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Autism spectrum disorder (ASD) is a major neurodevelopmental disorder affecting 1 in 36 children in the United States. While neurons have been the focus of understanding ASD, an altered neuro-immune response in the brain may be closely associated with ASD, and a neuro-immune interaction could play a role in the disease progression. As the resident immune cells of the brain, microglia regulate brain development and homeostasis via core functions including phagocytosis of synapses. While ASD has been traditionally considered a polygenic disorder, recent large-scale human genetic studies have identified SCN2A deficiency as a leading monogenic cause of ASD and intellectual disability. We generated a Scn2a-deficient mouse model, which displays major behavioral and neuronal phenotypes. However, the role of microglia in this disease model is unknown. Here, we reported that Scn2a-deficient mice have impaired learning and memory, accompanied by reduced synaptic transmission and lower spine density in neurons of the hippocampus. Microglia in Scn2a-deficient mice are partially activated, exerting excessive phagocytic pruning of post-synapses related to the complement C3 cascades during selective developmental stages. The ablation of microglia using PLX3397 partially restores synaptic transmission and spine density. To extend our findings from rodents to human cells, we established a microglia-incorporated human cerebral organoid model carrying an SCN2A protein-truncating mutation identified in children with ASD. We found that human microglia display increased elimination of post-synapse in cerebral organoids carrying the SCN2A mutation. Our study establishes a key role of microglia in multi-species autism-associated models of SCN2A deficiency from mouse to human cells.
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BACKGROUND: α-Ketoglutarate (AKG) plays a pivotal role in mitigating inflammation and enhancing intestinal health. OBJECTIVES: This study aimed to investigate whether AKG could protect against lipopolysaccharide (LPS)-induced intestinal injury by alleviating disorders in mitochondria-associated endoplasmic reticulum (MAM) membranes, dysfunctional mitochondrial dynamics, and endoplasmic reticulum (ER) stress in a piglet model. METHODS: Twenty-four piglets were subjected to a 2 × 2 factorial design with dietary factors (basal diet or 1% AKG diet) and LPS treatment (LPS or saline). After 21 d of consuming either the basal diet or AKG diet, piglets received injections of LPS or saline. The experiment was divided into 4 treatment groups [control (CON) group: basal diet + saline; LPS group: basal diet +LPS; AKG group: AKG diet + saline; and AKG_LPS group: AKG + LPS], each consisting of 6 piglets. RESULTS: The results demonstrated that compared with the CON group, AKG enhanced jejunal morphology, antioxidant capacity, and the messenger RNA and protein expression of tight junction proteins. Moreover, it has shown a reduction in serum diamine oxidase activity and D-lactic acid content in piglets. In addition, fewer disorders in the ER-mitochondrial system were reflected by AKG, as evidenced by AKG regulating the expression of key molecules of mitochondrial dynamics (mitochondrial calcium uniporter, optic atrophy 1, fission 1, and dynamin-related protein 1), ER stress [activating transcription factor (ATF) 4, ATF 6, CCAAT/enhancer binding protein homologous protein, eukaryotic initiation factor 2α, glucose-regulated protein (GRP) 78, and protein kinase R-like ER kinase], and MAM membranes [mitofusin (Mfn)-1, Mfn-2, GRP 75, and voltage-dependent anion channel-1]. CONCLUSIONS: Dietary AKG can prevent mitochondrial dynamic dysfunction, ER stress, and MAM membrane disorder, ultimately alleviating LPS-induced intestinal damage in piglets.
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Estrés del Retículo Endoplásmico , Retículo Endoplásmico , Ácidos Cetoglutáricos , Lipopolisacáridos , Mitocondrias , Animales , Lipopolisacáridos/toxicidad , Ácidos Cetoglutáricos/farmacología , Porcinos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Retículo Endoplásmico/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Escherichia coli , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Dieta/veterinaria , Intestinos/efectos de los fármacosRESUMEN
BACKGROUND: Glutamine (Gln) has an important effect on the growth performance and immune function of piglets. However, the effect of Gln on intestinal immunity in piglets through modulating the signaling pathways of the helper T cells 17 (Th17)/regulatory T cells (Treg) immune response has not been reported. OBJECTIVE: This study aimed to determine the effect of Gln on piglet growth performance and immune stress response and its mechanism in piglets. METHODS: Twenty-four weaned piglets were randomly assigned to 4 treatments with 6 replicates each, using a 2 × 2 factorial arrangement: diet (basal diet or 1% Gln diet) and immunological challenge [saline or lipopolysaccharide (LPS)]. After 21 d, half of the piglets on the basal diet and 1% Gln diet received the intraperitoneal injection of LPS and the other half received the same volume of normal saline. RESULTS: The results showed that Gln increased average daily feed intake and average daily weight gain in comparison with the control group (P < 0.05). Dietary Gln increased the villus height, villus height-to-crypt depth ratio, and the abundance of Bacteroidetes, Lactobacillus sp., and Ruminococcus sp. while reducing the abundance of Firmicutes, Clostridium sensu stricto 1 sp., and Terrisporobacter sp. (P < 0.05). Furthermore, Gln increased the concentration of short-chain fatty acids in the colon and the expression of genes of interleukin (IL)-10, transforming growth factor-beta-1, forkhead box P3 while downregulating the expression of genes of IL-6, IL-8, IL-1ß, tumor necrosis factor-α, IL-17A, IL-21, signal transducer and activator of transcription 3, and rar-related orphan receptor c in ileum (P < 0.05). Correlation analysis demonstrated a strong association between colonic microbiota, short-chain fatty acids, and ileal inflammatory cytokines. CONCLUSIONS: These results suggest that dietary Gln could improve growth performance and attenuate LPS-challenged intestinal inflammation by modulating microbiota and the Th17/Treg immune response signaling pathway in piglets.
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Suplementos Dietéticos , Microbioma Gastrointestinal , Glutamina , Lipopolisacáridos , Transducción de Señal , Linfocitos T Reguladores , Células Th17 , Animales , Glutamina/farmacología , Glutamina/administración & dosificación , Porcinos , Microbioma Gastrointestinal/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Alimentación Animal/análisis , Dieta/veterinariaRESUMEN
Stroke, the second-largest cause of death and the leading cause of disability globally, presents significant challenges in terms of prognosis and treatment. Identifying reliable prognosis biomarkers and treatment targets is crucial to address these challenges. Circular RNA (circRNA) has emerged as a promising research biomarkers and therapeutic targets because of its tissue specificity and conservation. However, the potential role of circRNA in stroke prognosis and treatment remains largely unexplored. This review briefly elucidate the mechanism underlying circRNA's involvement in stroke pathophysiology. Additionally, this review summarizes the impact of circRNA on different forms of strokes, including ischemic stroke and hemorrhagic stroke. And, this article discusses the positive effects of circRNA on promoting cerebrovascular repair and regeneration, maintaining the integrity of the blood-brain barrier (BBB), and reducing neuronal injury and immune inflammatory response. In conclusion, the significance of circRNA as a potential prognostic biomarker and a viable therapeutic target was underscored.
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Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , ARN Circular/genética , Accidente Cerebrovascular/genética , Accidente Cerebrovascular/terapia , Biomarcadores , Barrera HematoencefálicaRESUMEN
The current standard second-line treatment is immune checkpoint inhibitors monotherapy for nonsmall cell lung cancer (NSCLC) patients. The objective of this phase 2 study was to evaluate the efficacy and safety of nivolumab plus docetaxel compared with nivolumab monotherapy for second-line therapy in immunotherapy-naive patients with advanced NSCLC. Progression-free survival (PFS) was the primary endpoint of this phase 2 study. Patients were randomized to receive nivolumab plus docetaxel or nivolumab monotherapy. From July 2019 to June 2022, a total of 22 patients were recruited, with significantly longer median PFS observed in the nivolumab plus docetaxel group (4.0 months) compared to the nivolumab group (2.0 months), P â =â 0.0019. The study was closed in June 2022 due to slow recruitment. The objective response rate was 10.0% [95% confidence interval (CI), 0-28.6] in the nivolumab group and 25% (95% CI, 0.5-49.5) in the nivolumab + docetaxel group ( P â =â 0.346). Disease control was significantly higher in the nivolumab plus docetaxel arm (40.0% versus 83.3%, P â =â 0.035). There was also an improvement in overall survival (OS) in the nivolumab + docetaxel arm, but this was not statistically significant (10.0 months versus 7.2 months, P â =â 0.129). The addition of docetaxel to nivolumab was well-tolerated, with adverse events more common in the combination group. Despite the small sample size, the results suggest that the addition of docetaxel to nivolumab may be a promising treatment option for NSCLC patients progressing on platinum-based chemotherapy, with trends towards improved OS observed.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Docetaxel/uso terapéutico , Nivolumab/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológico , Taxoides/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
INTRODUCTION: The effectiveness of thromboelastography (TEG)-guided antiplatelet therapy in patients with ischemic cerebrocardiovascular diseases is not well-established. This systematic review evaluates the efficacy and safety of TEG-guided antiplatelet therapy compared to standard treatment in patients with ischemic cerebrocardiovascular diseases. METHODS: Randomized controlled trials (RCTs) and observational studies comparing TEG-guided antiplatelet therapy with standard therapy in patients suffering from ischemic stroke (IS) or coronary artery disease (CAD) were identified. The primary efficacy measure was a composite of ischemic and hemorrhagic events. Secondary efficacy measures included any ischemic events, while safety was assessed by the occurrence of bleeding events. RESULTS: Ten studies involving 4 RCTs and 6 observational studies with a total of 1,678 patients were included. When considering a composite of ischemic and hemorrhagic events in RCTs, a significant reduction was observed in IS or CAD patients under TEG-guided therapy compared to standard therapy (OR: 0.45, 95% CI: 0.27-0.75, p = 0.002). After pooling RCTs and observational studies together, compared to standard antiplatelet therapy, TEG-guided therapy significantly reduced the risk of a composite of ischemic and hemorrhagic events (OR: 0.26, 95% CI: 0.19-0.37; p < 0.00001), ischemic events (OR: 0.28, 95% CI: 0.19-0.41; p < 0.00001), and bleeding events (OR: 0.31, 95% CI: 0.16-0.62; p = 0.0009) in patients with IS or CAD. CONCLUSION: TEG-guided antiplatelet therapy appears to be both effective and safe for patients with IS or CAD. These findings support the use of TEG testing to tailor antiplatelet therapy in individuals with ischemic cerebrocardiovascular diseases.
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OBJECTIVES: Large biological variation hinders application of patient-based real-time quality control (PBRTQC). The effect of analyte ratios on the ability of PBRTQC to improve error detection was investigated. METHODS: Four single analyte-ratio pairs (alanine aminotransferase [ALT] vs. ALT to aspartate aminotransferase ratio [RALT]; creatinine [Cr] vs. Cr to cystatin C ratio [RCr]; lactate dehydrogenase [LDH] vs. LDH to hydroxybutyrate dehydrogenase ratio [RLDH]; total bilirubin [TB] vs. TB to direct bilirubin ratio [RTB]) were chosen for comparison. Various procedures, including four conventional algorithms (moving average [MA], moving median [MM], exponentially weighted moving average [EWMA] and moving standard deviation [MSD]) were assessed. A new algorithm that monitors the number of defect reports per analytical run (NDR) was also evaluated. RESULTS: When a single analyte and calculated ratio used the same PBRTQC parameters, fewer samples were needed to detect systematic errors (SE) by taking ratios (p<0.05). Application of ratios in MA, MM and EWMA significantly enhanced their ability to detect SE. The influence of ratio on random error (RE) detection depended upon the analytes and PBRTQC parameters, as consistent advantage was not demonstrated. The NDR method performed well when appropriate parameters were used, but was only effective for unilateral SE. Rearrangement of sample order led to a significant deterioration of conventional algorithms' performance, while NDR remained almost unaffected. CONCLUSIONS: For analytes with large variation and poor PBRTQC performance, using ratios as PBRTQC indexes may significantly improve performance and achieve better anti-interference ability, providing a new class of monitoring indicators for PBRTQC.
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Algoritmos , Bilirrubina , Humanos , Control de Calidad , Recolección de DatosRESUMEN
Filamentous fungi are prolific producers of bioactive natural products and play a vital role in drug discovery. Yet, their potential cannot be fully exploited since many biosynthetic genes are silent or cryptic under laboratory culture conditions. Several strategies have been applied to activate these genes, with heterologous expression as one of the most promising approaches. However, successful expression and identification of new products are often hindered by host-dependent factors, such as low gene targeting efficiencies, a high metabolite background, or a lack of selection markers. To overcome these challenges, we have constructed a Penicillium crustosum expression host in a pyrG deficient strain by combining the split-marker strategy and CRISPR-Cas9 technology. Deletion of ligD and pcribo improved gene targeting efficiencies and enabled the use of an additional selection marker in P. crustosum. Furthermore, we reduced the secondary metabolite background by inactivation of two highly expressed gene clusters and abolished the formation of the reactive ortho-quinone methide. Finally, we replaced the P. crustosum pigment gene pcr4401 with the commonly used Aspergillus nidulans wA expression site for convenient use of constructs originally designed for A. nidulans in our P. crustosum host strain. As proof of concept, we successfully expressed a single polyketide synthase gene and an entire gene cluster at the P. crustosum wA locus. Resulting transformants were easily detected by their albino phenotype. With this study, we provide a highly efficient platform for heterologous expression of fungal genes. KEY POINTS: Construction of a highly efficient Penicillium crustosum heterologous expression host Reduction of secondary metabolite background by genetic dereplication strategy Integration of wA site to provide an alternative host besides Aspergillus nidulans.
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Sistemas CRISPR-Cas , Penicillium , Metabolismo Secundario , Penicillium/genética , Penicillium/metabolismo , Metabolismo Secundario/genética , Aspergillus nidulans/genética , Aspergillus nidulans/metabolismo , Sintasas Poliquetidas/genética , Sintasas Poliquetidas/metabolismo , Familia de Multigenes , Marcación de Gen/métodos , Regulación Fúngica de la Expresión Génica , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Vías Biosintéticas/genética , Ingeniería Metabólica/métodos , Expresión GénicaRESUMEN
BACKGROUND Patients with urolithiasis often undergo transurethral ureteroscopic holmium laser lithotripsy, a procedure that can be affected by perioperative thermal management. This study examines the impact of compound thermal insulation management on patient recovery and comfort during transurethral ureteroscopic holmium laser lithotripsy. MATERIAL AND METHODS In this study, 551 patients who underwent transurethral ureteroscopic holmium laser lithotripsy from April 2019 to December 2022 were randomly assigned to either an observation group (n=276) or control group (n=275). Both groups received routine surgical care, with the observation group additionally receiving compound thermal insulation management. We recorded and compared perioperative body temperature changes, anesthetic resuscitation indicators (bispectral index recovery time, extubation time, fully awake time, Postanesthesia Care Unit retention time), comfort level (General Comfort Questionnaire), and quality of life (Nottingham Health Profile). We also compared the incidence of complications. RESULTS There was no significant difference in body temperature between groups at the start surgery. However, the observation group showed significantly higher temperatures during and at the end of surgery. Anesthetic resuscitation indicators were significantly better in the observation group. Both groups showed improved comfort and quality of life after surgery, with more significant improvements in the observation group. The observation group also had a lower incidence of complications, such as hypothermia and rigor. CONCLUSIONS Compound thermal insulation management during transurethral ureteroscopic holmium laser lithotripsy improved perioperative temperature maintenance, accelerated postoperative recovery, reduced complication rates, and enhanced patient comfort and quality of life.
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Anestésicos , Láseres de Estado Sólido , Litotripsia por Láser , Litotricia , Humanos , Litotripsia por Láser/métodos , Holmio , Calidad de Vida , Ureteroscopía/métodosRESUMEN
BACKGROUND: The relationship between serum vitamin D status and urinary leakage (UL) among middle-aged females needs to be further studied. The aim of this study was to evaluate the association of serum 25-hydroxyvitamin D [25(OH)D] concentrations with UL among American females ages 45 years and over. METHODS: Seven cycles of the National Health and Nutrition Examination Survey (NHANES) with self-report UL data, were used. A total of 9525 women aged 45 years and older were enrolled in this study. Univariate and multivariate logistic regression models and the smooth curve fitting were utilized to analyze the association between clinical UL and serum 25-hydroxyvitamin D [25(OH)D] concentrations. RESULTS: A non-linear relationship between serum 25(OH)D concentrations and clinical ULwas observed. When serum 25(OH)D concentration was higher than the inflection point 63.5 nmol/L, a positive correlation was observed between serum 25(OH)D concentrations and clinical UL ([OR]: 1.007, 95%CI: 1.005-1.009, P < 0.01). However, when serum 25(OH)D concentration was below the inflection point 63.5 nmol/L, a negative correlation was observed between serum 25(OH)D concentrations and clinical UL ([OR]: 0.993, 95%CI: 0.989-0.996, P < 0.01). CONCLUSIONS: The association between serum vitamin D and the risk of UL exhibited a U-shaped pattern among US middle-aged females, with an inflection point occurring at a serum 25(OH)D concentration of 63.5 nmol/L.
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Calcifediol , Incontinencia Urinaria , Vitamina D , Adulto , Femenino , Humanos , Persona de Mediana Edad , Estudios Transversales , Encuestas Nutricionales , Estados Unidos , Vitamina D/análogos & derivados , Vitamina D/sangreRESUMEN
Edible bird's nest (EBN), a most highly priced and valuable foodstuff, contains high percentage of proteins and carbohydrates. However, proteins adhering to these carbohydrates make the EBN hard and tough, which need to be boiled as the bird's nest soup to make the Chinese cuisine. To overcome the hard and tough texture of EBN and improve the digestion degrees, the present study screened and identified a probiotic strain Bacillus amyloliquefaciens YZW02 from 5-year stored EBN sample completely solubilizing EBN for the first time. The 24-h B. amyloliquefaciens fermented EBN contained 20.30-21.48 mg/mL of the soluble protein contents with a recovery rate of 98-100%, DPPH radical scavenging rate of 84.76% and ABTS radical scavenging capacity of 41.05%. The mixed fermentation of B. amyloliquefaciens YZW02 and Bacillus natto BN1 were further applied to improve the low-MW peptide percentages and antioxidant activities. The mixed-fermentation of B. natto BN1 with 4-h cultured B. amyloliquefaciens YZW02 had the lowest percentage (82.23%) of >12-kDa proteins/peptides and highest percentages of 3-12 kDa, 1-3 kDa and 0.1-1 kDa peptides of 8.6% ± 0.08, 7.57% ± 0.09, 1.77% ± 0.05 and 0.73% ± 0.05, with the highest DPPH, ABTS and â¢OH scavenging capacity of 90.23%, 46.45% and 49.12%, respectively. These findings would provide an efficient strategy for improving the solubility and antioxidant activities of EBNs.
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Antioxidantes , Bacillus amyloliquefaciens , Aves , Fermentación , Probióticos , Solubilidad , Bacillus amyloliquefaciens/química , Bacillus amyloliquefaciens/metabolismo , Antioxidantes/química , Antioxidantes/metabolismo , Animales , Probióticos/química , Probióticos/metabolismo , Aves/microbiologíaRESUMEN
Electromyography-based gesture recognition has become a challenging problem in the decoding of fine hand movements. Recent research has focused on improving the accuracy of gesture recognition by increasing the complexity of network models. However, training a complex model necessitates a significant amount of data, thereby escalating both user burden and computational costs. Moreover, owing to the considerable variability of surface electromyography (sEMG) signals across different users, conventional machine learning approaches reliant on a single feature fail to meet the demand for precise gesture recognition tailored to individual users. Therefore, to solve the problems of large computational cost and poor cross-user pattern recognition performance, we propose a feature selection method that combines mutual information, principal component analysis and the Pearson correlation coefficient (MPP). This method can filter out the optimal subset of features that match a specific user while combining with an SVM classifier to accurately and efficiently recognize the user's gesture movements. To validate the effectiveness of the above method, we designed an experiment including five gesture actions. The experimental results show that compared to the classification accuracy obtained using a single feature, we achieved an improvement of about 5% with the optimally selected feature as the input to any of the classifiers. This study provides an effective guarantee for user-specific fine hand movement decoding based on sEMG signals.
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Electromiografía , Antebrazo , Gestos , Mano , Reconocimiento de Normas Patrones Automatizadas , Humanos , Electromiografía/métodos , Mano/fisiología , Antebrazo/fisiología , Reconocimiento de Normas Patrones Automatizadas/métodos , Masculino , Adulto , Análisis de Componente Principal , Femenino , Algoritmos , Movimiento/fisiología , Adulto Joven , Máquina de Vectores de Soporte , Aprendizaje AutomáticoRESUMEN
Modular control of the muscle, which is called muscle synergy, simplifies control of the movement by the central nervous system. The purpose of this study was to explore the synergy in both the frequency and movement domains based on the non-negative Tucker decomposition (NTD) method. Surface electromyography (sEMG) data of 8 upper limb muscles in 10 healthy subjects under wrist flexion (WF) and wrist extension (WE) were recorded. NTD was selected for exploring the multi-domain muscle synergy from the sEMG data. The results showed two synergistic flexor pairs, Palmaris longus-Flexor Digitorum Superficialis (PL-FDS) and Extensor Carpi Radialis-Flexor Carpi Radialis (ECR-FCR), in the WF stage. Their spectral components are mainly in the respective bands 0-20 Hz and 25-50 Hz. And the spectral components of two extensor pairs, Extensor Digitorum-Extensor Carpi Ulnar (ED-ECU) and Extensor Carpi Radialis-Brachioradialis (ECR-B), are mainly in the respective bands 0-20 Hz and 7-45 Hz in the WE stage. Additionally, further analysis showed that the Biceps Brachii (BB) muscle was a shared muscle synergy module of the WE and WF stage, while the flexor muscles FCR, PL and FDS were the specific synergy modules of the WF stage, and the extensor muscles ED, ECU, ECR and B were the specific synergy modules of the WE stage. This study showed that NTD is a meaningful method to explore the multi-domain synergistic characteristics of multi-channel sEMG signals. The results can help us to better understand the frequency features of muscle synergy and shared and specific synergies, and expand the study perspective related to motor control in the nervous system.
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Electromiografía , Movimiento , Músculo Esquelético , Muñeca , Humanos , Músculo Esquelético/fisiología , Masculino , Muñeca/fisiología , Adulto , Movimiento/fisiología , Femenino , Adulto Joven , Procesamiento de Señales Asistido por ComputadorRESUMEN
Selenium (Se)-rich Cyclocarya paliurus is popular for its bioactive components, and exogenous Se fortification is the most effective means of enrichment. However, the effects of exogenous Se fortification on the nutritional quality of C. paliurus are not well known. To investigate the nutrient contents and antioxidant properties of C. paliurus following Se treatment, we used a foliar spray to apply Se in two forms-chemical nano-Se (Che-SeNPs) and sodium selenite (Na2SeO3). Sampling began 10 days after spraying and was conducted every 5 days until day 30. The Se, secondary metabolite, malondialdehyde contents, antioxidant enzyme activity, Se speciation, and Se-metabolism-related gene expression patterns were analyzed in the collected samples. Exogenous Se enhancement effectively increased the Se content of leaves, reaching a maximum on days 10 and 15 of sampling, while the contents of flavonoids, triterpenes, and polyphenols increased significantly during the same period. In addition, the application of Se significantly enhanced total antioxidant activity, especially the activity of the antioxidant enzyme peroxidase. Furthermore, a positive correlation between the alleviation of lipid peroxidation and Se content was observed, while methylselenocysteine formation was an effective means of alleviating Se stress. Finally, Na2SeO3 exhibited better absorption and conversion efficiency than Che-SeNPs in C. paliurus.
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Antioxidantes , Hojas de la Planta , Selenio , Selenito de Sodio , Antioxidantes/metabolismo , Selenio/metabolismo , Selenio/análisis , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Selenito de Sodio/farmacología , Selenito de Sodio/metabolismo , Juglandaceae/química , Flavonoides/metabolismo , Flavonoides/análisis , Peroxidación de Lípido/efectos de los fármacos , Malondialdehído/metabolismo , Polifenoles/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Triterpenos/metabolismoRESUMEN
BACKGROUND: This study aimed to evaluate the effects of N-carbamylglutamate (NCG) on piglets' growth performance and immune response, and to unravel the mechanisms of such effects. In a 2 × 2 factorial design including diet (with or without NCG) and immunological challenge (saline or lipopolysaccharide (LPS)), 24 piglets were randomly distributed into four groups. After being fed a basic diet or a NCG-supplemented diet for 21 days, piglets were administered LPS or saline intraperitoneally. RESULTS: The results showed that NCG increased the average daily gain and average daily feed intake, and the feed conversion ratio of piglets, and alleviated the adverse effects of LPS stimulation on intestinal morphology. At the phylum level, NCG reversed the increase in the abundance of Firmicutes and the reduction in that of Actinomycete caused by LPS stimulation. At the genus level, NCG increased the abundance of Lactobacillus, Blautia, norank_Butyricicoccaceae, Subdoligranulum, and Ruminococcus_gauvreauii_group, and LPS decreased the abundance of Escherichia-Shigella and Ruminococcus_gauvreauii_group. The short-chain fatty acid content was increased by NCG, but LPS reduced its content. N-Carbamylglutamate also inhibited significantly the LPS-induced increase in the relative expression of signal transducer and activator of transcription (STAT) 3, related orphan receptor (RAR) c, and pro-inflammatory cytokines, and the decrease in the relative expression of STAT5, forkhead box P3, IL-10 and transforming growth factor beta 1 mRNA. A significant correlation was found between intestinal microbiota and inflammatory cytokines and short-chain fatty acids. CONCLUSION: N-Carbamylglutamate can improve piglets' growth performance. It can also attenuate LPS-induced intestinal inflammation by modulating microbiota and Th17/Treg balance-related immune signaling pathways. © 2023 Society of Chemical Industry.
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Microbioma Gastrointestinal , Glutamatos , Lipopolisacáridos , Animales , Citocinas , Suplementos Dietéticos/análisis , Porcinos , Linfocitos T ReguladoresRESUMEN
BACKGROUND: Distillers dried grains with solubles (DDGS) are rich in nutrition, and they are potential protein feed raw material. However, the existence of cellulose, hemicellulose and lignin hinders animals' digestion and absorption of DDGS. Making full use of unconventional feed resources such as DDGS can alleviate the shortage of feed resources to a certain extent. This research investigated the effects of twin-screw extrusion on the macromolecular composition, physical and chemical properties, surface structure and in vitro protein digestibility (IVPD) of DDGS. RESULTS: The findings showed that extrusion puffing significantly increased the protein solubility, bulk density, water holding capacity, and swelling capacity, while significantly decreased hemicellulose and crude protein content, particle size and zeta potential of DDGS. The structure damage of DDGS induced by the extrusion was characterized by scanning electron microscopy (SEM), Fourier-transform infrared (FITR) spectroscopy and X-ray diffraction (XRD) analysis. Interestingly, no random coil was observed in the analysis of the secondary structure, and extrusion promoted the transformation of α-helix and ß-turn to ß-sheet, which led to significant increases in protein solubility and IVPD of DDGS (P < 0.05). Additionally, correlation analysis revealed that IVPD and PS had a positive relationship. CONCLUSION: Extrusion puffing was an ideal pretreatment method for DDGS modification to improve in vitro protein digestibility. © 2023 Society of Chemical Industry.
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Digestión , Zea mays , Animales , Zea mays/química , Alimentación Animal/análisis , Dieta , Estructura Secundaria de Proteína , Fenómenos Fisiológicos Nutricionales de los Animales , Grano Comestible/químicaRESUMEN
Given the escalating global crisis in feed protein availability, Jatropha curcas L. cake has attracted significant interest as a viable alternative protein source in animal feed. This experiment was conducted to investigate the effects of fermented Jatropha curcas L. cake (FJCC) as a protein feed in the diet of pigs. A total of 96 growing pigs with an average weight of 27.60 ± 1.59 kg were divided into three dietary groups with varying FJCC inclusion levels (0, 2.5, and 5%) for a 28 d trial. Results showed that the diet with 5% FJCC (FJCC5) demonstrated significant improvements in average daily gain (p = 0.009), feed-to-gain ratio (p = 0.036), nutrient digestibility, and intestinal morphology. Furthermore, the FJCC5 diet resulted in a decrease in pH values in different gut sections (jejunum p = 0.045, cecum p = 0.001, colon p = 0.012), and favorably altered the profile of short-chain fatty acids (SCFAs) with increased butyric acid content (p = 0.005) and total SCFAs (p = 0.019). Additionally, this diet notably decreased IL-6 levels in the jejunum (p = 0.008) and colon (=0.047), significantly reduced IL-1 levels in the hypothalamus (p < 0.001), and lowered IL-1, IL-6, and IL-10 levels in plasma (p < 0.05). Microbiota and metabolite profile analysis revealed an elevated abundance of beneficial microbes (p < 0.05) and key metabolites such as 4-aminobutyric acid (GABA) (p = 0.003) and serotonin (5-HT) (p = 0.022), linked to neuroactive ligand-receptor interaction. Moreover, FJCC5 significantly boosted circulating neurotransmitter levels of 5-HT (p = 0.006) and GABA (p = 0.002) in plasma and hypothalamus, with corresponding increases in precursor amino acids (p < 0.05). These findings suggest that FJCC, particularly at a 5% inclusion rate, can be an effective substitute for traditional protein sources like soybean meal, offering benefits beyond growth enhancement to gut health and potentially impacting the gut-brain axis. This research underscores FJCC's potential as a valuable component in sustainable animal nutrition strategies.
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Staphylococcus aureus (S. aureus), one of the most prevalent bacteria found in atopic dermatitis lesions, can induce ongoing infections and inflammation by downregulating the expression of host defence peptides in the skin. In addition, the emergence of the 'superbug' Methicillin-resistant S. aureus (MRSA) has made the treatment of these infections more challenging. Antimicrobial peptides (AMPs), due to their potent antimicrobial activity, limited evidence of resistance development, and potential immunomodulatory effects, have gained increasing attention as potential therapeutic agents for atopic dermatitis. In this study, we report a novel AMP, brevinin-1E-OG9, isolated from the skin secretions of Odorrana grahami, which shows potent antibacterial activity, especially against S. aureus. Based on the characteristics of the 'Rana Box', we designed a set of brevinin-1E-OG9 analogues to explore its structure-activity relationship. Brevinin-1E-OG9c-De-NH2 exhibited the most potent antimicrobial efficacy in both in vitro and ex vivo studies and attenuated inflammatory responses induced by lipoteichoic acid and heat-killed microbes. As a result, brevinin-1E-OG9c-De-NH2 might represent a promising candidate for the treatment of S. aureus skin infections.
Asunto(s)
Antiinfecciosos , Dermatitis Atópica , Staphylococcus aureus Resistente a Meticilina , Animales , Staphylococcus aureus , Secuencia de Aminoácidos , Péptidos Antimicrobianos , Dermatitis Atópica/tratamiento farmacológico , Antiinfecciosos/farmacología , Anuros , Antibacterianos/farmacología , Ranidae/metabolismo , Piel/metabolismo , Pruebas de Sensibilidad MicrobianaRESUMEN
This study investigated the effect of taurine (TAU) on the muscle fiber type transformation in porcine myoblasts and its molecular mechanisms. The findings revealed that TAU augmented the protein expression of slow MyHC and the enzyme activities of oxidative metabolism markers like malate dehydrogenase and succinic dehydrogenase. Conversely, it curtailed the expression of fast MyHC and glycolytic metabolism enzyme activity of lactate dehydrogenase. Moreover, TAU elevated the expression of genes associated with oxidative fiber while diminishing the expression of those linked to glycolytic fibers, suggesting that TAU promoted the muscle fiber type transformation from glycolytic fiber to oxidative fiber. Additionally, TAU notably enhanced the expression of key molecules of calcineurin (CaN)/nuclear factor of activated T cells c1 (NFATc1) signaling and the CaN activity in porcine myoblasts. However, CaN inhibitor cyclosporine A abolished these effects induced by TAU. Our results indicated that TAU regulated the muscle fiber type transformation from glycolytic to oxidative fiber by activation of CaN/NFATc1 signaling.
Asunto(s)
Fibras Musculares Esqueléticas , Taurina , Animales , Calcineurina/metabolismo , L-Lactato Deshidrogenasa/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Mioblastos/metabolismo , Cadenas Pesadas de Miosina/genética , Factores de Transcripción NFATC/metabolismo , Porcinos , Taurina/farmacología , Células CultivadasRESUMEN
We theoretically investigate the Goos-Hänchen (GH) shifts of reflected light beams in Thue-Morse photonic crystals. The systems are constituted by two Thue-Morse dielectrics multilayers and satisfy parity-time (PT) symmetry. Double coherent perfect absorption laser points (CPA-LPs) are achieved in the parameter space composed of the incident angle and the gain-loss factor. Dramatic changes in the phase of reflection coefficient induce giant positive and negative spatial GH shifts at the CPA-LPs, while great angular GH shifts exist around the exceptional points (EPs). The spatial GH shifts present non-reciprocity for the forward and backward incident light waves near the double CPA-LPs, while the angular GH shifts are quasi-reciprocal. Increasing the Thue-Morse sequence number, these characteristics are approved around multiple CPA-LPs as well. Our work could pave the way to explore high-accuracy optical sensors.