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BACKGROUND: In large-scale genomic studies, Sox17, an endothelial-specific transcription factor, has been suggested as a putative causal gene of pulmonary arterial hypertension (PAH); however, its role and molecular mechanisms remain to be elucidated. We investigated the functional impacts and acting mechanisms of impaired Sox17 (SRY-related HMG-box17) pathway in PAH and explored its potential as a therapeutic target. METHODS: In adult mice, Sox17 deletion in pulmonary endothelial cells (ECs) induced PAH under hypoxia with high penetrance and severity, but not under normoxia. RESULTS: Key features of PAH, such as hypermuscularization, EC hyperplasia, and inflammation in lung arterioles, right ventricular hypertrophy, and elevated pulmonary arterial pressure, persisted even after long rest in normoxia. Mechanistically, transcriptomic profiling predicted that the combination of Sox17 deficiency and hypoxia activated c-Met signaling in lung ECs. HGF (hepatocyte grow factor), a ligand of c-Met, was upregulated in Sox17-deficient lung ECs. Pharmacologic inhibition of HGF/c-Met signaling attenuated and reversed the features of PAH in both preventive and therapeutic settings. Similar to findings in animal models, Sox17 levels in lung ECs were repressed in 26.7% of PAH patients (4 of 15), while those were robust in all 14 non-PAH controls. HGF levels in pulmonary arterioles were increased in 86.7% of patients with PAH (13 of 15), but none of the controls showed that pattern. CONCLUSIONS: The downregulation of Sox17 levels in pulmonary arterioles increases the susceptibility to PAH, particularly when exposed to hypoxia. Our findings suggest the reactive upregulation of HGF/c-Met signaling as a novel druggable target for PAH treatment.
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Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Animales , Ratones , Células Endoteliales/metabolismo , Proteínas HMGB/metabolismo , Hipertensión Pulmonar/genética , Hipertensión Pulmonar/metabolismo , Hipoxia/complicaciones , Hipoxia/metabolismo , Hipertensión Arterial Pulmonar/genética , Arteria Pulmonar/metabolismo , Transducción de Señal , Factores de Transcripción SOXF/genética , Factores de Transcripción SOXF/metabolismo , Proteínas Proto-Oncogénicas c-met/metabolismoRESUMEN
BACKGROUND: The fresh-market tomato (Solanum lycopersicum) is bred for direct consumption and is selected for a high yield of large fruits. To understand the genetic variations (distinct types of DNA sequence polymorphism) that influence the yield, we collected the phenotypic variations in the yields of total fruit, extra-large-sized fruit, small-sized fruit, or red-colored fruit from 68 core inbred contemporary U.S. fresh-market tomatoes for three consecutive years and the genomic information in 8,289,741 single nucleotide polymorphism (SNP) positions from the whole-genome resequencing of these tomatoes. RESULTS: Genome-wide association (GWA) mapping using the SNP data with or without SNP filtering steps using the regularization methods, validated with quantitative trait loci (QTL) linkage mapping, identified 18 significant association signals for traits evaluated. Among them, 10 of which were not located within genomic regions previously identified as being associated with fruit size/shape. When mapping-driven association signals [558 SNPs associated with 28 yield (component) traits] were used to calculate genomic estimated breeding values (GEBVs) of evaluated traits, the prediction accuracies of the extra-large-sized fruit and small-sized fruit yields were higher than those of the total and red-colored fruit yields, as we tested the generated breeding values in inbred tomatoes and F2 populations. Improved accuracy in GEBV calculation of evaluated traits was achieved by using 364 SNPs identified using the regularization methods. CONCLUSIONS: Together, these results provide an understanding of the genetic variations underlying the heritable phenotypic variability in yield in contemporary tomato breeding and the information necessary for improving such economically important and complex quantitative trait through breeding.
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Solanum lycopersicum , Solanum lycopersicum/genética , Sitios de Carácter Cuantitativo/genética , Estudio de Asociación del Genoma Completo , Fitomejoramiento , Mapeo Cromosómico , Fenotipo , Polimorfismo de Nucleótido Simple/genética , Frutas/genéticaRESUMEN
Peracetic acid (PAA) and performic acid (PFA) are two major peroxyacid (POA) oxidants of growing usage. This study reports the first systematic evaluation of PAA, PFA, and chlorine for their disinfection byproduct (DBP) formation potential in wastewater with or without high halide (i.e., bromide or iodide) concentrations. Compared with chlorine, DBP formation by PAA and PFA was minimal in regular wastewater. However, during 24 h disinfection of saline wastewater, PAA surprisingly produced more brominated and iodinated DBPs than chlorine, while PFA effectively kept all tested DBPs at bay. To understand these phenomena, a kinetic model was developed based on the literature and an additional kinetic investigation of POA decay and DBP (e.g., bromate, iodate, and iodophenol) generation in the POA/halide systems. The results show that PFA not only oxidizes halides 4-5 times faster than PAA to the corresponding HOBr or HOI but also efficiently oxidizes HOI/IO- to IO3-, thereby mitigating iodinated DBP formation. Additionally, PFA's rapid self-decay and slow release of H2O2 limit the HOBr level over the long-term oxidation in bromide-containing water. For saline water, this paper reveals the DBP formation potential of PAA and identifies PFA as an alternative to minimize DBPs. The new kinetic model is useful to optimize oxidant selection and elucidate involved DBP chemistry.
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Desinfectantes , Contaminantes Químicos del Agua , Purificación del Agua , Ácido Peracético , Desinfección/métodos , Peróxido de Hidrógeno , Aguas Residuales , Cloro , Bromuros , Oxidantes , Cloruros , Halogenación , Purificación del Agua/métodos , Contaminantes Químicos del Agua/análisisRESUMEN
Metal-based advanced oxidation processes (AOPs) with peracetic acid (PAA) have been extensively studied to degrade micropollutants (MPs) in wastewater. Mn(II) is a commonly used homogeneous metal catalyst for oxidant activation, but it performs poorly with PAA. This study identifies that the biodegradable chelating ligand picolinic acid (PICA) can significantly mediate Mn(II) activation of PAA for accelerated MP degradation. Results show that, while Mn(II) alone has minimal reactivity toward PAA, the presence of PICA accelerates PAA loss by Mn(II). The PAA-Mn(II)-PICA system removes various MPs (methylene blue, bisphenol A, naproxen, sulfamethoxazole, carbamazepine, and trimethoprim) rapidly at neutral pH, achieving >60% removal within 10 min in clean and wastewater matrices. Coexistent H2O2 and acetic acid in PAA play a negligible role in rapid MP degradation. In-depth evaluation with scavengers and probe compounds (tert-butyl alcohol, methanol, methyl phenyl sulfoxide, and methyl phenyl sulfone) suggested that high-valent Mn species (Mn(V)) is a likely main reactive species leading to rapid MP degradation, whereas soluble Mn(III)-PICA and radicals (CH3C(O)O⢠and CH3C(O)OOâ¢) are minor reactive species. This study broadens the mechanistic understanding of metal-based AOPs using PAA in combination with chelating agents and indicates the PAA-Mn(II)-PICA system as a novel AOP for wastewater treatment.
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Ácido Peracético , Contaminantes Químicos del Agua , Peróxido de Hidrógeno , Aguas Residuales , Oxidación-ReducciónRESUMEN
Peroxyacids (POAs) are a promising alternative to chlorine for reducing the formation of disinfection byproducts. However, their capacity for microbial inactivation and mechanisms of action require further investigation. We evaluated the efficacy of three POAs (performic acid (PFA), peracetic acid (PAA), and perpropionic acid (PPA)) and chlor(am)ine for inactivation of four representative microorganisms (Escherichia coli (Gram-negative bacteria), Staphylococcus epidermidis (Gram-positive bacteria), MS2 bacteriophage (nonenveloped virus), and Φ6 (enveloped virus)) and for reaction rates with biomolecules (amino acids and nucleotides). Bacterial inactivation efficacy (in anaerobic membrane bioreactor (AnMBR) effluent) followed the order of PFA > chlorine > PAA ≈ PPA. Fluorescence microscopic analysis indicated that free chlorine induced surface damage and cell lysis rapidly, whereas POAs led to intracellular oxidative stress through penetrating the intact cell membrane. However, POAs (50 µM) were less effective than chlorine at inactivating viruses, achieving only â¼1-log PFU removal for MS2 and Φ6 after 30 min of reaction in phosphate buffer without genome damage. Results suggest that POAs' unique interaction with bacteria and ineffective viral inactivation could be attributed to their selectivity toward cysteine and methionine through oxygen-transfer reactions and limited reactivity for other biomolecules. These mechanistic insights could inform the application of POAs in water and wastewater treatment.
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Desinfectantes , Purificación del Agua , Desinfectantes/farmacología , Inactivación de Virus , Cloro/farmacología , Ácido Peracético/farmacología , Desinfección/métodos , BacteriasRESUMEN
BACKGROUND: This study aimed to identify the healthcare providers' experience and perspectives toward end-of-life care decisions focusing on end-of-life discussion and physician's order of life-sustaining treatment documentation in Korea which are major parts of the Life-Sustaining Treatment Act. METHODS: A cross-sectional survey was conducted using a questionnaire developed by the authors. A total of 474 subjects-94 attending physicians, 87 resident physicians, and 293 nurses-participated in the survey, and the data analysis was performed in terms of frequency, percentage, mean and standard deviation using the SPSS 24.0 program. RESULTS: Study results showed that respondents were aware of terminal illness and physician's order of life-sustaining treatment in Korea well enough except for some details. Physicians reported uncertainty in terminal state diagnosis and disease trajectory as the most challenging. Study participants regarded factors (related to relationships and communications) on the healthcare providers' side as the major impediment to end-of-life discussion. Study respondents suggested that simplification of the process and more staff are required to facilitate end-of-life discussion and documentation. CONCLUSION: Based on the study results, adequate education and training for better end-of-life discussion are required for future practice. Also, a simple and clear procedure for completing a physician's order of life-sustaining treatment in Korea should be prepared and legal and ethical advice would be required. Since the enactment of the Life-Sustaining Treatment Act, several revisions already have been made including disease categories, thus continuous education to update and support clinicians is also called for.
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Médicos , Cuidado Terminal , Humanos , Estudios Transversales , Muerte , República de CoreaRESUMEN
INTRODUCTION: The patient-to-nurse ratio is highly variable among dialysis facilities. However, there is little known about the association between nurse caseload and hemodialysis (HD) patient outcomes. We evaluated the association between patient-to-nurse ratio and mortality in the Korean patients undergoing HD. METHODS: We used HD quality assessment data and National Health Insurance Service claim data from the year of 2013 for collecting demographic and clinical data. Altogether, 21,817 patients who participated in the HD quality assessment in 2013 were included in the study. Nurse caseload was defined as the number of HD sessions performed by a nurse per working day. The patients were divided into two groups according to the nurse caseload as follows: low nurse caseload group (≤6.0) and high nurse caseload group (>6.0). We analyzed mortality risk based on nurse caseload using the Cox proportional hazard model. RESULTS: The mean age was 59.1 years, and males accounted for 58.5%. The mean hemoglobin was 10.6 g/dL and albumin was 3.99 g/dL. At the mean follow-up duration of 51.7 (20.6) months, the ratio between low and high groups was 69.6% (15,184 patients) versus 30.4% (6,633 patients). The patients in the high nurse caseload group were older and showed lower levels of hemoglobin, albumin, calcium, and iron saturation and higher levels of phosphorus than those in the low nurse caseload group. A high nurse caseload was associated with a lower survival rate. In the adjusted Cox analysis, a high nurse caseload was an independent risk factor for all-cause mortality (hazard ratio 1.08; 95% confidence interval, 1.02-1.14; p = 0.01). CONCLUSION: High nurse caseload was associated with an increased mortality risk among the patients undergoing HD. Further prospective studies are needed to determine whether a caseload of nursing staff can improve the prognosis of HD patients.
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Fallo Renal Crónico , Albúminas , Estudios de Cohortes , Hemoglobinas , Humanos , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Diálisis Renal , República de CoreaRESUMEN
RATIONALE: Central nervous system has low vascular permeability by organizing tight junction (TJ) and limiting endothelial transcytosis. While TJ has long been considered to be responsible for vascular barrier in central nervous system, suppressed transcytosis in endothelial cells is now emerging as a complementary mechanism. Whether transcytosis regulation is independent of TJ and its dysregulation dominantly causes diseases associated with edema remain elusive. Dll4 signaling is important for various vascular contexts, but its role in the maintenance of vascular barrier in central nervous system remains unknown. OBJECTIVE: To find a TJ-independent regulatory mechanism selective for transcytosis and identify its dysregulation as a cause of pathological leakage. METHODS AND RESULTS: We studied transcytosis in the adult mouse retina with low vascular permeability and employed a hypertension-induced retinal edema model for its pathological implication. Both antibody-based and genetic inactivation of Dll4 or Notch1 induce hyperpermeability by increasing transcytosis without junctional destabilization in arterial endothelial cells, leading to nonhemorrhagic leakage predominantly in the superficial retinal layer. Endothelial Sox17 deletion represses Dll4 in retinal arteries, phenocopying Dll4 blocking-driven vascular leakage. Ang II (angiotensin II)-induced hypertension represses arterial Sox17 and Dll4, followed by transcytosis-driven retinal edema, which is rescued by a gain of Notch activity. Transcriptomic profiling of retinal endothelial cells suggests that Dll4 blocking activates SREBP1 (sterol regulatory element-binding protein 1)-mediated lipogenic transcription and enriches gene sets favorable for caveolae formation. Profiling also predicts the activation of VEGF (vascular endothelial growth factor) signaling by Dll4 blockade. Inhibition of SREBP1 or VEGF-VEGFR2 (VEGF receptor 2) signaling attenuates both Dll4 blockade-driven and hypertension-induced retinal leakage. CONCLUSIONS: In the retina, Sox17-Dll4-SREBP1 signaling axis controls transcytosis independently of TJ in superficial arteries among heterogeneous regulations for the whole vessels. Uncontrolled transcytosis via dysregulated Dll4 underlies pathological leakage in hypertensive retina and could be a therapeutic target for treating hypertension-associated retinal edema.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Barrera Hematorretinal/metabolismo , Proteínas de Unión al Calcio/metabolismo , Retinopatía Hipertensiva/metabolismo , Transcitosis , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Arterias/metabolismo , Proteínas de Unión al Calcio/genética , Caveolas/metabolismo , Células Endoteliales/metabolismo , Proteínas HMGB/metabolismo , Homeostasis , Ratones , Ratones Endogámicos C57BL , Receptor Notch1/genética , Receptor Notch1/metabolismo , Factores de Transcripción SOXF/metabolismo , Transducción de Señal , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Uniones Estrechas/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Ferrate(VI) and peracetic acid (PAA) are two oxidants of growing importance in water treatment. Recently, our group found that simultaneous application of ferrate(VI) and PAA led to much faster degradation of micropollutants compared to that by a single oxidant, and this paper systematically evaluated the underlying mechanisms. First, we used benzoic acid and methyl phenyl sulfoxide as probe compounds and concluded that Fe(IV)/Fe(V) was the main reactive species, while organic radicals [CH3C(O)Oâ¢/CH3C(O)OOâ¢] had negligible contribution. Second, we removed the coexistent hydrogen peroxide (H2O2) in PAA stock solution with free chlorine and, to our surprise, found the second-order reaction rate constant between ferrate(VI) and PAA to be only about 1.44 ± 0.12 M-1s-1 while that of H2O2 was as high as (2.01 ± 0.12) × 101 M-1s-1 at pH 9.0. Finally, further experiments on ferrate(VI)-bisulfite and ferrate(VI)-2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic)acid systems confirmed that PAA was not an activator for ferrate(VI). Rather, PAA could enhance the oxidation capacity of Fe(IV)/Fe(V), making their oxidation outcompete self-decay. This study, for the first time, reveals the ability of PAA to promote electron transfer efficiency between high-valent metals and organic contaminants and confirms the benefits of co-application of ferrate(VI) and PAA for alkaline wastewater treatment.
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Contaminantes Químicos del Agua , Purificación del Agua , Electrones , Peróxido de Hidrógeno , Hierro , Oxidantes/química , Oxidación-Reducción , Ácido Peracético , Contaminantes Químicos del Agua/químicaRESUMEN
Activation of peracetic acid (PAA) with iron species is an emerging advanced oxidation process (AOP). This study investigates the use of the chelating agent picolinic acid (PICA) to extend the pH range and enhance the performance of the PAA-Fe(III) AOP. Compared to the PAA-Fe(III) system, the PAA-Fe(III)-PICA system degrades various micropollutants (MPs: methylene blue, naproxen, sulfamethoxazole, carbamazepine, trimethoprim, diclofenac, and bisphenol-A) much more rapidly at higher pH, achieving almost complete removal of parent compounds within 10 min. PAA significantly outperforms the coexistent H2O2 and is the key oxidant for rapid compound degradation. Other chelating agents, EDTA, NTA, citric acid, proline, and nicotinic acid, could not enhance MP degradation in the PAA-Fe(III) system, while 2,6-pyridinedicarboxylic acid with a structure similar to PICA moderately enhanced MP degradation. Experiments with scavengers (tert-butyl alcohol and methyl phenyl sulfoxide) and a probe compound (benzoic acid) confirmed that high-valent iron species [Fe(IV) and/or Fe(V)], rather than radicals, are the major reactive species contributing to MP degradation. The oxidation products of methylene blue, naproxen, and sulfamethoxazole by PAA-Fe(III)-PICA were characterized and supported the proposed mechanism. This work demonstrates that PICA is an effective complexing ligand to assist the Fenton reaction of PAA by extending the applicable pH range and accelerating the catalytic ability of Fe(III).
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Ácido Peracético , Contaminantes Químicos del Agua , Compuestos Férricos , Peróxido de Hidrógeno , Oxidación-Reducción , Ácidos PicolínicosRESUMEN
Efficient separation of harmful contaminants (e.g., per- and polyfluoroalkyl substances, PFASs) from valuable components (water and nutrients) is essential to the resource recovery from domestic wastewater for agricultural purposes. Such selective recovery requires precise separation at the angstrom scale. Although nanofiltration (NF) has the potential to achieve solute-solute separation, the state-of-the-art polyamide (PA) membranes are typically constrained by limited precision of solute-solute selectivity and their well-documented permeability-selectivity trade-off. Herein, we present a novel capillary-assisted interfacial polymerization (CAIP) approach to generate metal-organic framework (MOF)-PA nanocomposite membranes with reduced surface charges and more uniform pore sizes that favor solute selectivity by enhanced size exclusion. By uniquely regulating the PA-MOF interactions using the capillary force, CAIP results in effective exposure of MOF nanochannels on the membrane surface and a PA matrix with a high cross-linking gradient in the vertical direction, both of which contribute to an exceptional water permeance of â¼18.7 LMH/bar and an unprecedentedly high selectivity between nutrient ions and PFASs. Our CAIP approach breaks new ground for utilizing nanoparticles with nanochannels in fabricating the next-generation, fit-for-purpose NF membranes for improved solute-solute separations.
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Fluorocarburos , Nanocompuestos , Membranas Artificiales , Nylons , Aguas Residuales , AguaRESUMEN
BACKGROUND: Chronic stimulation of the mineralocorticoid receptor has been suggested as one of the potential causes of cardiovascular events and death in patients with end-stage renal disease. This observational cohort study was performed to demonstrate that serum cortisol might be a predictive marker for patient mortality and to evaluate its association with oxidized low-density lipoprotein (oxLDL) in hemodialysis (HD) patients. METHODS: Patients receiving HD three times a week were screened for enrollment at two institutions. Baseline cortisol levels were measured before each HD session, and the patients were divided into two groups according to the median value of serum cortisol before analysis. The baseline characteristics and laboratory values of the high and low cortisol groups were compared. Serum cortisol, adrenocorticotropic hormone, renin, aldosterone, and oxLDL were measured in 52 patients to evaluate the effect of oxidative stress on serum cortisol levels. RESULTS: A total of 133 HD patients were enrolled in this cohort study. Compared to the patients with low serum cortisol levels, the patients with high serum cortisol levels (baseline cortisol ≥ 10 µg/dL) showed higher rates of cardiovascular disease (59.7% vs. 39.4%, P=0.019) and left ventricular systolic dysfunction (LVSD) (25.9% vs. 8.0%, P=0.016). The patients in the high cortisol group demonstrated higher all-cause mortality than those in the low cortisol group. The serum cortisol level was an independent risk factor for patient mortality (hazard ratio 1.234, 95% confidence interval 1.022-1.49, P=0.029). Among the 52 patients with oxLDL measurements, oxLDL was an independent risk factor for elevated serum cortisol levels (Exp(B) 1.114, P=0.013) and LVSD (Exp(B) 12.308, P=0.045). However, plasma aldosterone levels did not affect serum cortisol levels. CONCLUSIONS: Serum cortisol is a useful predictive marker for all-cause death among patients receiving HD. OxLDL is an independent marker for elevated serum cortisol among HD patients.
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Hidrocortisona , Fallo Renal Crónico , Aldosterona , Biomarcadores , Estudios de Cohortes , Femenino , Humanos , Fallo Renal Crónico/complicaciones , Masculino , Estrés Oxidativo , Diálisis RenalRESUMEN
Cancer organoids are three-dimensional mini-organ analogues derived from cancer tissues and have been proposed as models capable of simulating the structure and function of human organs and tissues in vitro. We sought to establish gastric cancer patient-derived organoids (PDOs) from tissues obtained by endoscopic biopsies. Gastric cancer-PDOs were successfully established and cultured from cancer tissues with gastric adenocarcinoma by endoscopic biopsies. To confirm that gastric cancer-PDOs were derived from cancer tissue, the consistency of the original cancer tissue was assessed by histopathological examination. As a result, it was confirmed that the shape and internal structure of gastric cancer-PDO were derived from the original gastric cancer cells, and the tumor specificity of gastric cancer-PDO was confirmed through Periodic acid-Schiff (PAS) and polyclonal carcinoembryonic antigen antibody staining. These results demonstrate that gastric cancer-PDO models show the characteristics of primary tumors and have potential for drug screening and providing a personalized medicine platform.
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Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/patología , Biopsia , Humanos , Organoides/patología , Medicina de Precisión/métodos , Neoplasias Gástricas/patologíaRESUMEN
While the neuropathological characteristics of Niemann-Pick disease type C (NPC) result in a fatal diagnosis, the development of clinically available therapeutic agent remains a challenge. Here we propose graphene quantum dots (GQDs) as a potential candidate for the impaired functions in NPC in vivo. In addition to the previous findings that GQDs exhibit negligible long-term toxicity and are capable of penetrating the blood-brain barrier, GQD treatment reduces the aggregation of cholesterol in the lysosome through expressed physical interactions. GQDs also promote autophagy and restore defective autophagic flux, which, in turn, decreases the atypical accumulation of autophagic vacuoles. More importantly, the injection of GQDs inhibits the loss of Purkinje cells in the cerebellum while also demonstrating reduced activation of microglia. The ability of GQDs to alleviate impaired functions in NPC proves the promise and potential of the use of GQDs toward resolving NPC and other related disorders.
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Grafito , Enfermedad de Niemann-Pick Tipo C , Puntos Cuánticos , Autofagia , Humanos , Lisosomas , Enfermedad de Niemann-Pick Tipo C/tratamiento farmacológicoRESUMEN
Methyl p-coumarate (methyl p-hydroxycinnamate) (MH) is a natural compound found in a variety of plants. In the present study, we evaluated the ameliorative effects of MH on airway inflammation in an experimental model of allergic asthma (AA). In this in vitro study, MH was found to exert anti-inflammatory activity on PMA-stimulated A549 airway epithelial cells by suppressing the secretion of IL-6, IL-8, MCP-1, and ICAM-1. In addition, MH exerted an inhibitory effect not only on NF-κB (p-NF-κB and p-IκB) and AP-1 (p-c-Fos and p-c-Jun) activation but also on A549 cell and EOL-1 cell (eosinophil cell lines) adhesion. In LPS-stimulated RAW264.7 macrophages, MH had an inhibitory effect on TNF-α, IL-1ß, IL-6, and MCP-1. The results from in vivo study revealed that the increases in eosinophils/Th2 cytokines/MCP-1 in the bronchoalveolar lavage fluid (BALF) and IgE in the serum of OVA-induced mice with AA were effectively inhibited by MH administration. MH also exerted a reductive effect on the immune cell influx, mucus secretion, and iNOS/COX-2 expression in the lungs of mice with AA. The effects of MH were accompanied by the inactivation of NF-κB. Collectively, the findings of the present study indicated that MH attenuates airway inflammation in mice with AA, suggesting its potential as an adjuvant in asthma therapy.
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Asma , FN-kappa B , Animales , Ratones , Líquido del Lavado Bronquioalveolar , Citocinas/metabolismo , Modelos Animales de Enfermedad , Células Epiteliales/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Interleucina-6 , Ratones Endogámicos BALB C , FN-kappa B/metabolismo , OvalbúminaRESUMEN
To quantitatively probe iron intermediate species [Fe(V)/Fe(IV)] in Fe(VI) oxidation, this study systematically investigated the reaction kinetics of Fe(VI) oxidation of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic)acid (ABTS) at different ratios of [ABTS]0/[Fe(VI)]0 (i.e., >1.0, =1.0, and <1.0) in pH 7.0 phosphate (10 mM)-buffered solution. Compared to the literature, a more comprehensive and robust kinetic model for the Fe(VI)-ABTS system including interactions between high-valent iron species [Fe(VI), Fe(V), and Fe(IV)], ABTS, and the ABTSâ¢+ radical was proposed and validated. The oxidation of ABTS by Fe(VI) (k = (5.96 ± 0.9%) × 105 M-1 s-1), Fe(V) (k = (2.04 ± 0.0%) × 105 M-1 s-1), or Fe(IV) (k = (4.64 ± 13.0%) × 105 M-1 s-1) proceeds via one-electron transfer to generate ABTSâ¢+, which is subsequently oxidized by Fe(VI) (k = (8.5 ± 0.0%) × 102 M-1 s-1), Fe(V) (k = (1.0 ± 40.0%) × 105 M-1 s-1), or Fe(IV) (k = (1.9 ± 17.0%) × 103 M-1 s-1), respectively, via two-electron (oxygen atom) transfer to generate colorless ABTSox. At [ABTS]0/[Fe(VI)]0 > 1.0, experimental data and model simulation both indicated that the reaction stoichiometric ratio of Fe(VI)/ABTSâ¢+ increased from 1.0:1.0 to 1.0:1.2 as [ABTS]0 was increased. Furthermore, the Fe(VI)-ABTS-substrate model was developed to successfully determine reactivity of Fe(V) to different substrates (k = (0.7-1.42) × 106 M-1 s-1). Overall, the improved Fe(VI)-ABTS kinetic model provides a useful tool to quantitatively probe Fe(V)/Fe(IV) behaviors in Fe(VI) oxidation and gains new fundamental insights.
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Benzotiazoles , Ácidos Sulfónicos , Cinética , Oxidación-ReducciónRESUMEN
Interfacial solar distillation (ISD) is an approach with low cost and low energy demand useful for seawater desalination and freshwater production. However, the commercial potential of ISD for applications such as polluted seawater desalination or industrial wastewater reuse may be hindered by low rejection of volatile and semivolatile contaminants. For the first time, the results of this study showed that the transport (from bulk water (B) to distilled water (D)) of volatile and semivolatile contaminants during the solar desalination process was highly correlated with compound volatility (R2 = 0.858). The obtained relationship was verified to be capable of predicting the distillation concentration ratio (CD/CB,0) of different contaminants (KH = 6.29 × 10-7-2.94 × 10-4 atm·m3·mol-1) during the ISD process. Compounds such as phenols, which have relatively high volatilization and condensation rates, deserve the most attention as potential contaminants in the distilled water. Meanwhile, other compounds that are more volatile than phenol condensed less in distilled water. Adding an activated carbon adsorbent or a photothermal oxidant is a promising strategy to effectively mitigate the distillation of contaminants and ensure water safety. These results fill the knowledge gap in understanding the transport of volatile and semivolatile compounds in ISD for the treatment of complex source waters.
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Destilación , Purificación del Agua , Agua Dulce , Luz Solar , Aguas ResidualesRESUMEN
This paper presents an advanced oxidation process (AOP) of peracetic acid (PAA) and ruthenium(III) (Ru(III)) to oxidize micropollutants in water. Studies of PAA-Ru(III) oxidation of sulfamethoxazole (SMX), a sulfonamide antibiotic, in 0.5-20.0 mM phosphate solution at different pH values (5.0-9.0) showed an optimum pH of 7.0 with a complete transformation of SMX in 2.0 min. At pH 7.0, other metal ions (i.e., Fe(II), Fe(III), Mn(II), Mn(III), Co(II), Cu(II), and Ni(II)) in 10 mM phosphate could activate PAA to oxidize SMX only up to 20%. The PAA-Ru(III) oxidation process was also unaffected by the presence of chloride and carbonate ions in solution. Electron paramagnetic resonance (EPR) measurements and quenching experiments showed the dominant involvement of the acetyl(per)oxyl radicals (i.e., CH3C(O)O⢠and CH3C(O)OOâ¢) for degrading SMX in the PAA-Ru(III) oxidation process. The transformation pathways of SMX by PAA-Ru(III) were proposed based on the identified intermediates. Tests with other pharmaceuticals demonstrated that the PAA-Ru(III) oxidation system could remove efficiently a wide range of pharmaceuticals (9 compounds) in the presence of phosphate ions in 2.0 min at neutral pH. The knowledge gained herein on the effective role of Ru(III) to activate PAA to oxidize micropollutants may aid in developing Ru(III)-containing catalysts for PAA-based AOPs.
Asunto(s)
Rutenio , Contaminantes Químicos del Agua , Compuestos Férricos , Peróxido de Hidrógeno , Oxidación-Reducción , Ácido Peracético , AguaRESUMEN
High-volume online hemodiafiltration (HDF) has been reported to reduce the patient's mortality. However, achieving a high convection volume is challenging. In this prospective study, we investigated the feasibility of achieving high-volume HDF with ≥21 L substitution volume via modification of blood flow rate (BFR), needle size, and dialysis membrane. In 30 patients undergoing hemodialysis, we followed a stepwise protocol and gradually increased the BFR (280â300â330 ml/min; steps 1, 2, and 3) and needle size (16â15 G; step 4). After changing dialyzer surface area (1.8 m2 â2.5 m2 ), the BFR and needle size were similarly increased stepwise (steps 5, 6, 7, and 8). The mean substitution volume was 18.7 ± 2.2 L at step 1 and it significantly increased to 25.1 ± 2.6 L by step 8. A substitution volume of 21 L was achieved by 13.3% of patients in step 1 and by 96.7% after step 8. The substitution volume was higher for the dialyzer with a large surface area and for the larger needle (15 G). Between steps 1 and 8, the Kt/V and ß2 microglobulin reduction ratios also improved significantly. High-volume HDF is feasible through a stepwise increase in the BFR, needle size, and surface area of the dialysis membrane.
Asunto(s)
Hemodiafiltración , Convección , Hemodiafiltración/métodos , Humanos , Estudios Prospectivos , Diálisis Renal , Microglobulina beta-2RESUMEN
BACKGROUND: It has recently been emphasized that the unmet needs of cancer patients should be evaluated more holistically, for example, by exploring caregivers' perspectives and cross cultural differences. This study explored additional domains or items of unmet needs among Korean cancer patients in reference to the Sheffield Profile for Assessment and Referral to Care (SPARC). METHODS: We conducted four focus group discussions (FGDs) with 15 cancer patients, following a semi-structured format to elicit participants' health perceptions, comments on SPARC, and opinions on the roles of medical professionals to improve the health-related quality of life of cancer patients. We analyzed the verbatim transcripts using a content analysis method. RESULTS: The following themes were derived: living as a cancer patient, striving to overcome cancer, changing attitudes toward life after the cancer diagnosis, and ways to live a better life as a cancer patient. The participants asserted the significance of providing adequate treatment information that is easily understood by cancer patients during the conversation between patients and medical professionals. Besides the physical symptoms identified by SPARC, the participants struggled with numbness in their hands and feet and hair loss. Korean cancer patients prominently wished to avoid burdening their family or others in their daily life. They considered the improvement of health behaviors, such as diet and exercise, as part of the treatment, which was not limited to drugs. Furthermore, it was essential to evaluate the value of cancer patients' lives, as they desired to be helpful members of their families and society. CONCLUSIONS: This study identified additional domains and items of unmet needs of Korean cancer patients and broadened the understanding of unmet needs among cancer patients.