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Colorectal cancer and Crohn's disease patients develop pyogenic liver abscesses due to failures of immune cells to fight off bacterial infections. Here, we show that mice lacking iron regulatory protein 2 (Irp2), globally (Irp2-/-) or myeloid cell lineage (Lysozyme 2 promoter-driven, LysM)-specifically (Irp2ΔLysM), are highly susceptible to liver abscesses when the intestinal tissue was injured with dextran sodium sulfate treatment. Further studies demonstrated that Irp2 is required for lysosomal acidification and biogenesis, both of which are crucial for bacterial clearance. In Irp2-deficient liver tissue or macrophages, the nuclear location of transcription factor EB (Tfeb) was remarkably reduced, leading to the downregulation of Tfeb target genes that encode critical components for lysosomal biogenesis. Tfeb mislocalization was reversed by hypoxia-inducible factor 2 inhibitor PT2385 and, independently, through inhibition of lactic acid production. These experimental findings were confirmed clinically in patients with Crohn's disease and through bioinformatic searches in databases from Crohn's disease or ulcerative colitis biopsies showing loss of IRP2 and transcription factor EB (TFEB)-dependent lysosomal gene expression. Overall, our study highlights a mechanism whereby Irp2 supports nuclear translocation of Tfeb and lysosomal function, preserving macrophage antimicrobial activity and protecting the liver against invading bacteria during intestinal inflammation.
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Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Doença de Crohn , Proteína 2 Reguladora do Ferro , Lisossomos , Macrófagos , Animais , Lisossomos/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Camundongos , Humanos , Doença de Crohn/imunologia , Doença de Crohn/metabolismo , Proteína 2 Reguladora do Ferro/metabolismo , Proteína 2 Reguladora do Ferro/genética , Camundongos Knockout , Camundongos Endogâmicos C57BL , Fígado/metabolismo , Fígado/imunologia , Fígado/patologiaRESUMO
ABSTRACT: Voxelotor is an inhibitor of sickle hemoglobin polymerization that is used to treat sickle cell disease. Although voxelotor has been shown to improve anemia, the clinical benefit on the brain remains to be determined. This study quantified the cerebral hemodynamic effects of voxelotor in children with sickle cell anemia (SCA) using noninvasive diffuse optical spectroscopies. Specifically, frequency-domain near-infrared spectroscopy combined with diffuse correlation spectroscopy were used to noninvasively assess regional oxygen extraction fraction (OEF), cerebral blood volume, and an index of cerebral blood flow (CBFi). Estimates of CBFi were first validated against arterial spin-labeled magnetic resonance imaging (ASL-MRI) in 8 children with SCA aged 8 to 18 years. CBFi was significantly positively correlated with ASL-MRI-measured blood flow (R2 = 0.651; P = .015). Next, a single-center, open-label pilot study was completed in 8 children with SCA aged 4 to 17 years on voxelotor, monitored before treatment initiation and at 4, 8, and 12 weeks (NCT05018728). By 4 weeks, both OEF and CBFi significantly decreased, and these decreases persisted to 12 weeks (both P < .05). Decreases in CBFi were significantly correlated with increases in blood hemoglobin (Hb) concentration (P = .025), whereas the correlation between decreases in OEF and increases in Hb trended toward significance (P = .12). Given that previous work has shown that oxygen extraction and blood flow are elevated in pediatric SCA compared with controls, these results suggest that voxelotor may reduce cerebral hemodynamic impairments. This trial was registered at www.ClinicalTrials.gov as #NCT05018728.
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Anemia Falciforme , Circulação Cerebrovascular , Oxigênio , Humanos , Anemia Falciforme/sangue , Criança , Adolescente , Masculino , Feminino , Oxigênio/sangue , Oxigênio/metabolismo , Pré-Escolar , Imageamento por Ressonância Magnética/métodos , Pirazinas/uso terapêutico , Pirazinas/administração & dosagem , Projetos Piloto , Benzaldeídos/uso terapêutico , Benzaldeídos/farmacologia , Benzaldeídos/administração & dosagem , Espectroscopia de Luz Próxima ao Infravermelho/métodos , PirazóisRESUMO
NCOA4 is a selective cargo receptor for ferritinophagy, the autophagic turnover of ferritin (FTH), a process critical for regulating intracellular iron bioavailability. However, how ferritinophagy flux is controlled through NCOA4 in iron-dependent processes needs to be better understood. Here, we show that the C-terminal FTH-binding domain of NCOA4 harbors a [3Fe-4S]-binding site with a stoichiometry of approximately one labile [3Fe-4S] cluster per NCOA4 monomer. By analyzing the interaction between NCOA4 and HERC2 ubiquitin ligase or NCOA4 and FTH, we demonstrate that NCOA4 regulates ferritinophagy by sensing the intracellular iron-sulfur cluster levels. Under iron-repletion conditions, HERC2 recognizes and recruits holo-NCOA4 as a substrate for polyubiquitination and degradation, favoring ferritin iron storage. Under iron-depletion conditions, NCOA4 exists in the form of apo-protein and binds ferritin to promote the occurrence of ferritinophagy and release iron. Thus, we identify an iron-sulfur cluster [3Fe-4S] as a critical cofactor in determining the fate of NCOA4 in favoring iron storage in ferritin or iron release via ferritinophagy and provide a dual mechanism for selective interaction between HERC2 and [3Fe-4S]-NCOA4 for proteasomal degradation or between ferritin and apo-NCOA4 for ferritinophagy in the control of iron homeostasis.
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Homeostase , Ferro , Coativadores de Receptor Nuclear , Autofagia , Ferritinas/metabolismo , Ferro/química , Ferro/metabolismo , Coativadores de Receptor Nuclear/genética , Coativadores de Receptor Nuclear/metabolismo , Enxofre/química , Enxofre/metabolismo , Humanos , Animais , Camundongos , Domínios Proteicos , Linhagem Celular , Células Cultivadas , Ubiquitina-Proteína Ligases/metabolismo , Estabilidade Proteica , Complexo de Endopeptidases do Proteassoma/metabolismoRESUMO
The surfactant-enhanced bioremediation (SEBR) of organic-contaminated soil is a promising soil remediation technology, in which surfactants not only mobilize pollutants, but also alter the mobility of bacteria. However, the bacterial response and underlying mechanisms remain unclear. In this study, the effects and mechanisms of action of a selected nonionic surfactant (Tween 80) on Pseudomonas aeruginosa transport in soil and quartz sand were investigated. The results showed that bacterial migration in both quartz sand and soil was significantly enhanced with increasing Tween 80 concentration, and the greatest migration occurred at a critical micelle concentration (CMC) of 4 for quartz sand and 30 for soil, with increases of 185.2% and 27.3%, respectively. The experimental results and theoretical analysis indicated that Tween 80-facilitated bacterial migration could be mainly attributed to competition for soil/sand surface sorption sites between Tween 80 and bacteria. The prior sorption of Tween 80 onto sand/soil could diminish the available sorption sites for P. aeruginosa, resulting in significant decreases in deposition parameters (70.8% and 33.3% decrease in KD in sand and soil systems, respectively), thereby increasing bacterial transport. In the bacterial post-sorption scenario, the subsequent injection of Tween 80 washed out 69.8% of the bacteria retained in the quartz sand owing to the competition of Tween 80 with pre-sorbed bacteria, as compared with almost no bacteria being eluted by NaCl solution. Several machine learning models have been employed to predict Tween 80-faciliated bacterial transport. The results showed that back-propagation neural network (BPNN)-based machine learning could predict the transport of P. aeruginosa through quartz sand with Tween 80 in-sample (2 CMC) and out-of-sample (10 CMC) with errors of 0.79% and 3.77%, respectively. This study sheds light on the full understanding of SEBR from the viewpoint of degrader facilitation.
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Biodegradação Ambiental , Aprendizado de Máquina , Polissorbatos , Pseudomonas aeruginosa , Tensoativos , Polissorbatos/química , Tensoativos/química , Pseudomonas aeruginosa/efeitos dos fármacos , Microbiologia do Solo , Porosidade , Poluentes do Solo/químicaRESUMO
Although core-shell microparticles with a hard core and soft shell are often used to fabricate photonic crystal films, they are rarely applied to construct steady amorphous colloidal array (ACA) patterns. In this work, a series of monodisperse core-shell microparticles with a polystyrene (PS) core and poly(methyl methacrylate-butyl acrylate) (P(MMA-BA)) shell have been successfully synthesized, and the glass transition temperatures (Tg) of the shell layer have been well regulated. The synthesized core-shell microparticles were then used to fabricate ACA patterns via a convenient infiltration-driven assembly method. The results showed that the Tg of the shell significantly affected the microstructure of the amorphous colloidal arrays (ACAs). During the assembly process, the microparticles quickly contacted each other and the lower-Tg shells could merge with each other to form a continuous film. In this situation, the PS core was embedded and ranked in the P(MMA-BA) film, and both the refractive index contrast and order degree of the colloidal array became relatively low, resulting in a poor structural color. However, when the Tg of the shell layer was moderately high, a short-range ordered array was prepared via infiltration-driven assembly, thereby displaying a bright structural color. More importantly, the shell layers could merge with each other to some extent after short-time heating, resulting in fine mechanical stability. In brief, this study provides a facile and environmental approach to construct steady ACA patterns, which is promising in printing and painting industries.
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Numerous cationic magnetic nanoparticles (MNPs) have previously been developed for demulsifying oil-in-water (O/W) emulsion, and results showed that the cationic MNPs could effectively flocculate and remove the negatively charged oil droplets via charge attraction; however, to the best of our knowledge, there are no research reports regarding the synergetic influence of both the positive charge density and interfacial activity of MNPs on the demulsification performance. In this study, three tertiary amine polymer-grafted MNPs, namely, poly(2-dimethylaminoethyl acrylate)-grafted MNPs (M-PDMAEA), poly(2-dimethylamino)ethyl methacrylate)-grafted MNPs (M-PDMAEMA), and poly(2-diethylaminoethyl methacrylate)-grafted MNPs (M-PDEAEMA), were synthesized and evaluated for their demulsification performance. Results demonstrated that a high positive charge density and superior interfacial activity of MNPs could cause partial oil droplet re-dispersion when excessive MNPs were introduced, leading to a lower magnetic separation efficiency and narrower demulsification window. Herein, a demulsification window is defined as a range of nanoparticle dosages in which the MNPs can effectively demulsify the O/W emulsion under certain conditions. For highly positively charged MNPs, their good interfacial activity could aggravate the formation of a narrower demulsification window. When tertiary amine polymer-grafted MNPs carried a lower positive charge density or weak interfacial activity, that is, M-PDMAEA at pH 4.0, M-PDMAEMA at pH 5.0-9.0, and M-PDEAEMA at pH 9.0-10.0, wide demulsification windows were observed. Additionally, a recycling experiment suggested that MNPs could maintain high demulsification efficiency up to at least five cycles, indicating their satisfactory recyclability. The three tertiary amine polymer-grafted MNPs can be potentially used for efficient demulsification from surfactant-free O/W emulsion in various pH ranges.
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Oridonin, a well-known traditional Chinese herbal medicinal product isolated from Isodon rubescens (Hemsl.) H.Hara, has many potential properties, including anti-inflammatory and antioxidant activities. However, there is no evidence whether oridonin have a protective effect on atherosclerosis. This study focused on the effects of oridonin on oxidative stress and inflammation generated from atherosclerosis. The therapeutic effect on atherosclerosis was evaluated by intraperitoneal injection of oridonin in a high-fat fed ApoE-/- mouse model. We isolated mouse peritoneal macrophages and detected the effect of oridonin on oxidized low-density lipoprotein-induced lipid deposition. Oil red O staining, Masson's staining, dihydroethidium fluorescence staining, immunohistochemical staining, western blotting analysis, immunofluorescence, enzyme-linked immunosorbent assay and quantitative real-time PCR were used to evaluate the effect on atherosclerosis and explore the mechanisms. Oridonin treatment significantly alleviated the progression of atherosclerosis, reduced macrophage infiltration and stabilized plaques. Oridonin could significantly inhibit inflammation associated with NLRP3 activation. Oridonin significantly reduced oxidative stress by blocking Nrf2 ubiquitination and degradation. We also found that oridonin could prevent the formation of foam cells by increasing lipid efflux protein and reducing lipid uptake protein in macrophages. Oridonin has a protective effect on atherosclerosis in ApoE-/- mice, which may be related to the inhibition of NLRP3 and the stabilization of Nrf2. Therefore, oridonin may be a potential therapeutic agent for atherosclerosis.
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Aterosclerose , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Camundongos Knockout , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Inflamação/tratamento farmacológico , Apolipoproteínas E , Apolipoproteínas/uso terapêutico , Camundongos Endogâmicos C57BLRESUMO
Abnormal iron metabolism, mitochondrial dysfunction and the derived oxidative damage are the main pathogeneses of Friedrich's ataxia (FRDA), a single-gene inherited recessive neurodegenerative disease characterized by progressive cerebellar and sensory ataxia. This disease is caused by frataxin (FXN) mutation, which reduces FXN expression and impairs iron sulfur cluster biogenesis. To date, there is no effective therapy to treat this condition. Curcumin is proposed harboring excellent ability to resist oxidative stress through Nrf2 activation and its newly found ability to chelate iron. However, its limitation is its poor water solubility and permeability. Here, we synthesized slow-release nanoparticles (NPs) by loading curcumin (Cur) into silk fibroin (SF) to form NPs with an average size of 150 nm (Cur@SF NPs), which exhibited satisfactory therapeutic effects on the improvement of FRDA manifestation in lymphoblasts (1 µM) derived from FRDA patients and in YG8R mice (150 mg/kg/5 days). Cur@SF NPs not only removed iron from the heart and diminished oxidative stress in general but also potentiate iron-sulfur cluster biogenesis, which compensates FXN deficiency to improve the morphology and function of mitochondria. Cur@SF NPs showed a significant advantage in neuron and myocardial function, thereby improving FRDA mouse behavior scores. These data encourage us to propose that Cur@SF NPs are a promising therapeutic compound in the application of FRDA disease.
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Curcumina , Fibroínas , Ataxia de Friedreich , Nanopartículas , Doenças Neurodegenerativas , Animais , Antioxidantes/farmacologia , Curcumina/farmacologia , Curcumina/uso terapêutico , Ataxia de Friedreich/tratamento farmacológico , Ataxia de Friedreich/genética , Ataxia de Friedreich/metabolismo , Humanos , Quelantes de Ferro , CamundongosRESUMO
In this study, magnetic pomelo peel-derived biochar composite was fabricated and applied as a low-cost adsorbent for the simultaneous extraction of morphine-like opioids named morphine, codeine, and 6-monoacetylmorphine from wastewaters, prior to their determination via liquid chromatography-mass spectrometry. A total of four biochar products were synthesized under different pyrolytic temperatures of 400, 500, 600, and 700°C, respectively, and the 400°C biochar was found to have the greatest extraction ability, with enrichment factors of 34, 58, and 61 for the three drugs. The primary adsorption mechanism includes π-π interaction and H-bonding. Parameters affecting the extraction of opioids were optimized. Under optimum conditions (such as pH = 7; adsorbent amount = 15 mg; sample volume = 20 ml; eluent solvent, 200 µl of methanol), the method was proved to be linear in the range of 0.05-10.0 µg/L, with coefficients of determination greater than 0.99, and the limits of detection were 0.006-0.010 µg/L. In-batch and inter-batch precisions were 1.8%-6.5% and 4.8%-10.6%, respectively. The method was successfully applied to the determination of the target opioids in the samples of influent and effluent wastewater. The developed method by using magnetic pomelo peel-derived biochar could potentially be applied for the effective estimation of illicit drug consumption.
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Águas Residuárias , Poluentes Químicos da Água , Águas Residuárias/análise , Analgésicos Opioides , Poluentes Químicos da Água/análise , Cromatografia Líquida/métodos , Espectrometria de Massas , Codeína/análise , Fenômenos Magnéticos , Extração em Fase Sólida/métodos , Cromatografia Líquida de Alta Pressão/métodosRESUMO
In this study, a biochar-based magnetic solid-phase microextraction method, coupled with liquid chromatography-mass spectrometry, was developed for analyzing fentanyl analogs from urine sample. Magnetic biochar was fabricated through a one-step pyrolysis carbonization and magnetization process, followed by an alkali treatment. In order to achieve desired extraction efficiency, feed stocks (wood and bamboo) and different pyrolysis temperatures (300-700°C) were optimized. The magnetic bamboo biochar pyrolyzed at 400°C was found to have the greatest potential for extraction of fentanyls, with enrichment factors ranging from 58.9 to 93.7, presumably due to H-bonding and π-π interactions between biochar and fentanyls. Various extraction parameters, such as type and volume of desorption solvent, pH, and extraction time, were optimized, respectively, to achieve the highest extraction efficiency for the target fentanyls. Under optimized conditions, the developed method was found to have detection limits of 3.0-9.4 ng/L, a linear range of 0.05-10 µg/L, good precisions (1.9-9.4% for intrabatch, 2.9-9.9% for interbatch), and satisfactory recoveries (82.0-111.3%). The developed method by using magnetic bamboo biochar as adsorbent exhibited to be an efficient and promising pretreatment procedure and could potentially be applied for drug analysis in biological samples.
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Microextração em Fase Líquida , Sasa , Carvão Vegetal , Cromatografia Líquida de Alta Pressão , Fentanila , Limite de Detecção , Microextração em Fase Líquida/métodos , Fenômenos Magnéticos , Extração em Fase SólidaRESUMO
Surface-engineered coatings have been increasingly applied to functionalize fabrics due to the ease of deposition of the coatings and their effectiveness in endowing the fabric with abundant properties. Among the surface modification methods, layer-by-layer (LbL) self-assembly has emerged as an important approach for creating multifunctional surfaces on fabrics. In this review, bibliometric analysis with the visualization analysis of LbL self-assembly coatings on fabrics was performed on publications extracted from the Web of Science (WOS) from 2005 to 2021 based on the CiteSpace software. The analysis results showed that research on LbL self-assembly coatings on fabrics has attracted much attention, and this technique has plentiful and flexible applications. Moreover, research on the LbL self-assembly method in the field of functionalization of fabrics has been summarized, which include flame retardant fabric, antibacterial fabric, ultraviolet resistant fabric, hydrophobic fabric and electromagnetic shielding fabric. It was found that the functionalization of the fabric has been changing from singularity to diversification. Based on the review, several future research directions can be proposed. The weatherability, comfort, cost and environmental friendliness should be considered when the multifunctional coatings are designed.
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Retardadores de Chama , Antibacterianos , Interações Hidrofóbicas e Hidrofílicas , TêxteisRESUMO
BACKGROUND: The relative contributions of asymptomatic, presymptomatic, and symptomatic transmission of severe acute respiratory syndrome coronavirus 2 have not been clearly measured, although control measures may differ in response to the risk of spread posed by different types of cases. METHODS: We collected detailed information on transmission events and symptom status based on laboratory-confirmed patient data and contact tracing data from 4 provinces and 1 municipality in China. We estimated the variation in risk of transmission over time and the severity of secondary infections by symptomatic status of the infector. RESULTS: There were 393 symptomatic index cases with 3136 close contacts and 185 asymptomatic index cases with 1078 close contacts included in the study. The secondary attack rates among close contacts of symptomatic and asymptomatic index cases were 4.1% (128 of 3136) and 1.1% (12 of 1078), respectively, corresponding to a higher transmission risk from symptomatic cases than from asymptomatic cases (odds ratio, 3.79; 95% confidence interval, 2.06-6.95). Approximately 25% (32 of 128) and 50% (6 of 12) of the infected close contacts were asymptomatic from symptomatic and asymptomatic index cases, respectively, while more than one third (38%) of the infections in the close contacts of symptomatic cases were attributable to exposure to the index cases before symptom onset. CONCLUSIONS: Asymptomatic and presymptomatic transmissions play an important role in spreading infection, although asymptomatic cases pose a lower risk of transmission than symptomatic cases. Early case detection and effective test-and-trace measures are important to reduce transmission.
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COVID-19 , SARS-CoV-2 , China/epidemiologia , Busca de Comunicante , Humanos , IncidênciaRESUMO
We estimated the symptomatic, PCR-confirmed secondary attack rate (SAR) for 2,382 close contacts of 476 symptomatic persons with coronavirus disease in Yichang, Hubei Province, China, identified during January 23-February 25, 2020. The SAR among all close contacts was 6.5%; among close contacts who lived with an index case-patient, the SAR was 10.8%; among close-contact spouses of index case-patients, the SAR was 15.9%. The SAR varied by close contact age, from 3.0% for those <18 years of age to 12.5% for those >60 years of age. Multilevel logistic regression showed that factors significantly associated with increased SAR were living together, being a spouse, and being >60 years of age. Multilevel regression did not support SAR differing significantly by whether the most recent contact occurred before or after the index case-patient's onset of illness (p = 0.66). The relatively high SAR for coronavirus disease suggests relatively high virus transmissibility.
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COVID-19 , SARS-CoV-2 , Adolescente , Criança , China/epidemiologia , Humanos , Incidência , Modelos LogísticosRESUMO
In this work, defective Zr-based metal-organic framework was successfully synthesized and evaluated as a dispersive micro-solid-phase extraction sorbent for efficient preconcentration and determination of fungicides in complex water samples. The defective Zr-based metal-organic framework crystal with increased adsorption capacity was successfully synthesized by employing formic acid as the modulator. The extraction conditions, including the pH, extraction time, desorption solvent and desorption time, were comprehensively investigated. Under optimum conditions, it was found that dispersive micro-solid-phase extraction method, coupled with liquid chromatography/mass spectrometry, exhibited a good linear relationship with correlation coefficients greater than 0.9980. The relative standard deviations of inter-day and intra-day precisions ranged from 2.6 to 9.2% and the limits of detection ranged from 0.004 to 0.036 µg/L. These merits, combined with their satisfactory recoveries (>80%), suggested the great potential of defective Zr-based metal-organic framework as a new adsorbent for efficient extraction of trace fungicides. This method exhibits good application potential for the pretreatment of fungicides from environmental water samples.
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BACKGROUND: Increasing evidence suggests that multiple or long-time exposure to general anaesthesia (GA) could be detrimental to cognitive development in young subjects and might also contribute to accelerated neurodegeneration in the elderly. Iron is essential for normal neuronal function, and excess iron in the brain is implicated in several neurodegenerative diseases. However, the role of iron in GA-induced neurotoxicity and cognitive deficits remains elusive. METHODS: We used the primary hippocampal neurons and rodents including young rats and aged mice to examine whether GA impacted iron metabolism and whether the impact contributed to neuronal outcomes. In addition, a pharmacological suppression of iron metabolism was performed to explore the molecular mechanism underlying GA-mediated iron overload in the brain. RESULTS: Our results demonstrated that GA, induced by intravenous ketamine or inhalational sevoflurane, disturbed iron homeostasis and caused iron overload in both in vitro hippocampal neuron culture and in vivo hippocampus. Interestingly, ketamine- or sevoflurane-induced cognitive deficits, very likely, resulted from a novel iron-dependent regulated cell death, ferroptosis. Notably, iron chelator deferiprone attenuated the GA-induced mitochondrial dysfunction, ferroptosis, and further cognitive deficits. Moreover, we found that GA-induced iron overload was activated by NMDAR-RASD1 signalling via DMT1 action in the brain. CONCLUSION: We conclude that disturbed iron metabolism may be involved in the pathogenesis of GA-induced neurotoxicity and cognitive deficits. Our study provides new vision for consideration in GA-associated neurological disorders.
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Anestésicos Gerais/toxicidade , Neurônios/efeitos dos fármacos , Síndromes Neurotóxicas/patologia , Complicações Cognitivas Pós-Operatórias/induzido quimicamente , Anestesia Geral/efeitos adversos , Animais , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Ferro/metabolismo , Sobrecarga de Ferro/etiologia , Sobrecarga de Ferro/metabolismo , Sobrecarga de Ferro/patologia , Ketamina/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Neurônios/patologia , Síndromes Neurotóxicas/metabolismo , Complicações Cognitivas Pós-Operatórias/metabolismo , Complicações Cognitivas Pós-Operatórias/patologia , Ratos , Ratos Sprague-Dawley , Sevoflurano/toxicidadeRESUMO
In this study, an alternative method for synthesizing magnetic cobalt adeninate metal-organic frameworks was developed, and the synthesized materials were examined for their potential application for separating and enriching benzodiazepines from complex samples. Benzodiazepines, widely used as hypnotics, muscle relaxants, sedatives, and anxiolytics, are a class of drugs that require accurate detection and monitoring. Results showed that Fe3 O4 nanoparticles could be well anchored onto the external surface of cobalt adeninate metal-organic frameworks by using amino-silane as a linkage. Their adsorption of benzodiazepines was mainly promoted by intermolecular hydrogen binding, π-π interactions and electrostatic attraction. Their potential application was evaluated by extraction of benzodiazepines in urine and wastewater samples prior to liquid chromatography with mass spectrometry. Under optimum conditions, the calibration curves were linear with a correlation coefficient of ≥0.9928 in the concentration range of 10-5000 ng/L for lorazepam and 5-5000 ng/L for estazolam, chlordiazepoxide, alprazolam, midazolam and triazolam. The limits of detection were in the range of 0.71-2.49 ng/L. The percent of extraction recoveries were 80.2-94.5% for urine and 84.1-94.4% for wastewater, respectively. Results suggested that magnetic cobalt adeninate metal-organic frameworks could potentially be a promising material for enriching benzodiazepines from urine and wastewater with high accuracy and precision.
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Adenina/química , Benzodiazepinas/isolamento & purificação , Benzodiazepinas/urina , Estruturas Metalorgânicas/química , Águas Residuárias/análise , Zinco/química , Adenina/análogos & derivados , Benzodiazepinas/química , Fenômenos Magnéticos , Estruturas Metalorgânicas/síntese químicaRESUMO
A series of nanocomposite adsorbents were prepared by heterocoagulation of negatively charged delaminated montmorillonite (Mt) and positively charged synthetic layered double hydroxide (LDH) colloids with different LDH loading amounts. The mineralogy and physicochemical properties of the resulting nanocomposites were characterized. Their potential applications for phosphate (P) removal from aqueous solution, as a function of P concentration (2.5-200 mg/L), contact time (1 min-48 h) and pH (3-10), were evaluated by using batch adsorption modes. It was found that the adsorption data could be well described by both Freundlich and Langmuir isotherm models. The maximum adsorption capacity of three different LDH heterocoagulated montmorillonites (LDH-Mts) for P removal was found to increase with LDH loadings, reaching 12.6, 16.2 and 23.3 mg/g respectively; Adsorption kinetic data revealed that 90% of adsorption onto LDH-Mts was completed within 1 h (h) and the adsorption process could be well described by the pseudo-second-order model. These results demonstrated that heterocoagulation of Mt and LDH could preserve the adsorption capacity of LDH for P and enhance the stability of both clay minerals, and LDH-Mts could be effectively used as a potential promising filtration medium for P removal.
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Silicatos de Alumínio/química , Bentonita/química , Nanocompostos/química , Fosfatos/análise , Poluentes Químicos da Água/análise , Purificação da Água/métodos , Adsorção , Argila , Coloides , Hidróxidos/química , Cinética , Microscopia Eletrônica de Varredura , Modelos Teóricos , Fosfatos/química , Propriedades de Superfície , Poluentes Químicos da Água/química , Difração de Raios XRESUMO
Foam cell formation as a result of imbalance of modified cholesterol influx and efflux by macrophages is a key to the occurrence and development of atherosclerosis. Oxidative stress is thought to be involved in the pathogenesis of atherosclerosis. SS-31 is a member of the Szeto-Schiller (SS) peptides shown to specifically target the inner mitochondrial membrane to scavenge reactive oxygen species. In this study, we investigated whether SS-31 may provide protective effect on macrophage from foam cell formation in RAW264.7 cells. The results showed that SS-31 inhibited oxidized low-density lipoproteins (ox-LDL)-induced foam cell formation and cholesterol accumulation, demonstrated by intracellular oil red O staining and measurement of cholesterol content. The mechanism was revealed that SS-31 did not only significantly attenuated ox-LDL-induced generation of reactive oxygen species (ROS) and increased the activities of superoxide dismutases, but also dose-dependently inhibited the expression of CD36 and LOX-1, two scavenger receptors of ox-LDL, while the expression of ATP-binding cassette A1 and G1, playing a pivotal role in cholesterol efflux, was not affected. As a result, SS-31 decreased pro-inflammatory cytokines such as interleukin 6 and tumor necrosis factor alpha, suggesting the prevention of inflammatory responses. In conclusion, our results demonstrate that SS-31 provides a beneficial effect on macrophages from foam cell formation, likely, through both ROS scavenging and inhibition of cholesterol influx. Therefore, SS-31 may potentially be of therapeutic relevance in prevention of human atherogenesis.
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Colesterol/metabolismo , Células Espumosas/efeitos dos fármacos , Lipoproteínas LDL/metabolismo , Macrófagos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Oligopeptídeos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Animais , Transporte Biológico , Humanos , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos , Mitocôndrias/metabolismo , Células RAW 264.7RESUMO
Anabolic steroids and ß-agonists are commonly prohibited substances found in doping control studies; therefore, the determination of anabolic substances in biological samples is crucial. To analyze the anabolic compounds in urine, an adsorbent, polyethylene glycol (PEG)-grafted magnetic nanoparticle material (Fe3O4@SiO2-PEG), with low toxicity and strong biocompatibility was prepared in this investigation. Compared to those of Fe3O4 and Fe3O4@SiO2, the grafted PEG chains (approximately 5.4 wt.%) on the magnetic nanoparticles improved the extraction efficiencies by factors of 3.9-17.0 and 2.5-2.9, respectively, likely due to the electrostatic attraction and hydrogen bonding. To achieve maximum extraction efficiency, several extraction parameters were optimized, including the kind and volume of desorption solvent, pH, and the extraction and desorption time. The standard curves were linear within the range of 0.5-20 µg/L for methyltestosterone and trenbolone, and 0.02-5 µg/L for clenbuterol. The limits of detection for the three drugs were 0.01-0.12 µg/L. The limits of quantification were 0.02-0.40 µg/L. The levels of precision of the optimized method were assessed based on the respective intra- and inter-day and batch-to-batch relative standard deviations in the ranges of 3.2-5.2 % (n = 5), 5.9-11.3 % (n = 4), and 6.7-9.2 % (n = 3). The Fe3O4@SiO2-PEG nanoparticles could exclude urine matrix interferences (matrix effect of 91.8-98.1 %) and achieve satisfactory recoveries (75.5-116.1 %), affording sensitive and accurate determination of trace anabolic substances in urine.
Assuntos
Anabolizantes , Limite de Detecção , Nanopartículas de Magnetita , Polietilenoglicóis , Humanos , Polietilenoglicóis/química , Anabolizantes/urina , Anabolizantes/isolamento & purificação , Nanopartículas de Magnetita/química , Dopagem Esportivo , Adsorção , Reprodutibilidade dos Testes , Extração em Fase Sólida/métodos , Dióxido de Silício/químicaRESUMO
The rapid expansion of fast fashion has significantly increased microplastic fiber (MPF) release during laundry practices, accounting for approximately one-third of primary microplastics entering the ocean. Currently, a significant gap exists in global-scale research on the release of MPFs from washing textiles. This study introduces an innovative empirical model to assess the spatial distribution of MPF emissions. The model estimates an annual global emission of 5.69 million tons of MPFs from laundry. Of this total, machine washing accounts for the majority (93.7 %), with hand washing contributing the remaining 6.3 %. As the primary source of MPF pollution, Asia's emissions reach 3.71 million tons, far exceeding those of North America (1.18 million tons) and Europe (0.45 million tons). The primary issue is that wastewater management efficiency varies significantly worldwide. In Asia, there is persistently high discharge of MPFs into natural waters, and the removal efficiency of wastewater treatment plants is still comparatively low. In contrast, the United States and many European countries exhibit better MPF retention. The global nature of this challenge mandates international collaboration for comprehensive environmental conservation. Our study provides the first high-resolution global distribution map of MPF emissions and discharge into natural waters, establishing a data foundation for global and regional management of microplastics originating from household laundry sources.