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Abstract Background The Metabolic Insulin Resistance Score (METS-IR) is a non-invasive proxy for insulin resistance (IR) that has been newly developed in recent years and has been shown to be associated with diabetes risk. Our aim was to assess the predictive value of METS-IR for the future development of diabetes and its temporal differences in people of different sex, age, and body mass index (BMI). Methods The current study included 15,453 baseline non-diabetic subjects in the NAGALA cohort and then grouped according to the World Health Organization’s (WHO) recommended criteria for age and BMI. Multivariate Cox regression and time-dependent receiver operator characteristics (ROC) curves were used to analyze the value of METS-IR in assessing and predicting the risk of diabetes in people of different sexes, ages, and BMIs. Results 373 individuals developed diabetes during the observation period. By multivariate COX regression analysis, the development of future diabetes was significantly associated with increased METS-IR, and this positive association was stronger in women than in men and in individuals

Abstract Aims The value of the systemic immune‐inflammatory index (SII) in assessing adverse outcomes in various cardiovascular diseases has been extensively discussed. This study aims to evaluate the predictive value and risk stratification ability of SII for 30 day mortality in patients with acute decompensated heart failure (ADHF). Methods This analysis included 1452 patients hospitalized for ADHF, all the participants being part of the China Jiangxi‐acute decompensated heart failure1 project. The risk stratification capability of the SII in patients with ADHF, as well as its correlation with the 30 day mortality risk among ADHF patients, was evaluated utilizing Kaplan–Meier survival analysis and multivariable Cox regression models. A restricted cubic spline was employed to model the dose–response relationship between the two, and the receiver operating characteristic curve was utilized to assess the predictive ability of SII for 30 day mortality. Results The Kaplan–Meier analysis revealed that the risk of mortality in the high SII group (SII ≥ 980 × 109/L) was significantly greater than that in the low SII group (SII

Abstract Background Glycotoxicity and lipotoxicity are key pathophysiological mechanisms underlying the development of metabolic associated fatty liver disease (MAFLD). The primary objective of this study is to investigate the association between the newly proposed Plasma-Glycosylated Hemoglobin A1c/High-Density Lipoprotein Cholesterol Ratio (HbA1c/HDL-C ratio) and the risk of MAFLD. Methods A study population of 14,251 individuals undergoing health examinations was included. The association between the HbA1c/HDL-C ratio and MAFLD was analyzed using multivariable logistic regression and restricted cubic spline (RCS) analysis. Exploratory analyses were conducted to assess variations in this association across subgroups stratified by gender, age, body mass index (BMI), exercise habits, drinking status, and smoking status. The discriminatory value of the HbA1c/HDL-C ratio and its components for screening MAFLD was evaluated using receiver operating characteristic (ROC) curves. Results A total of 1,982 (13.91%) subjects were diagnosed with MAFLD. After adjusting for confounding factors, we found a significant positive association between the HbA1c/HDL-C ratio and MAFLD [odds ratio (OR) 1.34, 95% confidence interval (CI): 1.25, 1.44]. No significant differences in this association were observed across all subgroups (All P for interaction > 0.05). Furthermore, through RCS analysis, we observed a nonlinear positive correlation between the HbA1c/HDL-C ratio and MAFLD (P for non-linearity

Purpose: To establish a radiomics model using radiomics features from different region of interests (ROI) based on dosimetry-related regions in enhanced computed tomography (CT) simulated images to predict radiation pneumonitis (RP) in patients with non-small cell lung cancer (NSCLC). Methods: Our retrospective study was conducted based on a cohort of 236 NSCLC patients (59 of them with RP≥2) who were treated in 2 institutions and divided into the primary cohort (n = 182,46 of them with RP≥2) and external validation cohort (n = 54,13 of them with RP≥2). Radiomic features extracted from three ROIs were defined as the whole lung (WL), the dose volume histogram (DVH) of the lung V20 (V20_Lung) and the DVH of the V30 of lung minus the planning target volume (PTV) (V30 Lung-PTV). A total of 107 radiomics features were extracted from each ROIs. The U test, correlation coefficient and least absolute shrinkage and selection operator (LASSO) were performed for features selection. Six models based on different classification algorithms were developed to select the best radiomics model (R model).In addition, we built a dosimetry model then combined it with the best R model to create a mixed model (R+D model) The receiver operating characteristic (ROC) curve was delineated to assess the predictive efficacy of the models. Decision curve analysis could benefit from the model proposals through the assessment of clinical utility. Results: Among the three ROIs, the best R model constructed from the LightGBM algorithm demonstrated the strongest discriminative ability in the ROI of V30 Lung-PTV. The corresponding area under the curve (AUC) value was 0.930 (95 % confidence interval (CI): 0.829–0.941). The D model, R model and R+D model achieved AUC values of 0.798 (95 %CI: 0.732–0.865), 0.930 (95 %CI: 0.829–0.941) and 0.940 (95 %CI: 0.906–0.974) in primary cohort, and in external validation cohort, the AUC values were 0.793 (95 %CI:0.637–0.949), 0.887 (95 %CI:0.810–0.993), 0.951 (95CI%:0.891–1.000). Decision curve demonstrate that R+D model could benefit for patients through the assessment of clinical utility. Conclusion: The radiomics model was able to predict the acute RP more effectively in comparison with the traditional dosimetry model. Especially the radiomics model based on the V30 Lung-PTV region was able to achieve a higher accuracy when compared to the other regions.

Abstract Background Prediabetes is a high-risk state for diabetes, and numerous studies have shown that the body mass index (BMI) and triglyceride-glucose (TyG) index play significant roles in risk prediction for blood glucose metabolism. This study aims to evaluate the relative importance of BMI combination with TyG index (TyG-BMI) in predicting the recovery from prediabetic status to normal blood glucose levels. Methods A total of 25,397 prediabetic subjects recruited from 32 regions across China. Normal fasting glucose (NFG), prediabetes, and diabetes were defined referring to the American Diabetes Association (ADA) criteria. After normalizing the independent variables, the impact of TyG-BMI on the recovery or progression of prediabetes was analyzed through the Cox regression models. Receiver Operating Characteristic (ROC) curve analysis was utilized to visualize and compare the predictive value of TyG-BMI and its constituent components in prediabetes recovery/progression. Results During the average observation period of 2.96 years, 10,305 individuals (40.58%) remained in the prediabetic state, 11,278 individuals (44.41%) recovered to NFG, and 3,814 individuals (15.02%) progressed to diabetes. The results of multivariate Cox regression analysis demonstrated that TyG-BMI was negatively associated with recovery from prediabetes to NFG and positively associated with progression from prediabetes to diabetes. Further ROC analysis revealed that TyG-BMI had higher impact and predictive value in predicting prediabetes recovering to NFG or progressing to diabetes in comparison to the TyG index and BMI. Specifically, the TyG-BMI threshold for predicting prediabetes recovery was 214.68, while the threshold for predicting prediabetes progression was 220.27. Additionally, there were significant differences in the relationship of TyG-BMI with prediabetes recovering to NFG or progressing to diabetes within age subgroups. In summary, TyG-BMI is more suitable for assessing prediabetes recovery or progression in younger populations (

ObjectiveNutritional status is closely associated with the prognosis of heart failure. This study aims to assess the relationship between the Controlling Nutritional Status (CONUT) score and in-hospital mortality among patients with acute decompensated heart failure (ADHF) in Jiangxi, China.MethodsA retrospective cohort study was conducted. Multivariable Cox regression models and restricted cubic spline regression were employed to evaluate the relationship between the CONUT score and in-hospital mortality in ADHF patients from Jiangxi, China. The predictive value of the CONUT score for in-hospital mortality in ADHF patients was analyzed using receiver operating characteristic curves. Subgroup analyses were performed to identify risk dependencies of the CONUT score in specific populations.ResultsThe study included 1,230 ADHF patients, among whom 44 (3.58%) mortality events were recorded. After adjusting for confounding factors, a positive correlation was found between the CONUT score and the risk of in-hospital mortality in ADHF patients. Restricted cubic spline regression analysis indicated a non-linear relationship between the CONUT score and the risk of in-hospital mortality in ADHF patients, estimating a rapid increase in mortality risk when the CONUT score exceeded 5. Receiver operating characteristic analysis demonstrated a good predictive value of the CONUT score for all-cause mortality events in ADHF patients [area under the curve = 0.7625, optimal threshold = 5.5]. Additionally, a relatively higher risk associated with the CONUT score was observed in male patients and those with concomitant cerebral infarction.ConclusionThis study reveals a positive correlation between the CONUT score and the risk of in-hospital mortality in ADHF patients. Based on the findings of this study, we recommend maintaining a CONUT score below 5 for patients with ADHF in Jiangxi, China, as it may significantly contribute to reducing the risk of in-hospital all-cause mortality.

ObjectiveDiabetes is a significant risk factor for acute heart failure, associated with an increased risk of mortality. This study aims to analyze the prognostic significance of admission blood glucose (ABG) on 30-day mortality in Chinese patients with acute decompensated heart failure (ADHF), with or without diabetes.MethodsThis retrospective study included 1,462 participants from the JX-ADHF1 cohort established between January 2019 to December 2022. We conducted multivariate cox regression, restricted cubic spline, receiver operating characteristic curve analysis, and mediation analysis to explore the association and potential mechanistic pathways (inflammation, oxidative stress, and nutrition) between ABG and 30-day mortality in ADHF patients, with and without diabetes.ResultsDuring the 30-day follow-up, we recorded 20 (5.36%) deaths in diabetic subjects and 33 (3.03%) in non-diabetics. Multivariate Cox regression revealed that ABG was independently associated with 30-day mortality in ADHF patients, with a stronger association in diabetics than non-diabetics (hazard ratio: Model 1: 1.71 vs 1.16; Model 2: 1.26 vs 1.19; Model 3: 1.65 vs 1.37; Model 4: 1.76 vs 1.33). Further restricted cubic spline analysis indicated a U-shaped relationship between ABG and 30-day mortality in non-diabetic ADHF patients (P for non-linearity < 0.001), with the lowest risk at ABG levels approximately between 5-7 mmol/L. Additionally, receiver operating characteristic analysis demonstrated that ABG had a higher predictive accuracy for 30-day mortality in diabetics (area under curve = 0.8751), with an optimal threshold of 13.95mmol/L. Finally, mediation analysis indicated a significant role of inflammation in ABG-related 30-day mortality in ADHF, accounting for 11.15% and 8.77% of the effect in diabetics and non-diabetics, respectively (P-value of proportion mediate < 0.05).ConclusionOur study confirms that ABG is a vital indicator for assessing and predicting 30-day mortality risk in ADHF patients with diabetes. For ADHF patients, both with and without diabetes, our evidence suggests that physicians should be alert and closely monitor any changes in patient conditions when ABG exceeds 13.95 mmol/L for those with diabetes and 7.05 mmol/L for those without. Timely adjustments in therapeutic strategies, including endocrine and anti-inflammatory treatments, are advisable.

ObjectiveArteriosclerosis is a primary causative factor in cardiovascular diseases. This study aims to explore the correlation between the atherogenic index of plasma (AIP) and the 30-day mortality rate in patients with acute decompensated heart failure (ADHF).MethodsA total of 1,248 ADHF patients recruited from the Jiangxi-Acute Decompensated Heart Failure1 (JX-ADHF1) cohort between 2019 and 2022 were selected for this study. The primary outcome was the 30-day mortality rate. Multivariable Cox regression, restricted cubic splines (RCS), and stratified analyses were utilized to assess the relationship between AIP and the 30-day mortality rate in ADHF patients. Mediation models were employed for exploratory analysis of the roles of inflammation, oxidative stress, and nutrition in the association between AIP and the 30-day mortality rate in ADHF patients.ResultsDuring the 30-day follow-up, 42 (3.37%) of the ADHF patients died. The mortality rates corresponding to the quartiles of AIP were as follows: Q1: 1.28%, Q2: 2.88%, Q3: 2.88%, Q4: 6.41%. The multivariable Cox regression revealed a positive correlation between high AIP and the 30-day mortality rate in ADHF patients [Hazard ratio (HR) 3.94, 95% confidence interval (CI): 1.08–14.28], independent of age, gender, heart failure type, cardiac function classification, and comorbidities. It is important to note that there was a U-shaped curve association between AIP (

Abstract Background Obesity is the most important driver of non-alcoholic fatty liver disease (NAFLD); nevertheless, the relationship of weight-adjusted waist index (WWI), a new obesity index, with NAFLD is unclear. Methods This retrospective study used data from the NAGALA project from 1994 to 2016. WWI values were calculated using waist circumference (WC) and weight measurements of the participants. Three stepwise adjusted logistic regression models were developed to assess the relationship of WWI with NAFLD in the whole population and in both sexes. Additionally, we also conducted a series of exploratory analysis to test the potential impact of body mass index (BMI), age, smoking status and exercise habits on the association of WWI with NAFLD. Receiver operating characteristic (ROC) curves were used to estimate cut-off points for identifying NAFLD in the entire population and in both sexes. Results The current study included a population of 11,805 individuals who participated in health screenings, including 6,451 men and 5,354 women. After adjusting for all non-collinear variables in the multivariable logistic regression model, we found a significant positive correlation of WWI with NAFLD. For each unit increase in WWI, the risk of NAFLD increased by 72% in the entire population, by 84% in men, and by 63% in women. Furthermore, subgroup analyses revealed no significant discrepancies in the correlation of WWI with NAFLD across individuals with varying ages, exercise habits, and smoking status (all P-interaction > 0.05), except for different BMI groups (P-interaction

Background: Extracellular high mobility group box 1 (HMGB1) is a key mediator in driving allergic airway inflammation and contributes to asthma. Yet, mechanism of HMGB1 secretion in asthma is poorly defined. Pulmonary metabolic dysfunction is recently recognized as a driver of respiratory pathology. However, the altered metabolic signatures and the roles of metabolic to allergic airway inflammation remain unclear. Methods: Male C57BL/6 J mice were sensitized and challenged with toluene diisocyanate (TDI) to generate a chemically induced asthma model. Pulmonary untargeted metabolomics was employed. According to results, mice were orally administered allopurinol, a xanthine oxidase (XO) inhibitor. Human bronchial epithelial cells (16HBE) were stimulated by TDI-human serum albumin (HSA). Results: We identified the purine metabolism was the most enriched pathway in TDI-exposed lungs, corresponding to the increase of xanthine and uric acid, products of purine degradation mediated by XO. Inhibition of XO by allopurinol ameliorates TDI-induced oxidative stress and DNA damage, mixed granulocytic airway inflammation and Th1, Th2 and Th17 immunology as well as HMGB1 acetylation and secretion. Mechanistically, HMGB1 acetylation was caused by decreased activation of the NAD+-sirtuin 1 (SIRT1) axis triggered by hyperactivation of the DNA damage sensor poly (ADP-ribose)-polymerase 1 (PARP-1). This was rescued by allopurinol, PARP-1 inhibitor or supplementation with NAD+ precursor in a SIRT1-dependent manner. Meanwhile, allopurinol attenuated Nrf2 defect due to SIRT1 inactivation to help ROS scavenge. Conclusions: We demonstrated a novel regulation of HMGB1 acetylation and secretion by purine metabolism that is critical for asthma onset. Allopurinol may have therapeutic potential in patients with asthma.

Abstract A study of the effects of drifts on the particle flow pattern and in–out divertor plasma density asymmetry for L-mode and H-mode plasmas is carried out for EAST discharges by the edge plasma transport codes SOLPS and BOUT++ . The simulation of L-mode plasmas is done by SOLPS while the simulation of H-mode plasmas is done by BOUT++ . The toroidal magnetic field direction for the simulated discharge is artificially reversed in the codes to study the effects of different drift directions on the divertor particle flow pattern and the in–out asymmetry of divertor plasma density. The divertor particle flows induced by diamagnetic and E × B drifts are found to have similar directions in the divertor region for the same discharge. The directions of the flows induced by drifts would be reversed with the reverse of toroidal magnetic field direction. The diamagnetic drift seems to have no effect on the in–out asymmetry of divertor plasma density due to its divergence-free nature. However, the E × B drift could result in a pronounced asymmetry of plasma density between the inner and outer divertor targets. The density in–out asymmetry caused by E × B drift is reversed with the reverse of E × B drift flow direction. Detailed analysis shows that the radial component of the E × B drift flow is the main cause of density asymmetry. The results from the simulation of H-mode plasmas with BOUT++ are similar to those of the L-mode plasmas with SOLPS except that the drift effects seem to be slightly larger in the H-mode plasmas compared to the L-mode plasmas.

ObjectiveEvery distinct liver enzyme biomarker exhibits a strong correlation with non-alcoholic fatty liver disease (NAFLD). This study aims to comprehensively analyze and compare the associations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) with NAFLD from a gender perspective.MethodsThis study was conducted on 6,840 females and 7,411 males from the NAGALA cohort. Multivariable logistic regression analysis was used to compare the associations between liver enzyme markers and NAFLD in both genders, recording the corresponding adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Receiver operating characteristic (ROC) curves were used to evaluate the accuracy of individual liver enzyme markers and different combinations of them in identifying NAFLD.ResultsLiver enzyme markers ALT, AST, and GGT were all independently associated with NAFLD and exhibited significant gender differences (All P-interaction

ObjectiveBoth alanine aminotransferase (ALT) and high-density lipoprotein cholesterol (HDL-C) are closely related to glucose homeostasis in the body, and the main objective of this study was to investigate the association between ALT to HDL-C ratio (ALT/HDL-C ratio) and the risk of diabetes in a Chinese population.MethodsThe current study included 116,251 participants who underwent a healthy physical examination, and the study endpoint was defined as a diagnosis of new-onset diabetes. Multivariate Cox regression models and receiver operator characteristic curves were used to assess the association of the ALT/HDL-C ratio with diabetes onset.ResultsDuring the average observation period of 3.10 years, a total of 2,674 (2.3%) participants were diagnosed with new-onset diabetes, including 1,883 (1.62%) males and 791 (0.68%) females. After fully adjusting for confounding factors, we found a significant positive association between the ALT/HDL-C ratio and the risk of diabetes [Hazard ratios 1.06, 95% confidence intervals: 1.05, 1.06], and this association was significantly higher in males, obese individuals [body mass index ≥ 28 kg/m2] and individuals aged < 60 years (All P interaction < 0.05). In addition, the ALT/HDL-C ratio was significantly better than its components ALT and HDL-C in predicting diabetes in the Chinese population.ConclusionThere was a positive relationship between ALT/HDL-C ratio and diabetes risk in the Chinese population, and this relationship was significantly stronger in males, obese individuals, and individuals younger than 60 years old.

Abstract Background Lung fibroblast activation is associated with airway remodeling during asthma progression. Stearoyl-CoA desaturase 1 (SCD1) plays an important role in the response of fibroblasts to growth factors. This study aimed to explore the effects of SCD1 on fibroblast activation induced by transforming growth factor-β1 (TGF-β1) and the role of the phosphatidylinositol-3-kinase-AKT serine-threonine protein kinase-mechanistic target of rapamycin (PI3K-Akt-mTOR) pathway on the regulation of SCD1 expression in airway remodeling. Methods Female C57BL/6 mice were sensitized and challenged with house dust mites to generate a chronic asthma model. The inhibitor of SCD1 was injected i.g. before each challenge. The airway hyper-responsiveness to methacholine was evaluated, and airway remodeling and airway inflammation were assessed by histology. The effects of SCD1 on fibroblast activation were evaluated in vitro using an SCD1 inhibitor and oleic acid and via the knockdown of SCD1. The involvement of the PI3K-Akt-mTOR-sterol regulatory element-binding protein 1 (SREBP1) pathway in lung fibroblasts was investigated using relevant inhibitors. Results The expression of SCD1 was increased in fibroblasts exposed to TGF-β1. The inhibition of SCD1 markedly ameliorated airway remodeling and lung fibroblast activation in peripheral airways. The knockdown or inhibition of SCD1 resulted in significantly reduced extracellular matrix production in TGF-β1-treated fibroblasts, but this effect was reversed by the addition of exogenous oleic acid. The PI3K-Akt-mTOR-SREBP1 pathway was found to be involved in the regulation of SCD1 expression and lung fibroblast activation. Conclusions The data obtained in this study indicate that SCD1 expression contributes to fibroblast activation and airway remodeling and that the inhibition of SCD1 may be a therapeutic strategy for airway remodeling in asthma.

Abstract Background A cross-sectional association between the combination indicator of high-density lipoprotein cholesterol (HDL-C) and gamma-glutamyl transferase (GGT) and fatty liver has been described in several recent studies, and this study aims to further evaluate the longitudinal relationship between the ratio of GGT to HDL-C (GGT/HDL-C ratio) and nonalcoholic fatty liver disease (NAFLD). Methods This cohort study included 12,126 individuals without NAFLD at baseline, followed prospectively for 5 years, and the endpoint of interest was new-onset NAFLD. The relationship of the GGT/HDL-C ratio with new-onset NAFLD and the shape of the association was assessed by Cox regression models and restricted cubic spline (RCS) regression, respectively. Time-dependent receiver operator characteristics (ROC) curves were constructed to evaluate the predictive value of GGT, HDL-C, GGT/HDL-C ratio and BMI for the occurrence of NAFLD at different time points in the future. Results The prevalence of NAFLD was 72.46/1000 person-years during the 5-year follow-up period. Results of multivariate Cox regression analysis showed a positive association of the GGT/HDL-C ratio with new-onset NAFLD after adequate adjustment of the related confounding factors, and the degree of correlation was slightly higher than that of GGT, and further subgroup analysis found that this association was more significant in the population with elevated systolic blood pressure (SBP). In addition, we also found a nonlinear relationship of the GGT/HDL-C ratio with the risk of new-onset NAFLD using the RCS regression, where the saturation threshold was about 31.79 U/mmol. Time-dependent ROC analysis results showed that the GGT/HDL-C ratio was increasingly valuable in predicting NAFLD over time, and was better than HDL-C in predicting NAFLD in the early stage (1–3 years), but was not superior to BMI and GGT. Conclusions In this large longitudinal cohort study based on a Chinese population, our results supported that the GGT/HDL-C ratio was positively and nonlinearly associated with the risk of new-onset NAFLD in a non-obese population. In the assessment of future NAFLD risk, the GGT/HDL-C ratio was slightly better than GGT alone; However, the GGT/HDL-C ratio did not appear to have a significant advantage over GGT and BMI alone in predicting NAFLD.

ObjectiveAlanine aminotransferase (ALT) and high-density lipoprotein cholesterol (HDL-C) are important predictive factors for non-alcoholic fatty liver disease (NAFLD). The aim of this study was to analyze the association between the ALT/HDL-C ratio and NAFLD.MethodsWe conducted a retrospective analysis of data from 14,251 individuals participating in the NAGALA project’s health screening program. The presence of NAFLD was diagnosed based on the participants’ alcohol consumption status and liver ultrasonography images. Multivariable logistic regression models were used to assess the association between the ALT/HDL-C ratio and NAFLD. Receiver operating characteristic (ROC) analysis was performed to determine and compare the effectiveness of ALT, HDL-C, the aspartate aminotransferase to HDL-C (AST/HDL-C) ratio, the gamma-glutamyl transferase to HDL-C (GGT/HDL-C) ratio and the ALT/HDL-C ratio in identifying NAFLD.ResultsWe observed a significant positive association between the ALT/HDL-C ratio and the prevalence of NAFLD. For each standard deviation (SD) increase in the ALT/HDL-C ratio, the adjusted odds ratio (OR) for NAFLD among the participants was 3.05 [95% confidence interval (CI): 2.63, 3.53], with the highest quartile of ALT/HDL-C ratio having a 9.96-fold increased risk compared to the lowest quartile. In further subgroup analyses stratified by gender, age, and waist circumference (WC), we observed a significantly higher risk of NAFLD associated with the ALT/HDL-C ratio among individuals aged ≥45 years, males, and those who were abdominal obesity. Furthermore, based on the results of ROC analysis, we found that the ALT/HDL-C ratio [area under the curves (AUC): 0.8553] was significantly superior to ALT, HDL-C, AST/HDL-C ratio and GGT/HDL-C ratio in identifying NAFLD (All Delong P

ObjectiveVisceral adipose tissue assessment holds significant importance in diabetes prevention. This study aimed to explore the association between the newly proposed Metabolic Score for Visceral Fat (METS-VF) and diabetes risk and to further assess the predictive power of the baseline METS-VF for the occurrence of diabetes in different future periods.MethodsThis longitudinal cohort study included 15,464 subjects who underwent health screenings. The METS-VF, calculated using the formula developed by Bello-Chavolla et al., served as a surrogate marker for visceral fat obesity. The primary outcome of interest was the occurrence of diabetes during the follow-up period. Established multivariate Cox regression models and restricted cubic spline (RCS) regression models to assess the association between METS-VF and diabetes risk and its shape. Receiver operating characteristic (ROC) curves were used to compare the predictive power of METS-VF with body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), and visceral adiposity index (VAI) for diabetes, and time-dependent ROC analysis was conducted to assess the predictive capability of METS-VF for the occurrence of diabetes in various future periods.ResultsDuring a maximum follow-up period of 13 years, with a mean of 6.13 years, we observed that the cumulative risk of developing diabetes increased with increasing METS-VF quintiles. Multivariable-adjusted Cox regression analysis showed that each unit increase in METS-VF would increase the risk of diabetes by 68% (HR 1.68, 95% CI 1.13, 2.50), and further RCS regression analysis revealed a possible non-linear association between METS-VF and diabetes risk (P for non-linearity=0.002). In addition, after comparison by ROC analysis, we found that METS-VF had significantly higher predictive power for diabetes than other general/visceral adiposity indicators, and in time-dependent ROC analysis, we further considered the time-dependence of diabetes status and METS-VF and found that METS-VF had the highest predictive value for predicting medium- and long-term (6-10 years) diabetes risk.ConclusionMETS-VF, a novel indicator for assessing visceral adiposity, showed a significantly positive correlation with diabetes risk. It proved to be a superior risk marker in predicting the future onset of diabetes compared to other general/visceral adiposity indicators, particularly in forecasting medium- and long-term diabetes risk.

Background and purpose: Mitochondrial dysfunction is an essential part of the pathophysiology of asthma, and potential treatments that target the malfunctioning mitochondria have attracted widespread attention. We have previously demonstrated that aberrant epithelial β-catenin signaling played a crucial role in a toluene diisocyanate (TDI)-induced steroid-insensitive asthma model. The objective of this study was to determine if the mitochondrially targeted antioxidant mitoquinone(MitoQ) regulated the activation of β-catenin in TDI-induced asthma. Method: Mice were sensitized and challenged with TDI to generate a steroid-insensitive asthma model. Human bronchial epithelial cells (16HBE) were exposed to TDI-human serum albumin (HSA) and ethidium bromide(EB) to simulate the TDI-induced asthma model and mitochondrial dysfunction. Results: MitoQ dramatically attenuated TDI-induced AHR, airway inflammation, airway goblet cell metaplasia, and collagen deposition and markedly protected epithelial mitochondrial functions by preserving mass and diminishing the production of reactive oxygen species (ROS). MitoQ administration stabilized β‐catenin destruction complex from disintegration and inhibited the activation of β‐catenin. Similarly, YAP1, an important constituent of β‐catenin destruction complex, was inhibited by Dasatinib, which alleviated airway inflammation and the activation of β‐catenin, and restored mitochondrial mass. In vitro, treating 16HBE cells with EB led to the activation of YAP1 and β-catenin signaling, decreased the expression of glucocorticoid receptors and up-regulated interleukin (IL)-1β, IL6 and IL-8 expression. Conclusion: Our results indicated that mitochondria mediates airway inflammation by regulating the stability of the β-catenin destruction complex and MitoQ might be a promising therapeutic approach to improve airway inflammation and severe asthma. Availability of data and materials: The data that support the findings of this study are available from the corresponding author upon reasonable request. Some data may not be made available because of privacy or ethical restrictions.

Abstract Background The diversity of obesity-related metabolic characteristics generates different obesity phenotypes and corresponding metabolic diseases. This study aims to explore the correlation of different abdominal obesity phenotypes with non-alcoholic fatty liver disease (NAFLD). Methods The current study included 14,251 subjects, 7411 males and 6840 females. Abdominal obesity was defined as waist circumference ≥ 85 cm in males and ≥ 80 cm in females; according to the diagnostic criteria for metabolic syndrome recommended by the National Cholesterol Education Program Adult Treatment Panel III, having more than one metabolic abnormality (except waist circumference criteria) was defined as metabolically unhealthy. All subjects were divided into 4 abdominal obesity phenotypes based on the presence ( +) or absence (− ) of metabolically healthy/unhealthy (MH) and abdominal obesity (AO) at baseline: metabolically healthy + non-abdominal obesity (MH−AO−); metabolically healthy + abdominal obesity (MH−AO+); metabolically unhealthy + non-abdominal obesity (MH+AO−); metabolically unhealthy + abdominal obesity (MH+AO+). The relationship between each phenotype and NAFLD was analyzed using multivariate logistic regression. Results A total of 2507 (17.59%) subjects in this study were diagnosed with NAFLD. The prevalence rates of NAFLD in female subjects with MH−AO−, MH−AO+, MH+AO−, and MH+AO+ phenotypes were 1.73%, 24.42%, 7.60%, and 59.35%, respectively. Among male subjects with MH−AO−, MH−AO+, MH+AO−, and MH+AO+ phenotypes, the prevalence rates were 9.93%, 50.54%, 25.49%, and 73.22%, respectively. After fully adjusting for confounding factors, with the MH−AO− phenotype as the reference phenotype, male MH−AO+ and MH+AO+ phenotypes increased the risk of NAFLD by 42% and 47%, respectively (MH−AO+: OR 1.42, 95%CI 1.13,1.78; MH+AO+: OR 1.47, 95%CI 1.08,2.01); the corresponding risks of MH−AO+ and MH+AO+ in females increased by 113% and 134%, respectively (MH−AO+: OR 2.13, 95%CI 1.47,3.09; MH+AO+: OR 2.34, 95%CI 1.32,4.17); by contrast, there was no significant increase in the risk of NAFLD in the MH+AO− phenotype in both sexes. Conclusions This first report on the relationship of abdominal obesity phenotypes with NAFLD showed that both MH−AO+ and MH+AO+ phenotypes were associated with a higher risk of NAFLD, especially in the female population. These data provided a new reference for the screening and prevention of NAFLD.

Abstract Background Up-regulation of aerobic glycolysis has been reported as a characterization of asthma and facilitates airway inflammation. We has been previously reported that short isoform thymic stromal lymphopoietin (sTSLP) could reduce inflammation in asthmatic airway epithelial cells. Here we wanted to investigate whether the inhibition of sTSLP on asthma is related to aerobic glycolysis. Methods Asthmatic model was established in challenging Male BALB/c mice and 16-HBE (human bronchial epithelial) cell line with house dust mite (HDM). Indicators of glycolysis were assessed to measure whether involve in sTSLP regulating airway epithelial cells inflammation in asthmatic model in vivo and in vitro. Results sTSLP decreased inflammation of asthmatic airway and aerobic glycolysis in mice. HDM or long isoform thymic stromal lymphopoietin (lTSLP) promoted HIF-1α expression and aerobic glycolysis by miR-223 to target and inhibit VHL (von Hippel-Lindau) expression 16-HBE. Inhibition of aerobic glycolysis restrained HDM- and lTSLP-induced inflammatory cytokines production. sTSLP along had almost no potential to alter aerobic glycolysis of 16-HBE. But sTSLP decreased LDHA (lactate dehydrogenase A) and LD (Lactic acid) levels in BALF, and HIF-1α and LDHA protein levels in airway epithelial cells of asthma mice model. lTSLP and sTSLP both induced formation of TSLPR and IL-7R receptor complex, and lTSLP obviously facilitated phosphorylation of JAK1, JAK2 and STAT5, while sTSLP induced a little phosphorylation of JAK1 and STAT5. Conclusion We identified a novel mechanism that lTSLP could promote inflammatory cytokines production by miR-223/VHL/HIF-1α pathway to upregulate aerobic glycolysis in airway epithelial cells in asthma. This pathway is suppressed by sTSLP through occupying binding site of lTSLP in TSLPR and IL-7R receptor complex.

Abstract Background Exposure to toluene diisocyanate (TDI) is a significant pathogenic factor for asthma. We previously reported that the receptor for advanced glycation end products (RAGE) plays a key role in TDI-induced asthma. Histone deacetylase (HDAC) has been reported to be important in asthmatic pathogenesis. However, its effect on TDI-induced asthma is not known. The aim of this study was to determine the role of RAGE and HDAC in regulating airway inflammation using a TDI-induced murine asthma model. Methods BALB/c mice were sensitized and challenged with TDI to establish an asthma model. FPS-ZM1 (RAGE inhibitor), JNJ-26482585 and romidepsin (HDAC inhibitors) were administered intraperitoneally before each challenge. In vitro, the human bronchial epithelial cell line 16HBE was stimulated with TDI-human serum albumin (TDI-HSA). RAGE knockdown cells were constructed and evaluated, and MK2006 (AKT inhibitor) was also used in the experiments. Results In TDI-induced asthmatic mice, the expression of RAGE, HDAC1, and p-AKT/t-AKT was upregulated, and these expressions were attenuated by FPS-ZM1. Airway reactivity, Th2 cytokine levels in lymph supernatant, IgE, airway inflammation, and goblet cell metaplasia were significantly increased in the TDI-induced asthmatic mice. These increases were suppressed by JNJ-26482585 and romidepsin. In addition, JNJ-26482585 and romidepsin ameliorated the redistribution of E-cadherin and β-catenin in TDI-induced asthma. In TDI-HSA-stimulated 16HBE cells, knockdown of RAGE attenuated the upregulation of HDAC1 and phospho-AKT (p-AKT). Treatment with the AKT inhibitor MK2006 suppressed TDI-induced HDAC1 expression. Conclusions These findings indicate that RAGE modulates HDAC1 expression via the PI3K/AKT pathway, and that inhibition of HDAC prevents TDI-induced airway inflammation.

Water is a kind of vital natural resource, which acts as the lifeblood of the ecosystem and the energy source for the living and production activities of humans. Regularly mapping the conditions of water resources and taking effective measures to prevent them from pollutions and shortages are very important and necessary to maintain the sustainability of the ecosystem. As a preliminary step for image-based water resource analysis, the complete recognition and accurate extraction of water bodies are important prerequisites in many applications. Nevertheless, due to the issues of topology diversities, appearance variabilities, and land cover interferences, there is still a large gap to achieve the human-level water bodies interpretation quality. This paper presents a hierarchical attentive high-resolution network, abbreviated as WaterHRNet, for extracting water bodies from remote sensing imagery. First, by building a multibranch high-resolution feature extractor integrated with global feature semantics aggregation, the WaterHRNet behaves laudably to supply high-quality, strong-semantic feature representations. Furthermore, by inlaying an effective feature attention scheme with the comprehensive exploitation of both the spatial and channel feature significances, the WaterHRNet is forced to strengthen the semantic-determinate, task-aware feature encodings. In addition, by designing a hierarchical processing principle with the progressive enhancement of category-attentive feature semantics, the WaterHRNet performs effectively to export semantic-discriminative, target-oriented feature representations for precise water body segmentation. The WaterHRNet is elaborately verified both quantitatively and qualitatively on three remote sensing datasets. Evaluation results show that the WaterHRNet achieves an average precision of 98.44%, average recall of 97.84%, average IoU of 96.35%, and average F1-score of 98.14%. Comparative analyses also demonstrate the superior performance and excellent feasibility of the WaterHRNet in segmenting water bodies.

Object detection from remote sensing images serves as an important prerequisite to many applications. However, caused by scale and orientation variations, appearance and distribution diversities, occlusion and shadow contaminations, and complex environmental scenarios of the objects in remote sensing images, it brings great challenges to realize highly accurate recognition of geospatial objects. This paper proposes a novel one-stage anchor-free capsule network (OA-CapsNet) for detecting geospatial objects from remote sensing images. By employing a capsule feature pyramid network architecture as the backbone, a pyramid of high-quality, semantically strong feature representations are generated at multiple scales for object detection. Integrated with two types of capsule feature attention modules, the feature quality is further enhanced by emphasizing channel-wise informative features and class-specific spatial features. By designing a centreness-assisted one-stage anchor-free object detection strategy, the proposed OA-CapsNet performs effectively in recognizing arbitrarily-orientated and diverse-scale geospatial objects. Quantitative evaluations on two large remote sensing datasets show that a competitive overall accuracy with a precision, a recall, and an Fscore of 0.9625, 0.9228, and 0.9423, respectively, is achieved. Comparative studies also confirm the feasibility and superiority of the proposed OA-CapsNet in geospatial object detection tasks.

The information-accurate road network database is greatly significant and provides essential input to many transportation-related activities. Recently, remote sensing images have been an important data source for assisting rapid road network updating tasks. However, due to the diverse challenging scenarios of roads in remote sensing images, such as occlusions, shadows, material diversities, and topology variations, it is still difficult to realize highly accurate extraction of roads. This paper proposes a novel context-augmentation and self-attention capsule feature pyramid network (CS-CapsFPN) to extract roads from remote sensing images. By designing a capsule feature pyramid network architecture, the proposed CS-CapsFPN can extract and fuze different-level and different-scale high-order capsule features to provide a high-resolution and semantically strong feature representation for predicting the road region maps. By integrating the context-augmentation and self-attention modules, the proposed CS-CapsFPN can exploit multi-scale contextual properties at a high-resolution perspective and emphasize channel-wise informative features to further enhance the feature representation robustness. Quantitative evaluations on two test datasets show that the proposed CS-CapsFPN achieves a competitive performance with a precision, recall, intersection-over-union, and Fscore of 0.9470, 0.9407, 0.8957, and 0.9438, respectively. Comparative studies also confirm the feasibility and superiority of the proposed CS-CapsFPN in road extraction tasks.

Avasimibe (Ava) is an acetyl-CoA acetyltransferase 1 (ACAT1) specific inhibitor and an established medicine for atherosclerosis, owing to its excellent and safe anti-inflammation effects in humans. However, its efficacy in asthma has not yet been reported. We first administered varying concentrations of avasimibe to house dust mite (HDM)-induced asthmatic mice; results showed that 20 mg/kg avasimibe most significantly reduced IL-4 and IL-5 production in bronchoalveolar lavage fluid (BALF) and total IgE in serum, and the avasimibe treatment also exhibited lower mucus secretion, decreased goblet and basal cells but increased ciliated cells compared to the HDM group. And the redistribution of adherens junction (AJ) proteins induced by HDM was far more less upon avasimibe administration. However, avasimibe did not reduce the cholesterol ester ratio in lung tissues or intracellular cholesterol ester, which is avasimibe’s main effect. Further analysis confirmed that avasimibe impaired epithelial basal cell proliferation independent of regulating cholesterol metabolism and we analyzed datasets using the Gene Expression Omnibus (GEO) database and then found that the KRT5 gene (basal cell marker) expression is correlated with the β-catenin gene. Moreover, we found that β-catenin localized in cytomembrane upon avasimibe treatment. Avasimibe also reduced β-catenin phosphorylation in the cytoplasm and inactivated the Wnt/β-catenin signaling pathway induced by HDMs, thereby alleviating the airway epithelial barrier disruption. Taken together, these findings indicated that avasimibe has potential as a new therapeutic option for allergic asthma.

As the optical remote sensing techniques keep developing with a rapid pace, remote sensing images are positively considered in many fields. Accordingly, a great number of algorithms have been exploited for remote sensing image interpretation purposes. Thereinto, object recognition acts as an important ingredient to many applications. However, to achieve highly accurate object recognition is still challengeable caused by the orientation and size diversities, spatial distribution and density variations, shape and aspect ratio irregularities, occlusion and shadow impacts, as well as complex texture and surrounding environment changes. In this paper, a sparse anchoring guided high-resolution capsule network (SAHR-CapsNet) is proposed for geospatial object detection based on remote sensing images. First, formulated with the multibranch high-resolution capsule network architecture assisted by multiscale feature propagation and fusion, the SAHR-CapsNet can extract semantically strong and spatially accurate feature semantics at multiple scales. Second, integrated with the efficient capsule-based self-attention module, the SAHR-CapsNet functions promisingly to attend to target-specific spatial features and informative channel features. Finally, adopted with the capsule-based sparse anchoring network, the SAHR-CapsNet performs efficiently in generating a fixed number of lightweight, high-quality sparse region proposals. Quantitative assessments and comparative analyses on two challenging remote sensing image datasets demonstrate the applicability and effectiveness of the developed SAHR-CapsNet for geospatial object detection applications.

The location-based services can provide users with the requested location information. But users also need to disclose their current location to the location-based service provider. Therefore, how to protect user's location privacy is a major concern. In this paper, we propose a heterogeneous deniable authenticated encryption scheme called HDAE for location-based services. The proposed scheme permits a sender in a public key infrastructure environment to transmit a message to a receiver in an identity-based environment. Our design utilizes a hybrid encryption method combing the tag-key encapsulation mechanism (tag-KEM) and the data encapsulation mechanism (DEM), which is well adopted for location-based services applications. We give how to design an HDAE scheme utilizing a heterogeneous deniable authenticated tag-KEM (HDATK) and a DEM. We also construct an HDATK scheme and provide security proof in the random oracle model. Comprehensive analysis shows that our scheme is efficient and secure. In addition, we give an application of the HDAE to a location-based services system.

Atypical chronic myeloid leukemia (aCML) BCR-ABL1 negative is a rare myelodysplastic syndromes/myeloproliferative neoplasm (MDS/MPN) for which no standard treatment currently exists. The advent of next-generation sequencing has allowed our understanding of the molecular pathogenesis of aCML to be expanded and has made it possible for clinicians to more accurately differentiate aCML from similar MDS/MPN overlap syndrome and MPN counterparts, as MPN-associated driver mutations in JAK2, CALR , or MPL are typically absent in aCML. A 55-year old male with main complaints of weight loss and fatigue for more than half a year and night sweats for more than 2 months was admitted to our hospital. Further examination revealed increased white blood cells, splenomegaly, and grade 1 bone marrow fibrosis with JAK2 V617F, which supported a preliminary diagnosis of pre-primary marrow fibrosis. However, in addition to JAK2 V617F (51.00%), next-generation sequencing also detected SETBP1 D868N (46.00%), ASXL1 G645fs (36.09%), and SRSF2 P95_R102del (33.56%) mutations. According to the 2016 World Health Organization diagnostic criteria, the patient was ultimately diagnosed with rare aCML with concomitant JAK2 V617F and SETBP1 mutations. The patient received targeted therapy of ruxolitinib for 5 months and subsequently an additional four courses of combined hypomethylating therapy. The patient exhibited an optimal response, with decreased spleen volume by approximately 35% after therapy and improved symptom scores after therapy. In diagnosing primary bone marrow fibrosis, attention should be paid to the identification of MDS/MPN. In addition to basic cell morphology, mutational analysis using next-generation sequencing plays an increasingly important role in the differential diagnosis. aCML with concomitant JAK2 V617F and SETBP1 mutations has been rarely reported, and targeted therapy for mutated JAK2 may benefit patients, especially those not suitable recipients of hematopoietic stem cell transplants.

A smart grid, considered the next-generation type of power grid, combines a traditional power grid with information and communication technologies to effectively facilitate power generation and ensure transmission security and reliability in real-time. Only authorized consumers should be able to access the smart grid because the information gathered by smart meters includes users' private information. However, smart grid security is still a challenge. Motivated by this challenge, in this paper, we propose a heterogeneous signcryption (HSC) scheme for secure communication between smart meters and the utility. We demonstrate that this scheme is indistinguishable against adaptive chosen-ciphertext attacks (IND-CCA2), existentially unforgeable against adaptive chosen-message attacks (EUF-CMA) and ciphertext-anonymous against adaptive chosen ciphertext attacks (ANON-CCA2) under the computational Diffie-Hellman (CDH) problem in the random oracle model. Our scheme simultaneously achieves confidentiality, integrity, authentication, non-repudiation and ciphertext anonymity in a single logical step. It supports heterogeneous systems, allowing a meter in an identity-based cryptography (IBC) environment to transmit electrical usage data to a utility in a public key infrastructure (PKI) environment. Compared with other existing related schemes, our scheme has the lowest communication overhead and energy consumption for the smart grid. Based on these features, our scheme is highly suitable for secure power transmissions in a smart grid.

Activated macrophages play a vital role in rheumatoid arthritis (RA) pathophysiology. CD44 is an overexpressed receptor on activated macrophages that is a potential target site for RA treatment. In this study, we prepared hyaluronic acid (HA) coated acid-sensitive polymeric nanoparticles (HAPNPs) composed of egg phosphatidylcholine, polyethylenimine, and poly (cyclohexane-1,4-diyl acetone dimethylene ketal) (PCADK) loaded with dexamethasone (Dex) for the treatment of RA. PCADK was used to form polymeric cores because of its acid-sensitivity. The HAPNPs were about 150 nm in size and had a zeta potential of −2.84 mV. The release rate of Dex from HAPNPs/Dex in vitro increased markedly when the pH decreased from 7.4 to 4.5, indicating that the HAPNPs were pH-sensitive. In a cellular uptake study, stronger fluorescence signals were observed in activated macrophages treated with HAPNPs, suggesting that HAPNPs could be effective nanodevices target to activated macrophages. In rats with adjuvant-induced arthritis, HAPNPs could inhibited the progression of RA. Taken together, these results suggest that the HAPNPs could be useful in RA therapy.

The vegetation supply water index (VSWI = NDVI/LST) is an effective metric estimating soil moisture in areas with moderate to dense vegetation cover. However, the normalized difference vegetation index (NDVI) exhibits a long water stress lag and the land surface temperature (LST), sensitive to water stress, does not contribute considerably to surface soil moisture monitoring due to the constraints of the mathematical characteristics of VSWI: LST influences VSWI less when LST value is sufficiently high. This paper mathematically analyzes the characteristics of VSWI and proposes a new operational dryness index (surface water content temperature index, SWCTI) for the assessment of surface soil moisture status. SWCTI uses the surface water content index (SWCI), which provides a more accurate estimation of surface soil moisture than that of NDVI, as the numerator and the modified surface temperature, which has a greater influence on SWCTI than that of LST, as the denominator. The validation work includes comparison of SWCTI with in situ soil moisture and other remote sensing indices. The results show SWCTI demonstrates the highest correlation with in situ soil moisture; the highest correlation R = 0.801 is found between SWCTI and the 0–5 cm soil moisture in a sandy loam. SWCTI is a functional and effective method that has a great potential in surface soil moisture monitoring.