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1.
Plant Cell ; 36(7): 2607-2628, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38537937

RESUMEN

Cold injury is a major environmental stress affecting the growth and yield of crops. Brassinosteroids (BRs) and salicylic acid (SA) play important roles in plant cold tolerance. However, whether or how BR signaling interacts with the SA signaling pathway in response to cold stress is still unknown. Here, we identified an SA methyltransferase, TaSAMT1 that converts SA to methyl SA (MeSA) and confers freezing tolerance in wheat (Triticum aestivum). TaSAMT1 overexpression greatly enhanced wheat freezing tolerance, with plants accumulating more MeSA and less SA, whereas Tasamt1 knockout lines were sensitive to freezing stress and accumulated less MeSA and more SA. Spraying plants with MeSA conferred freezing tolerance to Tasamt1 mutants, but SA did not. We revealed that BRASSINAZOLE-RESISTANT 1 (TaBZR1) directly binds to the TaSAMT1 promoter and induces its transcription. Moreover, TaBZR1 interacts with the histone acetyltransferase TaHAG1, which potentiates TaSAMT1 expression via increased histone acetylation and modulates the SA pathway during freezing stress. Additionally, overexpression of TaBZR1 or TaHAG1 altered TaSAMT1 expression and improved freezing tolerance. Our results demonstrate a key regulatory node that connects the BR and SA pathways in the plant cold stress response. The regulatory factors or genes identified could be effective targets for the genetic improvement of freezing tolerance in crops.


Asunto(s)
Brasinoesteroides , Congelación , Regulación de la Expresión Génica de las Plantas , Metiltransferasas , Proteínas de Plantas , Ácido Salicílico , Transducción de Señal , Triticum , Triticum/genética , Triticum/fisiología , Triticum/metabolismo , Brasinoesteroides/metabolismo , Brasinoesteroides/farmacología , Ácido Salicílico/metabolismo , Ácido Salicílico/farmacología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Metiltransferasas/metabolismo , Metiltransferasas/genética , Plantas Modificadas Genéticamente , Regiones Promotoras Genéticas/genética , Histona Acetiltransferasas/metabolismo , Histona Acetiltransferasas/genética
2.
Proc Natl Acad Sci U S A ; 121(9): e2313464121, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38346211

RESUMEN

Creating tissue and organ equivalents with intricate architectures and multiscale functional feature sizes is the first step toward the reconstruction of transplantable human tissues and organs. Existing embedded ink writing approaches are limited by achievable feature sizes ranging from hundreds of microns to tens of millimeters, which hinders their ability to accurately duplicate structures found in various human tissues and organs. In this study, a multiscale embedded printing (MSEP) strategy is developed, in which a stimuli-responsive yield-stress fluid is applied to facilitate the printing process. A dynamic layer height control method is developed to print the cornea with a smooth surface on the order of microns, which can effectively overcome the layered morphology in conventional extrusion-based three-dimensional bioprinting methods. Since the support bath is sensitive to temperature change, it can be easily removed after printing by tuning the ambient temperature, which facilitates the fabrication of human eyeballs with optic nerves and aortic heart valves with overhanging leaflets on the order of a few millimeters. The thermosensitivity of the support bath also enables the reconstruction of the full-scale human heart on the order of tens of centimeters by on-demand adding support bath materials during printing. The proposed MSEP demonstrates broader printable functional feature sizes ranging from microns to centimeters, providing a viable and reliable technical solution for tissue and organ printing in the future.


Asunto(s)
Bioimpresión , Ingeniería de Tejidos , Humanos , Ingeniería de Tejidos/métodos , Córnea , Bioimpresión/métodos , Impresión Tridimensional , Andamios del Tejido/química , Hidrogeles/química
3.
Blood ; 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38657197

RESUMEN

Thrombotic microangiopathy (TMA) is characterized by immunothrombosis and life-threatening organ failure, but the precise underlying mechanism driving its pathogenesis remains elusive. In this study, we hypothesized that gasdermin D (GSDMD), a pore-forming protein serving as the final downstream effector of pyroptosis/interleukin (IL)-1pathway, contributes to TMA and its consequences by amplifying neutrophil maturation and subsequent necrosis. Using a murine model of focal crystalline TMA, we found that Gsdmd-deficiency ameliorated immunothrombosis, acute tissue injury and failure. Gsdmd-/- mice exhibited a decrease in mature IL-1, as well as in neutrophil maturation, 2 integrin activation, and recruitment to TMA lesions, where they formed reduced neutrophil extracellular traps both in arteries and interstitial tissue. The GSDMD inhibitor disulfiram dose-dependently suppressed human neutrophil pyroptosis in response to cholesterol crystals. Experiments with GSDMD-deficient human induced pluripotent stem cell-derived neutrophils confirmed the involvement of GSDMD in neutrophil 2 integrin activation, maturation as well as pyroptosis. Both prophylactic and therapeutic administration of disulfiram protected mice from focal TMA, acute tissue injury and failure. Our data identify GSDMD as a key mediator of focal crystalline TMA and its consequences: ischemic tissue infarction and organ failure. GSDMD could potentially serve as a therapeutic target for systemic forms of TMA.

4.
BMC Med ; 22(1): 147, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38561764

RESUMEN

BACKGROUND: Thyroid nodule (TN) patients in China are subject to overdiagnosis and overtreatment. The implementation of existing technologies such as thyroid ultrasonography has indeed contributed to the improved diagnostic accuracy of TNs. However, a significant issue persists, where many patients undergo unnecessary biopsies, and patients with malignant thyroid nodules (MTNs) are advised to undergo surgery therapy. METHODS: This study included a total of 293 patients diagnosed with TNs. Differential methylation haplotype blocks (MHBs) in blood leukocytes between MTNs and benign thyroid nodules (BTNs) were detected using reduced representation bisulfite sequencing (RRBS). Subsequently, an artificial intelligence blood leukocyte DNA methylation (BLDM) model was designed to optimize the management and treatment of patients with TNs for more effective outcomes. RESULTS: The DNA methylation profiles of peripheral blood leukocytes exhibited distinctions between MTNs and BTNs. The BLDM model we developed for diagnosing TNs achieved an area under the curve (AUC) of 0.858 in the validation cohort and 0.863 in the independent test cohort. Its specificity reached 90.91% and 88.68% in the validation and independent test cohorts, respectively, outperforming the specificity of ultrasonography (43.64% in the validation cohort and 47.17% in the independent test cohort), albeit with a slightly lower sensitivity (83.33% in the validation cohort and 82.86% in the independent test cohort) compared to ultrasonography (97.62% in the validation cohort and 100.00% in the independent test cohort). The BLDM model could correctly identify 89.83% patients whose nodules were suspected malignant by ultrasonography but finally histological benign. In micronodules, the model displayed higher specificity (93.33% in the validation cohort and 92.00% in the independent test cohort) and accuracy (88.24% in the validation cohort and 87.50% in the independent test cohort) for diagnosing TNs. This performance surpassed the specificity and accuracy observed with ultrasonography. A TN diagnostic and treatment framework that prioritizes patients is provided, with fine-needle aspiration (FNA) biopsy performed only on patients with indications of MTNs in both BLDM and ultrasonography results, thus avoiding unnecessary biopsies. CONCLUSIONS: This is the first study to demonstrate the potential of non-invasive blood leukocytes in diagnosing TNs, thereby making TN diagnosis and treatment more efficient in China.


Asunto(s)
Neoplasias de la Tiroides , Nódulo Tiroideo , Humanos , Nódulo Tiroideo/diagnóstico por imagen , Nódulo Tiroideo/genética , Estudios Prospectivos , Inteligencia Artificial , Ultrasonografía , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía , Estudios Retrospectivos
5.
FASEB J ; 37(4): e22867, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36906288

RESUMEN

Inflammatory osteolysis occurs primarily in the context of osteoarthritis, aseptic inflammation, prosthesis loosening, and other conditions. An excessive immune inflammatory response causes excessive activation of osteoclasts, leading to bone loss and bone destruction. The signaling protein stimulator of interferon gene (STING) can regulate the immune response of osteoclasts. C-176 is a furan derivative that can inhibit activation of the STING pathway and exert anti-inflammatory effects. The effect of C-176 on osteoclast differentiation is not yet clear. In this study, we found that C-176 could inhibit STING activation in osteoclast precursor cells and inhibit osteoclast activation induced by nuclear factor κB ligand receptor activator in a dose-dependent manner. After treatment with C-176, the expression of the osteoclast differentiation marker genes nuclear factor of activated T-cells c1(NFATc1), cathepsin K, calcitonin receptor, and V-ATPase a3 decreased. In addition, C-176 reduced actin loop formation and bone resorption capacity. The WB results showed that C-176 downregulated the expression of the osteoclast marker protein NFATc1 and inhibited activation of the STING-mediated NF-κB pathway. We also found that C-176 could inhibit the phosphorylation of mitogen-activated protein kinase signaling pathway factors induced by RANKL. Moreover, we verified that C-176 could reduce LPS-induced bone absorption in mice, reduce joint destruction in knee arthritis induced by meniscal instability, and protect against cartilage matrix loss in ankle arthritis induced by collagen immunity. In summary, our findings demonstrated that C-176 could inhibit the formation and activation of osteoclasts and could be used as a potential therapeutic agent for inflammatory osteolytic diseases.


Asunto(s)
Artritis , Resorción Ósea , Osteólisis , Animales , Ratones , Osteoclastos/metabolismo , Diferenciación Celular , Resorción Ósea/metabolismo , Transducción de Señal , Osteólisis/metabolismo , FN-kappa B/metabolismo , Ligando RANK/metabolismo , Factores de Transcripción NFATC/metabolismo , Osteogénesis
6.
Sensors (Basel) ; 24(5)2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38475127

RESUMEN

Conventional point prediction methods encounter challenges in accurately capturing the inherent uncertainty associated with photovoltaic power due to its stochastic and volatile nature. To address this challenge, we developed a robust prediction model called QRKDDN (quantile regression and kernel density estimation deep learning network) by leveraging historical meteorological data in conjunction with photovoltaic power data. Our aim is to enhance the accuracy of deterministic predictions, interval predictions, and probabilistic predictions by incorporating quantile regression (QR) and kernel density estimation (KDE) techniques. The proposed method utilizes the Pearson correlation coefficient for selecting relevant meteorological factors, employs a Gaussian Mixture Model (GMM) for clustering similar days, and constructs a deep learning prediction model based on a convolutional neural network (CNN) combined with a bidirectional gated recurrent unit (BiGRU) and attention mechanism. The experimental results obtained using the dataset from the Australian DKASC Research Centre unequivocally demonstrate the exceptional performance of QRKDDN in deterministic, interval, and probabilistic predictions for photovoltaic (PV) power generation. The effectiveness of QRKDDN was further validated through ablation experiments and comparisons with classical machine learning models.

7.
Int J Environ Health Res ; 34(2): 1156-1167, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37158781

RESUMEN

A retrospective analysis of birth data hospital-based obtained from 14 monitoring areas in the Huaihe River Basin from 2009 to 2019 was conducted. Trend in the total prevalence of birth defects (BDs) and subgroups were analyzed using the Joinpoint Regression model. The incidence of BDs increased gradually from 118.87 per 10,000 in 2009 to 241.18 per 10,000 in 2019 (AAPC = 5.91, P < 0.001). Congenital heart diseases were the most common subtype of BDs. The proportion of maternal age younger than 25 decreased but the age 25-40 years increased significantly (AAPC<20=-5.58; AAPC20-24=-6.38; AAPC25-29 = 5.15; AAPC30-35 = 7.07; AAPC35-40 = 8.27; All P < 0.05). Compared with the one-child policy period, the risk of BDs was greater for groups among maternal age younger than 40 years during the partial and universal two-child policy period (P < 0.001). The incidence of BDs and the proportion of women with advanced maternal age in Huaihe River Basin is increasing. There was an interaction between changes in birth policy and the mother's age on the risk of BDs.


Asunto(s)
Políticas , Humanos , Femenino , Adulto , Estudios Transversales , Estudios Retrospectivos , Edad Materna , China/epidemiología
8.
Nephrol Dial Transplant ; 38(1): 93-105, 2023 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-36102665

RESUMEN

BACKGROUND: Cholesterol crystal (CC) embolism causes acute kidney injury (AKI) and ischaemic cortical necrosis associated with high mortality. We speculated that sustaining the fibrinolytic system with Glu-plasminogen (Glu-Plg) could be a safe way to attenuate AKI and prevent ischaemic infarction upon CC embolism. METHODS: We induced CC embolism by injecting CC into the left kidney artery of C57BL/6J mice. The primary endpoint was glomerular filtration rate (GFR). RESULTS: Starting as early as 2 h after CC embolism, thrombotic angiopathy progressed gradually in the interlobular, arcuate and interlobar arteries. This was associated with a decrease of GFR reaching a peak at 18 h, i.e. AKI, and progressive ischaemic kidney necrosis developing between 12-48 h after CC injection. Human plasma Glu-Plg extracts injected intravenously 4 h after CC embolism attenuated thrombotic angiopathy, GFR loss as well as ischaemic necrosis in a dose-dependent manner. No bleeding complications occurred after Glu-Plg injection. Injection of an intermediate dose (0.6 mg/kg) had only a transient protective effect on microvascular occlusions lasting for a few hours without a sustained protective effect on AKI at 18-48 h or cortical necrosis, while 1.5 mg/kg were fully protective. Importantly, no bleeding complications occurred. CONCLUSIONS: These results provide the first experimental evidence that Glu-Plg could be an innovative therapeutic strategy to attenuate thrombotic angiopathy, AKI, kidney necrosis and potentially other clinical manifestations of CC embolism syndrome.


Asunto(s)
Lesión Renal Aguda , Embolia , Trombosis , Humanos , Ratones , Animales , Plasminógeno , Ratones Endogámicos C57BL , Riñón , Infarto , Colesterol , Necrosis
9.
BMC Gastroenterol ; 23(1): 80, 2023 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-36944920

RESUMEN

BACKGROUND: To evaluate the prognostic value of the pre-treatment aspartate transaminase (AST)/alanine transaminase (ALT) ratio in hepatocellular carcinoma (HCC) patients receiving radiofrequency ablation (RFA)/microwave ablation (MWA) combined with simultaneous TACE. METHODS: The data for 117 patients were retrospectively analyzed in this study. The endpoint of prognosis was overall survival (OS). The Youden index was used to choose the optimal cut-off value of the pre-treatment AST/ALT ratio for OS prediction. Univariate and multivariate analyses were used to identify independent risk factors, then integrated to establish the nomogram. RESULTS: The AST/ALT ratio cut-off value for OS prediction was 0.89, and patients with a higher AST/ALT ratio had poorer OS. The median OS for the high-value AST/ALT group was not reached, while the median OS for the low-value AST/ALT group was 48.5 months (P = 0.0047). The univariate and multivariate analysis showed that AST/ALT ratio, AFP, and tumor numbers were independent prognostic indicators for OS. The integrated nomogram showed higher predictive accuracy for OS (C-index 0.674, 95%CI: 0.600-0.748). CONCLUSIONS: The preoperative AST/ALT ratio could be a prognostic indicator for HCC patients receiving thermal ablation combined with simultaneous TACE.


Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Pronóstico , Alanina Transaminasa , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Estudios Retrospectivos , Aspartato Aminotransferasas , Resultado del Tratamiento
10.
Small ; 18(5): e2104439, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34816595

RESUMEN

The commercialization of MXenes as anodes for lithium-ion batteries is largely impeded by low initial coulombic efficiency (ICE) and unfavorable cycling stability, which are closely associated with defects such as Ti vacancies (VTi ) in Ti3 C2 MXenes. Herein, an effective strategy is developed to deactivate VTi defects by in situ growing Al2 O3 nanoclusters on MXenes to alleviate the irreversible electrolyte decomposition and Li dendrites formation trend induced by defects, improving ICE and cycling stability. Furthermore, it is revealed that excessively lithiophilic VTi defects would impede Li ions diffusion due to their strong adsorption, leading to a locally nonuniform Li flux to these "hot spots," setting scene for the formation of Li dendrites. The Al2 O3 nanoclusters anchored on VTi sites can not only improve Li diffusion kinetics but also promote the homogeneous solid electrolyte interphase formation with small charge transfer resistance, achieving uniform Li deposition in a smaller overpotential without formation of Li dendrites. As expected, Ti3 C2 @Al2 O3 -11 electrode delivers a high ICE of 76.6% and an outstanding specific capacity of 285.5 mAh g-1 after 500 cycles, which is much higher than that of pristine Ti3 C2 sample. This work sheds light on modulating defects for high-performance energy storage materials.

11.
Clin Exp Nephrol ; 26(9): 917-924, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35579723

RESUMEN

OBJECTIVE: No epidemiological evidence has investigated the effect of albumin to alkaline phosphatase ratio (AAPR) on the prognosis among critically ill patients with acute kidney injury (AKI). We aimed to explore the prognostic value of AAPR in these patients. METHODS: We extracted all clinical data from MIMIC III. ROC curve analysis was used to evaluate the discrimination of AAPR for predicting in-hospital mortality. A generalized additive model was applied to identify a nonlinear association between AAPR and in-hospital mortality. The Cox proportional hazards models were used to determine the association between AAPR and in-hospital and 30-day mortality. RESULTS: A total of 6894 eligible subjects were enrolled in this study. The relationship between AAPR and in-hospital mortality was nonlinear. Multivariate analysis demonstrated that lower AAPR (AAPR < 0.35) was an independent predictor of in-hospital and 30-day mortality after adjusting for potential confounders (HR 1.74, 95% CI 1.72-2.20, P < 0.001; HR 1.89, 95% CI 1.66-2.14, P < 0.001, respectively). CONCLUSIONS: AAPR may serve as a potential prognostic biomarker in critically ill patients with AKI and lower AAPR was associated with increased risk of in-hospital and 30-day mortality among these patients.


Asunto(s)
Lesión Renal Aguda , Fosfatasa Alcalina , Lesión Renal Aguda/diagnóstico , Albúminas , Enfermedad Crítica , Humanos , Pronóstico
12.
Mikrochim Acta ; 189(3): 90, 2022 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-35129715

RESUMEN

A novel molecular imprint photoelectrochemical (PEC) sensor has been prepared based on oriented single-crystalline TiO2 nanoarray (TNA) material for sensitive detection of diclofenac (DCF). The TNA obtained by the one-step hydrothermal method was characterized by XRD, SEM, and TEM. Polypyrrole film was formed on the TNA by electrochemical method, and DCF was imprinted on the polymer film as the template molecule. After the removal of DCF, there appeared lots of specific recognition sites that matched template molecules. The experimental results demonstrated that the constructed PEC sensor has good sensitivity and selectivity for the detection of DCF, which can be attributed to the high photoelectric conversion efficiency of TNA and the high selectivity of molecular imprinting technology. The fabricated PEC sensor showed a wide detection range (0.05-1000 µM) and a low limit of detection (0.0034 µM) for DCF, as well as good repeatability and stability. The proposed PEC sensor provided an effective strategy in the monitoring of environmental pollutants.

13.
Environ Monit Assess ; 194(3): 188, 2022 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-35165790

RESUMEN

An in-depth understanding of the rainfall-runoff process is essential for effective stormwater management. However, the understanding of the hierarchy of rainfall characteristics in terms of their importance in influencing runoff generation is limited. This paper investigates the influence of rainfall characteristics and catchment characteristics on runoff generation in urban catchments. The outcomes showed that there are 4 dominant factors affecting runoff generation: total precipitation TP and maximum 60-min rainfall intensity MAX60 are the two top-ranked factors while average rainfall intensity RI and maximum 5-min rainfall intensity MAX5 are ranked second. Additionally, compared to the moderate rainfall regime (MR), the heavy rainfall regime (HR) tends to produce higher peak flow rates, higher total inflow per unit area, and lower runoff control effect. Note that the antecedent precipitation has a more significant effect on runoff generation and is even the dominant factor when rainstorm events with daily rainfall larger than 50 mm are not considered. The results of analyzing the influence of catchment characteristics suggest that only under HR regime conditions do the catchment characteristics have an impact on runoff generation and behave as smaller catchment areas, and higher proportions of green landscapes always lead lower peak flow rates, lower total inflows per unit area, and higher runoff control effects.


Asunto(s)
Movimientos del Agua , Contaminantes Químicos del Agua , China , Monitoreo del Ambiente , Lluvia , Contaminantes Químicos del Agua/análisis
14.
Inflamm Res ; 70(6): 705-717, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34014331

RESUMEN

BACKGROUND: Previous studies have demonstrated that Luteolin has a positive effect on epithelial barrier integrity by promoting the function of tight protein, however, little is known about the underline mechanism of Luteolin. In this study, we constructed Caco-2 cell monolayer to explore the effects and the regulation mechanism of Luteolin in intestinal epithelial barrier integrity. METHODS: Caco-2 cells were co-treated with TNF-α, Interferon-γ (IFN-γ) and Luteolin for 24 h. Overexpression or knockdown of SHP-1 was applied to study the effects of protein phosphoserine phosphatase-1 (SHP-1) on epithelial barrier integrity. Cell viability was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Barrier function was detected by trans-epithelial electrical resistance (TEER) and FITC-dextran assay. The expression levels of SHP-1, phosphorylation signal transducer and activator of transcription 3 (p-STAT3), STAT3 and tight junction proteins were measured by qRT-PCR or western blot. In vivo model of ulcerative colitis was established to detect the function of Luteolin in ulcerative colitis. RESULTS: We clarified that Luteolin protected intestinal epithelial barrier function of Caco-2 monolayers by increasing the resistance values and tight junction (TJ) protein expression. The expression of OCLN, CLDN1, and ZO1 was increased by Luteolin, while the expression of CLDN2 was decreased. Furthermore, Luteolin significantly alleviated the symptom of ulcerative colitis in DSS-induced mice. The in vitro cell model proved that overexpression of SHP-1 promotes the epithelial barrier function and knockdown of SHP-1 or STAT3 activation destroyed the protective effects of Luteolin on the expression of TJ proteins. CONCLUSION: We found that the treatment of Luteolin promoted epithelial barrier function and Luteolin might preserve intestinal epithelial barrier function through suppression of STAT3 signaling pathway by SHP-1.


Asunto(s)
Colitis Ulcerosa/tratamiento farmacológico , Luteolina/uso terapéutico , Proteína Tirosina Fosfatasa no Receptora Tipo 6/metabolismo , Factor de Transcripción STAT3/metabolismo , Animales , Células CACO-2 , Permeabilidad de la Membrana Celular/efectos de los fármacos , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/metabolismo , Colitis Ulcerosa/patología , Colon/efectos de los fármacos , Colon/metabolismo , Colon/patología , Sulfato de Dextran , Humanos , Luteolina/farmacología , Masculino , Ratones Endogámicos C57BL , Proteína Tirosina Fosfatasa no Receptora Tipo 6/genética , Transducción de Señal/efectos de los fármacos , Proteínas de Uniones Estrechas/genética , Proteínas de Uniones Estrechas/metabolismo
15.
Med Sci Monit ; 27: e930688, 2021 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-33934098

RESUMEN

BACKGROUND Influenza-associated acute necrotizing encephalopathy (IANE) can be lethal and disabling and have a sudden onset and deteriorate rapidly but lacks early diagnostic indicators. We aimed to examine the early clinical diagnostic indicators in children with IANE. MATERIAL AND METHODS Acute influenza patients were grouped according to their clinical manifestations: flu alone (FA), flu with febrile seizure (FS), influenza-associated encephalopathy (IAE), and IANE. The clinical features, biomarkers, neuroelectrophysiological results, and neuroimaging examination results were compared. RESULTS A total of 31 patients were included (FA (n=4), FS (n=8), IAE (n=14), and IANE (n=5)). The IANE group, whose mean age was 3.7 years, was more likely to show rapid-onset seizure, acute disturbance of consciousness (ADOC), Babinski's sign, and death/sequela. More patients in the IANE group required tracheal intubation mechanical ventilation and received intravenous immunoglobulins (IVIG) and glucocorticoids. The alanine aminotransferase (ALT), aspartate transaminase (AST), and lactate dehydrogenase (LDH) levels in the IANE group were significantly higher than in the FS and IAE groups. The aquaporin-4 (AQP-4) antibody and malondialdehyde (MDA) levels in the serum and cerebrospinal fluid (CSF) were notably higher in IANE patients in the acute stage compared with FS and IAE patients. All patients in the IANE group had positive neuroimaging findings. CONCLUSIONS Early clinical warning factors for IANE include rapid-onset seizures in patients under 4 years of age, ADOC, and pathological signs. Increased AQP-4 antibodies and MDA levels in CSF might contribute to early diagnosis. Early magnetic resonance venography (MRV) and susceptibility-weighted imaging (SWI) sequences, or thrombelastography to identify deep vein thrombosis, might indicate clinical deterioration.


Asunto(s)
Encefalopatías/diagnóstico , Gripe Humana/diagnóstico , Enfermedad Aguda , Alanina Transaminasa/sangre , Alanina Transaminasa/metabolismo , Acuaporinas/sangre , Acuaporinas/metabolismo , Aspartato Aminotransferasas/sangre , Aspartato Aminotransferasas/metabolismo , Biomarcadores/sangre , Biomarcadores/metabolismo , Encefalopatías/sangre , Encefalopatías/metabolismo , Líquido Cefalorraquídeo/metabolismo , Preescolar , Femenino , Glucocorticoides/sangre , Glucocorticoides/metabolismo , Humanos , Inmunoglobulinas Intravenosas/sangre , Inmunoglobulinas Intravenosas/metabolismo , Gripe Humana/sangre , Gripe Humana/metabolismo , L-Lactato Deshidrogenasa/sangre , L-Lactato Deshidrogenasa/metabolismo , Masculino , Malondialdehído/sangre , Malondialdehído/metabolismo , Neuroimagen/métodos , Convulsiones/sangre , Convulsiones/diagnóstico , Convulsiones/metabolismo
16.
Ecotoxicol Environ Saf ; 221: 112421, 2021 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-34147865

RESUMEN

A wide variety of organic micropollutants in drinking water pose a serious threat to human health. This study was aimed to reveal the characteristics of organic micropollution profiles in water from a drinking water treatment plant (DWTP) in the Yangtze River Delta, China and investigate the mutagenicity, health risk and disease burden through mixed exposure to micropollutants in water. The presence of organic micropollutants in seven categories in organic extracts (OEs) of water from the DWTP was determined, and Ames test was conducted to test the mutagenic effect of OEs. Meanwhile, health risk of exposure to organic micropollutants in finished water through three exposure routes (ingestion, dermal absorption and inhalation) was assessed with the method proposed by U.S. EPA, and disability-adjusted life years (DALYs) were combined to estimate the disease burden of cancer based on the carcinogenic risk (CR) assessment. The results showed that 28 organic micropollutants were detected in the raw and finished water at total concentrations of 967.28 ng/L and 1073.45 ng/L, respectively, of which phthalate esters (PAEs) were the dominant category (95.79% in the raw water and 96.61% in the finished water). Although the results of the Ames test for OEs were negative and the non-carcinogenic hazard index of the organic micropollutants in the finished water was less than 1 in all age groups, the total CR was 2.17 × 10-5, higher than the negligible risk level (1.00 × 10-6). The total DALYs caused by the organic micropollutants in the finished water was 2945.59 person-years, and the average individual DALYs was 2.21 × 10-6 per person-year (ppy), which was 2.21 times the reference risk level (1.00 × 10-6 ppy) defined by the WHO. Exposure to nitrosamines (NAms) was the major contributor to the total CR (92.06%) and average individual DALYs (94.58%). This study demonstrated that despite the negative result of the mutagenicity test with TA98 and TA100 strains, the health risk of exposure to organic micropollutants in drinking water should not be neglected.


Asunto(s)
Agua Potable/análisis , Mutágenos/análisis , Compuestos Orgánicos/análisis , Contaminantes Químicos del Agua/análisis , China , Costo de Enfermedad , Monitoreo del Ambiente , Humanos , Pruebas de Mutagenicidad , Mutágenos/toxicidad , Compuestos Orgánicos/toxicidad , Medición de Riesgo , Ríos , Contaminantes Químicos del Agua/toxicidad , Purificación del Agua
17.
FASEB J ; 33(12): 13254-13266, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31539281

RESUMEN

Macrophages (Mφs) can be used as a part of cell-based cancer immunotherapy. However, they may be hampered by a failure to effectively and stably regulate their polarization state to enhance their tumoricidal effects. In this work, mechanical stretch (MS), as a biology-free modulatory method, was shown to enhance M1 polarization and tumoricidal effects. By using an in vitro Flexcell Tension system, we found that murine Mφ RAW264.7 cells showed higher M1 polarization-related mRNA expression and cytokine release after MS. Further molecular analyses found that focal adhesion kinase and NF-κB activation occurred in the MS-induced M1 polarization. Coculture of MS-preconditioned Mφ with B16F10 skin melanoma cells in vitro showed that the proliferation of B16F10 cells decreased, whereas caspase-3-induced apoptosis increased. Importantly, the injection of MS-preconditioned Mφ into murine skin melanomas in vivo impeded tumor growth; lesions were characterized by increased amounts of M1 Mφ, decreased tumor cell proliferation, and increased tumor cell apoptosis in the tumor microenvironment. Together, our results suggest that MS could be used as a simple preconditioning approach to prepare tumoricidal M1 Mφ for cancer immunotherapy.-Shan, S., Fang, B., Zhang, Y., Wang, C., Zhou, J., Niu, C., Gao, Y., Zhao, D., He, J., Wang, J., Zhang, X., Li, Q. Mechanical stretch promotes tumoricidal M1 polarization via the FAK/NF-κB signaling pathway.


Asunto(s)
Proteína-Tirosina Quinasas de Adhesión Focal/metabolismo , FN-kappa B/metabolismo , Transducción de Señal/fisiología , Animales , Western Blotting , Citocinas/metabolismo , Femenino , Proteína-Tirosina Quinasas de Adhesión Focal/genética , Etiquetado Corte-Fin in Situ , Ratones , Ratones Endogámicos C57BL , FN-kappa B/genética , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Células RAW 264.7 , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de Señal/genética
18.
Liver Int ; 40(3): 622-637, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31782595

RESUMEN

BACKGROUND & AIMS: Nonalcoholic fatty liver disease encompasses isolated steatosis or nonalcoholic fatty liver and nonalcoholic steatohepatitis (NASH). NASH develops from isolated steatosis with obscure driving forces. We aim to identify key factors promoting this transition. METHODS: Following 21-week of high-fat diet feeding, obese mice were classified into two groups termed as isolated steatosis and NASH based on hematoxylin-eosin staining of liver histology. The integrated multi-omics analysis of lipidome, transcriptome and gut microbiome were performed in mice with isolated steatosis and NASH, and confirmed in human samples. RESULTS: Livers in mice with NASH lost most lipids, and the transcriptional landscape was also changed dramatically in mice with NASH in relative to mice with isolated steatosis. Plasma lipidome analysis demonstrated a very clear difference between these two groups of mice, which was partially recapitulated in serum of patients with isolated steatosis and NASH. The microbiota composition revealed that Bacteroides genus and Bacteroides uniformis species decreased while Mucispirillum genus and Mucispirillum schaedleri species increased largely in mice with NASH. More importantly, we found that Bacteroides uniformis correlated positively with triglycerides (TGs) and negatively with free fatty acids (FFAs) and PE(18:1/20:4), while Mucispirillum schaedleri correlated positively with FFAs, LysoPC(20:3), LysoPC(20:4) and DG(16:1/18:2). Mechanically, administration of Bacteroides uniformis increased specific TGs, and decreased hepatic injury and inflammation in diet-induced mice. CONCLUSIONS: Overall, through multi-omics integration, we identified a microbiota-lipid axis promoting the initiation of NASH from isolated steatosis, which might provide a novel perspective on NASH pathogenesis and treatment.


Asunto(s)
Microbioma Gastrointestinal , Enfermedad del Hígado Graso no Alcohólico , Animales , Bacterias , Bacteroides , Humanos , Lipidómica , Hígado , Ratones
19.
Phys Chem Chem Phys ; 22(44): 25430-25444, 2020 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-33169125

RESUMEN

Covering about 70% of the earth's surface, water contains considerable energy that remains unexploited. Superhydrophobic surfaces (SHSs) possess excellent water repellency, and energy conversion based on SHSs has opened up a new avenue for efficient collection and utilization of water energy. Therefore, it is of great significance to efficiently prepare SHSs and apply them for energy conversion in different fields. In this review, we first summarize the fabrication methods of SHSs, and then provide an overview of the energy conversion forms based on SHSs. Finally, the related applications corresponding to the energy conversion forms are introduced, including renewable energy collection and utilization, wearable device design, use of liquid sensors, surface cooling and heat dissipation, self-propelled devices, droplet manipulation and lab-on-a-chip devices; and their challenges and future perspectives are highlighted.

20.
Med Sci Monit ; 26: e928835, 2020 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-33335084

RESUMEN

BACKGROUND This study summarizes the characteristics of children screened for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and reports the case of 1 child who was diagnosed with SARS-CoV-2 infection in Guangzhou Women and Children's Medical Center and the cases of his family members. MATERIAL AND METHODS The medical records of 159 children who were admitted to our hospital from January 23 to March 20, 2020, were retrospectively analyzed. Samples from pharyngeal or/and anal swabs were subjected to reverse-transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 within 12 h of patient admission; a second RT-PCR test was done 24 h after the first test. RESULTS Of the 159 patients, 151 patients had epidemiological histories, 14 patients had cluster onset, and 8 patients had no epidemiological history but had symptoms similar to coronavirus disease 2019 (COVID-19). The most common symptom was fever (n=125), followed by respiratory and gastrointestinal symptoms. A 7-year-old boy in a cluster family from Wuhan was confirmed with asymptomatic SARS-CoV-2 infection with ground-glass opacity shadows on his lung computed tomography scan, and his swab RT-PCR test had not turned negative until day 19 of his hospitalization. In patients who did not test positive for SARS-CoV-2, influenza, respiratory syncytial virus, and adenovirus were observed. A total of 158 patients recovered, were discharged, and experienced no abnormalities during follow-up. CONCLUSIONS For SARS-CoV-2 nosocomial infections, taking a "standard prevention & contact isolation & droplet isolation & air isolation" strategy can prevent infection effectively. Children with clustered disease need close monitoring.


Asunto(s)
COVID-19/diagnóstico , COVID-19/epidemiología , Prueba de Ácido Nucleico para COVID-19/métodos , Niño , Preescolar , China/epidemiología , Coronavirus/metabolismo , Coronavirus/patogenicidad , Infección Hospitalaria/epidemiología , Femenino , Fiebre , Hospitalización , Hospitales , Humanos , Masculino , Registros Médicos , Alta del Paciente , Estudios Retrospectivos , SARS-CoV-2/metabolismo , SARS-CoV-2/patogenicidad
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