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Background and Aims: As practice patterns and hepatitis C virus (HCV) genotypes (GT) vary geographically, a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal. This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs, focusing on GT3 and GT6. Methods: We analyzed the sustained virological response (SVR12) of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific, North America, and Europe between 07/01/2014-07/01/2021. Results: The mean age was 62±13 years, with 49.6% male. The demographic breakdown was 91.1% Asian (52.9% Japanese, 25.7% Chinese/Taiwanese, 5.4% Korean, 3.3% Malaysian, and 2.9% Vietnamese), 6.4% White, 1.3% Hispanic/Latino, and 1% Black/African-American. Additionally, 34.8% had cirrhosis, 8.6% had hepatocellular carcinoma (HCC), and 24.9% were treatment-experienced (20.7% with interferon, 4.3% with direct-acting antivirals). The largest group was GT1 (10,246 [64.6%]), followed by GT2 (3,686 [23.2%]), GT3 (1,151 [7.2%]), GT6 (457 [2.8%]), GT4 (47 [0.3%]), GT5 (1 [0.006%]), and untyped GTs (261 [1.6%]). The overall SVR12 was 96.9%, with rates over 95% for GT1/2/3/6 but 91.5% for GT4. SVR12 for GT3 was 95.1% overall, 98.2% for GT3a, and 94.0% for GT3b. SVR12 was 98.3% overall for GT6, lower for patients with cirrhosis and treatment-experienced (TE) (93.8%) but ≥97.5% for treatment-naive patients regardless of cirrhosis status. On multivariable analysis, advanced age, prior treatment failure, cirrhosis, active HCC, and GT3/4 were independent predictors of lower SVR12, while being Asian was a significant predictor of achieving SVR12. Conclusions: In this diverse multinational real-world cohort of patients with various GTs, the overall cure rate was 96.9%, despite large numbers of patients with cirrhosis, HCC, TE, and GT3/6. SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent (>91%).
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The visceral adiposity index (VAI) and handgrip strength (HGS) are identified as important objectives for the prevention of illness. Nevertheless, there is limited understanding regarding the impact of the VAI and HGS on cardiometabolic multimorbidity (CMM). We aimed to ascertain the impact of the VAI and HGS on CMM among middle-aged and older people. Data spanning from 2011 to 2020 were derived from the China Health and Retirement Longitudinal Study (CHARLS). In total, 7909 individuals aged 45 years and older were included. Cox proportional hazard regression was utilized to examine the correlation among the VAI, HGS, and CMM. Throughout the 10-year follow-up, we determined that both the VAI (HR = 1.330; 95%CI = 1.179-1.500) and HGS (HR = 0.745, 95%CI = 0.645-0.861) exhibited significant associations with CMM risk. Individuals exposed to both a high VAI and low HGS were found to have higher hazards of CMM (HR = 1.377, 95%CI = 1.120-1.694) in contrast to participants exposed to one or none of these conditions. The older (HR = 1.414; 95%CI = 1.053-1.899) and male (HR = 1.586; 95%CI = 1.114-2.256) groups are more likely to experience CMM risk. Our findings suggest that both the VAI and HGS have significant effects on CMM risk. Appropriate interventions focused on vulnerable groups are recommended to prevent the incidence of CMM.
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Fuerza de la Mano , Multimorbilidad , Humanos , Masculino , Persona de Mediana Edad , Femenino , Anciano , Estudios Longitudinales , China/epidemiología , Obesidad Abdominal/epidemiología , Grasa Intraabdominal , Enfermedades Cardiovasculares/epidemiología , Modelos de Riesgos ProporcionalesRESUMEN
The intricate structure of lignin in straw makes it challenging to hydrolyze, making it a key focus of current research. However, there has been limited study on the effect of enzyme inducer (MnSO4) combined with functional microorganisms on lignin degradation during straw composting. Based on this, four composting treatment groups were set up in this study. Control (CK), functional microorganism addition treatment (F), Mn2+ enzyme inducer (Mn), and Mn2+ enzyme inducer coupled with functional microorganism addition treatment (FMn) were tested for composting. Manganese(II)-coupled microorganisms improved lignin degradation: FMn > Mn > F > CK. They increased the lignin loss rate from 25.54 % to 42.61 %. Laccase activity increased from 3.45 to 43.74 U/g and manganese peroxidase activity increased from 145.52 to 264.91 U/g. And gene abundance was increased. Microbial community structure and dominant genera changed. Structural equations support the idea that functional microorganisms coupled with manganese can modify physicochemical indices, thereby regulating gene expression and enhancing enzyme activity. Furthermore, the stimulation of fungal growth and increased extracellular laccase and manganese peroxidase activities can affect the degradation of lignin. This study provides new insights and theoretical support for efficient lignin degradation and efficient resource utilization of compost products.
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Pulmonary hypertension (PH) is characterized by excessive proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs), in which inflammatory signaling caused by activation of the NF-κB pathway plays an important role. A20 is an important negative regulator of the NF-κB pathway, and zinc promotes the expression of A20 and exerts a protective effect against various diseases (e.g. COVID19) by inhibiting the inflammatory signaling. The role of A20 and intracellular zinc signaling in PH has been explored, but the extracellular zinc signaling is not well understood, and whether zinc has protective effects on PH is still elusive. Using inductively coupled plasma mass spectrometry (ICP-MS), we studied the alteration of trace elements during the progression of monocrotaline (MCT)-induced PH and found that serum zinc concentration was decreased with the onset of PH accompanied by abnormalities of other three elements, including copper, chromium, and magnesium. Zinc chloride injection with the dosage of 5 mg/kg intraperitoneally partially corrected this abnormality and inhibited the progression of PH. Zinc supplementation induced the expression of A20 in lung tissue and reduce the inflammatory responses. In vitro, zinc supplementation time-dependently upregulated the expression of A20 in PASMCs, therefore correcting the excessive proliferation and migration of cells caused by hypoxia. Using genetically encoded-FRET based zinc probe, we found that these effects of zinc ions are not achieved by entering cells, but most likely by activating cell surface zinc receptor (ZnR/GPR39). These results provide the first evidence of the effectiveness of zinc supplementation in the treatment of PH.
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Background: The most common metastatic site of follicular variant of papillary thyroid carcinoma (FVPTC) is the central lymph nodes, which may be associated with the prognosis and survival of patients. In the present study, we establish a combined model based on preoperative clinical and ultrasound (US) features of FVPTC to predict the risk of central lymph node metastasis (CLNM). Methods: From January 2013 to December 2022, 315 patients with FVPTC were enrolled and randomly divided into the training and validation cohorts in a ratio of 7:3. The independent risk factors for CLNM in FVPTC were analysed using univariate and multivariate logistic regression analyses. Then, three different models were established based on clinical and US data. Subsequently, a nomogram was constructed to predict CLNM. Its predictive effect was evaluated via receiver operating characteristic and calibration curve analyses. Results: Backward multivariate regression analysis revealed that age (P=0.001), thyroid peroxidase antibody (TPOAb) (P=0.11), diameter (P=0.047), irregular/lobulated margin (P=0.15), extrathyroidal extension (P=0.001), nodules with macrocalcifications (P=0.009), nodules with microcalcification (P=0.003) and Thyroid Imaging Reporting and Data System (ACR-TI-RADS) category 5 (P=0.33) were independent risk factors for CLNM in FVPTC. The areas under the curve of the matching nomogram in the training (N=221) and validation cohorts (N=94) were 0.841 [95% confidence interval (CI): 0.788-0.895] and 0.735 (95% CI: 0.621-0.872), respectively. Conclusions: Preoperative thyroid US provides useful features for prediction of CLNM. The nomogram constructed based on combining US and clinical features can better predict the risk of CLNM and may facilitate decision-making in clinical settings.
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High TRABD expression is associated with tau pathology in patients with Alzheimer's disease; however, the function of TRABD is unknown. Human TRABD encodes a mitochondrial outer-membrane protein. The loss of TRABD resulted in mitochondrial fragmentation, and TRABD overexpression led to mitochondrial clustering and fusion. The C-terminal tail of the TRABD anchored to the mitochondrial outer membrane and the TraB domain could form homocomplexes. Additionally, TRABD forms complexes with MFN2, MIGA2, and PLD6 to facilitate mitochondrial fusion. Flies lacking dTRABD are viable and have normal lifespans. However, aging flies exhibit reduced climbing ability and abnormal mitochondrial morphology in their muscles. The expression of dTRABD is increased in aged flies. dTRABD overexpression leads to neurodegeneration and enhances tau toxicity in fly eyes. The overexpression of dTRABD also increased reactive oxygen species (ROS), ATP production, and protein turnover in the mitochondria. This study suggested that TRABD-induced mitochondrial malfunctions contribute to age-related neurodegeneration.
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Drosophila melanogaster , Homeostasis , Mitocondrias , Especies Reactivas de Oxígeno , Animales , Mitocondrias/metabolismo , Humanos , Especies Reactivas de Oxígeno/metabolismo , Drosophila melanogaster/metabolismo , Proteínas tau/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Dinámicas Mitocondriales , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Membranas Mitocondriales/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Envejecimiento/metabolismo , GTP Fosfohidrolasas/metabolismoRESUMEN
Parkinson's disease (PD), the second most common neurodegenerative disorder, is linked to α-synuclein (α-Syn) aggregation. Despite no specific drug being available for its treatment, curcumin, from the spice turmeric, shows promise. However, its application in PD is limited by a lack of understanding of its anti-amyloidogenic mechanisms. In this study, we first reconstructed the liquid-liquid phase separation (LLPS) of α-Syn in vitro under different conditions, which may be an initial step in entraining the pathogenic aggregation. Subsequently, we evaluated the effects of curcumin on the formation of droplets, oligomers, and aggregated fibers during the LLPS of α-synuclein, as well as its impact on the toxicity of aggregated α-synuclein to cultured cells. Importantly, we found that curcumin can inhibit amyloid formation by inhibiting the occurrence of LLPS and the subsequent formation of oligomers of α-Syn in the early stages of aggregation. Finally, the molecular dynamic simulations of interactions between α-Syn decamer fibrils and curcumin showed that van der Waal's interactions make the largest contribution to the anti-aggregation effect of curcumin. These results may help to clarify the mechanism by which curcumin inhibits the formation of α-Syn aggregates during the development of PD.
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The preservation of fresh-cut fruits and vegetables has attracted attention to the shelf-life reduction caused by high humidity. Herein, alginate/copper ions cross-linking, in-situ growth and self-assembly techniques of metal-organic frameworks (MOFs) were utilized to prepare a moisture responsive hydrogel bead (HKUST-1@ALG). As the multistage porous structure formation, tea tree essential oil (TTO) load capacity in hydrogel bead (TTO-HKUST-1@ALG) was increased from 6.1% to 21.6%. TTO-HKUST-1@ALG had excellent moisture response performance, and the release rates of TTO increased from 33.89% to 70.98% with moisture increasing from 45% to 95%. Besides, TTO-HKUST-1@ALG exhibited excellent antimicrobial, antioxidant capacity, and biocompatibility. During storage, TTO-HKUST-1@ALG effectively improved the cell membrane integrity by maintaining the balance of reactive oxygen species metabolism. The degradation of cell wall structure and tissue softening were delayed by inhibiting the cell wall-degrading enzymes activity. Briefly, TTO-HKUST-1@ALG improved the storage quality and extended shelf-life of fresh-cut pineapple, which was a promising preservative.
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Ananas , Conservación de Alimentos , Hidrogeles , Estructuras Metalorgánicas , Aceites Volátiles , Ananas/química , Aceites Volátiles/química , Hidrogeles/química , Estructuras Metalorgánicas/química , Conservación de Alimentos/métodos , Conservación de Alimentos/instrumentación , Frutas/química , Antioxidantes/química , Conservantes de Alimentos/farmacología , Conservantes de Alimentos/químicaRESUMEN
BACKGROUND: Acute-on-chronic liver disease (AoCLD) accounts for the majority of patients hospitalized in the Department of Hepatology or Infectious Diseases. AIM: To explore the characterization of AoCLD to provide theoretical guidance for the accurate diagnosis and prognosis of AoCLD. METHODS: Patients with AoCLD from the Chinese Acute-on-Chronic Liver Failure (ACLF) study cohort were included in this study. The clinical characteristics and outcomes, and the 90-d survival rate associated with each clinical type of AoCLD were analyzed, using the Kaplan-Meier method and the log-rank test. RESULTS: A total of 3375 patients with AoCLD were enrolled, including 1679 (49.7%) patients with liver cirrhosis acute decompensation (LC-AD), 850 (25.2%) patients with ACLF, 577 (17.1%) patients with chronic hepatitis acute exacerbation (CHAE), and 269 (8.0%) patients with liver cirrhosis active phase (LC-A). The most common cause of chronic liver disease (CLD) was HBV infection (71.4%). The most common precipitants of AoCLD was bacterial infection (22.8%). The 90-d mortality rates of each clinical subtype of AoCLD were 43.4% (232/535) for type-C ACLF, 36.0% (36/100) for type-B ACLF, 27.0% (58/215) for type-A ACLF, 9.0% (151/1679) for LC-AD, 3.0% (8/269) for LC-A, and 1.2% (7/577) for CHAE. CONCLUSION: HBV infection is the main cause of CLD, and bacterial infection is the main precipitant of AoCLD. The most common clinical type of AoCLD is LC-AD. Early diagnosis and timely intervention are needed to reduce the mortality of patients with LC-AD or ACLF.
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BACKGROUND: Poor nurse-patient relationship poses an obstacle to care delivery, jeopardizing patient experience and patient care outcomes. Measuring nurse-patient relationship is challenging given its multi-dimensional nature and a lack of well-established scales. PURPOSE: This study aimed to develop a multi-dimensional scale measuring nurse-patient relationship in China. METHODS: A preliminary scale was constructed based on the existing literature and Delphi consultations with 12 nursing experts. The face validity of the scale was tested through a survey of 45 clinical nurses. This was followed by a validation study on 620 clinical nurses. Cronbach's α, content validity and known-group validity of the scale were assessed. The study sample was further divided into two for Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA), respectively, to assess the construct validity of the scale. RESULTS: The Nurse-Patient Relationship Scale (NPRS) containing 23 items was developed and validated, measuring five dimensions: nursing behavior, nurse understanding and respect for patient, patient misunderstanding and mistrust in nurse, communication with patient, and interaction with patient. The Cronbach's α of the NPRS ranged from 0.725 to 0.932, indicating high internal consistency. The CFA showed excellent fitness of data into the five-factor structure: χ2/df = 2.431, GFI = 0.933, TLI = 0.923, CFI = 0.939, IFI = 0.923, RMSEA = 0.070. Good content and construct validity are demonstrated through expert consensus and psychometric tests. CONCLUSION: The NPRS is a valid tool measuring nurse-patient relationship in China.
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An experiment was conducted to determine the effects of pressure loss, combined spacing, and. coefficients of uniformity on the dynamic fluidic sprinkler. Spline interpolation was used to convert the radial water volume into grid-type data and various pressure conditions were used to simulate the three-dimensional water distribution under square and triangular combinations of sprinklers. For each of the combinations of the sprinklers, experiments were performed at operating pressures of 0.15, 0.2, 0.25, and 0.3 MPa, respectively. To find the optimum spatial distribution of sprinklers, three different sprinkler intervals, 1R, 1.2R, and 1.4R, were performed for the square and triangular combinations. The droplet size distributions were also measured along a radial transect from the sprinkler for each operational pressure using the Thies Clima Laser Precipitation Monitor. The results demonstrated that the average values of the inclination angles of the water droplet trajectory curves were 60.78° and 68.85° as the pressure rose from 0.15 MPa to 0.3 MPa. When the pressure exceeds 0.2 MPa, the square combination's distribution uniformity coefficients of 25% low and high values were higher than those of the triangle combination. Triangular combination coefficients of uniformity (CU) values initially decreased and then increased as sprinkler spacing increased, with the CU value under 1.4R spacing reaching 73.85%. At a 1.2R interval, the CU value of a triangular combination was 8.49% lower than that of a square combination, which is a significant difference. Peak irrigation values for the square combination, when the pressure was changed from 0.1 to 0.3 MPa, were 29.97, 22.9, 19.8, 19.91, and 19.21 mm h-1, respectively. The CU values at 0.2, 0.25, and 0.3 MPa decreased at rates of 0.07%, 1.36%, and 0.8%, respectively, when the pressure was reduced by 10%.
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Targeted regulation of composting to convert organic matter into humic acid (HA) holds significant importance in compost quality. Owing to its low carbon content, chicken manure compost often requires carbon supplements to promote the humification progress. The addition of lignite can increase HA content through biotic pathways, however, its structure was not explored. The Parallel factor analysis revealed that lignite can significantly increase the complexity of highly humified components. The lignite addition improved phenol oxidase activity, particularly laccase, during the thermophilic and cooling phases. The abundance and transformation functions of core bacteria also indicated that lignite addition can influence the activity of microbial transformation of HA components. The structural equation model further confirmed that lignite addition had a direct and indirect impact on enhancing the complexity of HA components through core bacteria and phenol oxidase. Therefore, lignite addition can improve HA structure complexity during composting through biotic pathways.
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Compostaje , Sustancias Húmicas , Animales , Sustancias Húmicas/análisis , Suelo , Estiércol , Pollos , Carbón Mineral , Monofenol Monooxigenasa , CarbonoRESUMEN
Objectives: Invasive fungal super-infection (IFSI) is an added diagnostic and therapeutic dilemma. We aimed to develop and assess a nomogram of IFSI in patients with healthcare-associated bacterial infection (HABI). Methods: An ambispective cohort study was conducted in ICU patients with HABI from a tertiary hospital of China. Predictors of IFSI were selected by both the least absolute shrinkage and selection operator (LASSO) method and the two-way stepwise method. The predictive performance of two models built by logistic regression was internal-validated and compared. Then external validity was assessed and a web-based nomogram was deployed. Results: Between Jan 1, 2019 and June 30, 2023, 12,305 patients with HABI were screened in 14 ICUs, of whom 372 (3.0%) developed IFSI. Among the fungal strains causing IFSI, the most common was C.albicans (34.7%) with a decreasing proportion, followed by C.tropicalis (30.9%), A.fumigatus (13.9%) and C.glabrata (10.1%) with increasing proportions year by year. Compared with LASSO-model that included five predictors (combination of priority antimicrobials, immunosuppressant, MDRO, aCCI and S.aureus), the discriminability of stepwise-model was improved by 6.8% after adding two more predictors of COVID-19 and microbiological test before antibiotics use (P<0.01).And the stepwise-model showed similar discriminability in the derivation (the area under curve, AUC=0.87) and external validation cohorts (AUC=0.84, P=0.46). No significant gaps existed between the proportion of actual diagnosed IFSI and the frequency of IFSI predicted by both two models in derivation cohort and by stepwise-model in external validation cohort (P=0.16, 0.30 and 0.35, respectively). Conclusion: The incidence of IFSI in ICU patients with HABI appeared to be a temporal rising, and our externally validated nomogram will facilitate the development of targeted and timely prevention and control measures based on specific risks of IFSI.
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Infecciones Bacterianas , Infección Hospitalaria , Infecciones Fúngicas Invasoras , Humanos , Estudios de Cohortes , Nomogramas , Infección Hospitalaria/epidemiología , Unidades de Cuidados Intensivos , China/epidemiología , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/epidemiología , Atención a la SaludRESUMEN
Transport of microplastics (MPs) in coastal zones is influenced not only by their own characteristics, but also by the hydrodynamic conditions and coastal environment. In this article, we first summarized the source, distribution and abundance of MPs in coastal zones around the world through the induction of in-situ observation literature, and then comprehensively reviewed the different transports of MPs in coastal zones, including sedimentation, vertical mixing, resuspension, drift and biofouling. Afterwards, we conducted a comparative analysis of relevant experimental literature, and found that the current experimental research on microplastic transport mainly focused on the settling velocity under static water and the transport distribution under dynamic water. Based on the relevant literature on numerical simulation of microplastic transport in coastal zones, it was also found that the Euler-Lagrange method is the most widely used. The main influencing factor in the Euler method is hydrodynamic, while the Lagrange method and Euler-Lagrange method is hydrodynamic and microplastic particle characteristics. Tides in hydrodynamics are mentioned the most frequently, and the role of turbulence in almost all the literature. The density of MPs is the most influencing factor on transport results, followed by size, while shape is only studied in small-scale models. Some literature has also found that the influence of biofilms is mainly reflected in the changes in the density and size of MPs.
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Microplásticos , Contaminantes Químicos del Agua , Plásticos , Contaminantes Químicos del Agua/análisis , Monitoreo del Ambiente , AguaRESUMEN
INTRODUCTION: Obesity and constipation are both global problems, but the factors associated with constipation in individuals with obesity are currently understudied. The aim of our study was to explore the factors associated with constipation in people with obesity. METHODS: From three cycles of the National Health and Nutrition Examination Survey (NHANES) 2005-2010, data from 14,048 persons aged ≥20 years were collected. Variables included demographics, lifestyle, comorbidities, and dietary data. Multiple logistic regression analysis was used to calculate adjusted prevalence odds ratio (OR) and assess the relationship between different variables and constipation in population with obesity. RESULTS: Using stool consistency definition, multivariate analysis revealed that education ≥12th grade (OR: 0.456; 95% CI: 0.300, 0.694; p = 0.00024), hypertension (OR: 0.505; 95% CI: 0.334, 0.763; p = 0.00119), polypharmacy (OR: 1.669; 95% CI: 1.104, 2.521; p = 0.01507), high cholesterol (OR: 0.400; 95% CI: 0.213, 0.750; p = 0.00430), and high dietary fiber (OR: 0.454; 95% CI: 0.245, 0.841; p = 0.01206) were substantially linked with constipation in the population with obesity. For constipation defined using stool frequency, multivariate regression analysis show constipation in people with obesity had a significant association with the female sex (OR: 2.684; 95% CI: 1.379, 5.223; p = 0.00366 multivariate), Mexican American (OR: 0.142; 95% CI, 0.033, 0.616; p = 0.00914 multivariate), hypertension (OR: 0.569; 95% CI: 0.324, 0.998; p = 0.04916), depression (OR: 2.280; 95% CI: 1.240, 4.195; p = 0.00803), occasional/often milk consumption (OR: 0.473; 95% CI: 0.286, 0.782; p = 0.00356), medium energy (OR: 0.318; 95% CI: 0.118, 0.856; p = 0.02338), polypharmacy (OR: 1.939; 95% CI: 1.115, 3.373; p = 0.01907), and medium moisture (OR: 0.534; 95% CI: 0.285, 0.999; p = 0.04959). In nonobese people, constipation was significantly associated with the female sex and high moisture but not with hypertension and polypharmacy. CONCLUSION: This study suggests that the population with obesity has many factors that affect constipation such as hypertension, polypharmacy, cholesterol, dietary fiber, depression, and so on, of which hypertension and polypharmacy were significant associated with constipation, regardless of definitions of constipation. Notably, hypertension might be associated with a reduced risk of constipation in people with obesity.
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Estreñimiento , Hipertensión , Humanos , Femenino , Encuestas Nutricionales , Estreñimiento/epidemiología , Estreñimiento/etiología , Obesidad/complicaciones , Obesidad/epidemiología , Fibras de la Dieta , Hipertensión/epidemiología , Hipertensión/etiologíaRESUMEN
AIM: This study tested the mediating role of the nurse-patient relationship and self-rated health in the effect of emotional labour on turnover intention among nurses in China. BACKGROUND: The underlying mechanism behind the effect of emotional labour on turnover intention remains inadequately understood. INTRODUCTION: Nurses with a high level of emotional labour are predisposed to experiencing poor health and tension in their relationships with patients, which may increase turnover intention. METHODS: A cross-sectional survey of 527 nurses in a public tertiary hospital in Qiqihar, located in China's Heilongjiang province, was conducted. Emotional labour and turnover intention were assessed using existing validated scales containing multiple items, while the nurse-patient relationship and self-rated health were assessed using single items, respectively. Baron and Kenny's causal steps and the Karlson/Holm/Breen method were adopted to test the mediating effects of the nurse-patient relationship and self-rated health in the association between emotional labour and turnover intention after adjusting for variations in sociodemographic and job characteristics. RESULTS: Emotional labour was positively associated with turnover intention. Self-rated poor health and a disharmonious nurse-patient relationship partially mediated the positive effect of emotional labour on turnover intention. CONCLUSIONS: Emotional labour significantly affects the turnover intention of nurses working in public tertiary hospitals in China, and this effect is partially mediated by self-rated health and the nurse-patient relationship. IMPLICATIONS FOR NURSING PRACTICE AND NURSING POLICY: Giving more attention to nurses' negative emotions and work attitudes is crucial. Developing comprehensive strategies for enhancing nurses' emotional management ability, promoting their physical and psychological well-being, and improving nurse-patient relationship to reduce nurses' turnover.
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Stabilization of a G-quadruplex (G4) in the promotor of the c-MYC proto-oncogene leads to inhibition of gene expression, and it thus represents a potentially attractive new strategy for cancer treatment. However, most G4 stabilizers show little selectivity among the many G4s present in the cellular complement of DNA and RNA. Intriguingly, a crescent-shaped cell-penetrating thiazole peptide, TH3, preferentially stabilizes the c-MYC G4 over other promotor G4s, but the mechanisms leading to this selective binding remain obscure. To investigate these mechanisms at the atomic level, we performed an in silico comparative investigation of the binding of TH3 and its analogue TH1 to the G4s from the promotors of c-MYC, c-KIT1, c-KIT2, and BCL2. Molecular docking and molecular dynamics simulations, combined with in-depth analyses of non-covalent interactions and bulk and per-nucleotide binding free energies, revealed that both TH3 and TH1 can induce the formation of a sandwich-like framework through stacking with both the top and bottom G-tetrads of the c-MYC G4 and the adjacent terminal capping nucleotides. This framework produces enhanced binding affinities for c-MYC G4 relative to other promotor G4s, with TH3 exhibiting an outstanding binding priority. Van der Waals interactions were identified to be the key factor in complex formation in all cases. Collectively, our findings fully agree with available experimental data. Therefore, the identified mechanisms leading to specific binding of TH3 towards c-MYC G4 provide valuable information to guide the development of new selective G4 stabilizers.
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Genes myc , Simulación del Acoplamiento Molecular , Péptidos/farmacología , Tiazoles/farmacologíaRESUMEN
Phenolic acids are promising inhibitors of polyphenol oxidase (PPO), but the effects of carboxyl group and pH on their inhibition effects are still unclear. In this study, methyl cinnamate, cinnamic acid and 4-carboxycinnamic acid were investigated by their inhibitory effects with pH varied from 6.8 to 5.0. Results showed that 4-carboxycinnamic acid had the strongest inhibitory effect on PPO, followed by cinnamic acid and methyl cinnamate. Acidic pH enhanced the inhibitory effects of cinnamic acid and its derivatives on PPO, and the enhancement degree, IC50 and Ki declining degree were followed as 4-carboxycinnamic acid > cinnamic acid > methyl cinnamate. Methyl cinnamate exhibited competitive inhibition on PPO, while cinnamic acid and 4-carboxycinnamic acid exhibited mixed-type inhibition. Inhibitors induced slight changes in the secondary and tertiary structures of PPO, which were enhanced by acidic pH. Molecular docking results showed that 4-carboxycinnamic acid exhibited the strongest binding ability, and the main interaction forces were around carboxyl groups, and acidic pH enhanced the binding effect through more interactions and lower binding energy. This study could provide new insights into industrial application of cinnamic acid and its derivatives for the control of enzymatic browning of fruits and vegetables.
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Catecol Oxidasa , Cinamatos , Catecol Oxidasa/química , Simulación del Acoplamiento Molecular , Concentración de Iones de HidrógenoRESUMEN
Children, as a special group, have their own peculiarities in terms of individualized medication use compared to adults. Adverse drug reactions have been an important issue that needs to be addressed in the hope of safe medication use in children, and the occurrence of adverse drug reactions is partly due to genetic factors. Anti-infective drugs are widely used in children, and they have always been an important cause of the occurrence of adverse reactions in children. Pharmacogenomic technologies are becoming increasingly sophisticated, and there are now many guidelines describing the pharmacogenomics of anti-infective drugs. However, data from paediatric-based studies are scarce. This review provides a systematic review of the pharmacogenomics of anti-infective drugs recommended for gene-guided use in CPIC guidelines by exploring the relationship between pharmacogenetic frequencies and the incidence of adverse reactions, which will help inform future studies of individualized medication use in children.