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The relationship between third-hand smoke (THS) exposure and lifespan remains inadequately explored. Our study sought to clarify the effects of THS on aging and lifespan. In this pursuit, our cross-sectional analysis assessed hematological aging markers in 986 non-smokers and examined lifespan alterations using a Drosophila model. THS exposure levels were quantified through survey metrics consistent with the Global Adult Tobacco Survey. The findings revealed that THS exposure significantly accelerated biological aging, with exposed individuals exhibiting an average increase in biological age of 3.04 years compared to their unexposed counterparts (p < 0.05). Correspondingly, the Drosophila model reflected these outcomes, showing a reduction in lifespan by 16.07 days (p < 0.01). Proteomic analyses identified MRPL2 as a pivotal protein in THS-induced aging, linking its expression to mitochondrial dysfunction and oxidative stress. Further metabolomic profiling highlighted disruptions in energy metabolism pathways. Follow-up in vitro experiments confirmed the role of MRPL2 in the aging processes at the cellular level. Overall, our results indicate that THS exposure is a significant accelerant of aging, providing new perspectives on the health consequences of environmental smoke residues.
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OBJECTIVE: To describe the level and trend of energy consumption and percentage energy from macronutrients of three meals in Chinese adults from 1997 to 2011. METHODS: The China Health and Nutrition Survey database(1997-2011) was used to analyze the trends of energy consumption of three meals and percentage energy from macronutrients of adult men and women aged 18-80 years. The dietary survey was conducted using the 3-day 24-hour dietary review survey method, and the energy consumption of three meals was calculated through self-reported. RESULTS: From 1997 to 2011, there were significant differences in age, gender, smoking rate, alcohol consumption rate, physical activity amount, body mass index and urbanization index among the Chinese Health and Nutrition Survey populations, and the total energy intake of the whole day showed a decreasing trend year by year, the percentage energy from carbohydrates showed a decreasing trend year by year, and the percentage energy from fat and protein showed an increasing trend year by year. Stratified by gender, age and BMI, the percentage energy from macronutrients of three meals was consistent with the change trend of total daily intake. In addition, the energy and percentage energy from macronutrients of lunch and dinner were significantly higher than those of breakfast. CONCLUSION: From 1997 to 2011, the percentage energy from macronutrients for lunch and dinner of Chinese adults was significantly higher than that of breakfast, energy consumption and percentage energy from carbohydrate of three meals decreased year by year, and the percentage energy from fat and protein of three meals increased year by year.
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Ingestión de Energía , Nutrientes , Encuestas Nutricionales , Humanos , Masculino , Adulto , Femenino , Persona de Mediana Edad , China , Anciano , Adolescente , Adulto Joven , Nutrientes/administración & dosificación , Anciano de 80 o más Años , Encuestas sobre Dietas , Carbohidratos de la Dieta/administración & dosificación , Comidas , Grasas de la Dieta/administración & dosificación , Proteínas en la Dieta/administración & dosificación , Dieta/estadística & datos numéricos , Dieta/tendenciasRESUMEN
BACKGROUND: Although previous research has indicated a correlation between smoking and the mortality rate in patients with lung cancer, the impact of early life factors on this relationship remains unclear and requires further investigation. This study aimed to investigate the hypothesis that breastfeeding reduces the risk of lung cancer-related death. METHODS: The authors conducted a prospective cohort study involving 501 859 participants recruited from the United Kingdom Biobank to explore the potential association between breastfeeding and the risk of lung cancer mortality using a Cox proportional hazards model. Subsequently, the polygenic risk score for lung cancer was calculated to detect interactions between genes and the environment. RESULTS: Over a median follow-up duration of 11.8 years, encompassing a total of 501 859 participants, breastfeeding was found to reduce the risk of lung cancer-related death and the impact of maternal smoking on lung cancer mortality in adult offspring. This association remained consistent after stratification. Furthermore, the influence of maternal smoking and breastfeeding on the risk of lung cancer mortality was significant at a high genetic risk level. CONCLUSION: Breastfeeding can reduce the risk of lung cancer-related death and the impact of maternal smoking on lung cancer mortality in adult offspring. This correlation has the potential to reduce the probability of lung-cancer-related deaths in subsequent generations.
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Lactancia Materna , Neoplasias Pulmonares , Fumar , Humanos , Estudios Prospectivos , Femenino , Neoplasias Pulmonares/mortalidad , Lactancia Materna/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Adulto , Fumar/efectos adversos , Reino Unido/epidemiología , Modelos de Riesgos Proporcionales , Hijos Adultos , Factores de Riesgo , Anciano , EmbarazoRESUMEN
OBJECTIVE: This study aims to prospectively examine the association between temperatures and the occurrence of type 2 diabetes (T2D). METHODS: We used the CPH models to analyze 103,215 non-diabetic participants in the UK Biobank cohort who answered questions about workplace temperature, to evaluate the survival relationship, and the interaction effects of working environmental temperature and T2D-related genetic risk scores (GRS) on the occurrence of T2D. The occurrence of T2D was assessed by hospital inpatient records. The weighted T2D-related GRS were calculated. RESULTS: During 1,355,200.6 person-years follow-up, a total of 2436 participants were documented as having diagnosed T2D. After adjustment, compared to the comfortable group, the participants working in non-comfortable environmental temperature had greater risk of T2D (HR: 1.27, 95 %CI: 1.04 to 1.55, for cold; HR: 1.32, 95 %CI: 1.17 to 1.48 for hot; HR: 1.51, 95 %CI: 1.38 to 1.65 for alternate). Similarly, individuals exposed to different levels of genetic risk scores in alternating hot and cold work environments had a higher risk of developing type 2 diabetes. CONCLUSIONS: This study found working in single non-comfortable environmental temperatures was associated with greater risk of T2D occurrence, and exposure to alternating environmental temperatures had the highest risk of range and severity.
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Bancos de Muestras Biológicas , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Masculino , Femenino , Reino Unido/epidemiología , Estudios Prospectivos , Persona de Mediana Edad , Anciano , Factores de Riesgo , Adulto , Temperatura , Frío/efectos adversos , Predisposición Genética a la Enfermedad , Biobanco del Reino UnidoRESUMEN
The prevalence of obesity has been increasing in the US. Among the multifactorial contributors to obesity, dietary factors stand out as primary drivers. Using data from NHANES, we investigated the trends and disparities in diet quality and nutrient intake among US adults with different bodyweight statuses. Participants were divided into normal weight, overweight, and obese groups based on BMI. Diet quality was examined using HEI-2020. Nutrient intake was estimated based on the USDA Food and Nutrient Database for Dietary Studies. From 1999 to 2020, Despite an overall improvement in diet quality among overweight and obese US adults, disparities persisted for most HEI-2020 components, and worsened for whole grains, seafood and plant proteins, and fatty acids between normal weight and obese participants. Overweight and obese participants tended to consume less energy from total carbohydrates and more from total fat. The estimated total energy intake increased among obese participants over the past two decades, while no significant changes were observed among normal weight and overweight participants. In the 2017-2020 period, obese participants had lower HEI-2020 scores than both normal weight and overweight participants. However, no significant differences in total energy intake were observed among normal weight, overweight, and obese populations.
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Peso Corporal , Dieta , Ingestión de Energía , Encuestas Nutricionales , Obesidad , Humanos , Adulto , Masculino , Femenino , Estados Unidos/epidemiología , Persona de Mediana Edad , Obesidad/epidemiología , Dieta/tendencias , Dieta/estadística & datos numéricos , Sobrepeso/epidemiología , Índice de Masa Corporal , Adulto Joven , Nutrientes , AncianoRESUMEN
BACKGROUND: Cellular communication among different types of vascular cells is indispensable for maintaining vascular homeostasis and preventing atherosclerosis. However, the biological mechanism involved in cellular communication among these cells and whether this biological mechanism can be used to treat atherosclerosis remain unknown. We hypothesized that endothelial autophagy mediates the cellular communication in vascular tissue through exosome-mediated delivery of atherosclerosis-related genes. METHODS: Rapamycin and adeno-associated virus carrying Atg7 short hairpin RNA under the Tie (TEK receptor tyrosine kinase) promoter were used to activate and inhibit vascular endothelial autophagy in high-fat diet-fed ApoE-/- mice, respectively. miRNA microarray, in vivo and in vitro experiments, and human vascular tissue were used to explore the effects of endothelial autophagy on endothelial function and atherosclerosis and its molecular mechanisms. Quantitative polymerase chain reaction and miRNA sequencing were performed to determine changes in miRNA expression in exosomes. Immunofluorescence and exosome coculture experiments were conducted to examine the role of endothelial autophagy in regulating the communication between endothelial cells and smooth muscle cells (SMCs) via exosomal miRNA. RESULTS: Endothelial autophagy was inhibited in thoracic aortas of high-fat diet-fed ApoE-/- mice. Furthermore, rapamycin alleviated high-fat diet-induced atherosclerotic burden and endothelial dysfunction, while endothelial-specific Atg7 depletion aggravated the atherosclerotic burden. miRNA microarray, in vivo and in vitro experiments, and human vascular tissue analysis revealed that miR-204-5p was significantly increased in endothelial cells after high-fat diet exposure, which directly targeted Bcl2 to regulate endothelial cell apoptosis. Importantly, endothelial autophagy activation decreased excess miR-204-5p by loading miR-204-5p into multivesicular bodies and secreting it through exosomes. Moreover, exosomal miR-204-5p can effectively transport to SMCs, alleviating SMC calcification by regulating target proteins such as RUNX2 (runt-related transcription factor 2). CONCLUSIONS: Our study revealed the exosomal pathway by which endothelial autophagy protects atherosclerosis: endothelial autophagy activation transfers miR-204-5p from endothelial cells to SMCs via exosomes, both preventing endothelial apoptosis and alleviating SMC calcification. REGISTRATION: URL: https://www.chictr.org.cn/; Unique identifier: ChiCTR2200064155.
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Aterosclerosis , Autofagia , Comunicación Celular , Modelos Animales de Enfermedad , Exosomas , Ratones Endogámicos C57BL , Ratones Noqueados para ApoE , MicroARNs , Miocitos del Músculo Liso , MicroARNs/metabolismo , MicroARNs/genética , Exosomas/metabolismo , Exosomas/genética , Animales , Aterosclerosis/patología , Aterosclerosis/genética , Aterosclerosis/metabolismo , Aterosclerosis/prevención & control , Humanos , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Masculino , Ratones , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Células Endoteliales de la Vena Umbilical Humana/patología , Células Endoteliales/metabolismo , Células Endoteliales/patología , Proteína 7 Relacionada con la Autofagia/metabolismo , Proteína 7 Relacionada con la Autofagia/genética , Células Cultivadas , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Placa Aterosclerótica , Enfermedades de la Aorta/patología , Enfermedades de la Aorta/genética , Enfermedades de la Aorta/prevención & control , Enfermedades de la Aorta/metabolismo , Técnicas de Cocultivo , Transducción de Señal , Aorta Torácica/metabolismo , Aorta Torácica/patología , Dieta Alta en GrasaRESUMEN
OBJECTIVES: This study aimed to explore the temporal relationship between blood glucose, lipids and body mass index (BMI), and their impacts on atherosclerosis (AS). DESIGN: A prospective cohort study was designed. SETTING AND PARTICIPANTS: A total of 2659 subjects from Harbin Cohort Study on Diet, Nutrition and Chronic Non-communicable Diseases, and aged from 20 to 74 years were included. PRIMARY AND SECONDARY OUTCOME MEASURES: Body weight, height, fasting blood glucose (FBG) and 2-hour postprandial glucose (2-h PG), blood lipids including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) were measured at baseline and follow-up. Brachial ankle pulse wave velocity (baPWV) was examined at follow-up as a marker of AS risk. Logistic regression analysis, cross-lagged path analysis and mediation analysis were performed to explore the temporal relationships between blood glucose, lipids and BMI, and their impacts on AS risk. RESULTS: Logistic regression analysis indicated that increased FBG, 2-h PG, TC, TG, LDL-c and BMI were positively associated with AS risk, while increased HDL-c was negatively associated with AS risk. The path coefficients from baseline blood parameters to the follow-up BMI were significantly greater than those from baseline BMI to the follow-up blood parameters. Mediation analysis suggested that increased FBG, 2-h PG, TC, TG and LDL-c could increase AS risk via increasing BMI, the effect intensity from strong to weak was LDL-c>TC>TG>FBG>2 h PG, while increased HDL-c could decrease AS risk via decreasing BMI. CONCLUSIONS: Changes in blood glucose and lipids could cause change in BMI, which mediated the impacts of blood glucose and lipids on AS risk. These results highlight the importance and provide support for the early and comprehensive strategies of AS prevention and control.
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Aterosclerosis , Glucemia , Índice de Masa Corporal , Lípidos , Humanos , Persona de Mediana Edad , Masculino , Estudios Prospectivos , Glucemia/metabolismo , Glucemia/análisis , Femenino , Aterosclerosis/sangre , Aterosclerosis/etiología , Adulto , Lípidos/sangre , Anciano , Factores de Riesgo , Análisis de la Onda del Pulso , Adulto Joven , China/epidemiología , Índice Tobillo Braquial , Triglicéridos/sangre , Modelos LogísticosRESUMEN
BACKGROUND: Spermidine (SPD) has a number of advantageous effects, including life extension and neuroprotection. However, few observational studies have investigated the association of dietary SPD intake with depression. METHODS: We used data from the 2005-2014 National Health and Nutrition Examination Survey (NHANES) and the corresponding Food Patterns Equivalents Database (FPED). SPD content of food groups from published data were merged with the appropriate FPED data to estimate the SPD intake for each subject. Patients with Patient Health Questionnaire-9 (PHQ-9) scores of 10 or above were thought to experience clinically relevant depression symptoms. Logistic regression, sensitivity analysis, and restricted cubic spline (RCS) were used. RESULTS: Among the 19,306 participants, the overall prevalence of depression was 8.72 %. After controlling for relevant confounders, individuals in the highest tertile or quartile of total SPD and SPD derived from fruits, vegetables, cereals, nuts, eggs and seafood had a significantly lower prevalence of depression (OR total SPD = 0.77, 95 % CI: 0.63-0.93); OR fruit-sourced SPD = 0.81, 95 % CI: 0.68-0.95; OR vegetable-sourced SPD = 0.72, 95 % CI: 0.61-0.85; OR cereals-sourced SPD = 0.73,95 % CI:0.60-0.88; OR nuts- sourced SPD = 0.80, 95 % CI: 0.71-0.91; OR egg-sourced = 0.72, 95 % CI: 0.62-0.84 and OR seafood-sourced SPD = 0.65, 95 % CI: 0.55-0.77) comparing those in the lowest tertile or quartile. CONCLOUSION: Our fndings reveal a negative association between dietary SPD intake and depression.
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Depresión , Dieta , Encuestas Nutricionales , Espermidina , Humanos , Masculino , Femenino , Adulto , Estados Unidos/epidemiología , Depresión/epidemiología , Persona de Mediana Edad , Dieta/estadística & datos numéricos , Prevalencia , Adulto Joven , Estudios Transversales , AncianoRESUMEN
OBJECTIVE: To evaluate the safety and efficacy of genicular artery embolization (GAE) in patients with mild-to-severe knee osteoarthritis up to 12 months after GAE. MATERIALS & METHODS: This prospective single-center study included patients who had knee osteoarthritis for >1 year with moderate-to-severe pain after failed conservative treatment for >6 months. Baseline imaging features were evaluated to determine Kellgren-Lawrence (KL) grade and magnetic resonance imaging (MOAKS) scores. GAE was performed using 150-350 µm embolic polyvinyl alcohol particles. The visual analog scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were used to evaluate knee pain, stiffness, and function at baseline and follow-up. The primary endpoints were changes in VAS and WOMAC scores at 12 months. RESULTS: Thirty-three patients (n = 37 knees) aged 66.6 ± 8.7 years were enrolled. The patients were categorized into two groups: mild-to-moderate osteoarthritis (n = 28, KL grades 2-3) and severe osteoarthritis (n = 9, KL grade 4). GAE was successfully performed in all patients, with no major adverse events. Three to six branches of the genicular artery were embolized. The mean VAS and WOMAC scores in the mild-to-moderate group significantly decreased (6.6 at baseline vs. 3.0 at 12 months and 49.4 vs. 27.4, respectively, all P < 0.001). The mean VAS and WOMAC scores in the severe group significantly decreased at 12 months (7.3 vs. 4.4 and 58.1 vs. 40.6, respectively, all P < 0.001). CONCLUSION: GAE is a well-tolerated and effective treatment that significantly improves pain symptoms and function in patients with mild-to-severe knee osteoarthritis.
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Embolización Terapéutica , Osteoartritis de la Rodilla , Humanos , Osteoartritis de la Rodilla/terapia , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/complicaciones , Femenino , Masculino , Embolización Terapéutica/métodos , Anciano , Resultado del Tratamiento , Estudios Prospectivos , Dimensión del Dolor , Persona de Mediana Edad , Artralgia/etiología , Artralgia/terapia , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: This study aims to investigate potential interactions between maternal smoking around birth (MSAB) and type 2 diabetes (T2D) pathway-specific genetic risks in relation to the development of T2D in offspring. Additionally, it seeks to determine whether and how nutritional factors during different life stages may modify the association between MSAB and risk of T2D. METHODS: This study included 460,234 participants aged 40 to 69 years, who were initially free of T2D from the UK Biobank. MSAB and breastfeeding were collected by questionnaire. The Alternative health eating index(AHEI) and dietary inflammation index(DII) were calculated. The polygenic risk scores(PRS) of T2D and pathway-specific were established, including ß-cell function, proinsulin, obesity, lipodystrophy, liver function and glycated haemoglobin(HbA1c). Cox proportion hazards models were performed to evaluate the gene/diet-MSAB interaction on T2D. The relative excess risk due to additive interaction (RERI) were calculated. RESULTS: During a median follow-up period of 12.7 years, we identified 27,342 cases of incident T2D. After adjustment for potential confounders, participants exposed to MSAB had an increased risk of T2D (HR=1.11, 95%CI:1.08-1.14), and this association remained significant among the participants with breastfeeding (HR= HR=1.10, 95%CI: 1.06-1.14). Moreover, among the participants in the highest quartile of AHEI or in the lowest quartile of DII, the association between MSAB and the increased risk of T2D become non-significant (HR=0.94, 95%CI: 0.79-1.13 for AHEI; HR=1.09, 95%CI:0.99-1.20 for DII). Additionally, the association between MSAB and risk of T2D became non-significant among the participants with lower genetic risk of lipodystrophy (HR=1.06, 95%CI:0.99-1.14), and exposed to MSAB with a higher genetic risk for ß-cell dysfunction or lipodystrophy additively elevated the risk of T2D(RERI=0.18, 95%CI:0.06-0.30 for ß-cell function; RERI=0.16, 95%CI:0.04-0.28 for lipodystrophy). CONCLUSIONS: This study indicates that maintaining a high dietary quality or lower dietary inflammation in diet may reduce the risk of T2D associated with MSAB, and the combination of higher genetic risk of ß-cell dysfunction or lipodystrophy and MSAB significantly elevate the risk of T2D in offspring.
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Diabetes Mellitus Tipo 2 , Lipodistrofia , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/etiología , Estudios Prospectivos , Biobanco del Reino Unido , Bancos de Muestras Biológicas , Factores de Riesgo , Inflamación/complicaciones , Fumar , Lipodistrofia/complicacionesRESUMEN
Although the formation control of multi-agent systems has been widely investigated from various aspects, the problem is still not well resolved, especially for the case of distributed output-feedback formation controller design without input information exchange among neighboring agents. Using relative output information, this paper presents a novel distributed reduced-order estimation of the formation error at a predefined time. Based on the proposed distributed observer, a neural-network-based formation controller is then designed for multi-agent systems with connected graphs. The results are verified by both theoretical demonstration and simulation example.
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BACKGROUND: Type 2 diabetes (T2D) is the most common type of diabetes. However, research on the relationship between blue light exposure and diabetes development is limited. OBJECTIVE: The present study aimed to investigate the relationship between blue light exposure and T2D incidence and whether it is affected by sleep duration, physical activity, outdoor activity time, and genetic susceptibility. METHODS: A total of 471,686 participants without diabetes were recruited from the UK Biobank cohort. T2D incidence was assessed using hospital inpatient records. Blue light exposure was calculated based on the time spent watching TV, using a computer, and playing computer games, which was determined using an online questionnaire. Cox proportional hazards regression models were used to assess the survival relationship between blue light exposure and T2D, as well as the potential modification effects. RESULT: A total of 18,738 cases of T2D were documented during the median follow-up of 13.04 years. After adjusting for potential confounders, the participants with heavy blue light exposure had a greater risk of T2D compared to those with mild blue light exposure (hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.12-1.23). A significant association between blue light exposure and T2D risk was observed among the participants with heavy physical activity (HR = 1.39, 95%CI: 1.25-1.55), healthy sleep habits (HR = 1.23, 95%CI: 1.10-1.36), higher outdoor activity time (HR = 1.14, 95%CI: 1.07-1.22), or high genetic susceptibility (HR = 1.24, 95%CI: 1.14-1.35). However, this association became non-significant among the participants with low genetic susceptibility (HR = 1.05, 95%CI: 0.97-1.15). CONCLUSION: The present study showed that blue light exposure is associated with a greater risk of T2D independent of classical T2D risk factors.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/etiología , Estudios Prospectivos , Factores de Riesgo , Incidencia , Bancos de Muestras Biológicas , Luz Azul , Biobanco del Reino Unido , Predisposición Genética a la EnfermedadRESUMEN
A creatively designed novel two-step enhancement technique is presented in which B vitamin molecules are dynamically adsorbed onto the surface of silver nanoparticles by sodium borohydride, followed by local plasmon resonance in the presence of cations (calcium ions), ultimately achieving synergistic chemical and physical enhancement on the same molecule and constructing a "surface hot spots" two-step enhancement platform for vitamin detection. The Raman signal of the promoted vitamin molecule is enhanced by nine orders of magnitude. In a subsequent study it was observed that the vitamin B2 molecules were in a near-vertical image on the surface of the silver nanoparticles, which may also contribute to the Raman signal enhancement. Combined with deep learning techniques, the method has been successfully applied to the detection of B vitamins in body fluids. As an accurate, rapid, reproducible, non-invasive, and versatile assay platform, it holds great promise for the intelligent identification of trace B molecules in food, pharmaceuticals, and the human body.
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Nanopartículas del Metal , Complejo Vitamínico B , Humanos , Espectrometría Raman/métodos , Nanopartículas del Metal/química , Plata/química , BorohidrurosRESUMEN
BACKGROUND: A long-term consumption of saturated fat significantly increases the concentration of saturated fatty acids in serum, which accelerates the appearance of senescence markers in ß-cells and leads to their dysfunction. An understanding of the mechanisms underlying ß-cell senescence induced by stearic acid and the exploration of effective agents preventing it remains largely unclear. Here, we aimed to investigate the protective effect of metformin against stearic acid-treated ß-cell senescence and to assess the involvement of miR-297b-5p in this process. METHODS: To identify senescence, we measured senescence-associated ß-galactosidase activity and the expression of senescence-related genes. Gain and loss of function approaches were applied to explore the role of miR-297b-5p in stearic acid-induced ß-cell senescence. Bioinformatics analysis and a luciferase activity assay were used to predict the downstream targets of miR-297b-5p. RESULTS: Stearic acid markedly induced senescence and suppressed miR-297b-5p expression in mouse ß-TC6 cells, which were significantly alleviated by metformin. After transfection of miR-297b-5p mimics, stearic acid-evoked ß-cell senescence was remarkably prevented. Insulin-like growth factor-1 receptor was identified as a direct target of miR-297b-5p. Inhibition of the insulin-like growth factor-1 receptor prevented stearic acid-induced ß-cell senescence and dysfunction. Moreover, metformin alleviates the impairment of the miR-297b-5p inhibitor in ß-TC6 cells. Additionally, long-term consumption of a high-stearic-acid diet significantly increased senescence and reduced miR-297b-5p expression in mouse islets. CONCLUSIONS: These findings imply that metformin alleviates ß-cell senescence by stearic acid through upregulating miR-297b-5p to suppress insulin-like growth factor-1 receptor expression, thereby providing a potential target to not only prevent high fat-diet-induced ß-cell dysfunction but also for metformin therapy in type 2 diabetes.
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Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Metformina , MicroARNs , Receptor IGF Tipo 1 , Animales , Ratones , Factor I del Crecimiento Similar a la Insulina , Metformina/farmacología , MicroARNs/genética , Ácidos Esteáricos/farmacología , Receptor IGF Tipo 1/genéticaRESUMEN
AIMS: This study aims to examine the association between the rest-activity rhythm (RAR) and the incidence of type 2 diabetes (T2D). MATERIALS AND METHODS: In total, 97 503 participants without diabetes in the UK Biobank cohort were recruited. Wearable accelerometry was used to monitor circadian behaviour. The parameters of RAR including inter-daily stability, intra-daily variability, relative amplitude (RA), most active continuous 10 h period (M10), and least active continuous 5 h period (L5) were calculated to evaluate the robustness and regularity of the RAR. The weighted polygenic risk score for T2D (T2D-PRS) was calculated. Cox proportion hazards models were used to evaluate the survival relationship and the joint and interaction effects of RAR parameters and T2D-PRS on the occurrence of T2D. RESULTS: During 692 257 person-years follow-ups, a total of 2434 participants were documented. After adjustment for potential confounders, compared with participants in the highest quartile of RA and M10, the participants in the lowest quartile had a greater risk of T2D (HRRA = 2.06, 95% CI: 1.76-2.41; HRM10 = 1.33, 95% CI: 1.19-1.49). Meanwhile, the highest quartile of L5 was related to a higher risk of T2D (HR = 1.78, 95% CI: 1.55-2.24). The joint analysis showed that the high T2D-PRS with the lowest quartile of RA and M10, or highest quartile of L5 jointly increased the risk of T2D (HRRA = 4.46, 95% CI: 3.36-6.42; HRM10 = 3.15, 95% CI: 2.29-4.32; HRL5 = 3.09, 95% CI: 2.40-3.99). No modification effects of T2D-PRS on the association between the RAR parameters and risk of T2D were observed (p > .05). CONCLUSION: The unbalanced RAR are associated with a greater risk of T2D, which are independent of known risk factors of T2D.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/genética , Estudios Prospectivos , Predisposición Genética a la Enfermedad , Bancos de Muestras Biológicas , Factores de Riesgo , Reino Unido/epidemiologíaRESUMEN
In recent years, neural networks have made pioneering achievements in the field of medical imaging. In particular, deep neural networks based on U-shaped structures are widely used in different medical image segmentation tasks. In order to improve the early diagnosis and clinical decision-making system of lung diseases, it has become a key step to use the neural network for lung segmentation to assist in positioning and observing the shape. There is still the problem of low precision. For the sake of achieving better segmentation accuracy, an optimized pure Transformer U-shaped segmentation is proposed in this article. The optimization segmentation network adopts the method of adding skip connections and performing special splicing processing, which reduces the information loss in the encoding process and increases the information in the decoding process, so as to achieve the purpose of improving the segmentation accuracy. The final experiment shows that our improved network achieves 97.86% accuracy in segmentation of the "Chest Xray Masks and Labels" dataset, which is better than the full convolutional network or the combination of Transformer and convolution.
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A high-purity germanium (HPGe) gamma-ray spectrometer and an Alpha-GUARD radon monitor are the activity and activity concentration transfer standards of 222Rn, respectively. The gaseous 222Rn standard source traceable to the NIM's absolute standardization apparatus of 222Rn was developed for calibrating these transfer standards. The calibration results of HPGe detector at three different distances show that the uncertainties of experimental efficiency are less than 0.77% (k = 1). Meanwhile, the Monte Carlo (MC) simulation was carried out at wider distances range for the HPGe calibration as well, and the deviation at same three distances between experiments and simulations results is within ±3.0%. The advantage of calibration using MC simulation and the possible reasons for the deviation were discussed in detail in this article. In addition, a reference activity concentration environment based on the gaseous 222Rn standard source was also developed to calibrate the radon monitor, and the typical uncertainty for calibration factor of Alpha-GUARD radon monitor could be reduced to 1.9% (k = 1).
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Emerging evidence suggests that in addition to metabolic, genetic and environmental factors, circadian rhythm also plays a role in non-alcoholic fatty liver disease (NAFLD). This study aimed to explore the association of 24 h behavior rhythm (activity-rest and feeding-fasting rhythm) with NAFLD. A total of 4502 adult participants with overweight/obesity from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 were included in the current study. The behavior rhythm indices were calculated and divided into quintiles for logistic regression models. Compared to those in the lowest quintile, participants in the highest quintile of relative amplitude (RA) had a lower risk of NAFLD (OR = 0.71, 95% CI, 0.55-0.91); participants in the highest quintile of the average activity of the least active continuous 5 h period (L5) were associated with a higher risk of NAFLD (OR = 1.35, 95% CI, 1.07-1.71). Additionally, participants in the highest quintile of fasting duration and feeding rhythm score were associated with a lower risk of NAFLD relative to those in the lowest quintile (OR = 0.76, 95% CI, 0.59-0.98 for fasting duration, OR = 0.74, 95% CI, 0.58-0.95 for feeding rhythm score). The associations were stronger among participants with obesity. No significant associations were found in the relationship of other behavior rhythm indices with NAFLD. This study indicated a significant association of 24 h behavior rhythm with NAFLD among American adults with overweight/obesity.
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Enfermedad del Hígado Graso no Alcohólico , Sobrepeso , Adulto , Humanos , Sobrepeso/complicaciones , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Encuestas Nutricionales , Obesidad/complicaciones , Ritmo CircadianoRESUMEN
In this study, monoamine oxidase B (MAOB) was activated under pathological conditions, and was the novel source of cardiovascular reactive oxygen species (ROS). ROS-induced endothelial dysfunction results in sustained and chronic vascular inflammation, which is central to atherosclerotic diseases. However, whether MAOB regulates endothelial oxidative stress and its related mechanism and whether gut microbiota mediates the anti-atherosclerosis effect of MAOB inhibitor remains unclear. In our study, MAOB expressions were elevated in high-fat diet (HFD) fed mice aortas, but only in vascular endothelial cells (not in smooth muscle cells). MAOB small interfering RNA significantly attenuated the palmitic-acid (PA)-induced endothelial oxidative stress and dysfunction. Furthermore, RNA-sequencing data revealed that MAOB knockdown decreased the levels of proinflammatory and apoptotic gene induced by PA. Microarray analysis and qPCR assay showed that miR-3620-5p was significantly decreased under the HFD condition. The dual-luciferase reporter, Western blot and qPCR assay confirmed that miR-3620-5p directly regulated MAOB by binding to its mRNA 3'UTR. Moreover, inhibition of MAOB by selegiline significantly ameliorated endothelial dysfunction and reduced atherosclerotic burden in HFD-fed ApoE-/- mice. Finally, 16S rRNA sequencing showed that selegiline significantly altered the community compositional structure of gut microbiota. Specifically, selegiline treatment enriched the abundance of Faecalibaculum and Akkermansia, decreased the abundance of unclassified_f__Lachnospiraceae, Desulfovibrio, and Blautia, and these genera were significantly correlated with the serum biochemical indices. Taken together, our findings showed that MAOB controlled endothelial oxidative stress homeostasis, and revealed the anti-atherosclerotic effect of selegiline by ameliorating endothelial dysfunction and modulating the composition and function of gut microbiota.
Asunto(s)
Aterosclerosis , Microbioma Gastrointestinal , MicroARNs , Ratones , Animales , Dieta Alta en Grasa/efectos adversos , Especies Reactivas de Oxígeno/metabolismo , Células Endoteliales/metabolismo , Monoaminooxidasa/metabolismo , ARN Ribosómico 16S/genética , Selegilina/metabolismo , Selegilina/farmacología , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/etiología , Aterosclerosis/prevención & control , Inflamación/metabolismo , MicroARNs/metabolismo , Ratones Endogámicos C57BLRESUMEN
The objective was to evaluate the association between serum carotenoid levels and respiratory morbidity and mortality in a nationally representative sample of US adults. We assessed the association of serum carotenoid levels with respiratory morbidity and mortality using logistic regression and proportional hazards regression models. Meanwhile, a series of confounders were controlled in regression models and restricted cubic spline, which included age, sex, race, marriage, education, income, drinking, smoking, regular exercise, BMI, daily energy intake, vitamin E, vitamin C, fruit intake, vegetable intake, diabetes, hypertension, asthma, emphysema and chronic bronchitis. Compared with participants in the lowest tertiles, participants in the highest tertiles of serum total carotenoids, ß-cryptoxanthin and lutein/zeaxanthin levels had a significantly lower prevalence of emphysema (ORtotal carotenoids = 0·61, 95% CI: 0·41-0·89, ORß-cryptoxanthin = 0·67, 95% CI: 0·49-0·92), chronic bronchitis (ORß-cryptoxanthin = 0·66, 95% CI: 0·50-0·87) and asthma (Q2: ORlutein/zeaxanthin = 0·78, 95% CI: 0·62-0·97); participants in the highest tertiles of total carotenoids, α-carotene, lutein/zeaxanthin and lycopene had a lower risk of respiratory mortality (hazard ratio (HR)total carotenoids = 0·62, 95% CI: 0·42-0·90, HRα-carotene = 0·54, 95% CI: 0·36-0·82, HRlutein/zeaxanthin = 0·48, 95% CI: 0·33-0·71, HRlycopene = 0·66, 95% CI: 0·45-0·96) than those in the lowest tertiles. Higher serum total carotenoids and ß-cryptoxanthin levels is associated with decreased prevalence of emphysema and chronic bronchitis, and higher serum total carotenoids, α-carotene, lutein/zeaxanthin and lycopene levels had a lower mortality of respiratory disease.