Partner of neuropeptide bursicon homodimer pburs mediates a novel antimicrobial peptide Ten3LP via Dif/Dorsal2 in Tribolium castaneum.

Bursicon is a cystine knot family neuropeptide, composed of two subunits, bursicon (burs) and partner of burs (pburs). The subunits can form heterodimers to regulate cuticle tanning and wing maturation and homodimers to signal different biological functions in innate immunity, midgut stem cell proliferation and energy homeostasis, and reproductive physiology in the model insects Drosophila melanogaster or Tribolium castaneum. Here, we report on the role of the pburs homodimer in signaling innate immunity in T. castaneum larvae. Through transcriptome analysis we identified a set of immune-related genes that respond to pburs RNAi. Treating larvae with recombinant-pburs protein led to up-regulation of antimicrobial peptide (AMP) genes in vivo and in vitro. The upregulation of most AMP genes was dependent on the NF-κB transcription factor Relish. Most importantly, we identified a novel AMP, Tenecin 3-like peptide (Ten3LP), regulated by pburs via NF-κB transcription factor Dorsal-related immunity factor (Dif)/Dorsal2, but not Relish. We conducted Ten3LP RNAi, synthesized recombinant Ten3LP protein for microbial inhibition assays and functionally characterized Ten3LP as an AMP specific for fungi and Gram-positive bacteria. We demonstrate that expression of Ten3LP is activated by pburs via the Toll pathway. These findings identify new molecular targets for development of potential antibiotics for treating microbial infections and perhaps for RNAi based pest management technology.

Associations between dietary copper intake, general obesity and abdominal obesity risk: A nationwide cohort study in China.

Objective: Copper plays a crucial role in redox reactions. The aims of this research are to examine the effects of copper consumption on general obesity and abdominal obesity risk. Methods: Overall, data of 13,282 participants were obtained from the China Health and Nutrition Survey (1997-2011). A combination of individual 24-h recall and household survey was used to assess dietary intake. Time-dependent mixed effect Cox regression model treating family as a random effect were used to assess the associations between quintiles of copper intake, general obesity and abdominal obesity risk. Obesity was defined by BMI ≥ 28 kg/m2, and abdominal obesity was defined as waist circumference ≥85 cm in men and ≥80 cm in women. Results: During follow-up, 1,073 and 4,583 incident cases of general obesity and abdominal obesity occurred respectively. There were U-shaped associations of dietary copper intakes with general obesity and abdominal obesity (P for nonlinearity <0.001). In the general obesity track, compared with quintile 3 (reference category), participants in the top quintile and bottom quintile showed higher general obesity risk (HR, 2.00; 95%CI: 1.63, 2.45 for the top quintile, HR, 1.34; 95%CI: 1.08, 1.68 for the bottom quintile). In the abdominal obesity track, compared with quintile 3, the top quintile and bottom quintile were also associated with a significantly increased risk of abdominal obesity (HR, 1.68; 95%CI: 1.52, 1.87 for the top quintile, HR, 1.36; 95%CI: 1.22, 1.52 for the bottom quintile). Conclusions: We demonstrated U-shaped associations between dietary copper, general and abdominal obesity risk in Chinese and emphasized the importance of maintaining appropriate copper intake level for the prevention of obesity.

Association between trajectories of fasting plasma glucose and risk of osteoporosis in non-diabetic and diabetic populations.

Introduction: Previous studies based on a single measure of fasting plasma glucose (FPG) showed an inconsistent conclusion about the association between FPG and osteoporosis risk. Not accounting for time-varying and cumulative average of FPG over time could bias the true relation between FPG and osteoporosis. Our study aims to investigate the association between the trajectories of FPG and osteoporosis risk for non-diabetic and diabetic populations. Methods: A total of 18,313 participants who attended physical examinations during 2008-2018 were included. They were free of osteoporosis at their first physical examination and followed until their last physical examination before December 31, 2018. We recorded their incidence of osteoporosis and at least three FPG values during follow-up. Their longitudinal FPG trajectories were identified by the latent class growth analysis model based on the changes in FPG. Multivariable logistic regression models were used to analyze the association between the trajectories of FPG and osteoporosis diagnosed in the follow-up physical examination in both non-diabetics and diabetics. Results: There were 752 incident osteoporosis among 16,966 non-diabetic participants, and 57 incident osteoporosis among 1,347 diabetic participants. Among non-diabetics, the elevated-increasing FPG trajectory was negatively associated with osteoporosis risk in women (odds ratio (OR), 0.62; 95% confidence interval (CI), 0.43-0.88). Premenopausal women with elevated-increasing FPG trajectory had lower osteoporosis risk than those women with normal-stable FPG trajectory (OR, 0.41; 95% CI, 0.20-0.88), while this association was insignificant in postmenopausal women. Among diabetics, those whose longitudinal FPG is kept at a very high level had the highest risk of osteoporosis (OR, 3.09; 95% CI, 1.16-8.22), whereas those whose FPG starts with the high level and keeps on increasing did not exhibit a significantly increased risk (OR, 1.75; 95% CI, 0.81-3.76) compared with those who keep stable moderate-high level of FPG, except in men (OR, 2.49; 95% CI, 1.02-6.12). Conclusion: Distinct trajectories of FPG are associated with differential risk of osteoporosis in non-diabetic and diabetic populations. Controlling a proper FPG level in different populations is necessary for osteoporosis prevention.

Prevalence and risk factors of MRI-defined brain infarcts among Chinese adults.

Background: Few studies have explored the prevalence and risk factors of brain infarcts (BI) detected by magnetic resonance imaging (MRI) in China. The purpose was to evaluate the prevalence and risk factors of brain infarcts (BI) detected by magnetic resonance imaging (MRI) in 1.4 million Chinese adults. Methods: This was a multicenter cross-sectional study conducted on 1,431,527 participants aged ≥18 years (mean age: 46.4 years) who underwent MRI scans in health examinations from 28 provinces of China in 2018. MRI-defined BI was defined as focal parenchymal lesions ≥3 mm. Multivariable logistic regression analyses were performed to evaluate risk factors associated with MRI-defined BI. Results: The age- and sex-standardized prevalence of MRI-defined BI, lacunar and non-lacunar infarcts were 5.79% (5.75-5.83%), 4.56% (4.52-4.60%), and 1.23% (1.21-1.25%), respectively. The sex-standardized prevalence of MRI-defined BI ranged from 0.46% among those aged 18-29 years to 37.33% among those aged ≥80 years. Men (6.30%) had a higher age-standardized prevalence of MRI-defined BI than women (5.28%). The highest age- and sex-standardized prevalence of MRI-defined BI was observed in the Northwest (8.34%) and Northeast (8.02%) regions, while the lowest prevalence was observed in the Southwest (4.02%). A higher risk of MRI-defined BI was associated with being male [odd ratio (OR) 1.17, 95% CI 1.15-1.19], older age (OR per 10-year increments 2.33, 2.31-2.35), overweight (1.12, 1.10-1.14) or obesity (1.18, 1.16-1.21), hypertension (1.80, 1.77-1.83), diabetes (1.24, 1.21-1.26), and dyslipidemia (1.07, 1.05-1.08). Conclusion: MRI-defined BI is highly prevalent in China, even among young adults. MRI-defined BI was associated with being male, older age, living in the northern region, and metabolic conditions.

Prevalence and risk factors of atrioventricular block among 15 million Chinese health examination participants in 2018: a nation-wide cross-sectional study.

BACKGROUND: Nationwide data on the prevalence of atrioventricular (AV) block are currently unavailable in China. Thus, we aimed to assess the prevalence and risk factors of AV block among Chinese health examination adults. METHODS: A total of 15,181,402 participants aged ≥ 18 years (mean age 41.5 ± 13.4 years, 53.2% men) who underwent an electrocardiogram as a part of routine health examination in 2018 were analyzed. AV block was diagnosed by physicians using 12-lead electrocardiogram. Overall and stratified prevalence (by age, sex, and city size) of all, first-, second- and third-degree AV block were calculated. Multivariable logistic regression analyses were performed to explore risk factors associated with AV block. RESULTS: AV block was observed in 88,842 participants, including 86,153 with first-degree, 2249 with second-degree and 440 with third-degree AV block. The age- and sex-standardized prevalence rate [95% confidence interval (CI)] of all, first-, second- and third-degree AV block were 7.06‰ (7.01-7.11), 6.84‰ (6.79-6.89), 0.18‰ (0.17-0.18) and 0.04‰ (0.03-0.04) respectively. After multivariable adjustment, the risk of AV block was positively associated with older age, being male, lower heart rate, higher body mass index, hypertension, diabetes and low high-density lipoprotein cholesterol. High total cholesterol was associated with a lower risk of AV block. CONCLUSION: First-degree AV block is relatively common while severe AV block is rare in health examination adults. Besides, AV block was highly prevalent among the elderly. The risk of AV block was associated with older age, being male and metabolic factors.

Association between Ambient Air Pollution and MRI-Defined Brain Infarcts in Health Examinations in China.

The study aimed to evaluate the relationships between air pollutants and risk of magnetic resonance imaging (MRI)-defined brain infarcts (BI). We used data from routine health examinations of 1,400,503 participants aged ≥18 years who underwent brain MRI scans in 174 cities in 30 provinces in China in 2018. We assessed exposures to particulate matter (PM)2.5, PM10, nitrogen dioxide (NO2), and carbon monoxide (CO) from 2015 to 2017. MRI-defined BI was defined as lesions ≥3 mm in diameter. Air pollutants were associated with a higher risk of MRI-defined BI. The odds ratio (OR) (95% CI) for MRI-defined BI comparing the highest with the lowest tertiles of air pollutant concentrations was 2.00 (1.96-2.03) for PM2.5, 1.68 (1.65-1.71) for PM10, 1.58 (1.55-1.61) for NO2, and 1.57 (1.54-1.60) for CO. Each SD increase in air pollutants was associated with 16-42% increases in the risk of MRI-defined BI. The associations were stronger in the elderly subgroup. This is the largest survey to evaluate the association between air pollution and MRI-defined BI. Our findings indicate that ambient air pollution was significantly associated with a higher risk of MRI-defined BI.

Extent reflecting overall dietary amino acids composition adherence to the human requirement amino acids pattern is associated with the development of type 2 diabetes.

This study aimed to elucidate whether dietary amino acids (AAs) composition is associated with type 2 diabetes mellitus (T2DM) and to investigate how serum AAs profiles mediated this association. Two prospective cohorts of 1750 and 4024 adults were enrolled. Dietary AAs compositions index (AACI) was developed to reflect the overall quality of dietary AAs composition. Multivariate linear regression and logistic regression models were used to examine associations of AACI and T2DM. The AACI was associated with the incidence of T2DM with the relative risk and 95%CI from the bottom to the top tertiles being 1.00, 1.49 (0.88-2.51) and 2.27 (1.20-4.28), and 1.00, 1.58 (1.13-2.19) and 2.33 (1.56-3.47) in the two cohorts, respectively. The AACI was positively associated with serum valine, isoleucine, glutamic acid and phenylalanine, and it was negatively associated with serum glycine and histidine in both cohorts (P<0.01). Valine, glutamic acid and histidine consistently and partially mediated the association between the AACI and T2DM in the two cohorts, with total mediation effects of 33.4% and 54.6%, respectively. Dietary AAs composition was associated with the incidence of T2DM, meanwhile, the relationship was mediated by some degree of serum AAs. Future dietary strategies should focus on the improvement of the overall quality of dietary AAs compositions.

Incidence and Risk Factors of Hyperuricemia among 2.5 Million Chinese Adults during the Years 2017-2018.

Objective: To assess the incidence and risk factors of hyperuricemia among Chinese adults in 2017-2018. Methods: A total of 2,015,847 adults (mean age 41.2 ± 12.7, 53.1% men) with serum uric acid concentrations assayed on at least two separate days in routine health examinations during 2017-2018 were analyzed. Hyperuricemia was defined as fasting serum urate concentration >420 µmol/L in men and >360 µmol/L in women. The overall and sex-specific incidence rate were stratified according to age, urban population size, geographical region, annual average temperature and certain diseases. Logistic regression analyses were performed to explore risk factors associated with hyperuricemia. Results: 225,240 adults were newly diagnosed with hyperuricemia. The age- and sex-standardized incidence rate per 100 person-years was 11.1 (95%CI: 11.0-11.1) (15.2 for men and 6.80 for women). The risk of hyperuricemia was positively associated with younger age, being male, larger urban population size, higher annual temperature, higher body mass index, lower estimate glomerular filtration rate, hypertension, dyslipidemia and fat liver. Conclusions: The incidence of hyperuricemia was substantial and exhibited a rising trend among younger adults, especially among men. Socioeconomic and geographic variation in incidence were observed. The risk of hyperuricemia was associated with estimate glomerular filtration rate, fat liver and metabolic factors.

Dietary iron and vitamins in association with mortality.

BACKGROUND & AIMS: Although disorders of iron metabolism are among the most common diseases and dietary intakes of vitamin A, B2, B6, C, E, and folic acid are known to affect the absorption or oxidation of iron, limited data are available on the association of dietary iron and these vitamins with mortality in the same population. Specifically, the holistic dietary vitamins intake and its combined effect with iron on mortality are unclear. The purpose of this study was to evaluate the association of dietary iron, holistic dietary vitamins, and their interactive effect with total and cause-specific mortality. METHODS: We evaluated the effects of dietary total/heme/non-heme iron, vitamins, and their interaction on all-cause/cardiovascular disease (CVD)/cancer mortality among 14,826 US adults in the National Health and Nutrition Examination Survey (NHANES), a population-based nationally representative study. We developed a vitamin score to represent the holistic dietary intakes of vitamin A, B2, B6, C, E, and folic acid. RESULTS: A total of 2154 deaths occurred during a median follow-up of 9.3 years. Results from multivariate Cox proportional hazards models showed that higher vitamin score was associated lower risk of all-cause mortality (P-trend = 0.027). Negative interactions between dietary heme iron and vitamin score were observed on all-cause/CVD mortality. Dietary higher vitamins combined with lower heme iron was associated with lower risk of all-cause and CVD mortality (HR (95% confidence intervals (CIs)): 0.80 (0.64-0.98) and 0.55 (0.31-0.98), respectively). Higher dietary vitamins combined with higher total/non-heme iron was associated with lower risk of CVD mortality (HR (95%CIs): 0.69 (0.48-0.99) and 0.70 (0.48-0.99), respectively). These results remained significant even excluding participants with iron supplementation. CONCLUSION: Our findings suggested that interactive effect of holistic dietary vitamins and iron play a protective role in decreasing all-cause and CVD mortality. Future studies, including cohort studies and clinical trials, are necessary to confirm these findings.

Temporal relationship between hyperuricemia and obesity, and its association with future risk of type 2 diabetes.

BACKGROUND/OBJECTIVES: Although hyperuricemia and obesity are significantly correlated, their temporal relationship and whether this relationship is associated with future risk of diabetes are largely unknown. This study examined temporal relationship between hyperuricemia and obesity, and its association with future risk of type 2 diabetes. SUBJECTS/METHODS: This study examined two longitudinal cohorts totally including 17,044 subjects from China with an average of 6.0 years follow-up. Measurements of body mass index (BMI), waist circumference (WC), percentage of body fat and fasting serum uric acid were obtained at two time points. Cross-lagged panel and mediation analysis were used to examine the temporal relationship between hyperuricemia and obesity, and the association of this temporal relationship with follow-up diabetes. RESULTS: In combined data of the two cohorts, the cross-lagged path coefficient (ß1 = 0.121; 95% confidence interval (CI): 0.108-0.135) from baseline uric acid to the follow-up BMI was significantly greater than the path coefficient (ß2 = 0.055, 95% CI: 0.038-0.072) from baseline BMI to the follow-up uric acid (P = 8.14e-10 for the difference between ß1 and ß2) with adjustment for covariates. The separate cross-lagged path models of uric acid with WC and percentage of body fat showed temporal patterns similar to that noted for uric acid with BMI. Further, the path coefficient (ß1) from baseline uric acid to follow-up BMI in the group with diabetes was significantly greater than without diabetes (P = 0.003 for the difference of ß1s in the two groups). BMI partially mediated the association of uric acid with risk of diabetes, and the percentage of mediated-association was estimated at 20.3% (95% CI: 15.7-24.8%). Results of these analyses in the combined data were consistent with those in the two cohorts, respectively. CONCLUSIONS: These findings indicated that increased uric acid levels probably associated with obesity and type 2 diabetes, and more definite research is needed to define any role for uric acid in relation to these diseases.

Low-Carbohydrate, High-Protein, High-Fat Diets Rich in Livestock, Poultry and Their Products Predict Impending Risk of Type 2 Diabetes in Chinese Individuals that Exceed Their Calculated Caloric Requirement.

The evidence on the association between long-term low-carbohydrate, high-fat and high-protein diets and type 2 diabetes (T2D) is controversial. Until now, data is limited for Chinese populations, especially in considering the influence of extra energy intake. In this paper, we aimed to investigate the association of low-carbohydrate, high-fat and high-protein diets with type 2 diabetes (T2D) risk in populations consuming extra calories and those with normal caloric intake, We also determined whether the association is mediated by insulin resistance (IR) or ß-cell dysfunction. A total of 3644 subjects in the Harbin People's Health Study (Cohort 1, 2008-2012) and 7111 subjects in the Harbin Cohort Study on Diet, Nutrition and Chronic Non-Communicable Diseases (Cohort 2, 2010-2015) were analyzed, with a median follow-up of 4.2 and 5.3 years, respectively. Multivariate relative risks (RRs) and their 95% confidence intervals (95% CIs) were calculated to estimate the association between low-carbohydrate, high-fat and high-protein diet and T2D in logistic regression models. The multivariate RRs (95% CIs) were 1.00, 2.24 (1.07, 4.72) and 2.29 (1.07, 4.88) (Ptrend = 0.04), and 1.00, 1.45 (0.91, 2.31) and 1.64 (1.03, 2.61) (Ptrend = 0.04) across tertiles of low-carbohydrate, high-fat and high-protein diet scores in the population consuming extra calories in Cohort 1 and Cohort 2, respectively. The association was no longer significant after adjustment for livestock and its products, or poultry and its products. The mediation analysis discovered that this association in the population consuming extra calories was insulin resistance mediated, in both Cohort 1 and Cohort 2. However, the association was not significant among participants overall and participants with normal caloric intake. Our results indicated that long-term low-carbohydrate, high-fat and high-protein diets were associated with increased T2D risk among the population consuming extra calories, which may be caused by higher intake of animal-origin fat and protein as well as lower intake of vegetables, fruit and fiber. Additionally, the association was mediated by IR. In the population consuming extra calories, reducing the intake of livestock, poultry and their products and increasing the intake of vegetables, fruit and fiber might protect this population from developing T2D.

Potential Mediating Biomarkers underlying the Association of Body Mass Index or Waist Circumference with Blood Pressure: Results from Three Population-based Studies.

We conducted a comprehensive and in-depth assessment of body mass index (BMI) or waist circumference (WC) related to blood pressure (BP) and determined whether the association is mediated by the possible potential mediators in the cross-sectional survey of the Harbin Cohort Study on Diet, Nutrition and Chronic Non-communicable Diseases of 7094 participants aged 20-74 years, and validated the significant findings in the US National Health and Nutrition Examination Survey four cross-sectional cohorts (2005-2006, 2007-2008, 2009-2010, and 2011-2012) and the cohort data of the Harbin People's Health Study (a median of 4.2 follow-up years). We observed that BMI or WC was positively associated with BP (all P-values < 0.0001). Mediation analyses consistently indicated that these associations were mediated mainly by insulin resistance (IR) as measured by the homeostasis model (HOMA-IR), followed by triglyceride (TG) and total cholesterol (TC), and fasting glucose (FG) in the three studies. The proportions via the mediation of insulin/HOMA-IR were 25~40%, TG and TC were 15~20%, and FG was 2~8%, respectively. These findings suggest that the mediators, insulin/insulin resistance, TG, TC, and FG, could be targeted for preventing hypertension among populations who were overweight or obesity.

Dietary Vitamin C Intake Reduces the Risk of Type 2 Diabetes in Chinese Adults: HOMA-IR and T-AOC as Potential Mediators.

Despite growing interest in the protective role that dietary antioxidant vitamins may have in the development of type 2 diabetes (T2D), little epidemiological evidence is available in non-Western populations especially about the possible mediators underlying in this role. The present study aimed to investigate the association of vitamin C and vitamin E intakes with T2D risk in Chinese adults and examine the potential mediators. 178 incident T2D cases among 3483 participants in the Harbin People Health Study (HPHS), and 522 newly diagnosed T2D among 7595 participants in the Harbin Cohort Study on Diet, Nutrition and Chronic Non-communicable Diseases (HDNNCDS) were studied. In the multivariable-adjusted logistics regression model, the relative risks (RRs) were 1.00, 0.75, and 0.76 (Ptrend = 0.003) across tertiles of vitamin C intake in the HDNNCDS, and this association was validated in the HPHS with RRs of 1.00, 0.47, and 0.46 (Ptrend = 0.002). The RRs were 1.00, 0.72, and 0.76 (Ptrend = 0.039) when T2D diagnosed by haemoglobin A1c in the HDNNCDS. The mediation analysis discovered that insulin resistance (indicated by homeostasis model assessment) and oxidative stress (indicated by plasma total antioxidative capacity) partly mediated this association. But no association was evident between vitamin E intake and T2D. In conclusion, our research adds further support to the role of vitamin C intake in reducing the development of T2D in the broader population studied. The results also suggested that this association was partly mediated by inhibiting or ameliorating oxidative stress and insulin resistance.