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The relationship between green and grey urban infrastructure, local meteorological conditions, and traffic-related air pollution is complex and dynamic. This case study examined the effect of evolving morphologies around a city square park in Dublin and explores the twin impacts of local urban development (grey) and maturing parks (green) on particulate matter (PM) pollution. A fixed air quality monitoring campaign and computational fluid dynamic modelling (ENVI-met) were used to assess current (baseline) and future scenarios. The baseline results presented the distribution of PM in the study area, with bimodal (PM2.5) and unimodal (PM10) diurnal profiles. The optimal vegetation height for air quality within the park also differed by wind direction with 21 m vegetation optimal for parallel winds (10.45% reduction) and 7 m vegetation optimal for perpendicular winds (30.36% reduction). Increased building heights led to higher PM2.5 concentrations on both footpaths ranging from 25.3 to 37.0% under perpendicular winds, whilst increasing the height of leeward buildings increased PM2.5 concentrations by up to 30.9% under parallel winds. The findings from this study provide evidence of the importance of more in-depth analysis of green and grey urban infrastructure in the urban planning decision-making process to avoid deteriorating air quality conditions around city square parks.
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In near-road neighborhoods, residents are more frequently exposed to traffic-related air pollution (TRAP), and they are increasingly aware of pollution levels. Given this consideration, this study adopted portable air pollutant sensors to conduct a mobile monitoring campaign in two near-road neighborhoods, one in an urban area and one in a suburban area of Shanghai, China. The campaign characterized spatiotemporal distributions of fine particulate matter (PM2.5) and black carbon (BC) to help identify appropriate mitigation measures in these near-road micro-environments. The study identified higher mean TRAP concentrations (up to 4.7-fold and 1.7-fold higher for PM2.5 and BC, respectively), lower spatial variability, and a stronger inter-pollutant correlation in winter compared to summer. The temporal variations of TRAP between peak hour and off-peak hour were also investigated. It was identified that district-level PM2.5 increments occurred from off-peak to peak hours, with BC concentrations attributed more to traffic emissions. In addition, the spatiotemporal distribution of TRAP inside neighborhoods revealed that PM2.5 concentrations presented great temporal variability but almost remained invariant in space, while the BC concentrations showed notable spatiotemporal variability. These findings provide valuable insights into the unique spatiotemporal distributions of TRAP in different near-road neighborhoods, highlighting the important role of hyperlocal monitoring in urban micro-environments to support tailored designing and implementing appropriate mitigation measures.
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Poluentes Atmosféricos , Monitoramento Ambiental , Material Particulado , Emissões de Veículos , Poluentes Atmosféricos/análise , Material Particulado/análise , Emissões de Veículos/análise , China , Poluição do Ar/estatística & dados numéricos , Poluição Relacionada com o Tráfego/análise , Fuligem/análiseRESUMO
Struvite biomineralization is an ecologically sound technology, adept at the efficient recovery and recycling of phosphorus from wastewater. However, the biomineralization process is often perturbed by the presence of antibiotics, notably tetracycline (TC), the impact of which on the biomineralization system has not been elucidated. This study examines the efficacy of Bacillus cereus LB-9 in struvite biomineralization, focusing on the precipitates' composition, morphology, and TC content. LB-9 facilitate an alkaline environment that effectively recovering nitrogen and phosphorus. These findings indicate that TC retards the initial formation of struvite and the concurrent recovery of nitrogen and phosphorus. However, at concentrations below 10 mg/L TC concentrations, TC enhanced struvite production (0.38g) by stimulating LB-9's growth and metabolic activity. Conversely, at a concentration of 10 mg/L TC, the strain's activity was markedly suppressed within the initial four days. This data suggests that TC promotes the strain's proliferation and metabolism, potentially through cellular secretions, thereby augmenting phosphorus recovery from wastewater. Notably, the recovered struvite doesn't contain TC, aligning with regulatory standards for agricultural application. In summary, LB-9-mediated struvite recovery is an effective strategy for producing phosphorus-enriched fertilizers and mitigating TC contamination, offering significant implications for wastewater treatment and industrial process development, particularly in the context of prevalent TC in wastewater.
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Bacillus cereus , Fósforo , Estruvita , Tetraciclina , Águas Residuárias , Fósforo/metabolismo , Águas Residuárias/química , Bacillus cereus/metabolismo , Estruvita/química , Biomineralização , Antibacterianos , Poluentes Químicos da Água/metabolismo , Eliminação de Resíduos Líquidos/métodos , Nitrogênio/metabolismo , FertilizantesRESUMO
Dopamine (DA), ascorbic acid (AA), and uric acid (UA) are crucial neurochemicals, and their abnormal levels are involved in various neurological disorders. While electrodes for their detection have been developed, achieving the sensitivity required for in vivo applications remains a challenge. In this study, we proposed a synthetic Au24Cd nanoenzyme (ACNE) that significantly enhanced the electrochemical performance of metal electrodes. ACNE-modified electrodes demonstrated a remarkable 10-fold reduction in impedance compared to silver microelectrodes. Furthermore, we validated their excellent electrocatalytic activity and sensitivity using five electrochemical detection methods, including cyclic voltammetry, differential pulse voltammetry, square-wave pulse voltammetry, normal pulse voltammetry, and linear scanning voltammetry. Importantly, the stability of gold microelectrodes (Au MEs) modified with ACNEs was significantly improved, exhibiting a 30-fold enhancement compared to Au MEs. This improved performance suggests that ACNE functionalization holds great promise for developing micro-biosensors with enhanced sensitivity and stability for detecting small molecules.
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Ácido Ascórbico , Técnicas Biossensoriais , Dopamina , Técnicas Eletroquímicas , Ouro , Microeletrodos , Ácido Úrico , Dopamina/análise , Ouro/química , Ácido Ascórbico/análise , Ácido Úrico/análise , Prata/química , Cádmio/análiseRESUMO
Objectives: Endotracheal tube (ETT) intubation is a life-saving procedure in patients with respiratory failure. However, the presence of an ETT can cause significant discomfort. A tracheostomy tube is used to administer a mechanical ventilator, resulting in a more stable airway and fewer serious injuries. Noninvasive ventilators (NIPPVs) administer ventilation through masks and must be tightly fixed to the face. ETT, tracheostomy, and NIPPV are the most common methods of ventilator maintenance. However, these interventions often cause discomfort to patients. This study aimed to compare discomfort associated with ETT, tracheostomy, and NIPPV. Materials and Methods: Forty-nine conscious patients with postextubation NIPPV and eight conscious patients who underwent postextubation tracheotomy were evaluated for discomfort. A questionnaire survey on discomfort was performed before and after NIPPV or tracheostomy. These patients reported their level of discomfort on a visual analog scale. Results: The levels of sore throat, nasal pain, body pain, activity limitation, respiratory discomfort, oral discomfort, difficulty coughing sputum, worry about respiratory tube disconnection, back pain, anxiety, worry about long-term admission, sleep disturbance, and general discomfort during ETT intubation were higher than during tracheostomy or NIPPV (all P < 0.05). The mean level of discomfort was approximately 5-6 points (moderate) in patients with ETT and 2-3 points (mild) in patients with NIPPV or tracheostomy. Conclusion: The level of discomfort was higher in patients who underwent ETT intubation than in those who underwent NIPPV or tracheostomy. However, the level of discomfort was similar between the patients with NIPPV and those who underwent tracheostomy.
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Aluminum batteries have become the most attractive next-generation energy storage battery due to their advantages of high safety, high abundance, and low cost. However, the dendrite problem associated with inhomogeneous electrodeposition during cycling leads to low Coulombic efficiency and rapid short-circuit failure of the aluminum metal anode, which severely hampers the cycling stability of aluminum battery. Here we show an aluminum anode material that achieves high lattice matching between the substrate and the deposit, allowing the aluminum deposits to maintain preferred crystal plane growth on the substrate surface. It not only reduces the nucleation barrier of aluminum and decreases electrode polarization, but also enables uniform deposition of aluminum, improving the cycling stability of aluminum batteries. Aluminum anode with (111) preferred crystal plane can stably 25000 cycles at the current density of 5 A·g-1, with a capacity retention rate of over 80%.
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This study collected 80 samples of suspected kratom plant powder. A polymerase chain reaction sequence analysis was conducted using two sets of DNA barcode primers for plant ribosomal (r)DNA internal transcribed spacers (ITSs), namely, ITS3/ITS4 and ITS-p3/ITS-u4. Among the 80 samples, 40 were analyzed using the ITS3/ITS4 primer pair, and then DNA sequences were subjected to a National Center for Biotechnology Information-Basic Local Alignment Search Tool (NCBI-BLAST) comparison. Results showed that 29 samples had a 100% match (364/364) with Mitragyna speciosa (kratom), and 6 samples had a 99.73% match (363/364) with M. speciosa, whereas 5 samples had disordered and unreadable sequences. The 5 unreadable samples and an additional 40 suspected kratom samples were then analyzed using the ITS-p3/ITS-u4 primer pair, followed by an NCBI-BLAST comparison. Among these, 32 samples had a 100% match (404/404) with M. speciosa, and 11 samples had a 99.75% match (403/404) with M. speciosa. Among the samples with sequences matching M. speciosa, three distinct types were observed (no variance/404, 287M/404, and 287A/404). One sample had a 99.51% match (404/406) with Neolamarckia cadamba, and another sample had a sequencing length of 305 bp, with 25 positions showing mixed base pairs, indicating a mixture of different species. Analysis of the mixed base pair pattern suggested a possible mixture of M. speciosa and N. cadamba. Actually, M. speciosa and N. cadamba have very similar external morphologies. This indicates that the ITS-p3/ITS-u4 primer pair is effective in distinguishing mixtures of M. speciosa and N. cadamba and is thus more suitable than ITS3/ITS4 for identifying and analyzing samples of suspected kratom plant powder.
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The immunosuppressive characteristics and acquired immune resistance can restrain the therapy-initiated anti-tumor immunity. In this work, an antibody free programmed death receptor ligand 1 (PD-L1) downregulator (designated as CeSe) is fabricated to boost photodynamic activated immunotherapy through cyclin-dependent kinase 5 (CDK5) inhibition. Among which, FDA approved photosensitizer of chlorin e6 (Ce6) and preclinical available CDK5 inhibitor of seliciclib (Se) are utilized to prepare the nanomedicine of CeSe through self-assembly technique without drug excipient. Nanoscale CeSe exhibits an increased stability and drug delivery efficiency, contributing to intracellular production of reactive oxygen species (ROS) for robust photodynamic therapy (PDT). The PDT of CeSe can not only suppress the primary tumor growth, but also induce the immunogenic cell death (ICD) to release tumor associated antigens. More importantly, the CDK5 inhibition by CeSe can downregulate PD-L1 to re-activate the systemic anti-tumor immunity by decreasing the tumor immune escape and therapy-induced acquired immune resistance. This work provides an antibody free strategy to activate systemic immune response for metastatic tumor treatment, which may accelerate the development of translational nanomedicine with sophisticated mechanism.
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Antígeno B7-H1 , Quinase 5 Dependente de Ciclina , Imunoterapia , Fotoquimioterapia , Fotoquimioterapia/métodos , Antígeno B7-H1/metabolismo , Antígeno B7-H1/antagonistas & inibidores , Imunoterapia/métodos , Animais , Quinase 5 Dependente de Ciclina/metabolismo , Quinase 5 Dependente de Ciclina/antagonistas & inibidores , Humanos , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Camundongos , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Porfirinas/química , Porfirinas/farmacologia , Porfirinas/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , ClorofilídeosRESUMO
To enhance the cellular uptake of liposomes, we prepared conventional liposomes with targeting molecules and surface-charged liposomes and evaluated their potential as nano-carriers and vaccine adjuvants by comparing their endocytosis efficiencies using immune cells. Surface-charged liposomes were synthesized via a one-step microfluidic method, which provided a novel, simple, fast, and highly reproducible method for preparing liposomes. Flow cytometry revealed that cationic polyelectrolyte-coated liposomes exhibited higher endocytosis efficiencies (of up to a factor of 100) in A774A.1 cells and JAWs II cells compared with uncoated liposomes or those coated with anionic polyelectrolytes. Positively charged liposomes exhibited some cytotoxicity at quaternary-chitosan coating concentrations higher than 6â¯mg/mL; however, significantly lower cytotoxicities (by a factor of almost ten) were obtained by protein mixing. Furthermore, BALB/c mice vaccinated with a mixture of Anthrax vaccine adsorbed (AVA) and quaternary chitosan-coated liposomes showed faster and stronger anti-PA IgG inductions compared to those vaccinated with AVA alone, with titers positively correlating with the amount of cationic liposome used. This finding clearly reveals that quaternary chitosan-coated liposomes act as both nano-carriers and vaccine adjuvants that significantly enhance in-vivo immune responses to vaccines with low immunogenicities.
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Endocitose , Lipossomos , Camundongos Endogâmicos BALB C , Lipossomos/química , Animais , Endocitose/efeitos dos fármacos , Camundongos , Polieletrólitos/química , Quitosana/química , Microfluídica/métodos , FemininoRESUMO
Introduction: Hepatocellular carcinoma (HCC) is one of the major types of liver cancer. Previous studies have shown that the centromere protein family is associated with malignant biological behaviors such as HCC proliferation. As a member of the centromere protein family, centromere protein Q (CENPQ) is closely associated with immunotherapy and immune cell infiltration in various tumors. However, the role and mechanism of CENPQ in HCC remain unclear. Methods: Multiple public databases and RT-qPCR were used to study the expression of CENPQ in HCC. Based on TCGA data, the correlation between CENPQ and clinicopathological characteristics and prognosis of HCC patients was analyzed, and its diagnostic value was evaluated. The potential biological functions of CENPQ in HCC were explored by functional enrichment analysis of differentially expressed genes. The distribution of tumor-infiltrating immune cell types was assessed using single-sample GSEA, and immune checkpoint gene expression was analyzed using Spearman correlation. Subsequently, loss-of-function experiments were performed to determine the function of CENPQ on the cell cycle and proliferation of HCC cells in vitro. Results: CENPQ was found highly expressed in HCC and correlated with weight, BMI, age, AFP, T stage, pathologic stage, histologic grade, and prothrombin time (all p < 0.05). ROC and Kaplan-Meier analyses indicated that CENPQ may be potentially used as a diagnostic marker for HCC (AUC = 0.881), and its upregulation is associated with decreased OS (p = 0.002), DSS (p < 0.001), and PFI (p = 0.002). Functional enrichment analysis revealed an association of CENPQ with biological processes such as immune cell infiltration, cell cycle, and hippo-merlin signaling deregulation in HCC. Furthermore, knockdown of CENPQ manifested in HCC cells with G0/1 phase cycle arrest and decreased proliferative capacity. Conclusion: CENPQ expression was higher in HCC tissues than in normal liver tissues. It was significantly associated with poor prognosis, immune cell infiltration, cell cycle, and proliferation. Therefore, CENPQ may become a promising prognostic biomarker for HCC patients.
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The vertical settling of plastic debris in oceans is poorly understood. A large share of low-density microplastics (LDMPs) are largely absent from sea surfaces. The present study employs a model that considers the potential of an overlooked microbially induced calcium carbonate precipitation (MICP) process and new motion equations for irregular LDMPs. Here we show that the motion of LDMPs in the present model, exhibiting a damped oscillation pattern, is quite different from that in biofouling models. Furthermore, LDMPs in the size range of 10-200 µm are most likely to gain sufficient density at the biofouling/MICP stage to independently sink to the ocean floor with relatively small drag coefficients, potentially explaining the selective enrichment of LDMPs in the oceanic sediment. The size and shape exhibit strong non-linear effects on the settling patterns of LDMPs. Overall, the present study highlights the importance of calcite-mediated sinking of LDMPs in open oceans.
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Three Stemona alkaloids named stemotuberines A-C (1-3) with unique C17N frameworks, presumably formed by elimination of the C-11-C-15 lactone ring of the stichoneurine skeleton, were isolated from the roots of Stemona tuberosa. Their structures were elucidated by spectroscopic analysis, X-ray diffraction, and computational methods. Compounds 2 and 3 showed inhibition (IC50 values of 37.1 and 23.2 µM, respectively) against LPS-induced nitric oxide production in RAW 264.7 cells. In addition, concern was expressed about the reported plant origin (S. sessilifolia) of the recently described alkaloids tuberostemonols O-R (4-7), which should be S. tuberosa. NMR calculations indicated structural misassignment of these compounds except for 6. Isolation of tuberostemonol P (5) from our material of S. tuberosa allowed for a close examination of the spectroscopic data leading to the revised structure 5a. Tuberostemonol R (7) was found to have identical 1H and 13C NMR data to the well-known alkaloid croomine, and therefore its structure including relative stereochemistry must be revised as 7a.
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Alcaloides , Óxido Nítrico , Compostos Fitoquímicos , Raízes de Plantas , Stemonaceae , Estrutura Molecular , Stemonaceae/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Alcaloides/química , Camundongos , Raízes de Plantas/química , Células RAW 264.7 , Animais , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologiaRESUMO
BACKGROUND: This study aimed to identify potential subtypes of hepatocellular carcinoma (HCC) associated with cirrhosis and to investigate key markers using bioinformatic analysis of gene expression datasets-0. METHODS: Three data sets (GSE17548, GSE56140, and GSE87630) were extracted from the Gene Expression Omnibus (GEO) database and normalized using the Limma package in R. Principal component analysis (PCA) and cluster analysis was performed to examine data distribution and identify subtypes. Differential gene expression analysis was performed using the Limma software package. Protein-protein interaction analysis and functional annotation were performed using the STRING database and Cytoscape software. Important signaling pathways and processes were identified using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway Analysis. RESULTS: The analysis revealed different subtypes of HCC associated with cirrhosis and identified several key genes, including CCNB2, MCM4, and CDC20, with strong binding power and prognostic value. Functional annotation indicated involvement in cell cycle regulation and metabolic pathways. ROC analysis showed high sensitivity and specificity of these genes in predicting HCC prognosis. CONCLUSION: These results suggest that CCNB2, MCM4, and CDC20 may serve as potential biomarkers for predicting HCC prognosis in patients with cirrhosis and provide insights into the molecular mechanisms of HCC progression.
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BACKGROUND: Exploring networks of mental and behavioral problems in children and adolescents may identify differences between one-child and multi-child families. This study compared the network structures of mental and behavioral problems in children and adolescents in one-child families versus multi-child families based on a nationwide survey. METHODS: Propensity score matching (PSM) was used to match children and adolescents from one-child families with those from multi-child families. Mental and behavioral problems were assessed using the Achenbach's Child Behavior Checklist (CBCL) with eight syndromal subscales. In the network analysis, strength centrality index was used to estimate central symptoms, and case-dropping bootstrap method was used to assess network stability. RESULTS: The study included 39,648 children and adolescents (19,824 from one-child families and 19,824 from multi-child families). Children and adolescents from multi-child families exhibited different network structure and higher global strength compared to those from one-child families. In one-child families, the most central symptoms were "Social problems", "Anxious/depressed" and "Withdrawn/depressed", while in multi-child families, the most central symptoms were "Social problems", "Rule-breaking behavior" and "Anxious/depressed". CONCLUSION: Differences in mental and behavioral problems among children and adolescents between one-child and multi-child families were found. To address these problems, interventions targeting "Social problems" and "Anxious/depressed" symptoms should be developed for children and adolescents in both one-child and multi-child families, while other interventions targeting "Withdrawn/depressed" and "Rule-breaking behavior" symptoms could be useful for those in one-child and multi-child families, respectively.
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Comportamento Problema , Pontuação de Propensão , Humanos , Criança , Adolescente , Masculino , Feminino , China , Comportamento Problema/psicologia , Transtornos do Comportamento Infantil/psicologia , Transtornos Mentais/psicologia , Inquéritos e Questionários , Família/psicologiaRESUMO
Bisphenol analogues (BPs) are commonly found in riverine and coastal waters. However, the lack of a reliable and robust passive sampling method has hindered our ability to monitor these compounds in aquatic systems. The study developed a novel organic-diffusive gradients in thin film (o-DGT) sampler based on stainless steel mesh membrane, polyacrylamide diffusive gel, and hydrophilic-lipophilic balance (HLB) binding gel. This innovative design tackled issues of filter membrane sorption in traditional o-DGT devices and potential gel damage in membrane-less o-DGT devices, showing promising application prospects. The mass accumulation of 15 target BPs was linear over 10 days in both freshwater (r2 ≥ 0.92) and seawater (r2 ≥ 0.94), with no saturation observed. The diffusion coefficients (D) through polyacrylamide diffusive gels ranged from 4.04 × 10-6 to 5.77 × 10-6 cm2 s-1 in freshwater and from 1.74 × 10-6 to 4.69 × 10-6 cm2 s-1 in seawater for the target BPs (except for bisphenol PH) at 22 °C. The D values of the target BPs in seawater were lower than those in freshwater due to the high salinity in seawater (35 ). The o-DGT samplers demonstrated good integrity in field applications. The total concentrations of the eight detected BPs ranged from 9.2 to 323 ng L-1, which was consistent with the measurements obtained by grab sampling. Among all BPs, bisphenol S, bisphenol F, and bisphenol A were consistently detected at all sites using both sampling methods. The concentrations of some novel BPs in coastal water measured by grab sampling were comparable to those measured in rivers, suggesting the need to strengthen pollution control of BPs in coastal areas. These results indicate that the o-DGT passive sampling method developed in the present study can be effectively used for monitoring BPs in freshwater and coastal environments.
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Per- and polyfluoroalkyl substances (PFAS) have been shown to penetrate the blood-brain barrier (BBB) and accumulate in human brain. The BBB transmission and accumulation efficiency of PFAS, as well as the potential health risks from human co-exposure to legacy and emerging PFAS due to differences in transport efficiency, need to be further elucidated. In the present pilot study, 23 plasma samples from glioma patients were analyzed for 17 PFAS. The concentrations of PFAS in six paired brain tissue and plasma samples were used to calculate the BBB transmission efficiency of PFAS (RPFAS). This RPFAS analysis was conducted with utmost care and consideration amid the limited availability of valuable paired samples. The results indicated that low molecular weight PFAS, including short-chain and emerging PFAS, may have a greater potential for accumulation in brain tissue than long-chain PFAS. As an alternative to perfluorooctane sulfonic acid (PFOS), 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) exhibited brain accumulation potential similar to that of PFOS, suggesting it may not be a suitable substitute concerning health risk in brain. The BBB transmission efficiencies of perfluorooctanoic acid, PFOS, and 6:2 Cl-PFESA showed similar trends with age, which may be an important factor influencing the entry of exogenous compounds into the brain. A favorable link between perfluorooctane sulfonamide (FOSA) and the development and/or progression of glioma may be implicated by a strong positive correlation (r2 = 0.94; p < 0.01) between RFOSA and Ki-67 (a molecular marker of glioma). However, a causal relationship between RFOSA and glioma incidence were not established in the present study. The present pilot study conducted the first examination of BBB transmission efficiency of PFAS from plasma to brain tissue and highlighted the importance of reducing and/or controlling exposure to PFAS.
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Barreira Hematoencefálica , Fluorocarbonos , Humanos , Barreira Hematoencefálica/metabolismo , Projetos Piloto , Fluorocarbonos/sangue , Pessoa de Meia-Idade , Feminino , Adulto , Masculino , Glioma , Idoso , Poluentes Ambientais/sangue , Exposição Ambiental , Ácidos Alcanossulfônicos/sangue , Encéfalo/metabolismoRESUMO
A new fluorescent sensor for the determination of lemon yellow was developed based on nitrogen-doped carbon quantum dots (N-CQDs), which were prepared via a hydrothermal method with dried pomelo peel and L-tyrosine. The N-CQDs exhibited the blue fluorescence with a quantum yield of 28 %. The sensing principle of N-CQDs was quenched by lemon yellow via static quenching. The potential interfering substances showed no influence on the detection of lemon yellow. The limit of detection was 0.023 mg/L and lower than that of national standard. Furthermore, the synthesized N-CQDs have been successfully applied to the measurement of lemon yellow in real samples. Hence, the N-CQDs would be a promising sensor in food analysis.
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Carbono , Nitrogênio , Pontos Quânticos , Espectrometria de Fluorescência , Pontos Quânticos/química , Carbono/química , Nitrogênio/química , Bebidas Gaseificadas/análise , Química Verde/métodos , Limite de Detecção , Citrus/química , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese químicaRESUMO
Enterovirus 71 (EV71) causes hand-foot-and-mouth disease (HFMD), neurological complications, and even fatalities in infants. Clinically, the increase of extracellular vesicles (EVs) in EV71 patients' serum was highly associated with the severity of HFMD. EV71 boosts EVs biogenesis in an endosomal sorting complex required for transport (ESCRT)-dependent manner to facilitate viral replication. Yet, the impact of EVs-derived from ESCRT-independent pathway on EV71 replication and pathogenesis is highly concerned. Here, we assessed the effects of EV71-induced EVs from ESCRT-independent pathway on viral replication and pathogenesis by GW4869, a neutral sphingomyelinase inhibitor. Detailly, in EV71-infected mice, blockade of the biogenesis of tissue-derived EVs in the presence of GW4869 restored body weight loss, attenuated clinical scores, and improved survival rates. Furthermore, GW4869 dampens EVs biogenesis to reduce viral load and pathogenesis in multiple tissues of EV71-infected mice. Consistently, GW4869 treatment in a human intestinal epithelial HT29 cells decreased the biogenesis of EVs, in which the progeny EV71 particle was cloaked, leading to the reduction of viral infection and replication. Collectively, GW4869 inhibits EV71-induced EVs in an ESCRT-independent pathway and ultimately suppresses EV71 replication and pathogenesis. Our study provides a novel strategy for the development of therapeutic agents in the treatment for EV71-associated HFMD.
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Compostos de Anilina , Complexos Endossomais de Distribuição Requeridos para Transporte , Enterovirus Humano A , Vesículas Extracelulares , Replicação Viral , Animais , Replicação Viral/efeitos dos fármacos , Enterovirus Humano A/efeitos dos fármacos , Enterovirus Humano A/fisiologia , Camundongos , Vesículas Extracelulares/metabolismo , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Humanos , Compostos de Benzilideno/farmacologia , Infecções por Enterovirus/virologia , Infecções por Enterovirus/tratamento farmacológico , Infecções por Enterovirus/metabolismo , Carga Viral/efeitos dos fármacos , FemininoRESUMO
The CMC-PNIPAM hydrogel with semi-interpenetrating structure and temperature-sensitivity was prepared by in-situ polymerization of N-isopropylacrylamide (NIPAM) in sodium carboxymethylcellulose (CMC) solution at room temperature. The mass ratio of CMC to NIPAM was a key factor influencing the network structure and property of CMC-PNIPAM hydrogel. The low critical phase transition temperature (LCST) of CMC-PNIPAM hydrogels increased from 34.4⯰C to 35.8⯰C with the mass ratio of CMC to NIPAM rising from 0 to 1.2. The maximum compressive stress of CMC-PNIPAM hydrogel reached to 26.7â¯kPa and the relaxation elasticity was 52â¯% at strain of 60â¯%. The viscoelasticity of CMC-PNIPAM hydrogel was consistent with the generalized Maxwell model. The maximum swelling ratio in deionized water was 170.25â¯g·g-1 (dried hydrogel) with swelling rate of 2.57â¯g·g-1·min-1 at 25⯰C. CMC-PNIPAM hydrogel hardly absorbed water above LCST, but the swollen hydrogel could release water at the rate of 0.36â¯g·g-1·min-1 once exceeding LCST. The test of water retention showed that soil mixed with 2â¯wt% dried CMC-PNIPAM hydrogel could retain 13.08â¯wt% water after 30â¯days at 25⯰C that was 4.4 times than that of controlled soil without CMC-PNIPAM hydrogel. The semi-interpenetrating CMC-PNIPAM hydrogel showed a potential to conserve water responding to temperature.
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Resinas Acrílicas , Carboximetilcelulose Sódica , Hidrogéis , Temperatura , Água , Resinas Acrílicas/química , Água/química , Hidrogéis/química , Carboximetilcelulose Sódica/química , Transição de Fase , Viscosidade , Acrilamidas/químicaRESUMO
Intervertebral disc degeneration (IDD) diseases are common and frequent diseases in orthopedics. The caspase recruitment domain (CARD) and membrane-associated guanylate kinase-like protein 3 (CARMA3) is crucial in the activation of the NF-κB pathway. However, the biological function of CARMA3 in IDD remains unknown. Here, CARMA3 expression was elevated in nucleus pulposus (NP) tissues of IDD rats and nutrient deprivation (ND)-induced NP cells. The main pathological manifestations observed in IDD rats were shrinkage of the NP, reduction of NP cells, fibrosis of NP tissues, and massive reduction of proteoglycans. These changes were accompanied by a decrease in the expression of collagen II and aggrecan, an increase in the expression of the extracellular matrix (ECM) catabolic proteases MMP-3, MMP-13, and metalloprotease with ADAMTS-5, and an increase in the activity of the pro-apoptotic protease caspase-3. The expression of p-IκBαSer32/36 and p-p65Ser536 was also upregulated. However, these effects were reversed with the knockdown of CARMA3. Mechanistically, CARMA3 bound to BCL10 and MALT1 to form a signalosome. Knockdown of CARMA3 reduced the CARMA3-BCL10-MALT1 signalosome-mediated NF-κB activation. CARMA3 activated the NF-κB signaling pathway in a manner that bound to BCL10 and MALT1 to form a signalosome, which affects NP cell damage and is involved in the development of IDD. This supports CARMA3-BCL10-MALT1-NF-κB as a promising targeting axis for the treatment of IDD.