal (MSM) solar-blind ultraviolet (UV) photodetector (PD) by utilizing Al0.55Ga0.45N/Al0.4Ga0.6N/Al0.65Ga0.35N heterostructures. The interdigital Ni/Au metal stack is deposited on the Al0.55Ga0.45N layer to form Schottky contacts. The AlGaN hetero-epilayers with varying Al content contribute to the formation of a two-dimensional electron gas (2DEG) conduction channel and the enhancement of the built-in electric field in the Al0.4Ga0.6N absorption layer. This strong electric field facilitates the efficient separation of photogenerated electron-hole pairs. Consequently, the fabricated PD exhibits an ultra-low dark current of 1.6 × 10-11 A and a broad spectral response ranging from 220 to 280 nm, with a peak responsivity of 14.08 A/W at -20 V. Besides, the PD demonstrates an ultrahigh detectivity of 2.28 × 1013 Jones at -5 V. Furthermore, to investigate the underlying physical mechanism of the designed solar-blind UV PD, we have conducted comprehensive two-dimensional device simulations.

8.
Nanotechnology ; 34(50)2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37748477

RESUMO

Two-dimensional (2D) p-n heterojunctions have attracted great attention due to their outstanding properties in electronic and optoelectronic devices, especially in photodetectors. Various types of heterojunctions have been constituted by mechanical exfoliation and stacking. However, achieving controlled growth of heterojunction structures remains a tremendous challenge. Here, we employed a two-step KI-assisted confined-space chemical vapor deposition method to prepare multilayer WSe2/SnS2p-n heterojunctions. Optical characterization results revealed that the prepared WSe2/SnS2vertical heterostructures have clear interfaces as well as vertical heterostructures. The electrical and optoelectronic properties were investigated by constructing the corresponding heterojunction devices, which exhibited good rectification characteristics and obtained a high detectivity of 7.85 × 1012Jones and a photoresponse of 227.3 A W-1under visible light irradiation, as well as a fast rise/fall time of 166/440µs. These remarkable performances are likely attributed to the ultra-low dark current generated in the depletion region at the junction and the high direct tunneling current during illumination. This work demonstrates the value of multilayer WSe2/SnS2heterojunctions for applications in high-performance photodetectors.

9.
Environ Res ; 231(Pt 1): 115958, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37086880

RESUMO

The shift in focus towards biofuels has led to the attention towards fourth-generation fuels, particularly microalgae, due to its high oil productivity and simple cultivation processes. The current study aimed to examine the effects of spirulina microalgae blends in a naturally aspirated diesel engine by testing two blend percentages (15% and 30%) and incorporating Fe2O3 nanoparticles (75 ppm). A series of test conducted in a single-cylinder engine with an optimum compression ratio of 17.5. The fuels tested include 100% diesel (D0), diesel with Fe2O3 nanoparticles (DF), diesel with 15% microalgae blends (B15), diesel with 15% microalgae blends and Fe2O3 nanoparticles (B15F), diesel with 30% microalgae blends (B30), and diesel with 30% microalgae blends and Fe2O3 nanoparticles (B30F). The results showed that the addition of microalgae blends led to a marginal increase in engine performance, while the addition of Fe2O3 nanoparticles led to a significant increase in brake thermal efficiency and decreased fuel consumption. The emissions rate was also lower compared to diesel, but the addition of Fe2O3 nanoparticles increased the oxygen content in the fuel, thereby improving the combustion rates. By ensuring the complete combustion the formation of CO2, HC and smoke intensity was also found to be significantly lower compared to diesel fuel. On the contrary, NOx increased due to the cylinder temperatures. This research highlights the potential of using microalgae as a sustainable source of biofuel, and the positive effects of adding Fe2O3 nanoparticles to enhance the fuel's efficiency.


Assuntos
Gases de Efeito Estufa , Microalgas , Spirulina , Emissões de Veículos/análise , Gasolina/análise , Biocombustíveis/análise , Monóxido de Carbono/análise
10.
Int J Mol Sci ; 24(8)2023 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-37108358

RESUMO

A physiological disease of the pineapple fruit called pineapple translucency causes the pulp to become water-soaked, which affects the fruit's taste, flavor, shelf life, and integrity. In the present study, we analyzed seven pineapple varieties, of which three were watery and four were non-watery. There were no apparent macronutritional (K, P, or N) differences in their pulp, but the non-watery pineapple varieties had higher dry matter and soluble sugar content. The metabolomic analysis found 641 metabolites and revealed differential expression of alkaloids, phenolic acids, nucleotide derivatives, lipids, and other metabolites among the seven species. Transcriptome analysis and further KEGG enrichment showed downregulation of 'flavonoid biosynthesis' pathways, differential expression of metabolic pathways, secondary metabolites biosynthesis, plant-pathogen interaction, and plant hormone signal transduction. We believe this study will provide critical molecular data supporting a deeper understanding of pineapple translucency formation and greatly benefit future research on this commercially important crop.


Assuntos
Ananas , Ananas/genética , Ananas/metabolismo , Frutas/genética , Frutas/metabolismo , Redes e Vias Metabólicas , Perfilação da Expressão Gênica , Metaboloma , Transcriptoma
11.
J Fish Biol ; 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38009685

RESUMO

Assessing the nutritional status and identifying major causes of mortality in larvae experiencing varying degrees of starvation are crucial for establishing appropriate feeding protocols and enhancing the welfare of hatchery-reared fish. The black rockfish Sebastes schlegelii is an important species in aquaculture and stock enhancement efforts in China, Japan, and Korea. This study aimed to identify optimal diagnostic morphometric indicators of starvation in newly hatched (0-6 days post-hatch, DPH) and postlarval stages (27-37 DPH) of this valuable fish species through histological analyses. Our findings revealed that certain morphometric parameters, including body length, the ratios of eye diameter to head height, body height to body length, and abdomen height to body height, exhibit sensitivity to starvation during both larval and postlarval stages. Particularly, the ratios of body height to body length and abdomen height to body height emerged as the most sensitive morphometric indicators of starvation. Histological examinations of the digestive system revealed rapid alterations in the morphology of hepatic parenchymal cells, accompanied by a significant decrease in the number of lipid cells in the liver during episodes of food deprivation. Starvation induced cellular degeneration in the digestive organs, manifested by reduced heights of epithelial cells and mucosal layers in the intestine, oesophagus, and stomach, along with degeneration and separation of muscle fibers. Among these variables, the height of the intestinal submucosa and muscle layer emerged as the most sensitive indicators reflecting nutritional conditions in newly hatched larvae. In contrast, the height of intestinal striated borders and mucosal folds proved to be the most sensitive indicators in the postlarval stage. Furthermore, the height of intestinal epithelial cells and the number of lipid vacuoles in enterocytes exhibited high sensitivity to food deprivation in both newly hatched larvae and postlarvae. These findings underscore the varying resilience of fish to starvation during different developmental phases and highlight the utility of morphological sensitivity characteristics as reliable diagnostic indices for assessing nutritional status in relation to starvation or suboptimal feeding during the early developmental stages of black rockfish in hatchery-reared processes.

12.
Int J Mol Sci ; 24(22)2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-38003574

RESUMO

Pineapple color yellowing and quality promotion gradually manifest as pineapple fruit ripening progresses. To understand the molecular mechanism underlying yellowing in pineapples during ripening, coupled with alterations in fruit quality, comprehensive metabolome and transcriptome investigations were carried out. These investigations were conducted using pulp samples collected at three distinct stages of maturity: young fruit (YF), mature fruit (MF), and fully mature fruit (FMF). This study revealed a noteworthy increase in the levels of total phenols and flavones, coupled with a concurrent decline in lignin and total acid contents as the fruit transitioned from YF to FMF. Furthermore, the analysis yielded 167 differentially accumulated metabolites (DAMs) and 2194 differentially expressed genes (DEGs). Integration analysis based on DAMs and DEGs revealed that the biosynthesis of plant secondary metabolites, particularly the flavonol, flavonoid, and phenypropanoid pathways, plays a pivotal role in fruit yellowing. Additionally, RNA-seq analysis showed that structural genes, such as FLS, FNS, F3H, DFR, ANR, and GST, in the flavonoid biosynthetic pathway were upregulated, whereas the COMT, CCR, and CAD genes involved in lignin metabolism were downregulated as fruit ripening progressed. APX as well as PPO, and ACO genes related to the organic acid accumulations were upregulated and downregulated, respectively. Importantly, a comprehensive regulatory network encompassing genes that contribute to the metabolism of flavones, flavonols, lignin, and organic acids was proposed. This network sheds light on the intricate processes that underlie fruit yellowing and quality alterations. These findings enhance our understanding of the regulatory pathways governing pineapple ripening and offer valuable scientific insight into the molecular breeding of pineapples.


Assuntos
Ananas , Flavonas , Frutas/genética , Frutas/metabolismo , Transcriptoma , Ananas/metabolismo , Lignina/metabolismo , Metabolômica , Flavonoides/metabolismo , Flavonas/metabolismo , Regulação da Expressão Gênica de Plantas
13.
Int J Mol Sci ; 24(24)2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38138962

RESUMO

Exogenous ethylene is commonly utilized to initiate flower induction in pineapple (Ananas comosus (L.) Merr.). However, the molecular mechanisms and metabolic changes involved are not well understood. In this study, we explored the genetic network and metabolic shifts in the 'Comte de Paris' pineapple variety during ethylene-induced flowering. This was achieved through an integrative analysis of metabolome and transcriptome profiles at vegetative shoot apexes (0 d after ethephon treatment named BL_0d), the stage of bract primordia (8 d after ethephon treatment named BL_8d), stage of flower primordia (18 d after ethephon treatment named BL_18d), and the stage of stopped floret differentiation (34 d after ethephon treatment named BL_34d). We isolated and identified 804 metabolites in the pineapple shoot apex and inflorescence, categorized into 24 classes. Notably, 29, 31, and 46 metabolites showed significant changes from BL_0d to BL_8d, BL_8d to BL_18d, and BL_18d to BL_34d, respectively. A marked decrease in indole was observed, suggesting its role as a characteristic metabolite during flower induction. Transcriptomic analysis revealed 956, 1768, and 4483 differentially expressed genes (DEGs) for BL_0d vs. BL_8d, BL_8d vs. BL_18d, and BL_18d vs. BL_34d, respectively. These DEGs were significantly enriched in carbohydrate metabolism and hormone signaling pathways, indicating their potential involvement in flower induction. Integrating metabolomic and transcriptomic data, we identified several candidate genes, such as Agamous-Like9 (AGL9), Ethylene Insensitive 3-like (ETIL3), Apetala2 (AP2), AP2-like ethylene-responsive transcription factor ANT (ANT), and Sucrose synthase 2 (SS2), that play potentially crucial roles in ethylene-induced flower induction in pineapple. We also established a regulatory network for pineapple flower induction, correlating metabolites and DEGs, based on the Arabidopsis thaliana pathway as a reference. Overall, our findings offer a deeper understanding of the metabolomic and molecular mechanisms driving pineapple flowering.


Assuntos
Ananas , Transcriptoma , Ananas/genética , Ananas/metabolismo , Redes Reguladoras de Genes , Etilenos/metabolismo , Flores/genética , Flores/metabolismo , Metaboloma , Regulação da Expressão Gênica de Plantas
14.
J Environ Manage ; 330: 117108, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36584472

RESUMO

Seagrass systems are in decline, mainly due to anthropogenic pressures and ongoing climate change. Implementing seagrass protection and restoration measures requires accurate assessment of suitable habitats. Commonly, such assessments have been performed using single-algorithm habitat suitability models, nearly always based on low environmental resolution information and short-term species data series. Here we address eelgrass (Zoostera marina) meadows' large-scale decline (>80%) in Shandong province (Yellow Sea, China) by developing an ensemble habitat model (EHM) to inform eelgrass conservation and restoration strategies in the Swan Lake (SL). For this, we applied a weighted EHM derived from ten single-algorithm models including profile, regression, classification, and machine learning methods to generate a high-resolution habitat suitability map. The EHM was constructed based on the predictive performances of each model, by combining a series of present-absent eelgrass datasets from recent years coupled with oceanographic and sediment data. The model was cross-validated with independent historical datasets, and a final habitat suitability map for conservation and restoration was generated. Our EHM scheme outperformed all single models in terms of habitat suitability, scoring ∼0.95 for both true statistic skill (TSS) and area under the curve (AUC) performance criteria. Machine learning methods outperformed profile, regression and classification methods. Regarding model explanatory variables, overall, topographic characteristics such as depth (DEP) and seafloor slope (SSL) are the most significant factors determining the distribution of eelgrass. The EHM predicted that the overlapping area was almost 90% of the current eelgrass habitat. Using results from our EHM, a LOESS regression model for the relationship of the habitat suitability to both the biomass and density of Z. marina outperformed better than the classic Ordinary Least Squares regression model. The EHM is a promising tool for supporting eelgrass protection and restoration areas in temperate lagoons as data availability improves.


Assuntos
Ecossistema , Zosteraceae , Biomassa , Mudança Climática , China
15.
Fish Shellfish Immunol ; 122: 170-180, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35150828

RESUMO

Glutaminolysis has been proved to play an irreplaceable role in vertebrate immunity, including effects on cytokine production, bacterial killing, and redox homeostasis maintenance. Our previous metabolomics analysis indicated that glutaminolysis metabolic substrates glutamine (Gln) and metabolites glutamate (Glu) were significantly lower in Skin ulceration syndrome (SUS)-diseased Apostichopus japonicus. To further delineate the role of glutaminolysis, we assayed the levels of Gln and Glu. We found that their contents in coelomocytes were decreased, accompanied by an increase in glutathione (GSH) in pathogen-challenged Apostichopus japonicus. Consistently, the mRNA transcripts of three key genes in glutaminolysis (AjASCT2, AjGOT, and AjGCS) were significantly induced. Moreover, the increased MDA and NADPH/NADP + levels in response to pathogen infection indicated that oxidative stress occurs during the immune response. The metabolic regulator AMPKß could regulate glutaminolysis in vertebrates by inducing cells to take up extracellular Gln. To explore the underlying regulatory mechanism behind glutaminolysis that occurred in coelomocytes, the full-length cDNA of AMPKß was identified from A. japonicus (designated as AjAMPKß). AjAMPKß expression was significantly induced in the coelomocytes after pathogen challenge, which was consistent with the expression of key genes of glutaminolysis. A functional assay indicated that AjAMPKß silencing by siRNA transfection could increase the levels of Gln and Glu and depress the production of GSH. Moreover, the expression of glutaminolysis-related genes was significantly inhibited, and the reduction of redox homeostasis indexes (MDA and NADPH/NADP+) was also observed. Contrastingly, AjAMPKß overexpression promoted redox homeostasis balance. Intracellular ROS is mostly responsible for breaking redox homeostasis and leading to oxidative stress, contributing to cell fate changes in immune cells. Exogenous Gln and GSH treatments could significantly reduce ROS level while the AjAMPKß silencing induced the level of ROS and accelerated the necrosis rate. All these results collectively revealed that AjAMPKß could modulate cellular redox homeostasis by affecting the glutaminolysis in A. japonicus.


Assuntos
Stichopus , Vibrio , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Homeostase , Imunidade Inata/genética , Oxirredução , Vibrio/fisiologia
16.
Phys Chem Chem Phys ; 24(11): 6616-6626, 2022 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-35234236

RESUMO

The high carrier mobility, appropriate band gap and good environmental stability of two-dimensional (2D) MoSi2N4 enable it to be an appropriate channel material for transistors with excellent performance. Therefore, we predict the performance of double-gate (DG) metal-oxide-semiconductor field-effect transistors (MOSFETs) based on monolayer (ML) MoSi2N4 by ab initio quantum-transport calculations. The results show that the on-state current of the p-type device is remarkable when the gate length is greater than 4 nm, which can meet the high performance requirements of the International Technology Roadmap for Semiconductors (ITRS), 2013 version. Moreover, the gate length can be reduced to 3 nm when an underlap (UL) structure is employed in the MOSFET, and the sub-threshold swing, intrinsic delay time and power consumption also perform well. The calculation results reveal that ML MoSi2N4 will be a promising alternative for transistor channel materials in the post-silicon era.

17.
Dig Dis Sci ; 67(3): 880-891, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-33721161

RESUMO

BACKGROUND: Proteasome subunit alpha type 7 (PSMA7) shows a carcinogenic effect on various human malignancies, but its role and regulatory mechanism in gastric carcinoma (GC) remain unclear. AIMS: This study aimed to explore the role and mechanism of PSMA7 in GC. METHODS: In this study, PSMA7 expressions in GC cells and tissues were detected, and relationships between PSMA7 and clinicopathological features were explored. Then, PSMA7 levels in human GC cells were intervened, and changes in cell biological behavior were observed in vitro and vivo. Key proteins and downstream factors of MAPK signaling pathway were detected after PSMA7 intervention. RESULTS: PSMA7 was upregulated in GC tissues and cell lines. PSMA7 overexpression was significantly associated with poor pTNM, cTNM stage, and high HP infection. PSMA7 can promote proliferation, invasion, and metastasis of GC cells in vitro and vivo. Furthermore, PSMA7 expression affected the phosphorylation level of JNK, P38, ERK and the expressions of their downstream factors Ap-1, c-myc, P53. CONCLUSION: PSMA7 can promote GC proliferation, invasion, and metastasis through MAPK signaling pathway in GC cells.


Assuntos
Complexo de Endopeptidases do Proteassoma/metabolismo , Neoplasias Gástricas , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , Sistema de Sinalização das MAP Quinases , Transdução de Sinais , Neoplasias Gástricas/patologia
18.
Dis Esophagus ; 35(4)2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-34750620

RESUMO

BACKGROUND: Heterotopic gastric mucosa in the upper esophagus (HGMUE) is reported to be related to gastroesophageal reflux disease (GERD). This study investigated the prevalence of GERD and the use of salivary pepsin to diagnose gastroesophageal reflux, especially proximal reflux, in HGMUE patients. METHODS: One hundred and fifty-three HGMUE patients and 50 healthy volunteers were studied. All subjects took a reflux symptom index questionnaire (RSI); underwent endoscopy, barium esophagogram, high-resolution manometry (HRM), and 24-hour multichannel intraluminal impedance-pH-metry (MII-pH); and salivary pepsin test. RESULTS: Ninety-five (62.1%) HGMUE patients but no control subjects were diagnosed with GERD. The salivary pepsin concentration, RSI score, DeMeester score, acid exposure time (AET), total reflux episodes, proximal acidic reflux episodes, and proximal weakly acidic reflux episodes were significantly higher in the HGMUE group than in the control group (P < 0.05). The salivary pepsin test showed a sensitivity of 85.9% and specificity of 56.9% for diagnosing GERD using the optimal cut-off value of 75 ng/mL. One hundred and seven (69.9%) and 46 (30.1%) HGMUE patients were categorized as pepsin (+) and pepsin (-), respectively when 75 ng/mL was used as a cut-off value. Male sex, RSI, AET, and proximal acid reflux episodes were positive predictive factors for the occurrence of pepsin (+) in HGMUE patients. CONCLUSIONS: GERD, especially GERD with proximal acid reflux and related symptoms, was common in HGMUE patients. The salivary pepsin test could be an additional useful test for testing reflux in HGMUE patients, but it will not replace the MII-pH.


Assuntos
Refluxo Gastroesofágico , Pepsina A , Humanos , Masculino , Impedância Elétrica , Endoscopia Gastrointestinal , Monitoramento do pH Esofágico , Mucosa Gástrica , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/diagnóstico , Azia
19.
J Ultrasound Med ; 41(9): 2317-2322, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34927280

RESUMO

OBJECTIVES: To identify the ultrasonographic characteristics of primary squamous cell carcinoma of the thyroid (PSCCT), and to assess the value of the 2015 American Thyroid Association (ATA) guideline and 2017 American College of Radiology (ACR) Thyroid Imaging, Reporting and Data System (TI-RADS) in the evaluation of this disease. METHODS: Eight patients with 9 PSCCTs over a 20-year study period were enrolled. Ultrasonic characteristics including nodule echogenicity, composition, shape, margin, calcification, size, vascularity, and cervical lymphadenopathy were reviewed. All nodules were then evaluated by 2017 ACR TI-RADS and 2015 ATA guidelines. RESULTS: The average size of PSCCTs was 3.87 ± 1.41 cm. All PSCCTs were hypoechoic or very hypoechoic, solid nodules with intranodular vascularity. The average resistive index (RI) was 0.84 ± 0.18. Near half of PSCCTs (44.4%) demonstrated extrathyroidal extension. Taller-than-wide signs and cervical lymphadenopathy were observed in 33.3% of PSCCTs, and microcalcification was observed in 11.1% of them. All PSCCTs were classified as high suspicion patterns by 2015 ATA and recommended for fine-needle aspiration (FNA). Six PSCCTs (66.7%) were classified as grade 5 by 2017 ACR TI-RADS, while the remaining were grade 4. 88.9% of PSCCTs were recommended for FNA based on 2017 ACR TI-RADS. CONCLUSION: PSCCT has certain ultrasonic features, including relatively large, hypoechoic, or very hypoechoic solid nodules with intranodular vascularity and extrathyroidal extension. Both 2015 ATA and 2017 ACR TI-RADS could identify PSCCT as suspicious for malignancy.


Assuntos
Carcinoma de Células Escamosas , Linfadenopatia , Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Carcinoma de Células Escamosas/diagnóstico por imagem , Humanos , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/patologia , Ultrassom , Ultrassonografia/métodos , Estados Unidos
20.
Genomics ; 113(2): 474-489, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33359830

RESUMO

The APETALA2/ethylene-responsive factor (AP2/ERF) has important roles in regulating developmental processes and hormone signaling transduction in plants. Pineapple demonstrates a special sensitivity to ethylene, and AP2/ERFs may contribute to this distinct sensitivity of pineapples to ethylene. However, little information is available on the AP2/ERF of pineapple. In this study, 97 AP2/ERF family members were identified from the pineapple genome. The AcAP2/ERF superfamily could be further divided into five subfamilies, and different subfamily existed functional divergence in multifarious biological processes. ERF and RAV subfamily genes might play important roles in the process of ethylene response of pineapple; ERF and DREB subfamily genes had particular functions in the floral organ development. This study is the first to provide detailed information on the features of AP2/ERFs in pineapple, provide new insights into the potential functional roles of the AP2/ERF superfamily members, and will facilitate a better understanding of the molecular mechanism of flower in pineapple.


Assuntos
Ananas/genética , Flores/genética , Proteínas de Plantas/genética , Fatores de Transcrição/genética , Ananas/crescimento & desenvolvimento , Etilenos/metabolismo , Etilenos/farmacologia , Flores/efeitos dos fármacos , Flores/crescimento & desenvolvimento , Regulação da Expressão Gênica no Desenvolvimento , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo
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