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One potential advantage of perovskite solar cells (PSCs) is the ability to solution process the precursors and deposit films from solution1,2. At present, spin coating, blade coating, spray coating, inkjet printing and slot-die printing have been investigated to deposit hybrid perovskite thin films3-6. Here we expand the range of deposition methods to include screen-printing, enabled by a stable and viscosity-adjustable (40-44,000 cP) perovskite ink made from a methylammonium acetate ionic liquid solvent. We demonstrate control over perovskite thin-film thickness (from about 120 nm to about 1,200 nm), area (from 0.5 × 0.5 cm2 to 5 × 5 cm2) and patterning on different substrates. Printing rates in excess of 20 cm s-1 and close to 100% ink use were achieved. Using this deposition method in ambient air and regardless of humidity, we obtained the best efficiencies of 20.52% (0.05 cm2) and 18.12% (1 cm2) compared with 20.13% and 12.52%, respectively, for the spin-coated thin films in normal devices with thermally evaporated metal electrodes. Most notably, fully screen-printing devices with a single machine in ambient air have been successfully explored. The corresponding photovoltaic cells exhibit high efficiencies of 14.98%, 13.53% and 11.80% on 0.05-cm2, 1.00-cm2 and 16.37-cm2 (small-module) areas, respectively, along with 96.75% of the initial efficiency retained over 300 h of operation at maximum power point.
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Compuestos de Calcio , Óxidos , Electrodos , HumedadRESUMEN
BACKGROUND: Isolated methylmalonic acidemia, an autosomal recessive disorder of propionate metabolism, is usually caused by mutations in the methylmalonyl-CoA mutase gene (mut-type). Because no universal consensus was made on whether mut-type methylmalonic acidemia should be included in newborn screening (NBS), we aimed to compare the outcome of this disorder detected by NBS with that detected clinically and investigate the influence of NBS on the disease course. DESIGN & METHODS: In this study, 168 patients with mut-type methylmalonic acidemia diagnosed by NBS were compared to 210 patients diagnosed after disease onset while NBS was not performed. Clinical data of these patients from 7 metabolic centers in China were analyzed retrospectively, including initial manifestations, biochemical metabolites, the responsiveness of vitamin B12 therapy, and gene variation, to explore different factors on the long-term outcome. RESULTS: By comparison of the clinically-diagnosed patients, NBS-detected patients showed younger age at diagnosis, less incidence of disease onset, better responsiveness of vitamin B12, younger age at start of treatment, lower levels of biochemical features before and after treatment, and better long-term prognosis (P < 0.01). Onset of disease, blood C3/C2 ratio and unresponsiveness of vitamin B12 were more positively associated with poor outcomes of patients whether identified by NBS. Moreover, the factors above as well as older age at start of treatment were positively associated with mortality. CONCLUSIONS: This research highly demonstrated NBS could prevent major disease-related events and allow an earlier treatment initiation. As a key prognostic factor, NBS is beneficial for improving the overall survival of infants with mut-type methylmalonic acidemia.
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Errores Innatos del Metabolismo de los Aminoácidos , Metilmalonil-CoA Mutasa , Tamizaje Neonatal , Vitamina B 12 , Humanos , Errores Innatos del Metabolismo de los Aminoácidos/genética , Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Errores Innatos del Metabolismo de los Aminoácidos/patología , Errores Innatos del Metabolismo de los Aminoácidos/sangre , Recién Nacido , Metilmalonil-CoA Mutasa/genética , China/epidemiología , Masculino , Femenino , Vitamina B 12/sangre , Vitamina B 12/genética , Lactante , Estudios Retrospectivos , Mutación/genética , Pronóstico , Resultado del Tratamiento , PreescolarRESUMEN
Metal halide perovskites hold great potential for next-generation light-emitting diodes (PeLEDs). Despite significant progress, achieving high-performance PeLEDs hinges on optimizing the interface between the perovskite crystal film and the charge transport layers, especially the buried interface, which serves as the starting point for perovskite growth. Here, we develop a bottom-up perovskite film modulation strategy using formamidine acetate (FAAc) to enhance the buried interface. This multifaceted approach facilitates the vertical-oriented growth of high-quality perovskites with minimized defects. Meanwhile, the in situ deprotonation between FA+ and ZnO could eliminate the hydroxyl (-OH) defects and modulate the energy level of ZnO. The resulting FAPbI3-PeLED exhibits a champion EQE of 23.84% with enhanced operational stability and suppressed EQE roll-off. This strategy is also successfully extended to other mixed-halide PeLEDs (e.g., Cs0.17FA0.83Pb(I0.75Br0.25)3), demonstrating its versatility as an efficient and straightforward method for enhancing the PeLEDs' performance.
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Musashi-2 (MSI2), implicated in the oncogenesis and propagation of a broad array of malignancies, inclusive of certain leukemia, remains a nascent field of study within the context of acute lymphoblastic leukemia (ALL). Using lentiviral transfection, ALL cells with stable MSI2 knockdown were engineered. A suite of analytic techniques - a CCK-8 assay, flow cytometry, qRT-PCR, and western blotting - were employed to evaluate cellular proliferation, cell cycle arrest, and apoptosis and to confirm differential gene expression. The suppression of MSI2 expression yielded significant results: inhibition of cell proliferation, G0/G1 cell cycle arrest, and induced apoptosis in ALL cell lines. Furthermore, it was noted that MSI2 inhibition heightened the responsiveness of ALL cells to dexamethasone. Significantly, the depletion of MSI2 prompted the translocation of GR from the cytoplasm to the nucleus upon dexamethasone treatment, consequently leading to enhanced sensitivity. Additionally, the FOXO1/4 signaling pathway contributed to the biological effects of ALL cells evoked by MSI2 silencing. Our study offers novel insight into the inhibitory effects of MSI2 suppression on ALL cells, positing MSI2 as a promising therapeutic target in the treatment of ALL.
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Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Regulación hacia Abajo , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Proliferación Celular , Transducción de Señal , Apoptosis , Dexametasona/farmacología , Línea Celular Tumoral , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/farmacologíaRESUMEN
BACKGROUND: Methylmalonic acidemia (MMA), which results from defects in methylmalonyl-CoA mutase (mut type) or its cofactor, is the most common inherited organic acid metabolic disease in China. This study aimed to investigate the phenotype and genotype of mut-type MMA in Chinese patients. METHODS: We recruited 365 patients with mut-type MMA; investigated their disease onset, newborn screening (NBS) status, biochemical metabolite levels, gene variations and prognosis; and explored the relationship between phenotype and genotype. RESULTS: There were 152 patients diagnosed by tandem mass spectrometry (MS/MS) expanded NBS, 209 patients diagnosed because of disease onset without NBS and 4 cases diagnosed because of sibling diagnosis. The median age of onset was 15 days old, with a variety of symptoms without specificity. Urinary levels of methylmalonic acid and methylcitric acid (MCA) decreased after treatment. Regarding the prognosis, among the 152 patients with NBS, 50.6% were healthy, 30.3% had neurocognitive impairment and/or movement disorders and 13.8% died. Among the 209 patients without NBS, 15.3% were healthy, 45.9% had neurocognitive impairment and/or movement disorders and 33.0% died. In total, 179 variants were detected in the MMUT gene, including 52 novel variations. c.729_730insTT, c.1106G>A, c.323G>A, c.914T>C and c.1663G>A were the five most frequent variations. The c.1663G>A variation led to a milder phenotype and better prognosis. CONCLUSION: There is a wide spectrum of variations in the MMUT gene with several common variations. Although the overall prognosis of mut-type MMA was poor, participation in MS/MS expanded NBS, vitamin B12 responsive and late onset are favourable factors for the prognosis.
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Trastornos del Movimiento , Espectrometría de Masas en Tándem , Recién Nacido , Humanos , Mutación , Genotipo , China/epidemiologíaRESUMEN
For nearly half a century, the scientific community has been unable to agree upon the safety profile of carrageenan (CGN), a ubiquitous food additive. Little is known about the mechanisms by which consumption of CGN aggravates the etiopathogenesis of murine colitis. However, analyses of gut microbiota and intestinal barrier integrity have provided a breakthrough in explaining the synergistic effect of CGN upon colitis. In Citrobacter rodentium-induced infectious murine colitis, inflammation and the clinical severity of gut tissue were aggravated in the presence of λ-CGN. Using fecal transplantation and germ-free mice experiments, we evaluated the role of intestinal microbiota on the pro-inflammatory effect of λ-CGN. Mice with high dietary λ-CGN consumption showed altered colonic microbiota composition that resulted in degradation of the colonic mucus layer, a raised fecal LPS level, and a decrease in the presence of bacterially derived short-chain fatty acids (SCFAs). Mucus layer defects and altered fecal LPS and SCFA levels could be reproduced in germ-free mice by fecal transplantation from CGN-H-fed mice, but not from germ-free CGN-H-fed mice. Our results confirm that λ-CGN may create an environment that favors inflammation by altering gut microbiota composition and gut bacterial metabolism. The present study provides evidence that the "gut microbiota-barrier axis" could be an alternative target for ameliorating the colitis promoting effect of λ-CGN.
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Carragenina/efectos adversos , Citrobacter rodentium , Colitis , Infecciones por Enterobacteriaceae , Microbioma Gastrointestinal/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Animales , Colitis/etiología , Colitis/metabolismo , Colitis/microbiología , Citocinas/análisis , Infecciones por Enterobacteriaceae/complicaciones , Infecciones por Enterobacteriaceae/metabolismo , Infecciones por Enterobacteriaceae/microbiología , Ácidos Grasos Volátiles/metabolismo , Heces/química , Heces/microbiología , Microbioma Gastrointestinal/genética , Mucosa Intestinal/metabolismo , Lipopolisacáridos/análisis , Masculino , Ratones Endogámicos C57BL , ARN Ribosómico 16SRESUMEN
Carrageenan (CGN) is a common food additive, and questions have been raised regarding its safety for human consumption. The purpose of this study was to investigate the impact of κ-CGN on glucose intolerance and insulin resistance from the perspective that κ-CGN may interfere with insulin receptor function and affect insulin sensitivity and signaling, thereby leading to body weight loss. The health effects of κ-CGN on C57BL/6 mice were assessed over a 90-d period by monitoring changes in body weight, glucose tolerance, insulin tolerance, fasting glucose and insulin levels, and expression of insulin-pathway-related proteins. Furthermore, HepG2 cells were used to detect the binding of κ-CGN on insulin receptor and measure its effect on downstream signal transduction. In mice, κ-CGN treatment reduced weight gain without affecting food intake. Glucose and insulin tolerance tests revealed that κ-CGN treatment increased blood glucose levels and glycosylated hemoglobin levels, while hepatic and muscle glycogen levels were decreased, suggesting that κ-CGN affected glucose metabolism in mice. Interestingly, κ-CGN treatment did not cause typical diabetic symptoms in mice, as indicated by low levels of fasting and postprandial blood glucose, in addition to normal pancreatic tissue and insulin secretion. The binding studies revealed that κ-CGN could competitively bind to the insulin receptor with FITC-insulin and thereby disrupt PI3K and Akt activation, thus suppressing expression of glucose transporters and glycogen synthase. In summary, this study revealed that κ-CGN reduced weight gain without affecting food intake, but impaired glucose metabolism in mice by interfering with insulin binding to receptors, thereby affecting the sensitivity of insulin and inhibiting the insulin PI3K/AKT signaling pathway, causing non-diabetic weight gain reduction.
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Carragenina/efectos adversos , Antagonistas de Insulina/efectos adversos , Insulina/metabolismo , Enfermedades Metabólicas/inducido químicamente , Animales , Western Blotting , Citometría de Flujo , Glucosa/metabolismo , Células Hep G2 , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de Señal/efectos de los fármacos , Aumento de Peso/efectos de los fármacosRESUMEN
A sensitive fluorescent probe (E)-4-(3-(benzo[d]thiazol-2-yl)-4-hydroxy-5-methylstyryl)-1-methylpyridin-1-ium iodide (HBTMP) for the monitoring of pH in mitochondria was rationally exploited. This novel probe exhibited remarkable pH-dependent behavior in the linear range of 5.5-8.0, along with a pKa value of 6.829 ± 0.02627. A large Stokes shift of 205 nm was obtained. This fluorescent probe demonstrated good biocompatibility and high sensitivity for detecting the dynamic changes in mitochondrial pH in living cells and zebrafish. The results of the CCCP (m-chlorophenyl hydrazone) treatment experiment indicated that the probe can effectively monitor changes in mitochondrial pH caused by cell damage.
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Colorantes Fluorescentes/química , Mitocondrias/química , Animales , Supervivencia Celular , Células HeLa , Humanos , Concentración de Iones de Hidrógeno , Piridinas/química , Pez CebraRESUMEN
Esophageal cancer is the ninth most common cancer and the sixth most common cause of cancer-related death worldwide, and the esophageal squamous cell carcinoma (ESCC) subtype accounts for about 90% of all cases of esophageal cancer globally. Currently, ESCC is usually diagnosed in late stages, and targeted therapy is lacking. Therefore, the development of ESCC-specific recognition molecules for an early detection and targeted treatment of ESCC is urgently needed. Aptamers are an excellent molecular recognition tool with unique advantages. In this manuscript, three aptamers (S2, S3, and S8) specific to ESCC cells were successfully screened via cell-SELEX. The experimental results displayed the high affinities of the three aptamers for target KYSE150 cells with dissociation constants in the nanomolar range. The specificity evaluation showed that S2 only bound target KYSE150 cells, but S3 and S8 were capable of targeting a series of ESCC cells. Moreover, several truncated aptamers were generated through sequence optimization. In particular, an ultrashort aptamer S3-2-3 with only 18 bases was successfully obtained; after labeling with Cy5 dyes, it was feasible for the specific imaging of ESCC tissues. Furthermore, the target types of the selected aptamers were preliminarily identified as membrane proteins, and target proteins could be captured by S3-2-3, which may be useful for biomarker discovery. Therefore, the selected aptamers hold great potential for clinical diagnosis, biomarker discovery, and the targeted therapy of ESCC.
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Aptámeros de Nucleótidos , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Línea Celular Tumoral , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas de Esófago/genética , Humanos , Técnica SELEX de Producción de AptámerosRESUMEN
Electron-transport-layer free perovskite solar cells (ETL-free PSCs) have attracted great attention due to their low cost and simple manufacturing process. However, an additional interface layer has to be introduced, and the currently achieved efficiency remains far from full-structure PSCs. Here, we report an in situ interface engineering strategy by the methylammonium acetate (MAAc) ionic liquid perovskite precursor. We found that a dipole layer was in situ constructed through the physical adsorption of the residual MAAc polar molecules on the indium tin oxide electrode, which is significantly different from the treatment by the interface layer in previous reports. This allows a decrease of the effective work function and enables in situ band bending in the perovskite semiconductor. The in situ band bending facilitates charge collection and hinders interfacial charge recombination, leading to ETL-free PSCs with a maximum power conversion efficiency of 21.08%, which is the highest report to date.
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The effects of mesenchymal stem cells (MSCs) on different types of diseases are controversial, and the inner mechanisms remain unknown, which retards the utilization of MSCs in disease therapy. In this study, we aimed to elucidate the mechanisms of MSCs-extracellular vesicles (EVs) carrying transforming growth factor-beta 1 (TGF-ß1) in M2 polarization in mouse macrophages via the microRNA-132 (miR-132)/E3 ubiquitin ligase myc binding protein 2 (Mycbp2)/tuberous sclerosis complex 2 (TSC2) axis. Mouse MSCs were isolated for adipogenic and osteogenic induction, followed by co-culture with mouse macrophages RAW264.7. Besides, mouse macrophages RAW264.7 were co-cultured with MSCs-EVs in vitro, where the proportion of macrophages and inflammation were detected by flow cytometry and ELISA. The experimental data revealed that MSCs-EVs promoted M2 polarization of macrophages, and elevated interleukin (IL)-10 expression and inhibited levels of IL-1ß, tumour necrosis factor (TNF)-α and IL-6. MSC-EV-treated macrophages RAW264.7 increased TGF-ß1 expression, thus elevating miR-132 expression. MiR-132 directly bound to Mycbp2, as confirmed by luciferase activity assay. Meanwhile, E3 ubiquitin ligase Mycbp2 could ubiquitinate TSC2 protein. Furthermore, silencing TGF-ß1 inhibited M2 polarization of MSC-EV-treated macrophages. Taken conjointly, this study provides evidence reporting that MSC-secreted EVs carry TGF-ß1 to promote M2 polarization of macrophages via modulation of the miR-132/Mycbp2/TSC2 axis.
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Polaridad Celular/genética , Vesículas Extracelulares/metabolismo , Macrófagos/citología , Macrófagos/metabolismo , Células Madre Mesenquimatosas/metabolismo , MicroARNs/genética , Factor de Crecimiento Transformador beta1/metabolismo , Regulación hacia Arriba/genética , Animales , Secuencia de Bases , Separación Celular , Regulación hacia Abajo/genética , Células HEK293 , Humanos , Lipopolisacáridos , Ratones , Ratones Endogámicos C57BL , MicroARNs/metabolismo , Modelos Biológicos , Fenotipo , Proteolisis , Células RAW 264.7 , Proteína 2 del Complejo de la Esclerosis Tuberosa/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , UbiquitinaciónRESUMEN
Natural astaxanthin is the strongest antioxidant ever discovered, with many biological functions, and it is widely used in the fields of health food and biomedical research. In the present study, we aimed to investigate the plasma concentration, distribution and safety of astaxanthin from Haematococcus pluvialis in pregnant mice. In the acute studies, the oral LD50 of astaxanthin was greater than 20 g/kg·bw. In mouse bone marrow micronucleus test, 10 g/kg·bw astaxanthin did not cause damage to chromosomes and mitotic apparatus of pregnant mice. After treatment with a single dose of 500 mg/kg·bw astaxanthin, the concentration of astaxanthin in plasma reached the maximum at 8 h (55.7 µg/L), which was completely metabolized after 48 h. In the repeat-dose toxicity test, 100, 250 and 500 mg/kg·bw astaxanthin showed no abnormalities in terms of body and organ weight as well as hematological and biochemical parameters in clinical observation throughout the pregnancy. During pregnancy, the liver accumulated the highest content of astaxanthin, while the eye exhibited the least. The results indicated that administration of astaxanthin from H. pluvialis throughout pregnancy had no adverse effect on mice.
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Antioxidantes/farmacocinética , Antioxidantes/toxicidad , Animales , Chlorophyceae , Ojo/metabolismo , Femenino , Riñón/metabolismo , Hígado/metabolismo , Pulmón/metabolismo , Masculino , Ratones Endogámicos ICR , Pruebas de Micronúcleos , Miocardio/metabolismo , Embarazo , Bazo/metabolismo , Pruebas de Toxicidad Aguda , Xantófilas/sangre , Xantófilas/farmacocinética , Xantófilas/toxicidadRESUMEN
Floridoside is a low-molecular-weight organic compound, which can be accumulated by red algae under stressful conditions to protect cells via its excellent antioxidant properties. In the present study, we investigated the antioxidant mechanism of floridoside toward human hepatocyte L-02 cells. We found that floridoside had no toxicity to L-02 cells, and no reactive oxidative species were induced by it either. However, the expression of hemoxygenase-1 (HO-1) protein was up-regulated upon exposure to floridoside, and two antioxidant enzymes, superoxide dismutase (SOD) and GSH-Px, were activated by floridoside. Moreover, we investigated the pathway involved in the production of these antioxidants, p38/extracellular signal-regulated kinase (ERK) MAPK-nuclear factor-erythroid-2-related factor 2 (Nrf2) pathway. ERK1/2 and p38 phosphorylation, nuclear translocation of Nrf2, and activation of ARE luciferase activity were observed upon exposure to floridoside. siRNA interference and inhibitor treatment suppressed the HO-1 expression and the phosphorylation of ERK1/2 and p38, respectively. These results indicated that floridoside exerted its antioxidant activity by activating HO-1 expression via p38/ERK MAPK-Nrf2 pathway in human hepatocyte L-02 cells.
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Antioxidantes/farmacología , Glicerol/análogos & derivados , Hemo-Oxigenasa 1/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Línea Celular , Supervivencia Celular , Flavonoides/farmacología , Glicerol/farmacología , Hemo-Oxigenasa 1/genética , Hepatocitos , Humanos , Imidazoles/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Piridinas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Superóxido Dismutasa/metabolismoRESUMEN
We report a novel fluorescent probe HBN-TCF for the detection of SO2 derivatives. This probe exhibited near-infrared fluorescence emission with an excitation wavelength of 620 nm. After reacting with SO32-, the emission channel at 664 nm decreased, while the new strong emission channel at 482 nm increased (λex = 400 nm), with a large emission distance (Δλ = 182 nm) observed. This probe exhibited the rapid and selective detection of SO2 derivatives compared with other sulfur-containing species and featured a low detection limit (82 nM). This colorimetric and ratiometric fluorescent probe showed high selectivity and sensitivity for detecting SO2 derivatives. The probe was also successfully exploited for the fluorescence imaging of intracellular and exogenous SO2 derivatives in BEL-7402 cells.
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Bencimidazoles/química , Compuestos de Bencilideno/química , Colorantes Fluorescentes/química , Sulfitos/análisis , Dióxido de Azufre/análisis , Bencimidazoles/síntesis química , Bencimidazoles/efectos de la radiación , Bencimidazoles/toxicidad , Compuestos de Bencilideno/síntesis química , Compuestos de Bencilideno/efectos de la radiación , Compuestos de Bencilideno/toxicidad , Línea Celular Tumoral , Colorimetría/métodos , Fluorescencia , Colorantes Fluorescentes/síntesis química , Colorantes Fluorescentes/efectos de la radiación , Colorantes Fluorescentes/toxicidad , Células Endoteliales de la Vena Umbilical Humana , Humanos , Luz , Límite de Detección , Microscopía Fluorescente/métodosRESUMEN
BACKGROUND: Serological tests are indispensable in the diagnosis of early infection. At present, only procalcitonin (PCT) and C-reactive protein (CRP) are commonly used in clinical practice. Recently, serum amyloid A1 (SAA1) and heparin binding protein (HBP) have been shown to be new biomarkers, because SAA1 is highly sensitive and specific for viral infections, and HBP is predictive for septic shock. In this study, PCT, CRP, HBP, and SAA1 were detected in different combinations to improve the diagnostic accuracy of early infection using the biotin-avidin amplifying system-based time-resolved fluorescent immunoassay (BA-TRFIA). METHODS: A time-resolved fluorescent immunoassay for PCT, CRP, HBP, and SAA1 was developed and then tested in a clinical setting. All experiments were carried out using the DR6608 time-resolved fluorescent immunoassay analyzer. RESULTS: The cutoff values of PCT, CRP, HBP, and SAA1 were 0.05 µg/L, 5.59 mg/L, 3.83 µg/L, and 1.56 mg/L, respectively. The area under the ROC curve (AUC) showed that PCT Ë SAA1 Ë CRP Ë HBP > 0.8. A methodological comparison of the results showed that a combination of the four biomarkers had the highest accuracy for the diagnosis of infectious diseases. CONCLUSION: The time-resolved fluorescent immunoassay-based combined detection of PCT, CRP, HBP, and SAA1 was shown to significantly improve the diagnostic accuracy of early infection. Thus, our results indicate that combined detection based on BA-TRFIA may represent a promising strategy in the clinical diagnosis of infection.
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Péptidos Catiónicos Antimicrobianos/sangre , Infecciones Bacterianas/diagnóstico , Proteína C-Reactiva/análisis , Proteínas Portadoras/sangre , Técnica del Anticuerpo Fluorescente/métodos , Polipéptido alfa Relacionado con Calcitonina/sangre , Proteína Amiloide A Sérica/análisis , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Infecciones Bacterianas/sangre , Biomarcadores/sangre , Proteínas Sanguíneas , Niño , Preescolar , Diagnóstico Precoz , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Virosis/sangre , Virosis/diagnóstico , Adulto JovenRESUMEN
Studying numerous biologically important species simultaneously is crucial to understanding cellular functions and the root causes of related diseases. Direct visualization of endogenous biothiols in biological systems is of great value to understanding their biological roles. Herein, a novel multi-signal fluorescent probe was rationally designed and exploited for the simultaneous sensing of homocysteine (Hcy), cysteine (Cys), and glutathione (GSH) using different emission channels. This probe was successfully applied to the simultaneous discrimination between and visualization of endogenous Hcy, Cys, GSH, and their transformation in living cells.
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Cisteína/metabolismo , Colorantes Fluorescentes/metabolismo , Glutatión/metabolismo , Animales , Línea Celular , Cisteína/análogos & derivados , Cisteína/química , Colorantes Fluorescentes/síntesis química , Colorantes Fluorescentes/química , Glutatión/química , Humanos , Ratones , Estructura Molecular , Imagen Óptica , Células RAW 264.7 , Espectrometría de FluorescenciaRESUMEN
Photodetection in the short-wave infrared (SWIR) spectrum is a challenging task achieved often by costly low bandgap compound semiconductors involving highly toxic elements. In this work, an alternative low-cost approach is reported for SWIR sensors that rely on the plasmonic-induced photothermal effect of solution-processed colloidal gold nanorods (Au NRs). A series of uniform solution-processed Au NRs of various aspect ratios are prepared exhibiting a strong and well-defined longitudinal localized surface plasmon resonance (L-LSPR) maximum from 900 nm to 1.3 µm. A hybrid device structure is fabricated by applying Au NRs on the surface of a thermistor. Under a monochromatic illumination, hybrid Au-NR/thermistor devices exhibit a clear photoresponse in the form of photoinduced resistance drop in the wavelength window from 1.0 to 1.8 µm. The photoresponsivity of such hybrid devices reaches a maximum value of 4.44 × 107 Ω W-1 at λ = 1.4 µm (intensity = 0.28 mW cm-2 ), a wavelength in agreement with the L-LSPR of the Au NRs applied. Colloidal Au NRs, capable to perform fast conversion between photon absorption and thermal energy, thus open an interesting avenue for alternative low-cost SWIR photodetection.
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A novel fluorescent probe was developed by integrating chlorinated coumarin and benzothiazolylacetonitrile and exploited for simultaneous detection of cysteine (Cys), homocysteine (Hcy), and glutathione (GSH). Featuring four binding sites and different reaction mechanisms for different biothiols, this probe exhibited rapid fluorescence turn-on for distinguishing Cys, Hcy, and GSH with 108-, 128-, 30-fold fluorescence increases at 457, 559, 529â nm, respectively, across different excitation wavelengths. Furthermore, the probe was successfully applied to the fluorescence imaging of endogenous Cys and GSH and exogenous Cys, Hcy, and GSH in living cells.
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Cisteína/análisis , Colorantes Fluorescentes/química , Glutatión/análisis , Homocisteína/análisis , Sitios de Unión , Colorantes Fluorescentes/síntesis química , Imagen ÓpticaRESUMEN
Background. The dietary usage of carrageenan as common food additive has increased observably over the last 50 years. But there is substantial controversy about its safety. Methods. We investigated whether the κ-carrageenan could enhance lipopolysaccharide-induced IL-8 expression by studying its actions on the TLR4-NF-κB pathway. The aggravating effect of κ-carrageenan on Citrobacter freundii DBS100-induced intestinal inflammation was also investigated in a mouse model. Results. Our data show that κ-carrageenan pretreatment promoted LPS-induced IL-8 expression in HT-29 cells. Although CD14, MD-2, and TLR4 were upregulated, the binding of LPS was not enhanced. However, the pathway of Bcl10-NF-κB was triggered. Interestingly, κ-carrageenan competitively blocked the binding of FITC-LPS. Furthermore, pretreatment with κ-carrageenan for one week previous to gavage with C. freundii DBS100 markedly aggravated weight loss, mortality, and colonic damage. The secretion of cytokines was unbalanced and the ratio of Tregs was decreased significantly. In addition, κ-carrageenan, together with C. freundii DBS100, enhanced the transcription and secretion of TLR4 and NF-κB. Conclusions. κ-Carrageenan can synergistically activate LPS-induced inflammatory through the Bcl10-NF-κB pathway, as indicated by its aggravation of C. freundii DBS100-induced colitis in mice. General Significance. Our results suggest that κ-carrageenan serves as a potential inflammatory agent that magnifies existing intestinal inflammation.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Carragenina/farmacología , Citrobacter freundii/patogenicidad , Inflamación/inducido químicamente , Inflamación/inmunología , Interleucina-8/metabolismo , Lipopolisacáridos/toxicidad , FN-kappa B/metabolismo , Animales , Proteína 10 de la LLC-Linfoma de Células B , Western Blotting , Citrobacter freundii/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Citometría de Flujo , Células HT29 , Humanos , Inmunohistoquímica , Inflamación/microbiología , Receptores de Lipopolisacáridos/metabolismo , Masculino , Ratones , FN-kappa B/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptor Toll-Like 4/metabolismoRESUMEN
BACKGROUND: Carrageenan is a traditional ingredient that has been widely used in the food industry. In the present study, we propose a hypothesis that carrageenan is a conditional inflammatory agent. When the intestinal tract is in an "unhealthy" state such as that during bacterial infection or acute inflammation, carrageenan can synergistically enhance the inflammatory response. METHODS: BALB/C mice received κ-carrageenan via intragastric administration prior to the induction of oxazolone colitis. Weight changes, survival rate, histologic change, secretion of inflammatory cytokines, ratio of regulatory T cells (Tregs) in peripheral blood, and expression of genes and proteins involved in inflammation and cell proliferation in the colonic mucosa were examined. RESULTS: Intragastric administration of κ-carrageenan to BALB/c mice prior to the induction of oxazolone colitis resulted in an aggravation of body weight loss, a decrease in the survival ratio, aggravation of colonic inflammation, and decrease in the ratio of CD4 + CD25+/CD4+. The secretion of interleukin-4 (IL-4), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) also significantly increased after κ-carrageenan administration. κ-Carrageenan, together with oxazolone, suppressed the expression of forkhead box p3 (FOXp3) and increased the expression of Toll-like receptor 4 (TLR4), Nuclear factor-κB (NF-κB), and proliferating cell nuclear antigen in the colonic mucosa. These results were confirmed by qRT-PCR and western blot analyses at the molecular and protein levels, respectively. CONCLUSIONS: κ-Carrageenan aggravated oxazolone-induced intestinal inflammation in BALB/c mice. This effect is associated with an activation of the TLR4-NF-κB pathway, a decreased ratio of Tregs, and the induction of Th2-dependent immune responses.