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ObjectiveThis study aims to explore the relationship between cardiovascular calcification (CVC) and serum levels of high-density lipoprotein cholesterol (HDL-C) and its subfractions in hemodialysis (HD) patients.MethodsHD patients and healthy participants were recruited based on specific inclusion and exclusion criteria. Various blood indicators were measured, and demographic information was recorded. HDL-C particle levels were quantified using lipophilic fluorescent dye staining and capillary electrophoresis (microfluidic platform). Coronary artery calcium scores and valve calcification were used to classify HD patients into calcification and non-calcification groups.ResultsCompared to healthy participants, HD patients showed a significant increase in HDL-C, high-density lipoprotein 2 cholesterol (HDL2-C), and high-density lipoprotein 3 cholesterol (HDL3-C) levels (p

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 (

ObjectiveWhile hypertension is a well-recognized risk factor for non-alcoholic fatty liver disease (NAFLD), the specific roles of various common blood pressure measurements [diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse pressure (PP), mean arterial pressure (MAP)] in detecting NAFLD and evaluating the associated risk in adults remain unclear.MethodsA retrospective analysis was conducted on 14,251 adult participants undergoing health screenings in the NAfld in the Gifu Area, Longitudinal Analysis project (NAGALA). Following the Z-transformation of the independent variables, we evaluated the relationships between the four blood pressure indices and NAFLD through multivariable logistic regression models. This analysis documented the odds ratio (OR) and 95% confidence interval (CI) for each standard deviation (SD) increase. Additionally, the effectiveness of these indices in identifying NAFLD was comparatively analyzed using receiver operating characteristic (ROC) curves.ResultsAfter adequately adjusting for confounders, all blood pressure indices except PP showed a positive correlation with NAFLD. For each SD increment, MAP had the strongest association with NAFLD compared to SBP and DBP. This finding was confirmed in populations without exercise habits, under 60 years of age, with normal blood pressure, and in non-obese groups. Furthermore, based on ROC analysis, MAP was found to have the highest accuracy in identifying NAFLD compared to the other three blood pressure indices.ConclusionAmong the four blood pressure indices evaluated, MAP demonstrates the greatest efficacy in identifying NAFLD and assessing its associated risk. These findings underscore the potential of MAP as the most promising blood pressure index for screening NAFLD.

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.

ObjectiveThe newly proposed Metabolic Visceral Fat Score (METS-VF) is considered a more effective measure for visceral adipose tissue (VAT) than other obesity indicators. This study aimed to reveal the association between METS-VF and non-alcoholic fatty liver disease (NAFLD), and its variations across age groups within both sexes.MethodsData from 14,251 medical examiners in the NAGALA project were employed in this study. 3D fitted surface plots were constructed based on multivariate logistic regression models to visualize the isolated and combined effects of aging and METS-VF on NAFLD. Receiver operating characteristic curve (ROC) analysis was conducted to compare the diagnostic performance of METS-VF with other VAT surrogate markers in predicting NAFLD.ResultsThe results of multivariate logistic regression analysis showed that each unit increase in METS-VF was independently associated with a 333% and 312% increase in the odds of NAFLD in males and females, respectively. Additionally, the 3D fitted surface plot showed that age significantly influenced the association between METS-VF and the odds of NAFLD in both sexes, as follows: (i) In males, when METS-VF was less than 6.2, the METS-VF-related odds of NAFLD increased gradually with age in the 20-45 age group, reached a plateau in the 45-65 age group, and then decreased in the group above 65 years old; however, when male METS-VF exceeded 6.2, aging and METS-VF combined to further increase the odds of NAFLD in all age groups, particularly in the 45-65 age group. (ii) In females, aging seemed to reduce METS-VF-related odds of NAFLD in the 18-40 age group, but significantly increased it in the 40-60 age group, particularly for those with higher METS-VF levels. Further ROC analysis revealed that compared to other VAT surrogate markers, METS-VF showed the highest diagnostic accuracy for NAFLD in females, especially in those under 45 years of age [area under the curve (AUC) = 0.9256].ConclusionsThis study firstly revealed a significant positive correlation between METS-VF and the odds of NAFLD, with METS-VF surpassing other VAT surrogate markers in NAFLD diagnosis. Moreover, age significantly influenced the METS-VF-related odds of NAFLD and METS-VF’s diagnostic efficacy for NAFLD in both sexes.

This study investigates the critical issue of mental health disparities within diverse populations in modern workplaces, a concern that significantly affects both individuals and organizational structures. By focusing on how prevailing workplace behaviors, including implicit biases, microaggressions, and the scarcity of diversity in leadership, exacerbate these disparities, the research highlights the urgent need for attention and action in this area. The mental health gap—disparities in conditions and access to care among different workplace groups—emerges from systemic inequalities and stigmatization, deeply influencing employee productivity, creativity, collaboration, and retention. Our research underscores the disproportionate impact of this gap on diverse populations, characterized by varying ethnicity, gender, age, socio-economic status, and other unique identity attributes. The paper articulates the substantial economic repercussions for organizations, manifesting as reduced productivity, increased absenteeism, and higher turnover rates. Recommendations include the implementation of cultural competency training, promotion of inclusive leadership, investment in tailored mental health resources and fostering open dialog about mental health. These strategies are pivotal in creating an inclusive, resilient, and harmonious work environment. Our findings aim to catalyze a shift in organizational practices toward mental well-being, advocating for comprehensive strategies to bridge the mental health divide in workplaces, thereby enhancing overall organizational health and cohesion.

ObjectiveThe increasing prevalence of diabetes is strongly associated with visceral adipose tissue (VAT), and gender differences in VAT remarkably affect the risk of developing diabetes. This study aimed to assess the predictive significance of lipid accumulation products (LAP) for the future onset of diabetes from a gender perspective.MethodsA total of 8,430 male and 7,034 female non-diabetic participants in the NAGALA (NAfld in the Gifu Area, Longitudinal Analysis) program were included. The ability of LAP to assess the risk of future new-onset diabetes in both genders was analyzed using multivariate Cox regression. Subgroup analysis was conducted to explore the impact of potential modifiers on the association between LAP and diabetes. Additionally, time-dependent receiver operator characteristics (ROC) curves were used to assess the predictive power of LAP in both genders for new-onset diabetes over the next 2-12 years.ResultsOver an average follow-up of 6.13 years (maximum 13.14 years), 373 participants developed diabetes. Multivariate Cox regression analysis showed a significant gender difference in the association between LAP and future diabetes risk (P-interaction

ObjectiveSeveral recent reports have suggested the use of mean arterial blood pressure (MAP) to assess/predict the risk of developing atherosclerosis, chronic kidney disease, diabetes, metabolic syndrome, and poor prognosis in a variety of cardiovascular and cerebrovascular diseases. The current study aimed to investigate the association of MAP with non-alcoholic fatty liver disease (NAFLD) and to explore the differences in this association across populations.MethodsThis study used data from the NAGALA study from 1994 to 2016. MAP was calculated as 1/3 systolic blood pressure (SBP) + 2/3 diastolic blood pressure (DBP). Restricted cubic spline (RCS) and logistic regression models were used to examine the correlation of MAP with NAFLD.ResultsThe study population was 14,251 general people undergoing health screening, with a median (interquartile range) age of 42 (36–50) years; among them, 48% were women, and 2,507 (17.59%) were diagnosed with NAFLD. After fully controlling for confounders in the current dataset, MAP was positively and non-linearly associated with NAFLD [(odds ratios (ORs): 1.39, 95% confidence intervals (CIs): 1.15, 1.68); P for non-linearity = 0.024]; the dose-response curve showed that there was a transient saturation effect interval when MAP was between 85 and 95 mmHg, where the risk of NAFLD was neither increased nor decreased. The results of the stratified analysis showed that the risk of NAFLD associated with MAP appeared to be influenced only by age (P-interaction = 0.002), but not by sex, body mass index (BMI), habits of exercise, drinking status, or smoking status (P-interaction > 0.05); further age-stratified RCS analysis showed that the non-linear association between MAP and NAFLD in the young and middle-aged and the middle-aged and elderly populations was consistent with the results of the whole population, whereas, in the elderly population, a U-shaped curve association between MAP and NAFLD was observed, with both low and high MAP increasing the risk of NAFLD.ConclusionIn the general population, MAP was positively and non-linearly associated with NAFLD, and this association only differed significantly by age, but not by sex, BMI, habits of exercise, drinking status, and smoking status.

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.

ObjectiveThe relationship between body composition fat mass (FM) and lean body mass (LBM) and diabetes risk is currently debated, and the purpose of this study was to examine the association of predicted FM and LBM with diabetes in both sexes.MethodsThe current study was a secondary analysis of data from the NAGALA (NAfld in the Gifu Area, Longitudinal Analysis) cohort study of 15,463 baseline normoglycemic participants. Predicted LBM and FM were calculated for each participant using anthropometric prediction equations developed and validated for different sexes based on the National Health and Nutrition Examination Survey (NHANES) database, and the outcome of interest was diabetes (types not distinguished) onset. Multivariate Cox regression analyses were applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of predicted FM and LBM with diabetes risk and further visualized their associations using a restricted cubic spline function.ResultsThe incidence density of diabetes was 3.93/1000 person-years over a mean observation period of 6.13 years. In women, predicted LBM and FM were linearly associated with diabetes risk, with each kilogram increase in predicted LBM reducing the diabetes risk by 65% (HR 0.35, 95%CI 0.17, 0.71; P < 0.05), whereas each kilogram increase in predicted FM increased the diabetes risk by 84% (HR 1.84, 95%CI 1.26, 2.69; P < 0.05). In contrast, predicted LBM and FM were non-linearly associated with diabetes risk in men (all P for non-linearity < 0.05), with an L-shaped association between predicted LBM and diabetes risk and a saturation point that minimized the risk of diabetes was 45.4 kg, while predicted FM was associated with diabetes risk in a U-shape pattern and a threshold point with the lowest predicted FM-related diabetes risk was 13.76 kg.ConclusionIn this Asian population cohort, we found that high LBM and low FM were associated with lower diabetes risk according to anthropometric equations. Based on the results of the non-linear analysis, we believed that it may be appropriate for Asian men to keep their LBM above 45.4 kg and their FM around 13.76 kg.

ObjectiveThe metabolic score for insulin resistance (MetS-IR) is an emerging surrogate marker for insulin resistance (IR). This study aimed to investigate the association and sex differences between MetS-IR and prediabetes risk in a Chinese population.MethodsThis cohort study included 100,309 adults with normoglycemia at baseline and had followed longitudinally for 5 years, and with prediabetes, defined according to the 2018 American Diabetes Association (ADA) recommended diagnostic criteria, as the outcome of interest. Multivariate Cox proportional hazards regression and restricted cubic spline (RCS) regression models were used to assess the association between MetS-IR and prediabetes risk.ResultsDuring an observation period of 312,843 person-years, 7,735 (14.84%) men and 4,617 (9.57%) women with pre-diabetes onset were recorded. After fully adjusting for confounders, we found an independent and positive correlation between MetS-IR and the risk of prediabetes in the Chinese population, and the degree of correlation was stronger in women than in men (HR: 1.24 vs 1.16, P-interaction

ObjectiveTriglyceride glucose body mass index (TyG-BMI) has been shown to be strongly associated with a variety of chronic diseases. However, little is known about the associations between TyG-BMI and normal-high blood pressure (BP) values and hypertension (HTN).MethodThe current study was cross-sectional in design and included 15,464 non-diabetic participants recruited between 1994 and 2016 in the NAGALA (NAfld in the Gifu Area, Longitudinal Analysis) study. Associations between TyG-BMI and normal-high BP values and HTN were assessed using multivariate logistic regression. The ability of the TyG index, BMI, and their combined index TyG-BMI to identify normal-high BP values and HTN was compared by receiver operating characteristic (ROC) curves.ResultsAmong the 15,464 eligible non-diabetic participants, 28.56% (4,416/15,464) and 6.23% (964/15,464) had normal-high BP values and HTN, respectively. Multivariate logistic regression analysis showed positive correlations between BMI, TyG index, TyG-BMI and normal-high BP values/HTN; after standardized regression coefficients, TyG-BMI had the strongest association with normal-high BP values and HTN compared to BMI and TyG index. In the fully adjusted model, the odds ratio (OR) value corresponding to the relationship between TyG-BMI and HTN/normal-high BP values was 2.35; when TyG-BMI was used as a categorical variable, compared with the lowest quartile of TyG-BMI the regression coefficient for the association of the highest quartile of TyG-BMI with normal-high BP values increased by 426%, while the regression coefficient for the association with HTN increased by 527%. In further spline regression analysis, we also found that there was a linearly positive correlation between TyG-BMI and systolic BP/diastolic BP (SBP/DBP), which supported the linear trend between TyG-BMI and HTN/normal-high BP values (P-trend

A massive amount of crustaceans and bivalves are consumed each year, leading to millions of tons of processing side streams from the seafood industry. Considering the current trend of (bio)circular and zero-waste food production, crustacean and bivalve processing side streams (CBPS) seem a promising and emerging resource for producing high-value-added products. This paper highlights the general composition of CBPS with high commercial values, namely, protein, lipids, carotenoids, minerals and chitins. The extraction strategies of these fractions, including conventional chemical and environmentally friendly methods, are also discussed. This review presents and summarises CBPS as raw materials for developing fast time-to-market products complying with specific EU regulations, including animal feeds, bio-pesticide/stimulants, and cosmetic ingredients. This paper also provides insights into challenges of applying CBPS as raw materials to generate products for human consumption.

The shear behavior of shear connectors in steel-concrete composite structures mainly depends on its load-slip relationship. The load-slip relationship not only reflects the shear capacity and slip capacity of the shear connectors, but also the degradation of shear stiffness during loading. In this study, fifteen push-out tests were carried out to investigate the load-slip relationship of the novel bearing-shear (B-S) connectors, which consist of pressuring-bearing plates and shear plates. Based on push-out tests, the influence of the shape and height of the pressure-bearing plate, and the shear plate shape on the load-slip relationship of the B-S connectors was analyzed. Then, an effective finite element model, validated by push-out tests, was used to study the influence of the concrete strength, and the thickness and tensile strength of the shear plate on the load-slip relationship of B-S connectors. Finally, based on the push-out tests, numerical analysis and theoretical analysis, an analytical model expressing the load-slip relationship of the B-S connectors was proposed.

Nuclear factor-kappa B (NF-κB) pathways have a close relationship with many diseases, especially in terms of the regulation of inflammation and the immune response. Non-coding RNAs (ncRNAs) are a heterogeneous subset of endogenous RNAs that directly affect cellular function in the absence of proteins or peptide products; these include microRNAs (miRNAs), long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), etc. Studies on the roles of ncRNAs in targeting the NF-κB pathways in aquatic animals are scarce. A few research studies have confirmed detailed regulatory mechanisms among ncRNAs and the NF-κB pathways in aquatic animals. This comprehensive review is presented concerning ncRNAs targeting the NF-κB pathway in aquatic animals and provides new insights into NF-κB pathways regulatory mechanisms of aquatic animals. The review discusses new possibilities for developing non-coding-RNA-based antiviral applications in fisheries.

ObjectiveHigh body mass index (BMI) is an important risk factor for non-alcoholic fatty liver disease (NAFLD). However, the association of body composition such as fat mass (FM) and lean body mass (LBM) with NAFLD has not been adequately studied. The purpose of this study was to clarify the contribution of body composition FM and LBM to NAFLD.MethodsWe analyzed data from 7,411 men and 6,840 women in the NAGALA cohort study. LBM and FM were estimated for all subjects using validated anthropometric prediction equations previously developed from the National Health and Nutrition Examination Survey (NHANES). Using multiple logistic regression and restricted cubic spline (RCS) to analyze the association and the dose-response curve of predicted LBM and FM with NAFLD in both sexes.ResultsThe prevalence of NAFLD in man and woman subjects was 27.37 and 6.99%, respectively. Predicted FM was positively and linearly associated with NAFLD in both sexes, with each 1 kg increase in predicted FM associated with a 27 and 40% increased risk of NAFLD in men and women, respectively. In contrast, predicted LBM was negatively associated with NAFLD in both sexes, with each 1 kg increase in predicted LBM reducing the risk of NAFLD by 4 and 19% in men and women, respectively. In addition, according to the RCS curve, the risk of NAFLD did not change in men when the predicted LBM was between 47 and 52 kg, and there seemed to be a saturation effect; further, the threshold value of the saturation effect was calculated to be about 52.08 kg by two-piecewise logistic regression, and the protective effect on NAFLD would be significantly enhanced when the man predicted LBM was greater than 52.08 kg.ConclusionThe current findings suggested that body composition LBM and FM had opposite associations with NAFLD in both sexes, with higher LBM associated with a lower risk of NAFLD and higher FM increasing the risk of NAFLD, especially in women.

ObjectiveObesity is the prominent modifiable risk factor known to influence the occurrence and progression of diabetes other than age, and the objective of this study was to evaluate and compare the predictive value of three simple baseline anthropometric indicators of obesity, body mass index (BMI), waist circumference (WC), and waist-height ratio (WHtR), for the occurrence of diabetes at different time points in the future.MethodsThe study subjects were 12,823 individuals with normoglycemic at baseline who underwent health screening and had measurements of BMI, WC, and WHtR. The outcome of interest was new-onset diabetes during follow-up. Time-dependent receiver operator characteristics (ROC) curves of baseline BMI, WC, and WHtR for predicting the risk of diabetes in the next 2 to 12 years were constructed and their area under the ROC curves (AUCs) and corresponding optimal threshold values were calculated for each time point, which were used to compare the accuracy and stability of the above three indicators for predicting the occurrence of diabetes in different future periods.ResultsDuring a median follow-up period of 7.02 years, with a maximum follow-up of 13 years, 320 new-onset diabetes were recorded. After adjusting for confounders and comparing standardized hazard ratios (HRs), WC was shown to be the best simple anthropometric indicator of obesity reflecting diabetes risk in all models, followed by WHtR. Time-dependent ROC analysis showed that WC had the highest AUC in predicting the occurrence of diabetes in the short term (2-5 years), and WHtR had the highest AUC in predicting the occurrence of diabetes in the medium to long term (6-12 years), while in any time point, both WC and WHtR had higher AUC than BMI in predicting future diabetes. In addition, we found relatively larger fluctuations in the thresholds of BMI and WC for predicting diabetes over time, while the thresholds of WHtR consistently remained between 0.47-0.50; comparatively speaking, WHtR may have greater application value in predicting future diabetes.ConclusionsOur analysis sustained that central obesity is a more important predictor of diabetes, and in clinical practice, we proposed measuring WHtR as a useful tool for predicting future diabetes.

BackgroundTimely access to emergency medical services (EMS) can significantly reduce mortality. In China, the evidence of the accessibility of complete EMS which considers two related trips and involves large rural areas is insufficient. This study aimed to explore the accessibility of ambulance services and complete EMS in Chongqing and its regional differences, and to provide a reference for improving spatial accessibility of EMS in Chongqing and optimizing allocation of EMS resources.MethodsThe nearest neighbor method was used to measure spatial accessibility of ambulance services and complete EMS. Spatial aggregation patterns and influencing factors of spatial accessibility of complete EMS were analyzed using Moran's I index, Pearson correlation and multiple linear regression.ResultsThe medians of shortest travel time for ambulance, monitoring ambulance, primary EMS and advanced EMS in Chongqing were 7.0, 18.6, 36.2, and 47.8 min. The shortest travel time for complete EMS showed significant spatial aggregation characteristics. The Low-Low types that referred to cluster of short EMS travel time mainly distributed in city proper. The High-High types that referred to cluster of long EMS travel time mainly distributed in northeast and southeast of Chongqing. Urbanization rate was a negative influencing factor on shortest travel time for primary EMS, while average elevation and the number of settlements were positive influencing factors. GDP per capita and urbanization rate were negative influencing factors on shortest travel time for advanced EMS, while the number of settlements was a positive influencing factor.ConclusionThis study evaluated the accessibility of EMS which considers two related trips in Chongqing. Although the accessibility of ambulances in Chongqing was relatively high, the accessibility of monitoring ambulance was relatively low. Regional and urban-rural differences in the accessibility of complete EMS integrating two related trips were obvious. It was recommended to increase financial investment in economic backward areas, increase high-quality EMS resources, enhance EMS capacity of central township health centers, strengthen road construction in mountainous areas, and provide reasonable planning of rural settlements for improving the spatial accessibility of EMS, narrowing the urban-rural gap and improving equity in getting EMS for all the people.

Misato mitochondrial distribution and morphology regulator 1 (MSTO1) is a nuclear-encoded cytoplasmic protein involved in mitochondrial fusion and distribution. Its disruption causes an extremely rare mitochondrial disorder characterized by early-onset myopathy and cerebellar ataxia. The genotype-phenotype correlation in the MSTO1 gene is rarely studied before 2017, and only 25 mutations have been described in the patients. Here, we reported two siblings with progressive cerebellar atrophy and ataxia in a Chinese family. Two compound heterozygous mutations in the MSTO1 gene, a novel missense mutation c.571C>T (p.Arg191Trp), and a reported frameshift mutation c.1259delG (p.Gly420ValfsTer2) were identified in the patients by whole exome sequencing. in vitro experiments found both of the mutations lead to reduced protein abundance and link to decreased mtDNA content. Except for ataxia and delayed motor, both of the siblings also have low birth weights, learning difficulties, and dysarthria. Our report enriched the genotype and phenotype spectrums of the MSTO1-related disorder and supported the recessive inheritance of the disease.

Objective: This study was designed to compare the biomechanical properties of lumbar spondylolysis repairs using different fixation methods by using three-dimensional finite element analysis.Methods: Five finite element models (A, B, C, D, and E) of L4-S1 vertebral body were reconstructed by CT images of a male patient (A: intact model; B: spondylolysis model; C: spondylolysis model with intrasegmental direct fixation by Buck screw; D: spondylolysis model with intersegmental indirect fixation by pedicle screw system; E: spondylolysis model with hybrid internal fixation). L5-S1 level was defined as the operative level. After the intact model was verified, six physiological motion states were simulated by applying 500 N concentrated force and 10 Nm torque on the upper surface of L4. The biomechanical properties of the three different internal fixation methods were evaluated by comparing the range of motion (ROM), maximum stress, and maximum displacement.Results: Compared with Model B, the ROM and maximum displacement of Model C, D, and E decreased. The maximum stress on L5/S1 disc in models A, B, and C was much higher than that in Model D and E under extension and lateral bending conditions. Under axial rotation and lateral bending conditions, the maximum stress of interarticular muscle and internal fixation system in Model B and Model C was significantly higher than that in Model D and Model E. In contrast to Model D, the stress in Model E was distributed in two internal fixation systems.Conclusion: In several mechanical comparisons, hybrid fixation had better biomechanical properties than other fixation methods. The experimental results show that hybrid fixation can stabilize the isthmus and reduce intervertebral disc stress, which making it the preferred treatment for lumbar spondylolysis.

Toxoplasmosis is an important zoonotic parasitic disease caused by Toxoplasma gondii (T. gondii). However, the functions of circRNAs and miRNAs in response to T. gondii infection in the livers of mice at acute and chronic stages remain unknown. Here, high-throughput RNA sequencing was performed for detecting the expression of circRNAs and miRNAs in livers of mice infected with 20 T. gondii cysts at the acute and chronic stages, in order to understand the potential molecular mechanisms underlying hepatic toxoplasmosis. Overall, 265 and 97 differentially expressed (DE) circRNAs were found in livers at the acute and chronic infection stages in comparison with controls, respectively. In addition, 171 and 77 DEmiRNAs were found in livers at the acute and chronic infection stages, respectively. Functional annotation showed that some immunity-related Gene ontology terms, such as “positive regulation of cytokine production”, “regulation of T cell activation”, and “immune receptor activity”, were enriched at the two infection stages. Moreover, the pathways “Valine, leucine, and isoleucine degradation”, “Fatty acid metabolism”, and “Glycine, serine, and threonine metabolism” were involved in liver disease. Remarkably, DEcircRNA 6:124519352|124575359 was significantly correlated with DEmiRNAs mmu-miR-146a-5p and mmu-miR-150-5p in the network that was associated with liver immunity and pathogenesis of disease. This study revealed that the expression profiling of circRNAs in the livers was changed after T. gondii infection, and improved our understanding of the transcriptomic landscape of hepatic toxoplasmosis in mice.

BackgroundPrevious studies suggest that alcohol dependence is associated with depression, however, the effect of alcohol dependence varies from individual to individual, which may be due to different genetic backgrounds. The interactions between alcohol dependence and different gene polymorphisms may finally shape the onset of depression. Neuropeptide Y (NPY), which can maintain homeostasis from high-stress stimulation, may protect individuals from the onset of depression. Here, we explored whether the NPY rs16147:T>C has an association with depression in individuals with alcohol dependence during the period of alcohol dependence withdrawal.MethodsA total of 455 males with alcohol dependence were recruited. The scale of Michigan Alcoholism Screening Test (MAST) and Self-Depression Scale (SDS) were respectively used to analyze the condition of alcohol dependence and depression. Genomic DNA was extracted from each blood sample and NPY polymorphisms were genotyped. The interaction between NPY rs16147:T>C and alcohol dependence on depression was first analyzed. Then, region of significance analysis was used to confirm which model provided the best fit for the interaction (diathesis-stress or differential susceptibility). Finally, by using internal replication analyses, the accuracy and robustness of the interaction results were improved.ResultsAlcohol dependence was positively correlated with depression. CC homozygotes of NPY rs16147:T>C exhibited less depression when exposed to low alcohol dependence, but more depression when exposed to high alcohol dependence. Individuals with the T allele showed the opposite result.ConclusionNPY rs16147:T>C might be correlated with susceptibility for depression in males during alcohol dependence withdrawal. The findings support the differential susceptibility model.

A global lipidomic analysis using liquid chromatography–tandem mass spectrometry was performed on the liver of beagle dogs infected with Toxocara canis to profile hepatic lipid species at 12 h post-infection (hpi), 24 hpi, and 36 days post-infection (dpi). This analysis identified six categories and 42 subclasses of lipids, including 173, 64, and 116 differentially abundant lipid species at 12 hpi, 24 hpi, and 36 dpi, respectively. Many of the identified lysophospholipids, such as lysophosphatidylglycerol, lysophosphatidylserine, and lysophosphatidylcholine, may contribute to the migration and development of T. canis during the early infection stage. Pathway analysis revealed significant alterations of several immune-inflammatory pathways, such as the B-cell receptor signaling pathway, the NF-kappa B signaling pathway, and the C-type lectin receptor signaling pathway at 12 and 24 hpi. These findings demonstrate the value of lipidomic profiling in revealing the extent of changes in the composition and abundance of hepatic lipidome caused by T. canis infection and their relevance to the pathophysiology of toxocariasis in beagle dogs.

Background: Intrahepatic cholestasis of pregnancy (ICP) is associated with a high incidence of fetal morbidity and mortality. Therefore, revealing the mechanisms involved in ICP and its association with fetal complications is very important.Methods: Here, we used a whole-exome sequencing (WES) approach to detect novel mutations of organic anion transporting polypeptide (OTAP) genes, ATP-binding cassette transporter (ABC) genes, and receptor genes associated with ICP in 249 individuals and 1,029 local control individuals. Two available tools, SIFT and PolyPhen-2, were used to predict protein damage. Protein structuremodeling and comparison between the reference and modified protein structures were conducted by SWISS-MODEL and Chimera 1.14rc software, respectively.Results: A total of 5,583 mutations were identified in 82 genes related to bile acid transporters and receptors, of which 62 were novel mutations. These novel mutations were absent in the 1,029 control individuals and three databases, including the 1,000 Genome Project (1000G_ALL), Exome Aggregation Consortium (ExAC), and Single-Nucleotide Polymorphism Database (dbSNP). We classified the 62 novel loci into two groups (damaging and probably damaging) according to the results of SIFT and PolyPhen-2. Out of the 62 novel mutations, 24 were detected in the damaging group. Of these, five novel possibly pathogenic variants were identified that were located in known functional genes, including ABCB4 (Ile377Asn), ABCB11 (Ala588Pro), ABCC2 (Ile681Lys and Met688Thr), and NR1H4 (Tyr149Ter). Moreover, compared to the wild-type protein structure, ABCC2 Ile681Lys and Met688Thr protein structures showed a slight change in the chemical bond lengths of ATP-ligand binding amino acid side chains. The combined 32 clinical data points indicate that the mutation group had a significantly (p = 0.04) lower level of Cl ions than the wild-type group. Particularly, patients with the 24 novel mutations had higher average values of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total bile acids (TBA), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) than patients with the 38 novel mutations in the probably damaging group and the local control individuals.Conclusion: The present study provides new insights into the genetic architecture of ICP involving these novel mutations.

To study the effects of structural alterations of chromosomes caused by tandem repeats on the meiotic recombination, the wheat (Triticum aestivum L.) 5A chromosomes with different structure from ten wheat cultivars were used to investigate their meiotic recombination using non-denaturing fluorescence in situ hybridization (ND-FISH) technology. Fifteen cross combinations were carried out and they were divided into seven F1 categories. The structural difference between the intercalary regions of the long arms of the two 5A chromosomes (5AL) in the F1 categories III, VI, and VII was greater than that in the categories I and II, subsequently, the recombination frequencies in the distal regions of the 5AL arm in the progenies from the three categories were significantly lower than that from the categories I and II. For the two 5A chromosomes in the F1 categories VI and VII, the structural differences in the distal regions of both of the two arms were greater than that in the categories IV and V. So, the recombination frequencies in the intercalary region of the 5AL arm in the progeny from the categories IV and V were higher than that in the progeny from the categories VI and VII. The breakage of 5A chromosome together with the 5A translocations and the breakage of some other chromosomes were observed in the progeny from the F1 categories V, VI, and VII. These chromosomal variations were not observed in the progenies from the other four F1 categories. In conclusion, the smaller structural difference between the 5A chromosomes in distal regions of the two arms resulted in a higher recombination frequency in interstitial region and vice versa. The 5A chromosome with complex cytological structure can be used to induce genetic variations of wheat genome.

MicroRNA-7 (miR-7) is a highly conserved short non-coding RNA involved in various bioprocesses via the regulation of multiple target genes. To enrich our knowledge of the functions of miR-7 in innate immune regulation in echinoderms, we first investigated the targeting relationship between miR-7 and PAK1 in the sea cucumber Apostichopus japonicus and then explored the functions of miR-7, the PAK1 gene, and the miR-7/PAK1 axis in the pathogen-induced immune response of A. japonicus. Our results showed that miR-7 can bind to the 3ʹUTR of PAK1 and negatively regulate the expression of PAK1 in A. japonicus. Overexpression and inhibition of miR-7 and inhibition of the expression of PAK1 can alter phagocytosis, cellular agglutination, and lysozyme contents in A. japonicus. Both miR-7 and the PAK1 gene are involved in immune defense against Vibrio splendidus infection; the miR-7/AjPAK1 axis showed immune regulatory function at 48 to 72 h post-infection (hpi) after V. splendidus infection in A. japonicus. In summary, the results of this study established that miR-7 regulates the pathogen-induced immune response by targeting PAK1 in A. japonicus.

Enterocytozoon bieneusi is a common opportunistic intestinal pathogen that can cause acute diarrhea in immunosuppressed humans and animals. Though E. bieneusi has been widely detected in pigs around the world, little is known of its prevalence and genotype distribution in pigs in Shanxi province, north China. In this study, a total of 362 fecal samples were collected from pigs in three representative counties in north, south, and central Shanxi province, China. The prevalence and genotypes of E. bieneusi were investigated by nested PCR amplification of the ribosomal internal transcribed spacer (ITS) region of the ribosomal RNA (rRNA) gene. Overall, the prevalence of E. bieneusi in pigs in Shanxi province was 54.70% (198/362). Statistical analysis showed the difference in prevalence was statistically significant between regions (χ2 = 41.94, df = 2, P < 0.001) and ages (χ2 = 80.37, df = 1, P < 0.001). In addition, 16 genotypes of E. bieneusi were identified in this study by sequence analysis of the ITS region, including 15 known genotypes (EbpC, EbpA, EbpB, pigEb4, PigEBITS5, I, Henan-I, G, WildBoar 7, SH10, EbpD, CHC5, PigSpEb1, PigSpEb2, and CHG19) and one novel genotype (designated as PigSX-1). Phylogenetic analysis revealed that 14 known genotypes and the novel genotype were clustered into Group 1, whereas genotype I belonged to Group 2. To the best of our knowledge, this is the first report on the prevalence and genotypes of E. bieneusi in pigs in Shanxi province. These findings enrich the genetic diversity of E. bieneusi and provide the baseline data for the prevention and control of E. bieneusi in pigs in the study regions.

The outbreak of COVID-19 epidemic has increased work demands for medical staff and has a certain impact on their mental health. The present study aimed to examine the role of perceived stress and social support in explaining the association between the occupational stressors and three mental health symptoms (i.e., anxiety, depression, and insomnia) of frontline medical staff. Five hundred twenty five frontline medical staff were investigated online after the outbreak of the COVID-19 (16 February, 2020–2 March, 2020) in China. The results found that the prevalence of anxiety, depression, and insomnia among frontline medical staff were 39.8, 29.9, and 37.9%, respectively. Occupational stressors were associated with anxiety, depression, and insomnia symptoms. Perceived stress significantly mediated this link. Social support moderated the second half of the indirect effect of occupational stressors on anxiety and depression symptoms. Under the epidemic situation of COVID-19, for frontline medical staff, high perceived stress and low social support may increase vulnerability for mental health symptoms triggered by occupational stressors. Thus, improving the social support and promoting the cognitive reappraisal of perceived stress may help to maintain mental health among medical staff.

ObjectiveAlcohol dependence can increase the level of anxiety. A growing body of research has identified a link between anxiety symptoms of problem drinkers and their genetic or environment factors, respectively. However, to date few studies have directly examined gene-environment (G × E) interaction on their anxiety symptoms during the acute alcohol withdrawal. The present study aims to examine the interaction between the proopiomelanocortin (POMC) rs2071345 polymorphism and alcohol dependence on anxiety symptoms of male problem drinkers, and further test the exact form of interaction on two competing models: the diathesis-stress model vs. the differential susceptibility model.MethodsA total of 440 male problem drinkers (Mage = 44.5 years, SD = 9.45) were recruited from nine main psychiatric hospitals of northern China during acute alcohol withdrawal. Blood samples were collected for genotyping, self-reported anxiety symptoms, and levels of alcohol dependence were assessed.ResultsResults indicated that the POMC rs2071345 polymorphism significantly moderated anxiety symptoms associated with alcohol dependence. A region of significance (RoS) test showed that male problem drinkers with T allele were more likely to experience more anxiety symptoms than those with CC homozygote when the standardized score of concurrent alcohol dependence was above 0.31. Confirmatory model evaluation indicated that the interaction effect involving POMC gene polymorphism conformed to the diathesis-stress model rather than differential-susceptibility model of person × environment interaction.ConclusionsThis study suggested that the SNP in POMC rs2071345 was associated with alcohol dependence in anxiety symptoms of male problem drinkers and further provided evidence in support of the diathesis-stress hypothesis of alcohol dependence in terms of anxiety symptoms.

BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive and devastating chronic lung condition affecting over 3 million people worldwide with a high mortality rate and there are no effective drugs. Angiotensin II (Ang II), as a major effector peptide of the renin angiotensin aldosterone system, has been shown to act in tandem with the transforming growth factor-β (TGF-β) signaling pathway to promote the infiltration of inflammatory cells, production of reactive oxygen species (ROS) and profibrotic factors after lung injury, and to participate in the process of epithelial mesenchymal transition (EMT). Catalpol (CAT) has been shown to have anti-inflammatory and antifibrotic effects. However, the effects and mechanisms of CAT on pulmonary fibrosis are not clear.PurposeTo assess the effects and mechanisms of catalpol on bleomycin-induced pulmonary fibrosis in mice.MethodsWe used bleomycin-induced mouse model of pulmonary fibrosis to evaluate the alleviation effect of CAT at 7, 14, 28d, respectively. Next, enzyme-linked immunosorbent assay, hematoxylin-eosin staining, immunofluorescence, Masson trichrome staining and western blotting were used to study the underlying mechanism of CAT on bleomycin-induced pulmonary fibrosis.ResultsIt's demonstrated that CAT exerted a potent anti-fibrotic function in BLM-induced mice pulmonary fibrosis via alleviating inflammatory, ameliorating collagen deposition, reducing the level of Ang II and HYP and alleviating the degree of EMT. Moreover, CAT attenuate BLM-induced fibrosis by targeting Ang II/AT1 and TGF-β/Smad signaling in vivo.ConclusionCAT may serve as a novel therapeutic candidate for the simultaneous blockade of Ang II and TGF-β pathway to attenuate pulmonary fibrosis.

The assembly construction of prefabricated UHPC elements can well balance quality reliability and construction convenience, thus it has excellent application prospects in bridge engineering. The joints between prefabricated elements are the key to ensuring the overall force performance of the structure, which directly determine the load-bearing capacity and the life of structure. To clarify the bending behavior of epoxy adhesive joints between prefabricated UHPC elements, four groups of 12 bending tests were carried out with different interface treatment forms as parameters. The failure modes, load-deflection curves, and ultimate bending strength of the interface were investigated. The results reveal that the interfacial failure modes mainly include the interfacial stripping failure of epoxy-UHPC surface, steel fibers and fine aggregates into UHPC surface by pulling out, and tensile damage of UHPC at the root of key teeth on the side of the keyway interface. The load-deflection curves of all specimens exhibit the two-fold lines form. The load tends to rise linearly during the loading phase, and there is no yielding phase before the failure. The load-carrying capacity of the specimen is lost immediately after the failure, and no reliable residual strength is available except for the keyway interface. In addition, the bending strength of rough interface, groove interface, and keyway interface are respectively improved by −24.02, 2.34, and 4.64%, compared with the natural interface. So it is recommended that the joint between prefabricated UHPC elements take the form of keyway interface. Finally, a simplified force model of the keytooth adhesive joint is proposed, and a calculation formula for the flexural bearing capacity is established based on the principal of Mohr’s circle, based on the experimental results and theoretical analysis. The mean ratio of the proposed adhesive joint calculation equation to the experimental results was 0.925 with a standard deviation of 0.065.

Bone marrow is the main hematopoietic organ that produces red blood cells, granulocytes, monocyte/macrophages, megakaryocytes, lymphocytes, and myeloid dendritic cells. Many of these cells play roles in the pathogenesis of Toxocara canis infection, and understanding how infection alters the dynamics of transcription regulation in bone marrow is therefore critical for deciphering the global changes in the dog transcriptional signatures during T. canis infection. In this study, long non-coding RNA (lncRNA) and messenger RNA (mRNA) expression profiles in the bone marrow of Beagle dogs infected with T. canis were determined at 12 h post-infection (hpi), 24 hpi, 96 hpi, and 36 days post-infection (dpi). RNA-sequencing and bioinformatics analysis identified 1,098, 984, 1,120, and 1,305 differentially expressed lncRNAs (DElncRNAs), and 196, 253, 223, and 328 differentially expressed mRNAs (DEmRNAs) at 12 h, 24 h, 96 h, and 36 days after infection, respectively. We also identified 29, 36, 38, and 68 DEmRNAs potentially cis-regulated by 44, 44, 51, and 80 DElncRNAs at 12 hpi, 24 hpi, 96 hpi, and 36 dpi, respectively. To validate the sequencing findings, qRT-PCR was performed on 10 randomly selected transcripts. Many altered genes were involved in the differentiation of bone marrow cells. GO of DElncRNAs and GO and KEGG pathway analyses of DEmRNAs revealed alterations in several signaling pathways, including pathways involved in energy metabolism, amino acid biosynthesis and metabolism, Wnt signaling pathway, Huntington's disease, HIF-1 signaling pathway, cGMP–PKG signaling pathway, dilated cardiomyopathy, and adrenergic signaling in cardiomyocytes. These findings revealed that bone marrow of T. canis-infected dogs exhibits distinct lncRNA and mRNA expression patterns compared to healthy control dogs. Our data provide novel insights into T. canis interaction with the definitive host and shed light on the significance of the non-coding portion of the dog genome in the pathogenesis of toxocariasis.

Cysteine S-sulphenylation (CSO), as a novel post-translational modification (PTM), has emerged as a potential mechanism to regulate protein functions and affect signal networks. Because of its functional significance, several prediction approaches have been developed. Nevertheless, they are based on a limited dataset from Homo sapiens and there is a lack of prediction tools for the CSO sites of other species. Recently, this modification has been investigated at the proteomics scale for a few species and the number of identified CSO sites has significantly increased. Thus, it is essential to explore the characteristics of this modification across different species and construct prediction models with better performances based on the enlarged dataset. In this study, we constructed several classifiers and found that the long short-term memory model with the word-embedding encoding approach, dubbed LSTMWE, performs favorably to the traditional machine-learning models and other deep-learning models across different species, in terms of cross-validation and independent test. The area under the receiver operating characteristic (ROC) curve for LSTMWE ranged from 0.82 to 0.85 for different organisms, which was superior to the reported CSO predictors. Moreover, we developed the general model based on the integrated data from different species and it showed great universality and effectiveness. We provided the on-line prediction service called DeepCSO that included both species-specific and general models, which is accessible through http://www.bioinfogo.org/DeepCSO.

Toxocara canis is a neglected zoonotic parasite, which threatens the health of dogs and humans worldwide. The molecular mechanisms that underlie the progression of T. canis infection remain mostly unknown. MicroRNAs (miRNAs) are small non-coding RNAs that have been identified in T. canis; however, the regulation and role of miRNAs in the host during infection remain incompletely understood. In this study, we determined hepatic miRNA expression at different stages of T. canis infection in beagle dogs. Individual dogs were infected by 300 embryonated T. canis eggs, and their livers were collected at 12 hpi (hours post-infection), 24 hpi, and 36 dpi (days post-infection). The expression profiles of liver miRNAs were determined using RNA-sequencing. Compared to the control groups, 9, 16, and 34 differentially expressed miRNAs (DEmiRNAs) were detected in the livers of infected dogs at the three infection stages, respectively. Among those DEmiRNAs, the novel-294 and cfa-miR-885 were predicted to regulate inflammation-related genes at the initial stage of infection (12 hpi). The cfa-miR-1839 was predicted to regulate the target gene TRIM71, which may influence the development of T. canis larvae at 24 hpi. Moreover, cfa-miR-370 and cfa-miR-133c were associated with immune response at the final stage of infection (36 dpi). Some immunity-related Gene Ontology terms were enriched particularly at 24 hpi. Likewise, Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that many significantly enriched pathways were involved in inflammation and immune responses. The expression level of nine DEmiRNAs was validated using quantitative real-time PCR (qRT-PCR). These results show that miRNAs play critical roles in the pathogenesis of T. canis during the hepatic phase of parasite development. Our data provide fundamental information for further investigation of the roles of miRNAs in the innate/adaptive immune response of dogs infected by T. canis.

Significantly increased imported schistosomiasis cases have been reported in China as the economy grows. The aim of this study is to review and summarize the current status, clinical features, and transmission risk of imported infections of Schistosoma mansoni and Schistosoma haematobium in China. A retrospective study was performed to review all information regarding the imported cases of schistosomiasis collected from published literature and the database of the National Notifiable Disease Report System from 1979 to 2019. The characterization of epidemiological and clinical features was analyzed. A total of 355 cases of imported schistosomiasis have been reported in 15 provinces (autonomous regions, municipalities) in China since 1979, including 78 cases of infection with S. mansoni (21.97%), 262 cases with S. haematobium (73.80%), and 15 cases with unidentified Schistosoma species. Eosinophilia was the most common sign of the infection with S. mansoni (91.03%). The parasitological findings were confirmed in 89.74% (70/78) of cases infected with S. mansoni and 32.06% (84/262) of cases infected with S. haematobium. There was no imported case of infection of Schistosoma japonicum, Schistosoma intercalatum, or Schistosoma mekongi reported in China during this period. Praziquantel is the best therapeutic drug for curing imported schistosomiasis. In addition, Biomphalaria straminea, the intermediate host of S. mansoni, has already been found in Guangdong province in south China. There is a rising risk that the existence of the intermediate host B. straminea and the imported cases of S. mansoni infection could cause the spread of the infections and make these endemic. Thus, better understanding of the clinical features and the transmission pattern of these Schistosoma infections would assist Chinese physicians in the diagnosis and treatment of these imported schistosomiasis cases.

Infection by the protozoan Toxoplasma gondii can have a devastating impact on the structure and function of the brain of the infected individuals, particularly immunocompromised patients. A systems biology view of the brain transcriptome can identify key molecular targets and pathways that mediate the neuropathogenesis of cerebral toxoplasmosis. Here, we performed transcriptomic analysis of the brain of mice infected by T. gondii Pru strain oocysts at 11 and 33 days post-infection (dpi) compared to uninfected (control) mice using RNA sequencing (RNA-seq). T. gondii altered the expression of 936 and 2,081 transcripts at 11 and 33 dpi, respectively, and most of these were upregulated in the infected brains. Gene Ontology (GO) enrichment and pathway analysis showed that immune response, such as interferon-gamma (IFN-γ) responsive genes were strongly affected at 11dpi. Likewise, differentially expressed transcripts (DETs) related to T cell activation, cytokine production and immune cell proliferation were significantly altered at 33 dpi. Host-parasite interactome analysis showed that some DETs were involved in immune signaling, metabolism, biosynthesis-related processes and interspecies interaction. These findings should increase knowledge of the mouse brain transcriptome and the changes in transcriptional regulation and downstream signaling pathways during acute and chronic T. gondii infections.

A Gram-positive, α-hemolytic, catalase-negative, facultative anaerobic and non-motile coccus was isolated form throat swabs taken from the oropharynx of healthy children. The genome was shown to be 1.950,659 bp long and contained 42.03 mol% G + C bases with 1,942 protein-coding and 53 RNA coding genes. The results of 16S rRNA gene sequencing strongly suggested that the strain is a member of the Streptococcus genus, with 98.04, 98.11, and 97.34% similarities to Streptococcus australis ATCC 700641T, Streptococcus rubneri LMG 27207T and Streptococcus parasanguinis ATCC 15912T, respectively. A sodA gene comparison exhibited a sequence identity of 92.6% with the closest strain Streptococcus australis ATCC 700641T. In silico DNA-DNA hybridization showed a highest DNA similarity value of 52% with Streptococcus australis ATCC 700641T. Comparing 18 biochemical traits, the similarities of the Streptococcus strain E24 were 72% with Streptococcus rubneri LMG 27207T, 78% with Streptococcus australis ATCC 700641T and 44% with Streptococcus parasanguinis ATCC 15912T. We suggest that based on the genotypic and phenotypic results that the strain E24 is a novel species of the Streptococcus genus and propose the name Streptococcus xiaochunlingii sp. nov. E24.

As a novel type of post-translational modification, lysine 2-Hydroxyisobutyrylation (Khib) plays an important role in gene transcription and signal transduction. In order to understand its regulatory mechanism, the essential step is the recognition of Khib sites. Thousands of Khib sites have been experimentally verified across five different species. However, there are only a couple traditional machine-learning algorithms developed to predict Khib sites for limited species, lacking a general prediction algorithm. We constructed a deep-learning algorithm based on convolutional neural network with the one-hot encoding approach, dubbed CNNOH. It performs favorably to the traditional machine-learning models and other deep-learning models across different species, in terms of cross-validation and independent test. The area under the ROC curve (AUC) values for CNNOH ranged from 0.82 to 0.87 for different organisms, which is superior to the currently available Khib predictors. Moreover, we developed the general model based on the integrated data from multiple species and it showed great universality and effectiveness with the AUC values in the range of 0.79–0.87. Accordingly, we constructed the on-line prediction tool dubbed DeepKhib for easily identifying Khib sites, which includes both species-specific and general models. DeepKhib is available at http://www.bioinfogo.org/DeepKhib.

Induction of humoural immunity is critical for clinical protection against malaria. More than 100 malaria vaccine candidates have been investigated at different developmental stages, but with limited protection. One of the roadblocks constrains the development of malaria vaccines is the poor immunogenicity of the antigens. The objective of this study was to map the linear B-cell epitopes of the Plasmodium falciparum erythrocyte invasion-associated antigens with a purpose of understanding humoural responses and protection. We conducted a large-scale screen using overlapping peptide microarrays of 37 proteins from the P. falciparum parasite, most of which are invasion-associated antigens which have been tested in clinical settings as vaccine candidates, with sera from individuals with various infection episodes. Analysis of the epitome of the antigens revealed that the most immunogenic epitopes were predominantly located in the low-complexity regions of the proteins containing repetitive and/or glutamate-rich motifs in different sequence contexts. However, in vitro assay showed the antibodies specific for these epitopes did not show invasion inhibitory effect. These discoveries indicated that the low-complexity regions of the parasite proteins might drive immune responses away from functional domains, which may be an instructive finding for the rational design of vaccine candidates.

Congenital contractural arachnodactyly (CCA) is an extremely rare monogenic disorder in humans, and the prevalence of CCA is estimated to be less than 1 in 10,000 worldwide. CCA is characterized by arachnodactyly, camptodactyly, the contracture of major joints, scoliosis, pectus deformities, and crumpled ears. Mutations in FBN2 (which encodes fibrillin-2) are responsible for causing this disease. A family with CCA was investigated in this study, and a novel variant, c.3724+3A > C (also identified as IVS28+3A > C), in FBN2 was found in nine patients from the family but was not found in seven unaffected relatives. Reverse transcription-PCR (RT-PCR) and complementary DNA (cDNA) sequencing data showed that exon 28 was skipped in the FBN2 gene. The FBN2 c.3724+3A > C variant led to an in-frame deletion during transcription, which eventually triggered CCA in the Chinese family.

Background and Purpose: The clinical use of tirofiban for patients with acute ischemic stroke (AIS) who underwent mechanical thrombectomy (MT) remains controversial. We aimed to evaluate the safety and efficacy of tirofiban combined with MT in AIS patients.Methods: Patients with AIS who underwent MT from January 2014 to December 2018 were enrolled in three stroke units in China. Subgroup analyses were performed based on stroke etiology which was classified according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria. Safety outcomes were in-hospital intracerebral hemorrhage (ICH), symptomatic intracerebral hemorrhage (sICH) and mortality at 3-month. Efficacy outcomes were favorable functional outcome and functional independence at 3-month and neurological improvement at 24 h, 3 d and discharge.Results: In patients with large artery atherosclerosis (LAA) stroke, multivariate analyses revealed that tirofiban significantly decreased the odds of in-hospital ICH (adjusted OR = 0.382, 95% CI 0.180–0.809) and tended to increase the odds of favorable functional outcome at 3-month (adjusted OR = 3.050, 95% CI 0.969–9.598). By contrast, in patients with cardioembolism (CE) stroke, tirofiban was not associated with higher odds of favorable functional outcome at 3-month (adjusted OR = 0.719, 95% CI 0.107–4.807), but significantly decreased the odds of neurological improvement at 24 h and 3d (adjusted OR = 0.185, 95% CI 0.047–0.726; adjusted OR = 0.268, 95% CI 0.087–0.825).Conclusions: Tirofiban combined with MT appears to be safe and effective in LAA patients, but has no beneficial effect on CE patients.

Toxoplasmosis, one of the most important health-threatening diseases worldwide, is caused by Toxoplasma gondii, which infects a wide range of warm-blooded animals and humans, leading to enormous health and socioeconomic concerns. T. gondii can establish chronic infection to evade the immune response in hosts. Once a chronic infection has been established, the available treatments cannot efficiently control this stage of T. gondii efficiently. Moreover, the available treatments rely only on a few drugs, such as sulfapyridine and pyrimethamine, that tend to have severe side effects. Given these factors, vaccination has been considered to be the most efficient method to prevent and control this disease. However, there is currently lack of effective vaccine available for use to prevent toxoplasmosis apart form Toxovax®, the only available vaccine, which is used in sheep to prevent abortion. To address this problem, we knocked out the NPT1 gene of the type I T. gondii strain using the CRISPR-Cas9 system, constructed a live-attenuated vaccine and evaluated its protective efficacy in a mouse model. Immunization of mice with RH:ΔNPT1 induced a high level of Toxoplasma-specific IgG1, IgG2a and total IgG 42 days after immunization. There was a significant increase in the levels of cytokines in the splenocyte suspensions of RH:ΔNPT1-infected mice, and a mixed Th1/Th2 response was induced in the mice. Remarkably, after heterologous challenges with tachyzoites of the RH, PYS and Pru strains and cysts of the Pru strain by different infection routes, the immunized animals were protected from toxoplasmosis with a 100% survival rate, in both acute and chronic infection. In addition, compared with control mice, the Pru cyst load was clearly reduced in the brains of RH:ΔNPT1-infected immunization-mice. Our study demonstrated that the RH:ΔNPT1 strain was able to evoke strong anti-Toxoplasma immune responses and provide effective protection against parasite strains with different levels of virulence, suggesting that the RH:ΔNPT1 strain may represent a promising live-attenuated vaccine against toxoplasmosis, which is worthy of further evaluation in food-producing animals and in definitive feline host.

Brain microRNAs (miRNAs) change in abundance in response to Toxoplasma gondii infection. However, their precise role in the pathogenesis of cerebral infection with T. gondii oocyst remains unclear. We studied the abundance of miRNAs in the brain of mice on days 11 and 33 post-infection (dpi) in order to identify miRNA pattern specific to early (11 dpi) and late (33 dpi) T. gondii infection. Mice were challenged with T. gondii oocysts (Type II strain) and on 11 and 33 dpi, the expression of miRNAs in mouse brain was investigated using small RNA (sRNA) sequencing. miRNA expression was confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to identify the biological processes, molecular functions, and cellular components, as well as pathways involved in infection. More than 1,500 miRNAs (1,352 known and 150 novel miRNAs) were detected in the infected and control mice. The expression of miRNAs varied across time after infection; 3, 38, and 108 differentially expressed miRNAs (P < 0.05) were detected during acute infection, chronic infection and chronic vs. acute infection, respectively. GO analysis showed that chronically infected mice had more predicted targets of dysregulated miRNAs than acutely infected mice. KEGG analysis indicated that most predicted targets were involved in immune- or disease-related pathways. Our data indicate that T. gondii infection alters the abundance of miRNAs in mouse brain particularly at the chronic stage, probably to fine-tune conditions required for the establishment of a latent brain infection.

T-cell immunoglobulin and mucin-domain-containing molecule 3 (Tim-3) has complicated roles in regulating monocytes and macrophages in various diseases and it tends to be an inhibitory molecule to facilitate the immune escape of parasites in malaria. However, the mechanisms of Tim-3 mediated responses in monocytes and macrophages in malaria have not been clear. In this study, we found that Plasmodium infection down-regulated Tim-3 expression in peripheral monocytes of patients suffering from Plasmodium falciparum malaria and in splenic macrophages of Plasmodium berghei ANKA-infected mice. Tim-3 signal blockade with anti-Tim-3 antibodies enhanced phagocytosis and parasitical mediator production of murine splenic macrophages during Plasmodium infection. In conclusion, Tim-3 constricts monocytes/macrophages activity, and anti-Tim-3 treatment facilitates parasite clearance, especially in the early stage of Plasmodium infection.

Alzheimer’s disease (AD) is the most prevalent form of late-life dementia in the population, characterised by amyloid plaque formation and increased tau deposition, which is modulated by Rho-associated coiled-coil kinase 1 (ROCK1). In this study, we further analyse whether ROCK1 regulates the metabolism of amyloid precursor protein (APP). We show that ROCK1 is colocalised with mature Aβ plaques in patients with AD, in that ROCK1 enhances the amyloidogenic pathway, and that ROCK1 mediated autophagy enhances the intracellular buildup of Aβ in a cell model of AD, (confirmed by increased ROCK1 and decreased Beclin 1 protein levels, with neuronal autophagosome accumulation in prefrontal cortex of AD APP/PS1 mouse model). In vitro over-expression of ROCK1 leads to a decrease in Aβ secretion and an increase in the expression of autophagy-related molecules. ROCK1 interacts with Beclin1, an autophagy initiator, and enhances the intracellular accumulation of Aβ. Reciprocally, overexpression of APP/Aβ promotes ROCK1 expression. Our data suggest ROCK1 participates in regulating Aβ secretion, APP shedding and autophagosome accumulation, and that ROCK1, rather than other kinases, is more likely to be a targetable enzyme for AD therapy.