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BACKGROUND AND AIMS: Our study examined the trends of cardiovascular health metrics in individuals with coronary heart disease (CHD) and their associations with all-cause and cardiovascular disease mortality in the US. METHODS AND RESULTS: The cohort study was conducted based on the National Health and Nutrition Examination Survey 1999-2018 and their linked mortality files (through 2019). Baseline CHD was defined as a composite of self-reported doctor-diagnosed coronary heart disease, myocardial infarction, and angina pectoris. Cardiovascular health metrics were assessed according to the American Heart Association recommendations. Long-term all-cause and cardiovascular disease mortality were the primary outcomes. Survey-adjusted Cox regression models were used to estimate hazard ratios and corresponding 95% confidence intervals for the associations between cardiovascular health metrics and all-cause and cardiovascular disease mortality. The prevalence of one or fewer ideal cardiovascular health metrics increased from 14.15% to 22.79% (P < 0.001) in CHD, while the prevalence of more than four ideal cardiovascular health metrics decreased from 21.65% to 15.70 % (P < 0.001) from 1999 to 2018, respectively. Compared with CHD participants with one or fewer ideal cardiovascular health metrics, those with four or more ideal cardiovascular health metrics had a 35% lower risk (hazard ratio, 0.65; 95% confidence interval: 0.51, 0.82) and a 44% lower risk (0.56; 0.38, 0.84) in all-cause and cardiovascular disease mortality, respectively. CONCLUSION: Substantial declines were noted in ideal cardiovascular health metrics in US adults with CHD. A higher number of cardiovascular health metrics was associated with lower all-cause and cardiovascular disease mortality in them.
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Causas de Muerte , Enfermedad Coronaria , Encuestas Nutricionales , Humanos , Masculino , Femenino , Estados Unidos/epidemiología , Persona de Mediana Edad , Enfermedad Coronaria/mortalidad , Enfermedad Coronaria/diagnóstico , Enfermedad Coronaria/epidemiología , Factores de Tiempo , Anciano , Medición de Riesgo , Adulto , Pronóstico , Estado de Salud , Prevalencia , Factores Protectores , Factores de Riesgo , Factores de Riesgo de Enfermedad Cardiaca , Indicadores de Salud , Conducta de Reducción del RiesgoRESUMEN
BACKGROUND AND AIMS: Since the global burden of chronic kidney disease (CKD) is rising rapidly, the study aimed to assess the association of cardiovascular health (CVH) metrics with all-cause and cardiovascular disease (CVD) mortality among individuals with CKD. METHODS AND RESULTS: The cohort study included 5834 participants with CKD from the National Health and Nutrition Examination Survey 1999-2018. A composite CVH score was calculated based on smoking status, physical activity, body mass index, blood pressure, total cholesterol, diet quality, and glucose control. Primary outcomes were all-cause and CVD mortality as of December 31, 2019. Multivariable-adjusted Cox proportional hazards models were used to estimate the association between CVH metrics and deaths in CKD patients. During a median follow-up of 7.2 years, 2178 all-cause deaths and 779 CVD deaths were documented. Compared to participants with ideal CVH, individuals with intermediate CVH exhibited a 46.0% increase in all-cause mortality (hazard ratio, 1.46; 95% confidence interval: 1.17, 1.83), while those with poor CVH demonstrated a 101.0% increase (2.01; 1.54, 2.62). For CVD mortality, individuals with intermediate CVH experienced a 56.0% increase (1.56; 1.02, 2.39), and those with poor CVH demonstrated a 143.0% increase (2.43; 1.51, 3.91). Linear trends were noted for the associations of CVH with both all-cause mortality (P for trend <0.001) and CVD mortality (P for trend = 0.02). CONCLUSIONS: Lower CVH levels were associated with higher all-cause and CVD mortality in individuals with CKD, which highlights the importance of maintaining good CVH in CKD patients.
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Enfermedades Cardiovasculares , Causas de Muerte , Factores de Riesgo de Enfermedad Cardiaca , Encuestas Nutricionales , Insuficiencia Renal Crónica , Humanos , Masculino , Femenino , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/diagnóstico , Insuficiencia Renal Crónica/mortalidad , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/fisiopatología , Persona de Mediana Edad , Medición de Riesgo , Anciano , Factores de Tiempo , Estados Unidos/epidemiología , Pronóstico , Adulto , Presión Sanguínea , Glucemia/metabolismo , Ejercicio Físico , Dieta Saludable , Colesterol/sangre , Fumar/efectos adversos , Fumar/mortalidad , Fumar/epidemiología , Estado de Salud , Índice de Masa Corporal , Factores de RiesgoRESUMEN
Chemical modifications of proteins induced by ambient ozone (O3) and nitrogen oxides (NOx) are of public health concerns due to their potential to trigger respiratory diseases. The laboratory and environmental exposure systems have been widely used to investigate their relevant mechanism in the atmosphere. Using bovine serum albumin (BSA) as a model protein, we evaluated the two systems and aimed to reduce the uncertainties of both the reactants and products in the corresponding kinetic study. In the laboratory simulation system, the generated gaseous pollutants showed negligible losses. Ten layers of BSA were coated on the flow tube with protein extraction recovery of 87.4%. For environmental exposure experiment, quartz fiber filter was selected as the upper filter with low gaseous O3 (8.0%) and NO2 (1.7%) losses, and cellulose acetate filter was appropriate for the lower filter with protein extraction efficiency of 95.2%. The protein degradation process was observed without the exposure to atmospheric oxidants and contributed to the loss of protein monomer mass fractions, while environmental factors (e.g., molecular oxygen and ultraviolet) may cause greater protein monomer losses. Based on the evaluation, the study exemplarily applied the two systems to protein modification and both showed that O3 promotes the protein oligomerization and nitration, while increased temperature can accelerate the oligomerization and increased relative humidity can inhibit the nitration in the environmental exposure samples. The developed laboratory and environmental systems are suitable for studying protein modifications formed under different atmospheric conditions. A combination of the two will further reveal the actual mechanism of protein modifications.
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Contaminantes Atmosféricos , Ozono , Ozono/química , Contaminantes Atmosféricos/análisis , Albúmina Sérica Bovina/química , Exposición a Riesgos Ambientales , Óxidos de Nitrógeno/análisis , Proteínas/químicaRESUMEN
Proteins in atmospheric aerosol can react with atmospheric pollutants such as ozone (O3) and nitrogen dioxide (NO2) in the atmosphere via the reactions of oxidation, nitration, and cross-linking etc. Currently, the reactions have been more thoroughly studied in the laboratory but rarely investigated in the ambient environment. In this study, we used bovine serum albumin (BSA) as the model protein to conduct the exposure experiment in the ambient environment in southern China, an area with increasing oxidative capacity, to investigate the reactions of proteins in the atmosphere. We observed the occurrence of oligomerization, nitration and degradation of BSA upon exposure. The mass fraction of BSA monomer decreased by 5.86 ± 1.61% after exposure and those of dimers, trimers and higher oligomers increased by 1.04 ± 0.49%, 1.37 ± 0.74% and 3.40 ± 1.06%, respectively. Simultaneously, the nitration degrees of monomers, dimers, trimers and higher oligomers increased by 0.42 ± 0.15%, 0.53 ± 0.15%, 0.55 ± 0.28% and 2.15 ± 1.01%, respectively. The results show that oligomerization was significantly affected by O3 and temperature and nitration was jointly affected by O3, temperature and relative humidity, indicating the important role of atmospheric oxidants in the atmospheric reactions of protein. Atmospheric degradation of BSA was observed with the release of free amino acids (FAAs) such as glycine, alanine, serine and methionine. Glycine was the dominant FAA with a molar yield ranging from â¼8% to 33% for BSA. The estimated stoichiometric coefficient (α) of glycine is 10-7-10-6 for the degradation of BSA upon O3. Our observation suggests the occurrence of protein reactions in the oxidative ambient environment, leading to the production of nitrated products, oligomers and low molecular weight products such as peptides and FAAs. This study may deepen the current understanding of the atmospheric reaction mechanisms and reveal the influence of environmental factors in the atmosphere.
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Contaminantes Atmosféricos , Ozono , Albúmina Sérica Bovina/química , Péptidos , Aminoácidos , Contaminantes Atmosféricos/química , Glicina , Ozono/químicaRESUMEN
Cervical cancer poses a significant health challenge in developing countries, emphasizing the need for appropriate screening strategies to accelerate the elimination of this disease. This study summarized the results of a large-scale community-based cervical cancer screening program conducted in Chengdu, China, to understand the prevalence of HPV infection and cervical lesions in the population, and to compare the real-world effectiveness of two different screening methods implemented in the program. From January 2021 to December 2022, a total of 363,376 women aged 35-64 years in Chengdu received free screenings. Among these participants, 70.1% received cytology screening and 29.9% received HPV testing combined with 16/18 genotyping and cytology triage. Ultimately, 824 cases of high-grade lesions and cervical cancer were detected, with a total detection rate of cervical cancer and precancerous lesions of 226.8 per 100,000. The follow-up rate of patients with high-grade lesions and above was 98.9%, and the treatment rate was 86.6%. The overall high-risk HPV infection rate was 11.7%, with the HPV 16/18 infection rate of 1.4%. The rate of abnormal cytology results was 2.8%. The attendance rates for colposcopy and histopathology were 71.6% and 86.1%, respectively. By calculating the age-standardized rates to eliminate the different age composition between the two group, the HPV-based screening strategy had a higher rate of primary screening abnormalities (3.4% vs. 2.8%, P<0.001), higher attendance rates of colposcopy (76.5% vs. 68.9%, P<0.001) and histopathological diagnosis (94.1% vs. 78.0%, P<0.001), higher percentage of abnormal colposcopy results (76.0% vs. 44.0%, P<0.001), and higher detection rate of cervical precancerous lesions and cancer (393.1 per 100,000 vs. 156.4 per 100,000, P<0.001) compared to cytology screening. Our study indicates that the combination of HPV testing with 16/18 genotyping and cytology triage has demonstrated superior performance in cervical cancer screening compared to cytology alone in large-scale population.
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Infecciones por Papillomavirus , Lesiones Precancerosas , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/patología , Displasia del Cuello del Útero/diagnóstico , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Papillomavirus Humano 16 , Detección Precoz del Cáncer/métodos , Estudios Transversales , Papillomavirus Humano 18RESUMEN
Cirrhosis is an aggressive disease, and over 80 % of liver cancer patients are complicated by cirrhosis, which lacks effective therapies. Transplantation of mesenchymal stem cells (MSCs) is a promising option for treating liver cirrhosis. However, this therapeutic approach is often challenged by the low homing ability and short survival time of transplanted MSCs in vivo. Therefore, a novel and efficient cell delivery system for MSCs is urgently required. This new system can effectively extend the persistence and duration of MSCs in vivo. In this study, we present novel porous microspheres with microfluidic electrospray technology for the encapsulation of bone marrow-derived MSCs (BMSCs) in the treatment of liver cirrhosis. Porous microspheres loaded with BMSCs (Mi-BMSCs) exhibit good biocompatibility and demonstrate better anti-inflammatory properties than BMSCs alone. Mi-BMSCs significantly increase the duration of BMSCs and exert potent anti-inflammatory and anti-fibrosis effects against CCl4 and TAA-induced liver cirrhosis by targeting the TGF-ß/Smad signaling pathway to ameliorate cirrhosis, which highlight the potential of Mi-BMSCs as a promising therapeutic approach for early liver cirrhosis.
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BACKGROUND: Previous studies have reported associations of specific maternal and paternal lifestyle factors with offspring's cognitive development during early childhood. This study aimed to investigate the prospective associations between overall parental lifestyle and offspring's cognitive performance during adolescence and young adulthood in China. METHODS: We included 2531 adolescents aged 10-15 years at baseline in 2010 from the China Family Panel Studies. A healthy parental lifestyle score (ranged 0-5) was constructed based on the following five modifiable lifestyle factors: Smoking, drinking, exercise, sleep, and diet. Generalized estimating equation models were used to examine the association between baseline parental healthy lifestyle scores and offspring's fluid and crystallized intelligence in subsequent years (2012, 2014, 2016, and 2018). RESULTS: Offspring in the top tertile of parental healthy lifestyle scores performed better in overall fluid intelligence (multivariable-adjusted ß = 0.53, 95% confidence interval [CI]: 0.29-0.77) and overall crystallized intelligence (multivariable-adjusted ß = 0.35, 95% CI: 0.16-0.54) than those in the bottom tertile of parental healthy lifestyle scores. The results were similar after further adjustment for the offspring's healthy lifestyle scores and persisted across the subgroups of parental socioeconomic status. Additionally, maternal and paternal healthy lifestyle scores were independently associated with better offspring's cognitive performance, with significant contribution observed for paternal never-smoking, weekly exercise, and diversified diet. When both parents and offspring adhered to a healthier lifestyle, we observed the highest level of the offspring's overall crystallized intelligence. CONCLUSIONS: Our study indicates that parental adherence to a healthier lifestyle is associated with significantly better offspring's cognitive performance during adolescence and early adulthood, regardless of socioeconomic status. These findings highlight the potential cognitive benefits of promoting healthy lifestyles among parents of adolescents.
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Estilo de Vida Saludable , Padres , Adolescente , Humanos , Preescolar , Adulto Joven , Adulto , Estudios Prospectivos , Padres/psicología , Fumar , Estilo de VidaRESUMEN
BACKGROUND: We aimed to analyse genome-wide transcriptome differences between Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) patients and identify biomarkers that correlate well with muscle magnetic resonance imaging (MRI) and histological fibrofatty replacement in both patients, which have not been reported. METHODS: One hundred and one male patients with dystrophinopathies (55 DMD and 46 BMD) were enrolled. Muscle-derived genome-wide RNA-sequencing was performed in 31 DMD patients, 29 BMD patients, and 11 normal controls. Fibrofatty replacement was scored on muscle MRI and histological levels in all patients. A unique pipeline, single-sample gene set enrichment analysis combined with Spearman's rank correlations (ssGSEA-Cor) was developed to identify the most correlated gene signature for fibrofatty replacement. Quantitative real-time PCR (qRT-PCR) analysis, western blot analysis, and single-nucleus RNA-sequencing (snRNA-seq) were performed in the remaining patients to validate the most correlated gene signature. RESULTS: Comparative transcriptomic analysis revealed that 31 DMD muscles were characterized by a significant increase of inflammation/immune response and extracellular matrix remodelling compared with 29 BMD muscles (P < 0.05). The ssGSEA-Cor pipeline revealed that the gene set of CDKN2A and CDKN2B was the most correlated gene signature for fibrofatty replacement (histological rs = 0.744, P < 0.001; MRI rs = 0.718, P < 0.001). Muscle qRT-PCR confirmed that CDKN2A mRNA expression in both 15 DMD (median = 25.007, P < 0.001) and 12 BMD (median = 5.654, P < 0.001) patients were significantly higher than that in controls (median = 1.101), while no significant difference in CDKN2B mRNA expression was found among DMD, BMD, and control groups. In the 27 patients, muscle CDKN2A mRNA expression respectively correlated with muscle MRI (rs = 0.883, P < 0.001) and histological fibrofatty replacement (rs = 0.804, P < 0.001) and disease duration (rs = 0.645, P < 0.001) and North Star Ambulatory Assessment total scores (rs = -0.698, P < 0.001). Muscle western blot analysis confirmed that both four DMD (median = 2.958, P < 0.05) and four BMD (median = 1.959, P < 0.01) patients had a significantly higher level of CDKN2A protein expression than controls (median = 1.068). The snRNA-seq analysis of two DMD muscles revealed that CDKN2A was mainly expressed in fibro-adipogenic progenitors, satellite cells, and myoblasts. CONCLUSIONS: We identify CDKN2A expression as a novel biomarker of fibrofatty replacement, which might be a new target for antifibrotic therapy in dystrophinopathies.
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Distrofia Muscular de Duchenne , Transcriptoma , Humanos , Masculino , Distrofia Muscular de Duchenne/diagnóstico por imagen , Distrofia Muscular de Duchenne/genética , Músculo Esquelético/patología , Biomarcadores , Imagen por Resonancia Magnética , ARN Mensajero , ARN , ARN Nuclear PequeñoRESUMEN
Magnesium matrix composites have been extensively investigated due to their light weight and machinability. The interfaces are the most important part of these composites, and their properties determine the properties of composites to a large extent. However, there are still many problems with interface bonding. The reinforcements are faced with the dilemma of poor dispersion, bad interfacial reaction, and poor wettability, which limits further improvements in the mechanical properties. Surface coating treatment of reinforcements is considered to be one of the effective methods to protect reinforcements and modify the interface. This review presents an overview of different coating materials on various reinforcements. The major roles of coatings in the composites and the properties of the composites are discussed. Future directions and potential research areas in the field of magnesium matrix composites reinforced with coated reinforcements are also highlighted.
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ß-Elemene (C15H24), a sesquiterpenoid compound isolated from the volatile oil of Curcuma wenyujin, has been proven to be effective for multiple cancers and is widely used in clinical treatment. Unfortunately, the ß-elemene content in C. wenyujin is very low, which cannot meet market demands. Our previous research showed that methyl jasmonate (MeJA) induced the accumulation of ß-elemene in C. wenyujin. However, the regulatory mechanism is unclear. In this study, 20 jasmonate ZIM-domain (JAZ) proteins in C. wenyujin were identified, which are the core regulatory factors of the JA signaling pathway. Then, the conservative domains, motifs composition, and evolutionary relationships of CwJAZs were analyzed comprehensively and systematically. The interaction analysis indicated that CwJAZs can form homodimers or heterodimers. Fifteen out of twenty CwJAZs were significantly induced via MeJA treatment. As the master switch of the JA signaling pathway, the CwMYC2-like protein has also been identified and demonstrated to interact with CwJAZ2/3/4/5/7/15/17/20. Further research found that the overexpression of the CwMYC2-like gene increased the accumulation of ß-elemene in C. wenyujin leaves. Simultaneously, the expressions of HMGR, HMGS, DXS, DXR, MCT, HDS, HDR, and FPPS related to ß-elemene biosynthesis were also up-regulated by the CwMYC2-like protein. These results indicate that CwJAZs and the CwMYC2-like protein respond to the JA signal to regulate the biosynthesis of ß-elemene in C. wenyujin.
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Curcuma , Sesquiterpenos , Curcuma/metabolismo , Sesquiterpenos/farmacología , Ciclopentanos/farmacología , Ciclopentanos/metabolismoRESUMEN
PURPOSE: Adherence to overall 24-hour Movement Guidelines (24HGs) has been associated with childhood obesity in cross-sectional studies. However, few longitudinal studies have examined such associations, especially in China. We aimed to explore prospective associations between adherence to recommendations of 24HGs and risks of developing overweight and obesity among children and adolescents. METHODS: We included participants (aged 6-17 years) without overweight and obesity at enrollment from the China Health and Nutrition Survey in 2004-2011 surveys and followed them till 2015. We assigned one point each to the adherence of guidelines for moderate-to-vigorous physical activity, recreational screen time and sleep, and summed them up to indicate the overall level of adherence to 24HGs (range: 0-3 points). The primary outcome was the first occurrence of overweight or obesity. Multivariable cox proportional hazard models were used to evaluate the corresponding associations. RESULTS: Among 1,382 participants (mean age: 10.3 ± 3.2 years; 48.4% girls), a total of 152 (11%) individuals were identified as incident overweight and obesity during an average of 4.7 years of follow-up. Compared with participants nonadherent to any of the guidelines, those adhering to one (hazard ratio [HR] = 0.38, 95% confidence interval [CI]: 0.21-0.71, p < .01), two (HR = 0.49, 95% CI: 0.28-0.88, p = .02), and three (HR = 0.40, 95% CI: 0.17-0.91, p = .03) recommendations had significantly lower risks of developing overweight and obesity. DISCUSSION: Children and adolescents who met any recommendations of 24HGs had significantly lower risks of developing subsequent overweight and obesity. Setting achievable goals such as adopting at least one recommendation could be considered in future public health recommendations to accelerate progress in childhood obesity prevention.
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Sobrepeso , Obesidad Infantil , Femenino , Humanos , Niño , Adolescente , Masculino , Sobrepeso/epidemiología , Obesidad Infantil/epidemiología , Obesidad Infantil/prevención & control , Estudios Transversales , Ejercicio Físico , SueñoRESUMEN
(1) Background: it is unclear whether serum vitamin B12 and circulating methylmalonic acid (MMA) are related with a poor prognosis among individuals with chronic kidney disease (CKD); (2) Methods: this prospective cohort study included 2589 individuals with CKD who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004, and from 2011 to 2014, respectively. Hazard ratios (HRs) and 95% Cis for the associations of MMA and vitamin B12 levels with the risk of all-cause and cardiovascular disease (CVD) mortality were calculated using multivariable Cox proportional hazards regression models. Restricted cubic spline analyses were used to examine the non-linear association of MMA levels with all-cause and CVD mortality. (3) Results: among the 2589 participants, we identified 1192 all-cause deaths and 446 CVD deaths, respectively, with a median follow-up of 7.7 years. Compared with participants with MMA < 123 nmol/L, those with MMA ≥ 240 nmol/L had an increased all-cause and CVD mortality in the multivariable-adjusted model [HR (95% CI), 2.01 (1.54-2.62) and 1.76 (1.18-2.63), respectively]; (4) Conclusions: higher circulating MMA levels were found to be strongly associated with an elevated all-cause and CVD mortality among individuals with CKD, while serum vitamin B12 levels were not associated.
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Enfermedades Cardiovasculares , Insuficiencia Renal Crónica , Humanos , Ácido Metilmalónico , Encuestas Nutricionales , Estudios Prospectivos , Vitamina B 12 , VitaminasRESUMEN
OBJECTIVE: Polychlorinated biphenyls (PCBs) have been reported to be a risk factor for premature death, while a high diet quality is thought to lower mortality risk. We aimed to examine whether PCBs were associated with higher all-cause and cause-specific mortality risk and whether such associations could be modified by the diet quality among US middle-aged and older adults. METHODS: Included were 1259 participants aged 40 years or older from the 1999-2004 National Health and Nutrition Examination surveys. Exposure to PCBs was assessed in non-fasting serum samples, and mortality status was ascertained through December 31, 2019 using the public-use, linked mortality files. Diet quality was assessed using the Healthy Eating Index-2015 based on 24-h dietary recalls. Cox proportional hazard regression was applied to assess the associations of different PCB congener groups with mortality and the modifying effect by the diet quality. RESULTS: During a median follow-up of 17.75 years, 419 deaths occurred, including 131 from cardiovascular disease (CVD) and 102 from cancer. Serum concentrations of dioxin-like PCBs and non-dioxin-like PCBs were significantly associated with all-cause mortality, with hazard ratios (HRs) of 1.84 (95% confidence interval [CI], 1.10, 2.99) and 1.82 (1.09, 3.03) for extreme-tertile comparisons. A significant interaction was noted between dioxin-like PCBs and diet quality (P for interaction: 0.012), with a substantially more pronounced association among participants with a low diet quality (HR, 3.47; 95% CI: 1.29, 9.32), compared to those with a high diet quality (HR, 0.98; 95% CI: 0.40, 2.43). A similar weaker association was observed for total PCBs in participants with a high diet quality (P for interaction: 0.032). However, effect modifications by diet quality were not noted for the associations between different PCB groups and CVD mortality. CONCLUSIONS: While our findings need to be validated in other populations and mechanistic studies, they may suggest that a high quality diet could potentially attenuate the harmful effects of chronic PCB exposure.
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Enfermedades Cardiovasculares , Dioxinas , Bifenilos Policlorados , Persona de Mediana Edad , Humanos , Anciano , Bifenilos Policlorados/análisis , Mortalidad Prematura , Dieta , Enfermedades Cardiovasculares/inducido químicamenteRESUMEN
BACKGROUND: Enhancer of Zeste homologue 2 (EZH2) is a polycomb group gene and an epigenetic regulator that inhibits transcription, a modification associated with gene silencing. EZH2 plays an essential role in humoral and cell-mediated adaptive immunity. The purpose of the current study is to investigate the prognostic potential of EZH2 and to comprehensively analyse the correlation between EZH2 and immune infiltration in multiple cancer cases, especially liver hepatocellular carcinoma. METHODS: EZH2 expression across cancers was explored through Oncomine, HPA, and GEPIA2. Additionally, the prognostic value of EZH2 analysis across cancers was based on the GEPIA2, TCGA portal, Kaplan-Meier Plotter, and LOGpc databases. Based on GO and KEGG analyses, GSEA helped demonstrate the biological processes through which EZH2 might lead to HCC development. GEPIA and TIMER were adopted to detect the possible relationship of EZH2 expression with tumour-infiltrating immune cells (TIICs). RESULTS: EZH2 overexpression levels were associated with poor prognosis of cancer, especially hepatocellular carcinoma. A high EZH2 expression level is related to a poor prognosis of HCC, especially in disease histology and stage III. The EZH2 expression level was positively correlated with critical gene markers of TAMs, M2 macrophages, M1 macrophages, and monocytes. Further analysis revealed that EZH2 genes were mainly related to DNA recombination, mitotic cell cycle phase transition, and chromosome segregation. CONCLUSION: EZH2 plays an essential role in the immune microenvironment and is a potential prognostic marker and immunotherapy target for hepatocellular carcinoma.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Proteína Potenciadora del Homólogo Zeste 2/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Pronóstico , Microambiente Tumoral/genéticaRESUMEN
BACKGROUND: MKI67 plays a vital role in the tumour microenvironment (TME) and congenital immunity. The present work focuses on exploring the prognosis prediction performance of MKI67 and its associations with T cell activity and immune infiltration within numerous cancers, especially hepatocellular liver carcinoma (LIHC). METHODS: Oncomine, GEPIA2, and HPA were adopted to analyse MKI67 levels in different types of cancers. The prognostic prediction performance of MKI67 was evaluated through the TCGA portal, GEPIA2, LOGpc, and Kaplan-Meier Plotter databases. The associations of MKI67 with related gene marker sets and immune infiltration were inspected through TISIDB, GEPIA2, and TIMER. We chose MKI67 to analyse biological processes (BPs) and KEGG pathways related to the coexpressed genes. Furthermore, the gene-miRNA interaction network for MKI67 in liver cancer was also examined based on the miRWalk database. RESULTS: MKI67 expression decreased in many cancers related to the dismal prognostic outcome of LIHC. We found that MKI67 significantly affected the prognosis of LIHC in terms of histology and grade. Increased MKI67 levels were directly proportional to the increased immune infiltration degrees of numerous immune cells and functional T cells, such as exhausted T cells. In addition, several critical genes related to exhausted T cells, including TIM-3, TIGIT, PD-1, LAG3, and CXCL13, were strongly related to MKI67. Further analyses showed that MKI67 was associated with adaptive immunity, cell adhesion molecules (CAMs), and chemokine/immune response signal transduction pathways. CONCLUSION: MKI67 acts as a prognostic prediction biomarker in several cancers, particularly LIHC. Upregulation of MKI67 elevates the degree of immune infiltration of many immune cell subtypes, including functional T cells, CD4+ T cells, and CD8+ T cells. Furthermore, MKI67 shows a close correlation with T cell exhaustion, which plays a vital role in promoting T cell exhaustion within LIHC. Detection of the MKI67 level contributes to prognosis prediction and MKI67 modulation within exhausted T cells, thus providing a new method to optimize the efficacy of anti-LIHC immunotherapy.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores de Tumor/genética , Linfocitos T CD8-positivos , Humanos , Pronóstico , Microambiente TumoralRESUMEN
With globalization, the cases of Chinese enterprises' cross-border mergers and acquisitions (M&A) are increasing rapidly. The institutional environment of the host country has become an important factor influencing M&A performance, which has a profound impact on the success or failure of cross-border M&A. Based on this, for our study, we selected cases of cross-border M&A of listed companies in China from 2007 to 2018 as research samples to empirically test the impact of the host country's governance capacity on the cross-border M&A performance of acquirers. It was found that the host country's governance capacity has a negative effect on the M&A performance in the short term, but in the long term, it can effectively improve the cross-border M&A performance of acquirers. At the same time, specific to the relationship between the governmental governance capacity of six different dimensions and long-term M&A performance, the government effectiveness, regulation quality, and rule of law have the most significant promotional effect on long-term M&A performance. This implies that acquirers should focus on the long-term impact of governmental governance capacity on M&A, and consciously lean toward countries with strong governance capacity in order to obtain long-term value growth when arranging overseas M&A activities. The conclusion of this paper provides a reliable basis on which for companies to achieve sustainable growth in complex economic activities.
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Gobierno , Emigración e InmigraciónRESUMEN
With Li-6400-09 chamber, the soil respiration rate in adjacent stands of temperate secondary forest and Larix gmelinii plantation in Maoershan Mountain of Heilongjiang Province was measured from May to October, 2006. The results showed that similar to the variation of soil temperature, the daily pattern of soil respiration could be expressed as a one-humped curve. Over the study period, soil respiration rate varied from 0.43 to 7.26 micromol CO2 x m(-2) x s(-1) in secondary forest, and from 0.63 to 4.70 micromol CO2 x m(-2) x s(-1) in L. gmelinii plantation. The maximum soil respiration rate occurred from July to August, and the minimum in October. From May to August, soil respiration rate was obviously higher in secondary forest than in L. gmelinii plantation. The respiration rate of litter layer during the study period varied from -0.65 to 1.26 micromol CO2 x m(-2) x s(-1) in secondary forest, and from -0.43 to 0.47 micromol CO2 x m(-2 ) x s(-1) in L. gmelinii plantation. Soil respiration had a strong exponential correlation with soil temperature, especially the temperature at 5 cm depth. The Q10 value at 5 cm depth was 3.61 and 3.07, respectively in secondary forest and L. gmelinii plantation. There was a significant correlation between soil respiration and the soil water content at 10-20 cm depth in secondary forest, but less correlation was observed between them in L. gmelinii plantation.