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Red mud (RM), a hazardous solid waste generated in the alumina production process, of which the mineral composition is mainly hematite, is unable to be applied directly in the cement industry due to its high alkalinity. With the rise of geopolymers, RM-based grouting materials play an essential role in disaster prevention and underground engineering. To adequately reduce the land-based stockpiling of solid wastes, ultrafine calcium oxide, red mud, and slag were utilized as the main raw materials to prepare geopolymers, the C-R-S (calcium oxide-red mud-slag) grouting cementitious materials. The direct impact of red mud addition on the setting time, fluidity, water secretion, mechanical properties, and rheological properties of C-R-S were also investigated. In addition, a scanning electron microscope (SEM), X-ray diffraction (XRD), three-dimensional CT (3D-CT), Fourier transform infrared spectroscopy (FT-IR), and other characterization techniques were used to analyze the microstructure and polymerization mechanism. The related results reveal that the increase in red mud addition leads to an enhanced setting time, and the C-R-S-40 grouting cementitious material (40% red mud addition) exhibits the best fluidity of 27.5 cm, the lowest water secretion rate of 5.7%, and a high mechanical strength of 57.7 MPa. The C-R-S polymer grout conforms to the Herschel-Bulkley model, and the fitted value of R2 is above 0.99. All analyses confirm that the preparation process of C-R-S grouting cementitious material not only substantially improves the utilization rate of red mud, but also provides a theoretical basis for the high-volume application of red mud in the field of grouting.
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BACKGROUND: The triglyceride-glucose (TyG) index is linked to both the development and progression of diabetes, while obesity remains a significant risk factor for this disease. However, the relationship between the TyG index and overweight or obese diabetes remains unclear. METHODS: This study was a cross-sectional analysis of data from 40,633 participants with body mass index (BMI) ≥ 24 kg/m2 who were screened from January 2018 to December 2023 at Henan Provincial People's Hospital. Participants were divided into groups of overweight or obese individuals with diabetes and those without diabetes according to the diabetes diagnostic criteria. The TyG index, the dependent variable, was determined using the equation ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. We explored the association between TyG index and diabetes in overweight or obese individuals through multivariate logistic regression, subgroup analysis, generalized additive models, smoothed curve fitting, and analysis of threshold effects. RESULTS: Patients who were overweight or obese and had diabetes had higher TyG index levels than those without diabetes. After adjusting for confounders, our findings indicated a significant association between the TyG index and the risk of diabetes in overweight or obese individuals [odds ratio (OR) = 7.38, 95% confidence interval (CI): 6.98-7.81]. There was a J-shaped nonlinear association between TyG index and diabetes. When TyG index was > 4.46, the risk of diabetes increased sharply. Notably, a high baseline TyG index (Q4 group) correlated with a notably greater risk of diabetes than did the Q1 group, with an OR of 22.72 (95% CI: 20.52-25.16). Subgroup analysis revealed that the association between TyG and diabetes was stronger in females than in males (OR = 7.57, 95% CI: 6.76-8.48,), more significant in individuals with a BMI of 24-28 kg/m2 than in those with a BMI ≥ 28 kg/m2 (OR = 8.40, 95% CI: 7.83-9.02), and increased with age (OR = 8.15, 95% CI: 7.25-9.17) (all P for interaction < 0.001). CONCLUSION: Among overweight or obese individuals, a higher TyG index is associated with an elevated risk of diabetes, especially when TyG is > 4.46. Furthermore, factors such as sex, age, and BMI significantly influence the risk of diabetes in overweight or obese individuals. Specifically, older women with a BMI of 24-28 kg/m2 are at a greater risk of diabetes under similar TyG index conditions.
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BACKGROUND: The atherogenic index of plasma (AIP) is closely associated with the onset of diabetes, with obesity being a significant risk factor for type 2 diabetes mellitus (T2DM). However, the association between the AIP and T2DM in overweight and obese populations has been infrequently studied. Therefore, this study aimed to explore this association in overweight and obese individuals with T2DM. METHODS: This cross-sectional analysis utilized data from 40,633 participants with a body mass index (BMI) ≥ 24 kg/m2 who were screened from January 2018 to December 2023 at Henan Provincial People's Hospital. Participants were categorized into groups of overweight and obese individuals with and without diabetes according to the T2DM criteria. The AIP, our dependent variable, was calculated using the formula log10 [(TG mol/L)/HDL-C (mol/L)]. We investigated the association between the AIP and T2DM in overweight and obese individuals using multivariate logistic regression, subgroup analysis, generalized additive models, smoothed curve fitting, and threshold effect analysis. Additionally, mediation analysis evaluated the role of inflammatory cells in AIP-related T2DM. RESULTS: Overweight and obese patients with T2DM exhibited higher AIP levels than those without diabetes. After adjusting for confounders, our results indicated a significant association between the AIP and the risk of T2DM in overweight and obese individuals (odds ratio (OR) = 5.17, 95% confidence interval (CI) 4.69-5.69). Notably, participants with a high baseline AIP (Q4 group) had a significantly greater risk of T2DM than those in the Q1 group, with an OR of 3.18 (95% CI 2.94-3.45). Subgroup analysis revealed that the association between the AIP and T2DM decreased with increasing age (interaction P < 0.001). In overweight and obese populations, the association between AIP and T2DM risk displayed a J-shaped nonlinear pattern, with AIP > - 0.07 indicating a significant increase in T2DM risk. Various inflammatory cells, including neutrophils, leukocytes, and monocytes, mediated 4.66%, 4.16%, and 1.93% of the associations, respectively. CONCLUSION: In overweight and obese individuals, the AIP was independently associated with T2DM, exhibiting a nonlinear association. Additionally, the association between the AIP and T2DM decreased with advancing age. Multiple types of inflammatory cells mediate this association.
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Biomarcadores , Diabetes Mellitus Tipo 2 , Obesidad , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Aterosclerosis/epidemiología , Aterosclerosis/sangre , Aterosclerosis/diagnóstico , Biomarcadores/sangre , Índice de Masa Corporal , China/epidemiología , HDL-Colesterol/sangre , Estudios Transversales , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/epidemiología , Pueblos del Este de Asia , Obesidad/diagnóstico , Obesidad/sangre , Obesidad/epidemiología , Sobrepeso/epidemiología , Sobrepeso/sangre , Sobrepeso/diagnóstico , Sobrepeso/complicaciones , Pronóstico , Medición de Riesgo , Factores de Riesgo , Triglicéridos/sangreRESUMEN
BACKGROUND: The most near-term clinical application of genome-wide association studies in lung cancer is a polygenic risk score (PRS). METHODS: A case-control dataset was generated consisting of 4002 lung cancer cases from the LORD project and 20,010 ethnically matched controls from CARTaGENE. A genome-wide PRS including >1.1 million genetic variants was derived and validated in UK Biobank (n = 5419 lung cancer cases). The predictive ability and diagnostic discrimination performance of the PRS was tested in LORD/CARTaGENE and benchmarked against previous PRSs from the literature. Stratified analyses were performed by smoking status and genetic risk groups defined as low (<20th percentile), intermediate (20-80th percentile) and high (>80th percentile) PRS. FINDINGS: The phenotypic variance explained and the effect size of the genome-wide PRS numerically outperformed previous PRSs. Individuals with high genetic risk had a 2-fold odds of lung cancer compared to low genetic risk. The PRS was an independent predictor of lung cancer beyond conventional clinical risk factors, but its diagnostic discrimination performance was incremental in an integrated risk model. Smoking increased the odds of lung cancer by 7.7-fold in low genetic risk and by 11.3-fold in high genetic risk. Smoking with high genetic risk was associated with a 17-fold increase in the odds of lung cancer compared to individuals who never smoked and with low genetic risk. INTERPRETATION: Individuals at low genetic risk are not protected against the smoking-related risk of lung cancer. The joint multiplicative effect of PRS and smoking increases the odds of lung cancer by nearly 20-fold. FUNDING: This work was supported by the CQDM and the IUCPQ Foundation owing to a generous donation from Mr. Normand Lord.
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Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Neoplasias Pulmonares , Herencia Multifactorial , Fumar , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/etiología , Estudios de Casos y Controles , Fumar/efectos adversos , Fumar/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Anciano , Factores de Riesgo , Canadá/epidemiología , Polimorfismo de Nucleótido Simple , Francia/epidemiologíaRESUMEN
Rationale Dysanapsis refers to a mismatch between airway tree caliber and lung size arising early in life. Dysanapsis assessed by computed tomography (CT) is evident by early adulthood and associated with chronic obstructive pulmonary disease (COPD) risk later in life. Objective By examining the genetic factors associated with CT-assessed dysanapsis, we aimed to elucidate its molecular underpinnings and physiological significance across the lifespan. Methods We performed a genome-wide association study (GWAS) of CT-assessed dysanapsis in 11,951 adults, including individuals from two population-based and two COPD-enriched studies. We applied colocalization analysis to integrate GWAS and gene expression data from whole blood and lung. Genetic variants associated with dysanapsis were combined into a genetic risk score that was applied to examine association with lung function in children from a population-based birth cohort (n=1,278) and adults from the UK Biobank (n=369,157). Measurements and Main Results CT-assessed dysanapsis was associated with genetic variants from 21 independent signals in 19 gene regions, implicating HHIP, DSP, and NPNT as potential molecular targets based on colocalization of their expression. Higher dysanapsis genetic risk score was associated with obstructive spirometry among 5 year old children and among adults in the 5th, 6th and 7th decades of life. Conclusions CT-assessed dysanapsis is associated with variation in genes previously implicated in lung development and dysanapsis genetic risk is associated with obstructive lung function from early life through older adulthood. Dysanapsis may represent an endo-phenotype link between the genetic variations associated with lung function and COPD.
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BACKGROUND: Hypertension development is predominantly influenced by inflammation, excessive fat deposition, and metabolic irregularities. Among these factors, liver fat accumulation is a critical metabolic disorder. However, the quantification of liver fat levels and its associated risk for hypertension incidence remain ambiguous. This project is designed to explore the association between liver fat levels and the risk of hypertension in a healthy population. METHODS: This cross-sectional study involved 4955 participants from the Health Management Center at Henan Provincial People's Hospital who were surveyed between February 2020 and February 2023. Participants were categorized into four groups based on liver fat quartiles. Subgroup analyses, restricted cubic spline regression models, and logistic regression were utilized to assess the association between liver fat levels and hypertension risk. The relationships between liver fat levels and inflammatory markers were examined using multiple linear regression models. Additionally, a mediation analysis was conducted to explore the role of inflammatory factors in the relationship between liver fat and hypertension risk. RESULTS: Participants with hypertension exhibited greater liver fat levels than did those without hypertension. An increased risk of hypertension was associated with elevated liver fat levels, even after adjusting for other covariates [Q4 vs. Q1 in model II: odds ratio (ORâ=â1.28), 95% confidence interval (CI)â=â1.04-1.59, P â=â0.022; P for trendâ=â0.039]. A nonlinear relationship was observed between liver fat level and hypertension risk, with a notable increase in hypertension risk occurring at liver fat levels greater than 8.65%. Additionally, a positive correlation was found between inflammatory markers and liver fat levels. A mediation effect of 4.76% was noted, linking hypertension risk and liver fat levels through neutrophils. CONCLUSION: Liver fat levels exceeding 8.65% significantly elevated the risk of hypertension. Inflammatory factors serve as crucial mediators of the relationship between liver fat and hypertension.
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Hipertensión , Humanos , Hipertensión/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Estudios Transversales , China/epidemiología , Adulto , Factores de Riesgo , Hígado/patología , Hígado Graso , InflamaciónRESUMEN
BACKGROUND: Metabolic associated fatty liver disease (MAFLD) is a novel concept proposed in 2020, which is more practical for identifying patients with fatty liver disease with high risk of disease progression. Fatty liver is a driver for extrahepatic complications, particularly cardiovascular diseases (CVD). Although the risk of CVD in MAFLD could be predicted by carotid ultrasound test, a very early stage prediction method before the formation of pathological damage is still lacking. METHODS: Stool microbiomes and plasma metabolites were compared across 196 well-characterized participants encompassing normal controls, simple MAFLD patients, MAFLD patients with carotid artery pathological changes, and MAFLD patients with diagnosed coronary artery disease (CAD). 16S rDNA sequencing data and untargeted metabolomic profiles were interrogatively analyzed using differential abundance analysis and random forest (RF) machine learning algorithm to identify discriminatory gut microbiomes and metabolomic. RESULTS: Characteristic microbial changes in MAFLD patients with CVD risk were represented by the increase of Clostridia and Firmicutes-to-Bacteroidetes ratios. Faecalibacterium was negatively correlated with mean-intima-media thickness (IMT), TC, and TG. Megamonas, Bacteroides, Parabacteroides, and Escherichia were positively correlated with the exacerbation of pathological indexes. MAFLD patients with CVD risk were characterized by the decrease of lithocholic acid taurine conjugate, and the increase of ethylvanillin propylene glycol acetal, both of which had close relationship with Ruminococcus and Gemmiger. Biotin l-sulfoxide had positive correlation with mean-IMT, TG, and weight. The general auxin pesticide beta-naphthoxyacetic acid and the food additive glucosyl steviol were both positively correlated with the increase of mean-IMT. The model combining the metabolite signatures with 9 clinical parameters accurately distinguished MAFLD with CVD risk in the proband and validation cohort. It was found that citral was the most important discriminative metabolite marker, which was validated by both in vitro and in vivo experiments. CONCLUSIONS: Simple MAFLD patients and MAFLD patients with CVD risk had divergent gut microbes and plasma metabolites. The predictive model based on metabolites and 9 clinical parameters could effectively discriminate MAFLD patients with CVD risk at a very early stage.
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Heces , Microbioma Gastrointestinal , Humanos , Masculino , Femenino , Persona de Mediana Edad , Heces/microbiología , Metabolómica/métodos , Enfermedades Cardiovasculares/sangre , Biomarcadores/sangre , Medición de Riesgo , Estudios de Casos y Controles , Anciano , Valor Predictivo de las Pruebas , Bacterias , Factores de Riesgo de Enfermedad Cardiaca , Adulto , Enfermedad del Hígado Graso no Alcohólico/sangre , Aprendizaje Automático , Grosor Intima-Media CarotídeoRESUMEN
Rechargeable aqueous zinc-ion batteries (RAZIBs) are attractive due to their affordability, safety, and eco-friendliness. However, their potential is limited by the lack of high-capacity cathodes and compatible electrolytes needed for reliable performance. Herein, we have presented a compatibility strategy for the development of a durable and long-lasting RAZIBs. The covalent organic frameworks (COFs) based on anthraquinone (DAAQ-COF) is created and utilized as the cathode, with zinc metal serving as the anode. The electrolyte is made up of an aqueous solution containing zinc salts at various concentrations. The COF cathode has been designed to be endowed with a rich array of redox-active groups, enhancing its electrochemical properties. Meanwhile, the electrolyte is formulated using triflate anions, which have exhibited superiority over sulfate anions. This strategy lead to the development of an optimized COF cathode with fast charging capability, high Coulombic efficiency (nearly 100 %) and long-term cyclability (retention rate of nearly 100 % at 1â A g-1 after 10000 cycles). Moreover, through experimental analysis, a co-insertion mechanism involving Zn2+ and H+ in this cathode is discovered for the first time. These findings represent a promising path for the advancement of organic cathode materials in high-performance and sustainable RAZIBs.
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There is currently no medical therapy to prevent calcific aortic valve stenosis (CAVS). Multi-omics approaches could lead to the identification of novel molecular targets. Here, we perform a genome-wide association study (GWAS) meta-analysis including 14,819 cases among 941,863 participants of European ancestry. We report 32 genomic loci, among which 20 are novel. RNA sequencing of 500 human aortic valves highlights an enrichment in expression regulation at these loci and prioritizes candidate causal genes. Homozygous genotype for a risk variant near TWIST1, a gene involved in endothelial-mesenchymal transition, has a profound impact on aortic valve transcriptomics. We identify five genes outside of GWAS loci by combining a transcriptome-wide association study, colocalization, and Mendelian randomization analyses. Using cross-phenotype and phenome-wide approaches, we highlight the role of circulating lipoproteins, blood pressure and inflammation in the disease process. Our findings pave the way for the development of novel therapies for CAVS.
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Estenosis de la Válvula Aórtica , Válvula Aórtica , Válvula Aórtica/patología , Calcinosis , Humanos , Válvula Aórtica/metabolismo , Estudio de Asociación del Genoma Completo , Estenosis de la Válvula Aórtica/genética , GenómicaRESUMEN
According to recent research, metabolic-associated fatty liver disease (MAFLD) has emerged as an important underlying etiology of hepatocellular carcinoma (HCC). However, the molecular mechanism of MAFLD-HCC is still unclear. Tumor necrosis factor receptor-associated factor 2 (TRAF2) is the key molecule to mediate the signal of inflammatory NF-κB pathway. This study aims to investigate the potential dysregulation of TRAF2 and its biological function in MAFLD-HCC. Huh7 TRAF2-/- demonstrated increased tumor formation ability compared to huh7 TRAF2+/+ when stimulated with transforming growth factor-ß (TGF-ß). The decisive role of TGF-ß in the development of MAFLD-HCC was confirmed through the specific depletion of TGF-ß receptor II gene in the hepatocytes (Tgfbr2ΔHep) of mice. In TRAF2-/- cells treated with TGF-ß, both the glycolysis rate and lipid synthesis were enhanced. We proved the signal of the mechanistic target of rapamycin complex 1 (mTORC1) could be activated in the presence of TGF-ß, and was enhanced in TRAF2-/- cells. The coimmunoprecipitation (co-IP) experiments revealed that TRAF2 fortified the Smurf2-mediated ubiquitination degradation of AXIN1. Hence, TRAF2 depletion resulted in increased Smad7 degradation induced by AXIN1, thus promoting the TGF-ß signal. We also discovered that PLX-4720 could bind with AXIN1 and restrained the tumor proliferation of TRAF2-/- in mice fed with high-fat diet (HFD). Our findings indicate that TRAF2 plays a significant role in the pathogenesis of MAFLD-HCC. The reduction of TRAF2 expression leads to the enhancement of the TGF-ß-mTORC1 pathway by facilitating AXIN1-mediated Smad7 degradation.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Ratones , Animales , Carcinoma Hepatocelular/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Factor 2 Asociado a Receptor de TNF/genética , Factor 2 Asociado a Receptor de TNF/metabolismo , Neoplasias Hepáticas/metabolismo , Hepatocitos/metabolismo , Proteína smad7/genética , Proteína smad7/metabolismoRESUMEN
The recent European Respiratory Society statement on familial pulmonary fibrosis supports the need for genetic testing in the care of patients and their relatives. However, no solution (i.e., a concrete test) was provided to implement genetic testing in daily practice. Herein, we tabulated and standardized the nomenclature of 128 genetic variants in 20 genes implicated in adult-onset pulmonary fibrosis. The objective was to develop a laboratory-developed test (LDT) on the basis of standard Sanger sequencing to capture all known familial pulmonary fibrosis-associated variants. Targeted DNA fragments were amplified using harmonized PCR conditions to perform the LDT in a single 96-well plate. The new genetic test was evaluated in 62 sporadic cases of idiopathic pulmonary fibrosis. As expected in this population, we observed a low yield of disease-causing mutations. More important, 100% of targeted variants by the LDT were successfully evaluated. Furthermore, four variants of uncertain significance with in silico-predicted deleterious scores were identified in three patients, suggesting novel pathogenic variants in genes known to cause idiopathic pulmonary fibrosis. Finally, the MUC5B promoter variant rs35705950 was strongly enriched in these patients with a minor allele frequency of 41.1% compared with 10.6% in a matched population-based cohort (n = 29,060), leading to an estimation that this variant may explain up to 35% of the population-attributable risk. This LDT provides a solution for rapid clinical translation. Technical laboratory details are provided so that specialized pulmonary centers can implement the LDT in house to expedite the clinical recommendations of expert panels.
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Predisposición Genética a la Enfermedad , Pruebas Genéticas , Fibrosis Pulmonar Idiopática , Mucina 5B , Humanos , Fibrosis Pulmonar Idiopática/genética , Masculino , Femenino , Pruebas Genéticas/métodos , Mucina 5B/genética , Persona de Mediana Edad , Frecuencia de los Genes , Mutación/genética , Anciano , Adulto , Regiones Promotoras Genéticas/genéticaRESUMEN
BACKGROUND: The association between lipid and bone metabolism, particularly the role of high-density lipoprotein cholesterol (HDL-C) in regulating bone mineral density (BMD), is of significant interest. Despite numerous studies, findings on this relationship remain inconclusive, especially since evidence from large, sexually diverse Chinese populations is sparse. This study, therefore, investigates the correlation between HDL-C and lumbar BMD in people of different genders using extensive population-based data from physical examinations conducted in China. METHODS: Data from a cross-sectional survey involving 20,351 individuals aged > = 20 years drawn from medical records of health check-ups at the Health Management Centre of the Henan Provincial People's Hospital formed the basis of this study. The primary objective was to determine the correlation between HDL-C levels and lumbar BMD across genders. The analysis methodology included demographic data analysis, one-way ANOVA, subgroup analyses, multifactorial regression equations, smoothed curve fitting, and threshold and saturation effect analyses. RESULTS: Multifactorial regression analysis revealed a significant inverse relationship between HDL-C levels and lumbar BMD in both sexes, controlling for potential confounders (Male: ß = -8.77, 95% CI -11.65 to -5.88, P < 0.001; Female: ß = -4.77, 95% CI -8.63 to -0.90, P = 0.015). Subgroup and threshold saturation effect analyses indicated a stronger association in males, showing that increased HDL-C correlates with reduced lumbar BMD irrespective of age and body mass index (BMI). The most significant effect was observed in males with BMI > 28 kg/m2 and HDL-C > 1.45 mmol/L and in females with a BMI between 24 and 28 kg/m2. CONCLUSION: Elevated HDL-C is associated with decreased bone mass, particularly in obese males. These findings indicate that individuals with high HDL-C levels should receive careful clinical monitoring to mitigate osteoporosis risk. TRIAL REGISTRATION: The research protocol received ethics approval from the Ethics Committee at Beijing Jishuitan Hospital, in conformity with the Declaration of Helsinki guidelines (No. 2015-12-02). These data are a contribution of the China Health Quantitative CT Big Data Research team, registered at clinicaltrials.gov (code: NCT03699228).
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Densidad Ósea , HDL-Colesterol , Pueblos del Este de Asia , Femenino , Humanos , Masculino , China , HDL-Colesterol/sangre , Estudios TransversalesRESUMEN
In this study, we conducted measurements of the independent fission cross-sections of 238U(n, f)97m+gNb, 238U(n, f)133gTe reactions and the cumulative cross section of 238U(n, f)130gSb reactions induced by neutron at energies around 14 MeV, i.e., 14.1 ± 0.3, 14.5 ± 0.3 and 14.7 ± 0.3 MeV. The measurement results were obtained by the neutron activation method in combination with off-line γ-ray spectrometry techniques. The neutron flux was monitored on line by the accompanying α-particle from T(d, n)4He reaction, and the neutron energies were determined by the cross-section ratio of 90Zr(n, 2n)8+gZr to 93Nb(n, 2n)92mNb reactions. The independent fission cross-sections of the fission reactions were obtained by subtracting the influence of precursor nuclei or excited states. The obtained results are as follows: for 238U(n, f)97m+gNb, the independent cross sections are 1.0 ± 0.89, 0.98 ± 0.85 and 0.78 ± 0.70 mb at the specified neutron energy points. For 238U(n, f)133gTe, the independent fission cross-sections are 26.8 ± 2.8, 27.7 ± 2.9 and 20.5 ± 2.3 mb, respectively, at the same neutron energy points. As for 238U(n, f)130gSb, the obtained cumulative fission cross-sections are 5.35 ± 0.58, 5.05 ± 0.53 and 4.03 ± 0.44 mb, respectively, at the specified neutron energy points.
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BACKGROUND: The impact of total cholesterol (TC) on lumbar bone mineral density (BMD) is a topic of interest. However, empirical evidence on this association from demographic surveys conducted in China is lacking. Therefore, this study aimed to examine the relationship between serum TC and lumbar BMD in a sample of 20,544 Chinese adults between the ages of 20 and 80 years over a period of 5 years, from February 2018 to February 2023. Thus, we investigated the effect of serum TC level on lumbar BMD and its relationship with bone reduction in a Chinese adult population. METHODS: This cross-sectional study used data obtained from the Department of Health Management at Henan Provincial People's Hospital between February 2018 and February 2023. The aim of this study was to examine the correlation between serum TC and lumbar BMD in individuals of different sexes. The research methodology encompassed population description, analysis of stratification, single-factor and multiple-equation regression analyses, smooth curve fitting, and analysis of threshold and saturation effects. The R and EmpowerStats software packages were used for statistical analysis. RESULTS: After adjusting for confounding variables, a multiple linear regression model revealed a significant correlation between TC and lumbar BMD in men. In subgroup analysis, serum TC was found to have a positive association with lumbar BMD in men, specifically those aged 45 years or older, with a body mass index (BMI) ranging from 24 to 28 kg/m2. A U-shaped correlation arose between serum TC and lumbar BMD was detected in women of different ages and BMI, the inflection point was 4.27 mmol/L for women aged ≥ 45 years and 4.35 mmol/L for women with a BMI of ≥ 28 kg/m2. CONCLUSION: In this study, Chinese adults aged 20-80 years displayed different effects of serum TC on lumbar BMD in sex-specific populations. Therefore, monitoring BMI and serum TC levels in women of different ages could prevent osteoporosis and osteopenia. TRIAL REGISTRATION: The research protocol was approved by the Ethics Committee of Beijing Jishuitan Hospital, in accordance with the Declaration of Helsinki guidelines (No. 2015-12-02). These data are part of the China Health Quantitative CT Big Data Research team, which has been registered at clinicaltrials.gov (code: NCT03699228).
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Densidad Ósea , Colesterol , Osteoporosis , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Colesterol/sangre , Estudios Transversales , Pueblos del Este de Asia , Vértebras Lumbares/diagnóstico por imagen , Osteoporosis/diagnóstico por imagenRESUMEN
Background: Intermittent energy restriction (IER) is an effective weight loss strategy. However, the accompanying changes in spontaneous neural activity are unclear, and the relationship among anthropometric measurements, biochemical indicators, and adipokines remains ambiguous. Methods: Thirty-five obese adults were recruited and received a 2-month IER intervention. Data were collected from anthropometric measurements, blood samples, and resting-state functional magnetic resonance imaging at four time points. The regional homogeneity (ReHo) method was used to explore the effects of the IER intervention. The relationships between the ReHo values of altered brain regions and changes in anthropometric measurements, biochemical indicators, and adipokines (leptin and adiponectin) were analyzed. Results: Results showed that IER significantly improved anthropometric measurements, biochemical indicators, and adipokine levels in the successful weight loss group. The IER intervention for weight loss was associated with a significant increase in ReHo in the bilateral lingual gyrus, left calcarine, and left postcentral gyrus and a significant decrease in the right middle temporal gyrus and right cerebellum (VIII). Follow-up analyses showed that the increase in ReHo values in the right LG had a significant positive correlation with a reduction in Three-factor Eating Questionnaire (TFEQ)-disinhibition and a significant negative correlation with an increase in TFEQ-cognitive control. Furthermore, the increase in ReHo values in the left calcarine had a significant positive correlation with the reduction in TFEQ-disinhibition. However, no significant difference in ReHo was observed in the failed weight loss group. Conclusion: Our study provides objective evidence that the IER intervention reshaped the ReHo of some brain regions in obese individuals, accompanied with improved anthropometric measurements, biochemical indicators, and adipokines. These results illustrated that the IER intervention for weight loss may act by decreasing the motivational drive to eat, reducing reward responses to food cues, and repairing damaged food-related self-control processes. These findings enhance our understanding of the neurobiological basis of IER for weight loss in obesity.
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Recently the roles of gut microbiota are highly regarded in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). The intestinal bacteria regulate the metabolism of bile acids depending on bile salt hydrolase (BSH), 7-dehydroxylation, hydroxysteroid dehydrogenase (HSDH), or amide conjugation reaction, thus exerting effects on NAFLD development through bile acid receptors such as farnesoid X receptor (FXR), Takeda G-protein-coupled bile acid protein 5 (TGR5), and vitamin D receptor (VDR), which modulate nutrient metabolism and insulin sensitivity via interacting with downstream molecules. Reversely, the composition of gut microbiota is also affected by the level of bile acids in turn. We summarize the mutual regulation between the specific bacteria and bile acids in NAFLD and the latest clinical research based on microbiota and bile acids, which facilitate the development of novel treatment modalities in NAFLD.
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Pulmonary surfactant is a lipoprotein synthesized and secreted by alveolar type II cells in lung. We evaluated the associations between 200,139 single nucleotide polymorphisms (SNPs) of 40 surfactant-related genes and lung cancer risk using genotyped data from two independent lung cancer genome-wide association studies. Discovery data included 18,082 cases and 13,780 controls of European ancestry. Replication data included 1,914 cases and 3,065 controls of European descent. Using multivariate logistic regression, we found novel SNPs in surfactant-related genes CTSH [rs34577742 C > T, odds ratio (OR) = 0.90, 95% confidence interval (CI) = 0.89-0.93, P = 7.64 × 10-9] and SFTA2 (rs3095153 G > A, OR = 1.16, 95% CI = 1.10-1.21, P = 1.27 × 10-9) associated with overall lung cancer in the discovery data and validated in an independent replication data-CTSH (rs34577742 C > T, OR = 0.88, 95% CI = 0.80-0.96, P = 5.76 × 10-3) and SFTA2 (rs3095153 G > A, OR = 1.14, 95% CI = 1.01-1.28, P = 3.25 × 10-2). Among ever smokers, we found SNPs in CTSH (rs34577742 C > T, OR = 0.89, 95% CI = 0.85-0.92, P = 1.94 × 10-7) and SFTA2 (rs3095152 G > A, OR = 1.20, 95% CI = 1.14-1.27, P = 4.25 × 10-11) associated with overall lung cancer in the discovery data and validated in the replication data-CTSH (rs34577742 C > T, OR = 0.88, 95% CI = 0.79-0.97, P = 1.64 × 10-2) and SFTA2 (rs3095152 G > A, OR = 1.15, 95% CI = 1.01-1.30, P = 3.81 × 10-2). Subsequent transcriptome-wide association study using expression weights from a lung expression quantitative trait loci study revealed genes most strongly associated with lung cancer are CTSH (PTWAS = 2.44 × 10-4) and SFTA2 (PTWAS = 2.32 × 10-6).
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Neoplasias Pulmonares , Surfactantes Pulmonares , Humanos , Estudio de Asociación del Genoma Completo , Pulmón/metabolismo , Genotipo , Surfactantes Pulmonares/metabolismo , Tensoactivos/metabolismo , Polimorfismo de Nucleótido Simple , Predisposición Genética a la Enfermedad , Catepsina H/genética , Catepsina H/metabolismoRESUMEN
Real-time functional MRI neurofeedback (rtfMRI-NF) is a noninvasive technique that extracts concurrent brain states and provides feedback to subjects in an online method. Our study aims to investigate the effect of rtfMRI-NF on amygdala-based emotion self-regulation by analyzing resting-state functional connectivity. We conducted a task experiment to train subjects in self-regulating amygdala activity in response to emotional stimuli. Twenty subjects were divided into two groups. The up-regulate group (URG) viewed positive stimulus, while the down-regulate group (DRG) viewed negative stimulus. The rtfMRI-NF experiment paradigm consisted of three conditions. The URG's percent amplitude fluctuation (PerAF) scores are significant, indicating that positive emotions may be a partial side effect, with increased activity in the left hemisphere. Resting-state functional connectivity was analyzed via a paired-sample t-test before and after neurofeedback training. Brain network properties and functional connectivity analysis showed a significant difference between the default mode network (DMN) and the brain region associated with the limbic system. These results reveal to some extent the mechanism of neurofeedback training to improve individuals' emotional regulate regulation ability. Our study has shown that rtfMRI-neurofeedback training can effectively enhance the ability to voluntarily control brain responses. Furthermore, the results of the functional analysis have revealed distinct changes in the amygdala functional connectivity circuits following rtfMRI-neurofeedback training. These findings may suggest the potential clinical applications of rtfMRI-neurofeedback as a new therapy for emotionally related mental disorders.
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Regulación Emocional , Humanos , Amígdala del Cerebelo/diagnóstico por imagen , Sistema Límbico , Emociones , Imagen por Resonancia MagnéticaRESUMEN
As an emerging two-dimensional material, MXenes exhibit enormous potentials in the fields of energy storage and conversion, due to their superior conductivity, effective surface chemistry, accordion-like layered structure, and numerous ordered nanochannels. However, interlayer accumulation and chemical sluggishness of structural elements have hampered the demonstration of the superiorities of MXenes. By metal preintercalation and in situ electrochemical oxidization strategies on V2 CTx , MXene has enlarged its interplanar spacing and excited the outermost vanadium atoms to achieve frequent transfer and high storage capacity of Zn ions in aqueous zinc-ion batteries (ZIBs). Benefiting from the synergistic effects of these strategies, the resulting VOx /Mn-V2 C electrode exhibits the high capacity of 530 mA h g-1 at 0.1 A g-1 , together with a remarkable energy density of 415 W h kg-1 and a power density of 5500 W kg-1 . Impressively, the electrode delivers excellent cycling stability with Coulombic efficiency of nearly 100% in 2000 cycles at 5 A g-1 . The satisfactory electrochemical performances bear comparison with those in reported vanadium-based and MXene-based aqueous ZIBs. This work provides a new methodology for safe preparation of outstanding vanadium-based electrodes and extends the applications of MXenes in the energy storage field.
RESUMEN
Hematopoietic stem cells (HSCs) transplantation is an established therapy for many diseases of the hematopoietic system, for example aplastic anemia, acute myeloid leukemia and acute lymphoblastic leukemia. With the development of the HSCs research, HSCs provide an attractive method for treating hereditary blood disorders and immunotherapy of cancer by introducing gene modification. Compared with allogenic HSCs transplantation, using autologous HSCs or HSCs from induced pluripotent stem cells (iPSCs) would eliminate the probability of alloimmunization and transfusion-transmitted infectious diseases. The methods for obtaining autologous HSCs include amplifying patients' HSCs or inducing patients' somatic cells to HSCs (graph abstract). However, the biggest problem is inducing HSCs to proliferate in vitro and maintaining their stemness at the same time. Although many tests have been made to transform iPSCs to HSCs, the artificially generated HSCs still have substantial disparity compared with physiological HSCs. This review summarized the application status and obstacles to implantation of autologous HSCs and iPSC-derived HSCs. Meanwhile, we summarized the latest research progress in HSCs amplification and iPSCs reprogramming methods, which will help to solve the problems mentioned above.