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Background and Aims: Cardiometabolic multimorbidity has become increasingly common over the past few decades. Little is known about how risk factors affect temporal progression of cardiometabolic multimorbidity. We aim to explore the role of socioeconomic, lifestyle, and clinical risk factors in the progression of cardiometabolic multimorbidity.Methods and Results: This prospective cohort study included 56,587 participants aged ≥45 years who were free of diabetes, stroke, and heart disease. Three clusters of risk factors were assessed and each on a 5-point scale: socioeconomic, lifestyle, and clinical factors. We used multi-state models (MSMs) to examine the roles of risk factors in five transitions of multimorbidity trajectory: from healthy to first cardiometabolic disease, first cardiometabolic disease to cardiometabolic multimorbidity, health to mortality, first cardiometabolic disease to mortality, and cardiometabolic multimorbidity to mortality. In MSMs, socioeconomic (HR: 1.21; 95% CI: 1.19-1.25) and clinical (HR: 1.53; 95% CI: 1.51-1.56) scales were associated with the transition from health to first cardiometabolic. Socioeconomic (HR: 2.39; 95% CI: 2.24-2.54) and lifestyle (HR: 1.22; 95% CI: 1.18-1.26) scales were associated with the transitions from first disease to cardiometabolic multimorbidity. In addition, socioeconomic and lifestyle scales were associated with increased risk of mortality in people without cardiometabolic disease, with first cardiometabolic disease, and with cardiometabolic multimorbidity.Conclusions: Socioeconomic and lifestyle factors were not only important predictors of multimorbidity in those with existing cardiometabolic disease, but also important in shaping risk of mortality. However, clinical factors were the only key determinants of incidence of a first cardiometabolic disease. [ABSTRACT FROM AUTHOR]

Ankle-brachial index (ABI) is a noninvasive diagnostic method for peripheral arterial disease (PAD) and a predictor of cardiovascular events. The present study aimed to evaluate the association between individual or combined essential metals and ABI, as well as assess the collective impact of essential metals when coupled with healthy lifestyle on ABI. A total of 2865 participants were recruited in Wuhan Tongji Hospital between August 2018 and March 2019. Concentrations of essential metals in urine were measured by inductively coupled plasma mass spectrometer. The results of general linear regression models demonstrated that after adjusting for confounding factors, there was a positive association between ABI increase and per unit increase of log 10-transformed, creatinine-corrected urinary Cr (β (95 % CI): 0.010 (0.004, 0.016), P FDR = 0.007), Fe (β (95 % CI): 0.010 (0.003, 0.017), P FDR = 0.018), and Co (β (95 % CI): 0.013 (0.005, 0.021), P FDR = 0.007). The WQS regression revealed a positive relationship between the mixture of essential metals and ABI (β (95 % CI): 0.006 (0.003, 0.010), P < 0.001), with Cr and Co contributing most to the relationship (weighted 45.48 % and 40.14 %, respectively). Compared to individuals with unfavorable lifestyle and the lowest quartile of Cr, Fe and Co, those with favorable lifestyle and the highest quartile of Cr, Fe and Co exhibited the most increase in ABI (β (95 % CI): 0.030 (0.017, 0.044) for Cr, β (95 % CI): 0.027 (0.013, 0.040) for Fe, and β (95 % CI): 0.030 (0.016, 0.044) for Co). In summary, our study indicates that adequate essential metal intake together with healthy lifestyle behaviors perform crucial roles in PAD protection. [Display omitted] • Cr, Fe, and Co were positively associated with ankle-brachial index (ABI). • A positive relationship between essential metal mixture and ABI was observed. • Essential metal may decrease the risk of peripheral arterial disease (PAD). • Healthy lifestyle enhanced the prevention of essential metals on PAD. [ABSTRACT FROM AUTHOR]

Background and Aims: The relationship between dynamic changes in metabolic syndrome (MetS) status and lifetime risk of cardiovascular disease (CVD) has not been reliably quantified. This study aimed to estimate lifetime risk of CVD and life expectancy with and without CVD according to dynamic MetS status.Methods and Results: Dynamic changes in MetS status were assessed: MetS-free, MetS-chronic, MetS-developed, and MetS-recovery groups. We used Modified Kaplan-Meier method to estimate lifetime risk and used multistate life table method to calculate life expectancy. Participants free of CVD at index ages 35 (n = 40 168), 45 (n = 33 569), and 55 (n = 18 546) years. At index age 35 years, we recorded 1341 CVD events during a median follow-up of 6.1 years. Lifetime risk of 33.9% (95% CI: 26.9%-41.0%) in MetS-recovery group was lower than that of 39.4% (95% CI: 36.1%-42.8%) in MetS-chronic group. Lifetime risk of 37.8% (95% CI: 30.6%-45.1%) in MetS-developed group was higher than that of 26.4% (95% CI: 22.7%-30.0%) in MetS-free group. At index age 35 years, life expectancy free of CVD for MetS-recovery group (44.1 years) was higher than that for MetS-chronic group (38.8 years). Life expectancy free of CVD for MetS-developed group (41.9 years) was lower than that for MetS-free group (46.7 years).Conclusions: Recovery from MetS was associated with decreased lifetime risk of CVD and a longer life expectancy free of CVD, whereas development of MetS was associated with increased lifetime risk of CVD and a shorter life expectancy free of CVD. [ABSTRACT FROM AUTHOR]

MDG, a polysaccharide derived from Ophiopogon japonicus , displays a protective effect against obesity and non-alcoholic fatty liver disease (NAFLD). However, there is no definitive evidence proving the specific mechanism of MDG against NAFLD. The results showed MDG supplementation ameliorated lipid accumulation, liver steatosis, and chronic inflammation in high-fat diet-induced NAFLD mice. Besides, MDG increased the abundance and diversity of microbial communities in the gut. These effects were mediated by the colonization of fecal microbiota. Further investigation revealed that Akkermansia muciniphila levels correlated negatively with NAFLD development, and lipid metabolism-related signaling might be the key regulator. Our study suggested that MDG treatment could inhibit obesity and the NAFLD process by modulating lipid-related pathways via altering the structure and diversity of gut microbiota. In addition, Akkermansia miniciphila might be a promising candidate in future research into NAFLD. • MDG ameliorates high-fat diet induced lipid disorder and hepatic steatosis. • MDG protects gut barrier integrity and alters gut microbial structure. • muciniphila is a potential target bacterium for future NAFLD therapy. • Lipid metabolism-related signaling may be the key regulator in the modulation of NAFLD. [ABSTRACT FROM AUTHOR]

The purpose of this study is to develop a new polysaccharide-based hydrogel. The Box-Behnken design was used to optimize the optimal synthesis conditions of the hydrogel, with the swelling parameters as indicators. The findings of rheologic tests confirm that free radical polymerization and the introduction of linear polymers improved the mechanical strength of the hydrogel. Combined with the characterization results, the gel mechanism of BSP-g-PAA/PVA DN hydrogel was proposed. The intermolecular association and entanglement increase, which effectively dissipates energy, thereby enhancing the mechanical properties of the hydrogel. In vitro blood compatibility experiments show that DN hydrogel has a low hemolysis rate and a good coagulation effect. The material is non-cytotoxic to L929 cells. The hepatic haemorrhage and mouse-tail amputation models of rats and mice were used to further evaluate the in vivo wound sealing and hemostatic properties of the hydrogel. The blood loss and hemostatic time were significantly lower than those of the control group, indicating that the hydrogel has excellent hemostatic effects. Therefore, the obtained BSP-g-PAA/PVA DN network hydrogel has good comprehensive properties and is expected to be used as a hemostatic material or a precursor of a drug carrier and a tissue engineering scaffold. [ABSTRACT FROM AUTHOR]

Background and Aims: The risk of adverse health conditions varied according to the number of metabolic syndrome components. We aimed to evaluate the risk of mortality and incident cardiovascular events according to the number of components with high variability.Methods and Results: A total of 43,737 Kailuan Study participants with ≥3 examinations of waist circumference, fasting blood glucose, systolic blood pressure, triglyceride, and high-density lipoprotein during 2006-2013 were included in the present study. Visit-to-visit variability in each parameter was defined by the intraindividual standard deviation across visits. High variability was defined as the highest quartile of variability. Participants were classified numerically according to the number of high-variability components (e.g., a score of 0 indicated no high-variability component). There were 1551 deaths during a median follow-up of 5.9 years, and 950 incident cardiovascular disease (CVD) cases during a median follow-up of 4.9 years. In the multivariable adjusted model, compared with participants with low variability for all components, participants with ≥3 high-variability components had significantly higher risks for all-cause mortality (hazards ratio [HR], 1.61; 95 % confidence interval [CI], 1.35-1.91) and incident CVD event (HR, 1.45; 95 % CI, 1.16-1.82). Additionally, participants with ≥3 high-variability components had increased odds of arterial stiffness, as measured by brachia-ankle pulse wave velocity (odds ratio [OR], 1.39; 95 % CI, 1.19-1.63).Conclusions: Our findings suggest that participants with at least three metabolic parameters with high variability experienced increased risk of CVD and all-cause mortality. [ABSTRACT FROM AUTHOR]

Growing evidence suggested that lifestyle factors including dietary habits may influence the telomere length which is a reliable marker of biological aging and predictor for chronic diseases. However, the role of dietary selenium intake in telomere length maintenance is rarely examined. We aimed to test the relationship between dietary selenium intake and telomere length among middle-aged and older adults in America. A total of 3194 United States adults older than 45 years old were extracted from the National Health and Nutrition Examination Survey (NHANES) in 1999–2000 and 2001–2002. Leukocyte telomere length was measured using the quantitative real-time polymerase chain reaction (qPCR). Dietary selenium intake was assessed by a trained interviewer using 24-h dietary recall method. Generalized linear models were performed to evaluate the association of dietary selenium intake with telomere length. The restricted cubic spline analysis was used to further explore the nonlinear dose–response relationship between dietary selenium intake and telomere length. After adjusting potential confounders, every 20 μg increase in dietary selenium intake was associated with 0.42% (95% CI: 0.02%, 0.82%) longer telomere length in all participants. In the subgroup analyses, dietary selenium intake was related to longer telomere length in females (Percentage change: 0.87%; 95% CI: 0.26%, 1.49%) and non-obese participants (Percentage change: 0.53%; 95% CI: 0.04%, 1.02%), but not in males (Percentage change: 0.04%; 95% CI: −0.49%, 0.57%) and obese participants (Percentage change: 0.21%; 95% CI: −0.47%, 0.91%). The restricted cubic spline analysis showed a linear association between dietary selenium intake and telomere length. This study indicated that the increased dietary selenium intake was associated with longer telomere length among middle-aged and older adults in America. These findings require further corroboration from future prospective studies. • The first study to date on the relationship between dietary selenium intake and leukocyte telomere length in American. • This study indicated that the increased dietary selenium intake was associated with longer telomere length. • The association of dietary selenium intake with telomere length was more prominent among females and non-obese participants. [ABSTRACT FROM AUTHOR]

Aluminum is a widely distributed metal that has been reported to have embryotoxicity and fetotoxicity in animal studies. However, there has been no study of the association between prenatal aluminum exposure and newborn mitochondrial DNA copy number (mtDNAcn). We aimed to investigate the effect of prenatal aluminum exposure on newborn mtDNAcn. A total of 762 mother-newborn pairs were recruited between November 2013 and March 2015 in Wuhan city, China. We measured maternal urinary aluminum concentrations at three trimesters of pregnancy. Relative mtDNAcn was measured in DNA extracted from umbilical cord blood samples. We used generalized estimating equations to assess the relationship between prenatal aluminum exposure and newborn mtDNAcn. The geometric means of creatinine corrected aluminum concentrations were 31.0 μg/g Cr (95% CI: 27.6, 34.7), 40.9 μg/g Cr (95% CI: 35.7, 46.8) and 58.4 μg/g Cr (95% CI: 51.2, 67.4) for the first, second and third trimesters, respectively. After adjustment for potential confounding factors, a doubling of maternal urinary aluminum concentrations during the second and third trimesters was related to 3.16% (95% CI: 0.88, 5.49) and 4.20% (95% CI: 1.64, 6.81) increases in newborn mtDNAcn, respectively, while the association between maternal urinary aluminum concentration during the first trimester and newborn mtDNAcn was not significant (percent difference: 0.70%, 95% CI: −2.25, 3.73). Prenatal aluminum exposure during the second and third trimesters was positively associated with newborn mtDNAcn. Further studies are essential to elucidate on the potential health consequences of newborn mtDNAcn. Image 1 • We assessed the trimester-specific associations between prenatal aluminum exposures and newborn mtDNAcn. • Prenatal aluminum exposures during the second and third trimesters were associated with higher newborn mtDNAcn. • The association between prenatal aluminum exposure during the first trimester and newborn mtDNAcn was not significant. This is the first study on the association between prenatal aluminum exposure and mitochondrial DNA copy number. [ABSTRACT FROM AUTHOR]

Abstract The relation between nonalcoholic fatty liver disease (NAFLD) and hypertension is not fully understood. To examine the effect of the change in NAFLD status on the risk of incident hypertension, and vice versa, 6704 eligible hypertension-free subjects and 9328 NAFLD-free subjects from the Dongfeng-Tongji cohort study at baseline were enrolled in the study. Among the hypertension-free subjects, development and persistence of NAFLD were associated with an increased odds ratio (OR) for incident hypertension (OR: 1.49, 95% confidence interval [CI]: 1.26–1.76, P <.0001; OR: 1.50, 95% CI: 1.27–1.78, P <.0001). However, the resolution of NAFLD was not a risk factor for incident hypertension. Among the NAFLD-free subjects, the risk of new-emerging NAFLD was robust for hypertension status both in no-yes (OR: 1.45, CI: 1.23–1.71) and yes-yes (OR: 1.61, CI: 1.35–1.92). Moreover, stratified analysis by diabetes and overweight/obese for the risk of incident NAFLD showed that incident hypertension (no-yes) and persistent hypertension (yes-yes) were associated with risk of incident NAFLD in subjects without diabetes or overweight/obesity. In the overweight/obese participants, persistent hypertension (yes-yes) was a risk factor for incident NAFLD (OR: 1.29, 95% CI: 1.01–1.64, P =.0387). Conclusively, incidence and persistence of NAFLD are associated with increased risk of hypertension, and vice versa. Highlights • There are bidirectional associations between nonalcoholic fatty liver disease (NAFLD) and hypertension. • Hypertension is associated with increased risk of NAFLD. • Incident hypertension and persistent hypertension were associated with risk of incident NAFLD in subjects without diabetes or overweight/obesity. [ABSTRACT FROM AUTHOR]

Chromium exposure from increasing industrial releases has become a threat for pregnant women due to the potential health effects on vulnerable embryos. Previous studies have suggested that maternal chromium exposure is associated with adverse birth outcomes, but no epidemiological research has been conducted to examine the relationship between chromium exposure and premature rupture of membranes (PROM). This study aimed at investigating the association of maternal urinary chromium exposure levels with PROM and was performed with 5408 pregnant women recruited from 2012 to 2014 in the city of Wuhan, China. Maternal urinary chromium collected before labor was adjusted with creatinine, and its association with PROM was evaluated using logistic regression. Each one unit increase in the natural logarithm transformed maternal urinary chromium concentration (μg/g creatinine), an odds ratio (OR) of 1.47 [95% confidence interval (CI): 1.36, 1.58] for PROM was observed. Compared to the lowest tertile of maternal urinary chromium, PROM was positively correlated with increased urinary levels of chromium (adjusted OR = 1.42; 95% CI: 1.09, 1.84 for the medium tertile; adjusted OR = 2.77; 95% CI: 2.18, 3.52 for the highest tertile). Additionally, the association of chromium with PROM appeared to be more significant among male infants (adjusted OR = 3.52; 95% CI: 2.51, 4.94 for the highest tertile) than female infants (adjusted OR = 2.16; 95% CI: 1.52, 3.06 for the highest tertile) ( p for interaction = 0.05). Our large birth cohort showed an association between maternal urinary chromium levels and PROM, and the association may differ by infant gender. Further studies from different populations are needed to confirm the observed association. [ABSTRACT FROM AUTHOR]

[Display omitted] • Chemical investigation of cold-seep Bacillus sp. HDN20-1259 led to the isolation of three new compounds, and this was the first report of secondary metabolites obtained from cold-seep-derived Bacillus sp. • Compounds 1 , 2 , 5 , and 6 showed broad antibacterial activity, among which 1 and 2 showed antibacterial activity against Staphylococcus aureus with MIC value of 50 µg/ mL. One new glycosylated macrolactin compound, 6′- O -succinyl methyl ester macrolactin O (1), two new hydroxy unsaturated fatty acids (3 and 4), together with three known compounds succinyl macrolactin O (2), macrolactin O and F (5 and 6), were isolated from the liquid culture of Bacillus sp. HDN20-1259. The chemical structures of 1 – 6 were elucidated by extensive NMR, MS, ECD, Mosher's method and thiocarbamoyl-thiazolidine derivatization with reversed-phase HPLC analysis. Compounds 1 , 2 , 5 , and 6 showed extensive antibacterial activity against Bacillus cereus , Staphylococcus aureus , and Escherichia coli , among which 1 and 2 showed antibacterial activity against Staphylococcus aureus with MIC value of 50 µ g/ mL. This is the first report of secondary metabolites obtained from cold-seep-derived Bacillus sp.. [ABSTRACT FROM AUTHOR]

Background: Evidence shows that exposure to poor conditions in early life is associated with an increased risk of chronic diseases in adults.Objective: We investigated whether exposure to the Chinese famine (1959-1961) in the fetal stage or in childhood (0-9 y) was associated with type 2 diabetes (T2D) and hyperglycemia in adulthood.Methods: We included 7801 subjects aged 56.4 ± 3.3 y from the Dongfeng-Tongji cohort. Subjects were classified into late-, middle-, and early-childhood-exposed, fetal-exposed, and unexposed groups. Excess mortality rate was used to evaluate the severity of famine. Logistic regression models were used to analyze the famine-dysglycemia associations. Generalized linear models were used to assess the famine effects on dysglycemia risk during the 5-y follow-up period among 3100 subjects.Results: In descriptive analyses, the risk of T2D was significantly greater in the middle-childhood-exposed group (OR: 1.44; 95% CI: 1.10, 1.87; P = 0.007), and the risk of hyperglycemia was higher in the middle- and late-childhood-exposed groups than in the unexposed group (OR: 1.54; 95% CI: 1.26, 1.88 and OR: 1.51; 95% CI: 1.23, 1.85, respectively). In sex-specific analyses, women exposed in middle childhood (OR: 1.55; 95% CI: 1.16, 2.06) and late childhood (OR: 1.40; 95% CI: 1.05, 1.87) had a higher risk of T2D than unexposed women. This association was not found in men. Similar associations were found for hyperglycemia risk. Moreover, subjects who experienced severe famine in childhood had a 38% higher T2D risk (95% CI: 1.05, 1.81) than those exposed to less severe famine. In retrospective cohort analyses, participants who experienced famine in middle childhood had a higher hyperglycemia risk relative to the unexposed group (RR: 2.06; 95% CI: 1.08, 3.90).Conclusion: Exposure to the Chinese famine in childhood was related to an increased risk of adulthood T2D and hyperglycemia, particularly in women. [ABSTRACT FROM AUTHOR]

Organophosphate esters (OPEs) are widely added to various industrial and consumer products, and are mainly used as flame retardants and plasticizers. Existing epidemiological studies suggest that OPE exposure may be linked to increased blood pressure (BP) and hypertension risk in adults. However, it remains unclear whether OPE exposure is associated with increased BP in children and adolescents. Here, we investigated the associations between OPE exposure and BP levels in 6–18-year-old children and adolescents from a cross-sectional study in Liuzhou, China. OPE metabolites were determined in spot urine samples (n = 1194) collected between April and May 2018. Three measurements of systolic and diastolic BP for each participant were averaged as study outcomes. Associations of OPE exposure with age-, sex- and height-standardized BP were assessed using linear regression models. We found that each natural log unit increment of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) was associated with a 0.06 standard deviation unit (95% confidant interval (CI): 0.01, 0.11) increase in systolic BP z-score. When conducting stratified analysis based on sex, age, and BMI category, BDCIPP was shown to be positively associated with systolic/diastolic BP z-score in females, but not in males. The associations between bis(2-butoxyethyl) phosphate (BBOEP) and systolic/diastolic BP z-score were pronounced in adolescents, but not in children. Moreover, a significant positive association between 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP) and diastolic BP z-score was observed in obese subjects. The present study provides the first evidence that OPE exposure was related to increased BP in children and adolescents. Given the scarcity of high-quality evidence supporting these results, the health effects of OPEs are warrant investigation in well-designed prospective studies. [Display omitted] • The first study to explore the association of OPE exposure with blood pressure (BP) in children and adolescents. • A positive linear association was observed between urinary BDCIPP and systolic BP z-score. • OPEs-BP z-score associations were more evident in females, adolescents, or obese subjects. [ABSTRACT FROM AUTHOR]

Abstract: Background: The “Electronic Tongue” is an instrument that can be trained to screen the taste attributes of formulations within a rapid timeframe when used in conjunction with sensory panel taste assessment data. Purpose: The purpose of this research was to demonstrate that a sensory instrument for taste (e-Tongue) could be used to evaluate the bitterness of berberine hydrochloride from Chinese medicinal herbs. Methods: Several flavorful native compounds were tested by the e-Tongue. Data from a human sensory panel was collected to train the e-Tongue. The e-Tongue was then used to establish the correlation between data from the sensory panel, and to predict the bitterness scores of berberine hydrochloride. Results: The e-Tongue showed different response patterns for different tastes or strengths of flavor compounds. No significant differences were found between the results of the e-Tongue and the sensory taste panel. Conclusions: The e-Tongue could be used to evaluate the effect of bitterness of berberine hydrochloride. Therefore, e-Tongues showed potential to replace sensory panel evaluations in future experiments regarding Chinese traditional medicine. [Copyright &y& Elsevier]

This study aimed to explore the associations between maternal folic acid (FA) supplementation during different trimesters of pregnancy and newborn telomere length (TL). Data were collected from a birth cohort study of 746 mother-newborn pairs conducted from November 2013 to March 2015 in Wuhan, China. After adjustment for potential confounders, maternal FA supplementation after the first trimester and throughout pregnancy were associated with longer newborn TL [β = 0.29, 95 % confidence interval (CI): 0.20, 0.38 and β = 0.24, 95 % CI: 0.16, 0.32, respectively]. No significant association was found between maternal FA supplementation in the first trimester and newborn TL. In conclusion, a possible association between maternal FA supplementation during pregnancy with longer newborn TL was suggested in the present study. This study provides insight into the benefit of newborn TL by maternal FA supplementation during pregnancy. • Telomere length is important for age-related diseases. • Folic acid is essential for fetal development. • Maternal folic acid supplementation is associated with newborn telomere length. • Maternal folic acid supplementation after the first trimester is beneficial for offspring. [ABSTRACT FROM AUTHOR]

• ApoB/ApoA-1 ratio was thought to be a reliable parameter to reflect lipid disturbance. • Maternal serum ApoB and ApoB/ ApoA-1 ratio were positively related to the risk of preterm birth. • Monitoring serum apolipoprotein levels may help to identify the high-risk population of preterm birth. Elevated lipid levels during pregnancy have been shown to be related to the risk of preterm birth. Despite the importance of apolipoprotein (Apo) in lipid metabolism and transportation, evidence regarding apolipoprotein levels during pregnancy and preterm birth is still limited. Therefore, we aim to investigate the associations between maternal ApoA-1, ApoB, ApoB/ApoA-1 ratio and preterm birth. Data were extracted from the information system of Guangdong Women and Children Hospital. Lipoprotein levels were tested using Beckman Coulter AU5800 in mid-pregnancy at a median gestational age of 18 w. Maternal serum ApoB, ApoA-1 and ApoB/ApoA-1 ratio were categorized into tertiles. Logistic regression models were performed to evaluate the odds ratios and 95% confidence intervals for preterm birth. A total of 5,986 maternal-newborn pairs were included in this study. The rate of preterm birth was 5.7% (n = 344). The multivariate-adjusted ORs (95% CI) of preterm birth were 1.51 (1.06, 2.10) for individuals with high ApoB (>90th), 0.63 (0.38, 0.99) for those with low ApoB (<10th), and 1.64 (1.18, 2.24) for those with high ApoB/ApoA-1 (>90th). Subgroup analyses showed that the association of ApoB and preterm birth was only significant among women with pre-pregnancy BMI 18.5-24 kg/m2 (OR = 1.36, 95% CI: 1.12–1.65), age at delivery ≥ 35 years (OR = 1.43, 95% CI: 1.12–1.83). Elevated maternal ApoB level and ApoB/ApoA-1 ratio during mid-pregnancy were related to increased risk of preterm birth. Monitoring maternal serum apolipoprotein levels may help to identify the high-risk population of preterm birth. [ABSTRACT FROM AUTHOR]

Exposure to environmental contaminants and the development of hypertension and diabetes represent crucial risk factors for chronic kidney disease (CKD). Toxicological studies have revealed that organophosphate esters (OPEs) impair kidney function. However, the joint effects of OPE exposure on kidney injury and the interactions of OPE exposure with hypertension or diabetes on kidney injury remain unclear. Our study aimed to investigate the individual and joint effects of OPE exposure on renal injury, as well as the potential interaction between OPE exposure and hypertension or diabetes on kidney injury. The study enrolled 1938 participants from Wuhan, China. To explore the relationship between OPE exposure and renal injury, we conducted multivariate linear and logistic regression analysis. The results indicated that each unit increase in 4-hydroxyphenyl diphenyl phosphate (4-HO-DPHP), bis(2-butoxyethyl) phosphate (BBOEP), and tris(2-chloroethyl) phosphate (TCEP) (1 μg/L-ln transformed) was associated with a decreased 0.57 mL/min/1.73 m2 (95%CI: -1.05, −0.09), 0.85 mL/min/1.73 m2 (95%CI: -1.52, −0.19) and 1.24 mL/min/1.73 m2 (95%CI: -2.26, −0.23) of estimated glomerular filtration rate (eGFR), while each unit increase in 4-HO-DPHP and BBOEP (1 μg/L-ln transformed) was associated with 14% and 20% elevation of incident impaired renal function (IRF) risk. Notably the highest tertile of BCIPHIPP was positively associated with eGFR, although the p for trend ＞ 0.05. We employed Bayesian kernel machine regression (BKMR) and quartile-based g-computation (qgcomp) models to explore the joint effects of OPE mixtures on eGFR and IRF. Both the results of BKMR and qgcomp model consistently demonstrated negative associations between OPE mixtures and eGFR, and TCEP and 4-HO-DPHP were major contributors. Furthermore, we observed multiplicative interactions of diphenyl phosphate (DPHP), BBOEP, di-ocresyl phosphate (DoCP) & di-p-cresyl phosphate (DpCP), 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP) and hypertension or diabetes on kidney injury (all P ＜0.05). Those with diabetes or hypertension and higher OPE metabolite concentrations had increased risk of kidney function impairment compared to those who did not have diabetes or hypertension. These findings suggest that specific OPE exposure may elevate the risk of renal injury, particularly among hypertensive and diabetic populations. [Display omitted] • Urinary 4-HO-DPHP, BBOEP and TCEP were significantly associated with decreased eGFR level. • Urinary 4-HO-DPHP and BBOEP were associated with increased IRF risk. • OPE mixtures were related to decreased eGFR levels. • Significant interactions between OPE exposure and hypertension or diabetes on kidney injury were identified. [ABSTRACT FROM AUTHOR]

Deep learning has achieved significant advances in the fault diagnosis of rotating machinery. However, it still suffers many challenges such as various working conditions, large environmental noise interference and insufficient effective data samples. Signal time–frequency analysis and feature transfer learning methods can help solve these problems. Combining wavelet packet transform (WPT) and multi-kernel maximum mean discrepancy (MK-MMD), this paper proposes a novel residual network (ResNet)-based deep transfer diagnosis model for bearing faults. Firstly, this paper devises a distinctive WPT time–frequency feature map (WPT-TFFM) construction method using WPT for time–frequency analysis on nonlinear and non-stationary vibration signals. Then, a modified multi-group parallel ResNet network is structured to extract the depth features of WPT-TFFM for the characteristics of small size and feature dispersion. Then, MK-MMD is further applied to evaluate the distribution difference between the depth features of the source and target domain data. Combining with the classification loss of the sample set with the source domain, the depth features extraction network is optimized to achieve better cross-domain invariance and fault state differentiation capability of the depth features. To evaluate the proposed method, this work conducts comparative experiments on two test rigs under different working loads and speeds. The results reveal that the proposed method offers excellent fault diagnosis and noise prevention capability for working condition transfer tasks. • A WPT-based time–frequency feature map construction method is proposed to extract time–frequency features from vibration signals. • A multi group Resnet (MGRN) structure is established to extract the depth features of multi-scale and multi-resolution WPT-TFFMs. • MK-MMD is employed to evaluate the distribution difference of depth features between the source and target domain. • The proposed method offers excellent fault diagnosis and noise prevention capability in working condition transfer tasks. [ABSTRACT FROM AUTHOR]

Background: Evidence about associations of pollutants with sleep is limited, and most of studies focused on individual sleep behaviors, neglecting their interrelation. We aimed to assess the relationship between ambient air pollution and road traffic noise with overall sleep health.Methods: The study included 378,223 participants from the UK Biobank. Including five sleep behaviors (chronotype, sleep duration, insomnia, snoring, and daytime sleepiness) to construct overall sleep pattern. Ambient air pollution exposure was estimated using Land Use Regression model. Road traffic noise exposure was estimated using a simplified version of the Common Noise Assessment Methods model. Using multinomial and binary logistic regression models to identify the associations between pollutants with overall and individual sleep behaviors, respectively.Results: Participants were derived in three sleep patterns: healthy (n = 140,490), intermediate (n = 220,627), and poor (n = 17,106). After adjustment for potential confounders, compared with the lowest quartile of PM2.5, the highest quartile had higher odds of intermediate and poor compared to healthy sleep pattern [OR (95% CI) for poor: 1.28 (1.21-1.36); for intermediate: 1.11 (1.09-1.14)]. We observed similar relationships for PM10, PM2.5 absorbance, PMcoarse, NOx, and NO2. In unadjusted model, compared with low exposure of Lnight, high Lnight exposure had higher odds of intermediate and poor compared to healthy sleep pattern [OR (95% CI) for poor: 1.13 (1.06-1.20); for intermediate: 1.03 (1.00-1.06)]. However, such associations disappeared after further adjustment for potential confounders.Conclusions: Long-term ambient air pollution is associated with overall sleep health. Road traffic noise itself is weakly associated with overall sleep health. [ABSTRACT FROM AUTHOR]

Human pose estimation in crowded scenes is a challenging task. Due to overlap and occlusion, it is difficult to infer pose clues from individual keypoints. We proposed PFFormer, a new transformer-based approach that treats pose estimation as a hierarchical set prediction problem that first focuses on human windows and coarsely predicts whole-body poses globally within them. In PFFormer, we designed a Windows Clustering Transformer (WCT), which reorganizes the image windows by filtering the attentive windows and fusing the inattentive ones, allowing the transformer to focus on the important regions while reducing the interference from the complex background, followed by compensating for the loss of information with a global transformer. Then we partition the learned body pose into a set of structural parts and perform the Inter-Part Relation Module (IPRM) to capture the correlation between multiple parts. These full-body poses and component features are refined at a finer level through the Part-to-Joint Decoder (PJD). Extensive experiments show that PFFormer performs favorably against its counterpart on challenging datasets, including COCO2017, CrowdPose, and OChuman datasets. The performance of crowded scenes, in particular, demonstrates the robustness of the proposed methods to deal with occlusion. [ABSTRACT FROM AUTHOR]

• Long-term PM2.5 exposure was associated with a higher risk of major depressive disorder. • High levels of vitamin D may attenuate the relationship between PM2.5 and major depressive disorder among elderly adults. • Physical activity may attenuate the relationship between PM2.5 and major depressive disorder among elderly adults. The present study aims to investigate the association between PM 2.5 exposure and major depressive disorder, and to examine whether vitamin D and physical activity could attenuate the impact of PM 2.5 on major depressive disorder. 39168 elderly adults (age≥60 years) who had valid estimates on exposure of PM 2.5 in 2010 and data on major depressive disorder were extracted from the UK Biobank. Major depressive disorder was assessed by lifetime experience of mild, moderate, and severe major depression with validated instruments. Logistic regression models were used to estimate the association between PM 2.5 exposure and major depressive disorder. A total of 9079 participants had major depressive disorder, with a prevalence of 23.2%. The odds ratio (OR) of major depressive disorder was 1.096 (1.023, 1.175) for participants in the highest quartile compared with the lowest quartile of PM 2.5. The correlation of PM 2.5 with major depressive disorder generally increased with the decreasing levels of vitamin D. For instance, in participants with the highest quartile of PM 2.5 , the corresponding ORs were 1.141 (0.951, 1.369), 1.232 (1.027, 1.478), 1.286 (1.072, 1.543), and 1.390 (1.159, 1.667) for those who had adequate, desirable, insufficient, and deficient levels of vitamin D, respectively. Additionally, significant modification effects of physical activity on the relationship between PM 2.5 and major depressive disorder were also observed. Our study suggests that high levels of vitamin D and physical activity may attenuate the relationship between PM 2.5 and major depressive disorder among elderly adults. [ABSTRACT FROM AUTHOR]

Women with multiple pregnancies are vulnerable to experience postpartum depression (PPD). Emerging evidence indicates an association between poly- and perfluoroalkyl substances (PFAS) exposure and PPD in women delivering singletons. The health risks of PFAS may also be present in women delivering twins. To estimate the impacts of prenatal PFAS exposure on the risk of PPD in women with twin pregnancies. Our study included 150 mothers who gave birth to twins and were enrolled in the Wuhan Twin Birth Cohort. The concentrations of maternal plasma PFAS were measured in each trimester and averaged. Eight individual PFAS were included in analyses. We used Edinburgh Postnatal Depression Scale to evaluate maternal depression at early pregnancy and 1 and 6 months after childbirth. The outcome was dichotomized using a cutoff value of ≥10 for main analyses. Associations were examined using multiple informant models and modified Poisson regressions. PFAS mixture effects were estimated using quantile g-computation. Using quantile g-computation models, a quartile increase in the PFAS mixture during the first, second, third, and average pregnancy was significantly associated with a relative risk (RR) of 1.73 (95% CI: 1.42, 2.12), 1.54 (95% CI: 1.27, 1.84), 1.75 (95% CI: 1.49, 2.08), and 1.63 (95% CI: 1.35, 1.97) for PPD at 6 months after childbirth, respectively. The results of the single-PFAS models also indicated significant positive associations between individual PFAS and PPD at both 1 and 6 months. The first study of women with twin pregnancies suggests that prenatal exposure to PFAS increases PPD risk up to 6 months postpartum. Twin pregnant women should receive long-term follow-up after delivery and extensive social support. [Display omitted] [ABSTRACT FROM AUTHOR]

• A classification method was established based on the functional parameters of powder; • w , a , k G , y 0 , k a , k b , b , k FES , k E3 are considered as key functional parameters; • The properties of each category of powder were analyzed in detail; • b is considered the most critical functional parameter affecting tablet quality; • In addition, w , k a , k G , and a related parameter affect the qualities of the tablet. Direct compaction (DC) is the ideal method for tablet production. However, DC requires the highest quality powder functional properties, such as good flowability, compressibility, compactibility, and appropriate elasticity. In the present study, 24 types of natural plant product (NPP) powders, prepared using three commonly used methods, and 18 types of fillers were evaluated for their fundamental and functional properties. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) were used to classify the powders and analyze the characteristics of each category of powder, based on functional properties. Partial least squares (PLS) regression models were established to predict the tensile strength (TS), ejection force (EF), disintegration time (DT), and solid fraction (SF) based on the powder's functional properties. The results show that: (i) Except for the direct pulverization powder, the fundamental properties among the NPP powders were similar; however, the functional properties were quite different; (ii) The powders could be classified well based on their functional parameters (w , a , k G , y 0 , k a , k b , b , k FES , k E3). The order of powders suitable for DC is Group 4 > Group 5 > Group 2 > Group 3 > Group 1; (iii) The compressibility and compactibility of the powder are beneficial to the TS and EF of the tablet. The compressibility of the powders correlated negatively with DT; nevertheless, the compactibility correlated positively with DT and SF. The true density (ρ true), median particle size (D 0.5) of the powders correlated negatively with SF. Overall, this study systematically evaluated the properties of commonly used NPP powders and fillers and found the key properties that affect the quality of tablets. [ABSTRACT FROM AUTHOR]

Imbalance or deficiencies of essential metals can lead to oxidative stress, that can damage mitochondrial DNA (mtDNA) molecule. Knowledge on effects of exposure to essential metals and their mixture remains limited. We aimed to evaluate individual and joint associations of prenatal essential metals with neonatal mtDNA copy number. We recruited 746 mother-newborn pairs from a birth cohort study conducted in Wuhan City, China, and collected trimester-specific urine and cord blood samples. We measured the concentrations of seven urinary essential metals, include zinc (Zn), iron (Fe), selenium (Se), cobalt (Co), manganese (Mn), copper (Cu), and chromium (Cr), using inductively coupled plasma mass spectrometry, and measured cord blood mtDNA copy number using real-time quantitative polymerase chain reaction. We estimated the trimester-specific associations of individual essential metal concentrations with mtDNA copy number using a multiple informant model, and assessed their joint association using weighted quantile sum (WQS) regression. For individual essential metal, a doubling of maternal urinary Zn concentrations during the second trimester was associated with a 7.47% (95% CI: 1.17–14.17%) higher level of neonatal mtDNA copy number. For the essential metal mixture, one-unit increased in the WQS index of the essential metals mixture during the second trimester resulted in a 10.41% (95% CI: 3.04–18.30%) increase in neonatal mtDNA copy number. Our findings suggest that exposure to both Zn and essential metal mixture during the second trimester is associated with a higher neonatal mtDNA copy number. Further research should assess whether mtDNA copy number is associated with child health. [Display omitted] • Newborn mitochondrial DNA copy number increased with the mixture of Fe, Mn, Zn, Cu, Se, Cr, and Co. • Single Zn exposure was positively associated with newborn mitochondrial DNA copy number. • The second trimester was the critical window of susceptibility for essential metals exposure. [ABSTRACT FROM AUTHOR]

Our study aimed to explore the causal effect of depression on the risk of gallstone disease, and the mediation effects of metabolic traits. A retrospective cohort study on Chinese elderly from the Dongfeng-Tongji cohort (including 18,141 individuals) was conducted to estimate the adverse effect of probable depression on the risk of gallstone disease. Two-sample Mendelian randomization was performed in European and East-Asian ancestries, to verify the causal relationship between major depression and gallstone disease. We further applied two-step Mendelian randomization to explore the mediation effects of metabolic traits. In the cohort study, probable depression was associated with an increased risk of gallstone disease within 5 years, with RR (95% CI) of 1.33 (1.12, 1.58) in multivariable regression, and 1.34 (1.11, 1.61) following propensity score weighting. Bidirectional Mendelian randomization in European ancestry revealed a positive causal effect (OR: 1.21; 95% CI : 1.07 to 1.37) of genetically predicted major depression liability on gallstone disease, based on the inverse variance weighted method. Little evidence was presented from other complementary approaches, and the analysis in East-Asian ancestry (IVW estimated OR : 1.03; 95% CI : 0.92 to 1.15). The indirect effect via waist circumference and HDL-C were 1.06 (95% CI : 1.02 to 1.10) and 1.01 (95% CI : 1.00 to 1.01) respectively, which mediated 25.8% and 3.78% of the causal relationship. Our study suggested a higher risk of gallstone disease in the population with probable depression, while the two-sample Mendelian randomization provided weak evidence for the causal relationship, which was moderately mediated by abdominal obesity. • Depression is associated with a higher risk of gallstone disease. • Mendelian randomization is a valuable approach for causal inference. • Major depression may causally predict the incidence of gallstone disease. • Abdominal obesity mediates the causal effect of depression on gallstone disease. • The causal relationship needs to be further verified in East-Asian populations. [ABSTRACT FROM AUTHOR]

Prenatal exposure to thallium is related to adverse birth outcomes. However, little is known about the effects of prenatal exposure to thallium on the mitochondrial DNA copy number (mtDNAcn) in newborns; such knowledge might reveal a potential mechanism linking maternal thallium exposure and adverse birth outcomes. To investigate the trimester-specific associations of maternal thallium exposure with cord blood leukocyte mtDNAcn. A total of 746 pregnant women with trimester-specific urinary samples and cord blood samples were recruited from Wuhan Children Hospital between November 2013 and March 2015 in Wuhan City, China. The concentration of thallium in maternal urine was quantified using inductively coupled plasma mass spectrometry (ICP-MS). Cord blood leukocyte mtDNAcn was measured by real-time quantitative polymerase chain reaction (qPCR). Trimester-specific associations of specific gravity (SG)–adjusted urinary thallium concentrations with mtDNAcn were estimated using a multiple informant model. The geometric mean value of maternal urinary thallium was 0.34 μg/L, 0.36 μg/L, and 0.34 μg/L for the first, second, and third trimesters, respectively. Prenatal exposure to thallium during the first trimester, rather than during the second or the third trimester, was identified as negatively related to mtDNAcn. The multiple informant model showed a 10.4% lower level of mtDNAcn with each doubling increase of thallium levels (95% CI, −16.4%, −3.9%; P = 0.002). The observed associations were stronger among female newborns and among newborns born to older mothers. The present study revealed a significant negative association between maternal thallium exposure during early pregnancy and cord blood leukocyte mtDNAcn in Chinese newborns, pointing to the important role of mitochondria as a target of thallium toxicity in early pregnancy. • The first study to date on the association of prenatal thallium exposure with mitochondrial DNA copy number in China. • The first trimester was the window of susceptibility to thallium exposure. • The inverse associations were more prominent in female newborns and newborns born to older mothers. [ABSTRACT FROM AUTHOR]

Telomere length (TL) is considered as a surrogate of biological aging and has been related to aging-related diseases. The initial setting of newborn TL has important implications for telomere dynamics in adulthood, and is affected by the intrauterine environment. However, the effects of prenatal air pollution exposure on the initial setting of newborn TL are poor understood. We aimed to explore the trimester-specific relationships between maternal air pollution exposure and newborn TL. Between November 2013 and March 2015, a total of 762 mother-newborn pairs were recruited in a birth cohort study in Wuhan, China. Relative cord blood TL was assessed using quantitative real-time polymerase chain reaction. Maternal exposures to PM 2.5 , PM 10 , SO 2 , CO, and NO 2 , were determined using spatial-temporal land use regression models. Multiple informant models were applied to explore the trimester-specific associations of maternal air pollution exposure with cord blood TL. In single-pollutant models, a 10 μg/m3 increase in PM 2.5 , PM 10 , SO 2 , and a 100 μg/m3 increase in CO during the third trimester were related to 3.71% (95% confidence interval [CI]: −6.06%, −1.30%), 3.24% (95% CI: −5.29%, −1.14%), 11.07% (95% CI: −18.86%, −2.53%), and 3.67% (95% CI: −6.27%, −1.00%) shorter cord blood TL, respectively. The inverse relationships between exposures to PM 2.5 , PM 10 , SO 2 , and CO during the third trimester and cord blood TL were more evident in male infants. In multi-pollutant models, exposures to PM 2.5 and PM 10 during the third trimester were both related to shorter cord blood TL, but not SO 2 and CO. This study suggested that maternal exposures to PM 2.5 , PM 10 , CO, and SO 2 during the third trimester were related to shorter newborn TL, which highlights the importance of improving air quality in favor of subsequent health in later life of newborns. • This is the first study to assess the trimester-specific associations between multiple air pollutants exposure and newborn TL. • Maternal exposure to PM 2.5 , PM 10 , SO 2 , and CO during the third trimester were related to shorter newborn TL. • The inverse effects of PM 2.5 , PM 10 , SO 2 , and CO during the third trimester on newborn TL were more evident in male infants. [ABSTRACT FROM AUTHOR]

Abstract Background An increasing number of epidemiological studies have shown that daily hot and cold temperatures are associated with preterm birth (PTB). However, the relationship between daily temperature variation and PTB is poorly understood. Objectives This study aimed to investigate the role of prenatal exposure to diurnal temperature range (DTR), the difference between the daily maximum and minimum temperatures, in the risk of PTB. Methods A total of 11,056 women who gave birth to a live singleton infant were recruited from the Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), from September 2012 to October 2014. Daily temperature data were obtained from the official website of China Meteorological Administration. A binary logistic regression model was used to estimate the association between DTR and PTB. Results Among the 11,056 live singleton births, 618 (5.6%) infants were PTB. Prenatal exposure to large DTR during the second week before delivery was significantly associated with an increased risk of PTB. After adjusting for the daily mean temperature, daily mean humidity, socioeconomic, obstetrical and lifestyle factors, each 1 °C incremental increase in DTR was associated with a 5.4% (95% CIs: 1.006, 1.104; P = 0.026) increased risk of PTB. The association between large DTR exposure and PTB was stronger for pregnant women with a higher pre-pregnancy BMI, older maternal age, and with delivery in cold season. Conclusions This is the first study to reveal the association between DTR and PTB in China. Health professionals and pregnant women should be aware of the influence of unstable temperature conditions on the risk of PTB. Graphical abstract Unlabelled Image Highlights • The first study to date on the risk assessment of diurnal temperature range to preterm birth. • A series of exposure windows covered the late pregnancy. • The second week before delivery was the sensitive window for DTR exposure. • Pregnant women with older age and higher BMI were more sensitive to the exposure of DTR. [ABSTRACT FROM AUTHOR]

Objective: Although afternoon napping is very common, particularly in China, there are limited data regarding the potential health effects of afternoon napping during pregnancy on perinatal outcomes. We aimed to investigate the relationship between afternoon napping during late pregnancy and low birth weight (LBW).Methods: A total of 10,111 women aged 15-50 years were recruited from the ongoing Healthy Baby Cohort study in China, in 2012-2014. Information on sleep habits during pregnancy was obtained by questionnaires at the time of institutional delivery. Logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs).Results: Compared with women who reported no napping, the multivariate-adjusted ORs for LBW were 0.83 (95% CI 0.58-1.18) and 0.61 (0.44-0.83) for those who reported ≤1 h and >1 h of napping, respectively (P for trend <0.001). LBW risk reached a threshold at approximately 1.5 h of afternoon napping. The inverse relationship between afternoon napping during late pregnancy and LBW was stronger among women with lower educational level (P for interaction = 0.011). For frequency of afternoon napping, the multivariate analysis suggested a significant inverse association between LBW and napping 5-7 days/week (OR 0.68; 95% CI 0.50-0.92).Conclusion: To our knowledge, this is the first study to estimate the association between afternoon napping and frequency of afternoon napping during late pregnancy and LBW risk. Our findings suggest that appropriate afternoon napping and frequency of afternoon napping for pregnant women might reduce the risk of LBW. [ABSTRACT FROM AUTHOR]

Organophosphate esters (OPEs), used as flame retardants and plasticizers, have been indicated to impair growth and development in toxicological studies, but current epidemiological data on their associations with body mass index (BMI) are limited and the underlying biological mechanisms remain unclear. In this study, we aim to explore the association of OPE metabolites with BMI z-score, and assess whether sex hormones mediate the relationships between OPE exposure and BMI z-score. We measured weight and height, and determined OPE metabolites in spot urine samples and sex hormones in serum samples among 1156 children and adolescents aged 6–18 years in Liuzhou city, China. The results showed that di-o-cresyl phosphate and di-pcresyl phosphate (DoCP & DpCP) levels were associated with lower BMI z-score of all participants and a similar pattern of associations were presented in prepubertal boys stratified by sex-puberty groups and male children stratified by sex-age groups. In addition, sex hormone binding globulin (SHBG) were related to reduced BMI z-score among all subgroups including prepubertal boys, prepubertal girls, pubertal boys, and pubertal girls (all P trend <0.05). We also found that DoCP & DpCP showed positive associations with SHBG among prepubertal boys. Mediation analysis further showed that SHBG mediated 35.0% of the association between DoCP & DpCP and reduced BMI z-score in prepubertal boys. Our results indicated that OPEs may impair growth and development by disrupting the sex hormones in prepubertal boys. [Display omitted] • The mediating role of sex hormones in association between OPE exposure and BMI z-score was examined. • Urinary DoCP & DpCP was associated with lower BMI z-score in prepubertal boys. • Urinary DoCP & DpCP showed positive associations with serum SHBG levels in prepubertal boys. • Serum SHBG levels were related to reduced BMI z-score in prepubertal boys. • SHBG mediated the effect of DoCP & DpCP on reduced BMI z-score in prepubertal boys. [ABSTRACT FROM AUTHOR]

In this study, a new type of mixed micelles was developed using Soluplus ® (SOL) and Pluronic ® P105 (P105) for the encapsulation of Oridonin (ORN). Oridonin-loaded micelles (ORN-M) were simply prepared using solvent evaporation and characterized for particle size, particle morphology, encapsulation efficiency, and drug loading. In addition, the in vitro drug release behavior of ORN-M was assessed using the widely applied dialysis bag technique. The pharmacokinetic property of ORN was explored in rats after oral administration of ORN-M. Optimized ORN-M were of a small size (137.2 ± 1.65 nm) and spherical shape when the ratio of SOL:P105 was 3:1, with entrapment efficiency 90.48 ± 1.85% and drug loading 15.08 ± 0.38%. Oral absorption capacity of ORN was greatly enhanced with a relative bioavailability of 210.55% in comparison to that of in-house suspensions, which suggests that ORN-M shows significantly improved bioavailability and drug absorption characteristics. Overall, the optimized SOL-P105 dual mixed micelles show great potential for use as oral drug carriers for cancer treatment. [ABSTRACT FROM AUTHOR]

Aims: Studies indicate that elevated serum total bilirubin (TBil) levels are associated with lower risk of diabetic kidney disease (DKD). Few studies examined the associations of direct bilirubin (DBil) and indirect bilirubin (IBil) with the development of DKD.Methods: Type 2 diabetes patients (n=2,958) with estimated glomerular filtration (eGFR)≥60mlmin(-1) 1.73m(-2) from the Dongfeng-Tongji cohort were selected and followed up for 5years. Development of DKD was defined as decline in eGFR≥30% during follow-up. Generalize linear model was used to assess the associations of bilirubin levels with DKD development.Results: Compared with those in the first tertile of serum TBil, the relative risks (RRs) and 95% confidence intervals (CIs) of incident eGFR decline for tertile 2 to 3 were 0.83 (0.64-1.09) and 0.74 (0.56-0.98), Ptrend=0.04. The counterpart RRs (95% CIs) in IBil were 0.74 (0.57-0.97) and 0.75 (0.57-0.98), Ptrend=0.04. No significant associations were observed in DBil. Moreover, TBil and IBil interacted with smoking, the bilirubin-DKD associations were evident in ever smokers.Conclusions: Our findings suggest that elevation of serum TBil or IBil levels are independent protective factors for development of DKD, particularly in smokers. [ABSTRACT FROM AUTHOR]

We investigated the association between prenatal exposure to lead (Pb) and the risk of preterm low birth weight (PLBW). Pb concentrations in maternal urine collected at birth from 408 subjects (102 cases and 306 matched controls) were analyzed and adjusted by creatinine. The median Pb concentration in the PLBW cases (10.60 μg Pb/g creatinine) was higher than that of the controls (7.28 μg Pb/g creatinine). An adjusted odds ratio (OR) of 2.96 (95% CI = 1.49–5.87) for PLBW was observed when the highest tertile was compared to the lowest tertile of Pb levels. The association was more pronounced among female infants (adjusted OR = 3.67 for the highest tertile; 95% CI = 1.35–9.93) than male infants (adjusted OR = 1.91 for the highest tertile; 95% CI = 0.74–4.95). Our study suggests that prenatal exposure to levels of Pb encountered today in China is associated with an elevated risk of PLBW. [ABSTRACT FROM AUTHOR]

Growing evidence suggests that metal exposure contributes to metabolic syndrome (MetS), but little is known about the effects of combined exposure to metal mixtures. This cross-sectional study included 3748 adults who were recruited from the Medical Physical Examination Center of Tongji Hospital, Wuhan, China. The levels of 21 metal(loid)s in urine were measured by inductively coupled plasma mass spectrometry. MetS was diagnosed according to National Cholesterol Education Program's Adult Treatment Panel III recommendations. Multivariate logistic regression model was uesd to explore the effects of single-metal and multi-metal exposures. The elastic net (ENET) regularization with an environmental risk score (ERS) was performed to estimate the joint effects of exposure to metal mixtures. A total of 636 participants (17%) were diagnosed with MetS. In single metal models, MetS was positively associated with zinc (Zn) and negatively associated with nickel (Ni). In multiple metal models, the associations remained significant after adjusting for the other metals. In the joint association analysis, the ENET models selected Zn as the strongest predictor of MetS. Compared to the lowest quartile, the highest quartile of ERS was associated with an elevated risk of MetS (OR = 3.72; 95% CI: 2.77, 5.91; P -trend < 0.001). Overall, we identified that the combined effect of multiple metals was related to an increased MetS risk, with Zn being the major contributor. These findings need further validation in prospective studies. [Display omitted] • Twenty-one metals were included, both individually and as mixtures. • Urinary zinc and nickel were related to the risk of MetS. • ENET was used to model the joint effect of the mixture components flexibly. • A positive association between metals mixture exposure and MetS was observed. [ABSTRACT FROM AUTHOR]

A new parameter named Strain/Stress Max was found to be highly relevant to tablet friability. A design space was developed to achieve <1% tablet friability at various combinations of Strain/Stress Max and tensile strength. [Display omitted] • The tablet quality attributes and texture performances of five excipients were studied systematically. • A new parameter highly relevant to tablet friability, named Strain/Stress Max, was discovered. • Strain/Stress Max was directly obtained from the diametrical breaking test. • Tablet friability values of binary mixtures were satisfactorily predicted through the constructed correlation model. • A design space of <1% tablet friability was constructed based on Strain/Stress Max and tensile strength. In this paper, a new parameter highly relevant to tablet friability is proposed based on a systematical study of the tablet quality attributes and texture performances of five different direct compression excipients, including microcrystalline cellulose, starch, lactose, mannitol, and dicalcium phosphate anhydrous. The new parameter, named Strain/Stress Max, could indicate the tablet's ability against external force to maintain integrity. It was directly obtained from the diametrical breaking test which is extensively used to assess tablet mechanical strength, and thus no extra work is required. The values varied significantly among the tablets formed by materials with different mechanical properties under the same compression pressure. A design space was developed to achieve <1% tablet friability at various combinations of Strain/Stress Max and tensile strength. Additionally, data from binary mixture tablets validated the availability of the constructed design space. And the upper limit of Strain/Stress Max value was advisable for 1.5 MPa−1 for pharmaceutical tablets. In conclusion, the new parameter and design space are available for fast identification of the tablets with acceptable friability to facilitate the development of tablet formulation using as few active pharmaceutic ingredients as possible. [ABSTRACT FROM AUTHOR]

[Display omitted] • A high-dose, high-hydrophobicity API was used for HSWG. • Failure Modes and Effect Analysis was used to evaluate CPPs and CQAs in detail. • Evaluated the influence of process variables on granule and tablet properties. • Combination of QbD and MVA provides a paradigm for HSWG–based product development. High shear wet granulation (HSWG), as a widely used granulation technology, has been studied extensively. However, for the HSWG of formulations containing hydrophobic components, the influence of process variables on the properties of granules and tablets has not been reported. In the present study, based on a combination of quality by design and multivariate analysis (MVA) approaches, quercetin with high-dose and high-hydrophobicity was used to study the relationship between process variables, granule properties, and tablet properties in HSWG systematically. Control and response variables were determined using risk assessment. The optimal fitting empirical models established by Box-Behnken design showed that the liquid to solid ratio and impeller speed were the most important factors, which affected all product properties except Carr's index and yield pressure. Instead, the influence of wet massing time was relatively small (only the effects on yield, granule size, granule hardness, and compression ratio were significant). Then, the process design space was obtained by limiting the related critical quality attributes, which was verified effectively. Scanning electron microscope images showed that smooth granules were produced using higher process parameters, whereas rough and porous granules resulted at lower process parameters. Furthermore, the MVA results demonstrated that increasing the granule hardness led to an increase in the compression ratio and a decrease in tensile strength of the tablets. Tablet fragility and disintegration time were mainly affected by granule density and bulk density, respectively, and both were negatively correlated. The established research paradigm is not only conducive to the successful development of quercetin products, but also provides valuable guidance for improving HSWG–based product development with such formulation characteristics. [ABSTRACT FROM AUTHOR]

There is a lack of actively targeting drug delivery carriers for the topical treatment of epidermal diseases, which results in drug waste and an increased incidence of toxic side effects in the clinic. We recently discovered that epidermal cells (HaCaT cells) have homologous targeting functions and developed HaCaT cell membrane-coated pH-sensitive micelles for therapeutic active targeting of skin disease. We encapsulated shikonin in these biomimetic nanocarriers and found that the nanocarriers accumulated mainly in the active epidermis when delivered with karaya gum-fabricated water-soluble microneedles. The nanocarriers were internalized by the target cells, resulting in swelling of histidine fragments with protonation and subsequent triggering of drug release, which increased the therapeutic efficacy of shikonin against imiquimod-induced psoriatic epidermal hyperplasia. This emerging biomimetic delivery strategy is a new approach for improving the treatment of skin diseases and is also very promising for use in the field of cosmetics. Additionally, we found abnormally high protein expression of Na+/K+-ATPase in diseased skin; thus, this protein may be a biomarker of psoriasis. [ABSTRACT FROM AUTHOR]