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.

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.

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.

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.

Association of Ultraprocessed Food Consumption with Risk of Cardiovascular Disease Among Individuals with Type 2 Diabetes: Findings from the UK Biobank.

SCOPE: Among patients with diabetes, who have modified nutritional behavior and a higher risk of cardiovascular disease (CVD), the influence of ultraprocessed foods (UPFs) on CVD remains unknown. The study aims to evaluate the association between UPF intake and the risk of CVD among individuals with type 2 diabetes (T2D) and further examine the potential biological pathways linking the association. METHODS AND RESULTS: This study includes 5405 participants with T2D who provided at least one 24-h dietary recall from the UK Biobank study. In the fully adjusted models, a 10% increase in the proportion of UPFs is associated with higher hazards of overall CVD (hazard ratio [HR]: 1.10; 95% confidence interval [CI]: 1.04, 1.15), coronary heart disease (HR: 1.10; 95% CI: 1.04, 1.16), heart failure (HR: 1.14; 95% CI: 1.05, 1.25), but not stroke (HR: 1.01; 95% CI: 0.90, 1.12). Cystatin C, high-density lipoprotein cholesterol (HDL-C), apolipoprotein A, C-reactive protein, and body mass index collectively explain 26.9% (12.8%, 48.5%) of the association between UPF intake and the risk of overall CVD. CONCLUSION: Higher UPF intakes are associated with increased hazards of CVD among individuals with T2D, and the association is partly mediated through worsening biomarkers of renal function, lipid metabolism, inflammation, and body weight.

Cost-Effectiveness of a Workplace-Based Hypertension Management Program in Real-World Practice in the Kailuan Study.

BACKGROUND: In 2009, a workplace-based hypertension management program was launched among men with hypertension in the Kailuan study. This program involved monitoring blood pressure semimonthly, providing free antihypertensive medications, and offering personalized health consultations. However, the cost-effectiveness of this program remains unclear. METHODS AND RESULTS: This analysis included 12 240 participants, with 6120 in each of the management and control groups. Using a microsimulation model derived from 10-year follow-up data, we estimated costs, quality-adjusted life years (QALYs), life-years, and incremental cost-effectiveness ratios (ICERs) for workplace-based management compared with routine care in both the study period and over a lifetime. Analyses are conducted from the societal perspective. Over the 10-year follow-up, patients in the management group experienced an average gain of 0.06 QALYs with associated incremental costs of $633.17 (4366.85 RMB). Projecting over a lifetime, the management group was estimated to increase by 0.88 QALYs or 0.92 life-years compared with the control group, with an incremental cost of $1638.64 (11 301.37 RMB). This results in an incremental cost-effectiveness ratio of $1855.47 per QALY gained and $1780.27 per life-year gained, respectively, when comparing workplace-based management with routine care. In probabilistic sensitivity analyses, with a threshold willingness-to-pay of $30 765 per QALY (3 times 2019 gross domestic product per capita), the management group showed a 100% likelihood of being cost-effective in 10 000 samples. CONCLUSIONS: Workplace-based management, compared with routine care for Chinese men with hypertension, could be cost-effective both during the study period and over a lifetime, and might be considered in working populations in China and elsewhere.

Associations of serum 25-hydroxyvitamin D and vitamin D receptor polymorphisms with risks of cardiovascular disease and mortality among patients with chronic kidney disease: a prospective study.

BACKGROUND: Evidence regarding the relationships of serum 25-hydroxyvitamin D [25(OH)D] with cardiovascular diseases (CVD) and mortality among patients with chronic kidney disease (CKD) is limited and inconsistent. OBJECTIVES: This study aimed to investigate the associations between serum 25(OH)D and CVD incidence and mortality among patients with CKD. METHODS: This prospective study included 21,507 participants with CKD and free of CVD in the UK Biobank. Incidences of total and subtypes of CVD and mortality were ascertained via electronic health records. Cox proportional hazard regression models were used to estimate the hazard ratios (HRs) and 95% confidential intervals (CIs) for CVD incidence and mortality. RESULTS: The median serum 25(OH)D concentration was 44.0 nmol/L (interquartile range: 30.1, 60.6 nmol/L). After multivariable adjustment, compared with CKD patients with serum 25(OH)D concentrations of <25 nmol/L, those with serum 25(OH)D ≥75 nmol/L had HRs (95% CIs) of 0.80 (0.71, 0.90) for total CVD incidence, 0.82 (0.69, 0.97) for ischemic heart disease, 0.56 (0.41, 0.77) for stroke, 0.64 (0.46, 0.88) for myocardial infarction, 0.62 (0.49, 0.80) for heart failure, 0.60 (0.43, 0.85) for CVD mortality, and 0.62 (0.52, 0.74) for all-cause mortality. In addition, these associations were not modified by vitamin D receptor polymorphisms, with no significant interaction detected. CONCLUSIONS: Higher serum 25(OH)D concentrations were significantly associated with lower risks of total and subtypes of CVD incidence and mortality among individuals with CKD. These findings highlight the importance of maintaining adequate vitamin D status in the prevention of CVD and mortality in patients with CKD.

Association between sex hormones and gout: An analysis of the UK Biobank cohort.

OBJECTIVES: To investigate the associations between sex hormones and gout. METHODS: A total of 448,836 individuals free of gout at baseline were included from the UK Biobank. Cox regression models were used to estimate hazard ratios (HRs) for gout. Besides, we investigated the causal relationship between bioavailable testosterone (BAT) and gout using mendelian randomization (MR). RESULTS: There were differential effects in different testosterone active states in gout. One-unit higher log-transformed total testosterone (TT) was associated with a 52 % [95 % CI, 0.39-0.58] lower risk of gout in males. In contrast, free testosterone (FT) and BAT were associated with a 74 % [95 % CI, 1.38-2.20] and a 78 % [95 % CI, 1.41-2.25] higher risk of gout in males respectively. For MR, the weighted median [OR, 1.70; 95 % CI, 1.14-2.56;] and inverse variance-weighted [OR, 1.25; 95 % CI, 0.96-1.62; P = 0.09] method revealed significant and approximately significant positive effect of genetic liability to BAT levels on the risk of gout respectively. CONCLUSIONS: Sex hormones were potentially associated with gout. Notably, we were the first to explore different testosterone states on gout and found that FT and BAT may increase the risk of gout in males, which is opposite to TT. And the former are active states of androgens, may be more accurately reflect the association between androgens and gout.

Association between nighttime sleep duration, midday napping, and sleep quality during early pregnancy and risk of gestational diabetes mellitus: A prospective cohort study in China.

AIM: To evaluate the prospective associations of nighttime sleep duration, midday napping, and sleep quality during early pregnancy with gestational diabetes mellitus (GDM) risk among Chinese pregnant women. METHODS: Sleep-related information was assessed by the Pittsburgh Sleep Quality Index in baseline surveys during the 6-15 (mean 10.3) gestational weeks. GDM was diagnosed during 24-28 gestational weeks according to the Chinese Guidelines on Diagnosis and Management of Hyperglycemia in Pregnancy (2022). Multivariable logistic regression models with adjustments for socio-demographic and lifestyle factors were used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for the associations of sleep traits with GDM risk. RESULTS: We identified 503 incident GDM cases among 6993 participants. Compared with women who slept for 7-9 hours/night in early pregnancy, those who slept <7 hours/night showed a higher risk of GDM (OR, 1.75; 95 % CI: 1.20-2.54), whereas those who slept >9 hours/night showed no significant association for GDM risk (OR, 1.01; 95 % CI: 0.78-1.30). Compared with women with absolutely no napping, those with ≤60 and > 60 min/day midday napping showed no significant association for GDM risk (OR, 0.82; 95 % CI: 0.64-1.05 for ≤60 min/day midday napping; OR, 0.87; 95 % CI: 0.66-1.15 for >60 min/day midday napping). Poor sleep quality was not associated with GDM risk compared with good quality (OR, 0.90; 95 % CI: 0.72-1.12). CONCLUSION: A short nighttime sleep duration during early pregnancy was associated with a higher risk of GDM, which was independent of midday napping, sleep quality and lifestyle factors.

Associations Between Beverage Consumption and Risk of Microvascular Complications Among Individuals With Type 2 Diabetes.

CONTEXT: The relationship between the consumption of different beverages and the risk of microvascular complications in individuals with type 2 diabetes (T2D) is unclear. OBJECTIVE: To investigate the association of individual beverage consumption, including artificially sweetened beverages (ASBs), sugar-sweetened beverages (SSBs), tea, coffee, natural juice, and yogurt, with the risk of microvascular complications in adults with T2D. METHODS: This cohort study included 6676 participants with T2D who were free of macrovascular and microvascular complications at baseline in the UK Biobank. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a median follow-up of 11.7 years, 1116 cases of composite microvascular complications were documented. After multivariable adjustment, a linear dose-response relationship was demonstrated between the consumption of ASBs and SSBs and the risk of microvascular complications. Compared with nonconsumers, those who consumed ≥2.0 units/day of ASBs and SSBs had an HR (95% CI) of 1.44 (1.18-1.75) and 1.32 (1.00-1.76) for composite microvascular complications, respectively. In addition, higher tea consumption was associated with a lower risk of diabetic retinopathy, with an HR (95% CI) of 0.72 (0.57-0.92) for whom consuming ≥4.0 units/day. There was no significant association between individual beverage consumption and the risk of diabetic neuropathy. No significant association was observed between the consumption of coffee, natural juice, or yogurt and the risks of microvascular complications. Moreover, substituting half units/day of ASBs or SSBs with tea or coffee was associated with a 16% to 28% lower risk of microvascular complications. CONCLUSION: Higher consumption of ASBs and SSBs was linearly associated with an increased risk of microvascular complications in adults with T2D.

Associations of Lower-Carbohydrate and Lower-Fat Diets with Mortality among People with Cardiovascular Disease.

BACKGROUND: Although low-carbohydrate and low-fat diets have been shown to have short-term metabolic benefits, the associations of these dietary patterns, particularly different food sources and macronutrient quality, with mortality in people with cardiovascular disease (CVD) remain unclear. OBJECTIVES: To examine the associations of different types of lower-carbohydrate diets (LCDs) and lower-fat diets (LFDs) with mortality in individuals with CVD. METHODS: This study included 3971 adults with CVD from the NHANES 1999-2014. Mortality status was linked to National Death Index mortality data through 31 December 2019. Overall, unhealthy and healthy LCD and LFD scores were determined based on the percentages of energy from total and subtypes of carbohydrate, fat, and protein. Cox proportional hazards regression models were applied to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Higher healthy LCD score was associated with favorable blood lipids and higher homeostasis model assessment of insulin resistance, whereas higher unhealthy LFD score was associated with lower high-density lipoprotein and higher C-reactive protein at baseline (all P-trend < 0.05). During 35,150 person-years of follow-up, 2163 deaths occurred. For per 20-percentile increment in dietary scores, the multivariate-adjusted HRs of all-cause mortality were 0.91 (95% CI: 0.86, 0.96) for healthy LCD score (P < 0.001), 0.94 (95% CI: 0.89, 1.00) for healthy LFD score (P = 0.04), and 1.07 (95% CI: 1.00, 1.14) for unhealthy LFD score (P = 0.04). CONCLUSIONS: Overall LCD and LFD scores are not associated with total mortality. Unhealthy LFD scores are associated with higher total mortality, whereas healthy LCD and LFD scores are associated with lower mortality in people with CVD.

Circulating concentrations of bile acids and prevalent chronic kidney disease among newly diagnosed type 2 diabetes: a cross-sectional study.

BACKGROUND: The relationship between circulating bile acids (BAs) and kidney function among patients with type 2 diabetes is unclear. We aimed to investigate the associations of circulating concentrations of BAs, particularly individual BA subtypes, with chronic kidney disease (CKD) in patients of newly diagnosed type 2 diabetes. METHODS: In this cross-sectional study, we included 1234 newly diagnosed type 2 diabetes who participated in an ongoing prospective study, the Dongfeng-Tongji cohort. Circulating primary and secondary unconjugated BAs and their taurine- or glycine-conjugates were measured using ultraperformance liquid chromatography-tandem mass spectrometry. CKD was defined as eGFR < 60 ml/min per 1.73 m2. Logistic regression model was used to compute odds ratio (OR) and 95% confidence interval (CI). RESULTS: After adjusting for multiple testing, higher levels of total primary BAs (OR per standard deviation [SD] increment: 0.78; 95% CI: 0.65-0.92), cholate (OR per SD: 0.78; 95% CI: 0.66-0.92), chenodeoxycholate (OR per SD: 0.81; 95% CI: 0.69-0.96), glycocholate (OR per SD: 0.81; 95% CI: 0.68-0.96), and glycochenodeoxycholate (OR per SD: 0.82; 95% CI: 0.69-0.97) were associated with a lower likelihood of having CKD in patients with newly diagnosed type 2 diabetes. No significant relationships between secondary BAs and odds of CKD were observed. CONCLUSIONS: Our findings showed that higher concentrations of circulating unconjugated primary BAs and their glycine-conjugates, but not taurine-conjugates or secondary BAs, were associated with lower odds of having CKD in patients with type 2 diabetes.

Associations of Regional Body Fat with Risk of Cardiovascular Disease and Mortality among Individuals with Type 2 Diabetes.

OBJECTIVES: We aimed to prospectively examine the association between regional body fat and risk of cardiovascular disease (CVD) in individuals with type 2 diabetes (T2D), who often exhibit changes in relative fat distribution and have increased CVD risk. METHODS: The main analysis included 21,472 participants with T2D from the UK Biobank. Regional body fat was measured by bioelectric impedance assessment. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Over a median of 7.7 years of follow-up, 3,976 CVD events occurred. After multivariable adjustment, upper and lower body fat were independently and oppositely associated with CVD risk among patients with T2D. Higher arm fat percentage was linearly associated with increased CVD risk (P nonlinear >0.05), while higher trunk fat percentage was nonlinearly associated with increased CVD risk (P nonlinear <0.05). In contrast, higher leg fat percentage was nonlinearly associated with lower CVD risk (P nonlinear <0.05). When comparing extreme quartiles, the multivariable-adjusted HR (95% CI) of CVD was 0.72 (0.58, 0.90) for leg fat percentage, 1.63 (1.29, 2.05) for arm fat percentage, and 1.27 (1.06, 1.52) for trunk fat percentage. Similar patterns of associations were observed for all-cause and CVD mortality. In addition, leg fat percentage, but not other regional fat percentage, was associated with CVD risk independently of traditional measures of obesity. CONCLUSIONS: Among people with T2D, arm fat and trunk fat were positively, whereas leg fat was inversely, associated with the risk of CVD and mortality. These findings highlight the importance of considering both the amount and the location of body fat when assessing CVD and mortality risk among individuals with T2D.

Computational Imaging: The Next Revolution for Biophotonics and Biomedicine.

This Editorial is the preface for the topical collection of "Computational Imaging for Biophotonics and Biomedicine", which collates the 12 contributions listed in Table 1 [...].

Nonlinear relationship between high-density lipoprotein cholesterol and cardiovascular disease: an observational and Mendelian randomization analysis.

BACKGROUND: Clinical trials and Mendelian randomization (MR) studies reported null effects of high-density lipoprotein cholesterol (HDL-C) on risk of cardiovascular disease (CVD), which might have overlooked a nonlinear causal association. We aimed to investigate the dose-response relationship between circulating HDL-C concentrations and CVD in observational and MR frameworks. METHODS: We included 348,636 participants (52,919 CVD cases and 295,717 non-cases) of European ancestry with genetic data from the UK Biobank (UKB) and acquired genome-wide association summary data for HDL-C of Europeans from the Global Lipids Genetics Consortium (GLGC). Observational analyses were conducted in the UKB. Stratified MR analyses were conducted combing genetic data for CVD from UKB and lipids from GLGC. RESULTS: Observational analyses showed L-shaped associations of HDL-C with CVD, with no further risk reduction when HDL-C levels exceeded 70 mg/dL. Multivariable MR analyses across entire distribution of HDL-C found no association of HDL-C with CVD, after control of the pleiotropic effect on other lipids and unmeasured pleiotropism. However, in stratified MR analyses, significant inverse associations of HDL-C with CVD were observed in the stratum of participants with HDL-C ≤ 50 mg/dL (odds ratio per unit increase, 0.86; 95 % confidence interval, 0.79-0.94), while null associations were observed in any stratum above 50 mg/dL. CONCLUSIONS: Our data suggest a potentially causal inverse association of HDL-C at low levels with CVD risks. These findings advance our knowledge about the role of HDL as a potential target in CVD prevention and therapy.

Association of urinary and seminal plasma vanadium concentrations with semen quality: A repeated-measures study of 1135 healthy men.

Although animal studies have shown the reproductive toxicity of vanadium, less is known about its effects on semen quality in humans. Among 1135 healthy men who were screened as potential semen donors, we investigated the relationships of semen quality with urinary and seminal plasma vanadium levels via inductively coupled plasma-mass spectrometry (ICP-MS). Spearman rank correlation tests and linear regression models were used to assess the correlations between average urinary and within-individual pooled seminal plasma vanadium concentrations (n = 1135). We utilized linear mixed-effects models to evaluate the associations of urinary and seminal plasma vanadium levels (n = 1135) with repeated sperm quality parameters (n = 5576). Seminal plasma vanadium concentrations were not significantly correlated with urinary vanadium concentrations (r = 0.03). After adjusting for possible confounders, we observed inverse relationships of within-individual pooled seminal plasma vanadium levels with total count, semen volume, and sperm concentration (all P values for trend < 0.05). Specifically, subjects in the highest (vs. lowest) tertile of seminal plasma vanadium concentrations had - 11.3% (-16.4%, -5.9%), - 11.1% (-19.1%, -2.4%), and - 20.9% (-29.0%, -11.8%) lower sperm volume, concentration, and total count, respectively; moreover, urinary vanadium levels appeared to be negatively associated with sperm motility. These relationships showed monotonically decreasing dose-response patterns in the restricted cubic spline analyses. Our results demonstrated a poor correlation between urinary and seminal plasma levels of vanadium, and elevated vanadium concentrations in urine and seminal plasma may be adversely related to male semen quality.

Fourier Ptychographic Microscopy 10 Years on: A Review.

Fourier ptychographic microscopy (FPM) emerged as a prominent imaging technique in 2013, attracting significant interest due to its remarkable features such as precise phase retrieval, expansive field of view (FOV), and superior resolution. Over the past decade, FPM has become an essential tool in microscopy, with applications in metrology, scientific research, biomedicine, and inspection. This achievement arises from its ability to effectively address the persistent challenge of achieving a trade-off between FOV and resolution in imaging systems. It has a wide range of applications, including label-free imaging, drug screening, and digital pathology. In this comprehensive review, we present a concise overview of the fundamental principles of FPM and compare it with similar imaging techniques. In addition, we present a study on achieving colorization of restored photographs and enhancing the speed of FPM. Subsequently, we showcase several FPM applications utilizing the previously described technologies, with a specific focus on digital pathology, drug screening, and three-dimensional imaging. We thoroughly examine the benefits and challenges associated with integrating deep learning and FPM. To summarize, we express our own viewpoints on the technological progress of FPM and explore prospective avenues for its future developments.

Gut microbiota-derived secondary bile acids, bile acids receptor polymorphisms, and risk of cardiovascular disease in individuals with newly diagnosed type 2 diabetes: a cohort study.

BACKGROUND: Secondary bile acids (SBAs), the products of bacterial metabolism, are ligands of the nuclear farnesoid X receptor (FXR) and have been implicated in cardiovascular health. Diet can modulate gut microbiota composition and bile acid metabolism. OBJECTIVES: We aimed to examine the associations of circulating SBAs and their receptor polymorphisms with the risk of incident cardiovascular disease (CVD) among people with type 2 diabetes (T2D). METHODS: A total of 1234 participants with newly diagnosed T2D without CVD or cancer were included from the Dongfeng-Tongji Cohort study in China. Circulating SBAs and their conjugated forms were quantified using liquid chromatography-tandem mass spectrometry. Fifteen single-nucleotide polymorphisms in genes encoding bile acid receptors were genotyped. RESULTS: During a median follow-up of 5.7 y, 259 incident CVD cases were documented. After multivariable adjustment, higher levels of unconjugated SBAs [sum of deoxycholic acid (DCA), lithocholic acid, and ursodeoxycholic acid] and DCA were significantly associated with a higher risk of CVD among people with T2D, with hazard ratios (HRs) and 95% confidence intervals (CIs) of 1.62 (1.12, 2.35) and 1.46 (1.04, 2.06) comparing the extreme quartile of SBAs and DCA, respectively. Restricted cubic spline regression suggested a linear relationship of unconjugated SBAs and DCA with an elevated risk of CVD, and per standard deviation, an increment in natural log-transformed unconjugated SBAs and DCA was associated with an 18% (95% CI: 4%, 34%) and 16% (95% CI: 2%, 33%) higher risk of CVD, respectively. Moreover, genetic variants in FXR (rs56163822 TT compared with GG, and rs17030295 TT compared with CC) were significantly associated with a 121%-129% higher risk of CVD among individuals with T2D. CONCLUSIONS: A higher proportion of unconjugated SBAs, especially DCA, is linearly associated with a higher risk of CVD among people with newly diagnosed T2D. Our findings support the potential role of gut microbiota-derived SBAs in cardiovascular health in individuals with T2D.

Beverage Consumption, Genetic Predisposition, and Risk of Cardiovascular Disease among Adults with Type 2 Diabetes.

BACKGROUND: The evidence regarding the relationship between different types of beverages and cardiovascular health in individuals with type 2 diabetes (T2D) is scarce. AIMS: To prospectively examine the associations between individual beverage consumption, genetic predisposition, and risk of incident cardiovascular disease (CVD) among adults with T2D. METHODS: We analyzed the associations of individual beverage intake with risks of CVD and ischemic heart disease (IHD) in 7315 participants with T2D, overall or stratified by genetic risk to CVD, using data from the UK Biobank study. RESULTS: During a median follow-up of 6.1 years, 878 incident CVD cases were identified, including 517 IHD cases. Higher intakes of sugar-sweetened beverages (SSBs), artificially-sweetened beverages (ASBs), and natural juices were each linearly associated with a higher CVD (Pnonlinearity > 0.05). Comparing the highest to lowest groups of beverage consumption, the multivariable-adjusted HRs (95% CIs) of CVD were 1.54 (1.14, 2.07) for SSBs, 1.34 (1.07, 1.69) for ASBs, and 1.33 (1.01, 1.76) for natural juices. Similar results were observed for incident IHD. Moreover, no significant interactions between these beverages and the CVD genetic risk score were observed. Replacing half-unit/day of SSBs or natural juices with coffee, tea, or yogurt, but not ASBs, was associated with a 20%-46% lower risk of CVD and IHD. INTERPRETATION: Higher intakes of SSBs, ASBs, and natural juices were each linearly associated with an increased risk of CVD among individuals with T2D, regardless of genetic predisposition. Our findings highlight the importance of selecting healthy beverage options to improve cardiovascular health in patients with T2D.