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PURPOSE: Orbital venous malformations (VM) pose challenges in complete resection due to indistinct borders and bleeding proclivity. Current methods for aiding surgical excision of distensible orbital venous malformations are inadequate. We investigated whether external neck compression could facilitate intraoperative distension of venous orbital lesions during surgical excision in patients diagnosed with VM. METHODS: Eighteen patients (8 males and 10 females) diagnosed with distensible venous anomalies were enrolled. Neck compression technology, was employed to distend the lesions before puncture embolization using n-butyl-2-cyanoacrylate glue under general anesthesia. The surgical process, along with preoperative to postoperative changes in ocular symptoms, were recorded. RESULTS: The average surgical duration was 95 min. A mean of 3.41 ml surgical glue was used for embolization. The compression belt maintained pressure at 35-40 mmHg. Total lesion resection was achieved in 12 patients, with 6 patients undergoing subtotal removal not requiring supplementary surgery. Symptoms were entirely alleviated in 17 patients, and signs of distensible lesions during the Valsalva maneuver were absent. One patient underwent secondary surgery for residual eyelid lesions. Minor complications included mild ocular movement restriction, residual subcutaneous induration, transiently increased orbital pressure, and lower lid ectropion in four, three, four, and one patient, respectively. Three patients experienced a mild post-operative visual acuity decrease, although none experienced vision loss. CONCLUSIONS: Direct orbital embolization aided by a jugular vein compression device is safe and demonstrates satisfactory outcomes in orbital varicose vein treatment.
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Objectives: Anti-signal recognition particle (SRP) antibodies, markers of immune-mediated necrotising myopathy, are reportedly related to cardiac involvement; however, whether they are pathogenic to the myocardium remains unclear. We aimed, therefore, to explore the pathogenicity of anti-SRP antibodies against the myocardium through in vivo and in vitro studies. Methods: Total immunoglobulin G (IgG), purified from patients with positive anti-SRP antibodies, was passively transferred into C57BL/6 mice. Cardiac function was evaluated via echocardiography and the ventricular pressure-volume loop; cardiac histological changes were analysed using haematoxylin-eosin staining, picrosirius red staining, immunofluorescence and immunohistochemistry. Additionally, reactive oxygen species (ROS) formation was evaluated by dihydroethidium (DHE) staining; mitochondrial morphology and function were evaluated using transmission electron microscopy and seahorse mitochondrial respiration assay, respectively. The myositis cohort at our centre was subsequently reviewed in terms of cardiac assessments. Results: After the passive transfer of total IgG from patients with positive anti-SRP antibodies, C57BL/6 mice developed significant left ventricular diastolic dysfunction (LVDD). Transcriptomic analysis and corresponding experiments revealed increased oxidative stress and mitochondrial damage in the hearts of the experimental mice. Cardiomyocytes exposed to anti-SRP-specific IgG, however, recovered normal mitochondrial metabolism after treatment with N-acetylcysteine, an ROS scavenger. Moreover, patients positive for anti-SRP antibodies manifested worse diastolic but equivalent systolic function compared to their counterparts after propensity score matching. Conclusion: Anti-SRP antibodies may play a pathogenic role in the development of LVDD by promoting ROS production and subsequent myocardial mitochondrial impairment. The inhibition of oxidative stress was effective in reversing anti-SRP antibody-induced LVDD.
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BACKGROUND: CircRNA plays a regulatory role in multiple life processes. Circ_0122396 could participate in the regulation of age-related cataract (ARC) progression. However, the precise molecular mechanisms of circ_0122396 In ARC remain enigmatic. METHODS: Circ_0122396, microRNA (miR)-23a-3p, and matrix metalloprotease (MMP)-16 (MMP16) expression levels were detected via quantitative real-time polymerase chain reaction. Western blot was used to detect the levels of MMP16 and apoptosis-related proteins. Cell counting kit-8 analysis and 5-ethynyl-2'-deoxyuridine assay were used to assess human lens epithelial cells (HLECs) proliferation. Flow cytometry was performed to determine cell apoptosis. Levels of malondialdehyde (MDA) and glutathione peroxidase (GSH-PX) were measured using commercial kits. Luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RNA pull-down assay were used to examine the interaction among circ_0122396, miR-23a-3p, and MMP16. RESULTS: Circ_0122396 and MMP16 were down-regulated while miR-23a-3p was up-regulated in ARC. H2O2 constrained proliferation and GSH-PX level, promotes apoptosis and MDA level in HLECs, and overexpression of circ_0122396 attenuated these effects. miR-23a-3p was a direct target of circ_0122396, and MMP16 was a direct target of miR-23a-3p. The effect of circ_0122396 overexpression on H2O2-induced HLECs was reversed by miR-23a-3p, and MMP16 elevation overturned the impacts of miR-23a-3p in H2O2-induced HLECs. CONCLUSIONS: Circ_0122396 may regulate the progression of ARC via the miR-23a-3p/MMP16 pathway in H2O2-stimulated HLECs, which may serve as a potentially valuable biomarker and novel therapeutic target for ARC.
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Indoor formaldehyde pollution can cause inestimable harm to human health and even cancers, thus studies on the removal of formaldehyde attract extensive attentions. In this paper, an environmentally friendly and low-cost biomass material, sodium alginate (SA) was utilized to prepare pyrene functionalized amido-amine-alginic acid (AmAA-Py) by acidification and two-step amidation, which is subsequently self-assembled on reduced graphene oxide (rGO) by π-π stacking interaction, and the final composites were acidified to afford a highly porous composite material for chemical removal of formaldehyde. The formaldehyde chemical removal performance of composite is evaluated at different conditions and find that 1.0 g of acidified alginate derivatives and graphene composites (HCl·AmAA-Py-rGO) can adsorb 69.2 mg of HCHO. Simultaneously, amino groups in amido-amine derivative of acidified sodium alginate (AmAA) can react with acidic pollutants such as H2S and HCl via forming ionic bonding without generating any other by-products, which enables efficient and environment-friendly removal of acidic pollutants. The subtle design of the highly porous composite material utilizing low-cost SA and rGO with large specific surface area opens up a new methodology for fabricating highly porous materials for efficient removal of formaldehyde and other indoor hazardous pollutants.
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Alginatos , Aminas , Formaldeído , Grafite , Pirenos , Grafite/química , Formaldeído/química , Alginatos/química , Pirenos/química , Aminas/química , AdsorçãoRESUMO
Aim: Liquid biopsies analyzing cell-free DNA (cfDNA) methylation in plasma offer a noninvasive diagnostic for diseases, with the potential of aging biomarkers underexplored. Methods: Utilizing enzymatic methyl-seq (EM-seq), this study assessed cfDNA methylation patterns in aging with blood from 35 healthy individuals. Results: It found aging signatures, including higher cfDNA levels and variations in fragment sizes, plus approximately 2000 age-related differentially methylated CpG sites. A biological age predictive model based on 48 CpG sites showed a strong correlation with chronological age, verified by two datasets. Age-specific epigenetic shifts linked to inflammation were revealed through differentially methylated regions profiling and Olink proteomics. Conclusion: These findings suggest cfDNA methylation as a potential aging biomarker and might exacerbate immunoinflammatory reactivity in older individuals.
Our bodies undergo many changes as we age, some of which might affect our health. To better understand these changes, scientists study something called 'cell-free DNA' (cfDNA) in our blood. This cfDNA can give us clues about our health and the risk of diseases like cancer or heart conditions.In our research, we analyzed cfDNA from the blood of 35 people to identify patterns associated with aging. We discovered that approximately 2000 specific spots in our DNA change in a way that's linked to aging. These changes might help us figure out someone's biological age essentially, how old their body seems based on various health factors, which can differ from their actual age.We also found that these DNA changes could indicate how aging might make the body's defense system which fights off diseases react more intensely. Understanding this could be crucial for managing health as we get older.Our study suggests that cfDNA could be a useful marker for aging, offering a new approach to understanding and possibly managing the health effects associated with growing older.
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Envelhecimento , Ácidos Nucleicos Livres , Ilhas de CpG , Metilação de DNA , Epigênese Genética , Inflamação , Humanos , Envelhecimento/genética , Ácidos Nucleicos Livres/sangue , Ácidos Nucleicos Livres/genética , Feminino , Inflamação/genética , Masculino , Idoso , Pessoa de Meia-Idade , Adulto , Biomarcadores/sangue , Idoso de 80 Anos ou maisRESUMO
YCA1, the only metacaspase in Saccharomyces cerevisiae, plays important roles in the regulation of chronological lifespan, apoptosis, and cytokinesis. YCA1 has protein hydrolase activity and functions by cleaving itself and target proteins. However, there are few reports about the regulation of YCA1 activity. In this study, we observed that reactive sulfane sulfur (RSS) can inhibit the activity of YCA1. In vitro experiments demonstrated that RSS reacted with the Cys276 of YCA1, the residue central to its protein hydrolase activity, to form a persulfidation modification (protein-SSH). This modification inhibited both its self-cleavage and the cleavage of its substrate protein, BIR1. To investigate further, we constructed a low-endogenous-RSS mutant of S. cerevisiae, BY4742 Δcys3, in which the RSS-producing enzyme cystathionine-γ-lyase (CYS3) was knocked out. The activity of YCA1 was significantly increased by the deletion of CYS3. Moreover, increased YCA1 activity led to reduced chronological lifespan (CLS) and CLS-driven apoptosis. This study unveils the first endogenous factor that regulates YCA1 activity, introduces a novel mechanism of how yeast cells regulate chronological lifespan, and broadens our understanding of the multifaceted roles played by RSS.
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OBJECTIVES: To evaluate the effectiveness of the 2023 ACR/EULAR criteria for antiphospholipid syndrome (APS) in a Chinese cohort, and compare them with the Sapporo and revised Sapporo criteria. METHODS: A cohort comprising 436 patients diagnosed with APS and 514 control subjects was enrolled, including 83 with seronegative APS and 86 classified as antiphospholipid antibody (aPL) carriers. We assessed IgG and IgM anticardiolipin antibodies (aCL) and anti-ß2-glycoprotein I (aß2GPI) antibodies using ELISA, along with a systematic collection of lupus anticoagulant data. Subsequently, we compared the sensitivity and specificity across the three classification criteria. RESULTS: The 2023 ACR/EULAR criteria exhibited improved specificity at 98 %, surpassing the revised Sapporo (90 %) and original Sapporo (91 %) criteria. However, this came with decreased sensitivity at 82 %, in contrast to higher sensitivities in the revised Sapporo (98 %) and Sapporo (91 %) criteria. Examining individual components sheds light on the scoring system's rationale within the new criteria. The inclusion of microvascular thrombosis, cardiac valve disease, and thrombocytopenia improved the identification of nine patients previously classified as "probable APS". Insufficient scoring in 78 previously diagnosed APS individuals was linked to traditional risk factor evaluations for thrombotic events, the emphasis on determining whether obstetric events are linked to severe preeclampsia (PEC) or placental insufficiency (PI), and the lower scores assigned to IgM aCL and/or aß2GPI antibody. Seronegative APS remained a challenge, as non-criteria aPL and other methods were not included. CONCLUSIONS: The new criteria presented notable advancements in specificity. This study provides detailed insights into the strengths and possible challenges of the 2023 ACR/EULAR criteria, enhancing our understanding of their impact on clinical practice.
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Anticorpos Anticardiolipina , Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica , beta 2-Glicoproteína I , Humanos , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/imunologia , Síndrome Antifosfolipídica/sangue , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Anticorpos Antifosfolipídeos/sangue , Anticorpos Antifosfolipídeos/imunologia , beta 2-Glicoproteína I/imunologia , Anticorpos Anticardiolipina/sangue , China/epidemiologia , Gravidez , Estudos de Coortes , Inibidor de Coagulação do Lúpus/sangue , Sensibilidade e Especificidade , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Povo Asiático , População do Leste AsiáticoRESUMO
Asparagus, a vital economic contributor, is a well-liked vegetable grown around the globe, and some secondary metabolites in its spear are beneficial to human health. Asparagus spears possess a significant quantity of nutrients and phytochemicals; however, the difference in these chemical compositions among various varieties has not been sufficiently studied. This work aimed to detect the chemical compositions of 30 varieties of asparagus and to assess them by principal component analysis (PCA). The results showed that the contents of these chemical compositions varied in varieties. Selenium (Se, 1.12-2.9 µg/100 g dry-weight [DW]) was abundant in asparagus, with an average dry matter content of 8.25%. Free amino acids (5.60-9.98 g/100 g DW) and polyphenols (6.34-8.67 mg/g DW) were both present in high amounts, along with flavonoids (4.218-8.22 mg/g DW) and protodioscin (0.44-1.96 mg/g DW). Correlation analysis, PCA, and hierarchical cluster analysis were used to conduct a comprehensive evaluation of asparagus. Atlas, Appolo, Jinggang 111, Jingke 2, and WS-1 were the top five varieties with comprehensive scores. This study provided valuable data for the breeding, quality improvement, processing, and utilization of asparagus varieties in the future.
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α-succinimide-substituted allenoates were employed as phosphine acceptors in phosphine-catalyzed (4 + 2) annulation with 1,1-dicyanoalkenes. They served as C4 synthons in the annulation reaction under mild reaction conditions and produced hexahydroisoindole derivatives in moderate to high yields with good to excellent diastereoselectivities.
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Monitoring etoposide is important due to its wide usage in anti-tumor therapy; however, the commonly used HPLC method is expensive and often requires complicated extraction and detection procedures. Electrochemical analysis has great application prospects because of its rapid response and high specificity, sensitivity, and efficiency with low cost and high convenience. In this study, we constructed a nanoporous gold (NPG)-modified GCE for the detection of etoposide. The electrochemical oxidation of etoposide by NPG caused a sensitive current peak at +0.27 V with good reproductivity in 50 mM of phosphate buffer (pH 7.4). The relationship between etoposide concentration and peak current was linear in the range between 0.1 and 20 µM and between 20 and 150 µM, with a detection sensitivity of 681.8 µA mM-1 cm-2 and 197.2 µA mM-1 cm-2, respectively, and a limit of detection (LOD) reaching 20 nM. The electrode had a good anti-interference ability to several common anions and cations. Spiked recovery tests in serum, urine, and fermentation broth verified the excellent performance of the sensor in terms of sensitivity, reproducibility, and specificity. This may provide a promising tool for the detection of etoposide in biological samples.
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Antineoplásicos , Nanoporos , Etoposídeo , Ouro , Reprodutibilidade dos Testes , Técnicas Eletroquímicas/métodos , EletrodosRESUMO
Macrophage activation syndrome (MAS) is a potentially fatal consequence of adult-onset Still's disease (AOSD), driven by a cytokine storm. Efficient early diagnosis of AOSD-associated MAS requires a sensitive and specific biomarker. In this study, we demonstrated that pentraxin 3 (PTX3), an acute phase protein, was associated with AOSD disease activity and served as a biomarker for AOSD-MAS. PTX3 levels were significantly increased in AOSD patients compared to other autoimmune diseases and healthy controls. Plasma PTX3 levels showed positive correlations with inflammatory markers, the systemic score and the HScore. In active AOSD with MAS, PTX3 levels were higher compared to those in non-AOSD haemophagocytic lymphohistiocytosis (HLH) patients. Moreover, the PTX3's area under the curve value for distinguishing AOSD with MAS exceeded that of soluble interleukin-2 receptor, ferritin and C-reactive protein. Furthermore, plasma levels of PTX3 were associated with circulating NET-DNA levels. To fully understand the underlying mechanism of PTX3 prompting AOSD and AOSD-MAS progression, we discovered that neutrophils exhibited enhanced NET formation and mitogen-activated protein kinases (MAPK) pathway activation upon PTX3 stimulation. More importantly, PTX3-induced NET formation was effectively dampened by MAPK pathway inhibitors. These findings collectively revealed that PTX3 has a favorable correlation with disease activity and may serve as a potential biomarker to differentiate AOSD patients with MAS. Additionally, PTX3 induces NET release via the MAPK pathway, suggesting a pathogenic role in AOSD-MAS.
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Síndrome de Ativação Macrofágica , Componente Amiloide P Sérico , Doença de Still de Início Tardio , Adulto , Humanos , Biomarcadores , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Síndrome de Ativação Macrofágica/diagnóstico , Ativação de Neutrófilo , Componente Amiloide P Sérico/metabolismo , Doença de Still de Início Tardio/sangue , Doença de Still de Início Tardio/diagnóstico , Doença de Still de Início Tardio/imunologiaRESUMO
Horizontal gene transfer has been demonstrated to be an important driver for the emergency of multidrug-resistant pathogens. Recently, a transferable gene cluster tmexCD1-toprJ1 of the resistance-nodulation-division (RND) superfamily was identified in the plasmids of animal-derived Klebsiella pneumoniae strains, with a higher efflux capacity for various drugs than the Escherichia coli AcrAB-TolC homolog system. In this study, we focused on the differences in the inner membrane pump of these two systems and identified some key residues that contribute to the robust efflux activity of the TMexCD1 system. With the aid of homologous modeling and molecular docking, eight residues from the proximal binding pocket (PBP) and nine from the distal binding pocket (DBP) were selected and subjected to site-directed mutagenesis. Several of them, such as S134, I139, D181, and A290, were shown to be important for substrate binding in the DBP region, and all residues in PBP and DBP showed certain substrate preferences. Apart from the conservative switch loop (L613-623TMexD1) previously identified in the E. coli AcrB (EcAcrB), a relatively unconservative loop (L665-675TMexD1) at the bottom of PBP was proposed as a critical element for the robust activity of TMexD1, due to variations at sites E669, G670, N673, and S674 compared to EcAcrAB, and the significantly altered efflux activity due to their mutations. The conservation and flexibility of these key factors can contribute to the evolution of the RND efflux pumps and thus serve as potential targets for developing inhibitors to block the widespread of the TMexCD1 system.
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Proteínas de Escherichia coli , Escherichia coli , Animais , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Antibacterianos/química , Simulação de Acoplamento Molecular , Farmacorresistência Bacteriana Múltipla/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Testes de Sensibilidade MicrobianaRESUMO
Coastal lagoon is critical habitat for human and provides a wide range of ecosystem services. These vital habitats are now threatened by waste discharge and eutrophication. Previous studies suggest that the pollution mitigation of coastal lagoon relies on the water exchange with open sea, and the role of microbial processes inside the lagoon is overlooked. This study takes the Pinqing Lagoon which is the largest coastal lagoon in Chinese mainland as example. The distribution of nutrients, microbial activity of nitrogen removal and community structure of denitrifying bacteria in sediment are analyzed. The results showed that the nutrient in sediment represented by DIN (1.65-12.78 mg kg-1), TOM (0.59-8.72 %) and TN (0.14-1.93 mg g-1) are at high levels and are enriched at the terrestrial impacted zone (TZ). The microbial nitrogen removal is active at 0.27-19.76 µmol N kg-1 h-1 in sediment and denitrification is the dominate pathway taking 51.44-98.71 % of total N removal. The composition of the denitrifying microbial community in marine impacted zone (MZ) is close to that of ocean and estuary, but differs considerably with those of TZ and transition zone (TM). The denitrification activity is mainly controlled by salinity and pH, and the denitrifying bacterial community composition related to the nutrient parameters of TN, TOM, etc. Our study suggested that the distribution of nutrients, microbial activity of nitrogen removal and community structure in Lagoon are the combined effects of terrestrial input and exchange with open sea. The microbial processes play important role in the nitrogen removal of coastal lagoon.
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Desnitrificação , Ecossistema , Humanos , Nitrogênio/análise , Salinidade , China , Concentração de Íons de HidrogênioRESUMO
Accurate cancer survival prediction is crucial for oncologists to determine therapeutic plan, which directly influences the treatment efficacy and survival outcome of patient. Recently, multimodal fusion-based prognostic methods have demonstrated effectiveness for survival prediction by fusing diverse cancer-related data from different medical modalities, e.g., pathological images and genomic data. However, these works still face significant challenges. First, most approaches attempt multimodal fusion by simple one-shot fusion strategy, which is insufficient to explore complex interactions underlying in highly disparate multimodal data. Second, current methods for investigating multimodal interactions face the capability-efficiency dilemma, which is the difficult balance between powerful modeling capability and applicable computational efficiency, thus impeding effective multimodal fusion. In this study, to encounter these challenges, we propose an innovative multi-shot interactive fusion method named MIF for precise survival prediction by utilizing pathological and genomic data. Particularly, a novel multi-shot fusion framework is introduced to promote multimodal fusion by decomposing it into successive fusing stages, thus delicately integrating modalities in a progressive way. Moreover, to address the capacity-efficiency dilemma, various affinity-based interactive modules are introduced to synergize the multi-shot framework. Specifically, by harnessing comprehensive affinity information as guidance for mining interactions, the proposed interactive modules can efficiently generate low-dimensional discriminative multimodal representations. Extensive experiments on different cancer datasets unravel that our method not only successfully achieves state-of-the-art performance by performing effective multimodal fusion, but also possesses high computational efficiency compared to existing survival prediction methods.
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Zero-valent sulfur, commonly utilized as a fertilizer or fungicide, is prevalent in various environmental contexts. Its most stable and predominant form, octasulfur (S8), plays a crucial role in microbial sulfur metabolism, either through oxidation or reduction. However, the mechanism underlying its cellular uptake remains elusive. We presented evidence that zero-valent sulfur was adsorbed to the cell surface and then dissolved into the membrane lipid layer as lipid-soluble S8 molecules, which reacted with cellular low-molecular thiols to form persulfide, e.g., glutathione persulfide (GSSH), in the cytoplasm. The process brought extracellular zero-valent sulfur into the cells. When persulfide dioxygenase is present in the cells, GSSH will be oxidized. Otherwise, GSSH will react with another glutathione (GSH) to produce glutathione disulfide (GSSG) and hydrogen sulfide (H2S). The mechanism is different from simple diffusion, as insoluble S8 becomes soluble GSSH after crossing the cytoplasmic membrane. The uptake process is limited by physical contact of insoluble zero-valent sulfur with microbial cells and the regeneration of cellular thiols. Our findings elucidate the cellular uptake mechanism of zero-valent sulfur, which provides critical information for its application in agricultural practices and the bioremediation of sulfur contaminants and heavy metals.
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Sulfeto de Hidrogênio , Lipídeos de Membrana , Sulfetos/metabolismo , Oxirredução , Dissulfeto de Glutationa , Compostos de Sulfidrila , Enxofre/metabolismoRESUMO
BACKGROUND: In the Fontan palliation for single ventricle heart disease (SVHD), pulmonary blood flow is non-pulsatile/passive, low velocity, and low shear, making viscous power loss a critical determinant of cardiac output. The rheologic properties of blood in SVHD patients are essential for understanding and modulating their limited cardiac output and they have not been systematically studied. We hypothesize that viscosity is decreased in single ventricle circulation. METHODS: We evaluated whole blood viscosity, red blood cell (RBC) aggregation, and RBC deformability to evaluate changes in healthy children and SVHD patients. We altered suspending media to understand cellular and plasma differences contributing to rheologic differences. RESULTS: Whole blood viscosity was similar between SVHD and healthy at their native hematocrits, while viscosity was lower at equivalent hematocrits for SVHD patients. RBC deformability is increased, and RBC aggregation is decreased in SVHD patients. Suspending SVHD RBCs in healthy plasma resulted in increased RBC aggregation and suspending healthy RBCs in SVHD plasma resulted in lower RBC aggregation. CONCLUSIONS: Hematocrit corrected blood viscosity is lower in SVHD vs. healthy due to decreased RBC aggregation and higher RBC deformability, a viscous adaptation of blood in patients whose cardiac output is dependent on minimizing viscous power loss. IMPACT: Patients with single ventricle circulation have decreased red blood cell aggregation and increased red blood cell deformability, both of which result in a decrease in blood viscosity across a large shear rate range. Since the unique Fontan circulation has very low-shear and low velocity flow in the pulmonary arteries, blood viscosity plays an increased role in vascular resistance, therefore this work is the first to describe a novel mechanism to target pulmonary vascular resistance as a modifiable risk factor. This is a novel, modifiable risk factor in this patient population.
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Viscosidade Sanguínea , Agregação Eritrocítica , Deformação Eritrocítica , Técnica de Fontan , Humanos , Criança , Cardiopatias Congênitas/cirurgia , Cardiopatias Congênitas/fisiopatologia , Masculino , Feminino , Hematócrito , Coração Univentricular/cirurgia , Coração Univentricular/fisiopatologia , Pré-Escolar , Ventrículos do Coração/fisiopatologia , Ventrículos do Coração/anormalidades , Débito Cardíaco , Adolescente , EritrócitosRESUMO
Herein, we reported a general and green synthetic strategy for photochromic functional alginate derivatives grafting with isoindolinone spiroxanthenes. Under mild condition, diverse 2-aminoalkyl isoindolinone spiroxanthene derivatives have been prepared from organic photochromic isobenzofuranone spiroxanthenes (including rhodamine B, rhodamine 6G and fluorescein), and grafted on alginate chains through amidation reaction using diamine as a linkage with water as a green solvent at room temperature. The photochromic properties of the fluorophores-modified polymers and the effect of pH value have been explored. Under acid conditions, the spiroisoindolinone rings of alginate derivatives are opened resulting in showing absorption bands and fluorescence with orange to green emission, while the alginate derivatives turned to colourless under basic conditions which is reversibly. In addition to biodegradability and biocompatibility, the polymers exhibit good film-forming properties simultaneously. The films and fibers produced from the alginate derivatives also project good fluorescence properties.
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INTRODUCTION: This study aimed to characterize the morbidity, hospitalization, and mortality rates among patients with adult-onset Still's disease (AOSD) affected by coronavirus disease 2019 (COVID-19) and explore the impact of COVID-19 on the disease activity of AOSD. METHODS: Data on the clinical and demographic characteristics, COVID-19-related symptoms, and outcomes were retrospectively collected. Patients were stratified according to COVID-19 severity and associations between risk factors and outcomes were analyzed using multivariate logistic regression. The disease activity of patients with AOSD flares after COVID-19 was described. RESULTS: A total of 188 patients with AOSD were followed up, of whom 75.5% (n = 142) had a confirmed or highly suspected COVID-19. Patients on medium or high-dose oral glucocorticoids or Janus kinase (JAK) inhibitors were at increased risk of developing moderate to severe COVID-19. Six patients suffered flares of AOSD following COVID-19 in a short period; however, the relapse rate was not statistically increased compared with patients without COVID-19. CONCLUSION: Patients with AOSD receiving medium or high-dose glucocorticoid therapy or JAK inhibitors had worse COVID-19 outcomes. Further work is needed to explore risk factors affecting COVID-19 outcomes and the impact of COVID-19 on disease activity in AOSD.
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BACKGROUND: Adult-onset Still's disease (AOSD) is a systemic autoinflammatory disease characterized by innate immune system activation, with a high risk for macrophage activation syndrome (MAS). MAS development is associated with monocyte/macrophage activation and cytokine storm. Monocytes consist of three different subsets, classical monocytes (CMs, CD14brightCD16 -), intermediate monocytes (IMs, CD14brightCD16 +), and non-classical monocytes (NCMs, CD14dimCD16 +), each has distinct roles in inflammatory regulation. However, the frequencies and regulatory mechanism of monocyte subsets in AOSD patients have not been identified. METHODS: We performed flow cytometry, RNA sequencing, phagocytosis analysis, and enzyme-linked immunosorbent assay to evaluate monocyte subsets, cell functions, and potential biomarkers. The effect of neutrophil extracellular traps (NETs) on monocytes was determined by evaluating mRNA levels of DNA sensors, surface CD16 expression, and inflammasome pathway activation. RESULTS: Higher proportions of intermediate monocytes (IMs) were identified in active AOSD patients. IMs displayed higher expression of CD80, CD86, HLA-DR, and CD163 than CMs and NCMs. CD163 upregulation was noted on AOSD IMs, accompanied by increased phagocytic activity and elevated cytokine/chemokine production, including IL-1ß, IL-6, CCL8, and CXCL10. The frequencies of IMs were correlated with disease activity and higher in AOSD patients with MAS (AOSD-MAS). CCL8 and CXCL10 were highly expressed in RNA sequencing of monocytes from AOSD-MAS patients and plasma CXCL10 level could serve as a potential biomarker for AOSD-MAS. Moreover, DNA-sensing pathway was activated in monocytes from AOSD-MAS patients. Stimulation with NETs derived from AOSD induced DNA sensor expression, the expansion of IMs, and inflammasome pathway activation. These effects can be abrogated by DNase I treatment. CONCLUSIONS: Our results demonstrated that the proportions of IMs were elevated in AOSD and associated with MAS. The DNA component in NETs from AOSD plays an important role in the formation of IMs, shedding new light for the therapeutic target.