Habitual Iron Supplementation Associated with Elevated Risk of Chronic Kidney Disease in Individuals with Antihypertensive Medication.

The aim of this study was to examine the effects of habitual iron supplementation on the risk of CKD in individuals with different hypertensive statuses and antihypertension treatment statuses. We included a total of 427,939 participants in the UK Biobank study, who were free of CKD and with complete data on blood pressure at baseline. Cox proportional hazards regression models were used to examine the adjusted hazard ratios of habitual iron supplementation for CKD risk. After multivariable adjustment, habitual iron supplementation was found to be associated with a significantly higher risk of incident CKD in hypertensive participants (HR 1.12, 95% CI 1.02 to 1.22), particularly in those using antihypertensive medication (HR 1.21, 95% CI 1.08 to 1.35). In contrast, there was no significant association either in normotensive participants (HR 1.06, 95% CI 0.94 to 1.20) or in hypertensive participants without antihypertensive medication (HR 1.02, 95% CI 0.90 to 1.17). Consistently, significant multiplicative and additive interactions were observed between habitual iron supplementation and antihypertensive medication on the risk of incident CKD (p all interaction < 0.05). In conclusion, habitual iron supplementation was related to a higher risk of incident CKD among hypertensive patients, the association might be driven by the use of antihypertensive medication.

Novel Metabolites Associated With Blood Pressure After Dietary Interventions.

BACKGROUND: The blood pressure (BP) etiologic study is complex due to multifactorial influences, including genetic, environmental, lifestyle, and their intricate interplays. We used a metabolomics approach to capture internal pathways and external exposures and to study BP regulation mechanisms after well-controlled dietary interventions. METHODS: In the ProBP trail (Protein and Blood Pressure), a double-blinded crossover randomized controlled trial, participants underwent dietary interventions of carbohydrate, soy protein, and milk protein, receiving 40 g daily for 8 weeks, with 3-week washout periods. We measured plasma samples collected at baseline and at the end of each dietary intervention. Multivariate linear models were used to evaluate the association between metabolites and systolic/diastolic BP. Nominally significant metabolites were examined for enriching biological pathways. Significant ProBP findings were evaluated for replication among 1311 participants of the BHS (Bogalusa Heart Study), a population-based study conducted in the same area as ProBP. RESULTS: After Bonferroni correction for 77 independent metabolite clusters (α=6.49×10-4), 18 metabolites were significantly associated with BP at baseline or the end of a dietary intervention, of which 11 were replicated in BHS. Seven emerged as novel discoveries, which are as follows: 1-linoleoyl-GPE (18:2), 1-oleoyl-GPE (18:1), 1-stearoyl-2-linoleoyl-GPC (18:0/18:2), 1-palmitoyl-2-oleoyl-GPE (16:0/18:1), maltose, N-stearoyl-sphinganine (d18:0/18:0), and N6-carbamoylthreonyladenosine. Pathway enrichment analyses suggested dietary protein intervention might reduce BP through pathways related to G protein-coupled receptors, incretin function, selenium micronutrient network, and mitochondrial biogenesis. CONCLUSIONS: Seven novel metabolites were identified to be associated with BP at the end of different dietary interventions. The beneficial effects of protein interventions might be mediated through specific metabolic pathways.

Cumulative effect of metabolic risk factors on left ventricular geometry in those with versus without early-onset type 2 diabetes or prediabetes: The Coronary Artery Risk Development in Young Adults (CARDIA) study.

AIM: To investigate metabolic risk factors (RFs) that accumulated over 20 years related to left ventricular mass index (LVMI), relative wall thickness (RWT) and LV remodelling patterns in participants with versus without early-onset type 2 diabetes (T2D) or prediabetes (pre-D). METHODS: A total of 287 early-onset T2D/pre-D individuals versus 565 sociodemographic-matched euglycaemic individuals were selected from the Coronary Artery Risk Development in Young Adults (CARDIA) study, years 0-25. We used the area under the growth curve (AUC) derived from quadratic random-effects models of four or more repeated measures of RFs (fasting glucose [FG], insulin, triglycerides [TG], low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-c), total cholesterol (total-c), blood pressure and body mass index) to estimate the cumulative burden, and their associations with LV outcomes. RESULTS: One standard deviation greater AUC of log (TG) (per 0.48) and HDL-c (per 13.5 mg/dL) were associated with RWT (ß 0.21 and -0.2) in the early-onset T2D/pre-D group, but not in the euglycaemia group (ß 0.01 and 0.05, P interactions .02 and .03). In both the early-onset T2D/pre-D and euglycaemia groups, greater AUCs of log (FG) (per 0.17) and log (insulin) (per 0.43) were associated with higher RWT (ß ranges 0.12-0.24). Greater AUCs of systolic blood pressure (per 10 mmHg) and diastolic blood pressure (per 7.3 mmHg) were associated with higher RWT and LVMI, irrespective of glycaemic status (ß ranges 0.17-0.28). Cumulative TG (odds ratio 3.4, 95% confidence interval: 1.8-6.3), HDL-c (0.23, 0.09-0.59), total-c (1.9, 1.1-3.1) and FG (2.2, 1.25-3.9) were statistically associated with concentric hypertrophy in the T2D/pre-D group only. CONCLUSIONS: Sustained hyperglycaemia and hyperinsulinaemia are associated with RWT, and those individuals with early T2D/pre-D are potentially at greater risk because of their higher levels of glucose and insulin. Dyslipidaemia was associated with LV structural abnormalities in those individuals with early-onset T2D/pre-D.

Construction of Layer-Blocked Covalent Organic Framework Heterogenous Films via Surface-Initiated Polycondensations with Strongly Enhanced Photocatalytic Properties.

Imine-linked covalent organic frameworks (COFs) usually show high crystallinity and porosity, while vinyl-linked COFs have excellent semiconducting properties and stability. Therefore, achieving the advantages of imine- and vinyl-linkages in a single COF material is highly interesting but remains challenging. Herein, we demonstrate the fabrication of a layer-blocked COF (LB-COF) heterogeneous film that is composed of imine- and vinyl-linkages through two successive surface-initiated polycondensations. In brief, the bottom layer of imine-linked COF film was constructed on an amino-functionalized substrate via Schiff-base polycondensation, in which the unreacted aldehyde edges could be utilized for initiating aldol polycondensation to prepare the second layer of vinyl-linked COF film. The resultant LB-COF film displays excellent ordering due to the crystalline templating effect from the bottom imine-linked COF layer; meanwhile, the upper vinyl-linked COF layer could strongly enhance its stability and photocatalytic properties. The LB COF also presents superior performance in photocatalytic uranium extraction (320 mg g-1), which is higher than the imine-linked (35 mg g-1) and the vinyl-linked (295 mg g-1) counterpart. This study provides a novel surface-initiated strategy to synthesize layer-blocked COF heterogeneous films that combine the advantages of each building block.

Construction of Thiadiazole-Bridged sp2-Carbon-Conjugated Covalent Organic Frameworks with Diminished Excitation Binding Energy Toward Superior Photocatalysis.

Sp2-carbon-conjugated covalent organic frameworks (sp2c-COFs) have emerged as promising platforms for phototo-chemical energy conversion due to their tailorable optoelectronic properties, in-plane π-conjugations, and robust structures. However, the development of sp2c-COFs in photocatalysis is still highly hindered by their limited linkage chemistry. Herein, we report a novel thiadiazole-bridged sp2c-COF (sp2c-COF-ST) synthesized by thiadiazole-mediated aldol-type polycondensation. The resultant sp2c-COF-ST demonstrates high chemical stability under strong acids and bases (12 M HCl or 12 M NaOH). The electro-deficient thiadiazole together with fully conjugated and planar skeleton endows sp2c-COF-ST with superior photoelectrochemical performance and charge-carrier separation and migration ability. As a result, when employed as a photocathode, sp2c-COF-ST exhibits a significant photocurrent up to ∼14.5 µA cm-2 at 0.3 V vs reversible hydrogen electrode (RHE) under visible-light irradiation (>420 nm), which is much higher than those analogous COFs with partial imine linkages (mix-COF-SNT ∼ 9.5 µA cm-2) and full imine linkages (imi-COF-SNNT ∼ 4.9 µA cm-2), emphasizing the importance of the structure-property relationships. Further temperature-dependent photoluminescence spectra and density functional theory calculations demonstrate that the sp2c-COF-ST has smaller exciton binding energy as well as effective mass in comparison to mix-COF-SNT and imi-COF-SNNT, which suggests that the sp2c-conjugated skeleton enhances the exciton dissociation and carrier migration under light irradiation. This work highlights the design and preparation of thiadiazole-bridged sp2c-COFs with promising photocatalytic performance.