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In this paper, based on the fluorescence of carbon quantum dots (CQDs) quenched by mercury ions (Hg2+ ) and the nonresponse of Hg2+ to rhodamine B fluorescence, a dual emission ratio fluorescence sensor was constructed to realize the quantitative detection of Hg2+ . Under excitation at 365 nm, the fluorescence spectrum showed double emission peaks at 437 nm and 590 nm, corresponding to the fluorescence emissions of CQDs and rhodamine B, respectively. This method quantitatively detected Hg2+ based on the linear relationship between the ratio of the intensities of the two emission peaks F437 /F590 and the concentration of Hg2+ . The detection range was 10-70 nM, and the limit of detection (S/N = 3) was 3.3 nM. In addition, this method could also realize the qualitative and semiquantitative detection of Hg2+ according to the fluorescence colour change of the probe under ultraviolet light. After various evaluations, the method could be successfully applied to the quantitative and visual detection of Hg2+ in tap water, and demonstrated excellent selectivity, anti-interference performance, and repeatability of the method.
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Mercúrio , Pontos Quânticos , Carbono , Corantes Fluorescentes , Íons , Limite de Detecção , Espectrometria de FluorescênciaRESUMO
It is a highly attractive strategy to develop chemically recyclable polymers to establish a circular plastic economy. Despite the recent advancements, chemically recyclable polymers still face challenges including high energy cost for polymer preparation or recycling, poor monomer recovery selectivity and efficiency as well as undesired material performance. In this contribution, we present the chemoselective controlled ring-opening polymerization of bio-renewable bifunctional α-methylene-δ-valerolactone (MVL) to produce exclusive functionalizable polyester using strong base/urea binary catalysts. The obtained polyester with high molar mass exhibits good tensile strength comparable to that of some commodity plastics. Remarkably, the obtained polyester can be depolymerized to recover pristine monomer with a 96 % yield by thermolysis, thus successfully establishing a closed-loop life cycle.
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In order to explore the performance, kinetics characteristics and enhancement mechanisms in anammox process under ferrous iron enhanced conditions, a laboratory-scale UASB anammox reactor has been built up and operated for 534 days. Experimental results showed that the Anammox process was successfully started up in a short operation period and the TNRE reached 83.34 ± 2.96% with a maximum total nitrogen removal rate of 14.4 kg m-3 d-1 after long-term operated under influent Fe(II) concentration of 5.3 mg L-1. Simulation results using different kinetic models showed that the Stover-Kincannon model and the Grau second-order model were useful for describing the anammox performance under Fe(II) enhanced conditions. Extracellular polymeric substance (EPS) act a pivotal part in the granulation of Anammox sludge and the improvement of anammox activity. Iron improved the hydrophobicity of the sludge by reducing the PN/PS ratios, and also increased the Anammox granular diameter. The granular diameter of higher than 2.00 accounted for 58.3% of the total sludge. At the same time, the presence of iron decreased EPS levels, and also decreased the iron adsorption ability to sludge. More iron was transported into Anammox, which improved the nitrogen removal ability in the Anammox reactor.
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Reatores Biológicos , Matriz Extracelular de Substâncias Poliméricas , Biodegradação Ambiental , Compostos Ferrosos , Cinética , Nitrogênio , Oxirredução , EsgotosRESUMO
A total of 1 392 reports on liver injury associated adverse drug reaction(LI-ADR) related to bone diseases were retrospectively analyzed based on national ADR monitoring system [18.75% of the patients used traditional Chinese medicine(TCM) alone and 68.68% used Western medicine alone]. This kind of cases accounted for 2.5% of all drug-related liver injury adverse reactions, ranking top ten of all drug categories. The number of reported cases and the proportion of serious cases showed an increasing trend from 2012 to 2016. The average age of the patients was(54.2±15.8) years old, and there was little difference in overall gender(male-female 1.04â¶1). However, the number of female patients with rheumatoid arthritis was significantly higher than that of male patients(male-female 1â¶2.6), while the number of male patients with gout was significantly higher than that of female patients(male-female 7.16â¶1). The overall prognosis was good, with the recovery and improvement rate of 85.27%. The time from medication to liver injury varied due to different medicines. The median time to liver injury was 27 days in TCM alone group, later than 11 days in Western me-dicine alone group(P<0.05). Drugs for bone diseases have been one of the important categories for clinical drug-induced liver injury, and the number of reported cases on liver injury caused by drugs for bone diseases is increasing, so we should pay close attention to the safe and rational use of them. The LI-ADRs of male and female were different due to their different diseases, and the latency of adverse reactions in TCM group was generally longer than that in Western medicine group. In clinical medication, liver function should be monitored according to different diseases and characteristics of drugs to prevent the risk of liver injury.
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Doenças Ósseas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Medicamentos de Ervas Chinesas , Adulto , Idoso , Feminino , Humanos , Masculino , Medicina Tradicional Chinesa , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Obesity is one of the most important health problems worldwide. Panax ginseng has been reported to exert anti-obesity effect. However, the active constituents and the underlying mechanism remained uncertain. This study uncovered the anti-obesity effect of protopanaxadiol (PPD) and its potential mechanism. To investigate the anti-obesity effect of PPD, high-fat diet induced obesity (DIO) C57BL/6 mice were treated with PPD by both intraperitoneal injection (i.p.) and oral administration. Body weight and food intake were recorded. Energy expenditure was measured by CLAMS metabolic cages. For mechanism study, C-Fos in the hypothalamus of the mice was stained following the intracerebroventricular (i.c.v.) injection of PPD. Our results showed that with both injection and feeding, PPD reduced body weight, inhibited food intake, increased energy expenditure and improved liver damage in DIO mice. Mechanistically, i.c.v. injection of PPD inhibited feeding and increased C-Fos expression in paraventricular nucleus of the hypothalamus (PVH). The results suggest that PPD may reduce body weight of DIO mice via the activation of PVH neurons and PPD is a potential therapeutic candidate for the treatment of obesity.
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Obesidade/tratamento farmacológico , Núcleo Hipotalâmico Paraventricular/fisiologia , Sapogeninas/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica , Metabolismo Energético/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/lesões , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Obesidade/prevenção & controle , Núcleo Hipotalâmico Paraventricular/citologia , Núcleo Hipotalâmico Paraventricular/metabolismo , Sapogeninas/administração & dosagem , Sapogeninas/uso terapêuticoRESUMO
In this paper,the case reports on rug-induced liver injury( ADR cases) related to Gukang Capsules containing Psoralea corylifolia( Buguzhi,BGZ) were collected from the adverse reaction monitoring database from January 1,2012 to December 31,2016,and the in-patients cases with drug-induced liver injury admitted to a tertiary Class A liver disease hospital from January 1,2010 to December 31,2016 were also collected. These collected cases were re-evaluated and analyzed. 110 cases with liver injury related to this preparation were collected from adverse reaction monitoring database,and 55 cases of them received the preparation alone,mainly for fracture treatment( 52. 74%). Ninty one cases( 82. 72%) met the standard of the biochemical diagnostic criteria for drug-induced liver injury. 89. 01% of patients were over the age of 41 and women accounted for 60. 9%. The time from administration to liver injury was 1-208 days,with the median of 29 d. The dose of the preparation was 2. 4-4. 8 g per day,with a cumulative dose ranging from 3. 6-699. 6 g. The recovery and improvement rate reached 96. 70% after positive treatment. Seven inpatient cases related to the preparation were collected in a tertiary Class A liver disease hospital,6 females and 1 male. All of them were over 40 years old. Two cases reached the " suspicious diagnosis" standard and 5 cases reached the " clinical diagnosis" standard in Guidelines for the diagnosis and treatment of herb-induced liver injury. Six patients had a good prognosis effect,but another one had liver failure. This preparation is commonly used in fracture,osteoarthritis and other diseases,with remarkable curative effect. However,ADR cases and hospital cases all indicated the risk of liver injury. There was no significant correlation between the time and dose of drug use and the occurrence of liver injury.The induced-liver injury may have immunological heterogeneity,thus regular monitoring of liver function should be taken during clinical use.
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Doença Hepática Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas , Adulto , Bases de Dados Factuais , Feminino , Humanos , MasculinoRESUMO
Natural flavonoids are ubiquitous in dietary plants and vegetables and have been proposed to have antiviral, antioxidant, cardiovascular protective, and anticancer effects. Volume-regulated anion channels (VRACs), which are essential for cell volume regulation, have been proposed to play a key role in cell proliferation and migration, apoptosis, transepithelial transport, and cancer development. In this study, we screened a group of 53 structurally related natural flavonoids and three synthetic flavonoids for their inhibitory activities on VRAC currents. A whole-cell patch technique was used to record VRAC currents in the human embryonic kidney (HEK) 293 and human umbilical vein endothelial (HUVEC) cells. The 5'-bromo-2-deoxyuridine (BrdU) assay technique was used to investigate cell proliferation. At 100 µM, 34 of 53 compounds significantly inhibited hypotonic extrasolution-induced VRAC currents by > 50% in HEK293 cells. Among these compounds, luteolin, baicalein, eupatorin, galangin, quercetin, fisetin, karanjin, Dh-morin, genistein, irisolidone, and prunetin exhibited the highest efficacy for VRAC blockade (the mean inhibition > 80%) with IC50s of 5-13 µM and Emaxs of about 87-99%. We also studied the effects of three synthetic flavonoids on VRAC currents in HEK293 cells. Flavoxate showed high inhibition efficacy toward VRAC currents (IC50 = 2.3 ± 0.3 µM; Emax = 91.8% ± 2.7%). Finally, these flavonoids inhibited endogenous VRAC currents and cell proliferation in endothelial cells. This study demonstrates that natural and synthetic flavonoids are potent VRAC current inhibitors, and VRAC inhibition by flavonoids might be responsible for their anti-angiogenic effects.
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Proliferação de Células , Flavonoides/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Canais Iônicos/antagonistas & inibidores , Moduladores de Transporte de Membrana/farmacologia , Ânions/metabolismo , Tamanho Celular , Flavonoides/química , Células HEK293 , Células Endoteliais da Veia Umbilical Humana/fisiologia , Humanos , Potenciais da Membrana , Moduladores de Transporte de Membrana/químicaRESUMO
A novel series of 2-(4-sulfonamidophenyl)-indole 3-carboxamides was identified and optimized for activity against the HCV genotype 1b replicon resulting in compounds with potent and selective activity. Further evaluation of this series demonstrated potent activity across HCV genotypes 1a, 2a and 3a. Compound 4z had reduced activity against HCV genotype 1b replicons containing single mutations in the NS4B coding sequence (F98C and V105M) indicating that NS4B is the target. This novel series of 2-(4-sulfonamidophenyl)-indole 3-carboxamides serves as a promising starting point for a pan-genotype HCV discovery program.
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Antivirais/química , Antivirais/farmacologia , Hepacivirus/efeitos dos fármacos , Indóis/química , Indóis/farmacologia , Proteínas não Estruturais Virais/metabolismo , Sequência de Aminoácidos , Hepacivirus/química , Hepacivirus/genética , Hepacivirus/metabolismo , Hepatite C/tratamento farmacológico , Humanos , Dados de Sequência Molecular , Mutação , Replicon/efeitos dos fármacos , Sulfonamidas/química , Sulfonamidas/farmacologia , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/genéticaRESUMO
The pathophysiological mechanism underlying Hashimoto's thyroiditis (HT) is still unclear. Thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) are diagnostic hallmarks of HT. These IgG antibodies regulate the balance of immunologic tolerance and autoimmunity via Fcγ receptors (FcγRs). The aim of our study was to investigate the role of FcγRs in the pathogenesis of HT. The percentage of peripheral blood mononuclear cells (PBMCs) from HT patients bearing FcγRII was significantly lower than that seen in healthy donors, and the mean fluorescence intensity (MFI) value of FcγRII on PBMCs from HT patients was significantly higher. The percentage of PBMCs positive for FcγRIII also was significantly higher in HT patients, and the percentage of B cells bearing FcγRIIB in HT patients was significantly lower than that seen in healthy donors. Our study therefore provides evidence for FcγRs, especially FcγRIIB, being involved in the pathogenesis of HT.
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Linfócitos B/imunologia , Doença de Hashimoto/imunologia , Leucócitos Mononucleares/imunologia , Receptores de IgG/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/imunologia , Anticorpos Monoclonais/imunologia , Especificidade de Anticorpos/imunologia , Autoantígenos/imunologia , Autoimunidade/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Iodeto Peroxidase/imunologia , Proteínas de Ligação ao Ferro/imunologia , Masculino , Pessoa de Meia-Idade , Tireoglobulina/imunologia , Adulto JovemRESUMO
Rainfall serves as a significant factor contributing to slope stability challenges in mountainous areas, and simulating the process of slope rainwater movement is a crucial approach for analyzing the stability of slopes triggered by rainfall. By combining computer numerical simulation technology with traditional hydraulic and hydrological calculation theories, it is possible to create an efficient and precise rainwater movement model that can simulate and analyze the process of rainwater movement on slopes. Utilizing natural slopes as the focal point of our research, the cellular automaton method was applied to simulate rainfall runoff on slopes, and a Cellular Automata (CA) based model for rainwater movement process was developed. This model modified the Green-Ampt (G-A) infiltration model by adopting an elliptical water content curve and introducing a coefficient that quantifies the ratio of saturated to unsaturated depth. Additionally, we refined the rules governing runoff generation and convergence within the slope and on its surface, enabling a comprehensive simulation of the entire rainwater movement process on the slope. Furthermore, the effectiveness of the model was validated through analytical solutions derived from simplified assumptions, laboratory experiments on infiltration and runoff in the flume, and a case study of a natural slope. The results show that the infiltration calculation results of the rainwater movement model are closer to the experimental values, and their overall values are slightly higher than the measured values, which are basically consistent with the model test results; The runoff calculation results show a phenomenon of initially increasing and gradually approaching the measured values compared to the measured values. When applying the model to an actual slope, it was found that the model comprehensively accounts for the influence of slope seepage, infiltration and runoff process, has better performance compared to G-A modified model. The model can be used to describe the spatial distribution and temporal variation of infiltration and runoff processes.
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The prevalence of autoimmune diseases worldwide has risen rapidly over the past few decades. Increasing evidence has linked gut dysbiosis to the onset of various autoimmune diseases. Thanks to the significant advancements in high-throughput sequencing technology, the number of gut microbiome studies has increased. However, they have primarily focused on bacteria, so our understanding of the role and significance of eukaryotic microbes in the human gut microbial ecosystem remains quite limited. Here, we selected Graves' disease (GD) as an autoimmune disease model and investigated the gut multi-kingdom (bacteria, fungi, and protists) microbial communities from the health control, diseased, and medication-treated recovered patients. The results showed that physiological changes in GD increased homogenizing dispersal processes for bacterial community assembly and increased homogeneous selection processes for eukaryotic community assembly. The recovered patients vs. healthy controls had similar bacterial and protistan, but not fungal, community assembly processes. Additionally, eukaryotes (fungi and protists) may play a more significant role in gut ecosystem functions than bacteria. Overall, this study gives brief insights into the potential contributions of eukaryotes to gut and immune homeostasis in humans and their potential influence in relation to therapeutic interventions.
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Doenças Autoimunes , Microbioma Gastrointestinal , Doença de Graves , Microbiota , Humanos , Microbioma Gastrointestinal/fisiologia , Eucariotos , BactériasRESUMO
Background: Graves' disease (GD), characterized by immune aberration, is associated with gut dysbiosis. Despite the growing interest, substantial evidence detailing the precise impact of gut microbiota on GD's autoimmune processes remains exceedingly rare. Objective: This study was designed to investigate the influence of gut microbiota on immune dysregulation in GD. Methods: It encompassed 52 GD patients and 45 healthy controls (HCs), employing flow cytometry and enzyme-linked immunosorbent assay to examine lymphocyte and cytokine profiles, alongside lipopolysaccharide (LPS) levels. Gut microbiota profiles and metabolic features were assessed using 16S rRNA gene sequencing and targeted metabolomics. Results: Our observations revealed a disturbed B-cell distribution and elevated LPS and pro-inflammatory cytokines in GD patients compared to HCs. Significant differences in gut microbiota composition and a marked deficit in short-chain fatty acid (SCFA)-producing bacteria, including ASV263(Bacteroides), ASV1451(Dialister), and ASV503(Coprococcus), were observed in GD patients. These specific bacteria and SCFAs showed correlations with thyroid autoantibodies, B-cell subsets, and cytokine levels. In vitro studies further showed that LPS notably caused B-cell subsets imbalance, reducing conventional memory B cells while increasing naïve B cells. Additionally, acetate combined with propionate and butyrate showcased immunoregulatory functions, diminishing cytokine production in LPS-stimulated cells. Conclusion: Overall, our results highlight the role of gut dysbiosis in contributing to immune dysregulation in GD by affecting lymphocyte status and cytokine production.
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Microbioma Gastrointestinal , Doença de Graves , Humanos , Microbioma Gastrointestinal/genética , Disbiose/complicações , RNA Ribossômico 16S/genética , Lipopolissacarídeos , Doença de Graves/complicações , Bactérias/genética , CitocinasRESUMO
Current microbiome signatures for chronic diseases such as diabetic kidney disease (DKD) are mainly based on low-resolution taxa such as genus or phyla and are often inconsistent among studies. In microbial ecosystems, bacterial functions are strain specific, and taxonomically different bacteria tend to form co-abundance functional groups called guilds. Here, we identified guild-level signatures for DKD by performing in-depth metagenomic sequencing and conducting genome-centric and guild-based analysis on fecal samples from 116 DKD patients and 91 healthy subjects. Redundancy analysis on 1,543 high-quality metagenome-assembled genomes (HQMAGs) identified 54 HQMAGs that were differentially distributed among the young healthy control group, elderly healthy control group, early-stage DKD patients (EDG), and late-stage DKD patients (LDG). Co-abundance network analysis classified the 54 HQMAGs into two guilds. Compared to guild 2, guild 1 contained more short-chain fatty acid biosynthesis genes and fewer genes encoding uremic toxin indole biosynthesis, antibiotic resistance, and virulence factors. Guild indices, derived from the total abundance of guild members and their diversity, delineated DKD patients from healthy subjects and between different severities of DKD. Age-adjusted partial Spearman correlation analysis showed that the guild indices were correlated with DKD disease progression and with risk indicators of poor prognosis. We further validated that the random forest classification model established with the 54 HQMAGs was also applicable for classifying patients with end-stage renal disease and healthy subjects in an independent data set. Therefore, this genome-level, guild-based microbial analysis strategy may identify DKD patients with different severity at an earlier stage to guide clinical interventions. IMPORTANCE: Traditionally, microbiome research has been constrained by the reliance on taxonomic classifications that may not reflect the functional dynamics or the ecological interactions within microbial communities. By transcending these limitations with a genome-centric and guild-based analysis, our study sheds light on the intricate and specific interactions between microbial strains and diabetic kidney disease (DKD). We have unveiled two distinct microbial guilds with opposite influences on host health, which may redefine our understanding of microbial contributions to disease progression. The implications of our findings extend beyond mere association, providing potential pathways for intervention and opening new avenues for patient stratification in clinical settings. This work paves the way for a paradigm shift in microbiome research in DKD and potentially other chronic kidney diseases, from a focus on taxonomy to a more nuanced view of microbial ecology and function that is more closely aligned with clinical outcomes.
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Bactérias , Nefropatias Diabéticas , Fezes , Microbioma Gastrointestinal , Metagenoma , Metagenômica , Humanos , Microbioma Gastrointestinal/genética , Nefropatias Diabéticas/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Masculino , Feminino , Fezes/microbiologia , Pessoa de Meia-Idade , Adulto , IdosoRESUMO
The purpose of this study is to investigate the effects of supplementing Yeast-derived postbiotics (Y-dP) to the diet of sows during late pregnancy and lactation on fecal microbiota and short-chain fatty acids (SCFA) in sows and their offspring weaned piglets, as well as the relationship between gut microbiota and SCFA, serum cytokines, and sow reproductive performance. A total of 150 sows were divided into three groups: control diet (CON), CON + Y-dP 1.25 g/kg, and CON + Y-dP 2 g/kg. The results showed that supplementing 0.125% Y-dP to the diet of sows can increase the content of isobutyric acid (IBA) in the feces of pregnant sows and reduce the content of butyric acid (BA) in the feces of weaned piglets (p < 0.05). The fecal microbiota of pregnant sows ß diversity reduced and piglet fecal microbiota ß diversity increased (p < 0.05). Y-dP significantly increased the abundance of Actinobacteria and Limosilactobacilli in the feces of pregnant sows (p < 0.05), as well as the abundance of Verrucomicrobiota, Bacteroidota, and Fusobacteriota in the feces of piglets (p < 0.05). The abundance of Bacteroidota in the feces of pregnant sows is positively correlated with propionic acid (PA) (r > 0.5, p < 0.05). The abundance of Prevotellaceae_NK3B31_group was positively correlated with Acetic acid (AA), PA, Valerate acid (VA), and total volatile fatty acid (TVFA) in the feces of pregnant sows (r > 0.5, p < 0.05), and Bacteroidota and Prevotellaceae_NK3B31_group were negatively correlated with the number of stillbirths (r < -0.5, p < 0.05). The abundance of Lactobacillus and Holdemanella in piglet feces was positively correlated with TVFA in feces and negatively correlated with IgA in serum (r > 0.5, p < 0.05). In conclusion, supplementing Y-dP to the diet of sows from late gestation to lactation can increase the chao1 index and α diversity of fecal microorganisms in sows during lactation, increase the abundance of Actinobacteria and Limosilactobacilli in the feces of sows during pregnancy, and increase the abundance of beneficial bacteria such as Bacteroidetes in piglet feces, thereby improving intestinal health. These findings provide a reference for the application of Y-dP in sow production and a theoretical basis for Y-dP to improve sow production performance.
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Antimicrobial peptides have been extensively studied as potential alternatives to antibiotics. Porcine angiogenin 4 (pANG4) is a novel antimicrobial peptide in the angiogenin (ANG) family, which may have a regulatory effect on intestinal microflora. The object of present study is obtained pANG4 protein by heterologous expression, so as to explore the biological function of recombinant pANG4 (rpANG4). The pANG4 was expressed in Pichia pastoris (P. pastoris) and anti-inflammatory effects were investigated in intestinal porcine epithelial cell line-J2 (IPEC-J2) and mice. Purified rpANG4 had bacteriostatic activity and did not cause hemolysis or cytotoxicity at concentrations below 128 µg/mL. Purified rpANG4 increased the activity of IPEC-J2 and reduced apoptosis in vitro. rpANG4 reduced the pro-inflammatory gene expression and upregulated tight junction protein gene expression during inflammation. rpANG4 alleviated lipopolysaccharide (LPS)-induced liver and spleen damage, intestinal inflammation, jejunal apoptosis genes' expression, and improved immune function in an in vivo mice model. rpANG4 increased tight junction protein gene expression in jejunum, thereby improving the jejunum intestinal barrier function. In conclusion, rpANG4 had antibacterial activity, inhibited intestinal inflammation, improved intestinal barrier function, and alleviated liver and spleen damage. The current study contributes to the development of antibiotic substitutes and the improvement of animal health.
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Células Epiteliais , Mucosa Intestinal , Suínos , Animais , Camundongos , Mucosa Intestinal/metabolismo , Células Epiteliais/metabolismo , Proteínas de Junções Íntimas/metabolismo , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/metabolismoRESUMO
A novel series of 6-(indol-2-yl)pyridine-3-sulfonamides was prepared and evaluated for their ability to inhibit HCV RNA replication in the HCV replicon cell culture assay. Preliminary optimization of this series furnished compounds with low nanomolar potency against the HCV genotype 1b replicon. Among these, compound 8c has identified as a potent HCV replicon inhibitor (EC50=4 nM) with a selectivity index with respect to cellular GAPDH of more than 2500. Further, compound 8c had a good pharmacokinetic profile in rats with an IV half-life of 6h and oral bioavailability (F) of 62%. Selection of HCV replicon resistance identified an amino acid substitution in HCV NS4B that confers resistance to these compounds. These compounds hold promise as a new chemotype with anti-HCV activity mediated through an underexploited viral target.
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Antivirais/farmacologia , Descoberta de Drogas , Hepacivirus/efeitos dos fármacos , Indóis/farmacologia , Piridinas/farmacologia , Sulfonamidas/farmacologia , Proteínas não Estruturais Virais/antagonistas & inibidores , Replicação Viral/efeitos dos fármacos , Animais , Antivirais/administração & dosagem , Antivirais/química , Disponibilidade Biológica , Relação Dose-Resposta a Droga , Hepacivirus/genética , Humanos , Indóis/síntese química , Indóis/química , Testes de Sensibilidade Microbiana , Microssomos Hepáticos/metabolismo , Estrutura Molecular , Piridinas/síntese química , Piridinas/química , Ratos , Relação Estrutura-Atividade , Sulfonamidas/síntese química , Sulfonamidas/química , Proteínas não Estruturais Virais/metabolismo , Replicação Viral/genéticaRESUMO
Polymeric hydrogel materials with multiple functions are in great demand in practical biomedical scenarios. In this work, a self-healing hydrogel with both antimicrobial properties was prepared using a strategy that combines dynamic imine and borate ester bonds. In this hydrogel, polyvinyl alcohol (PVA) is used as the base network, and borax solution as the cross-linking agent, and borate ester bonds can be formed between these two. Dialdehyde carboxymethyl cellulose (DCMC) was selected to cross-link with the amino groups in carboxymethyl chitosan (CMCS) and polyethyleneimine (PEI) to form dynamic imine bonds. The PVA/PEI/DCMC/CMCS hydrogels prepared by double chemical cross-linking have good mechanical properties (maximum tensile strength up to 289 KPa and strain at the break up to 1025%). Due to the uniqueness of the two chemical bonds, the hydrogel material is self-healing at room temperature without additional stimulation. In addition, the inherent antibacterial properties of the raw materials in this hydrogel confer antibacterial properties, with a kill rate of up to 99% against E. coli and S. aureus. The multifunctional hydrogels developed in this study provide more ideas and references for the future application of hydrogel materials in practical scenarios.
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Boratos , Hidrogéis , Boratos/farmacologia , Hidrogéis/farmacologia , Escherichia coli , Staphylococcus aureus , Antibacterianos/farmacologia , Ésteres/farmacologiaRESUMO
This experiment was conducted to determine the effects of yeast-derived postbiotic (YDP) supplementation in sow diets during late gestation and lactation on the performance of sows and their offspring. At 90-d gestation, 150 sows (Landraceâ ×â Large White, parity: 3.93â ±â 0.11) were allocated to three dietary treatments (nâ =â 50 per treatment): 1) basal diet (control [CON]), 2) basal diet with 1.25 g/kg YDP (0.125 group), and 3) basal diet with 2.00 g/kg YDP (0.200 group). The experiment continued until the end of weaning (day 21 of lactation). Supplementation with YDP resulted in greater deposition of backfat in sows during late gestation and an increasing trend in average weaning weight of piglets than observed in the CON group (Pâ <â 0.01, Pâ =â 0.05). Supplementation with YDP decreased piglet mortality and diarrhea index in piglets (Pâ <â 0.05). In farrowing sows' serum, the glutathione peroxide content in the YDP group was lower than that in the CON group (Pâ <â 0.05); the content of immunoglobulin A (IgA) in the 0.200 group or YDP group was higher than that in the CON group (Pâ <â 0.05). In lactating sows' serum, malondialdehyde content was higher in the YDP group (Pâ <â 0.05). In day 3 milk of sows, the 0.200 group tended to increase the lactose content (Pâ =â 0.07), and tended to decrease the secretory immunoglobulin A (sIgA) content (Pâ =â 0.06) with respect to that in the CON group. The sIgA content in the YDP group was lower than that in the CON group (Pâ <â 0.05). In the milk of sows, the 0.200 group tended to increase the lactose content with respect to that in the CON group (Pâ =â 0.08); the immunoglobulin G (IgG) content in the 0.125 group or YDP group was higher than that in the CON group (Pâ <â 0.05). YDP supplementation increased the IgA content in the milk (Pâ <â 0.01). In sow placenta, the content of total anti-oxidant capacity in the YDP group was higher than that in the CON group (Pâ =â 0.05); and the content of transforming growth factor-ß in the YDP group was higher than that in the CON group (Pâ <â 0.05). In piglet serum, the content of IgG and immunoglobulin M in the 0.125 group was higher than that in the CON and 0.200 groups (Pâ <â 0.05). In summary, this study indicated that feeding sows diets supplemented with YDP from late gestation through lactation increased sows' backfat deposition in late gestation and piglets' weaning weight; decreased piglet mortality and diarrhea index in piglets; and improved maternal and offspring immunity.
Rapid fetal and reproductive tissue development in late gestation poses a challenge to sow health. Nutritional interventions have been shown to effectively improve animal performance. The present study investigated whether dietary supplementation with a yeast-derived postbiotic (YDP) during late gestation and lactation might improve the health and production performance of sows and piglets. At two tested dose levels (1.25 and 2.00 g/kg in the diet), dietary YDP supplementation increased backfat deposition in sows during late gestation and weaning weight in piglets, and decreased the diarrhea index in piglets. YDP supplementation tended to increase lactose content in sow milk. Dietary YDP supplementation improved immunity in sows at farrowing and piglets at weaning. These findings indicated that YDP use improves sows' production performance and may serve as an important approach to optimizing nutrient programs in sow production.
Assuntos
Lactação , Leite , Animais , Gravidez , Suínos , Feminino , Saccharomyces cerevisiae , Colostro , Lactose , Dieta/veterinária , Suplementos Nutricionais , Paridade , Imunoglobulina A , Imunoglobulina G , Imunoglobulina A Secretora/farmacologia , Diarreia/veterinária , Imunidade , Ração Animal/análiseRESUMO
The aim of this study was to investigate the effect of dietary supplementation of sows with yeast cultures (XPC) during late gestation and lactation on the immune performance of their weaned offspring under lipopolysaccharide (LPS) stress. A total of 40 Landrace × Yorkshire sows (parity 3 to 7) with similar backfat thickness were selected and randomly divided into two treatment groups: a control group (basal diet) and a yeast culture group (basal diet + 2.0 g/kg XPC). The trial was conducted from day 90 of gestation to day 21 of lactation. At the end of the experiment, 12 piglets with similar weights were selected from each group and slaughtered 4 h after intraperitoneal injection with either saline or LPS. The results showed that the concentrations of interleukin-6 (IL-6) in the thymus and tumor necrosis factor-α in the liver increased significantly (P < 0.05) in weaned piglets after LPS injection. Maternal dietary supplementation with XPC significantly reduced the concentration of inflammatory factors in the plasma and thymus of weaned piglets (P < 0.05). LPS injection significantly upregulated the expression of some tissue inflammation-related genes, significantly downregulated the expression of intestinal tight junction-related genes, and significantly elevated the protein expression of liver phospho-nuclear factor kappa B (p-NF-κB), the phospho-inhibitory subunit of NF-κB (p-IκBα), phospho-c-Jun N-terminal kinase (p-JNK), Nuclear factor kappa-B (NF-κB), and the inhibitory subunit of NF-κB (IκBα) in weaned piglets (P < 0.05). Maternal dietary supplementation with XPC significantly downregulated the gene expression of IL-6 and interleukin-10 (IL-10) in the thymus and decreased the protein expression of c-Jun N-terminal kinase (JNK) in the liver of weaned piglets (P < 0.05). In summary, injection of LPS induced an inflammatory response in weaned piglets and destroyed the intestinal barrier. Maternal dietary supplementation of XPC improved the immune performance of weaned piglets by inhibiting inflammatory responses.
Weaning older, more mature pigs helps prevent many of the adverse gastrointestinal effects associated with weaning stress, and maternal nutritional interventions can influence offspring gut health and growth performance. Therefore, it is important to explore the effects of maternal nutritional interventions on their offspring. Yeast cultures are a class of biological products consisting of metabolites produced during the anaerobic fermentation of yeast and some live yeast cells, and function to maintain the intestinal health of animals and improve production performance. The effect of sow dietary supplementation with yeast cultures on the immune performance of their weaned offspring under lipopolysaccharide stress has not so far been reported. This study provided a basis for understanding the effects of maternal transfer of yeast cultures to their offspring and provided data to support the application of yeast cultures in actual production.