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Autophagy is an intracellular degradation system for cytoplasmic constituents which is mediated by the formation of a double-membrane organelle termed the autophagosome and its subsequent fusion with the lysosome/vacuole. The formation of the autophagosome requires membrane from the endoplasmic reticulum (ER) and is tightly regulated by a series of autophagy-related (ATG) proteins and lipids. However, how the ER contacts autophagosomes and regulates autophagy remain elusive in plants. In this study, we identified and demonstrated the roles of Arabidopsis oxysterol-binding protein-related protein 2A (ORP2A) in mediating ER-autophagosomal membrane contacts and autophagosome biogenesis. We showed that ORP2A localizes to both ER-plasma membrane contact sites (EPCSs) and autophagosomes, and that ORP2A interacts with both the ER-localized VAMP-associated protein (VAP) 27-1 and ATG8e on the autophagosomes to mediate the membrane contact sites (MCSs). In ORP2A artificial microRNA knockdown (KD) plants, seedlings display retarded growth and impaired autophagy levels. Both ATG1a and ATG8e accumulated and associated with the ER membrane in ORP2A KD lines. Moreover, ORP2A binds multiple phospholipids and shows colocalization with phosphatidylinositol 3-phosphate (PI3P) in vivo. Taken together, ORP2A mediates ER-autophagosomal MCSs and regulates autophagy through PI3P redistribution.
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Arabidopsis , MicroARNs , Oxiesteroles , Arabidopsis/genética , Arabidopsis/metabolismo , Autofagia/fisiología , Proteínas Relacionadas con la Autofagia/genética , Proteínas Relacionadas con la Autofagia/metabolismo , Retículo Endoplásmico/metabolismo , MicroARNs/metabolismo , Oxiesteroles/metabolismoRESUMEN
BACKGROUND: The role of plant-based dietary patterns in preventing cardiovascular disease (CVD) among individuals with prediabetes and diabetes remains unclear. We aimed to evaluate the associations of plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI) with cardiovascular disease (CVD) risk and explore potential contributing factors among people with prediabetes and diabetes. METHODS: A total of 17,926 participants with prediabetes and 7798 with diabetes were enrolled from the UK Biobank between 2006 and 2010 and followed until the end of 2020. We calculated the PDI, hPDI, and uPDI based on 18 major food groups including plant-based foods and animal-based foods and applied Cox proportional hazard models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD risk related to PDI, hPDI, and uPDI. Decomposition analysis was performed to assess the role of dietary components, and mediation analysis was performed to assess the potential mediating role of serum biomarkers underlying these associations. RESULTS: A total of 2324 CVD events were documented among individuals with prediabetes, while 1461 events occurred among patients with diabetes. An inverse association was found between hPDI and CVD risk among individuals with prediabetes (HR T3 vs. T1 = 0.88, 95% CI = 0.79-0.98, Ptrend = 0.025) but not those with diabetes. A positive association was found between uPDI and CVD risk among individuals with prediabetes (HR T3 vs. T1 = 1.17, 95% CI = 1.05-1.30, Ptrend = 0.005) and those with diabetes (HR T3 vs. T1 = 1.14, 95% CI = 1.00-1.29, Ptrend = 0.043). High-sugar-sweetened beverages (SSB) intake accounted for 35% of the hPDI-CVD association and 15% of the uPDI-CVD association among individuals with prediabetes, whereas low intake of whole grain accounted for 36% of the association among patients with diabetes. Elevated cystatin C levels explained the largest proportion of the association between uPDI and CVD risk among individuals with prediabetes (15%, 95% CI = 7-30%) and diabetes (44%, 95% CI = 9-86%). CONCLUSIONS: Adherence to an unhealthy plant-based diet is associated with a higher CVD risk in people with prediabetes or diabetes, which may be partially attributed to low consumption of whole grains, high intake of SSB, and high blood cystatin C levels.
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Enfermedades Cardiovasculares , Dieta Vegetariana , Estado Prediabético , Humanos , Estado Prediabético/epidemiología , Enfermedades Cardiovasculares/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Diabetes Mellitus/epidemiología , Reino Unido/epidemiología , Factores de Riesgo , Dieta a Base de PlantasRESUMEN
OBJECTIVE: Nasopharyngeal adenoid cystic carcinoma (NACC) is a rare malignancy with special biological features. Controversies exist regarding the treatment approach and prognostic factors in the IMRT era. This study aimed to evaluate the long-term outcomes and management approaches in NACC. METHODS: Fifty patients with NACC at our institution between 2010 and 2020 were reviewed. Sixteen patients received primary radiotherapy (RT), and 34 patients underwent primary surgery. RESULTS: Between January 2010 and October 2020, a total of 50 patients with pathologically proven NACC were included in our analysis. The median follow-up time was 58.5 months (range: 6.0-151.0 months). The 5-year overall survival rate (OS) and progression-free survival rate (PFS) were 83.9% and 67.5%, respectively. The 5-year OS rates of patients whose primary treatment was surgery and RT were 90.0% and 67.3%, respectively (log-rank P = 0.028). The 5-year PFS rates of patients whose primary treatment was surgery or RT were 80.8% and 40.7%, respectively (log-rank P = 0.024). Multivariate analyses showed that nerve invasion and the pattern of primary treatment were independent factors associated with PFS. CONCLUSIONS: Due to the relative insensitivity to radiation, primary surgery seemed to provide a better chance of disease control and improved survival in NACC. Meanwhile, postoperative radiotherapy should be performed for advanced stage or residual tumours. Cranial nerve invasion and treatment pattern might be important factors affecting the prognosis of patients with NACC.
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Carcinoma Adenoide Quístico , Neoplasias Nasofaríngeas , Radioterapia de Intensidad Modulada , Humanos , Carcinoma Adenoide Quístico/radioterapia , Carcinoma Adenoide Quístico/mortalidad , Carcinoma Adenoide Quístico/patología , Carcinoma Adenoide Quístico/cirugía , Masculino , Femenino , Radioterapia de Intensidad Modulada/métodos , Persona de Mediana Edad , Adulto , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/patología , Anciano , Estudios Retrospectivos , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/patología , Adulto Joven , Pronóstico , Tasa de Supervivencia , Resultado del Tratamiento , Estudios de Seguimiento , Adolescente , Supervivencia sin ProgresiónRESUMEN
BACKGROUND: Although previous studies show that microRNAs (miRNAs) can potentially be used as diagnostic markers for epilepsy, there are very few analyses of pediatric epilepsy patients. METHODS: miRNA profiles using miRNA-seq was performed on plasma samples from 14 pediatric epileptic patients and 14 healthy children. miRNA miR-27a-3p that were significantly changed between two groups were further evaluated. The potential target genes of miR-27a-3p were screened through unbiased mRNA-seq and further validated using Western blot and immunohistochemistry in HEK-293T cells and in the brains of mice with epilepsy induced by lithium chloride-pilocarpine. RESULTS: We found 82 upregulated and 76 downregulated miRNAs in the plasma from pediatric patients compared with controls (p < 0.01), of which miR-27a-3p exhibited a very low p value (p < 0.0001) and validated in additional plasma samples. Two genes, GOLM1 and LIMK1, whose mRNA levels were decreased (p < 0.001) with the increase of miR-27a-3p were further validated in both HEK-293T cells and in epileptic mice. CONCLUSIONS: MiR-27a-3p exhibits potential as a diagnostic and therapeutic marker for epilepsy. We postulate that additional studies on the downstream targets of miR-27a-3p will unravel its roles in epileptogenesis or disease progression. IMPACT: A total of 158 differentially expressed miRNAs were detected in plasma between epileptic and control children. Plasma miR-27a-3p was one of the miRNAs with a low p value. GOLM1 and LIMK1 were validated as downstream target genes of miR-27a-3p. miR-27a-3p has potential as a diagnostic and therapeutic marker for epilepsy.
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Epilepsia , MicroARNs , Humanos , Ratones , Animales , Niño , MicroARNs/genética , Epilepsia/genética , Biomarcadores , Encéfalo , ARN Mensajero , Quinasas Lim , Proteínas de la MembranaRESUMEN
AIM: To investigate the association between fish oil supplementation and subsequent risk of chronic kidney disease (CKD) among patients with diabetes, and further evaluate the mediation effect of typical glycolipid and inflammatory biomarkers. METHODS: In total, 24 497 patients with diabetes from the UK Biobank were included. Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for CKD risk, and the rate advancement period was calculated to quantify and communicate the impact of fish oil upon that risk. In addition, we also used mediation analysis to assess the mediating role of plasma biomarkers. RESULTS: Overall, 7122 patients reported taking fish oil supplements. During a mean of 11.3 years of follow-up, 3533 CKD cases occurred. In the fully adjusted model, fish oil use was inversely associated with the incidence of CKD (HR 0.90; 95% CI: 0.83, 0.97), which was mediated by serum levels of HbA1c (4.7%), C-reactive protein (CRP) (3.4%) and high-density lipoprotein cholesterol (HDL-C) (2.3%). Participants who took fish oil supplements displayed the same risk of CKD events, but that risk was delayed by approximately 2.79 years compared with non-users of fish oil. CONCLUSIONS: Our findings advocate the beneficial role of fish oil use in preventing CKD among patients with diabetes, which may be mediated by serum levels of HbA1c, CRP and HDL-C, and support public health policies aiming to promote fish oil supplementation for the prevention of diabetes complications.
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Suplementos Dietéticos , Aceites de Pescado , Insuficiencia Renal Crónica , Humanos , Masculino , Femenino , Aceites de Pescado/uso terapéutico , Aceites de Pescado/administración & dosificación , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/sangre , Persona de Mediana Edad , Anciano , Biomarcadores/sangre , Adulto , Hemoglobina Glucada/análisis , Hemoglobina Glucada/metabolismo , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Reino Unido/epidemiología , Modelos de Riesgos Proporcionales , Incidencia , Nefropatías Diabéticas/epidemiología , Nefropatías Diabéticas/prevención & control , Nefropatías Diabéticas/sangre , Factores de Riesgo , HDL-Colesterol/sangre , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicacionesRESUMEN
The motion of passive particles in a confined square domain filled with active fluids has been numerically simulated using a direct-fictitious domain method. The ratio of particle diameter to the side length of the square domain (dp/L) is adopted to classify the degree of confinement (i.e., strong or weak confinement). The translational mean-squared displacement (MSDT) of weakly-confined particles scales well with the reported theoretical and experimental results in a short time and eventually reaches a plateau because of the confined environment. Additionally, the radial probability densities of the particle positions gradually increase with increasing distance from the center of the square domain at relatively high activity levels, displaying an apparent rise near the boundary and maximize near the corner. Conversely, the strongly confined particles migrate toward the center of the square domain or approach the corner with continuous rotation. In addition, the localized minima of the angular velocity of the particles show a periodic behavior, with the vortices periodically becoming more organized. Moreover, with increasing activity, two distinct linearly correlated regimes emerge in the relationship between the particle's rotational velocity and the activity. A comprehensive analysis of the collective dynamics reveals that the cutoff length is Rc ≈ 0.19(2.375dp), pointing to the distance at which the velocities of two particles are uncorrelated. Moreover, the spatial correlation function (Ip) shows a small peak at Rr ≈ 0.12(1.5dp), suggesting a relatively strong correlation between a given particle and another particle located at a distance Rr from it. Interestingly, both Rc and Rr are smaller than those observed in an unbounded flow, which indicates that boundary confinement significantly influences the ability of the particles to form coherent structures.
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A Pd-catalyzed thiocarbonylative cyclization of N-(o-iodoaryl)acrylamides with easily accessible thioformates has been developed. The reaction has a wide substrate scope with good yields and represents a powerful route to the synthesis of thioester-functionalized oxindoles. Both S-aryl and alkyl thioformates as the thioester sources were well tolerated. The active Pd-CO intermediate may play an important role in the transformation process.
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The number of topological defects in the shear flow of active nematic fluids is numerically investigated in this study. The evolution of the flow state of extensile active nematic fluids is explored by increasing the activity of active nematic fluids. Evidently, medium-activity active nematic fluids exhibit a highly ordered vortex lattice fluid state. However, high-activity active nematic fluids exhibit a meso-scale turbulent flow accompanied by topological defects. The number of topological defects (Ndef) increases with increasing shear Reynolds number (Res). Fluid viscosity strongly influences Ndef, while the influence of fluid density is relatively weak. Ndef decreases with increasing activity length scale (lζ) value. A small Res value strongly influences Ndef, whereas a large lζ value only weakly influences Ndef. As the activity increases, Ndef in contractile active nematic fluids becomes larger than that of extensile active nematic fluids.
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Ecological theory suggests that large-scale patterns such as community stability can be influenced by changes in interspecific interactions that arise from the behavioural and/or physiological responses of individual species varying over time. Although this theory has experimental support, evidence from natural ecosystems is lacking owing to the challenges of tracking rapid changes in interspecific interactions (known to occur on timescales much shorter than a generation time) and then identifying the effect of such changes on large-scale community dynamics. Here, using tools for analysing nonlinear time series and a 12-year-long dataset of fortnightly collected observations on a natural marine fish community in Maizuru Bay, Japan, we show that short-term changes in interaction networks influence overall community dynamics. Among the 15 dominant species, we identify 14 interspecific interactions to construct a dynamic interaction network. We show that the strengths, and even types, of interactions change with time; we also develop a time-varying stability measure based on local Lyapunov stability for attractor dynamics in non-equilibrium nonlinear systems. We use this dynamic stability measure to examine the link between the time-varying interaction network and community stability. We find seasonal patterns in dynamic stability for this fish community that broadly support expectations of current ecological theory. Specifically, the dominance of weak interactions and higher species diversity during summer months are associated with higher dynamic stability and smaller population fluctuations. We suggest that interspecific interactions, community network structure and community stability are dynamic properties, and that linking fluctuating interaction networks to community-level dynamic properties is key to understanding the maintenance of ecological communities in nature.
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Ecosistema , Peces/fisiología , Animales , Biodiversidad , Peces/clasificación , Japón , Modelos Lineales , Dinámica Poblacional , Conducta Predatoria , Estaciones del Año , Factores de TiempoRESUMEN
BACKGROUND & AIMS: Obesity has been linked to various detrimental health consequences. While there is established evidence of a negative correlation between seafood consumption and obesity in adults, the current research on the association between seafood intake in childhood/adolescence and the risk of obesity is lacking. Our aim was to evaluate the association between seafood intake in childhood/adolescence and the risk of obesity in a Chinese nationwide cohort. METHODS: We utilized data from the China Health and Nutrition Survey (CHNS) from the year of 1997 to 2015. Seafood consumption was evaluated through 3-day 24-hour recalls. In our study, overweight/obesity status was determined based on the Chinese Criteria of Overweight and Obesity in School-age Children and Adolescents (WS/T 586-2018), while abdominal obesity status was determined according to the Chinese Criteria of Waist Circumference Screening Threshold among Children and Adolescents (WS/T 611-2018). RESULTS: During an average follow-up of 7.9 years, 404 cases developed overweight/obesity among 2206 participants in the seafood-overweight/obesity analysis, while 381 cases developed abdominal obesity among 2256 participants in the seafood-abdominal-obesity analysis. The high-consumer group was associated with 35% lower risk of overweight/obesity risk and 26% lower risk of abdominal obesity after fully adjusting for sociodemographic and lifestyle factors, compared with the non-consumer group. Considering different cooking methods, boiled seafood consumption was associated with 43% lower risk of overweight/obesity and 23% lower risk of abdominal obesity in the fully adjusted model, while stir-fried seafood did not demonstrate a statistical significance. CONCLUSION: Higher intake of seafood in childhood/adolescents, particularly in a boiled way, was associated with lower obesity risk.
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Encuestas Nutricionales , Alimentos Marinos , Humanos , Niño , Femenino , Adolescente , Masculino , Alimentos Marinos/estadística & datos numéricos , China/epidemiología , Estudios de Cohortes , Encuestas Nutricionales/estadística & datos numéricos , Encuestas Nutricionales/métodos , Factores de Riesgo , Obesidad Infantil/epidemiología , Dieta/estadística & datos numéricos , Dieta/métodos , Dieta/efectos adversos , Obesidad Abdominal/epidemiología , Sobrepeso/epidemiologíaRESUMEN
BACKGROUNDS: The intestinal development in early life is profoundly influenced by multiple biological components of breast milk, in which milk-derived extracellular vesicles (mEVs) contain a large amount of vertically transmitted signal from the mother. However, little is known about how maternal fiber-rich diet regulates offspring intestinal development by influencing the mEVs. RESULTS: In this study, we found that maternal resistant starch (RS) consumption during late gestation and lactation improved the growth and intestinal health of offspring. The mEVs in breast milk are the primary factor driving these beneficial effects, especially enhancing intestinal cell proliferation and migration. To be specific, administration of mEVs after maternal RS intake enhanced intestinal cell proliferation and migration in vivo (performed in mice model and indicated by intestinal histological observation, EdU assay, and the quantification of cyclin proteins) and in vitro (indicated by CCK8, MTT, EdU, and wound healing experiments). Noteworthily, miR-146a-5p was found to be highly expressed in the mEVs from maternal RS group, which also promotes intestinal cell proliferation in cells and mice models. Mechanically, miR-146a-5p target to silence the expression of ubiquitin ligase 3 gene NEDD4L, thereby inhibiting DVL2 ubiquitination, activating the Wnt pathway, and promoting intestinal development. CONCLUSION: These findings demonstrated the beneficial role of mEVs in the connection between maternal fiber rich diet and offspring intestinal growth. In addition, we identified a novel miRNA-146a-5p-NEDD4L-ß-catenin/Wnt signaling axis in regulating early intestinal development. This work provided a new perspective for studying the influence of maternal diet on offspring development.
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Vesículas Extracelulares , MicroARNs , Animales , Femenino , Humanos , Ratones , Embarazo , Proliferación Celular , Dieta , Vesículas Extracelulares/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Leche , Sus scrofaRESUMEN
The ribose nucleic acid (RNA)-binding motif protein 24 (RBM24) has been recognized as a critical regulatory protein in various types of tumors. However, its specific role in glioblastoma (GBM) has not been thoroughly investigated. The objective of this study is to uncover the role of RBM24 in GBM and understand the underlying mechanism. The expression of RBM24 in GBM was initially analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA). Subsequently, the RBM24 expression levels in clinical samples of GBM were examined, and the survival curves of GBM patients were plotted based on high- and low-expression levels of RBM24 using Kaplan-Meier (KM) plotter. In addition, RBM24 knockdown cell lines and overexpression vectors were created to assess the effects on proliferation, apoptosis, and invasion abilities. Finally, the binding level of RBM24 protein to LATS1 messenger RNA (mRNA) was determined by RNA immunoprecipitation (RIP) assay, and the expression levels of RBM24 and LATS1 were measured through quantitative reverse-transcriptase-polymerase chain reaction (qRT-PCR) and Western blot (WB). Our data revealed a significant decrease in RBM24 mRNA and protein levels in GBM patients, indicating that those with low RBM24 expression had a worse prognosis. Overexpression of RBM24 led to inhibited cell proliferation, reduced invasion, and increased apoptosis in LN229 and U87 cells. In addition, knocking down LATS1 partially reversed the effects of RBM24 on cell proliferation, invasion, and apoptosis in GBM cells. In vivo xenograft model further demonstrated that RBM24 overexpression reduced the growth of subcutaneous tumors in nude mice, accompanied by a decrease in Ki-67 expression and an increase in apoptotic events in tumor tissues. There was also correlation between RBM24 and LATS1 protein expression in the xenograft tumors. RBM24 functions to stabilize LATS1 mRNA, thereby inhibiting the proliferation, suppressing invasion, and promoting apoptosis in GBM cells.
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BACKGROUND: Periodontal disease results in oral dysbiosis, increasing plaque virulence and oxidative stress. Stannous fluoride (SnF2) binds lipopolysaccharides to reduce plaque virulence. This study prospectively assessed SnF2 effects on oxidative stress in adults with gingivitis. METHODS: This was a 2-month, single-center, single-treatment clinical trial. Twenty "disease" (> 20 bleeding sites with ≥ 3 pockets 3 mm-4 mm deep) and 20 "healthy" (≤ 3 bleeding sites with pockets ≤ 2 mm deep) adults were enrolled. All participants were instructed to use SnF2 dentifrice twice daily for 2 months. An oral examination, Modified Gingival Index (MGI) examination and Gingival Bleeding Index (GBI) examination were conducted at baseline, 1 month and 2 months. Gingival crevicular fluid (GCF), saliva, oral lavage and supragingival plaque were collected at each visit to evaluate: Endotoxins, Protein Carbonyls, L-lactate dehydrogenase (LDH), Ferric reducing antioxidant power (FRAP), Oxidized low density lipoproteins (oxi-LDL), IL-6 and C-reactive protein (CRP). A subset-analysis examined participants considered at higher risk of cardiovascular disease. Change-from-baseline analyses within each group were of primary interest. RESULTS: The disease group showed statistically significant reductions in GBI at Month 1 (67%) and Month 2 (85%) and in MGI at Month 1 (36%) and Month 2 (51%) versus baseline (p < 0.001). At baseline, the disease group showed greater LDH in GCF and oxi-LDL levels in saliva versus the healthy group (p ≤ 0.01). Total antioxidant capacity (FRAP) in saliva increased versus baseline for the disease group at Months 1 and 2 (p < 0.05), and levels for the disease group were greater than the healthy group at both timepoints (p < 0.05). SnF2 treatment reduced endotoxins (lavage) for both disease and healthy groups at Month 2 (p ≤ 0.021) versus baseline. There was a reduction in oxidative stress markers, namely protein carbonyl in saliva, at Months 1 and 2 (p < 0.001) for both groups and a reduction in cytokine IL-6 (lavage) in the disease group at Month 2 (p = 0.005). A subset analysis of participants at higher coronary disease risk showed reductions in endotoxins in lavage, oxi-LDL, and CRP in saliva at Month 2 (p ≤ 0.04). CONCLUSION: SnF2 dentifrice use reversed gingival inflammation, suppressed endotoxins and reduced some harmful oxidant products in saliva and gingiva. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov NCT05326373, registered on 13/04/2022.
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Biomarcadores , Proteína C-Reactiva , Dentífricos , Líquido del Surco Gingival , Gingivitis , Interleucina-6 , Estrés Oxidativo , Índice Periodontal , Saliva , Fluoruros de Estaño , Humanos , Estrés Oxidativo/efectos de los fármacos , Estudios Prospectivos , Fluoruros de Estaño/uso terapéutico , Gingivitis/prevención & control , Femenino , Masculino , Adulto , Saliva/química , Dentífricos/uso terapéutico , Líquido del Surco Gingival/química , Interleucina-6/análisis , Interleucina-6/metabolismo , Proteína C-Reactiva/análisis , Biomarcadores/análisis , Carbonilación Proteica/efectos de los fármacos , Endotoxinas/análisis , Antioxidantes/uso terapéutico , Persona de Mediana Edad , L-Lactato Deshidrogenasa/análisis , Placa Dental/prevención & control , Lipoproteínas LDL , Estudios de Seguimiento , Adulto JovenRESUMEN
Poly-L-lactide (PLLA) offers a unique possibility for processing into biocompatible, biodegradable, and implantable piezoelectric structures. With such properties, PLLA has potential to be used as an advanced tool for mimicking biophysical processes that naturally occur during the self-repair of wounds and damaged tissues, including electrostimulated regeneration. The piezoelectricity of PLLA strongly depends on the possibility of controlling its crystallinity and molecular orientation. Here, it is shown that modifying PLLA with a small amount (1 wt%) of crystalline filler particles with a high aspect ratio, which act as nucleating agents during drawing-induced crystallization, promotes the formation of highly crystalline and oriented PLLA structures. This increases their piezoelectricity, and the filler-modified PLLA films provide a 20-fold larger voltage output than nonmodified PLLA during ultrasound (US)-assisted activation. With 99% PLLA content, the ability of the films to produce reactive oxygen species (ROS) and increase the local temperature during interactions with US is shown to be very low. US-assisted piezostimulation of adherent cells directly attach to their surface (such as skin keratinocytes), stimulate cytoskeleton formation, and as a result cells elongate and orient themselves in a specific direction that align with the direction of PLLA film drawing and PLLA dipole orientation.
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Materiales Biocompatibles , Poliésteres , Materiales Biocompatibles/química , Poliésteres/química , Temperatura , CristalizaciónRESUMEN
BACKGROUND: Liquid chromatography-high resolution mass spectrometry (LC-HRMS) is a popular approach for metabolomics data acquisition and requires many data processing software tools. The FAIR Principles - Findability, Accessibility, Interoperability, and Reusability - were proposed to promote open science and reusable data management, and to maximize the benefit obtained from contemporary and formal scholarly digital publishing. More recently, the FAIR principles were extended to include Research Software (FAIR4RS). AIM OF REVIEW: This study facilitates open science in metabolomics by providing an implementation solution for adopting FAIR4RS in the LC-HRMS metabolomics data processing software. We believe our evaluation guidelines and results can help improve the FAIRness of research software. KEY SCIENTIFIC CONCEPTS OF REVIEW: We evaluated 124 LC-HRMS metabolomics data processing software obtained from a systematic review and selected 61 software for detailed evaluation using FAIR4RS-related criteria, which were extracted from the literature along with internal discussions. We assigned each criterion one or more FAIR4RS categories through discussion. The minimum, median, and maximum percentages of criteria fulfillment of software were 21.6%, 47.7%, and 71.8%. Statistical analysis revealed no significant improvement in FAIRness over time. We identified four criteria covering multiple FAIR4RS categories but had a low %fulfillment: (1) No software had semantic annotation of key information; (2) only 6.3% of evaluated software were registered to Zenodo and received DOIs; (3) only 14.5% of selected software had official software containerization or virtual machine; (4) only 16.7% of evaluated software had a fully documented functions in code. According to the results, we discussed improvement strategies and future directions.
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Metabolómica , Programas Informáticos , Metabolómica/métodos , Cromatografía Liquida/métodos , Espectrometría de Masas/métodos , Manejo de DatosRESUMEN
BACKGROUND: Low-birth-weight (LBW) animals suffer from intestinal damage and inflammation in their early life. OBJECTIVES: The aim of this study was to investigate the role of macrophages in intestinal inflammation in LBW piglets and mice. METHODS: Major genes involved in intestinal barrier function such as claudin-1, zonula occludens-1 (ZO-1), occludin, and mucin 2 and inflammatory cytokines such as IL-1ß, TNF-α, IL-10, and IL-13 were evaluated in 21-day-old, normal-birth-weight (NBW) and LBW piglets and mice. Macrophage markers such as CD16/32, CD163, and CD206 were also assessed by immunofluorescence and flow cytometry. Polarized and unpolarized macrophages were further transferred into NBW and LBW mice, followed by an evaluation of intestinal permeability and inflammation. RESULTS: Claudin-1 mRNA in LBW piglets as well as claudin-1, occludin, ZO-1, and mucin 2 mRNAs in LBW mice, was significantly downregulated. IL-1ß and TNF-α were significantly upregulated in LBW piglets (P < 0.05). LBW mice showed a reduced expression of IL-10 and IL-13 (P < 0.05), with a heightened IL-6 level (P < 0.01) in the jejunum. CD16, a marker for M1 macrophages, was significantly elevated in the jejunum of LBW piglets, whereas CD163, a marker for M2 macrophages, was significantly decreased (P < 0.05). Similarly, LBW mice had more CD11b+CD16/32+ M1 macrophages (P < 0.05) and fewer CD206+ M2 macrophages (P < 0.01) than NBW mice. Moreover, the transfer of M1 macrophages exacerbated intestinal inflammation in LBW mice. Furthermore, 2 major glycolysis-associated genes, hexokinase 2 (HK2) and lactate dehydrogenase A (LDHA), were significantly upregulated in LBW piglets and mice (P < 0.05). CONCLUSIONS: This study revealed for the first time that the intestinal macrophages are polarized toward a proinflammatory phenotype in LBW piglets and mice, contributing to intestinal inflammation. The findings of this study provide new options for the management of intestinal inflammation in LBW animals.
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Interleucina-10 , Interleucina-13 , Animales , Porcinos , Ratones , Mucina 2 , Factor de Necrosis Tumoral alfa , Claudina-1 , Ocludina/genética , Macrófagos , InflamaciónRESUMEN
A palladium-catalyzed cyclization coupling of iodoarene-tethered alkynes with cyclobutanone-derived N-tosylhydrazones is reported, providing a convenient and efficient approach to benzofuran-3-cyclobutylidenes. On this basis, spirocyclobutanes can be generated smoothly in an efficient cascade manner by the addition of dienophiles. Good yields and scalability are demonstrated. Sequential intramolecular carbopalladation, palladium-carbene migratory insertion, δ-hydride elimination, and cycloaddition processes are involved.
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The weak electron-hole separation ability and the more severe photocorrosion of CdS largely limit its hydrogen precipitation performance. In this study, CoP loading on the surface of CdS was utilized to form a type I heterojunction. The photocurrent density increased from 2 µA cm-2 to 20 µA cm-2. When the loading of CoP was 10%, the best photocatalytic performance reached 4.43 mmolg-1 h-1 under visible light, which was 20.1 times higher than that of CdS (0.22 mmolg-1 h-1). In addition, the loading of CoP solved the problem of CdS photocorrosion. After 5 cycles of simulated solar irradiation, the performance of 10% CoP/CdS remained at 93% of the initial test. This work provides new ideas for the design of low photocorrosion and high-performance catalysts.
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A safe, biocompatible, and stimuli-responsive cucurbit[7]uril-mediated supramolecular bactericidal nanoparticle was fabricated by encapsulating a highly bioactive carbazole-decorated imidazolium salt (A1, EC50 = 0.647 µg/mL against phytopathogen Xanthomonas oryzae pv oryzae) into the host cucurbit[7]uril (CB[7]), thereby leading to self-assembled topographies from microsheets (A1) to nanospheroidal architectures (A1@CB[7]). The assembly behaviors were elucidated by acquired single-crystal structures, 1H NMR, ITC, and X-ray powder diffraction experiments. Complex A1@CB[7] displayed lower phytotoxicity and could efficiently switch on its potent antibacterial ability via introducing a simple competitor 1-adamantanamine hydrochloride (AD). In vivo antibacterial trials against rice bacterial blight revealed that A1@CB[7] could relieve the disease symptoms after being triggered by AD and provide a workable control efficiency of 42.6% at 100 µg/mL, which was superior to bismerthiazol (33.4%). These materials can provide a viable platform for fabricating diverse stimuli-responsive supramolecular bactericides for managing bacterial infections with improved safety.