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For the conventional type-II heterojunction photocatalyst, their photocatalytic activity is affected by the limited separation efficiency of electron-hole pairs, exquisitely designed heterojunction photocatalysts are highly prospective materials for inducing charge transfer efficiently. Typically, enhancing the separation efficiency of electron-hole pairs in photocatalysts has been a formidable challenge. Here, the hollow mesoporous TiO2 (H-TiO2), the bulk g-C3N4 (B-CN), and g-C3N4 with bamboo shape (BS-CN) are prepared by simple processes. Among them, it is surprising to find that the band structure of g-C3N4 can be regulated and controlled by adjusting its structure. The B-CN/H-TiO2/BS-CN (CNTOCN) dual-type-II heterojunction photocatalyst and B-CN/H-TiO2 (CNTO) type-II heterojunction photocatalyst are designed to improve the separation efficiency of electron-hole pairs. The superiority of CNTOCN dual-type-II heterojunction photocatalyst is demonstrated by the photocatalysis experiment, the band structure analysis, and the photoelectric characterization. The results show that CNTOCN (0.8428 h-1) has much higher photocatalytic activity than H-TiO2 (0.0812 h-1), B-CN (0.3569 h-1), and CNTO (0.5934 h-1). The improvement of photocatalytic activity is ascribed to the establishment of the dual-type-II heterojunction charge transfer mechanism. This work presents an approach to designing efficient dual-type-II heterojunction photocatalysts for the sustainable conversion of solar energy to photodegrade dyes in dyeing wastewater.
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INTRODUCTION: Transversus abdominis plane (TAP) blocks are commonly used for postoperative analgesia after various abdominal surgeries. There are several different approaches for performing TAP blocks, mainly including posterior, lateral and subcostal approaches. An increasing number of randomised controlled trials (RCTs) have compared the analgesic effects of different TAP block approaches, but the results have not been consistent. This protocol aims to determine the optimal approach of ultrasound-guided TAP blocks for postoperative analgesia after abdominal surgery. METHODS AND ANALYSIS: Four databases, including Web of Science, PubMed, EMBASE and the Cochrane Library will be systematically searched to identify RCTs that compared the analgesic effects of different ultrasound-guided TAP block approaches. The search interval will range from the inception of the databases to 30 July 2024. The postoperative opioid consumption over 24 hours will be defined as the primary outcome. The secondary outcomes will include the analgesia duration, postoperative pain scores at rest and during movement at different timepoints and the incidence of adverse effects. All the statistical analyses will be conducted using RevMan V.5.4. The quality of evidence will be evaluated by the Grading of Recommendations Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION: Ethical approval will not be needed. The results will be submitted to one peer-reviewed journal when completed. PROSPERO REGISTRATION NUMBER: CRD42024510141.
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Músculos Abdominais , Metanálise como Assunto , Bloqueio Nervoso , Dor Pós-Operatória , Revisões Sistemáticas como Assunto , Ultrassonografia de Intervenção , Humanos , Bloqueio Nervoso/métodos , Músculos Abdominais/inervação , Músculos Abdominais/diagnóstico por imagem , Ultrassonografia de Intervenção/métodos , Dor Pós-Operatória/prevenção & controle , Abdome/cirurgia , Projetos de Pesquisa , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Objective: To investigate the changes in gut microbes and their metabolites after administering synbiotics to patients with new-onset lupus nephritis (LN) treated using a conventional method and provide a theoretical basis for finding new targets for the diagnosis and treatment of LN. Methods: In this study, a total of 12 participants were divided into the lupus and synbiotic groups. Stool samples and clinical data were collected before and after treatment for metagenomic, nontargeted metabolomic, and statistical analyses. Results: The relative abundances of the pathogenic bacteria Prevotella, Bacteroides, and Enterobacteriaceae_unclassified decreased after synbiotic treatment, whereas the abundances of Actinobacteria and Firmicutes increased. Further, the Firmicutes to Bacteroidetes ratio increased; however, the difference was not statistically significant (p > 0.05). α diversity analysis showed no significant differences in the intestinal microbial richness and diversity index of patients with LN between the groups before and after treatment (p > 0.05). ß analysis showed the differences in the community structure between the samples of the two groups before and after treatment. Linear discriminant analysis effect size and receiver operating characteristic curve analyses revealed that Negativicutes (AUC = 0.9722) and Enterobacteriaceae_unclassified (AUC = 0.9722) were the best predictors of the lupus and synbiotic groups, respectively, before and after treatment. Joint analyses revealed that amino acid biosynthesis, aminoacyl-tRNA biosynthesis, purine metabolism, and other metabolic pathways may be involved in the changes in the metabolic function of patients with LN after the addition of synbiotics. Spearman's correlation analysis revealed the interaction between clinical features and flora, and flora exhibited a complex biological network regulatory relationship. Conclusion: Synbiotics regulate the metabolic functions of intestinal microorganisms in patients with LN and play a role in various biological functions. Synbiotic supplements may be safe and promising candidates for patients with LN.
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Hereditary hemochromatosis (HH) is a disease characterized by disordered iron metabolism. It often involves mutations of the HFE gene, which encodes the homeostatic iron regulator protein (HFE), as well as mutations affecting hepcidin antimicrobial peptide, hemojuvelin, or transferrin receptor 2. Historically, HH has been observed primarily in European and European diaspora populations, while classical HH is rare in Asian populations, including in China. In this article, we report a rare case of HH in a Chinese man that could be attributed to a heterozygous C282Y/H63D HFE mutation. Based on clinical examination, liver biopsy, and genetic testing results, the patient was diagnosed with HH. Clinical signs and symptoms and serum iron-related test results were recorded for a period of two years after the patient began treatment. Over this observation period, the patient was subjected to 25 phlebotomies (accounting for a total blood loss of 10.2 L). His serum ferritin levels decreased from 1550 µg/L to 454 µg/L, his serum iron concentration decreased from 40 µmol/L to 24.6 µmol/L, and his transferrin saturation decreased from 97.5% to 55.1%. Early diagnosis is essential for patients with HH to obtain good outcomes. Regular phlebotomy after diagnosis can improve HH symptoms and delay HH disease progression.
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Valproate (VPA) is broad-spectrum antiepileptic drug. Several adverse reactions including hepatotoxicity, fetal risk and pancreatitis are well known and labelled as boxed warnings in the USA. One adverse reaction that is less well known but clinically significant for its severe morbidity is hyperammonemic encephalopathy. We present a case of woman with hyperammonemic encephalopathy following the initiation of VPA therapy; she had a favourable outcome with discontinuation of the drug and prompt treatment with lactulose and L-carnitine.
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Encefalopatias , Hiperamonemia , Síndromes Neurotóxicas , Feminino , Humanos , Gravidez , Ácido Valproico/efeitos adversos , Hiperamonemia/tratamento farmacológico , Anticonvulsivantes/efeitos adversos , Síndromes Neurotóxicas/tratamento farmacológico , Encefalopatias/induzido quimicamente , Encefalopatias/tratamento farmacológicoRESUMO
Population-based association studies have identified many genetic risk loci for coronary artery disease (CAD), but it is often unclear how genes within these loci are linked to CAD. Here, we perform interaction proteomics for 11 CAD-risk genes to map their protein-protein interactions (PPIs) in human vascular cells and elucidate their roles in CAD. The resulting PPI networks contain interactions that are outside of known biology in the vasculature and are enriched for genes involved in immunity-related and arterial-wall-specific mechanisms. Several PPI networks derived from smooth muscle cells are significantly enriched for genetic variants associated with CAD and related vascular phenotypes. Furthermore, the networks identify 61 genes that are found in genetic loci associated with risk of CAD, prioritizing them as the causal candidates within these loci. These findings indicate that the PPI networks we have generated are a rich resource for guiding future research into the molecular pathogenesis of CAD.
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Doença da Artéria Coronariana , Humanos , Doença da Artéria Coronariana/genética , Mapas de Interação de Proteínas , Redes Reguladoras de Genes , Loci Gênicos , ProteômicaRESUMO
In this work, a salt-free and low alkali dyeing process was developed through cationic modification of cotton fabric with a series of quaternary ammonium salts (QAS). The dyeing performance indicated that the cationic cotton fabric treated with 3-chloro-2-hydroxypropyldimethyloctane ammonium chloride (CT-8) achieved better K/S value (8.87) and dye fixation (90.47 %) compared to the conventional dyeing process. Notably, the CT-8 treated fabric performed exceptionally under salt-free conditions and with a Na2CO3 concentration of 5 g/L. The rationale behind the adoption of a salt-free and low-alkali dyeing process was attributed to the positive charge of quaternary ammonium groups, which had an augmenting impact on the hydroxyl reaction activity of cotton fabrics. The condensed Fukui function, atomic charge, and HOMO orbital calculations showed that the QAS structure could regulate the hydroxyl reactivity of cationic cotton fabric. Our salt-free and low alkali dyeing process not only achieved the aim of reducing chemical consumption and emissions, but also contributed to better understand the effect of hydroxyl reactivity of cationic cotton on the fixation reaction with reactive dye, and provided a new direction to achieve the require of sustainable development and clean production for a variety of industrial crops and products.
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Compostos de Amônio , Corantes , Corantes/química , Celulose/química , Fibra de Algodão , Têxteis , Compostos de Amônio Quaternário , Cátions/químicaRESUMO
BACKGROUND: Ischemia-induced inflammatory response is the main pathological mechanism of myocardial infarction (MI)-caused heart tissue injury. It has been known that helminths and worm-derived proteins are capable of modulating host immune response to suppress excessive inflammation as a survival strategy. Excretory/secretory products from Trichinella spiralis adult worms (Ts-AES) have been shown to ameliorate inflammation-related diseases. In this study, Ts-AES were used to treat mice with MI to determine its therapeutic effect on reducing MI-induced heart inflammation and the immunological mechanism involved in the treatment. METHODS: The MI model was established by the ligation of the left anterior descending coronary artery, followed by the treatment of Ts-AES by intraperitoneal injection. The therapeutic effect of Ts-AES on MI was evaluated by measuring the heart/body weight ratio, cardiac systolic and diastolic functions, histopathological change in affected heart tissue and observing the 28-day survival rate. The effect of Ts-AES on mouse macrophage polarization was determined by stimulating mouse bone marrow macrophages in vitro with Ts-AES, and the macrophage phenotype was determined by flow cytometry. The protective effect of Ts-AES-regulated macrophage polarization on hypoxic cardiomyocytes was determined by in vitro co-culturing Ts-AES-induced mouse bone marrow macrophages with hypoxic cardiomyocytes and cardiomyocyte apoptosis determined by flow cytometry. RESULTS: We observed that treatment with Ts-AES significantly improved cardiac function and ventricular remodeling, reduced pathological damage and mortality in mice with MI, associated with decreased pro-inflammatory cytokine levels, increased regulatory cytokine expression and promoted macrophage polarization from M1 to M2 type in MI mice. Ts-AES-induced M2 macrophage polarization also reduced apoptosis of hypoxic cardiomyocytes in vitro. CONCLUSIONS: Our results demonstrate that Ts-AES ameliorates MI in mice by promoting the polarization of macrophages toward the M2 type. Ts-AES is a potential pharmaceutical agent for the treatment of MI and other inflammation-related diseases.
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Infarto do Miocárdio , Trichinella spiralis , Camundongos , Animais , Trichinella spiralis/metabolismo , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Modelos Animais de Doenças , Inflamação/metabolismo , Macrófagos , Citocinas/metabolismo , Proteínas de Helminto/metabolismo , Camundongos Endogâmicos C57BLRESUMO
Tricuspid regurgitation (TR) is a relatively common finding. There has been growing recognition of the morbidity and adverse prognosis of severe TR, which affects 1.6 million people in the US. However, symptomatic TR remains undertreated despite emerging therapeutic modalities. In this review, the pathophysiological and epidemiological features of TR are examined and the diagnosis, natural history, and clinical presentation are discussed. An overview of TR therapy is provided, including medical and surgical treatments, as well as novel percutaneous approaches. The currently available studies on percutaneous therapy demonstrate promise for transcatheter valve repair and replacement with favourable clinical outcomes and short-term durability. However, further study is needed.
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BACKGROUND: Despite the well-established benefits of cardiac rehabilitation (CR) for patients with cardiovascular disease (CVD), participation in CR remain low. Virtual CR programs present a unique opportunity to promote utilization. To date, few virtual CR cohorts have been analyzed for compliance. This study aims to determine factors that predict compliance within a large virtual CR program in the United States. METHODS: We analyzed 1409 patients enrolled in the Kaiser Permanente Mid-Atlantic States Virtual CR program that consists of 12 CR sessions via telephone. Demographic characteristics, as well as body weight, blood pressure, HbA1c level, and smoking status were collected at admission. Patients were further classified by CVD diagnosis codes. Compliance was defined as at least 75% (9/12 sessions) attendance. Data was analyzed using simple and multiple regression models with significance defined as P < 0.05. RESULTS: Age was the single strongest predictor for virtual CR compliance (adjusted R2 = 0.58; P < 0.001), and non-compliant patients were younger. HbA1C level, CVD diagnosis codes, and smoking status each moderately predicted compliance (adjusted R2 = 0.48, 0.42, and 0.31, respectively; P < 0.001). Smoking and HbA1C level combined in a multiple regression model significantly improved prediction of compliance (adjusted R2 = 0.79, P < 0.01). Sex, baseline weight or hypertension were not significant predictors of CR compliance. CONCLUSIONS: Age, diabetes, CVD diagnoses, smoking status at admission are independent predictors of compliance in a large virtual CR program. Targeted intervention could be designed accordingly to improve CR compliance.
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Reabilitação Cardíaca , Doenças Cardiovasculares , Humanos , Estados Unidos , Hemoglobinas Glicadas , Cooperação do Paciente , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , FumarRESUMO
The grafted modification TiO2@SiO2 composite was fabricated by a liquid-phase deposition method with Na2SiO3 and a grafting reaction with a silane coupling agent. First, the TiO2@SiO2 composite was prepared, and the effect of deposition rate and silica content on the morphology, particle size, dispersibility, and pigmentary property of TiO2@SiO2 composites was investigated by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy, energy-dispersive X-ray spectroscopy (EDX), X-ray photoelectron spectroscopy (XPS), and ζ-potential. The islandlike TiO2@SiO2 composite had a good particle size and printing performance compared with the dense TiO2@SiO2 composite. The presence of Si was confirmed by EDX elemental analysis and XPS, and a peak at 980 cm-1 belonging to Si-O was observed in the FTIR spectrum, confirming the presence of SiO2 anchored at TiO2 surfaces via Si-O-Ti bonds. Then, the islandlike TiO2@SiO2 composite was modified by grafting with a silane coupling agent. The effect of the silane coupling agent on the hydrophobicity and dispersibility was investigated. The peaks at 2919 and 2846 cm-1 belong to CH2 in the FTIR spectrum, and Si-C in the XPS confirmed the grafting of silane coupling agent to the TiO2@SiO2 composite. The grafted modification of the islandlike TiO2@SiO2 composite using 3-triethoxysilylpropylamine endowed it with weather durability, dispersibility, and good printing performance.
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In order to further develop and utilize shrimp processing by-products, in this study, a novel antibacterial hydrolysate of shrimp by-products by pepsin hydrolysis (SPH) was prepared. The antibacterial effect of SPH on specific spoilage organisms of squid after end storage at room temperature (SE-SSOs) was investigated. SPH showed an antibacterial effect on the growth of SE-SSOs, with (23.4 ± 0.2) mm of inhibition zone diameter. The cell permeability of SE-SSOs was enhanced after SPH treatment for 12 h. Some bacteria were twisted and shrunk, while pits and pores formed and intracellular contents leaked under scanning electron microscopy observation. The flora diversity of SE-SSOs treated with SPH was determined by a 16S rDNA sequencing technique. Results showed that SE-SSOs were mainly composed of the phyla of Firmicutes and Proteobacteria, among which Paraclostridium (47.29%) and Enterobacter (38.35%) were dominant genera. SPH treatment resulted in a significant reduction in the relative abundance of the genus Paraclostridium and increased the abundance of Enterococcus. Linear discriminant analysis (LDA) of LEfSe conveyed that SPH treatment had a significant impact on altering the bacterial structure of SE-SSOs. The 16S PICRUSt of Cluster of Orthologous Group (COG) annotation revealed that SPH treatment for 12 h could significantly increase the function of transcription level [K], while SPH treatment for 24 h could downregulate post-translational modifications, protein turnover, and chaperone metabolism functions [O]. In conclusion, SPH has a proper antibacterial effect on SE-SSOs and can change the flora structure of SE-SSOs. These findings will provide a technical basis for the development of inhibitors of squid SSOs.
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Decapodiformes , Alimentos Marinhos , Animais , Bactérias/genética , Antibacterianos/farmacologia , HidróliseRESUMO
Cationic modification of cotton fabric was an effective way to improve the inkjet printing performance with reactive dye ink. However, there were few research studies that focused on the effect of the cationic agent structure, especially the alkyl chain length of the quaternary ammonium salt (QAS) cationic modifier, on the K/S value, dye fixation, and diffusion of inkjet-printed cotton fabric. In our work, different alkyl chain lengths of QAS were synthesized, and the inkjet printing performance of cationic cotton fabrics treated with different QASs was investigated. Compared with untreated cotton fabric, the K/S value and dye fixation of cationic cotton fabric treated with different QASs improved by 10.7 to 69.3% and 16.9 to 27.7%, respectively. With the increase in alkyl chain length of QAS, the interaction force between anionic reactive dyes and cationic QAS gradually increased mainly due to the fact that more N-positive ions on the quaternary ammonium group were exposed under the action of steric hindrance of alkyl chain length through the XPS spectrum. The electrostatic attraction between cationic cotton and reactive dye contributed to the diffusion of reactive dye into the fiber interior and enhanced the reaction probability of nucleophilic substitution reaction between monochlorotriazine reactive dye and the hydroxyl group of cotton fabric. The antibacterial result of the inkjet-printed cotton fabric indicated that when the alkyl chain length of QAS was higher than 8, the cationic cotton fabric obtained good antibacterial property.
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One of the cardinal features of any liver replacement therapy is the ability to remove accumulated metabolites. However, an unsolved problem is the low dialyzability of lipophilic toxins. This study aimed to explore whether bilirubin and bile acids removal can be increased by free fatty acid (FFA) displacement and its synergy with albumin dialysis. First, we found that the protein binding of both bilirubin and bile acids decreased significantly with increasing FFA concentrations when co-incubated directly. Then, in vitro dialysis showed that fatty acid mixtures infusion prefilter effectively increased the fractional removals of bilirubin and bile acids, showing higher efficiency compared with albumin-based hemodialysis (HD); in vivo dialysis in liver failure rats showed that lipid emulsion administration resulted in higher reduction ratios and more total solute removals for bilirubin and bile acids after 4 h HD compared with control, which were also superior to albumin-based HD. Finally, the highest dialysis efficacy was always observed by their synergy whether in vitro or in vivo . These findings highlight that FFA displacement-based HD could efficiently improve the dialytic removal of bilirubin and bile acids, which might even be more efficient than albumin-based HD. Their synergy may represent a promising strategy to maximize the removal of circulating bilirubin and bile acids accumulated in liver failure.
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Ácidos Graxos não Esterificados , Falência Hepática , Ratos , Animais , Albumina Sérica , Diálise Renal/métodos , Bilirrubina , Ácidos e Sais Biliares , Falência Hepática/terapiaRESUMO
To explore the effect of surface charge properties of a photocatalyst on photocatalytic activity, quaternization TiO2 particles with different alkyl chain lengths (CT-X/P25) are first synthesized to boost the photocatalytic activity. The effect of a quaternary ammonium group with different alkyl chain lengths on the photocatalytic activity of CT-X/P25 is investigated. Interestingly, the introduction of a quaternary ammonium group on CT-X/P25 not only contributes to improving the photodegradation efficiency of anionic dyes due to enhancing of adsorption capacity through electrostatic attraction, but also it can improve the photodegradation efficiency of cationic dyes. Therefore, there seems to be another factor affecting the photocatalytic activity. The results of photoelectric characterization show that the photogenerated charge separation of CT-X/P25 is greatly enhanced, which is beneficial to improve the photocatalytic activity. Simultaneously, the results show that the difference in the photocatalytic activity of CT-X/P25 is mainly related to the charge intensity of -N+(CH3)2- in the quaternary amine salt. According to X-ray photoelectron spectroscopy, the charge intensity of -N+(CH3)2- in CT-X/P25 gradually increases with the increase in alkyl chain lengths, which is conducive to promoting photogenerated charge separation and improving the adsorption for anionic dyes. The photocatalytic activity has been further enhanced due to the enhancement of this synergy. In summary, the quaternary ammonium salt-modified CT-X/P25 shows an excellent synergistic effect on the process of photodegradation of anionic dyes: promoting photogenerated charge separation and adsorption.
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The clustering algorithms based on deep neural network perform clustering by obtaining the optimal feature representation. However, in the face of complex natural images, the cluster accuracy of existing clustering algorithms is still relatively low. This paper presents an image clustering algorithm based on predefined evenly-distributed class centroids (PEDCC) and composite cosine distance. Compared with the current popular auto-encoder structure, we design an encoder-only network structure with normalized latent features, and two effective loss functions in latent feature space by replacing the Euclidean distance with a composite cosine distance. We find that (1) contrastive learning plays a key role in the clustering algorithm and greatly improves the quality of learning latent features; (2) compared with the Euclidean distance, the composite cosine distance can be more suitable for the normalized latent features and PEDCC-based Maximum Mean Discrepancy (MMD) loss function; and (3) for complex natural images, a self-supervised pretrained model can be used to effectively improve clustering performance. Several experiments have been carried out on six common data sets, MNIST, Fashion-MNIST, COIL20, CIFAR-10, STL-10 and ImageNet-10. Experimental results show that our method achieves the best clustering effect compared with other latest clustering algorithms.
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A catalytic glycosyl fluoride activation system using the GeCl2·dioxane-AgBF4 combination was developed, which involves a reversible activation of the anomeric C-F bond by a [Ge(II)-Cl]+ cation and a reversible chloride ion transfer between Ge(II) and glycosyl cations. This catalytic glycosylation system is easy to operate, proceeds at room temperature, and offers a broad scope of substrates.
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Dioxanos , Fluoretos , Catálise , Fluoretos/química , GlicosilaçãoRESUMO
Caspases are evolutionarily conserved cysteine proteases that are essential for regulating cell death and are involved in multiple development and disease processes, including immunity. Here, we show that the bacterial type III secretion system (T3SS) effector CopC (Chromobacterium outer protein C) from the environmental pathogen Chromobacterium violaceum attacks caspase-3/-7/-8/-9 by ADPR-deacylization to dysregulate programmed cell death, including apoptosis, necroptosis, and pyroptosis. This modification involves ADP-ribosylation- and deamination-mediated cyclization on Arg207 of caspase-3 by a mechanism that requires the eukaryote-specific protein calmodulin (CaM), leading to inhibition of caspase activity. The manipulation of cell death signaling by CopC is essential for the virulence of C. violaceum in a mouse infection model. CopC represents a family of enzymes existing in taxonomically diverse bacteria associated with a wide spectrum of eukaryotes ranging from humans to plants. The unique activity of CopC establishes a mechanism by which bacteria counteract host defenses through a previously unrecognized post-translational modification.
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Arginina , Caspases , Animais , Apoptose , Caspase 3 , Caspases/genética , Caspases/metabolismo , Camundongos , PiroptoseRESUMO
AIMS: Genetic studies have implicated the ARHGEF26 locus in the risk of coronary artery disease (CAD). However, the causal pathways by which DNA variants at the ARHGEF26 locus confer risk for CAD are incompletely understood. We sought to elucidate the mechanism responsible for the enhanced risk of CAD associated with the ARHGEF26 locus. METHODS AND RESULTS: In a conditional analysis of the ARHGEF26 locus, we show that the sentinel CAD-risk signal is significantly associated with various non-lipid vascular phenotypes. In human endothelial cell (EC), ARHGEF26 promotes the angiogenic capacity, and interacts with known angiogenic factors and pathways. Quantitative mass spectrometry showed that one CAD-risk coding variant, rs12493885 (p.Val29Leu), resulted in a gain-of-function ARHGEF26 that enhances proangiogenic signalling and displays enhanced interactions with several proteins partially related to the angiogenic pathway. ARHGEF26 is required for endothelial angiogenesis by promoting macropinocytosis of Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) on cell membrane and is crucial to Vascular Endothelial Growth Factor (VEGF)-dependent murine vessel sprouting ex vivo. In vivo, global or tissue-specific deletion of ARHGEF26 in EC, but not in vascular smooth muscle cells, significantly reduced atherosclerosis in mice, with enhanced plaque stability. CONCLUSIONS: Our results demonstrate that ARHGEF26 is involved in angiogenesis signaling, and that DNA variants within ARHGEF26 that are associated with CAD risk could affect angiogenic processes by potentiating VEGF-dependent angiogenesis.
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Fatores de Troca do Nucleotídeo Guanina , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Animais , Humanos , Camundongos , Neovascularização Patológica , Neovascularização Fisiológica/fisiologia , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Fatores de Troca do Nucleotídeo Guanina/genéticaRESUMO
INTRODUCTION: Protein-bound uraemic toxins (PBUTs) are poorly removed by conventional dialytic techniques, given their high plasma protein binding, and thus low, free (dialysable) plasma concentration. Here, we evaluated and compared PBUTs removal among conventional haemodialysis (HD), adsorption-based HD, displacement-based HD, and their 2 combinations both in vitro and in vivo. METHODS: The removal of PBUTs, including 3-carboxy-4-methyl-5-propyl-2-furan-propanoic acid (CMPF), p-cresyl sulphate (PCS), indoxyl sulphate (IS), indole-3-acetic acid (3-IAA), and hippuric acid, was first evaluated in an in vitro single-pass HD model. Adsorption consisted of adding 40 g/L bovine serum albumin (Alb) to the dialysate and displacement involved infusing fatty acid (FA) mixtures predialyser. Then, uraemic rats were treated with either conventional HD, Alb-based HD, lipid emulsion infusion-based HD or their combination to calculate the reduction ratio (RR), and the total solute removal (TSR) of solutes after 4 h of therapy. RESULTS: In vitro dialysis revealed that FAs infusion prefilter increased the removal of PCS, IS, and 3-IAA 3.23-fold, 3.01-fold, and 2.24-fold, respectively, compared with baseline and increased the fractional removal of CMPF from undetectable at baseline to 14.33 ± 0.24%, with a dialysis efficacy markedly superior to Alb dialysis. In vivo dialysis showed that ω-6 soybean oil-based lipid emulsion administration resulted in higher RRs and more TSRs for PCS, IS, and 3-IAA after 4-h HD than the control, and the corresponding TSR values for PCS and IS were also significantly increased compared to that of Alb dialysis. Finally, the highest dialysis efficacy for highly bound solute removal was always observed with their combination both in vitro and in vivo. CONCLUSIONS: The concept of combined displacement- and adsorption-based dialysis may open up new avenues and possibilities in the field of dialysis to further enhance PBUTs removal in end-stage renal disease.