Blood trihalomethane and urinary haloacetic acid concentrations in relation to hypertension: An observational study among 1162 healthy men.

Disinfection byproducts (DBPs) have demonstrated cardiovascular and reproductive toxicity. However, the associations and mechanisms of DBP exposure in relation to hypertension among healthy young men, which are critical for gaining new insights into the prevention and treatment of male subfertility, remain unclear. In 2017-2018, we recruited 1162 healthy Chinese men. A single blood sample was collected and measured for trihalomethane (THM) concentrations (n = 956). Up to 2930 repeated urinary samples were collected at baseline and during follow-up periods and determined for haloacetic acid concentrations. Oxidative stress (OS) biomarkers were measured in within-subject pooled urinary samples (n = 1003). In total, 403 (34.68 %) participants were diagnosed with stage 1-2 hypertension (≥130/80 mmHg) and 108 (9.29 %) stage 2 hypertension (≥140/90 mmHg). In adjusted models, blood bromodichloromethane (BDCM) concentrations were positively associated with the risk of stage 1-2 and stage 2 hypertension [ORs= 1.48 (95 % CI: 1.15, 1. 91) and 1.65 (95 % CI: 1.08, 2.51), respectively, per 2.7-fold increase in BDCM concentrations]. Additionally, we found positive associations between DBP exposure biomarkers and urinary concentrations of 4-hydroxy-2-nonenal-mercapturic acid and 8-hydroxy-2-deoxyguanosine. However, these OS biomarkers were unrelated to hypertension. Our results suggest that BDCM exposure may be associated with a greater risk of hypertension among healthy young men.

Gut antibiotic resistome during pregnancy associates with the risk of gestational diabetes mellitus: New evidence from a prospective nested case-control study.

Antibiotic resistome has emerged as a global threat to public health. However, gestational antibiotic resistome and potential link with adverse pregnancy outcomes remains poorly understood. Our study reports for the first time an association between gut antibiotic resistome during early pregnancy and the risk of gestational diabetes mellitus (GDM) based on a prospective nested case-control cohort including 120 cases and 120 matched controls. A total of 214 antibiotic resistance gene (ARG) subtypes belonging to 17 ARG types were identified in > 10 % fecal samples collected during each trimester. The data revealed dynamic profiles of gut antibiotic resistome through pregnancy, and significant positive associations between selected features (i.e., ARG abundances and a GDM-ARG score which is a new feature characterizing the association between ARGs and GDM) of gut antibiotic resistome during early pregnancy and GDM risk as well as selected endogenous metabolites. The findings demonstrate ubiquitous presence of ARGs in pregnant women and suggest it could constitute an important risk factor for the development of GDM.

Associations of social determinants of health with life expectancy and future health risks among individuals with type 2 diabetes: two nationwide cohort studies in the UK and USA.

BACKGROUND: Social determinants of health (SDHs) are the primary drivers of preventable health inequities, and the associations between SDHs and health outcomes among individuals with type 2 diabetes remain unclear. This study aimed to estimate the associations of combined SDHs with life expectancy and future health risks among adults with type 2 diabetes from the UK and USA. METHODS: In an analysis of two nationwide cohort studies, adults with type 2 diabetes were identified from the UK Biobank from March 13, 2006, to Oct 1, 2010 (adults aged 37-73 years) and the US National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018 (adults aged ≥20 years). Participants with type 2 diabetes at baseline were included in our analysis. Participants without information on SDHs or follow-up were excluded. The UK Biobank assessed 17 SDHs and the US NHANES assessed ten SDHs, with each SDH dichotomised into advantaged and disadvantaged levels. The combined score of SDHs were calculated as the sum of the weighted scores for each SDH. Participants were then categorised into tertiles (favourable, medium, and unfavourable SDH groups). Primary outcomes were life expectancy and mortality in both cohorts, and incidences of cardiovascular disease, diabetes-related microvascular disease, dementia, and cancer in the UK Biobank. Outcomes were obtained from disease registries up until Dec 31, 2021, in the UK Biobank and Dec 31, 2019, in the US NHANES cohorts. FINDINGS: We included 17 321 participants from the UK Biobank cohort (median age 61·0 years [IQR 56·0-65·0]; 6028 [34·8%] women and 11 293 [65·2%] men) and 7885 participants from the NHANES cohort (mean age 59·2 years [95% CI 58·7-59·6]; 3835 [49·1%, weighted] women and 4050 [50·9%, weighted] men) in our analysis. In the UK Biobank, 3235 deaths (median follow-up 12·3 years [IQR 11·5-13·2]), 3010 incident cardiovascular disease (12·1 years [10·8-13·0]), 1997 diabetes-related microvascular disease (8·0 years [7·1-8·9]), 773 dementia (12·6 years [11·8-13·5]), and 2259 cancer cases (11·3 years [10·4-12·2]) were documented; and the US NHANES documented 2278 deaths during a median follow-up of 7·0 years (3·7-11·2). After multivariable adjustment, compared with the favourable SDH group, the hazard ratio was 1·33 (95% CI 1·21-1·46) in the medium SDH group and 1·89 (1·72-2·07) in the unfavourable SDH group in the UK Biobank cohort; 1·51 (1·34-1·70) in the medium SDH group and 2·02 (1·75-2·33) in the unfavourable SDH group in the US NHANES cohort for all-cause mortality; 1·13 (1·04-1·24) in the medium SDH group and 1·40 (1·27-1·53) in the unfavourable SDH group for incident cardiovascular disease; 1·13 (1·01-1·27) in the medium SDH group and 1·41 (1·26-1·59) in the unfavourable SDH group for incident diabetes-related microvascular disease; 1·35 (1·11-1·64) in the medium SDH group and 1·76 (1·46-2·13) in the unfavourable SDH group for incident dementia; and 1·02 (0·92-1·13) in the medium SDH group and 1·17 (1·05-1·30) in the unfavourable SDH group for incident cancer in the UK Biobank cohort (ptrend<0·010 for each category). At the age of 45 years, the mean life expectancy of participants was 1·6 years (0·6-2·3) shorter in the medium SDH group and 4·4 years (3·3-5·4) shorter in the unfavourable SDH group than in the favourable SDH group in the UK Biobank. In the US NHAHES cohort, the life expectancy was 1·7 years (0·6-2·7) shorter in the medium SDH group and 3·0 years (1·8-4·3) shorter in the unfavourable SDH group, compared with the favourable group. INTERPRETATION: Combined unfavourable SDHs were associated with a greater loss of life expectancy and higher risks of developing future adverse health outcomes among adults with type 2 diabetes. These associations were similar across two nationwide cohorts from varied social contexts, and were largely consistent across populations with different demographic, lifestyle, and clinical features. Thus, assessing the combined SDHs of individuals with type 2 diabetes might be a promising approach to incorporate into diabetes care to identify socially vulnerable groups and reduce disease burden. FUNDING: The National Natural Science Foundation of China, the National Key R&D Program of China, and the Fundamental Research Funds for the Central Universities.

Association of life's essential 8 with risk of recurrent cardiovascular events among patients with coronary heart disease.

AIMS: To examine the association of Life's Essential 8 (LE8) with the risk of recurrent cardiovascular events among patients with CHD. METHODS: This prospective cohort study included 11,997 patients with CHD from the UK Biobank. The LE8 score was generated using five lifestyle factors (diet, body mass index, physical activity, smoking, and sleep) and three biological factors (blood lipids, blood glucose, and blood pressure). LE8 score ranged from 0 to 100 and was categorized into quartiles. Cox proportional hazards regression models were applied to estimate the hazard ratio (HR) and 95% CI (confidence interval). RESULTS: During a median follow up of 12.5 years, we documented 3366 recurrent cardiovascular events, 1068 myocardial infarction, 1829 heart failure events, 703 strokes, and 934 cardiovascular deaths. The multivariable-adjusted HR (95% CI) for the highest versus the lowest quartile of LE8 score was 0.57 (0.50, 0.65) for recurrent cardiovascular events, 0.66 (0.52, 0.83) for myocardial infarction, 0.54 (0.45, 0.67) for heart failure, 0.50 (0.36, 0.68) for stroke, and 0.46 (0.37, 0.56) for cardiovascular death. Furthermore, the population attributable fraction of the lowest to the highest quartile of LE8 score were ranged from 16.2% to 32.5% for the various cardiovascular outcomes. In addition, biomarkers including renal function and inflammation collectively explained 47.6%-87.7% of the associations between the lifestyle factors and recurrent cardiovascular events. CONCLUSIONS: Better cardiovascular health as measured by LE8 was associated with significantly lower risk of recurrent cardiovascular events among patients with CHD. Clinicians should prioritize educating patients with CHD on the importance of optimal cardiovascular health for secondary prevention. In addition, our findings indicated significant mediation effect of biomarkers involving of glycemic control, renal function, liver function, lipid profile, and systemic inflammation on the associations between overall lifestyle factors and recurrent cardiovascular events.

Fish Oil, Plasma n-3 PUFAs, and Risk of Macro- and Microvascular Complications among Individuals with Type 2 Diabetes.

OBJECTIVE: To evaluate associations of fish oil supplementation and plasma omega 3 polyunsaturated fatty acids (n-3 PUFAs) with risks of macrovascular and microvascular complications among people with type 2 diabetes, and to further explore the potential mediating role of metabolism-related biomarkers. RESEARCH DESIGN AND METHODS: This study included 20,338 participants with type 2 diabetes from UK Biobank. Diabetic complications were identified through hospital inpatient records. RESULTS: During 13.2 years of follow-up, 5,396 people developed macrovascular complications, and 4,868 people developed microvascular complications. After multivariable adjustment, hazard ratios (HRs) and 95% confidence intervals (CIs) for patients with fish oil were 0.90 (0.85, 0.97) for composite macrovascular complications, 0.91 (0.84, 0.98) for coronary heart disease (CHD), 0.72 (0.61, 0.83) for peripheral artery disease; and 0.89 (0.83, 0.95) for composite microvascular complications, 0.87 (0.79, 0.95) for diabetic kidney disease, and 0.88 (0.80, 0.97) for diabetic retinopathy. In addition, higher n-3 PUFA levels, especially docosahexaenoic acid (DHA), were associated with lower risks of macrovascular and microvascular complications. Comparing extreme quartiles of plasma DHA, the HRs (95% CIs) were 0.68 (0.57, 0.81) for composite macrovascular complications, 0.63 (0.51, 0.77) for CHD; and 0.59 (0.38, 0.91) for diabetic neuropathy. Moreover, biomarkers including lipid profile and inflammation collectively explained 54.4% and 63.1% of associations of plasma DHA with risks of composite macrovascular complications and CHD. CONCLUSIONS: Habitual use of fish oil supplementation and higher plasma n-3 PUFA levels, especially DHA, were associated with lower risks of macrovascular and microvascular complications among individuals with type 2 diabetes, and the favorable associations were partially mediated through improving biomarkers of lipid profile and inflammation.

Adherence to a planetary health diet, genetic susceptibility, and incident cardiovascular disease: a prospective cohort study from the UK Biobank.

BACKGROUND: The influence of adherence to a planetary health diet (PHD) proposed by the EAT-Lancet Commission on cardiovascular disease (CVD) is inconclusive. Besides, whether genetic susceptibility to CVD can modify the association of PHD with CVD remains unknown. OBJECTIVE: We aimed to investigate the association between adherence to PHD and CVD, and to evaluate the interaction between PHD and genetic predisposition to CVD. METHODS: This study included 114,165 participants who completed at least two 24-h dietary recalls and were initially free of CVD from the UK Biobank. PHD score was calculated to assess adherence to PHD. Genetic risk was evaluated using the polygenic risk score. Incidence of total CVD, ischemic heart disease (IHD), atrial fibrillation (AF), heart failure (HF), and stroke were identified via electronic health records. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a median follow-up of 9.9 y, 10,071 (8.8%) incident CVD cases were documented. Compared with participants with the lowest adherence to PHD, HRs (95% CIs) for total CVD, IHD, AF, HF, and stroke among those with the highest adherence were 0.79 (0.74, 0.84), 0.73 (0.67, 0.79), 0.90 (0.82, 0.99), 0.69 (0.59, 0.82), and 0.88 (0.75, 1.04), respectively. No significant interaction between the genetic risk of CVD and PHD was observed. Participants with high genetic risk and low PHD score, as compared with those with low genetic risk and high PHD score, had a 48% (95% CI: 40%, 56%) higher risk of CVD. The population-attributable risk (95% CI) of CVD for poor adherence to PHD ranged from 8.79% (5.36%, 12.51%) to 14.00% (9.00%, 18.88%). CONCLUSIONS: These findings suggest that higher adherence to PHD was associated with lower risk of total CVD, IHD, AF, and HF in populations across all genetic risk categories.

Association of ultraprocessed food consumption with risk of microvascular complications among individuals with type 2 diabetes in the UK Biobank: a prospective cohort study.

BACKGROUND: The poor nutritional characteristics and potentially harmful molecules in ultraprocessed foods (UPFs) are risk factors for diabetic microvascular complications. However, the evidence regarding UPFs and diabetic microvascular complications remains limited. OBJECTIVES: We aimed to evaluate the associations between UPF consumption and risk of diabetic microvascular complications, to examine the underlying biological pathways (e.g., inflammation and lipid profile), and to identify whether the associations differ by type of UPF dietary patterns. METHODS: We included a prospective cohort of UK Biobank participants with type 2 diabetes (T2D) having at least one 24-h dietary recall (N = 5685). UPFs were defined using the Nova classification. Principal component analysis was used to derive UPF consumption patterns. Associations of UPFs and their consumption patterns with microvascular complications were assessed using Cox proportional hazards regression models. Mediation analyses were used to estimate the mediating effects of 22 biomarkers. RESULTS: During a median of 12.7 y of follow-up, 1243 composite microvascular complications events occurred (599 diabetic retinopathy, 237 diabetic neuropathy, and 662 diabetic kidney disease events). Five consumption patterns were identified (spread and bread, cereal prepared with liquids, dairy-based products, sugary beverage and snack, and mixed beverage and savory snack patterns). A 10% increment in the proportion of UPF was associated with higher hazards of the composite microvascular complications (hazard ratio [HR]: 1.08; 95% confidence interval [CI]: 1.03, 1.13) and diabetic kidney disease (HR: 1.13; 95% CI: 1.06, 1.20). Triglycerides, C-reactive protein, and body mass index collectively explained 22.0% (9.6%-43.0%) of the association between UPF intake and composite microvascular complications. Pattern high in mixed beverage and savory snack was associated with a higher risk of composite microvascular complications. CONCLUSIONS: Higher UPF consumption was associated with higher risks of diabetic microvascular complications, and the association was partly mediated through multiple potential ways.

Fourier ptychographic microscopy with adaptive resolution strategy.

Fourier ptychographic microscopy (FPM) is a method capable of reconstructing a high-resolution, wide field-of-view (FOV) image, where dark-field images provide the high-frequency information required for the iterative process. Theoretically, using more dark-field images can lead to results with higher resolution. However, the resolution required to clearly detect samples with different microscales varies. For certain samples, the limit resolution of the imaging system may exceed the one required to resolve the details. This suggests that simply increasing the number of dark-field images will not improve the recognition capability for such samples and may instead significantly increase the computational cost. To address this issue, this Letter proposes an adaptive resolution strategy that automatically assigns the resolution required for the sample. Based on a Tenengrad approach, this strategy determines the number of images required for reconstruction by evaluating a series of differential images among the reconstructions for a certain subregion and then efficiently completes the full-FOV reconstruction according to the determined resolution. We conducted the full-FOV reconstruction utilizing feature-domain FPM for both the USAF resolution test chart and a human red blood cell sample. Employing the adaptive resolution strategy, the preservation of reconstruction resolution can be ensured while respectively economizing approximately 76% and 89% of the time.

Serum 25-hydroxyvitamin D concentrations, vitamin D receptor polymorphisms, and risk of infections among individuals with type 2 diabetes: a prospective cohort study.

BACKGROUND: Evidence on the association between serum 25-hydroxyvitamin D [25(OH)D] and infections among patients with type 2 diabetes (T2D), a group susceptible to vitamin D deficiency and infections, is limited. OBJECTIVES: We aimed to examine this association in individuals with T2D, and to evaluate whether genetic variants in vitamin D receptor (VDR) would modify this association. METHODS: This study included 19,851 participants with T2D from United Kingdom Biobank. Infections were identified by linkage to hospital inpatient and death registers. Negative binomial regression models were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs), with adjustment of potential confounders. RESULTS: In patients with T2D, the incidence rate of infections was 29.3/1000 person-y. Compared with those with 25(OH)D of 50.0-74.9 nmol/L, the multivariable-adjusted IRRs and 95% CIs of total infections, pneumonia, gastrointestinal infections, and sepsis were 1.44 (1.31, 1.59), 1.49 (1.27, 1.75), 1.47 (1.22, 1.78), and 1.41 (1.14, 1.73), respectively, in patients with 25(OH)D <25.0 nmol/L. Nonlinear inverse associations between 25(OH)D concentrations and the risks of total infections (P-overall < 0.001; P-nonlinear = 0.002) and gastrointestinal infections (P-overall < 0.001; P-nonlinear = 0.040) were observed, with a threshold effect at ∼50.0 nmol/L. The vitamin D-infection association was not modified by genetic variants in VDR (all P-interaction > 0.050). CONCLUSIONS: In patients with T2D, lower serum 25(OH)D concentration (<50 nmol/L) was associated with higher risks of infections, regardless of genetic variants in VDR. Notably, nonlinear inverse associations between 25(OH)D concentrations and the risks of infections were found, with a threshold effect at ∼50.0 nmol/L. These findings highlighted the importance of maintaining adequate vitamin D in reducing the risk of infections in patients with T2D.

Association of trajectories and cumulative exposure of antenatal depression with high birth weight.

BACKGROUND: Inconsistent associations between antenatal depression and fetal birth weight were reported previously, and little is known about the dynamic changes and long-term cumulative effect of antenatal depression during pregnancy. METHODS: Participants were from the Tongji-Huaxi-Shuangliu Birth Cohort. Depressive symptoms were measured using the Edinburgh Postnatal Depression Scale in early, middle, and late pregnancy respectively. Trajectories of antenatal depression were assessed using the latent class mixed model. The percentage of days with depression (PDD) and frequency of antenatal depression were measured to assess the cumulative exposure. Multivariable logistic regression models were used to evaluate the associations of antenatal depression with macrosomia and large for gestational age (LGA). RESULTS: We identified four distinct trajectories, including the low stable group (n = 1,327, 27.99 %), the moderate stable group (n = 2,610, 55.05 %), the peak group (n = 407, 8.58 %), and the valley group (n = 397, 8.37 %). Compared with the low stable group, the valley group showed a higher risk of macrosomia (OR, 1.98; 95 % CI, 1.17, 3.38) and LGA (OR, 1.44; 95 % CI, 1.002, 2.09); the peak group showed a higher risk of LGA (OR, 1.52; 95 % CI, 1.07, 2.16), but the association was not significant for macrosomia (OR, 1.47; 95 % CI, 0.85, 2.55). Consistently, cumulative antenatal depression was also positively associated with the risks of macrosomia and LGA. LIMITATION: The antenatal depression was self-reported using a screening scale and information bias could not be ruled out. CONCLUSION: Certain trajectories and cumulative exposure of antenatal depression were associated with higher risks of high birth weight.

Vitamin D and major chronic diseases.

Numerous observational studies have demonstrated a significant inverse association between vitamin D status and the risk of major chronic disease, including type 2 diabetes (T2D), cardiovascular disease (CVD), and cancer. However, findings from Mendelian randomization (MR) studies and randomized controlled trials (RCTs) suggest minimal or no benefit of increased vitamin D levels. We provide an overview of recent literature linking vitamin D to major chronic diseases. Because emerging evidence indicates a potential threshold effect of vitamin D, future well-designed studies focused on diverse populations with vitamin D deficiency or insufficiency are warranted for a more comprehensive understanding of the effect of maintaining sufficient vitamin D status on the prevention of major chronic diseases.

Depth-of-field extended Fourier ptychographic microscopy without defocus distance priori.

Fourier ptychographic microscopy (FPM) provides a solution of high-throughput phase imaging. Thanks to its coherent imaging model, FPM has the capacity of depth-of-field (DOF) extension by simultaneously recovering the sample's transmittance function and pupil aberration, which contains a defocus term. However, existing phase retrieval algorithms (PRs) often struggle in the presence of a significant defocus. In this Letter, different PRs with embedded pupil recovery are compared, and the one based on the alternating direction multiplier method (ADMM-FPM) demonstrates promising potential for reconstructing highly defocused FPM images. Besides, we present a plug-and-play framework that integrates ADMM-FPM and total variation or Hessian denoiser for pupil function enhancement. Both simulations and experiments demonstrate that this framework enables robust reconstruction of defocused FPM images without any prior knowledge of defocus distance or sample characteristics. In experiments involving USAF 1951 targets and pathologic slides, ADMM-FPM combined with the Hessian denoiser successfully corrected the defocus up to approximately 200 µm, i.e., extending the DOF to 400 µm.

Trends in cardiovascular health metrics and associations with long-term mortality among US adults with coronary heart disease.

BACKGROUND AND AIMS: Our study examined the trends of cardiovascular health metrics in individuals with coronary heart disease (CHD) and their associations with all-cause and cardiovascular disease mortality in the US. METHODS AND RESULTS: The cohort study was conducted based on the National Health and Nutrition Examination Survey 1999-2018 and their linked mortality files (through 2019). Baseline CHD was defined as a composite of self-reported doctor-diagnosed coronary heart disease, myocardial infarction, and angina pectoris. Cardiovascular health metrics were assessed according to the American Heart Association recommendations. Long-term all-cause and cardiovascular disease mortality were the primary outcomes. Survey-adjusted Cox regression models were used to estimate hazard ratios and corresponding 95% confidence intervals for the associations between cardiovascular health metrics and all-cause and cardiovascular disease mortality. The prevalence of one or fewer ideal cardiovascular health metrics increased from 14.15% to 22.79% (P < 0.001) in CHD, while the prevalence of more than four ideal cardiovascular health metrics decreased from 21.65% to 15.70 % (P < 0.001) from 1999 to 2018, respectively. Compared with CHD participants with one or fewer ideal cardiovascular health metrics, those with four or more ideal cardiovascular health metrics had a 35% lower risk (hazard ratio, 0.65; 95% confidence interval: 0.51, 0.82) and a 44% lower risk (0.56; 0.38, 0.84) in all-cause and cardiovascular disease mortality, respectively. CONCLUSION: Substantial declines were noted in ideal cardiovascular health metrics in US adults with CHD. A higher number of cardiovascular health metrics was associated with lower all-cause and cardiovascular disease mortality in them.

Circulating metabolic biomarkers and risk of new-onset hypertension: findings from the UK Biobank.

OBJECTIVE: The evidence regarding the associations of circulating metabolic biomarkers with hypertension risk is scarce. We aimed to examine the associations between circulating metabolites and risk of hypertension. METHODS: We included 49 422 individuals free of hypertension at baseline with a mean (SD) age of 53.5 (8.0) years from the UK Biobank. Nuclear magnetic resonance spectroscopy was used to quantify 143 individual metabolites. Multivariable-adjusted Cox regression models were used to estimate hazard ratios and 95% confidence intervals (CIs). RESULTS: During a mean (SD) follow-up of 11.2 (1.8) years, 2686 incident hypertension cases occurred. Out of 143 metabolites, 76 were associated with incident hypertension, among which phenylalanine (hazard ratio: 1.40; 95% CI: 1.24-1.58) and apolipoprotein A1 (hazard ratio: 0.76; 95% CI: 0.66-0.87) had the strongest association when comparing the highest to the lowest quintile. In general, very-low-density lipoprotein (VLDL) particles were positively, whereas high-density lipoprotein (HDL) particles were inversely associated with risk of hypertension. Similar patterns of cholesterol, phospholipids, and total lipids within VLDL and HDL particles were observed. Triglycerides within all lipoproteins were positively associated with hypertension risk. Other metabolites showed significant associations with risk of hypertension included amino acids, fatty acids, ketone bodies, fluid balance and inflammation markers. Adding 10 selected metabolic biomarkers to the traditional hypertension risk model modestly improved discrimination (C-statistic from 0.745 to 0.752, P < 0.001) for prediction of 10-year hypertension incidence. CONCLUSION: Among UK adults, disturbances in metabolic biomarkers are associated with incident hypertension. Comprehensive metabolomic profiling may provide potential novel biomarkers to identify high-risk individuals.

Landscape of the gut mycobiome dynamics during pregnancy and its relationship with host metabolism and pregnancy health.

OBJECTIVE: The remodelling of gut mycobiome (ie, fungi) during pregnancy and its potential influence on host metabolism and pregnancy health remains largely unexplored. Here, we aim to examine the characteristics of gut fungi in pregnant women, and reveal the associations between gut mycobiome, host metabolome and pregnancy health. DESIGN: Based on a prospective birth cohort in central China (2017 to 2020): Tongji-Huaxi-Shuangliu Birth Cohort, we included 4800 participants who had available ITS2 sequencing data, dietary information and clinical records during their pregnancy. Additionally, we established a subcohort of 1059 participants, which included 514 women who gave birth to preterm, low birthweight or macrosomia infants, as well as 545 randomly selected controls. In this subcohort, a total of 750, 748 and 709 participants had ITS2 sequencing data, 16S sequencing data and serum metabolome data available, respectively, across all trimesters. RESULTS: The composition of gut fungi changes dramatically from early to late pregnancy, exhibiting a greater degree of variability and individuality compared with changes observed in gut bacteria. The multiomics data provide a landscape of the networks among gut mycobiome, biological functionality, serum metabolites and pregnancy health, pinpointing the link between Mucor and adverse pregnancy outcomes. The prepregnancy overweight status is a key factor influencing both gut mycobiome compositional alteration and the pattern of metabolic remodelling during pregnancy. CONCLUSION: This study provides a landscape of gut mycobiome dynamics during pregnancy and its relationship with host metabolism and pregnancy health, which lays the foundation of the future gut mycobiome investigation for healthy pregnancy.

Metal exposure and blood lipid biomarkers in early pregnancy: A cross-sectional study.

Recognizing the risk factors for dyslipidemia during pregnancy is crucial for safeguarding the health of both the mothers and the offspring. Growing evidence emerged and suggested links between environmental factors, including metals, and alteration in lipid levels or dyslipidemia in general populations. However, knowledge of the associations during pregnancy remains extremely lacking. Herein, we aimed to explore whether elevated metal exposure constitutes a risk factor for dyslipidemia in pregnant women. Based on the Tongji-Shuangliu Birth Cohort (TSBC), a total of 663 pregnant women were recruited and their urinary levels of 17 metals and blood lipid biomarkers in early pregnancy were measured, namely triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). The multivariable linear regression models revealed that exposure to selected metals during early pregnancy was significantly associated with some important biomarkers. In particular, after natural log-transformed for the levels of lipid biomarkers and metals, copper (Cu) exposure was positively associated with HDL-C (ß = 0.024, 95% CI: 0.001, 0.046), while zinc (Zn) was associated with TG (ß = 0.062, 95% CI: 0.013, 0.110) and selenium with TC (ß = 0.028, 95% CI: 0.004, 0.054). Exposure to rubidium (Rb) was positively associated with multiple lipid biomarkers, including HDL-C (ß = 0.020, 95% CI: 0.002, 0.037) and LDL-C (ß = 0.022, 95% CI: 0.001, 0.042). Mixture exposure analysis further identified significant associations between Cu and HDL-C, Zn and TG, Rb and HDL-C, when multiple metal exposures were considered in the Bayesian kernel machine regression model simultaneously. Our findings showed that exposure to several metals during early pregnancy was associated with an increased prevalence of blood lipid abnormalities in pregnant women. These findings underscore the potential impact of metal combinations on lipid metabolism and increase our understanding of the risk factors associated with abnormal lipid metabolism during pregnancy.

Association between consumption of fruits and vegetables in midlife and depressive symptoms in late life: the Singapore Chinese Health Study.

OBJECTIVES: Epidemiological evidence of how midlife intake of fruits and vegetables affects the likelihood of depressive symptoms in late life remains limited and controversial. We examined this association in an Asian cohort. DESIGN: Prospective population-based cohort study. SETTING: Chinese living in Singapore. PARTICIPANTS: A total of 13,738 adults from the Singapore Chinese Health Study. MEASUREMENTS: The consumption of 14 fruits and 25 vegetables were assessed using a validated 165-item food-frequency questionnaire at baseline (1993-1998), when participants were aged 45-74 years (mean age 52.4 years). Depressive symptoms were evaluated using the Geriatric Depression Scale during the third follow-up interviews (2014-2016), when participants were aged 61-96 years (mean age 72.5 years), and depression was defined by ≥5 out of 15 scores. Multivariable logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: After a mean follow-up of 19.6 years, depressive symptoms were identified among 3,180 participants. Consumption of fruits was inversely associated with the odds of depressive symptoms in a dose-response manner: comparing extreme quartiles, the OR (95% CI) of depressive symptoms was 0.71 (0.63-0.81; P-trend <0.01). Intake of several types of fruits, especially orange, tangerine, banana, papaya and watermelon, was associated with reduced odds, and this inverse association was similar across subgroups of fruits categorized by glycemic index. Conversely, intake of vegetables was not associated with the odds of depressive symptoms. CONCLUSIONS: Our findings support population-based recommendation of having sufficient fruit intake early in life to reduce the likelihood of depressive symptoms in late life.

Linear-space-variant model for Fourier ptychographic microscopy.

Fourier ptychographic microscopy (FPM) needs to realize well-accepted reconstruction by image segmentation and discarding problematic data due to artifacts caused by vignetting. However, the imaging results have long suffered from uneven color blocks and the consequent digital stitching artifacts, failing to bring satisfying experiences to researchers and users over the past decade since the invention of FPM. In fact, the fundamental reason for vignetting artifacts lies in that the acquired data does not match the adopted linear-space-invariant (LSI) forward model, i.e., the actual object function is modulated by a quadratic phase factor during data acquisition, which has been neglected in the advancement of FPM. In this Letter, we rederive a linear-space-variant (LSV) model for FPM and design the corresponding loss function for FPM, termed LSV-FPM. Utilizing LSV-FPM for optimization enables the efficient removal of wrinkle artifacts caused by vignetting in the reconstruction results, without the need of segmenting or discarding images. The effectiveness of LSV-FPM is validated through data acquired in both 4f and finite conjugate single-lens systems.

Association between Dietary Antioxidant Capacity in Midlife and Depressive Symptoms in Late Life: The Singapore Chinese Health Study.

Preclinical and limited epidemiological studies suggest that oxidative stress may be implicated in geriatric depression. Our study investigated the association between midlife dietary total antioxidant capacity (TAC) and depressive symptoms in late life among 13,712 participants in a population-based cohort of Chinese in Singapore. At baseline (1993-1998), intake of antioxidants from diet and supplements at a mean age of 52.4 years was estimated using a validated food frequency questionnaire to derive two dietary TAC indices from vitamins C and E, carotenoids and flavonoids: the Comprehensive Dietary Antioxidant Index (CDAI) and Vitamin C Equivalent Antioxidant Capacity (VCEAC). At follow-up 3 (2014-2016), when participants were at a mean age of 72.5 years, depressive symptoms were assessed using the Geriatric Depression Scale, and depression, defined as having ≥5 symptoms, was presented in 3173 (23.1%) participants. Both CDAI and VCEAC indices were inversely associated with odds of depressive symptoms in a stepwise manner: the OR (95% CI) comparing the extreme quartiles was 0.73 (0.64-0.83; Ptrend < 0.01) for the CDAI and 0.77 (0.68-0.87; Ptrend < 0.01) for the VCEAC. Specifically, higher intakes of vitamin C, carotenoids, and flavonoids were associated with a lower likelihood of depressive symptoms. Our findings support the recommendation of an antioxidant-rich diet for the prevention of depression.

A rare missense PAX6 mutation causes atypical aniridia in a three-generation Chinese family.

AIM: To investigate the molecular diagnosis of a three-generation Chinese family affected with aniridia, and further to identify clinically a PAX6 missense mutation in members with atypical aniridia. METHODS: Eleven family members with and without atypical aniridia were recruited. All family members underwent comprehensive ophthalmic examinations. A combination of whole exome sequencing (WES) and direct Sanger sequencing were performed to uncover the causative mutation. RESULTS: Among the 11 family members, 8 were clinically diagnosed with congenital aniridia (atypical aniridia phenotype). A rare heterozygous mutation c.622C>T (p.Arg208Trp) in exon 8 of PAX6 was identified in all affected family members but not in the unaffected members or in healthy control subjects. CONCLUSION: A rare missense mutation in the PAX6 gene is found in members of a three-generation Chinese family with congenital atypical aniridia. This result contributes to an increase in the phenotypic spectrum caused by PAX6 missense heterozygous variants and provides useful information for the clinical diagnosis of atypical aniridia, which may also contribute to genetic counselling and family planning.