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SIGNIFICANCE: This study on the relationship between early life high BMI and the development of CRC reveals the role of high BMI during childhood and adolescence in the occurrence and progression of CRC. It suggests the importance of restoring normal weight or reducing weight in individuals with high BMI early in life for the prevention of colorectal cancer.
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Índice de Massa Corporal , Neoplasias Colorretais , Humanos , Neoplasias Colorretais/prevenção & controle , Neoplasias Colorretais/patologia , Feminino , Masculino , Adolescente , Adulto , Criança , Fatores de Risco , Pessoa de Meia-Idade , Adulto JovemRESUMO
AIM: To develop a visual prediction model for gestational diabetes (GD) in pregnant women and to establish an effective and practical tool for clinical application. METHODS: To establish a prediction model, the modelling set included 1756 women enrolled in the Zunyi birth cohort, the internal validation set included 1234 enrolled women, and pregnant women in the Wuhan cohort were included in the external validation set. We established a demographic-lifestyle factor model (DLFM) and a demographic-lifestyle-environmental pollution factor model (DLEFM) based on whether the women were exposed to environmental pollutants. The least absolute shrinkage and selection lasso-logistic regression analyses were used to identify the independent predictors of GD and construct a nomogram for predicting its occurrence. RESULTS: The DLEFM regression analysis showed that a family history of diabetes (odd ratio [OR] 2.28; 95% confidence interval [CI] 1.05-4.71), a history of GD in pregnant women (OR 4.22; 95% CI 1.89-9.41), being overweight or obese before pregnancy (OR 1.71; 95% CI 1.27-2.29), a history of hypertension (OR 2.61; 95% CI 1.41-4.72), sedentary time (h/day) (OR 1.16; 95% CI 1.08-1.24), monobenzyl phthalate (OR 1.95; 95% CI 1.45-2.67) and Q4 mono-ethyl phthalate concentration (OR 1.85; 95% CI 1.26-2.73) were independent predictors. The area under the receiver operating curves for the internal validation of the DLEFM and the DLFM constructed using these seven factors was 0.827 and 0.783, respectively. The calibration curve of the DLEFM was close to the diagonal line. The DLEFM was thus the more optimal model, and the one which we chose. CONCLUSIONS: A nomogram based on preconception factors was constructed to predict the occurrence of GD in the second and third trimesters. It provided an effective tool for the early prediction and timely management of GD.
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Diabetes Gestacional , Ácidos Ftálicos , Gravidez , Feminino , Humanos , Diabetes Gestacional/epidemiologia , Estilo de Vida , CalibragemRESUMO
The discovery of the significant lethal impacts of the tire additive transformation product N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-Q) on coho salmon has garnered global attention. However, the bioaccumulation and trophic transfer of tire additives and their transformation products (TATPs) within food webs remain obscure. This study first characterized the levels and compositions of 15 TATPs in the Pearl River Estuary, estimated their bioaccumulation and trophic transfer potential in 21 estuarine species, and identified priority contaminants. Our observations indicated that TATPs were prevalent in the estuarine environment. Eight, six, seven, and 10 TATPs were first quantified in the shrimp, sea cucumber, snail, and fish samples, with total mean levels of 45, 56, 64, and 67 ng/g (wet weight), respectively. N,N'-Diphenyl-p-phenylenediamine (DPPD) and N,N'-bis(2-methylphenyl)-1,4-benzenediamine (DTPD) exhibited high bioaccumulation. Significant biodilution was only identified for benzothiazole, while DPPD and DTPD displayed biomagnification trends based on Monte Carlo simulations. The mechanisms of bioaccumulation and trophodynamics of TATPs could be explained by their chemical hydrophobicity, molecular mass, and metabolic rates. Based on a multicriteria scoring technique, DPPD, DTPD, and 6PPD-Q were characterized as priority contaminants. This work emphasizes the importance of biomonitoring, particularly for specific hydrophobic tire additives.
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Cadeia Alimentar , Fenilenodiaminas , Poluentes Químicos da Água , Animais , Bioacumulação , Monitoramento Ambiental , Poluentes Químicos da Água/análiseRESUMO
The identification of interaction between protein and ligand including binding positions and strength plays a critical role in drug discovery. Molecular docking and molecular dynamics (MD) techniques have been widely applied to predict binding positions and binding affinity. However, there are few works that describe the systematic exploration of the MD trajectory evolution in this context, potentially leaving out important information. To address the problem, we build a framework, Moira (molecular dynamics trajectory analysis), which enables automating the whole process ranging from docking, MD simulations and various analyses as well as visualizations. We utilized Moira to analyze 400 MD simulations in terms of their geometric features (root mean square deviation and protein-ligand interaction profiler) and energetics (molecular mechanics Poisson-Boltzmann surface area) for these trajectories. Finally, we demonstrate the performance of different analysis techniques in distinguishing native poses among four poses.
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Simulação de Dinâmica Molecular , Proteínas , Ligantes , Simulação de Acoplamento Molecular , Proteínas/química , Descoberta de Drogas , Ligação ProteicaRESUMO
Many studies have indicated that individual exposure to phthalates (PAEs) or polycyclic aromatic hydrocarbons (PAHs) affects pregnancy outcomes. However, combined exposure to PAEs and PAHs presents a more realistic situation, and research on the combined effects of PAEs and PAHs on gestational age and newborn size is still limited. This study aimed to assess the effects of combined exposure to PAEs and PAHs on neonatal gestational age and birth size. Levels of 9 PAE and 10 PAH metabolites were measured from the urine samples of 1030 women during early pregnancy from the Zunyi Birth Cohort in China. Various statistical models, including linear regression, restricted cubic spline, Bayesian kernel machine regression, and quantile g-computation, were used to study the individual effects, dose-response relationships, and combined effects, respectively. The results of this prospective study revealed that each ten-fold increase in the concentration of monoethyl phthalate (MEP), 2-hydroxynaphthalene (2-OHNap), 2-hydroxyphenanthrene (2-OHPhe), and 1-hydroxypyrene (1-OHPyr) decreased gestational age by 1.033 days (95â¯% CI: -1.748, -0.319), 0.647 days (95â¯% CI: -1.076, -0.219), 0.845 days (95â¯% CI: -1.430, -0.260), and 0.888 days (95â¯% CI: -1.398, -0.378), respectively. Moreover, when the concentrations of MEP, 2-OHNap, 2-OHPhe, and 1-OHPyr exceeded 0.528, 0.039, 0.012, and 0.002⯵g/g Cr, respectively, gestational age decreased in a dose-response manner. Upon analyzing the selected PAE and PAH metabolites as a mixture, we found that they were significantly negatively associated with gestational age, birth weight, and the ponderal index, with 1-OHPyr being the most important contributor. These findings highlight the adverse effects of single and combined exposure to PAEs and PAHs on gestational age. Therefore, future longitudinal cohort studies with larger sample sizes should be conducted across different geographic regions and ethnic groups to confirm the impact of combined exposure to PAEs and PAHs on birth outcomes.
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Truck hoisting detection constitutes a key focus in port security, for which no optimal resolution has been identified. To address the issues of high costs, susceptibility to weather conditions, and low accuracy in conventional methods for truck hoisting detection, a non-intrusive detection approach is proposed in this paper. The proposed approach utilizes a mathematical model and an extreme gradient boosting (XGBoost) model. Electrical signals, including voltage and current, collected by Hall sensors are processed by the mathematical model, which augments their physical information. Subsequently, the dataset filtered by the mathematical model is used to train the XGBoost model, enabling the XGBoost model to effectively identify abnormal hoists. Improvements were observed in the performance of the XGBoost model as utilized in this paper. Finally, experiments were conducted at several stations. The overall false positive rate did not exceed 0.7% and no false negatives occurred in the experiments. The experimental results demonstrated the excellent performance of the proposed approach, which can reduce the costs and improve the accuracy of detection in container hoisting.
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Complement activation is an important mediator of kidney injury in glomerulonephritis. Complement factor H (FH) and FH-related protein 5 (FHR-5) influence complement activation in C3 glomerulopathy and IgA nephropathy by differentially regulating glomerular complement. FH is a negative regulator of complement C3 activation. Conversely, FHR-5 in vitro promotes C3 activation either directly or by competing with FH for binding to complement C3b. The FH-C3b interaction is enhanced by surface glycosaminoglycans (GAGs) and the FH-GAG interaction is well-characterized. In contrast, the contributions of carbohydrates to the interaction of FHR-5 and C3b are unknown. Using plate-based and microarray technologies we demonstrate that FHR-5 interacts with sulfated GAGs and that this interaction is influenced by the pattern and degree of GAG sulfation. The FHR-5-GAG interaction that we identified has functional relevance as we could show that the ability of FHR-5 to prevent binding of FH to surface C3b is enhanced by surface kidney heparan sulfate. Our findings are important in understanding the molecular basis of the binding of FHR-5 to glomerular complement and the role of FHR-5 in complement-mediated glomerular disease.
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Fator H do Complemento , Glomerulonefrite por IGA , Ativação do Complemento , Complemento C3b , Glicosaminoglicanos , HumanosRESUMO
New models associated with frustrated geometry and an external electric field (EEF) were designed to qualitatively and quantitatively explore CO2 activation through density functional calculations. We investigated the influence on CO2 of the microenvironments of methylamine (CH3NH2) positioned at different heights above a Cu (111) surface in the presence and absence of an electric field. The results demonstrate that at an approximate distance of 4 ± 1 Å between N and the metal surface, neither lower nor higher, under an EEF over 0.4 V Å-1, there is a remarkable synergistic effect between the chemical interaction and EEF that activates CO2, and also lowers the required EEF strength. This is in contrast to the separate factors or any other combinations of them which do not achieve the synergistic effect. In addition, when H in was replaced by F, the O-C-O angle of CO2 is not affected. This phenomenon further illustrates that the synergistic effect is very sensitive to the nucleophilicity of NH2. Various other chemical groups and substrates were investigated, and PHCH3 also displays a distinctive chemisorption CO2 state. The substrate also plays a significant role, except that Au cannot generate a similar effect. Furthermore, constraining or facilitating CO2 activation strongly depends on the distance between the chemical group and the substrate. Appropriate combinations of the three factors related to the substrate Cu, the chemical group CH3NH2 and the EEF provide new protocols to make CO2 activation easier and controllable.
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The bile acid (BA) submetabolome can partially reflect either physiological or pathological status of vertebrates. The structural diversity, however, extensively hinders BA submetabolome clarification. Here, efforts were primarily devoted to enhance structural annotation confidences of BAs, in particular the conjugated BAs, through fortifying a new technology, namely, squared energy-resolved mass spectrometry (ER2-MS), to traditional liquid chromatography with tandem mass spectrometry (LC-MS/MS). Because of possessing two tandem-in-space collision cells, namely, q2 and linear ion trap (LIT) chambers, Qtrap-MS was employed as the fit-for-purpose tool to conduct ER2-MS measurements. The first ER-MS was undertaken in a q2 cell to gain first-generation breakdown graphs to disclose conjugation sites via applying the multiple-reaction monitoring (MRM) program, and the second ER-MS was accomplished in a LIT chamber through programming MRM cubed to acquire second-generation breakdown graphs of concerned ions for scaffold characterization. An authentic BA library consisting of commercial BAs together with their in vitro metabolites was built to record a reference breakdown graph set. Moreover, the so-called universal metabolome standard sample that was prepared by pooling diverse BA-enriched matrices was applied for structural deciphering potential evaluation and quasi-quantitative analysis of all detected BAs as well, according to applying a well-defined quasi-content concept. High-confidence structural analysis was achieved for as many as 201 BAs, and significant impacts occurred for the BA submetabolome of HepG2 cells after lithocholic acid treatment. Together, ER2-MS provides a promising tool to promote, although not limited to, LC-MS/MS-based BA-targeted metabolomics.
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Ácidos e Sais Biliares , Espectrometria de Massas em Tandem , Animais , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Metabolômica/métodos , MetabolomaRESUMO
Chikungunya virus (CHIKV) is an arthritogenic alphavirus that causes debilitating musculoskeletal disease. CHIKV displays broad cell, tissue, and species tropism, which may correlate with the attachment factors and entry receptors used by the virus. Cell surface glycosaminoglycans (GAGs) have been identified as CHIKV attachment factors. However, the specific types of GAGs and potentially other glycans to which CHIKV binds and whether there are strain-specific differences in GAG binding are not fully understood. To identify the types of glycans bound by CHIKV, we conducted glycan microarray analyses and discovered that CHIKV preferentially binds GAGs. Microarray results also indicate that sulfate groups on GAGs are essential for CHIKV binding and that CHIKV binds most strongly to longer GAG chains of heparin and heparan sulfate. To determine whether GAG binding capacity varies among CHIKV strains, a representative strain from each genetic clade was tested. While all strains directly bound to heparin and chondroitin sulfate in enzyme-linked immunosorbent assays (ELISAs) and depended on heparan sulfate for efficient cell binding and infection, we observed some variation by strain. Enzymatic removal of cell surface GAGs and genetic ablation that diminishes GAG expression reduced CHIKV binding and infectivity of all strains. Collectively, these data demonstrate that GAGs are the preferred glycan bound by CHIKV, enhance our understanding of the specific GAG moieties required for CHIKV binding, define strain differences in GAG engagement, and provide further evidence for a critical function of GAGs in CHIKV cell attachment and infection.IMPORTANCE Alphavirus infections are a global health threat, contributing to outbreaks of disease in many parts of the world. Recent epidemics caused by CHIKV, an arthritogenic alphavirus, resulted in more than 8.5 million cases as the virus has spread into new geographic regions, including the Western Hemisphere. CHIKV causes disease in the majority of people infected, leading to severe and debilitating arthritis. Despite the severity of CHIKV disease, there are no licensed therapeutics. Since attachment factors and receptors are determinants of viral tropism and pathogenesis, understanding these virus-host interactions can enhance our knowledge of CHIKV infection. We analyzed over 670 glycans and identified GAGs as the main glycan bound by CHIKV. We defined specific GAG components required for CHIKV binding and assessed strain-specific differences in GAG binding capacity. These studies provide insight about cell surface molecules that CHIKV binds, which could facilitate the development of antiviral therapeutics targeting the CHIKV attachment step.
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Vírus Chikungunya/fisiologia , Glicosaminoglicanos/metabolismo , Heparina/metabolismo , Ligação Viral , Animais , Artrite , Linhagem Celular , Febre de Chikungunya/virologia , Glucuronosiltransferase/genética , Heparitina Sulfato/metabolismo , Humanos , Polissacarídeos/metabolismo , Tropismo ViralRESUMO
Glycan antigens recognized by monoclonal antibodies have served as stem cell markers. To understand regulation of their biosynthesis and their roles in stem cell behavior precise assignments are required. We have applied state-of-the-art glycan array technologies to compare the glycans bound by five antibodies that recognize carbohydrates on human stem cells. These are: FC10.2, TRA-1-60, TRA-1-81, anti-i and R-10G. Microarray analyses with a panel of sequence-defined glycans corroborate that FC10.2, TRA-1-60, TRA-1-81 recognize the type 1-(Galß-3GlcNAc)-terminating backbone sequence, Galß-3GlcNAcß-3Galß-4GlcNAcß-3Galß-4GlcNAc, and anti-i, the type 2-(Galß-4GlcNAc) analog, Galß-4GlcNAcß-3Galß-4GlcNAcß-3Galß-4GlcNAc, and we determine substituents they can accommodate. They differ from R-10G, which requires sulfate. By Beam Search approach, starting with an antigen-positive keratan sulfate polysaccharide, followed by targeted iterative microarray analyses of glycan populations released with keratanases and mass spectrometric monitoring, R-10G is assigned as a mono-sulfated type 2 chain with 6-sulfation at the penultimate N-acetylglucosamine, Galß-4GlcNAc(6S)ß-3Galß-4GlcNAcß-3Galß-4GlcNAc. Microarray analyses using newly synthesized glycans corroborate the assignment of this unique determinant raising questions regarding involvement as a ligand in the stem cell niche.
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Anticorpos Monoclonais/metabolismo , Biomarcadores/análise , Células-Tronco Embrionárias/metabolismo , Polissacarídeos/análise , Antígenos de Superfície/metabolismo , Sequência de Carboidratos , Células Cultivadas , Células-Tronco Embrionárias/citologia , Humanos , Espectrometria de Massas , Polissacarídeos/imunologia , Análise Serial de Proteínas , Proteoglicanas/metabolismoRESUMO
Oligomannuronic acid (MOS) from seaweed has antioxidant and anti-inflammatory activities. In this study, MOS was activated at the terminal to obtain three different graft complexes modified with sialic acid moiety (MOS-Sia). The results show that MOS-Sia addition can reduce the ß-structure formation of Aß42, and the binding effect of MOS-Sia3 is more obvious. MOS-Sia conjugates also have a better complexing effect with Ca2+ while reducing the formation of Aß42 oligomers in solutions. MOS-Sia3 (25-50 µg/mL) can effectively inhibit the activation state of BV-2 cells stimulated by Aß42, whereas a higher dose of MOS-Sia3 (>50 µg/mL) can inhibit the proliferation of BV-2 cells to a certain extent. A lower dose of MOS-Sia3 can also inhibit the expression of IL-1ß, IL-6, TNF-α, and other proinflammatory factors in BV-2 cells induced by Aß42 activation. In the future, the MOS-Sia3 conjugate can be used to treat Alzheimer's disease.
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Ácido Algínico/metabolismo , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/farmacologia , Anti-Inflamatórios/farmacologia , Microglia/efeitos dos fármacos , Microglia/metabolismo , Ácido N-Acetilneuramínico/metabolismo , Fragmentos de Peptídeos/metabolismo , Fragmentos de Peptídeos/farmacologia , Agregados Proteicos/efeitos dos fármacos , Agregação Patológica de Proteínas/metabolismo , Doença de Alzheimer/metabolismo , Animais , Linhagem Celular Transformada , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Camundongos , Transdução de Sinais/efeitos dos fármacosRESUMO
OBJECTIVE: To explore the influence of social capital on the quality of life of patients with chronic non-communicable diseases. METHODS: A multi-phase stratified cluster sampling method was adopted to select the survey respondents. Professionally trained surveyors made home visits in order to conduct face-to-face questionnaire surveys in person. European Quality of Life Five Dimension Five Level Scale (EQ-5D-5L) and a self-developed social capital scale were used to investigate the quality of life and social capital of the respondents. Factor analysis and Cronbach's α coefficient test were done to verify the reliability and validity of the self-developed social capital scale. The χ 2 test and robust Tobit regression model were used to analyze the impact of social capital on the quality of life of patients with chronic non-communicable diseases. RESULTS: The self-developed social capital scale showed excellent performance. The Cronbach's α coefficient was 0.728, the KMO value was 0.716, and the result of Bartlett's test of sphericity was statistically significant ( P<0.001), indicating that the data were well suited for factor analysis. The four common factors cumulatively explained 68.27% of the total variation. The health utility value of the survey respondents was 0.869±0.181. Those who could walk around, shower and dress themselves, and perform usual activities without any problem accounted for 75.70%, 80.10%, and 74.1% of the respondents, respectively. Those who had pain or discomfort and anxiety or depression, with no self-perceived problem were 43.40% and 58.90%, respectively. In the EQ-5D-5L scale, the self-rated health influencing factors of the physical health dimension were community safety and interpersonal network relationships. The influencing factors of social function health was community safety and mental health was affected by community safety, community trust and interpersonal network relationships. When community safety improved by one level, the health utility value of patients with chronic non-communicable diseases increased by 0.046, and when interpersonal network relationships improved by an additional level, their health utility value increased by 0.037. CONCLUSION: The main problem of the quality of life of patients with chronic non-communicable diseases was found in the mental health dimension. In the process of treating chronic non-communicable diseases, attention should also be given to psychological counseling. Community safety and interpersonal network relationships are the protective factors for self-rated health status. Providing a safe community environment and expanding interpersonal networks help improve the health of patients.
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Qualidade de Vida , Capital Social , Doença Crônica , Nível de Saúde , Humanos , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: To understand the status of depression and its influencing factors in the middle-aged and older adult populations aged 45 and above in China on the basis of data from the 2018 China Family Panel Studies (CFPS), and to provide empirical evidence for the improvement of the mental health of the middle-aged and older adults and the alleviation of their depressive symptoms. METHODS: The source of the research data was the 2018 CFPS. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to assess the prevalence of depression. A two-level two-category unconditional logistics regression method was used to analyze the influencing factors of the prevalence of depressive symptoms. RESULTS: The 80th percentile interval score of depression score was used as the critical value, and the detection rate of depressive symptoms was 23.61%. It was more likely for women to suffer from depressive symptoms than it was for men. Widowed individuals were at an even higher risk for having depression. The more education one had, the lower the possibility of developing depression. Middle-aged and older adults in rural areas were more likely to suffer from depression. Middle-aged and older adults with chronic diseases and self-rated poor health were at higher risk of depression. Sleep time is a protective factor that suppressed symptoms. After controlling the above-mentioned individual-level factors, middle-aged and older adults in coastal and economically developed areas were less likely to suffer from depression than those from inland and economically underdeveloped areas did. CONCLUSION: The health departments concerned should focus on the depressive symptoms of women, widowed individuals, and middle-aged and older adults with chronic diseases. In rural areas and underdeveloped inland regions, the state should invest more health resources in the prevention and improvement of depression among middle-aged and older adults.
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Depressão , Idoso , China/epidemiologia , Doença Crônica , Depressão/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
Emerging evidence has reported that dysregulation of microRNAs (miRNAs) participated in the development of diverse types of cancers. Our initial microarray-based analysis identified differentially expressed NEK2 related to breast cancer and predicted the regulatory microRNA-128-3p (miR-128-3p). Herein, this study aimed to characterize the tumour-suppressive role of miR-128-3p in regulating the biological characteristics of breast cancer stem cells (BCSCs). CD44ï¼ CD24-/low cells were selected for subsequent experiments. After verification of the target relationship between miR-128-3p and NEK2, the relationship among miR-128-3p, NEK2 and BCSCs was further investigated with the involvement of the Wnt signalling pathway. The regulatory effects of miR-128-3p on proliferation, migration, invasion and self-renewal in vitro as well as tumorigenicity in vivo of BCSCs were examined via gain- and loss-of-function approaches. Highly expressed NEK2 was found in breast cancer based on GSE61304 expression profile. Breast cancer stem cells and breast cancer cells showed a down-regulation of miR-128-3p. Overexpression of miR-128-3p was found to inhibit proliferation, migration, invasion, self-renewal in vitro and tumorigenicity in vivo of BCSCs, which was further validated to be achieved through inhibition of Wnt signalling pathway by down-regulating NEK2. In summary, this study indicates that miR-128-3p inhibits the stem-like cell features of BCSCs via inhibition of the Wnt signalling pathway by down-regulating NEK2, which provides a new target for breast cancer treatment.
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Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Quinases Relacionadas a NIMA/genética , Células-Tronco Neoplásicas/patologia , Via de Sinalização Wnt , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/metabolismo , Sequência de Bases , Carcinogênese/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Autorrenovação Celular/genética , Feminino , Inativação Gênica , Humanos , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Modelos Biológicos , Quinases Relacionadas a NIMA/metabolismo , Invasividade Neoplásica , Células-Tronco Neoplásicas/metabolismo , Esferoides Celulares/metabolismo , Esferoides Celulares/patologia , Regulação para Cima/genéticaRESUMO
OBJECTIVE: To explore the reliability and validity of the EQ-5D-5L scale in the population of southwest China. METHODS: The internal consistency reliability is measured by Cronbach's α coefficient and the structural validity is measured by factor analysis. The difference in health utility value of different characteristic populations is compared by t test and analysis of variance. RESULTS: Cronbach's α coefficient was 0.857. Exploratory factor analysis extracts two common factors whose cumulative contribution rate is 77.311%. The first common factor represents mobility, self-care and uaual activities. The second common factor represents pain/discomfort and anxiety/depression. The results of confirmatory factor analysis showed that the correlation of the two common factors was 0.659, the average variance of the first common factor was 0.862 and the combination reliability was 0.949, and the average variance extracted of the second common factor was 0.587 and the composite reliability was 0.739. The factor loadings for mobility, self-care and uaual activities on the first common factor were 0.871, 0.945 and 0.967, respectively. The loadings for pain/discomfort and anxiety/depression on the second common factor were 0.708 and 0.820, respectively. CONCLUSION: EQ-5D-5L has good reliability and validity when it is applied to the measurement of healthy life quality of residents in Southwest China.
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Ansiedade , Depressão , Qualidade de Vida , Ansiedade/diagnóstico , China , Depressão/diagnóstico , Nível de Saúde , Humanos , Psicometria , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
Rad6 and Bre1, ubiquitin-conjugating E2 and E3 enzymes respectively, are responsible for histone H2B lysine 123 mono-ubiquitination (H2Bub1) in Saccharomyces cerevisiae. Previous studies have shown that Rad6 and Bre1 regulate telomere length and recombination. However, the underlying molecular mechanism remains largely unknown. Here we report that H2BK123 mutation results in telomere shortening, while inactivation of Ubp8 and/or Ubp10, deubiquitinases of H2Bub1, leads to telomere lengthening in Rad6-Bre1-dependent manner. In telomerase-deficient cells, inactivation of Rad6-Bre1 pathway retards telomere shortening rate and the onset of senescence, while deletion of UBP8 and/or UBP10 accelerates senescence. Thus, Rad6-Bre1 pathway regulates both telomere length and recombination through its role in H2Bub1. Additionally, inactivation of both Rad6-Bre1-H2Bub1 and Mre11-Rad50-Xrs2 (MRX) pathways causes synthetic growth defects and telomere shortening in telomerase-proficient cells, and significantly accelerates senescence and eliminates type II telomere recombination in telomerase-deficient cells. Furthermore, RAD6 or BRE1 deletion, or H2BK123R mutation decreases the accumulation of ssDNA at telomere ends. These results support the model that Rad6-Bre1-H2Bub1 cooperates with MRX to promote telomere-end resection and thus positively regulates both telomerase- and recombination-dependent telomere replication. This study provides a mechanistic link between histone H2B ubiquitination and telomere replication.
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Histonas/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Homeostase do Telômero , Telômero/metabolismo , Enzimas de Conjugação de Ubiquitina/metabolismo , Ubiquitinação , DNA de Cadeia Simples/metabolismo , Endopeptidases/metabolismo , Deleção de Genes , Viabilidade Microbiana , Proteínas Nucleares/metabolismo , Recombinação Genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/antagonistas & inibidores , Proteínas de Saccharomyces cerevisiae/genética , Encurtamento do Telômero , Proteínas de Ligação a Telômeros/genética , Ubiquitina Tiolesterase/metabolismo , Enzimas de Conjugação de Ubiquitina/antagonistas & inibidores , Enzimas de Conjugação de Ubiquitina/genéticaRESUMO
OBJECTIVE: To understand the effects of social capital on depressive symptoms of elderly patients with chronic diseases in urbanized communities, and to explore preventive measures to promote their mental health. METHODS: A multi-stage stratified cluster sampling method was used to extract 740 elderly patients with chronic diseases in the urbanized communities in Chengdu and Kunming. The questionnaire survey was conducted by using the center of depression rating scale (CES-D) and the self-made social capital scale. Multivariate unconditional logistic regression was used to analyze the impact of urbanized residents' social capital on depressive symptoms. RESULTS: The self-made social capital scale has good reliability and validity. The incidence of depressive symptoms in this study was 24.9%. The incidence of depressive symptoms in elderly females with chronic diseases was higher (P < 0.05); the residents with high "sense of social trust and security" had lower risk of incidence of depressive symptoms ãodds ratio (OR)=0.489ã; the residents with higher "community belonging" had a lower risk of incidence of depressive symptoms (OR=0.570), and the residents with higher "social support" scores had a lower risk of incidence of depressive symptoms (OR=0.233). CONCLUSION: Targeted measures should be taken to intervene in the social capital factors affecting the depressive symptoms of elderly patients with chronic diseases in urbanized communities to improve their mental health.
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Doença Crônica/psicologia , Depressão/epidemiologia , Capital Social , Idoso , China , Feminino , Humanos , Modelos Logísticos , Masculino , Reprodutibilidade dos Testes , Apoio Social , Inquéritos e Questionários , População UrbanaRESUMO
Paraneoplastic cerebellar degeneration (PCD) is one of the most common paraneoplastic neurological syndromes characterized by the rapid development of severe cerebellar ataxia. In this report, a 23-year-old female with noticeable dizziness and gait instability was described. The enhanced CT scanning suggested the presence of a pelvic tumor. Then, PCD was established. Postoperative pathological result defined it as a liposarcoma (LS) with dedifferentiation. Interestingly, clinical symptoms disappeared after the surgical removal of the pelvic tumor. To our knowledge, this was the first case report with PCD due to LS.