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Metabolically healthy obesity (MHO) might be an alternative valuable target in obesity treatment. We aimed to assess whether alternative Mediterranean (aMED) diet and Dietary Approaches to Stop Hypertension (DASH) diet were favourably associated with obesity and MHO phenotype in a Chinese multi-ethnic population. We conducted this cross-sectional analysis using the baseline data of the China Multi-Ethnic Cohort study that enrolled 99 556 participants from seven diverse ethnic groups. Participants with self-reported cardiometabolic diseases were excluded to eliminate possible reverse causality. Marginal structural logistic models were used to estimate the associations, with confounders determined by directed acyclic graph (DAG). Among 65 699 included participants, 11·2 % were with obesity. MHO phenotype was present in 5·7 % of total population and 52·7 % of population with obesity. Compared with the lowest quintile, the highest quintile of DASH diet score had 23 % decreased odds of obesity (OR = 0·77, 95 % CI 0·71, 0·83, Ptrend < 0·001) and 27 % increased odds of MHO (OR = 1·27, 95 % CI 1·10, 1·48, Ptrend = 0·001) in population with obesity. However, aMED diet showed no obvious favourable associations. Further adjusting for BMI did not change the associations between diet scores and MHO. Results were robust to various sensitivity analyses. In conclusion, DASH diet rather than aMED diet is associated with reduced risk of obesity and presents BMI-independent metabolic benefits in this large population-based study. Recommendation for adhering to DASH diet may benefit the prevention of obesity and related metabolic disorders in Chinese population.
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Dieta Mediterránea , Obesidad Metabólica Benigna , Humanos , Estudios Transversales , Estudios de Cohortes , Pueblos del Este de Asia , Obesidad/prevención & control , Fenotipo , Factores de RiesgoRESUMEN
BACKGROUND: Older adults with type 2 diabetes are at higher risk of developing common geriatric syndromes and have a lower quality of life. To prevent type 2 diabetes in older adults, it's unclear whether the health benefits of physical activity (PA) will be influenced by the harms caused by increased exposure to air pollution during PA, especially in developing countries with severe air pollution problem. We aimed to investigate the joint effects of PA and long-term exposure to air pollution on the type 2 diabetes in older adults from China. METHODS: This cross-sectional study was based on the China Multi-Ethnic cohort (CMEC) study. The metabolic equivalent of PA was calculated according to the PA scale during the CMEC baseline survey. High resolution air pollution datasets (PM10, PM2.5 and PM1) were collected from open products. The joint effects were assessed by the marginal structural mean model with generalized propensity score. RESULTS: A total of 36,562 participants aged 50 to 79 years were included in the study. The prevalence of type 2 diabetes was 10.88%. The mean (SD) level of PA was 24.93 (18.60) MET-h/d, and the mean (SD) level of PM10, PM2.5, and PM1 were 70.00 (23.32) µg/m3, 40.45 (15.66) µg/m3 and 27.62 (6.51) µg/m3, respectively. With PM10 < 92 µg/m3, PM2.5 < 61 µg/m3, and PM1 < 36 µg/m3, the benefit effects of PA on type 2 diabetes was significantly greater than the harms due to PMs when PA levels were roughly below 80 MET-h/d. With PM10 ≥ 92 µg/m3, PM2.5 ≥ 61 µg/m3, and PM1 ≥ 36 µg/m3, the odds ratio (OR) first decreased and then rose rapidly with confidence intervals progressively greater than 1 and break-even points close to or even below 40 MET-h/d. CONCLUSIONS: Our findings implied that for the prevention of type 2 diabetes in older adults, the PA health benefits outweighed the harms of air pollution except in extreme air pollution situations, and suggested that when the air quality of residence is severe, the PA levels should ideally not exceed 40 MET-h/d.
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Contaminantes Atmosféricos , Contaminación del Aire , Diabetes Mellitus Tipo 2 , Anciano , Humanos , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Estudios Transversales , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Exposición a Riesgos Ambientales , Ejercicio Físico , Material Particulado/efectos adversos , Material Particulado/análisis , Calidad de VidaRESUMEN
BACKGROUND: Little is known about the associations between healthy dietary patterns and metabolic dysfunction-associated fatty liver disease (MAFLD) in less-developed ethnic minority regions (LEMRs), where the prevalence of MAFLD is increasing rapidly and dietary habits are quite different from those in developed countries. Moreover, a significant subset of MAFLD individuals in LEMRs are nonobese, but the efficacy of dietary patterns on MAFLD individuals with different obese statuses is also unclear. We aimed to test the associations of two wildly recommended a priori dietary patterns-Alternate Mediterranean diet (AMED) and Dietary Approaches to Stop Hypertension (DASH)-with the risk of MAFLD in the total population, and further in nonobese and obese individuals. METHODS: We recruited 99,556 participants in the China Multi-Ethnic Cohort Study, an ongoing cohort study in less-developed southwest China. Using validated food frequency questionnaire, each participant was assigned an AMED score and a DASH score. MAFLD was ascertained as hepatic steatosis on ultrasound together with diabetes, overweight/obesity, or two other metabolic risk factors. We performed logistic regression with inverse probability of exposure weighting (IPEW) to examine associations between two dietary patterns and MAFLD, adjusting for potential confounders under the guidance of directed acyclic graphs. Further, analyses were stratified by body mass index. RESULTS: We included 66,526 participants (age 49.5±11.0; 62.6% women), and the prevalence of MAFLD was 16.1%. Participants in the highest quintile of DASH score showed strong inverse associations with risks of MAFLD (OR = 0.85; 95% CI, 0.80-0.91; Ptrend < 0.001) compared with participants in the lowest quintile. The association between DASH and nonobese MAFLD (OR = 0.69; 95% CI, 0.61-0.78; Ptrend < 0.001) was stronger (I2 = 78.5 % ; Pheterogeneity = 0.001) than that with obese MAFLD (OR = 0.90; 95% CI, 0.83-0.98; Ptrend = 0.002). There was a null association between AMED and MAFLD risk. CONCLUSIONS: In LEMRs, a DASH diet but not AMED was associated with MAFLD. The relationship appeared to be more pronounced in nonobese MAFLD individuals than in obese MAFLD individuals.
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Dieta Mediterránea , Enfermedad del Hígado Graso no Alcohólico , Adulto , Estudios de Cohortes , Estudios Transversales , Minorías Étnicas y Raciales , Etnicidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Grupos Minoritarios , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Obesidad/epidemiologíaRESUMEN
Limited studies have focused on how COVID-19 outbreak and thereby lockdown have affected the youth's diet patterns. This study aimed to assess changes in diet patterns among youths in China under the COVID-19 lockdown, based on the COVID-19 Impact on Lifestyle Change Survey (COINLICS), a nationwide retrospective survey distributed via social media platforms during 9-12 May 2020 where 10,082 youth participants in China have voluntarily reported their basic sociodemographic information and routine diet patterns in the months before and after COVID-19 lockdown. We used paired t-tests or χ2 tests to evaluate the significance of differences in consumption patterns of 12 major food groups and beverages across educational levels, between sexes, and before and after COVID-19 lockdown. During the COVID-19 lockdown, significant decreases were observed in the frequency of intake of rice, meat, poultry, fresh vegetables, fresh fruit, soybean products, and dairy products, with significant sex differences (females consuming more rice, fresh vegetables and fruit and less meat, poultry, soybean and dairy products than males). Significant increases were observed in the frequency of consumption of wheat products, other staple foods, and preserved vegetables, with males consuming these foods more frequently than females. Graduate students consumed most foods more frequently except rice and other staple foods and preserved vegetables. The frequency of sugar-sweetened beverage consumption had decreased while frequency of tea drinking had increased. The participating youths' diet patterns had significantly changed during the COVID-19 lockdown, with heterogeneities observed to different extents between sexes and across educational levels. Our findings would inform policy-makers and health professionals of these changes in time for better policy making and public health practice.
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COVID-19 , Dieta , Conducta Alimentaria , Estilo de Vida , Pandemias , Aislamiento Social , Adolescente , Adulto , COVID-19/epidemiología , China/epidemiología , Control de Enfermedades Transmisibles , Femenino , Humanos , Masculino , Encuestas Nutricionales , Distanciamiento Físico , Cuarentena , Estudios Retrospectivos , SARS-CoV-2 , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the value of autism screening checklists in the early identification of autism spectrum disorder (ASD). METHODS: A total of 2 571 children who attended the Children's Hospital of Chongqing Medical University and completed autism screening and diagnostic test were enrolled as subjects, among whom 2 074 were diagnosed with ASD, 261 were diagnosed with global developmental delay (GDD), 206 were diagnosed with developmental language disorder (DLD), and 30 had normal development. The sensitivity, specificity, and optimal threshold value of the Modified Checklist for Autism in Toddlers (M-CHAT) and the Autism Behavior Checklist (ABC) for the early identification of ASD were evaluated by the receiver operating characteristic (ROC) curve. RESULTS: The M-CHAT had a high sensitivity of 88.3% but a low specificity of 36.0% for the identification of ASD. Its sensitivity decreased with age, and was maintained above 80% for children aged 16 to < 48 months. The ABC had a high specificity of 87.3% but a low sensitivity of 27.2%, with an optimal cut-off value of 47.5 based on the ROC curve analysis. The multivariate linear regression model based on a combination of the M-CHAT and ABC for screening of ASD showed a specificity of 85.8% and a sensitivity of 56.6%. CONCLUSIONS: The M-CHAT has a high sensitivity and a low specificity in the identification of ASD, with a better effect in children aged 16 to < 48 months. The ABC has a high specificity and a low sensitivity. The multiple linear regression model method based on the combined M-CHAT and ABC to screen ASD appears to be effective.
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Trastorno del Espectro Autista , Trastorno Autístico , Adolescente , Trastorno del Espectro Autista/diagnóstico , Lista de Verificación , Humanos , Lactante , Tamizaje Masivo , Curva ROCRESUMEN
In vertebrates, IL-10 is an anti-inflammatory factor that serves as a key inhibitory role in a wide range of immune responses. IRAK1 (IL-1 receptor-associated kinase 1), a key molecule in the inflammatory signal of IL-1R/TLR, plays an important pivotal role in regulating the autoimmunity of body. STAT3 (Signal transducer and activator of transcription 3) activated by IRAK1 participates in inflammation, tumorigenesis, metabolic disorders and immune response. Under the stimulation of LPS, IRAK1 enters the nucleus to form a dimer with STAT3 and regulates the expression of IL-10. However, the relationship between fish IRAK1 and STAT3 has not been reported. To explain the anti-inflammation in fish, we amplified and identified the complete open reading frame of grass carp IRAK1 (CiIRAK1) and STAT3 (CiSTAT3) based on the existing sequences. The expression of CiIRAK1 and CiSTAT3 were up-regulated significantly under the stimulation of LPS. This result suggests that both CiIRAK1 and CiSTAT3 may be involved in LPS-induced TLR4 pathway. The subcellular localization experiment revealed that CiIRAK1 is distributed in cytoplasm and enters nucleus after LPS stimulation. CiSTAT3 is distributed in both cytoplasm and nucleus with or without LPS stimulation. Immunoprecipitation assay revealed that CiIRAK1 interacted with CiSTAT3 under LPS stimulation. However in absence of LPS stimulation, CiIRAK1 and CiSTAT3 cannot interact with each other. Subsequently, immunofluorescence colocalization experiment further proved the interaction of CiIRAK1 and CiSTAT3 in nucleus under LPS stimulation. The dual luciferase reporter assays indicated that the binding of CiIRAK1 and CiSTAT3 synergistically enhanced the activity of CiIL-10 promoter.
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Carpas/genética , Proteínas de Peces/genética , Quinasas Asociadas a Receptores de Interleucina-1/genética , Interleucina-10/genética , Factor de Transcripción STAT3/genética , Transcripción Genética , Regulación hacia Arriba , Animales , Carpas/inmunología , Proteínas de Peces/metabolismo , Quinasas Asociadas a Receptores de Interleucina-1/metabolismo , Interleucina-10/metabolismo , Lipopolisacáridos/administración & dosificación , Factor de Transcripción STAT3/metabolismoRESUMEN
Bcl-xl, Bax2, and NF-κB are well-known to be involved in anti-apoptosis response. Although Bcl-xl has been reported in fish, the NF-κB-mediated regulatory mechanism and anti-apoptotic function are still unclear. Here, we cloned and characterized the full-length cDNA sequence of grass carp (Ctenopharyngodon idella) Bcl-xl (CiBcl-xl) and its promoter region sequence. The full-length cDNA of CiBcl-xl is 2836 bp with an ORF of 627 bp encoding a polypeptide of 208 amino acids. Phylogenetic tree analysis revealed that CiBcl-xl shared high homology with Dario rerio Bcl-xl (DrBcl-xl). After stimulation with Poly I:C, the expression of CiBcl-xl in CIK cells and various tested tissues of grass carp were significantly upregulated. To further understand the transcriptional control of fish Bcl-xl induced by NF-κB, CiC-rel and Cip65 were expressed in Escherichia coli BL21 and purified by affinity chromatography with the Ni-NTA His-Bind resin. In vitro, gel mobility shift assays demonstrated the high affinity of CiC-rel and Cip65 with CiBcl-xl promoter. Dual-luciferase reporter assays showed that CiC-rel and Cip65 activated CiBcl-xl promoter. Also, knockdown of CiC-rel and Cip65 reduced the expression of Bcl-xl. Therefore, similar to those of mammals, fish C-rel and p65 can upregulate the transcription of Bcl-xl. In addition, we found that overexpression of CiBcl-xl in CIK cells increased the cell activity and inhibited cell apoptosis, while overexpression of Bax2 promoted cell apoptosis. Meanwhile, co-transfection of CiBcl-xl and CiBax2 into cells can ease up apoptotic rate. To further investigate the molecular basis of synergistic effect of Bcl-xl and Bax2, we showed that Bcl-xl and Bax2 interacted with each other. The results suggested that Bcl-xl executed its anti-apoptotic function by binding to and inhibiting the pro-apoptotic activity of Bax2.
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Apoptosis/genética , Carpas/genética , Proteínas de Peces/genética , Animales , Secuencia de Bases , ADN Complementario , Regulación de la Expresión Génica , Poli I-C , Regiones Promotoras GenéticasRESUMEN
IL-1R-associated kinase 4 (IRAK4), a central TIR signaling mediator in innate immunity, can initiate a cascade of signaling events and lead to induction of inflammatory target gene expression eventually. In the present study, we cloned and characterized an IRAK4 orthologue from grass carp (Ctenopharyngodon idella). The full length cDNA of CiIRAK4 was 2057 bp with an ORF of 1422 bp encoding a polypeptide of 472 amino acids. Multiple alignments showed that IRAK4s were highly conserved among different species. Phylogenetic tree analysis revealed that CiIRAK4 shared high homologous with zebra fish IRAK4. Expression analysis indicated that CiIRAK4 was widely expressed in all tested tissues. It was significantly up-regulated after treatment with poly I:C, especially obvious in liver and spleen. Also, CiIRAK4 could be induced by poly I:C and LPS in CIK cells. Fluorescence microscopy assays showed that CiIRAK4 localized in the cytoplasm. RNAi-mediated knockdown and overexpression assays indicated that CiIRAK4 might have little effect on NF-kappa B p65 translocation from cytoplasm to nucleus, indicating that CiIRAK4 was dispensable for activation of NF-kappa B p65. In addition, IRAK4 promoted IRF5 nuclear translocation, which has nothing to do with the interaction between IRAK4 and IRF5. It suggested that fish IRAK4 kinase regulated IRF5 activity through indirect ways.
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Carpas/genética , Carpas/inmunología , Enfermedades de los Peces/inmunología , Regulación de la Expresión Génica/inmunología , Inmunidad Innata/genética , Quinasas Asociadas a Receptores de Interleucina-1/genética , Quinasas Asociadas a Receptores de Interleucina-1/inmunología , Secuencia de Aminoácidos , Animales , Proteínas de Peces/química , Proteínas de Peces/genética , Proteínas de Peces/inmunología , Perfilación de la Expresión Génica/veterinaria , Quinasas Asociadas a Receptores de Interleucina-1/química , Lipopolisacáridos/farmacología , Filogenia , Poli I-C/farmacología , Alineación de Secuencia/veterinariaRESUMEN
BACKGROUND: Reliable measurements of infants obtained from routine clinical practice are scarce. AIM: To investigate the reliability of anthropometric measurements collected in routine clinical practice at primary care hospitals in Chongqing, PR China. SUBJECTS AND METHODS: The convenience sample comprised measurements from 739 infants aged <36 months. Using typical methods, child healthcare clinicians (CHCCs) measured four variables (recumbent and crown-rump lengths and head and chest circumferences); child healthcare nurses (CHCNs) performed re-measurement using standardized anthropometric techniques. Intra- and inter-observer measurement reliability were assessed mainly using technical error of measurement (TEM), mean absolute difference (MAD) and coefficient of reliability (R). RESULTS: Intra-observer MADs of the four measurements were significantly smaller among CHCNs than among CHCCs (p < 0.05). The inter-observer TEMs of recumbent length and head circumference measurements were 0.58-0.68 and 0.38-0.48 cm, MADs were 0.60-0.71 and 0.40-0.51 cm and Rs were 0.968-0.995 and 0.937-0.971. Crown-rump length TEMs and MADs were 0.77-0.83 and 0.81-0.87 cm and Rs were 0.896-0.961. Chest circumference TEMs and MADs were >1.00 cm and Rs were <0.90. CONCLUSIONS: Recumbent length and head circumference measurements were fair. Crown-rump length and chest circumference measurements were less reliable.
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Antropometría/métodos , Tamaño Corporal , Cefalometría , Preescolar , China , Ciudades , Estudios Transversales , Largo Cráneo-Cadera , Femenino , Hospitales , Humanos , Lactante , Recién Nacido , Masculino , Reproducibilidad de los Resultados , Tórax/fisiología , Población UrbanaRESUMEN
Wound infection and persistent inflammation are considered to be the main reasons for hindering wound healing. In this study, we developed an innovative hydrogel dressing, EPL-DA/ODEX/AMs, as a platform to inhibit bacteria and inflammation and promote wound healing. Polylysine (EPL) has cationic properties and can effectively disrupt bacterial cell membranes for antibacterial purposes. Polylysine-grafted levodopa (EPL-DA) with abundant amino and catechol groups can be cross-linked with oxidized dextran through Schiff base reaction to form antibacterial hydrogels with good adhesion and mechanical properties. In addition, asiaticoside, which can effectively inhibit inflammation and promote collagen regeneration, is made into PLGA microspheres to effectively deliver asiaticoside to the wound. The innovative antibacterial hydrogel of EPL-DA/ODEX/AMs may become a competitive wound dressing for infected wound.
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Hidrogeles , Polilisina , Humanos , Hidrogeles/farmacología , Preparaciones de Acción Retardada , Cicatrización de Heridas , Antibacterianos/farmacología , Bacterias , InflamaciónRESUMEN
BACKGROUND: The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) has been rising rapidly in western China. Diet acts as an effective therapy for MAFLD. However, there has been scarce research on the association between a posteriori diet patterns (DPs) and MAFLD in this region. METHOD: We identified three a posteriori DPs which were "Sichuan Basin pattern" characterized by a high intake of fish/seafood, poultry, fresh fruit and vegetables, indicating a balanced and modern DP; the "Yunnan-Guizhou Plateau dietary pattern" characterized mainly by a high intake of animal oil and salt, indicating an agricultural and poor DP; and the "Qinghai-Tibet Plateau dietary pattern" characterized by a high intake of coarse grains, wheat products, tubers and tea, respectively, indicating a high-altitude DP. Then, we performed marginal structural models that combined logistic regression and inverse probability exposure weighting (IPEW) to examine the associations between MAFLD and these a posteriori DPs. RESULT: We found the "Yunnan-Guizhou Plateau dietary pattern" revealed stronger positive association (OR = 1.50, 95% CI 1.40-1.60) with MAFLD than that of the "Qinghai-Tibet Plateau dietary pattern" (OR = 1.21, 95% CI 1.14-1.30). In contrast, the "Sichuan Basin dietary pattern" showed no significant association with MAFLD. In the further stratified analysis, we found those above associations were stronger in ethnic minorities and rural residents than their counterparts. CONCLUSION: Our study implied the unfavourable effects of "Yunnan-Guizhou Plateau dietary pattern" on MAFLD and provided evidence that reducing the intake of oil and sodium may be optimal for MAFLD control in the multi-ethnic region in western China.
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Hepatopatías , Humanos , China/epidemiología , Dieta/efectos adversos , VerdurasRESUMEN
Liver fibrosis refers to a reversible event of repair and reconstruction following injury due to various etiologies, and its continuous development will lead to cirrhosis and liver cancer. Abnormal alterations in intestinal microbiota can hasten the development of hepatic fibrosis and damage. Veronicastrum latifolium (Hemsl.) Yamazaki (VLY) is a classic drug applied extensively for managing acute and chronic hepatitis, liver cirrhosis and ascites in ethnic minority areas of Guizhou Province, China, which possesses broad-spectrum pharmacological activities. In view of the crucial role of intestinal microbiota in the development of liver fibrosis, the present study attempted to investigate the effects of VLY aqueous extract on ameliorating CCl4-elicited liver fibrosis in mice and on intestinal microbiota and to explore its possible mechanism. Phytochemical analysis showed that VLY water extract contained a variety of components, particularly rich in organic acids and their derivatives, flavonoids, phenolic acids, nucleotides and their derivatives, carbohydrates and other compounds. VLY water extract remarkably alleviated CCl4-induced liver damage and fibrosis in mice, improved liver histology, and improved liver function abnormalities. VLY water extract also inhibited the activation of hepatic stellate cells and invasion of intrahepatic inflammatory cells. Additionally, sequencing the 16 s rDNA gene revealed that VLY water extract changed the intestinal microbiota composition in liver fibrotic mice. It elevated the Firmicutes/Bacteroidota ratio and enriched the relative Lactobacillus richness, which is capable of mitigating fibrosis and inflammation in impaired liver. In summary, through modulation of inflammation and intestinal microbiota, VLY water extract can reduce the CCl4-elicited liver fibrosis.
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Tetracloruro de Carbono , Microbioma Gastrointestinal , Humanos , Ratones , Animales , Tetracloruro de Carbono/efectos adversos , Agua/efectos adversos , Etnicidad , Grupos Minoritarios , Estructura Molecular , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/patología , Hígado , Fibrosis , InflamaciónRESUMEN
Background: The study sought to assess the changes in physical activity (PA) and sedentary time among Chinese youths at different stages after the COVID-19 outbreak. Methods: It was based on a retrospective online survey conducted in May 2020. More than 10,000 youths voluntarily recalled their PA-related information at three stages: before COVID-19 (January), during lockdown (February), and after lockdown (May). χ2 tests were conducted to evaluate the significance of the differences in participants' characteristics between sexes, and Wilcoxon Rank Sum tests were performed to examine the significance of differences in changes in PA and sedentary behavior levels between sexes. Results: A total of 8,115 participants were included, with a mean age of 20. The percentage of no PA per week increased significantly and then slightly fell, and that of ≥150 min/week substantially decreased and then rebounded partially (all p < 0.001) (for instance, the percentage of ≥150 min/week of PA total decreased from 38.6 to 19.4%, then rebounded back to 25.3%). Means hours per day spent in sedentary behaviors had significantly increased during lockdown comparing to pre-COVID-19 (all p < 0.001). There were more participants reported reduced PA level than those indicated increased, and more participating youths had their sedentary behavior level increased than those who had it decreased. Conclusions: The study found COVID-19 had both immediate and longer-term impacts on self-reported physical activities and sedentary behaviors among Chinese youths. Relevant efforts should be strengthened to get youths physically moving again.
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COVID-19 , Ejercicio Físico , Conducta Sedentaria , Adolescente , Adulto , China , Femenino , Humanos , Modelos Logísticos , Masculino , Cuarentena , Estudios Retrospectivos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Interferon regulatory factor 8 (IRF8), also known as interferon consensus sequence-binding protein (ICSBP), is a negative regulatory factor of interferon (IFN) and plays an important role in cell differentiation and innate immunity in mammals. In recent years, some irf8 homologous genes have been cloned and confirmed to take part in innate immune response in fish, but the mechanism still remains unclear. In this paper, a grass carp (Ctenopharyngodon idella) irf8 gene (Ciirf8) was cloned and characterized. The deduced protein (CiIRF8) possesses a highly conserved N-terminal DNA binding domain but a less well-conserved C-terminal IRF association domain (IAD). Ciirf8 was widely expressed in all tested tissues of grass carp and up-regulated following poly(I:C) stimulation. Ciirf8 expression was also up-regulated in CIK cells upon treatment with poly(I:C). To explore the molecular mechanism of how fish IRF8 regulates ifn1 expression, the similarities and differences of grass carp IRF8 and IRF2 were compared and contrasted. Subcellular localization analysis showed that CiIRF8 is located both in the cytoplasm and nucleus; however, CiIRF2 is only located in the nucleus. The nuclear-cytoplasmic translocation of CiIRF8 was observed in CIK cells under stimulation with poly(I:C). The interaction of CiIRF8 and CiIRF2 was further confirmed by a co-immunoprecipitation assay in the nucleus. Dual-luciferase reporter assays showed that the promoter activity of Ciifn1 was significantly inhibited by co-transfection with CiIRF2 and CiIRF8. The transcription inhibition of Ciifn1 was alleviated by competitive binding of CiIRF2 and CiIRF8 to CiIRF1. In conclusion, CiIRF8 down-regulates Ciifn1 expression via interaction with CiIRF2 in cells.
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Carpas/genética , Regulación hacia Abajo/genética , Proteínas de Peces/genética , Factor 2 Regulador del Interferón/genética , Factores Reguladores del Interferón/genética , Interferones/genética , Animales , Células Cultivadas , Regulación de la Expresión Génica/genética , Células HEK293 , Humanos , Inmunidad Innata/genética , Poli I-C/genética , Regiones Promotoras Genéticas/genética , Transcripción Genética/genética , Regulación hacia Arriba/genéticaRESUMEN
Background In Western developed countries, food-based dietary patterns have been associated with the risk of cardiometabolic diseases, but little is known about such associations in less developed ethnic minority regions (LEMRs), where the cardiometabolic disease burden is growing rapidly and food patterns differ substantially. Methods Between May 2018 and September 2019, we recruited 99556 participants aged 30-79 years from the China Multi-Ethnic Cohort (CMEC) Study. We measured habitual dietary intake with validated food frequency questionnaire (FFQ) and then calculated dietary pattern scores for two of the most studied a priori dietary patterns, i.e., Dietary Approaches to Stop Hypertension (DASH) and alternative Mediterranean (aMED) style diets, and three a posteriori dietary patterns. Four cardiometabolic risks, including hypertension, diabetes, dyslipidaemia and metabolic syndrome (MetS), were newly diagnosed by medical examination and blood tests. We estimated adjusted odds ratios (OR) relating various dietary pattern scores to cardiometabolic risks using marginal structural models under the guidance of directed acyclic graphs. For the above associations, we further calculated the proportion mediated by overweight (PM) using regression-based mediation analysis for better public health implications. Findings The final study sample consisted of 68834 participants. Among them, we newly diagnosed 12803 hypertension, 3527 diabetes, 16342 hyperlipidaemia, and 8198 MetS cases. Overall, all 5 dietary patterns showed considerable associations with risks of hypertension and MetS. Comparing the highest with the lowest quintiles, the DASH score showed the strongest inverse associations with risks of hypertension (OR=0.74, 95% CI:0.70-0.79; PM=10%) and MetS (OR=0.79, 95% CI:0.74-0.85; PM=35%); conversely, scores of the localized a posteriori Yunnan-Guizhou plateau dietary pattern in LEMRs showed the strongest positive associations with risks of hypertension (OR=1.44, 95% CI:1.35-1.52; PM=10%) and MetS (OR=1.35, 95% CI:1.26-1.46; PM=33%), with all P values for trend <0.001. These associations were consistent in various subgroups defined by sex, age, smoking and physical activity, but with magnitudes that differed substantially across different ethnic regions and urbanicity. By investigating the single-component effects of dietary patterns, the dairy intake component contributed a major proportion to the beneficial effects of DASH (41.9% for hypertension and 100.5% for MetS). Interpretation Substantial socioeconomic status and ethnic disparities in diet quality and related cardiometabolic risks were seen in LEMRs, with hypertension being the top diet-related cardiometabolic risk. Our findings support that DASH provides superior dietary guidance compared to aMED for reducing cardiometabolic risks in LEMRs. In particular, the dairy intake encouraged by DASH may produce considerable beneficial effects. Funding This study was funded by the National Key R&D Program of China; full funding sources listed in the acknowledgements.
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Guided bone regeneration (GBR) has been regarded as a valuable way to effectively induce bone remodeling. The key factor of GBR is to place a barrier membrane between the soft tissue and bone defect, preventing the untimely intrusion of fibroblasts and permitting the prior settlement of internal osteoblasts. Notably, heterogeneous double-layer GBR membranes with a compact upper layer and a loose lower layer exhibit enhanced effectiveness in blocking fibroblasts and promoting the growth of osteoblasts. Herein, we present porous and interconnected collagen-based sponges with controllable pore size for the fabrication of absorbable GBR membranes with a heterogeneous double-layer structure. Dialdehyde carboxymethyl cellulose was used to fix collagen-based sponges. The pore size of the sponges can be well controlled by adjusting the cross-linking degree, which is decreased with an increase of cross-linking degree. The sponges show enhanced mechanical properties, inhibited swelling ability and biodegradation, good blood compatibility, and good cytocompatibility. The sponges are feasible to form a heterogeneous double-layer structure with a loose lower layer and a compact upper layer. Interestingly, the lower layer with the pore size of 200-300 µm can promote the adhesion, proliferation, and differentiation of osteoblasts MC3T3-E1 cells, while the upper layer with the pore size of 20-50 µm makes a great contribution to the growth of myoblast C2C12 cells. Overall, the collagen-based sponges have the potential to be used to fabricate heterogeneous double-layer bone barrier membranes for bone remodeling.
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Many strategies have been employed to artificially reconstruct adipose tissue in tissue engineering. The functionalization and survival of reconstructed adipose tissue depend on sufficient angiogenesis. Notably, agglomeration growth of adipose-derived stem cells (ASCs) is beneficial to promoting angiogenesis. Herein, we present a porous collagen-based hydrogel for spontaneous agglomeration growth of ASCs to promote angiogenesis. Oxidized starch with different oxidation degree was prepared and used to cross-link collagen to fabricate the porous hydrogel. The gelation time and pore size of hydrogels can be controlled by adjusting the oxidation degree of starch. Crosslinking enhances the mechanical properties, inhibits the swelling and biodegradation of the hydrogels. The hydrogels possess good blood compatibility and cytocompatibility. Significantly, ASCs tended to adhere to the hydrogels and spontaneously grew into spheres along with time. Effective expression of vascular endothelial growth and fibroblast growth factors were observed. Overall, the hydrogels have application prospects in vascularized adipose tissue engineering.
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Tejido Adiposo , Almidón , Células Madre , Colágeno , Hidrogeles/farmacología , Porosidad , Ingeniería de TejidosRESUMEN
The title compound, C(19)H(26)O(3), was synthesized directly from the condensation of 5,5-dimethyl-cyclo-hexane-1,3-dione with malononitrile catalysed by palladium chloride: there are two molecules in the asymmetric unit.
RESUMEN
In mammals, toll-like receptor 3 (TLR3) is capable of recognizing double-stranded RNA and then initiates transcription of IFN-ß. TLR3 can activate the innate immune system by phosphorylating extracellular signal-regulated kinase 1 (ERK1) in the mitogen-activated protein kinase (MAPK) pathway. As a downstream signaling protein of ERK1, ribosomal protein S6 kinase alpha 3 (RSK2) is activated through the "classical" MAPK pathway. So RSK2 plays a critical role in response to innate immune system induced by TRL3. However, the innate immune mechanism of RSK2 remains indistinct in fish. In this study, we cloned and characterized a full length cDNA sequence of RSK2 from Ctenopharyngodon idella (named CiRSK2, MH844551). The full length cDNA of CiRSK2 is 3930 bp with a coding sequence of 2202 bp encoding a polypeptide of 734 amino acids. The expression of CiRSK2 was ubiquitous and significantly up-regulated under the stimulation of poly (I:C) in eight different tissues of C. idella and C. idella kidney cells (CIK). In addition, poly (I:C) stimulation also up-regulated the expression of CiERK1 mRNA in CIK cells and the phosphorylation of CiERK1. We also demonstrated that the activated CiERK1 interacted with CiRSK2 by CO-IP assay and immunofluorescence assay. To further investigate the relationship between CiRSK2 and CiERK1, we performed subcellular localization of CiRSK2 at different periods of CiERK1 stimulation. The result showed that CiERK1 can make CiRSK2 enter the nucleus. Subsequently, we found that CiRSK2 increased the transcriptional level of CiBCL-2 and protein level of CiBCL-2 significantly. Then cell apoptosis was inhibited to a certain extent. Overall, our results suggested that CiRSK2 plays important roles in fish innate immunity and is able to inhibit cell apoptosis by up-regulating CiBCL-2.
Asunto(s)
Apoptosis/genética , Carpas/genética , Proteínas de Peces/genética , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Quinasas S6 Ribosómicas 90-kDa/genética , Animales , Apoptosis/efectos de los fármacos , Carpas/metabolismo , Células Cultivadas , Femenino , Proteínas de Peces/clasificación , Proteínas de Peces/metabolismo , Perfilación de la Expresión Génica/métodos , Células HEK293 , Humanos , Riñón/citología , Ovario/citología , Filogenia , Poli I-C/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Quinasas S6 Ribosómicas 90-kDa/clasificación , Proteínas Quinasas S6 Ribosómicas 90-kDa/metabolismoRESUMEN
BACKGROUND: Acute mortality effects of air pollution have been recognized in plenty of environmental epidemiologic studies. However, existing studies usually assume a universal lag association across sites and seasons. Such a strategy ignores the heterogeneity of lag structures and may lead to bias in the estimation of effects. METHODS: A Bayesian hierarchical model with flexible lag structures was applied to estimate the impact of particulate matter less than 10⯵m (PM10) on mortality and determine whether the lag structure varied by season and location. Data from nine US communities, obtained from the National Morbidity, Mortality, and Air Pollution Study (NMMAPS), was used to examine the lagged associations between PM10 and daily mortality. The estimates obtained from the flexible lag approaches were compared with those from the universal lag approach. RESULTS: Of potential varying lag structures, a 10-µg/m3 increase in PM10 was associated with 0.32% (95% credible interval: 0.16, 0.45) and 0.36% (0.18, 0.52) increases in mortality from nonaccidental and cardiovascular-respiratory death. The community-specific estimates of PM10 mortality effects were distinct between the flexible and the universal lag approaches, with relative change of the effects ranged from -7.21% to 9.25% for nonaccidental morality, and from -5.78% to 4.16% for cardiovascular-respiratory morality. Moreover, the lag structure varied by location and season. For instance, the nonaccidental mortality effect of PM10 attributable to the current and previous day was 29.8% in El Paso while 55.0% in Chicago; the overall effect attributable to the previous two to five days were 60.6%, 51.9%, 59.5%, and 59.3% in winter, spring, summer, and fall, respectively. CONCLUSION: The results indicated that a universal lag association across sites and seasons may bias the mortality effect of air pollution. The varying lag structures should be considered in studies of short-term environmental exposures to get a more precise effect estimate.