NLRP1 restricts porcine deltacoronavirus infection via IL-11 inhibiting the phosphorylation of the ERK signaling pathway.

Continuously emerging highly pathogenic coronaviruses remain a major threat to human and animal health. Porcine deltacoronavirus (PDCoV) is a newly emerging enterotropic swine coronavirus that causes large-scale outbreaks of severe diarrhea disease in piglets. Unlike other porcine coronaviruses, PDCoV has a wide range of species tissue tropism, including primary human cells, which poses a significant risk of cross-species transmission. Nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain-containing 1 (NLRP1) has a key role in linking host innate immunity to microbes and the regulation of inflammatory pathways. We now report a role for NLRP1 in the control of PDCoV infection. Overexpression of NLRP1 remarkably suppressed PDCoV infection, whereas knockout of NLRP1 led to a significant increase in PDCoV replication. A mechanistic study revealed that NLRP1 suppressed PDCoV replication in cells by upregulating IL-11 expression, which in turn inhibited the phosphorylation of the ERK signaling pathway. Furthermore, the ERK phosphorylation inhibitor U0126 effectively hindered PDCoV replication in pigs. Together, our results demonstrated that NLRP1 exerted an anti-PDCoV effect by IL-11-mediated inhibition of the phosphorylation of the ERK signaling pathway, providing a novel antiviral signal axis of NLRP1-IL-11-ERK. This study expands our understanding of the regulatory network of NLRP1 in the host defense against virus infection and provides a new insight into the treatment of coronaviruses and the development of corresponding drugs.IMPORTANCECoronavirus, which mainly infects gastrointestinal and respiratory epithelial cells in vivo, poses a huge threat to both humans and animals. Although porcine deltacoronavirus (PDCoV) is known to primarily cause fatal diarrhea in piglets, reports detected in plasma samples from Haitian children emphasize the potential risk of animal-to-human spillover. Finding effective therapeutics against coronaviruses is crucial for controlling viral infection. Nucleotide-binding oligomerization-like receptor (NLR) family pyrin domain-containing 1 (NLRP1), a key regulatory factor in the innate immune system, is highly expressed in epithelial cells and associated with the pathogenesis of viruses. We demonstrate here that NLRP1 inhibits the infection of the intestinal coronavirus PDCoV through IL-11-mediated phosphorylation inhibition of the ERK signaling pathway. Furthermore, the ERK phosphorylation inhibitor can control the infection of PDCoV in pigs. Our study emphasizes the importance of NLRP1 as an immune regulatory factor and may open up new avenues for the treatment of coronavirus infection.

Different Infectivity of Swine Enteric Coronaviruses in Cells of Various Species.

Swine enteric coronaviruses (SECoVs), including porcine deltacoronavirus (PDCoV), transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), and swine acute diarrhea syndrome coronavirus (SADS-CoV), have caused high mortality in piglets and, therefore, pose serious threats to the pork industry. Coronaviruses exhibit a trend of interspecies transmission, and understanding the host range of SECoVs is crucial for improving our ability to predict and control future epidemics. Here, the replication of PDCoV, TGEV, and PEDV in cells from different host species was compared by measuring viral genomic RNA transcription and protein synthesis. We demonstrated that PDCoV had a higher efficiency in infecting human lung adenocarcinoma cells (A549), Madin-Darby bovine kidney cells (MDBK), Madin-Darby canine kidney cells (MDCK), and chicken embryonic fibroblast cells (DF-1) than PEDV and TGEV. Moreover, trypsin can enhance the infectivity of PDCoV to MDCK cells that are nonsusceptible to TGEV. Additionally, structural analyses of the receptor ectodomain indicate that PDCoV S1 engages Aminopeptidase N (APN) via domain II, which is highly conserved among animal species of different vertebrates. Our findings provide a basis for understanding the interspecies transmission potential of these three porcine coronaviruses.

Effects of sodium arsenite exposure on behavior, ultrastructure and gene expression of brain in adult zebrafish (Danio rerio).

Arsenic, a common metal-like substance, has been demonstrated to pose potential health hazards and induce behavioral changes in humans and rodents. However, the chronic neurotoxic effects of arsenic on aquatic animals are still not fully understood. This study aimed to investigate the effects of arsenic exposure on adult zebrafish by subjecting 3-month-old zebrafish to three different sodium arsenite water concentrations: 0 µg/L (control group), 50 µg/L, and 500 µg/L, over a period of 30 days. To assess the risk associated with arsenic exposure in the aquatic environment, behavior analysis, transmission electron microscopy techniques, and quantitative real-time PCR were employed. The behavior of adult zebrafish was evaluated using six distinct tests: the mirror biting test, shoaling test, novel tank test, social preference test, social recognition test, and T maze. Following the behavioral tests, the brains of zebrafish were dissected and collected for ultrastructural examination and gene expression analysis. The results revealed that sodium arsenite exposure led to a significant reduction in aggression, cohesion, social ability, social cognition ability, learning, and memory capacity of zebrafish. Furthermore, ultrastructure and genes regulating behavior in the zebrafish brain were adversely affected by sodium arsenite exposure.

Sequentially Released Liposomes Enhance Anti-Liver Cancer Efficacy of Tetrandrine and Celastrol-Loaded Coix Seed Oil.

Background: A sequential release co-delivery system is an effective strategy to improve anti-cancer efficacy. Herein, multicomponent-based liposomes (TET-CTM/L) loaded with tetrandrine (TET) and celastrol (CEL)-loaded coix seed oil microemulsion (CTM) were fabricated, which showed synergistic anti-liver cancer activities. By virtue of Enhanced Permeability and Retention (EPR) effect, TET-CTM/L can achieve efficient accumulation at the tumor site. TET was released initially to repair abnormal vessels and decrease the fibroblasts, and CTM was released subsequently for eradication of tumor tissue. Methods: TEM (transmission electron microscopy) and DLS (dynamic light scattering) were adopted to characterize the TET-CTM/L. Flow cytometry was adopted to examine the cellular uptake and cytotoxicity of HepG2 cells. The HepG2 xenograft nude mice were adopted to evaluate the anti-tumor efficacy and systemic safety of TET-CTM/L. Results: TEM images of TET-CTM/L showed the structure of small particle size of CTM within large-size liposomes, indicating that CTM can be encapsulated in liposomes by film dispersion method. In in vitro studies, TET-CTM/L induced massive apoptosis toward HepG2 cells, indicating synergistic cytotoxicity against HepG2 cells. In in vivo studies, TET-CTM/L displayed diminished systemic toxicity compared to celastrol or TET used alone. TET-CTM/L showed the excellent potential for tumor-targeting ability in a biodistribution study. Conclusion: Our study provides a new strategy for combining anti-cancer therapy that has good potential not only in the treatment of liver cancer but also can be applied to the treatment of other solid tumors.

Distribution of picophytoplankton in the northern slope of the South China Sea under environmental variation induced by a warm eddy.

Mesoscale eddies have been reported to have a substantial impact on the distribution of phytoplankton through the regulation of environmental variables in the open ocean. However, the influence of warm eddies on phytoplankton in continental slopes remains largely unknown. To reveal the impact of mesoscale eddies within slope regions, we conducted a field investigation of picophytoplankton on the northern slope of the South China Sea during an anticyclonic warm eddy propagation. We observed different picophytoplankton distribution patterns. Synechococcus dominated the picophytoplankton community in the Kuroshio-affected eddy core rather than the previously reported Prochlorococcus, and Prochlorococcus dominated outside the eddy in the shelf. In addition, through further vertical study of typical layers, we found that the influence of warm eddy varied in different layers. Analysis of the mechanisms indicated that the distributions were attributed to warm eddy-induced nutrients and light variations and the physical processes in it.

The heterogeneous associations between gestational weight gain and adverse pregnancy outcomes in gestational diabetes mellitus according to abnormal glucose metabolism.

OBJECTIVES: The gestational weight gain (GWG) and hyperglycemia are two key factors affecting adverse pregnancy outcomes among women with gestational diabetes mellitus (GDM). We aimed to investigate the combinatorial effect of abnormal glucose metabolism and GWG on adverse outcomes in GDM. METHODS: This retrospective cohort study included 2611 pregnant women with GDM in Women's Hospital School of Medicine Zhejiang University. Bases on the OGTT glucose levels, we categorized the GDM cohort into three subgroups: impaired fasting glucose (IFG) group, impaired glucose tolerance (IGT) group, and combined impaired glucose (IFG&IGT) group. RESULTS: Among pregnant women with IGT, insufficient GWG (IGWG) was an independent protective factor for pregnancy-induced hypertension syndrome (PIH) (aOR 0.55, 95% CI 0.32-0.95), macrosomia (0.38, 0.19-0.74) and large for gestational age (0.45, 0.32-0.62), as well as an independent risk factor for low birth weight infants (2.29, 1.24-4.22) and small for gestational age (1.94, 1.17-3.19); and excessive GWG (EGWG) was related to increased risks of PIH (1.68, 1.12-2.52), preterm delivery (1.82, 1.28-2.58), postpartum hemorrhage (1.85, 1.05-3.28), cesarean delivery (1.84, 1.38-2.46) and low body weight infants (2.36, 1.33-4.20). Moreover, EGWG was positively associated with PIH (3.27, 1.09-9.80) in the IFG group. But there were no significant associations between either IGWG or EGWG and any pregnancy outcomes in women with combined IFG&IGT. CONCLUSIONS: The relationships between GWG and adverse outcomes were modified by abnormal glucose metabolism in women with GDM. Our results suggest that more specific GWG recommendations according to their metabolic state are needed for GDM.

Effect of Mifepristone vs Placebo for Treatment of Adenomyosis With Pain Symptoms: A Randomized Clinical Trial.

Importance: Adenomyosis is a common chronic gynecological disorder, and its treatment is an unmet need. New therapies need to be developed. Mifepristone is being tested for adenomyosis treatment. Objective: To determine whether mifepristone is effective and safe for adenomyosis treatment. Design, Setting, and Participants: This multicenter, placebo-controlled, double-blind randomized clinical trial was conducted in 10 hospitals in China. In total, 134 patients with adenomyosis pain symptoms were enrolled. Trial enrollment began in May 2018 and was completed in April 2019, and analyses were conducted from October 2019 to February 2020. Interventions: Participants were randomized 1:1 to receive mifepristone 10 mg or placebo orally once a day for 12 weeks. Main Outcomes and Measures: The primary end point was the change in adenomyosis-associated dysmenorrhea intensity, evaluated by the visual analog scale (VAS) after 12 weeks of treatment. Secondary end points included the change in menstrual blood loss, increased level of hemoglobin in patients with anemia, CA125 level, platelet count, and uterine volume after 12 weeks of treatment. Safety was assessed according to adverse events, vital signs, gynecological examinations, and laboratory evaluations. Results: In total, 134 patients with adenomyosis and dysmenorrhea were randomly assigned, and 126 patients were included in the efficacy analysis, including 61 patients (mean [SD] age, 40.2 [4.6] years) randomized to receive mifepristone and 65 patients (mean [SD] age, 41.7 [5.0] years) randomized to received the placebo. The characteristics of the included patients at baseline were similar between groups. The mean (SD) change in VAS score was -6.63 (1.92) in the mifepristone group and -0.95 (1.75) in the placebo group (P < .001). The total remission rates for dysmenorrhea in the mifepristone group were significantly better than those in the placebo group (effective remission: 56 patients [91.8%] vs 15 patients [23.1%]; complete remission: 54 patients [88.5%] vs 4 patients [6.2%]). All the secondary end points showed significant improvements after mifepristone treatment for menstrual blood loss, hemoglobin (mean [SD] change from baseline: 2.13 [1.38] g/dL vs 0.48 [0.97] g/dL; P < .001), CA125 (mean [SD] change from baseline: -62.23 [76.99] U/mL vs 26.89 [118.70] U/mL; P < .001), platelet count (mean [SD] change from baseline: -28.87 [54.30]×103/µL vs 2.06 [41.78]×103/µL; P < .001), and uterine volume (mean [SD] change from baseline: -29.32 [39.34] cm3 vs 18.39 [66.46] cm3; P < .001). Safety analysis revealed no significant difference between groups, and no serious adverse events were reported. Conclusions and Relevance: This randomized clinical trial showed that mifepristone could be a new option for treating patients with adenomyosis, based on its efficacy and acceptable tolerability. Trial Registration: ClinicalTrials.gov Identifier: NCT03520439.

Inverse correlations between serum carotenoids and respiratory morbidity and mortality: the Third National Health and Nutrition Examination Survey.

The objective was to evaluate the association between serum carotenoid levels and respiratory morbidity and mortality in a nationally representative sample of US adults. We assessed the association of serum carotenoid levels with respiratory morbidity and mortality using logistic regression and proportional hazards regression models. Meanwhile, a series of confounders were controlled in regression models and restricted cubic spline, which included age, sex, race, marriage, education, income, drinking, smoking, regular exercise, BMI, daily energy intake, vitamin E, vitamin C, fruit intake, vegetable intake, diabetes, hypertension, asthma, emphysema and chronic bronchitis. Compared with participants in the lowest tertiles, participants in the highest tertiles of serum total carotenoids, ß-cryptoxanthin and lutein/zeaxanthin levels had a significantly lower prevalence of emphysema (ORtotal carotenoids = 0·61, 95% CI: 0·41-0·89, ORß-cryptoxanthin = 0·67, 95% CI: 0·49-0·92), chronic bronchitis (ORß-cryptoxanthin = 0·66, 95% CI: 0·50-0·87) and asthma (Q2: ORlutein/zeaxanthin = 0·78, 95% CI: 0·62-0·97); participants in the highest tertiles of total carotenoids, α-carotene, lutein/zeaxanthin and lycopene had a lower risk of respiratory mortality (hazard ratio (HR)total carotenoids = 0·62, 95% CI: 0·42-0·90, HRα-carotene = 0·54, 95% CI: 0·36-0·82, HRlutein/zeaxanthin = 0·48, 95% CI: 0·33-0·71, HRlycopene = 0·66, 95% CI: 0·45-0·96) than those in the lowest tertiles. Higher serum total carotenoids and ß-cryptoxanthin levels is associated with decreased prevalence of emphysema and chronic bronchitis, and higher serum total carotenoids, α-carotene, lutein/zeaxanthin and lycopene levels had a lower mortality of respiratory disease.

Dysregulation of the microbiota-brain axis during long-term exposure to polystyrene nanoplastics in rats and the protective role of dihydrocaffeic acid.

Polystyrene nano-plastics (PS-NPs) can be accumulated in the food chain and can penetrate biological barriers to affect multiple physiological functions. However, the adverse effects of nano-plastics on mammals and the underlying mechanism still remain unknown. To fill the gaps, our study administrated low-dose PS-NPs (50 and 100 µg/L) for 24 consecutive weeks in rats. Behavioral and morphological evaluations were performed to assess the neurobehavoirs. A combined analysis of multiple omics was used to evaluate the dysfunctions of the gut-microbe-brain axis. After dihydrochalcone(NHDC) treatment in the PS-NPs rat model, the inflammation response and apoptosis process were assessed and proteomics was used to explore the underlying mechanism. Our results indicated that long-term exposure to low-dose PS-NPs could induce abnormal neurobehaviors and amygdaloid nucleus impairment, and stimulate inflammatory responses and apoptosis. Metagenomics results revealed that four microbial phyla including Proteobacteria, Firmicutes, Defferibacteres, and Bacteroidetes changed significantly compared to the control. Targeted metabolomics analysis in the feces showed alteration of 122 metabolites induced by the PS-NPs exposure, among which the content of dihydrocaffeic acid was significantly associated with the different microbial genera and pivotal differential metabolites in the amygdaloid nucleus. And NHDC treatment significantly alleviated PS-NP-induced neuroinflammation and apoptosis and the cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)/phosphorylated cAMP-response element binding protein(p-CREB)/plasma membrane calcium-transporting ATPase 2(Atp2b2) signaling pathway was identified in the proteomics. In conclusion, long-term exposure to low-dose PS-NPs has adverse effects on emotion through the dysregulation of the gut-brain axis, and dihydrocaffeic acid can alleviate these effects via the cAMP/PKA/p-CREB/Atp2b2 signaling pathway.

Exploration of active sites of ethyl alcohol electro-oxidation on porous gold nanoparticles with enhanced Raman spectroscopy.

Novel porous gold nanospheres are prepared by calcination of the gold-urea complexes. The enhanced Raman spectra of ethanol catalyzed by different doses of porous gold nanospheres are measured with a 532 nm laser as the excitation source, and an enhanced charge coupled device served in spectral detection and microscopic imaging. The electrochemical experiments show that the catalytic oxidation products of ethanol with porous gold nanoparticles are acetaldehyde, acetic acid, and water, which further proved that the porous gold nanoparticles can activate the -CH2 of ethanol.

Association of meal timing of energy, macronutrients and foods with hypercholesterolaemia in the US adults.

Few studies examined the association of energy, macronutrients and food consumption at dinner v. breakfast with hypercholesterolaemia. A total of 27 911 participants from the National Health and Nutrition Examination Survey (2003-2016) were included in the cross-sectional study. Energy, macronutrients and food consumption at breakfast, dinner and the difference at dinner v. breakfast (Δratio) were calculated. Multiple logistic regression models and substitution effects of foods at dinner with breakfast were also performed. After adjustment for potential covariates, compared with the lowest quintile, participants in the highest quintile of Δratio in terms of energy had a higher risk of prevalent hypercholesterolaemia (ORΔratio of energy 1·16, 95 % CI (1·01, 1·33)) mainly due to Δratio of low-quality carbohydrates and plant protein (ORΔratio of low-quality carbohydrates 1·19; 95 % CI (1·05, 1·35)); ORΔratio of plant protein 1·13; 95 % CI (1·01, 1·28)). ΔAdded sugars and Δnuts were associated with hypercholesterolaemia (ORΔadded sugars 1·01; 95 % CI (1·00, 1·02)); ORΔnuts 1·08; 95 % CI (1·01, 1·16)). Furthermore, the substitution of added sugars, nuts and processed meat at dinner with breakfast could reduce the OR of hypercholesterolaemia. This study indicated that among US adults, overconsumption of energy, macronutrients including low-quality carbohydrates and plant protein at dinner than breakfast was significantly associated with a higher risk of prevalent hypercholesterolaemia. The replacing of added sugar, nuts and processed meat at dinner with breakfast reduced the risk of prevalent hypercholesterolaemia. This study emphasised the importance of meal timing in the prevention of hypercholesterolaemia.

Self-emulsifying System Co-loaded with Paclitaxel and Coix Seed Oil Deeply Penetrated to Enhance Efficacy in Cervical Cancer.

BACKGROUND: Paclitaxel (PTX), voted as the promising natural medicine molecule, is widely used in the treatment of cancers. Nevertheless, its clinical application is strictly limited by its poor water solubility. OBJECTIVE: CP-MEs (Paclitaxel-coix seed oil coloaded microemulsion), a small-sized self-emulsifying nanoemulsion formed from a combination of PTX and coix seed oil (CSO), was developed in order to improve the solubility of paclitaxel and enhance anti-cervical cancer efficacy in vitro. CSO was selected as the oil phase to replace conventional organic solvents and achieve a synergistic anti-tumor effect with paclitaxel. METHODS: Pseudoternary phase diagram was applied to the study of CP-MEs formulation. CP-MEs were prepared and characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The encapsulation efficiency and drug loading efficiency (EE and LE) were detected by HPLC. MTT was adopted to evaluate the cytotoxicity of CP-MEs against HeLa cells. The cellular uptake and apoptotic ratio of CP-MEs were evaluated by flow cytometry. Notably, HeLa 3D tumor spheroid was adopted to evaluate tumor permeability of different size microemulsions as the model. RESULTS: The best self-emulsifying ability was exhibited by HS 15: PEG 400 combination. The appearance of CP-MEs was clear and transparent, which exhibited a small size (30.28 ± 0.36) and a slight negative surface charge (-4.40 ± 1.13) mV. The EE and LE of CP-MEs were 98.80% and 0.978%, respectively. The cumulative release rate within 48 h of the CP-MEs was 80.21%. In cellular studies, the uptake of fluorescein isothiocyanate (FITC) labeled CP-MEs (FITC/C-MEs) was 17.86-fold higher than the free FITC group, leading to significant synergistic anticancer activity in terms of cytotoxicity and apoptosis induction in vitro. The apoptotic rate of CP-MEs treated was 1.70-fold higher than PTXtreated. Notably, the penetration of CP-MEs in the HeLa 3D tumor sphere model was enhanced, which was related to deeply penetrated microemulsion of small size mediated at the tumor site. CONCLUSION: With the advantage of the small-sized self-emulsifying system, CP-MEs hold great potential to become an efficient nano drug delivery system for cervical cancer treatment in the clinic.

Independent and Joint Associations of Age, Pre-pregnancy BMI, and Gestational Weight Gain with Adverse Pregnancy Outcomes in Gestational Diabetes Mellitus.

INTRODUCTION: To explore the independent and combined effects of maternal age, pre-pregnancy body mass index (BMI), and gestational weight gain (GWG) on pregnancy outcomes in gestational diabetes mellitus (GDM). METHODS: A total of 2171 pregnant women with GDM attending the Women's Hospital of Zhejiang University were retrospectively included. We compared pregnancy outcomes in different age, BMI, and GWG groups after adjusting for confounding variables. RESULTS: Results showed that (1) advanced maternal age increased the risk of primary Cesarean section and hypertensive disorders of pregnancy (HDP) in normal weight; (2) independent of age and GWG, high BMI significantly increased the risk of HDP, primary Cesarean section, and macrosomia; (3) Women with excessive GWG had a higher risk of primary Cesarean section and HDP, even they were ≤ 29 years old or normal weight, respectively; (4) Pregnant women with inadequate GWG had a higher risk of preterm birth and a lower risk of macrosomia in both the 30-34 age group and the normal weight group; (5) BMI was a better predictor of HDP than GWG among women younger than 30. CONCLUSIONS: Among the GDM population, women over the age of 35, overweight and obese, or with an excessive GWG were more prone to adverse pregnancy outcomes, especially primary Cesarean delivery and HDP.

The association of dietary spermidine with all-cause mortality and CVD mortality: The U.S. National Health and Nutrition Examination Survey, 2003 to 2014.

Background: Current studies on the protective effects of dietary spermidine (SPD) on cardiovascular disease (CVD) are mainly limited to animal studies, and the relationship between dietary SPD and CVD mortality remains inconclusive. Objective: This study aims to evaluate the association between dietary SPD intake and CVD and all-cause mortality. Methods: A total of 23,894 people enrolled in the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2014 were recruited for this study. The dietary intake of SPD from 11 specific food origins and total SPD was categorized into tertiles or quartiles. Cox proportional hazard regression models were developed to evaluate the association of SPD intake with CVD and all-cause mortalities. Results: Among the 23,894 participants, 2,365 deaths, including 736 deaths due to CVD, were documented. After adjustment for potential confounders, compared with participants in the lowest quartile, participants in the highest quartile of total SPD had a significantly lower risk of CVD mortality (HR = 0.68, 95% CI: 0.51-0.91) and all-cause mortality (HR = 0.70, 95% CI: 0.60-0.82); participants in the highest tertiles or quartiles of vegetable-derived SPD, cereal-derived SPD, legume-derived SPD, nut-derived SPD, and cheese-derived SPD had a lower risk of CVD mortality (HR vegetable - derivedSPD = 0.68, 95% CI: 0.54-0.86; HR cereal - derivedSPD = 0.75, 95% CI: 0.57-0.97; HR legume - derivedSPD = 0.68, 95% CI: 0.52-0.88; HR nut - derivedSPD = 0.66, 95% CI: 0.53-0.80; HR cheese - derivedSPD = 0.68, 95% CI: 0.52-0.88) and all-cause mortality (HR vegetable - derivedSPD = 0.73, 95% CI: 0.64-0.84; HR cereal - derivedSPD = 0.80, 95% CI: 0.69-0.93; HR legume - derivedSPD = 0.70, 95% CI: 0.60-0.80;HR nut - derivedSPD = 0.72, 95% CI: 0.64-0.81; HR cheese - derivedSPD = 0.70, 95% CI: 0.61-0.81) than those in the lowest tertiles or quartiles. Moreover, subgroup analysis showed consistent associations among the people with hypertension and hyperlipidemia. Conclusion: Higher intake of dietary SPD is associated with decreased risk of CVD and all-cause mortality, and among specific food origin SPD, SPD derived from vegetables, cereals, legumes, nuts, and cheese was associated with reduced CVD and all-cause mortality.

Relationship Between Carbohydrate Intake (Quantity, Quality, and Time Eaten) and Mortality (Total, Cardiovascular, and Diabetes): Assessment of 2003-2014 National Health and Nutrition Examination Survey Participants.

OBJECTIVE: In this study we investigated the association of the quantity, quality, and timing of carbohydrate intake with all-cause, cardiovascular disease (CVD), and diabetes mortality. RESEARCH DESIGN AND METHODS: This secondary data analysis included use of National Health and Nutrition Examination Survey (2003-2014) and National Death Index data from adults (n = 27,623) for examination of the association of total daily and differences in carbohydrate intake with mortality. Participants were categorized into four carbohydrate intake patterns based on the median values of daily high- and low-quality carbohydrate intake. The differences (Δ) in carbohydrate intake between dinner and breakfast were calculated (Δ = dinner - breakfast). Cox regression models were used. RESULTS: The participants who consumed more high-quality carbohydrates throughout the day had lower all-cause mortality risk (hazard ratio [HR] 0.88; 95% CI 0.79-0.99), whereas more daily intake of low-quality carbohydrates was related to greater all-cause mortality risk (HR 1.13; 95% CI: 1.01-1.26). Among participants whose daily high- and low-quality carbohydrate intake were both below the median, the participants who consumed more high-quality carbohydrates at dinner had lower CVD (HR 0.70; 95% CI 0.52-0.93) and all-cause mortality (HR 0.82; 95% CI 0.70-0.97) risk; an isocaloric substitution of 1 serving low-quality carbohydrates intake at dinner with high-quality reduced the CVD and all-cause mortality risks by 25% and 19%. There was greater diabetes mortality among the participants who consumed more low-quality carbohydrates at dinner (HR 1.78; 95% CI 1.02-3.11), although their daily high-quality carbohydrate intake was above the median. CONCLUSIONS: Consuming more low-quality carbohydrates at dinner was associated with greater diabetes mortality, whereas consuming more high-quality carbohydrates at dinner was associated with lower all-cause and CVD mortality irrespective of the total daily quantity and quality of carbohydrates.

A Newly Developed Indicator of Overeating Saturated Fat Based on Serum Fatty Acids and Amino Acids and Its Association With Incidence of Type 2 Diabetes: Evidence From Two Randomized Controlled Feeding Trials and a Prospective Study.

Objective: Hyper-caloric intake of saturated fatty acids (SFAs) is common in modern societies, probably contributing to the epidemic of type 2 diabetes mellitus (T2DM). This study conducted two randomized controlled trials (RCTs) for developing a new indicator that can assess the nutritional status and examined its association with incidence of T2DM. Methods: In RCT 1, healthy participants were randomly assigned into three groups, namely, control group (n = 40), overfeeding group 1 (100 g butter per day, n = 37), and overfeeding group 2 (120 g butter per day, n = 37). In RCT 2, healthy subjects were randomly assigned into two groups, namely, control group (n = 52) and high-fat group (300-extra kcal/day from diet that was designed by high-fat diet, n = 58). In the prospective cohort, 4,057 participants aged 20-74 years were enrolled and followed up over 5.3 years. Serum profiles of fatty acids and amino acids were measured. Results: In RCT 1, serum fatty acids, including C14:0 and C18:0, increased, whereas C18:2, C20:4, C22:5, and C22:6 decreased; serum amino acids, including tyrosine, alanine, and aminobutyric acid, increased, whereas histidine and glycine decreased (p < 0.05). Among these serum fatty acids and amino acids, changes in C14:0, C20:4, tyrosine, histidine, and glycine were also observed in RCT 2. An indicator was developed based on the five fatty acids and amino acids, namely, C14:0 × tyrosine × 1,000/[C20:4 × (glycine + histidine)], and it significantly identified participants in the intervention group with area under the curve (AUC) (95% CI) being 0.85 (0.77-0.92). The indicator was significantly associated with incidence of T2DM in the prospective cohort with HRs (95% CIs) from bottom quartile to top quartile being 1,1.21 (0.82-1.77), 1.60 (1.12-2.30), 2.04 (1.42-2.94). Conclusion: The newly developed indicator in RCTs can be used in assessing the nutritional status of hypercaloric intake of SFA and predicting the development of T2DM.

The Influence of HbA1c and Gestational Weight Gain on Pregnancy Outcomes in Pregnant Women With Gestational Diabetes Mellitus.

Background: To investigate the influence of HbA1c level and GWG on pregnancy outcomes in pregnant women with GDM. Methods: A total of 2,171 pregnant women with GDM were retrospectively included and categorized as follows: (1) normal (HbA1c <6%) and elevated (HbA1c ≥6%) HbA1c groups according to the HbA1c level in the second trimester, and (2) inadequate, appropriate, and excessive GWG groups according to the IOM guidelines. Results: In pregnant women with GDM, advanced age and high pre-pregnancy BMI were high-risk factors for elevated HbA1c. Pregnant women with elevated HbA1c had higher OGTT levels than those with normal HbA1c, and the risks of adverse pregnancy outcomes were higher (P < 0.05). The risks of primary cesarean section, hypertensive disorders during pregnancy, and macrosomia in pregnant women with excessive GWG were significantly higher than those with inadequate and appropriate GWG (P < 0.05). When GWG was appropriate, the risk of hypertensive disorders during pregnancy in the elevated HbA1c group was higher than that in the normal HbA1c group. When GWG was excessive, the risks of postpartum hemorrhage, macrosomia, and neonatal asphyxia in the elevated HbA1c group were significantly higher than in the normal HbA1c group (P < 0.05). Conclusion: Monitoring and controlling blood glucose levels have shown effectiveness in reducing the adverse pregnancy outcomes in women with GDM, particularly for those who had excessive GWG.

Different occurrence rates of centrally located cytoplasmic granulation in one cohort oocytes show distinctive embryo competence and clinical outcomes.

Centrally located cytoplasmic granulation (central granulation) is a common cytoplasmic dysmorphism in human oocytes retrieved after controlled ovarian hyperstimulation (COH). In order to achieve a better understanding of its formation and effects on clinical outcomes, we retrospectively analyzed 422 ICSI treatment cycles. Three groups of patients were classified according to the ratio of central granulation occurrence in one egg cohort, as partial granulation, all granulation and control groups. The partial granulation group had a significantly lower BMI and higher AMH level compared to the control or all granulation groups. Consistent with these distinctive features in the partial granulation group, fertilization and blastocyst formation rates were reduced significantly in the partial granulation group but not in the all granulation group. Furthermore, the clinical outcomes in fresh embryo transfer cycles were dramatically reduced in the partial granulation group compared with the control group. However, in FET cycles, all three clinical outcomes were significantly reduced in the all granulation group but not in the partial granulation group. We propose that partial granulation may reflect a specific population of patients, and that the central granulation structure is sensitive to cryopreservation.

The Association of Consumption Time for Food With Cardiovascular Disease and All-Cause Mortality Among Diabetic Patients.

AIMS: This study aims to investigate whether food intake time across 3 meals is associated with long-term survival among the people with diabetes. MATERIALS AND METHODS: This study included 4642 diabetic patients participating in the National Health and Nutrition Examination Survey from 2003 to 2014. Food consumed across a day including the forenoon, afternoon, and evening was divided into quantiles based on their distribution. Cox proportional hazards regression models were used to analyze the survival relationship between food intakes time and mortality. RESULTS: In the forenoon, compared to the participants in the lowest quantile of potato and starchy vegetable, participants in the highest quantile had lower mortality risk of cardiovascular disease (CVD) [hazard ratio (HR)potato = 0.46, 95% CI 0.24-0.89; HRstarchy-vegetable = 0.32, 95% CI 0.15-0.72]. In the afternoon, participants who consumed whole grain had lower mortality of CVD (HRwhole grain = 0.67, 95% CI 0.48-0.95). In the evening, the highest quantile of dark vegetable and milk intake is related to lower mortality risk of CVD (HRdark vegetable = 0.55, 95% CI 0.35-0.87; HRmilk = 0.56, 95% CI 0.36-0.88) and all-cause mortality (HRmilk = 0.71, 95% CI 0.54-0.92), whereas participants in the highest quantile of intakes of processed meat are more likely to die due to CVD (HRprocessed-meat = 1.74, 95% CI 1.07-2.82). Isocalorically switching 0.1 serving potato or starchy vegetable consumed in the afternoon or evening to the forenoon, 0.1 serving dark vegetable consumed in the afternoon to the evening, and 0.1 serving whole grain consumed in the forenoon to the afternoon reduced the risk of CVD mortality. CONCLUSIONS: Higher intake of potato or starchy vegetable in forenoon, whole grain in the afternoon, and dark vegetable and milk in the evening and lower intake of processed meat in the evening was associated with better long-term survival in people with diabetes.

Association of folate intake with cardiovascular-disease mortality and all-cause mortality among people at high risk of cardiovascular-disease.

BACKGROUND & AIMS: Due to the beneficial effect of folate on cardiovascular disease (CVD), folic acid supplementation is a more common practice among people at high-risk of CVD. However, long-term prospective investigations regarding the association of folate-intake with CVD-mortality and all-cause mortality among this specific population are still lacking. Therefore, this study aims to assess the association of folate-intake with CVD-mortality and all-cause mortality. METHODS: A total of 14,234 participants at high-risk of CVD were enrolled. Total folate equivalent (TFE), dietary folate equivalent (DFE), food folate, folic acid in fortified food, folic acid supplements, serum folate and red blood cell (RBC) folate were measured. The main outcome measures were CVD-mortality and all-cause mortality from baseline until 31 December 2015. RESULTS: During the 98,890 person-year follow-up, 2036 deaths including 682 deaths due to CVD were documented. After multivariate adjustment, a J shaped association was found: modest intake of TFE and DFE was associated with lower risk of CVD-mortality and all-cause mortality, whereas higher intake did not persistently reduce these risks. Compared to the participants without folic acid supplementation matched 28-covariates using propensity score, folic acid supplementation was associated with higher risk of CVD-mortality (HR:1.44, 95%CI:1.06-1.97, P = 0.022) and all-cause mortality (HR:1.28,95%CI:1.09-1.51, P = 0.003). The levels of serum-folate and RBC-folate in participants with folic acid supplementation were significantly greater than participants without folic acid supplementation (41.8 nmol/l vs. 64.2 nmol/l, P < 0.001 for serum-folate; 1201 nmol/l vs. 1608 nmol/l, P < 0.001 for RBC-folate). Compared with the lowest-quintile of serum-folate, the second-quintile was consistently associated with CVD-mortality (HR:0.72, 95%CI:0.53-0.99, P = 0.048) and all-cause mortality (HR:0.78, 95%CI:0.64-0.94, P = 0.013). Compared to the lowest-quintile of RBC-folate, the second-quintile was associated with lower all-cause mortality (HR:0.71,95%CI:0.56-0.90, P = 0.005), whereas the highest-quintile was associated with higher CVD-mortality (HR:1.40,95%CI:1.02-1.93, P = 0.030). The J shaped association of serum-folate and RBC-folate with CVD-mortality and all-cause mortality was also demonstrated, further supporting the results of TFE and propensity score analysis. CONCLUSIONS: This study suggested the beneficial effects of modest folate-intake on the improvement of long-term survival, and emphasized the potentially deleterious effects of excess folic acid supplementation among US adults at high-risk of CVD.