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Background: Baitouweng decoction (BTW) is a classic botanical drugs formula that has been widely used clinically for the treatment of gut-related disorders in China. However, its role in ameliorating ulcerative colitis (UC) remains to be explored. Purpose: The study aimed to determine the therapeutic efficacy and potential mechanism of action of BTW on dextran sodium sulfate (DSS)-induced colitis mice. Methods: In vivo: 3.5% DSS-induced experimental colitis mice were treated with BTW (Pulsatilla chinensis (Bunge) Regel, Phellodendron chinense C. K. Schneid, Coptis chinensis Franch and Fraxinus chinensis Roxb), kynurenine or DOPA decarboxylase (DDC) inhibitor (carbidopa). In vitro: Caco-2 cells were stimulated with TNF-α to activate inflammation and later treated with various concentrations of BTW and carbidopa. Model evaluation included body weight, disease activity index (DAI) score, colon length and histopathology. Cytokine levels were measured by flow cytometry. Protein levels were analyzed by proteomics and functionally annotated. The levels of tryptophan metabolites in mouse serum and colon were detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Alcian Blue/Phosphate Acid Schiff (AB/PAS) staining, immunohistochemistry and western blot were used to assess the intestinal barrier function and detect the protein expression levels. Results: BTW significantly reduced the DAI, ameliorated colonic injury and regulated inflammatory cytokines in DSS-induced colitis mice. The botanical drugs formula also promoted intestinal epithelial barrier repair by enhancing the expression of the tight junction (TJ) proteins. Tryptophan metabolic signaling pathway was significantly enriched in DSS-induced UC mice, and BTW decreased the level of kynurenine, increased indole metabolites. The therapeutic effect of BTW was evidently reduced when kynurenine was given to mice. Also, BTW promoted DDC protein expression and activated the aryl hydrocarbon receptor (AHR)/IL-22 signaling pathway. Conclusion: BTW improves ulcerative colitis by promoting DDC expression, regulating the conversion of tryptophan metabolism from the kynurenine pathway to the indole metabolism pathway, thereby modulating tryptophan metabolism to increase indole metabolites, and activating AHR receptors to restore intestinal barrier function.
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High proportions of soybean meal in aquafeed have been confirmed to induce various intestinal pathologies. This study aims to investigate the regulatory effects of rosmarinic acid (RA), an antioxidant with anti-inflammatory and antimicrobial properties, when added to high soybean meal feeds in different doses, (0, 0.5, 1, and 4 g/kg). During the 56-day feeding trial, results indicated that, compared to the control group without RA (0 g/kg), the 1 g/kg and 4 g/kg RA groups increased bullfrog survival rates and total weight gain while reducing feed coefficient. Additionally, these doses markedly suppressed the expression of key intestinal inflammatory markers (tlr5, myd88, tnfα, il1ß, cxcl8, cxcl12) and the activity and content of intestinal antioxidants (CAT, MDA, GSH, GPX). Concurrently, RA significantly downregulated the transcription levels of antioxidant-related genes (cat, gpx5, cyba, cybb, mgst, gclc, gsta, gstp), suggesting RA's potential to alleviate intestinal inflammation and oxidative stress induced by high soybean meal and to help downregulate and restore normal expression of antioxidant enzyme genes. However, the 0.5 g/kg RA group did not show a significant improvement in survival rates; instead, it upregulated the transcription of some antioxidant genes (cat, gpx5, cyba, cybb), revealing the complexity and dose-dependency of RA's antioxidant action. Furthermore, RA supplementation significantly reshaped the intestinal microbial community structure and relative abundance in bullfrogs, particularly affecting the genera Hafnia, Phascolarctobacterium, and Lactococcus. Notably, high doses of RA (1 g/kg, 4 g/kg) were able to downregulate pathways associated with the enrichment of gut microbiota in diseases such as Parkinson's, Staphylococcus aureus infection, and Systemic lupus erythematosus, suggesting its potential in anti-inflammatory action and health maintenance to prevent potential diseases.
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Alimentación Animal , Cinamatos , Depsidos , Dieta , Suplementos Dietéticos , Glycine max , Estrés Oxidativo , Rana catesbeiana , Ácido Rosmarínico , Animales , Depsidos/farmacología , Depsidos/administración & dosificación , Glycine max/química , Cinamatos/farmacología , Cinamatos/administración & dosificación , Alimentación Animal/análisis , Dieta/veterinaria , Estrés Oxidativo/efectos de los fármacos , Rana catesbeiana/inmunología , Suplementos Dietéticos/análisis , Inflamación/veterinaria , Relación Dosis-Respuesta a Droga , Intestinos/efectos de los fármacos , Intestinos/inmunología , Distribución Aleatoria , Enfermedades de los Peces/inmunología , Microbioma Gastrointestinal/efectos de los fármacos , Antioxidantes/administración & dosificación , Antioxidantes/farmacología , Antioxidantes/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/administración & dosificaciónRESUMEN
To study the effects of basalt fibers (BFs), calcium sulfate whiskers (CSWs), and modified calcium sulfate whiskers (MCSWs) on the compressive strength and dynamic modulus of elasticity of concrete, this paper utilizes Mercury Intrusion Porosimetry (MIP) to measure the microstructure of concrete and calculate the fractal dimension of pore surface area. The results indicate that both CSWs and BFs can increase the compressive strength of concrete. CSWs can enhance the dynamic modulus of elasticity of concrete, while the effect of BFs on the dynamic modulus of elasticity is not significant. The improvement in compressive strength and dynamic modulus of elasticity provided by MCSWs is significantly greater than that provided by CSWs. Both CSWs and BFs can effectively improve the pore structure of concrete and have a significant impact on the surface fractal dimension. CSWs inhibit the formation of ink-bottle pores, while BFs increase the number of ink-bottle pores. Due to the ink-bottle pore effect, the fractal dimension of the capillary pore surface is generally greater than three, lacking fractal characteristics. The compressive strength and dynamic modulus of elasticity of concrete have a good correlation with the fractal dimensions of large pores and transition pores.
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BACKGROUND: Lung cancer (LC) is primarily responsible for cancer-related deaths worldwide. Epithelial-mesenchymal transition (EMT) is a process in which epithelial cells acquire mesenchymal features and is associated with the development of tumors. CBX8, a member of the PcG protein family, plays a critical role in various cancers, containing LC. However, specific regulatory mechanisms of CBX8 in LC progression are not fully understood. This study aimed to investigate the regulatory role of CBX8 in LC progression. METHODS: Bioinformatics was used to analyze the relationship between CBX8 level and tumor and the enrichment pathway of CBX8 enrichment. qRT-PCR was used to detect the differential expression of CBX8 in LC cells and normal lung epithelial cells. The effects of knockdown or overexpression of CBX8 on the proliferation, migration and invasion of LC cells were evaluated by CCK- -8 assay and Transwell assay, and the levels of proteins associated with the EMT pathway and Wnt/ ß-catenin signaling pathway were detected by western blot. RESULTS: Bioinformatics analysis revealed that CBX8 was highly expressed in LC and enriched on the Wnt/ß-catenin signaling pathway. The expression level of CBX8 was significantly elevated in LC cells. Knockdown of CBX8 significantly inhibited cell proliferation, migration and invasion, and decreased the expression levels of EMT-related proteins and Wnt/ß-catenin pathway-related proteins. Conversely, overexpression of CBX8 promoted cell proliferation, migration and invasion, and increased the expression levels of EMT-related proteins and Wnt/ß-catenin pathway-related proteins. The Wnt inhibitor IWP-4 alleviated the effects produced by overexpression of CBX8. CONCLUSION: Collectively, these data demonstrated that CBX8 induced EMT through Wnt/ß-- catenin signaling, driving migration and invasion of LC cells.
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Movimiento Celular , Proliferación Celular , Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares , Complejo Represivo Polycomb 1 , Vía de Señalización Wnt , Transición Epitelial-Mesenquimal/genética , Humanos , Vía de Señalización Wnt/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Movimiento Celular/genética , Proliferación Celular/genética , Complejo Represivo Polycomb 1/genética , Complejo Represivo Polycomb 1/metabolismo , Línea Celular Tumoral , Invasividad Neoplásica , beta Catenina/metabolismo , beta Catenina/genética , Técnicas de Silenciamiento del Gen , Células A549RESUMEN
Objective: This study aimed to evaluate the associations between dietary and microbiological factors, and the levels and dynamics of 5-amino valeric acid betaine (5-AVAB) in patients with type 2 diabetes (T2D) through a prospective nested case-control study. An added meta-analysis aimed to provide a comprehensive evaluation of the relationship between 5-AVAB levels and T2D risk. Methods: A total of 1200 T2D patients and 1200 age- and sex-matched controls were recruited for this study. Dietary information was collected through 24-hour dietary recall questionnaires, while fecal samples were analyzed for gut microbiota composition using 16S rRNA gene sequencing. 5-AVAB levels were measured in plasma samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Multivariate logistic regression and general linear models were applied to evaluate the associations between 5-AVAB levels, dietary factors, and gut microbiota composition. Results: The T2D patients exhibited significantly lower plasma 5-AVAB concentrations compared to the control group (P < .001). Lower 5-AVAB levels were associated with higher odds of T2D (adjusted OR = 2.89, 95% CI: 1.76-4.74). Higher intake of dietary factors, including fiber and polyunsaturated fatty acids (PUFAs), were positively associated with 5-AVAB levels. Furthermore, specific bacterial taxa were significantly associated with 5-AVAB levels. A meta-analysis of five studies corroborated the inverse association between 5-AVAB and T2D risk (pooled OR = 2.68, 95% CI: 1.61-4.46). Conclusion: Our findings suggest that lower 5-AVAB levels are associated with an increased risk of T2D. Dietary factors and gut microbiota composition appear to significantly influence 5-AVAB levels. The potential use of 5-AVAB as a therapeutic target in T2D management is an exciting area of research that requires further investigation. If successful, it could lead to new treatment options for T2D patients, ultimately improving their long-term health outcomes and quality of life.
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Powdered activated carbon (PAC) adsorption is regarded as an efficient method for removing odorants from drinking water. However, in eutrophic aquatic environments, the presence of algal organic matter (AOM) produced by cyanobacteria considerably impedes the adsorption of odorous compounds by activated carbon. This study focused on investigating the adsorption characteristics of three representative odorants: 2-methylisoborneol (2-MIB), ß-cyclocitral (ß-cyclo), and butyl sulfide (BS) by PAC and the effects of AOM on the PAC adsorption of odorants. The removal of the three odorants reached 83.5-97.5% at a PAC dosage of 10 mg/L after 12 h of exposure in a competition-free scenario. The adsorption kinetics demonstrated higher conformity (R2 > 0.9) with the pseudo-second-order model, whereas the adsorption capacity exhibited stronger conformity (R2 > 0.9) with the Freundlich model. The presence of AOM resulted in varying levels of competition for PAC for the adsorption of the three odorants. As the concentration of AOM increased from 0 to 5 mg C/L, the removal of 2-MIB was the most affected (from 83.5% to 10.0%), followed by ß-cyclo (from 86.6% to 55.0%), and BS (from 97.5% to 92.0%). The competitive adsorption of AOM at the molecular level was studied using density functional theory (DFT). The DFT results suggested that odorants with higher and more uniformly distributed electrostatic potentials exhibited a heightened affinity for PAC adsorption and a diminished susceptibility to disruption caused by AOM. This study provides valuable insights into the mitigation of odorous compounds during drinking water purification.
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Contaminantes Químicos del Agua , Purificación del Agua , Adsorción , Carbón Orgánico , Odorantes , Purificación del Agua/métodosRESUMEN
PURPOSE: To construct a nomogram for evaluation of the recurrence risk of upper urinary tract stones in patients. METHODS: We retrospectively reviewed the clinical data of 657 patients with upper urinary tract stones and divided them into stone recurrence group and non-recurrence group. Blood routine, urine routine, biochemical, and urological CT examinations were searched from the electronic medical record, relevant clinical data were collected, including age, BMI, stones number and location, maximum diameter, hyperglycemia, hypertension, and relevant blood and urine parameters. The Wilcoxon rank-sum test, independent sample t test, and Chi-square test were used to preliminarily analyze the data of the two groups, then LASSO and logistic regression analysis were used to find out the significant difference indicators. Finally, R software was used to draw a nomogram to construct the model, and ROC curve was drawn to evaluate the sensitivity and specificity. RESULTS: The results showed that multiple stones (OR: 1.832, 95% CI 1.240-2.706), bilateral stones (OR: 1.779, 95% CI 1.226-2.582), kidney stones (OR: 3.268, 95% CI 1.638-6.518), and kidney ureteral stones (OR: 3.375, 95% CI 1.649-6.906) were high risk factors. And the stone recurrence risk was positively correlated with creatinine (OR: 1.012, 95% CI 1.006-1.018), urine pH (OR: 1.967, 95% CI 1.343-2.883), Apo B (OR: 4.189, 95% CI 1.985-8.841) and negatively correlated with serum phosphorus (OR: 0.282, 95% CI 0.109-0.728). In addition, the sensitivity and specificity of the prediction model were 73.08% and 61.25%, diagnosis values were greater than any single variable. CONCLUSION: The nomogram model can effectively evaluate the recurrence risk of upper urinary stones, especially suitable for stone postoperative patients, to help reduce the possibility of postoperative stone recurrence.
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Cálculos Renales , Cálculos Urinarios , Sistema Urinario , Humanos , Estudios Retrospectivos , Cálculos Renales/diagnóstico , Factores de RiesgoRESUMEN
An eight-week trial was conducted to investigate the effects of sanguinarine supplementation (600 µg and 1200 µg/kg) in high-fat (crude fat: 10%) diets (HF) on the intestinal physiological function of Ctenopharyngodon idellus (initial weight 50.21 ± 0.68 g), based on a basic diet (5% crude fat, CON), which were named HFLS and HFHS, respectively. The results showed that the HF diet significantly impaired the intestinal immune and physical barrier function, and disrupted the balance of the intestinal microbiota in grass carp. Compared to the HF diet, sanguinarine supplementation significantly improved the levels of serum C4, C3, AKP, IgA, and IgM, and enhanced the intestinal antioxidant capacity (gr, CuZnsod, gpx4, cat, gsto, and nrf2 expression were significantly up-regulated). Sanguinarine significantly down-regulated the expression of claudin-15 and up-regulated the expression of claudin-b, claudin-c, occludin, and zo-1 by inhibiting MLCK signaling molecules. Additionally, sanguinarine significantly down-regulated the expression of il-6, il-1ß, and tnf-α and up-regulated the expression of il-10, tgf-ß2, and tgf-ß1 by inhibiting NF-κB signaling molecules, thereby alleviating intestinal inflammation caused by HF diets. Furthermore, compared to the HF diet, the abundance of Fusobacterium and Cetobacterium in the HFHS diet increased significantly, while the abundance of Firmicutes and Streptococcus showed the opposite trend. In conclusion, the HF diet had a negative impact on grass carp, while sanguinarine supplementation enhanced intestinal antioxidant ability, alleviated intestinal barrier damage, and ameliorated the homeostasis of the intestinal microbiota.
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Chlorella vulgaris (C. vulgaris) powder is a novel non-grain single-cell protein with enormous potential to be a protein source. However, it is poorly studied in aquatic animals. The purpose of the present study was to explore the optimum replacement ratio of C. vulgaris powder and the influence of the substitution of soybean meal with C. vulgaris on grass carp (Ctenopharyngodon idella) in terms of growth performance, intestinal integrity and the microbial community. Five isonitrogenous and isolipidic diets were formulated by replacing 0% (SM, containing 30% soybean meal), 25% (X25), 50% (X50), 75% (X75) and 100% (X100) soybean meal with C. vulgaris. The feeding trial period lasted 8 weeks. At the end of the experimental trial, the X50 group showed higher FW, WGR and PER than the SM group (p < 0.05). The feed conversion ratio (FCR) of the X50 group was significantly lower than that of the SM group (p < 0.05). The X50 group showed the highest value of the goblet cell number, intestinal amylase and trypsin activities when compared with the SM group (p < 0.05). Replacing 50% soybean meal with C. vulgaris improved the intestinal barrier integrity, as evidenced by upregulating zo-1, zo-2 and occluding transcript (p < 0.05), and alleviated oxidative stress by an increased SOD enzymatic activity and transcript level, probably mediated through the Nrf2-keap1 signaling pathway (p < 0.05). Meanwhile, the X50 group enhanced intestinal immunity, as manifested by increased ACP and LZM activities (p < 0.05), and downregulated the tlr-4, tlr-7, tlr-8 and il-6 through the tlr pathway (p < 0.05). The functionally predicting pathways related to the nitrate respiration and nitrogen respiration were observably activated in the X50 group (p < 0.05). The X50 group improved the biological barrier, as manifested by increased Firmicutes and Rhodobacter (p < 0.05). In conclusion, dietary C. vulgaris powder could promote the growth performance of grass carp by restoring intestinal morphology, increasing digestive enzyme activities, improving antioxidant properties and immunity and optimizing the microflora structure. A C. vulgaris powder replacement of 50% soybean meal was recommended as feed for grass carp.
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During eukaryotic cell division, organelles are distributed between daughter cells through a dynamic process to ensure that cells can differentiate and perform their functions correctly. Uncovering the mode of lipid droplet (LD) distribution may help reveal the mechanism of membrane remodeling during cell division and lipid droplet function. Our results showed that LDs were equally distributed in both daughter cells during cytokinesis. Further experiments demonstrated that the key factor regulating the movement of LDs is the microtubule (MT)-resident protein KIF5B. Because the KIF5B structure lacks a hydrophilic region, we believe that there are proteins that mediate the interaction between LDs and KIF5B. Mass spectrometric detection of KIF5B-interacting proteins on the surface of LDs demonstrated that LDs were first wrapped by intermediate filaments forming a meshwork and then contacted with MTs to mediate lipid droplet movement during cytokinesis. Disruption of the homogeneous distribution of LDs may hinder cell proliferation and even lead to apoptosis.
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Metabolismo de los Lípidos , Microtúbulos , Mitosis , Microtúbulos/metabolismo , Humanos , Células HeLa , Animales , Ratones , Cinesinas/metabolismoRESUMEN
An eight-week feeding trial explored the mechanism that supplemented methionine (0 g/kg, 4 g/kg, 8 g/kg, and 12 g/kg) in a high-fat diet (120 g/kg fat) on intestinal lipid transportation and gut microbiota of M. Albus (initial weight 25.03 ± 0.13 g) based on the diet (60 g/kg fat), named as Con, HFD+M0, HFD+M4, HFD+M8, and HFD+M12, respectively. Compared with Con, gastric amylase, lipase, trypsin (P < 0.05), and intestinal lipase, amylase, trypsin, Na+/K+ -Adenosinetriphosphatase, depth of gastric fovea, and the number of intestinal villus goblet cells of HFD+M0 were markedly declined (P < 0.05), while intestinal high-density lipoprotein-cholesterol, very low-density lipoprotein-cholesterol and microsomal triglyceride transfer protein of HFD+M0 were markedly enhanced (P < 0.05); compared with HFD+M0, gastric lipase, amylase, trypsin, and intestinal lipase, trypsin, Na+/K+ -Adenosinetriphosphatase, microsomal triglyceride transfer protein, very low-density lipoprotein-cholesterol, and apolipoprotein -A, the height of intestinal villus and the number of intestinal villus goblet cells of HFD+M8 were remarkably enhanced (P < 0.05). Compared with Con, intestinal occ, cl12, cl15, zo-1, zo-2 of HFD + M0 were markedly down-regulated (P <0.05), while intestinal vldlr, npc1l1, cd36, fatp1, fatp2, fatp6, fatp7, apo, apoa, apob, apof, apoo, mct1, mct2, mct4, mct7, mct12, lpl, mttp, moat2, dgat2 of HFD M0 were remarkably upregulated (P < 0.05); compared with HFD+M0, intestinal gcn2 and eif2α of HFD+M8 were remarkably downregulated (P < 0.05), intestinal occ, cl12, cl15, zo-1, zo-2, hdlbp, ldlrap, vldlr, cd36, fatp1, fatp2, fatp6, apo, apoa, apob, apof, apoo, mct1, mct2, mct8, mct12, lpl, mttp, moat2, and dgat2 were remarkably upregulated (P < 0.05). Compared with Con, the diversity of gut microbiota of HFD+M0 was significantly declined (P < 0.05), while the diversity of gut microbiota in HFD+M8 was significantly higher than that in HFD+M0 (P < 0.05). In conclusion, a high-fat methionine deficiency diet destroyed the intestinal barrier, reduced the capacity of intestinal digestion and absorption, and disrupted the balance of gut microbiota; supplemented methionine promoted the digestion and absorption of lipids, and also improved the balance of gut microbiota.
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Inflammatory bowel disease (IBD), which mainly comprises ulcerative colitis (UC) and Crohn's disease (CD), is a common chronic intestinal inflammatory disease that affects the ileum, rectum, and colon. Currently, the diagnosis of IBD is based on clinical history, physical examination and complementary diagnostic tests. It is challenging for physicians to make a definitive diagnosis. This study aimed to analyze the variation in amino acid metabolites in IBD serum and to identify potential predictive biomarkers of IBD diagnosis and progression. Serum samples were collected from 158 UC patients, 130 CD patients and 138 healthy controls (HCs). The 37 amino acids in serum were determined by ultra-high-pressure liquid chromatography coupled to a mass spectrometer. A panel of three-amino-acid metabolites (taurine, homocitrulline and kynurenine) was identified as a specific biomarker panel of IBD. Receiver operating characteristic analysis (ROC) showed that the panel had a sensitivity of 88.4% with a specificity of 84.6% for discriminating CD patients from UC patients. The biomarkers identified are increased in CD compared to UC. Our approach demonstrated a strong relationship between serum amino acid levels and IBD. We successfully identified serum amino acid biomarkers associated with CD and UC. The biomarker panel has potential in clinical practice for IBD diagnosis and will provide new insights into IBD pathogenesis.
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Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Humanos , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/patología , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/patología , Enfermedades Inflamatorias del Intestino/patología , BiomarcadoresRESUMEN
Under oxidative stress condition, the protective effects of dietary chlorogenic acid (CGA) supplementation on liver antioxidant capacity, intestinal inflammation and barrier function, muscle development and skin coloration in channel catfish Ictalurus punctatus were explored in the current study. With that purpose, I. punctatus were fed five experimental diets containing 2% fresh fish oil (FFO, 9.2 meqO2/kg) or 2% oxidized fish oil (OFO, 897.4 meqO2/kg) without or with CGA supplementation (0.02%, 0.04% and 0.08%) for 8 weeks. Upon comparative analysis, the oxidized fish oil consumption significantly lowered weight gain rate, decreased intestinal villi length and muscular thickness values and the tight junction proteins mRNA abundance, augmented the intestinal proinflammatory factors, attenuated hepatic antioxidant enzymes activities and related genes mRNA expression levels, influenced the myogenic regulatory factors expression profile and impacted the myocyte density, myocyte area values as well as the skin pigments contents compared to the FFO treatment. Collectively, long-term feeding of the oxidized fish oil diet suppressed the growth performance, destroyed intestinal structural integrity, caused intestinal inflammation and hepatic oxidative stress, impacted the skeletal development and skin color of I. punctatus. Whereas CGA supplementation in oxidized fish oil diets partially counteracted the negative effects of the oxidized fish oil on I. punctatus in terms of increasing the growth performance, improving the intestinal mucosal structure, alleviating hepatic oxidative stress and intestinal inflammation, recompiling the myogenic regulatory factors expression and improving skin color. In conclusion, CGA has great potential to be an aquatic feed additive.
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Grasas Insaturadas en la Dieta , Ictaluridae , Animales , Antioxidantes/metabolismo , Suplementos Dietéticos , Ácido Clorogénico , Pigmentación de la Piel , Dieta , Aceites de Pescado/metabolismo , Grasas Insaturadas en la Dieta/metabolismo , Hígado/metabolismo , Desarrollo de Músculos , Inflamación/metabolismo , Alimentación Animal/análisisRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Baitouweng decoction (BTW) has been used for hundreds of years to treat ulcerative colitis (UC) in China and has produced remarkable clinical results. However, the knowledge in protective mechanism of BTW against UC is still unclear. AIM OF THE STUDY: The present study was designed to investigate the anti-UC effects of BTW and the underlying mechanisms involved. METHODS: 3.5% dextran sulfate sodium (DSS)-induced experimental colitis was used to simulate human UC and the mice were treated with BTW (6.83 g/kg), leucine (200 mg/kg, Leu) or rapamycin (2 mg/kg, RAPA) as a positive control for 7 days. The clinical symptoms, serum myeloperoxidase (MPO) and malondialdehyde (MDA) levels were evaluated. Biological samples were collected to detect the effects of BTW on mechanistic target of rapamycin complex 1 (mTORC1) pathway and Leu metabolism. RESULTS: In our study, BTW notably improved the clinical symptoms and histopathological tissue damage and reduced the release of proinflammatory cytokines, including IL-6, IL-1ß and TNF-α in UC mice. BTW also alleviated oxidative stress by decreasing serum MPO and MDA levels. Additionally, BTW significantly suppressed mTORC1 activity in the colon tissues of UC mice. Serum metabolomics analysis revealed that the mice receiving BTW had lower Leu levels, which was in line with the decreased expression of branched-chain α-keto acid dehydrogenase kinase (BCKDK) in the colon tissues. Furthermore, oral administration of Leu aggravated DSS-induced acute colitis and enhanced mTORC1 activity in the colon. CONCLUSION: These data strongly demonstrated that BTW could ameliorate DSS-induced UC by regulating the Leu-related mTORC1 pathway and reducing oxidative stress.
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Colitis Ulcerosa , Colitis , Humanos , Animales , Ratones , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/patología , Sulfato de Dextran/toxicidad , Leucina/farmacología , Leucina/metabolismo , Leucina/uso terapéutico , Colon , Colitis/tratamiento farmacológico , Estrés Oxidativo , Ratones Endogámicos C57BL , Modelos Animales de EnfermedadRESUMEN
Fluorine 18(18F) fluorodeoxyglucose positron emission tomography and Computed Tomography (PET/CT) is the preferred imaging method of choice for the diagnosis and treatment of many cancers. However, factors such as low-contrast organ and tissue images, and the original scale of tumors pose huge obstacles to the accurate segmentation of tumors. In this work, we propose a novel model ASE-Net which is used for multimodality tumor segmentation. Firstly, we propose a pseudo-enhanced CT image generation method based on metabolic intensity to generate pseudo-enhanced CT images as additional input, which reduces the learning of the network in the spatial position of PET/CT and increases the discriminability of the corresponding structural positions of the high and low metabolic region. Second, unlike previous networks that directly segment tumors of all scales, we propose an Adaptive-Scale Attention Supervision Module at the skip connections, after combining the results of all paths, tumors of different scales will be given different receptive fields. Finally, Dual Path Block is used as the backbone of our network to leverage the ability of residual learning for feature reuse and dense connection for exploring new features. Our experimental results on two clinical PET/CT datasets demonstrate the effectiveness of our proposed network and achieve 78.56% and 72.57% in Dice Similarity Coefficient, respectively, which has better performance compared to state-of-the-art network models, whether for large or small tumors. The proposed model will help pathologists formulate more accurate diagnoses by providing reference opinions during diagnosis, consequently improving patient survival rate.
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Neoplasias , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Redes Neurales de la Computación , Procesamiento de Imagen Asistido por Computador/métodos , Neoplasias/diagnóstico por imagen , Imagen MultimodalRESUMEN
Autonomous emergency braking (AEB) systems are able to control vehicles as needed to avoid vehicle rear-end collisions. However, these systems are ineffective in scenarios with laterally cut-in vehicles and rapidly-changing dangerous scenes. This paper proposes a novel collision-free emergency braking system (CFEBS) that can enable intelligent connected vehicles (CAVs) to plan and execute a more conservative safety trajectory for the braking process in dangerous scenes by considering the longitudinal and lateral motion intentions of the surrounding vehicles. An intention identification model for surrounding vehicles is proposed based on long-short term memory (LSTM) networks and conditional random fields (CRFs). By considering the surrounding vehicles as risk sources and quantifying the risk with the speed of the risk flow, a potential risk flow model is built to calculate the potential risk map (PRM) around the ego vehicle. The global safest trajectory is generated via the PRM using the discrete method. The output trajectory profile is regarded as the reference for a model predictive controller (MPC). Simulation results show that the proposed CFEBS can predict vehicle intention with 91.6% accuracy and control the ego vehicle to perform effective collision-free braking operations in emergency traffic environments.
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Unfolded protein responses from endoplasmic reticulum (ER) stress have been implicated in inflammatory signaling. The vicious cycle of ER stress and inflammation makes regulation even more difficult. This study examined effects of farnesoid X receptor (FXR) in ER-stress regulation in large yellow croakers. The soybean-oil-diet-induced expression of ER stress markers was decreased in fish with FXR activated. In croaker macrophages, FXR activation or overexpression significantly reduced inflammation and ER stress caused by tunicamycin (TM), which was exacerbated by FXR knockdown. Further investigation showed that the TM-induced phosphorylation of PERK and EIF2α was inhibited by the overexpression of croaker FXR, and it was increased by FXR knockdown. Croaker NCK1 was then confirmed to be a regulator of PERK, and its expression in macrophages is increased by FXR overexpression and decreased by FXR knockdown. The promoter activity of croaker NCK1 was inhibited by yin-yang 1 (YY1). Furthermore, the results show that croaker FXR overexpression could suppress the P65-induced promoter activity of YY1 in HEK293t cells and decrease the TM-induced expression of yy1 in macrophages. These results indicate that FXR could suppress P65-induced yy1 expression and then increase NCK1 expression, thereby inhibiting the PERK pathway. This study may benefit the understanding of ER stress regulation in fish, demonstrating that FXR can be used in large yellow croakers as an effective target for regulating ER stress and inflammation.
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BACKGROUND: 3,6-dichlorobenzo[b]thiophene-2-carboxylic acid (BT2) is a benzothiophene carboxylate derivative that can suppress the catabolism of branched-chain amino acid (BCAA)-associated mammalian target of rapamycin complex 1 (mTORC1) activation. Previous studies have demonstrated the therapeutic effects of BT2 on arthritis, liver cancer, and kidney injury. However, the effects of BT2 on ulcerative colitis (UC) are unknown. AIM: To investigate the anti-UC effects of BT2 and the underlying mechanism. METHODS: Mouse UC models were created through the administration of 3.5% dextran sodium sulfate (DSS) for 7 d. The mice in the treated groups were administered salazosulfapyridine (300 mg/kg) or BT2 (20 mg/kg) orally from day 1 to day 7. At the end of the study, all of the mice were sacrificed, and colon tissues were removed for hematoxylin and eosin staining, immunoblot analyses, and immunohistochemical assays. Cytokine levels were measured by flow cytometry. The contents of BCAAs including valine, leucine, and isoleucine, in mouse serum were detected by liquid chromatography-tandem mass spectrometry, and the abundance of intestinal flora was analyzed by 16S ribosomal DNA sequencing. RESULTS: Our results revealed that BT2 significantly ameliorated the inflammatory symptoms and pathological damage induced by DSS in mice. BT2 also reduced the production of the proinflammatory cytokines interleukin 6 (IL-6), IL-9, and IL-2 and increased the anti-inflammatory cytokine IL-10 level. In addition, BT2 notably improved BCAA catabolism and suppressed mTORC1 activation and cyclooxygenase-2 expression in the colon tissues of UC mice. Furthermore, high-throughput sequencing revealed that BT2 restored the gut microbial abundance and diversity in mice with colitis. Compared with the DSS group, BT2 treatment increased the ratio of Firmicutes to Bacteroidetes and decreased the abundance of Enterobacteriaceae and Escherichia-Shigella. CONCLUSION: Our results indicated that BT2 significantly ameliorated DSS-induced UC and that the latent mechanism involved the suppression of BCAA-associated mTORC1 activation and modulation of the intestinal flora.
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Colitis Ulcerosa , Colitis , Microbioma Gastrointestinal , Animales , Ratones , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/patología , Colitis/inducido químicamente , Colon/patología , Citocinas/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Sulfato de Dextran/toxicidad , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , MamíferosRESUMEN
Carrying out early warning of systemic financial risk is a prerequisite for timely adjustment of monetary policy and macroprudential policy to effectively prevent and resolve systemic financial risks. This paper constructs a systemic financial risk monitoring and early warning system for China's banking industry based on isolated forest anomaly detection and neural network with autocorrelation mechanism and uses low-frequency data with high credibility to effectively identify the ten factors that have the greatest impact on systemic financial risk in China's banking industry, improving the prospective and accuracy of risk early warning. The conclusions can help regulators to adjust their policies prospectively to curb the rise of systemic financial risks.
Asunto(s)
Industrias , Redes Neurales de la Computación , China , Predicción , Estudios ProspectivosRESUMEN
Fish are extremely vulnerable to environmental stimulation and produce oxidative stress. Among them, hydrogen peroxide is an oxidative stress source that cannot be ignored in fish, which can cause physical disorders, inflammation and even death. Taurine was revealed to reduce oxidative damage and inflammation caused by toxic substances, but whether it can reduce toxicity of rice field eel caused by H2O2 has not been determined. Thus, the intervention effects of taurine on H2O2-induced oxidative stress, inflammation, apoptosis, and autophagy in rice field eel. The results showed that oxidative injury in the liver was determined after H2O2 injection, as indicated by enhanced serum AST and ALT activities, inhibited the antioxidant function (increased MDA and ROS contents, decreased antioxidant enzymes, inhibited nrf2 transcription level), and induced inflammatory response (upregulated il-1ß, il-6, il-8, and il-12ß gene expression, downregulated tgf-ß1 gene expression, activated the transcription level of nf-κb, tlr-3, and tlr-7). In addition, bax, caspase3, beclin1, and Lc3B gene expression were significantly upregulated after H2O2 injection, while bcl2 and p62 gene expression were downregulated, leading to the occurrence of apoptosis and autophagy. In contrast, adding 0.2 and 0.5% taurine to feed significantly alleviated this damage, as indicated by the recovery of the aforementioned bioindicators, and the effect of 0.5% taurine addition is better than 0.2%. Overall, these results suggested that taurine can relieve the liver toxicity induced by H2O2, which enriched the toxic mechanism of H2O2 on fish and provided evidence for the protective effect of taurine on liver.