Antigen identification and high-throughput interaction mapping by reprogramming viral entry.

Deciphering immune recognition is critical for understanding a broad range of diseases and for the development of effective vaccines and immunotherapies. Efforts to do so are limited by a lack of technologies capable of simultaneously capturing the complexity of adaptive immunoreceptor repertoires and the landscape of potential antigens. To address this, we present receptor-antigen pairing by targeted retroviruses, which combines viral pseudotyping and molecular engineering approaches to enable one-pot library-on-library interaction screens by displaying antigens on the surface of lentiviruses and encoding their identity in the viral genome. Antigen-specific viral infection of cell lines expressing human T or B cell receptors allows readout of both antigen and receptor identities via single-cell sequencing. The resulting system is modular, scalable and compatible with any cell type. These techniques provide a suite of tools for targeted viral entry, molecular engineering and interaction screens with broad potential applications.

Cell-intrinsic and -extrinsic roles of miRNAs in regulating T cell immunity.

T cells are crucial to generate an effective response against numerous invading microbial pathogens and play a pivotal role in tumor surveillance and elimination. However, unwanted T cell activation can also lead to deleterious immune-mediated inflammation and tissue damage. To ensure that an optimal T cell response can be established, each step, beginning from T cell development in the thymus to their activation and function in the periphery, is tightly regulated by many transcription factors and epigenetic regulators including microRNAs (miRNAs). Here, we first summarize recent progress in identifying major immune regulatory miRNAs in controlling the differentiation and function of distinct T cell subsets. Moreover, as emerging evidence has demonstrated that miRNAs can impact T cell immunity through targeting both immune- and non-immune cell populations that T cells closely interact with, the T cell-extrinsic role of miRNAs in regulating different aspects of T cell biology is also addressed. Finally, we discuss the complex nature of miRNA-mediated control of T cell immunity and highlight important questions that remain to be further investigated.

Diastereo- and Enantioselective Synthesis of Eight-Membered N-Heterocycles from Benzofuran-Derived Azadienes and Ynones.

Enantioselective synthesis of eight-membered N-heterocycles represents a long-standing challenge in organic synthesis. Here, by combining the squaramide and DBU catalysis, a sequential asymmetric conjugate addition/cyclization reaction between benzofuran-derived azadienes and ynones has been well-developed, providing straightforward access to chiral eight-membered N-heterocycles in high yields with stereoselectivities. This protocol features the use of a bifunctional squaramide catalyst for controlling the enantioselectivity of products, while the DBU is utilized to achieve intramolecular cyclization and improve the diastereoselectivity of products.

ALPL regulates pro-angiogenic capacity of mesenchymal stem cells through ATP-P2X7 axis controlled exosomes secretion.

BACKGROUND: Early-onset bone dysplasia is a common manifestation of hypophosphatasia (HPP), an autosomal inherited disease caused by ALPL mutation. ALPL ablation induces prototypical premature bone ageing characteristics, resulting in impaired osteogenic differentiation capacity of human bone marrow mesenchymal stem cells (hBMMSCs). As angiogenesis is tightly coupled with osteogenesis, it also plays a necessary role in sustaining bone homeostasis. We have previously observed a decrease in expression of angiogenesis marker gene CD31 in the metaphysis of long bone in Alpl+/- mice. However, the role of ALPL in regulation of angiogenesis in bone has remained largely unknown. METHODS: Exosomes derived from Normal and HPP hBMMSCs were isolated and identified by ultracentrifugation, transmission electron microscopy, and nanoparticle size measurement. The effects of ALPL on the angiogenic capacity of hBMMSCs from HPP patients were assessed by immunofluorescence, tube formation, wound healing and migration assay. exo-ELISA and Western Blot were used to evaluate the exosomes secretion of hBMMSCs from HPP, and the protein expression of VEGF, PDGFBB, Angiostatin and Endostatin in exosomes respectively. RESULTS: We verified that ALPL ablation resulted in impaired pro-angiogenic capacity of hBMMSCs, accounting for reduced migration and tube formation of human umbilical vein endothelial cells, as the quantities and proteins composition of exosomes varied with ALPL expression. Mechanistically, loss of function of ALPL enhanced ATP release. Additional ATP, in turn, led to markedly elevated level of ATP receptor P2X7, which consequently promoted exosomes secretion, resulting in a decreased capacity to promote angiogenesis. Conversely, inhibition of P2X7 increased the angiogenic induction capacity by preventing excessive release of anti-angiogenic exosomes in ALPL deficient-hBMMSCs. CONCLUSION: The ALPL-ATP axis regulates the pro-angiogenic ability of hBMMSCs by controlling exosomes secretion through the P2X7 receptor. Thus, P2X7 may be proved as an effective therapeutic target for accelerating neovascularization in ALPL-deficient bone defects.

scPreGAN, a deep generative model for predicting the response of single-cell expression to perturbation.

MOTIVATION: Rapid developments of single-cell RNA sequencing technologies allow study of responses to external perturbations at individual cell level. However, in many cases, it is hard to collect the perturbed cells, such as knowing the response of a cell type to the drug before actual medication to a patient. Prediction in silicon could alleviate the problem and save cost. Although several tools have been developed, their prediction accuracy leaves much room for improvement. RESULTS: In this article, we propose scPreGAN (Single-Cell data Prediction base on GAN), a deep generative model for predicting the response of single-cell expression to perturbation. ScPreGAN integrates autoencoder and generative adversarial network, the former is to extract common information of the unperturbed data and the perturbed data, the latter is to predict the perturbed data. Experiments on three real datasets show that scPreGAN outperforms three state-of-the-art methods, which can capture the complicated distribution of cell expression and generate the prediction data with the same expression abundance as the real data. AVAILABILITY AND IMPLEMENTATION: The implementation of scPreGAN is available via https://github.com/JaneJiayiDong/scPreGAN. To reproduce the results of this article, please visit https://github.com/JaneJiayiDong/scPreGAN-reproducibility. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

scSemiAE: a deep model with semi-supervised learning for single-cell transcriptomics.

BACKGROUND: With the development of modern sequencing technology, hundreds of thousands of single-cell RNA-sequencing (scRNA-seq) profiles allow to explore the heterogeneity in the cell level, but it faces the challenges of high dimensions and high sparsity. Dimensionality reduction is essential for downstream analysis, such as clustering to identify cell subpopulations. Usually, dimensionality reduction follows unsupervised approach. RESULTS: In this paper, we introduce a semi-supervised dimensionality reduction method named scSemiAE, which is based on an autoencoder model. It transfers the information contained in available datasets with cell subpopulation labels to guide the search of better low-dimensional representations, which can ease further analysis. CONCLUSIONS: Experiments on five public datasets show that, scSemiAE outperforms both unsupervised and semi-supervised baselines whether the transferred information embodied in the number of labeled cells and labeled cell subpopulations is much or less.

Global diversity of policy, coverage, and demand of COVID-19 vaccines: a descriptive study.

BACKGROUND: Hundreds of millions of doses of coronavirus disease 2019 (COVID-19) vaccines have been administered globally, but progress on vaccination varies considerably between countries. We aimed to provide an overall picture of COVID-19 vaccination campaigns, including policy, coverage, and demand of COVID-19 vaccines. METHODS: We conducted a descriptive study of vaccination policy and doses administered data obtained from multiple public sources as of 8 February 2022. We used these data to develop coverage indicators and explore associations of vaccine coverage with socioeconomic and healthcare-related factors. We estimated vaccine demand as numbers of doses required to complete vaccination of countries' target populations according to their national immunization program policies. RESULTS: Messenger RNA and adenovirus vectored vaccines were the most commonly used COVID-19 vaccines in high-income countries, while adenovirus vectored vaccines were the most widely used vaccines worldwide (180 countries). One hundred ninety-two countries have authorized vaccines for the general public, with 40.1% (77/192) targeting individuals over 12 years and 32.3% (62/192) targeting those ≥ 5 years. Forty-eight and 151 countries have started additional-dose and booster-dose vaccination programs, respectively. Globally, there have been 162.1 doses administered per 100 individuals in target populations, with marked inter-region and inter-country heterogeneity. Completed vaccination series coverage ranged from 0.1% to more than 95.0% of country target populations, and numbers of doses administered per 100 individuals in target populations ranged from 0.2 to 308.6. Doses administered per 100 individuals in whole populations correlated with healthcare access and quality index (R2 = 0.59), socio-demographic index (R2 = 0.52), and gross domestic product per capita (R2 = 0.61). At least 6.4 billion doses will be required to complete interim vaccination programs-3.3 billion for primary immunization and 3.1 billion for additional/booster programs. Globally, 0.53 and 0.74 doses per individual in target populations are needed for primary immunization and additional/booster dose programs, respectively. CONCLUSIONS: There is wide country-level disparity and inequity in COVID-19 vaccines rollout, suggesting large gaps in immunity, especially in low-income countries.

Benign prostatic hyperplasia and cardiovascular risk: a prospective study among Chinese men.

PURPOSE: To examine the prospective association of BPH with subsequent risk of CVD, including heart disease and stroke. METHODS: We used data from China Health and Retirement Longitudinal Study of 5242 Chinese men aged 45 years or older. During a follow-up of 7 years, we identified 613 cases of non-fatal CVD, including 417 heart diseases and 254 strokes. Cox proportional hazards models yielded hazard ratios (HRs) relating BPH to CVD, heart disease, and stroke incidence. RESULTS: Overall, 8.1% of men reported a history of BPH diagnosed by physicians at baseline. As compared with men without a history of BPH, those reporting a history of BPH had an increased risk of developing CVD (multivariable-adjusted HR = 1.43 [1.12, 1.83], heart disease (1.35 [1.00, 1.83]), and stroke (1.50 [1.03, 2.19]). The subgroup analysis by age at baseline (< 60 vs. ≥ 60 years) showed that the associations appeared to be evident among men < 60 years, particularly for CVD (1.82 [1.24, 2.69]) and heart disease (1.72 [1.06, 2.79]). However, interaction tests suggested the associations were not significantly modified by age (P for interaction > 0.10 for all outcomes). CONCLUSION: In Chinese men, BPH was associated with higher risks of CVD, heart disease and stroke, particularly among men aged < 60 years.

Meal frequency and incidence of type 2 diabetes: a prospective study.

Dietary habits play an important role in the development of obesity and type 2 diabetes. However, evidence on association between diet frequency and type 2 diabetes was limited and inconclusive. We aimed to examine the association between meal frequency and risk of type 2 diabetes. The cohort study used data from China Health and Retirement Longitudinal Study of 8874 community-dwelling people aged over 45 years. Participants were classified as eating two meals per day, three meals per day and four meals per day. Multiple Poisson regression models were used to examine risk of 4-year incident type 2 diabetes among people who ate more or less than three meals per day compared with people who ate three meals per day. We documented 706 type 2 diabetes cases during follow-up. After adjustment for known risk factors for type 2 diabetes, except for BMI, participants who ate four meals per day were at a lower risk of type 2 diabetes than those who ate three meals per day (relative risk(RR) = 0·73 (0·58, 0·92)). After further adjustment for baseline BMI, the association was slightly attenuated but remained statistically significant (RR = 0·76 (0·60, 0·97)). Subgroup analysis showed that the fully adjusted RR of type 2 diabetes for people eating four meals per day were 0·66 (0·48, 0·91) and 0·93 (0·65, 1·34) among those had a BMI < 25 and ≥ 25 kg/m2, respectively. Eating four meals per day, compared with eating three meals per day was associated with lower risk of developing type 2 diabetes in a Chinese population, particularly in those with a BMI < 25 kg/m2.

Dairy intake and the risk of pancreatic cancer: the Japan Collaborative Cohort Study (JACC Study) and meta-analysis of prospective cohort studies.

Dairy product intake was suggested to reduce the risk of gastrointestinal cancers. This study investigated the association between dairy product intake and the risk of pancreatic cancer (PAC) using a prospective cohort study and meta-analysis of prospective cohort studies. First, we included 59 774 people aged 40-79 years from the Japan Collaborative Cohort Study (JACC Study). The Cox regression was used to compute the hazard ratios (HR) and 95 % CI of incident PAC for individuals who reported the highest intakes of milk, cheese and yogurt compared with not consuming the corresponding dairy products. Then, we combined our results with those from other four prospective cohort studies that were eligible after searching several databases, in a meta-analysis, using the fixed-effects model before evaluating publication bias and heterogeneity across studies. In the JACC Study, the highest v. no intakes of milk, cheese and yogurt were not associated with the reduced risk of PAC after a median follow-up of 13·4 years: HR (95 % CI) = 0·93 (0·64, 1·33), 0·91 (0·51, 1·62) and 0·68 (0·38, 1·21), respectively. The results did not significantly change in the meta-analysis: 0·95 (0·82, 1·11) for milk, 1·16 (0·87, 1·55) for cheese and 0·91 (0·79, 1·05) for yogurt. The meta-analysis showed no signs of publication bias or heterogeneity across studies. To conclude, consumption of milk, cheese and yogurt was not associated with the risk of PAC either in the JACC Study or the meta-analysis.

Aligned Millineedle Arrays for Solar Power Seawater Desalination with Site-Specific Salt Formation.

As a sustainable and clean water production technology, solar thermal water evaporation has been extensively studied in the past few years. One challenge is that upon operation, salt would form on surface of the solar absorbers leading to inefficient water supply and light absorption and thus much reduced water vaporization rate. To address this problem, a simple solar evaporator based on an array of aligned millineedles for efficient solar water evaporation and controlled site-specific salt formation is demonstrated. The maximum solar evaporation rate achieved is 2.94 kg m-2 h-1 under one Sun irradiation in brine of high salinity (25 wt% NaCl), achieving energy conversion efficiency of 94.5% simultaneously. More importantly, the spontaneously site-specific salt formation on the tips of millineedles endows this solar evaporator with salt harvesting capacity. Rationally separating the clean water and salt from brine by condensation and gravity assistance, this tip-preferential crystallization solar evaporator is not affected by the salt clogging compared with conventional 2D solar evaporators. This study provides new insights on the design of solar evaporators and advances their applications in sustainable seawater desalination and wastewater management.

Stable and Efficient Blue-Emitting CsPbBr3 Nanoplatelets with Potassium Bromide Surface Passivation.

Colloidal all-inorganic perovskites nanocrystals (NCs) have emerged as a promising material for display and lighting due to their excellent optical properties. However, blue emissive NCs usually suffer from low photoluminescence quantum yields (PLQYs) and poor stability, rendering them the bottleneck for full-color all-perovskite optoelectronic applications. Herein, a facile approach is reported to enhance the emission efficiency and stability of blue emissive perovskite nano-structures via surface passivation with potassium bromide. By adding potassium oleate and excess PbBr2 to the perovskite precursor solutions, potassium bromide-passivated (KBr-passivated) blue-emitting (≈450 nm) CsPbBr3 nanoplatelets (NPLs) is successfully synthesized with a respectably high PLQY of 87%. In sharp contrast to most reported perovskite NPLs, no shifting in emission wavelength is observed in these passivated NPLs even after prolonged exposures to intense irradiations and elevated temperature, clearly revealing their excellent photo- and thermal-stabilities. The enhancements are attributed to the formation of K-Br bonding on the surface which suppresses ion migration and formation of Br-vacancies, thus improving both the PL emission and stability of CsPbBr3 NPLs. Furthermore, all-perovskite white light-emitting diodes (WLEDs) are successfully constructed, suggesting that the proposed KBr-passivated strategy can promote the development of the perovskite family for a wider range of optoelectronic applications.

Consumption of flavonoid-rich fruits, flavonoids from fruits and stroke risk: a prospective cohort study.

We sought to examine the prospective associations of specific fruit consumption, in particular flavonoid-rich fruit (FRF) consumption, with the risk of stroke and subtypes of stroke in a Japanese population. A study followed a total of 39 843 men and 47 334 women aged 44-76 years, and free of CVD, diabetes and cancer at baseline since 1995 and 1998 to the end of 2009 and 2012, respectively. Data on total and specific FRF consumption for each participant were obtained using a self-administrated FFQ. The hazard ratios (HR) of stroke in relation to total and specific FRF consumption were estimated through Cox proportional hazards regression models. During a median follow-up of 13·1 years, 4091 incident stroke cases (2557 cerebral infarctions and 1516 haemorrhagic strokes) were documented. After adjustment for age, BMI, study area, lifestyles, dietary factors and other risk factors, it was found that total FRF consumption was associated with a significantly lower risk of stroke in women (HR = 0·70; 95 % CI 0·58, 0·84), while the association in men was not significant (HR = 0·93; 95 % CI 0·79, 1·09). As for specific FRF, consumptions of citrus fruits, strawberries and grapes were found associated with a lower stroke risk in women. Higher consumptions of FRF, in particular citrus fruits, strawberries and grapes, were associated with a lower risk of developing stroke in Japanese women.

Smoking Cessation, Weight Gain, Cardiovascular Risk, and All-Cause Mortality: A Meta-analysis.

INTRODUCTION: Quitting smoking usually results in weight gain, rising the concern that weight gain after smoking cessation may attenuate the benefits of smoking quitting on cardiovascular health. AIMS AND METHODS: We aimed to examine the risk of cardiovascular disease (CVD) among smoking quitters compared with smokers, stratified by post-cessation weight change. We searched PubMed, Scopus, and Web of Science for eligible studies published before September 2020. Cohort studies examining the relative risk of CVD among smoking quitters stratified by post-cessation weight change, with smokers being treated as the reference, were included. Two investigators extracted the key characteristics of each included study using a standard electronic form. RESULTS: We identified nine studies for this meta-analysis. Compared with smokers, the pooled RRs (95% confidence interval) of CVD among quitters with weight gain and among those without were 0.74 [0.66, 0.83] and 0.86 [0.80, 0.92], with no evidence of heterogeneity between studies being observed. Moreover, the associations appeared to be significantly stronger among quitters with weight gain than those without, particularly in the analysis of coronary heart disease (CHD) and stroke (pooled RRs = 0.65 [0.59, 0.71] vs. 0.79 [0.71, 0.88] for CHD and 0.67 [0.62, 0.73] vs. 0.76 [0.72, 0.81] for stroke, respectively; p for interaction <.05). CONCLUSIONS: Smoking cessation was associated with a significantly lower risk of CVD and all-cause mortality, regardless of post-cessation weight gain. A greater risk reduction among quitters with weight gain than those without merits further investigations. IMPLICATIONS: Quitting smoking usually results in weight gain and increases the risk of type 2 diabetes. We found that the risk reduction in CVD and all-cause mortality associated with smoking cessation was greater in quitters with weight gain than that in quitters without, especially in CHD and stroke. Despite weight gain and increased risk of type 2 diabetes, quitting smoking remains effective in the prevention of CVD.

Soy consumption and incidence of gestational diabetes mellitus: the Japan Environment and Children's Study.

BACKGROUND: Intervention studies have shown that isoflavone treatment improved glucose metabolism, indicating that soy intake may have a potential role in diabetes prevention. OBJECTIVES: We aimed to investigate the prospective association of soy isoflavone and soy food intakes with incidence of gestational diabetes mellitus (GDM) in a birth cohort study. METHODS: We recruited 97,454 pregnant women (median gestational age 12 weeks) between January 2011 and March 2014. Dietary intakes during the 12 months preceding study enrollment were assessed by a semi-quantitative food frequency questionnaire. The relative risks of GDM associated with soy isoflavone and soy food intakes were obtained by Poisson regression. Demographic information, histories of diseases, socioeconomic status, lifestyles, and dietary habits, obtained by a self-administrated questionnaire, were used for covariate adjustments. RESULTS: We identified 1904 cases of GDM (2.2%) among 84,948 women. Compared with those in the lowest quintile of soy isoflavone intake, women in the highest quintile were found to have experienced a significantly lower risk of GDM (multivariate relative risk = 0.82; 95% confidence interval: 0.70, 0.95; P for trend = 0.05). Similar results were observed for genistein and daidzein. Regarding soy foods, intakes of miso soup and natto were inversely associated with GDM incidence (both P for trend ≤ 0.01), whereas the association for tofu intake appeared to be nonlinear (P for trend = 0.74). CONCLUSIONS: Higher intakes of miso soup and natto before and during early pregnancy, compared with lower intakes, may be associated with a lower incidence of GDM.

Consumption of soy products and cardiovascular mortality in people with and without cardiovascular disease: a prospective cohort study of 0.5 million individuals.

PURPOSE: We sought to examine the association of soy product consumption with risk of cardiovascular death in Chinese individuals with and without a history of cardiovascular disease (CVD). METHODS: The current analysis included 487,034 individuals free of CVD and 22,923 individuals with a history of CVD at study baseline. Data on consumption of soy products were collected by a food frequency questionnaire. The Cox regression was used to obtain the hazard ratios (HRs) of cardiovascular mortality associated with soy product consumption among people with and without a history of CVD at baseline. RESULTS: During the period of follow-up, 12,582 and 2860 cardiovascular deaths were recorded among people without and with a history of CVD. Compared with those who never or rarely ate soy products, the multivariable HRs (95% CIs) were 1.02 (0.96, 1.08) for those who ate soy products monthly, 1.01 (0.95, 1.07) for those who ate soy products 1-3 days per week, 0.95 (0.88, 1.04) for those who ate soy products ≥ 4 days per week. For cause-specific mortality, soy product consumption was inversely associated with mortality from acute myocardial infarction (HR [95% CI] = 0.75 [0.61, 0.92]). Among people with a history of CVD, higher soy product consumption was not associated with cardiovascular mortality. CONCLUSIONS: Soy consumption ≥ 4 days per week was associated with a significantly lower risk of mortality from acute myocardial infarction in comparison with never or rarely consumption among people without a history of CVD. Among people with a history of CVD, higher soy product consumption was not associated with cardiovascular mortality.

The association between smoking and risk of skin cancer: a meta-analysis of cohort studies.

PURPOSE: The association between smoking and the risk of skin cancers has been studied without reaching consistent findings. This study aims to assess this association through an updated meta-analysis of cohort studies. METHODS: We retrieved cohort studies that investigated the temporal association between smoking and the risk of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and malignant melanoma (MM). Pooled relative risks (RRs) and confidence intervals (CIs) of the included articles were calculated for current, former, and heavy smoking compared with never smoking. Publication bias was detected using the Egger's regression. RESULTS: A total of 15 studies, published between 1990 and 2018, were included. Current smoking was associated with a higher risk of SCC (pooled RR = 1.32, 95% CI 1.15, 1.52) but with a lower risk of BCC (pooled RR = 0.85, 95% CI 0.75, 0.96) and MM (pooled RR = 0.72, 95% CI 0.64, 0.82). No publication bias was detected, and no single study had a substantial impact on the pooled results. Similar results were detected for heavy smoking, while former smoking was not associated with the risk of skin cancer. CONCLUSION: Current smoking and heavy smoking were associated with a higher risk of SCC but a decreased risk of BCC and MM, while former smoking was not associated with skin cancer risk.

Effects of strawberry intervention on cardiovascular risk factors: a meta-analysis of randomised controlled trials.

We conducted a meta-analysis of randomised controlled trials (RCT) to examine the effects of strawberry interventions on cardiovascular risk factors. We searched multiple databases including PubMed, Web of Science and Scopus to identify eligible studies published before 19 May 2019. The endpoints were blood pressure, total cholesterol (TC), HDL-cholesterol, LDL-cholesterol, TAG, fasting blood glucose, endothelial function and inflammatory factors. Pooled analyses were performed using random- or fixed-effects models according to a heterogeneity test. We also conducted sub-group analyses by baseline endpoint levels. We included eleven RCT in this meta-analysis (six for blood pressure, seven for lipid profile, seven for fasting blood glucose and six for C-reactive protein (CRP)). Overall, the strawberry interventions significantly reduced CRP levels by 0·63 (95 % CI -1·04, -0·22) mg/l but did not affect blood pressure, lipid profile or fasting blood glucose in the main analyses. Our analysis stratified by baseline endpoint levels showed the strawberry interventions significantly reduced TC among people with baseline levels >5 mmol/l (-0·52 (95 % CI -0·88, -0·15) mmol/l) and reduced LDL-cholesterol among people with baseline levels >3 mmol/l (-0·31 (95 % CI -0·60, -0·02) mmol/l). There was little evidence of heterogeneity in the analysis and no evidence of publication bias. In summary, strawberry interventions significantly reduced CRP levels and may improve TC and LDL-cholesterol in individuals with high baseline levels.

Consumption of flavonoid-rich fruits and risk of CHD: a prospective cohort study.

Although the association between fruit consumption and CHD risk has been well studied, few studies have focused on flavonoid-rich fruits (FRF), in particular strawberries and grapes. We aimed to verify the association of total and specific FRF consumption with risk of CHD by a large prospective cohort study. A total of 87 177 men and women aged 44-75 years who were free of CVD and cancer at study baseline were eligible for the present analysis. FRF consumption was assessed using a FFQ. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) of CHD in relation to FRF consumption with adjustment for potential risk factors and confounders. During a mean follow-up of 13·2 years, we identified 1156 incident CHD cases. After full adjustment for covariates including demographics, lifestyles and dietary factors, the HR were 0·93 (95 % CI 0·77, 1·11), 0·91 (95 % CI 0·75, 1·11), 0·84 (95 % CI 0·67, 1·04) and 0·78 (95 % CI 0·62, 0·99) for the second, third, fourth and fifth quintiles compared with the lowest quintile of FRF consumption. Regarding specific fruits, we observed a significant inverse association for citrus fruit consumption and a borderline inverse association for strawberry consumption, while no association was observed for apple/pear or grape consumption. Although the associations appeared to be stronger in women, they were not significantly modified by sex. Higher consumption of FRF, in particular, citrus fruits, may be associated with a lower risk of developing CHD.

Chocolate consumption and risk of gestational diabetes mellitus: the Japan Environment and Children's Study.

The association of chocolate consumption with risk of gestational diabetes has not been examined. We aimed to investigate the prospective association between chocolate consumption and risk of gestational diabetes in a large birth cohort in Japan. A total of 97 454 pregnant women with a median gestational age of 12 weeks were recruited from January 2011 to March 2014. Data on demographic information, disease history, socio-economic status, lifestyle and dietary habits were obtained at the study enrolment. Dietary intake during the past 12 months before study enrolment was assessed through a semi-quantitative FFQ. The logistic regression was used to obtain the OR of gestational diabetes in relation to chocolate consumption. Among 84 948 women eligible for the analysis, 1904 cases of gestational diabetes (2·2 %) were identified during the period of pregnancy. After controlling for potential confounding factors including age, smoking status, drinking status, education level, occupation, pre-pregnant BMI, depression, previous history of macrosomia babies, parity, physical activity and dietary factors, women in the highest quartile of chocolate consumption, compared with those in the lowest quartile, had a significantly lower risk of developing gestational diabetes (OR 0·78, 95 % CI 0·67, 0·90; P for trend = 0·002). Stratified analyses suggested that the association was not significantly modified by pre-pregnancy BMI, age, parity, smoking status or drinking status. The present prospective cohort study provided evidence that chocolate consumption was associated with a significant lower risk of gestational diabetes in Japanese women.