Comprehensive Multiple Risk Factor Control in Type 2 Diabetes to Mitigate Heart Failure Risk: Insights From a Prospective Cohort Study.

OBJECTIVE: The impact of comprehensive risk factor control on heart failure (HF) risk and HF-free survival time in individuals with type 2 diabetes (T2D) was evaluated in this study. RESEARCH DESIGN AND METHODS: This prospective study included 11,949 individuals diagnosed with T2D, matched with 47,796 non-T2D control study participants from the UK Biobank cohort. The degree of comprehensive risk factor control was assessed on the basis of the major cardiovascular risk factors, including blood pressure, BMI, LDL cholesterol, hemoglobin A1c, renal function, smoking, diet, and physical activity. Cox proportional hazards models were used to measure the associations between the degree of risk factor control and HF risk. Irwin's restricted mean was used to evaluate HF-free survival time. RESULTS: During a median follow-up of 12.3 years, 702 individuals (5.87%) with T2D and 1,402 matched control participants (2.93%) developed HF. Each additional risk factor controlled was associated with an average 19% lower risk of HF. Optimal control of at least six risk factors was associated with a 67% lower HF risk (hazard ratio [HR] 0.33; 95% CI 0.20, 0.54). BMI was the primary attributable risk factor for HF. Notably, the excess risk of HF associated with T2D could be attenuated to levels comparable to those of non-T2D control participants when individuals had a high degree of risk factor control (HR 0.66; 95% CI 0.40, 1.07), and they exhibited a longer HF-free survival time. CONCLUSIONS: Comprehensive management of risk factors is inversely associated with HF risk, and optimal risk factor control may prolong HF-free survival time among individuals with T2D.

Predictive value of NT pro BNP for new-onset atrial fibrillation in heart failure and preserved ejection fraction.

AIMS: The prognostic significance of N-terminal pro B-type natriuretic peptide (NT-proBNP) in heart failure with preserved ejection fraction (HFpEF) has been well established. HFpEF and atrial fibrillation (AF) commonly coexist, and each contributes to poor outcomes independently. Nevertheless, the ability of NT-proBNP to predict AF in HFpEF patients remains uncertain. METHODS AND RESULTS: A total of 367 HFpEF patients without baseline AF from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial were included. The Cox proportional hazard model was used to assess the association of NT-proBNP with the risk of AF. The C-statistic, categorical net reclassification index (NRI), and integrated discrimination improvement (IDI) were used to evaluate the ability of NT-proBNP in new-onset AF prediction. During a median follow-up of 2.91 years, 17 (4.63%) new-onset AF cases occurred. Every 1000 pg/mL increase in NT-proBNP was associated with a 16% increase in the risk of AF occurrence after adjustments (hazard ratio, 1.16 [95% CI, 1.02-1.32]). NT-proBNP showed a moderate performance for new-onset AF at 3 years (C-statistic, 0.67). Adding NT-proBNP to CHADS2/R2CHADS2/CHA2DS2-VASc/C2HSET scores improved their predictive performance for AF risk (CHADS2: C-statistic, 0.63, CHADS2+NT: C-statistic, 0.69, NRI, 47.46%, IDI, 1.18%; R2CHADS2: C-statistic, 0.65, R2CHADS2+NT: C-statistic, 0.70, NRI, 48.03%, IDI, 0.51%; CHA2DS2-VASc: C-statistic, 0.67, CHA2DS2-VASc+NT: C-statistic, 0.72, NRI, 49.41%, IDI, 0.86%; C2HSET: C-statistic, 0.77, C2HSET+NT: C-statistic, 0.80, NRI, 50.32%, IDI, 1.58%). CONCLUSIONS: Among patients with HFpEF, the NT-proBNP level was positively associated with the incidence of new-onset AF and may be a promising predictor.

FTMT-dependent mitophagy is crucial for ferroptosis resistance in cardiac fibroblast.

Metabolic responses to cellular stress are pivotal in cell ferroptosis, with mitophagy serving as a crucial mechanism in both metabolic processes and ferroptosis. This study aims to elucidate the effects of high glucose on cardiomyocytes (CMs) and cardiac fibroblasts (CFs) regarding ferroptosis and to uncover the underlying mechanisms involved. We examined alterations in glycolysis, mitochondrial oxidative phosphorylation (OXPHOS), and mitophagy, which are essential for metabolic adaptations and ferroptosis. High glucose exposure induced ferroptosis specifically in CMs, while CFs exhibited resistance to ferroptosis, increased glycolytic activity, and no change in OXPHOS. Moreover, high glucose treatment enhanced mitophagy and upregulated mitochondrial ferritin (FTMT). Notably, the combination of FTMT and the autophagy-related protein nuclear receptor coactivator 4 (NCOA4) increased under high glucose conditions. Silencing FTMT significantly impeded mitophagy and eliminated ferroptosis resistance in CFs cultured under high glucose conditions. The transcription factor forkhead box A1 (FOXA1) was upregulated in CFs upon high glucose exposure, playing a crucial role in the increased expression of FTMT. Within the 5'-flanking sequence of the FTMT mRNA, approximately -500 nt from the transcription initiation site, three putative FOXA1 binding sites were identified. High glucose augmented the binding affinity between FOXA1 and these sequences, thereby promoting FTMT transcription. In summary, high glucose upregulated FOXA1 expression and stimulated FTMT promoter activity in CFs, thereby promoting FTMT-dependent mitophagy and conferring ferroptosis resistance in CFs.

Life's Essential 8, Genetic Susceptibility, and Incident Cardiac Arrhythmias: A Population-Based Prospective Cohort Study.

BACKGROUND: Ideal cardiovascular health (CVH) has been associated with reduced cardiovascular disease risk and mortality, but its association with cardiac arrhythmias was still unsettled. In this prospective cohort study, we investigated the relationship between CVH and subsequent arrhythmias risk, including atrial fibrillation (AF)/flutter, ventricular arrhythmias, and bradyarrhythmias. METHODS: Data from 287,264 participants initially free of arrhythmias in the UK Biobank were included in the analysis. Cox regression models were used to examine the relationship between CVH levels calculated by the American Heart Association's Life's Essential 8 (LE8) metrics, with cardiac arrhythmias risk. RESULTS: During a median follow-up period of 12.8 years, 16,802 incident AF, 2186 incident ventricular arrhythmias, and 4128 incident bradyarrhythmias were identified. After adjustment for confounding factors, participants with high initial CVH levels had significantly lower risks for AF (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.59-0.68), ventricular arrhythmias (HR, 0.48; 95% CI, 0.40-0.59), and bradyarrhythmias (HR, 0.64; 95% CI, 0.55-0.74) compared with those with low CVH levels. Furthermore, each standard deviation (SD) increase in LE8 scores was associated with a 15% lower risk of AF, 21% for ventricular arrhythmias, and 13% for bradyarrhythmias, respectively. In addition, a significant interaction was observed between CVH levels and the genetic risk of AF (P for interaction, 0.021). The reverse correlation seemed to be more noticeable in individuals with a lower genetic susceptibility to AF. CONCLUSIONS: We concluded that higher levels of CVH, estimated by the LE8 metrics, were associated with significantly reduced risks of AF, ventricular arrhythmias, and bradyarrhythmias.

Sirt5 improves cardiomyocytes fatty acid metabolism and ameliorates cardiac lipotoxicity in diabetic cardiomyopathy via CPT2 de-succinylation.

RATIONALE: The disruption of the balance between fatty acid (FA) uptake and oxidation (FAO) leads to cardiac lipotoxicity, serving as the driving force behind diabetic cardiomyopathy (DbCM). Sirtuin 5 (Sirt5), a lysine de-succinylase, could impact diverse metabolic pathways, including FA metabolism. Nevertheless, the precise roles of Sirt5 in cardiac lipotoxicity and DbCM remain unknown. OBJECTIVE: This study aims to elucidate the role and underlying mechanism of Sirt5 in the context of cardiac lipotoxicity and DbCM. METHODS AND RESULTS: The expression of myocardial Sirt5 was found to be modestly elevated in diabetic heart failure patients and mice. Cardiac dysfunction, hypertrophy and lipotoxicity were exacerbated by ablation of Sirt5 but improved by forced expression of Sirt5 in diabetic mice. Notably, Sirt5 deficiency impaired FAO without affecting the capacity of FA uptake in the diabetic heart, leading to accumulation of FA intermediate metabolites, which mainly included medium- and long-chain fatty acyl-carnitines. Mechanistically, succinylomics analyses identified carnitine palmitoyltransferase 2 (CPT2), a crucial enzyme involved in the reconversion of fatty acyl-carnitines to fatty acyl-CoA and facilitating FAO, as the functional succinylated substrate mediator of Sirt5. Succinylation of Lys424 in CPT2 was significantly increased by Sirt5 deficiency, leading to the inactivation of its enzymatic activity and the subsequent accumulation of fatty acyl-carnitines. CPT2 K424R mutation, which mitigated succinylation modification, counteracted the reduction of enzymatic activity in CPT2 mediated by Sirt5 deficiency, thereby attenuating Sirt5 knockout-induced FAO impairment and lipid deposition. CONCLUSIONS: Sirt5 deficiency impairs FAO, leading to cardiac lipotoxicity in the diabetic heart through the succinylation of Lys424 in CPT2. This underscores the potential roles of Sirt5 and CPT2 as therapeutic targets for addressing DbCM.

Low remnant cholesterol and the subsequent risk of new-onset atrial fibrillation: A prospective cohort study.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia with high morbidity and mortality implications. Several studies have described a paradoxical inverse relationship between serum cholesterol and the risk of AF, but it remains unknown whether remnant cholesterol (RC) is associated with AF incidence. OBJECTIVE: This study aims to prospectively investigate the association between RC and AF. METHODS: A total of 392,783 participants free of AF at baseline from the UK Biobank were included for the analysis. Cox proportional hazards model, subgroup analysis, and sensitivity analyses were used to evaluate the independent association between RC levels and the risk of new-onset AF. Furthermore, we performed a discordance analysis by using the median cutoff points of low-density lipoprotein cholesterol (LDL-C) and RC. RESULTS: After a median follow-up of 12.8 years (interquartile range 12.0-13.6 years), a total of 23,558 participants experienced incident AF. Compared with the highest RC level, the lower RC level was associated with an increased risk of AF incidence (quartile 1 vs quartile 4: hazard ratio 1.396; 95% confidence interval [CI] 1.343-1.452). The results remained robust across a series of sensitivity analyses. In the discordance analyses, a significantly higher risk of AF was observed in participants with discordant low RC/high LDL-C levels than in those with concordant high RC/LDL-C levels. In the low LDL-C group, RC reduction even contributed to an additional 15.8% increased rate of incident AF (low RC/low LDL-C: hazard ratio 1.303; 95% CI 1.260-1.348 vs high RC/low LDL-C: hazard ratio 1.125; 95% CI 1.079-1.172). CONCLUSION: Low RC levels were associated with an increased risk of incident AF independent of traditional cardiovascular risk factors.

SIRT3 suppression resulting from the enhanced ß-catenin signaling drives glycolysis and promotes hypoxia-induced cell growth in hepatocellular carcinoma cells.

The precise mechanisms underlying the inhibitory effects of SIRT3, a mitochondrial sirtuin protein, on hepatocellular carcinoma (HCC) development, as well as its impact on mitochondrial respiration, remain poorly understood. We assessed sirtuins 3 (SIRT3) levels in HCC tissues and Huh7 cells cultured under hypoxic condition. We investigated the effects of SIRT3 on cell proliferation, glycolytic metabolism, mitochondrial respiration, mitophagy, and mitochondrial biogenesis in Huh7 cells. Besides, we explored the potential mechanisms regulating SIRT3 expression in hypoxically cultured Huh7 cells. Gradual reduction in SIRT3 expressions were observed in both adjacent tumor tissues and tumor tissues. Similarly, SIRT3 expressions were diminished in Huh7 cells cultured under hypoxic condition. Forced expression of SIRT3 attenuated the growth of hypoxically cultured Huh7 cells. SIRT3 overexpression led to a decrease in extracellular acidification rate while increasing oxygen consumption rate. SIRT3 downregulated the levels of hexokinase 2 and pyruvate kinase M2. Moreover, SIRT3 enhanced mitophagy signaling, as indicated by mtKeima, and upregulated key proteins involved in various mitophagic pathways while reducing intracellular reactive oxygen species levels. Furthermore, SIRT3 increased proxisome proliferator-activated receptor-gamma coactivator 1α levels and the amount of mitochondrial DNA in Huh7 cells. Notably, ß-catenin expressions were elevated in Huh7 cells cultured under hypoxic condition. Antagonists and agonists of ß-catenin respectively upregulated and downregulated SIRT3 expressions in hypoxically cultured Huh7 cells. The modulationsof glycolysis and mitochondrial respiration represent the primary mechanism through which SIRT3, suppressed by ß-catenin, inhibits HCC cell proliferation.

Sleep Patterns and Traditional Cardiovascular Health Metrics: Joint Impact on Major Adverse Cardiovascular Events in a Prospective Cohort Study.

BACKGROUND: This study examines the association between traditional cardiovascular health (CVH) metrics and major adverse cardiovascular events (MACE) incidence in individuals with diverse sleep patterns. METHODS AND RESULTS: We analyzed data from 208 621 participants initially free of cardiovascular disease (CVD) in the UK Biobank study. Sleep patterns were assessed using scores for chronotype, duration, insomnia, snoring, and daytime dozing. Traditional CVH scores were derived from the Life's Simple 7 metrics. Cox proportional hazards multivariate regression assessed associations between distinct combinations of CVH and sleep scores and MACE, including nonfatal myocardial infarction, nonfatal stroke, and CVD mortality. Over a mean follow-up of 12.73 years, 9253 participants experienced incident MACE. Individuals with both a healthy sleep pattern and ideal CVH levels had the lowest MACE risk compared with those with a poor sleep pattern and poor CVH levels (hazard ratio, 0.306 [95% CI, 0.257-0.365]; P<0.001). Elevated CVH scores were associated with a reduced risk of MACE across different sleep patterns. Similar trends were observed for individual MACE components, heart failure, and all-cause mortality. These findings remained robust in sensitivity analyses and across various subgroups. CONCLUSIONS: In individuals without known CVD, maintaining a favorable sleep pattern and achieving optimal CVH levels, as measured by traditional metrics, were associated with the lowest MACE risk. Enhanced CVH significantly reduced CVD risk, even in individuals with a poor sleep pattern. These results emphasize the importance of considering multiple dimensions of sleep health alongside CVH to mitigate CVD risk. REGISTRATION: URL: https://www.ukbiobank.ac.uk; Unique identifier: 91090.

Dietary vitamin C and vitamin E with the risk of aortic aneurysm and dissection: A prospective population-based cohort study.

BACKGROUND AND AIMS: The associations between dietary vitamin C (VC), vitamin E (VE) intake and aortic aneurysm and dissection (AAD) remain unclear. This study aimed to prospectively investigate the associations between dietary VC and VE with the incident risk of AAD. METHODS AND RESULTS: A total of 139 477 participants of UK Biobank cohort were included in the analysis. Dietary VC and VE consumptions were acquired through a 24-h recall questionnaire. Cox proportional regression models were used to examine the associations between VC, VE intake and the risk of AAD. Incident AAD was ascertained through hospital inpatient records and death registers. During a median follow-up of 12.5 years, 962 incident AAD events were documented. Both dietary VC [adjusted hazard ratio (HR), 0.77; 95 % confidence intervals (CI), 0.63-0.93; P-trend = 0.008] and VE (adjusted HR, 0.70; 95 % CI, 0.57-0.87; P-trend = 0.002) were inversely associated with incident AAD when comparing the participants in the highest quartile with those in the lowest. In subgroup analyses, the associations were more pronounced in participants who were over 60 years old, participants with smoking history, hypertension or hyperlipidemia, who were under the high risk of AAD. CONCLUSION: Higher dietary VC and VE intakes are associated with reduced risk of AAD. Our study emphasizes the importance of diet adjustment strategies targeted on VC and VE to lower the incidence rate of AAD especially in the high-risk population.

Erratum to: Bioinformatic analysis for potential biological processes and key targets of heart failure-related stroke.

The original version of this article (Liu et al., 2021) unfortunately contained a mistake: statement of equal contribution is missing. This correction article shows that Chiyu LIU and Sixu CHEN contributed equally to this work. The original article has been corrected.

The Effect of Multi-Fields Synergy from Electric/Light/Thermal/Force Technologies on Photovoltaic Performance of Ba0.06 Bi0.47 Na0.47 TiO3 Ferroelectric Ceramics via the Mg/Co Substitution at A/B Sites.

Currently, it is widely reported that the photovoltaic effect in ferroelectric materials can be promoted by the application of a piezoelectric force, an external electric field, and intense light illumination. Here, a semiconducting ferroelectric composition is introduced, (1-x) Ba0.06 Bi0.47 Na0.47 TiO3 -xMgCoO3 (abbreviated as xMgCo, where x = 0.02-0.08), synthesized through Mg/Co ions codoping. This process effectively narrows the optical bandgaps to a spectrum of 1.38-3.06 eV. Notably, the system exhibits a substantial increase in short-circuit photocurrent density (Jsc ), by the synergy of the electric, light, and thermal fields. The Jsc can still be further enhanced by the extra introduction of a force field. Additionally, the Jsc also shows an obvious increase after the high field pre-poling. The generation of a considerable number of oxygen vacancies due to the Co2+ /Co3+ mixed valence state (in a 1:3 ratio) contributes to the reduced optimal bandgap. The integration of Mg2+ ion at the A-site restrains the loss and sustains robust ferroelectricity (Pr  = 24.1 µC cm-2 ), high polarizability under an electric field, and a significant piezoelectric coefficient (d33  = 102 pC N-1 ). This study provides a novel perspective on the physical phenomena arising from the synergy of multiple fields in ferroelectric photovoltaic materials.

The association between tinnitus and risk of cardiovascular events and all-cause mortality: insight from the UK Biobank.

BACKGROUND: The potential influence of tinnitus on cardiovascular disease (CVD) and all-cause mortality has yet to be explored. We aim to examine the correlations between tinnitus and the risk of cardiovascular events and all-cause mortality. METHODS: We conducted a prospective cohort study utilising data from the UK Biobank. The presence of tinnitus was evaluated through a questionnaire. The primary outcome was defined as a composition of cardiovascular events, including myocardial infarction (MI), stroke, and mortality from CVD, as well as all-cause mortality. Cox proportional hazard models were employed to examine the associations between tinnitus and both the primary outcome and its individual components. Sensitivity analyses were conducted to evaluate the robustness of the primary analysis. RESULTS: A total of 140,146 participants were included in the study. The presence of tinnitus was found to be associated with a higher incident rate of the primary outcome (HR = 1.057, 95%CI: 1.017-1.099, p = 0.005), MI (HR = 1.139, 95%CI: 1.061-1.222, p < 0.001) and all-cause mortality (HR = 1.053, 95%CI: 1.003-1.105, p = 0.038) after adjusting for confounders. However, there was no significant association between tinnitus and stroke or mortality from CVD. Subgroup analysis revealed that the association between tinnitus and the primary outcome was significant in females, participants with abnormal BMI, and those without hearing difficulty, depression or anxiety. Sensitivity analyses yielded consistent results. CONCLUSION: The findings from this study contribute to the existing body of evidence suggesting an association between tinnitus and an increased risk of cardiovascular events and all-cause mortality.

Association between daytime napping and incident arrhythmias: A prospective cohort study and mendelian randomization analysis.

BACKGROUND: Emerging evidence has linked daytime napping with the risk of cardiovascular events. Cardiac arrhythmias are considered an early clinical stage for cardiovascular diseases. However, whether napping frequency is associated with incident arrhythmias remains unknown. OBJECTIVE: This study aimed to prospectively investigate the association between napping frequency and cardiac arrhythmias. METHODS: Daytime napping frequency was self-reported in response to touchscreen questionnaires. The primary outcomes were incident arrhythmias including atrial fibrillation/flutter (AF/Af), ventricular arrhythmia, and bradyarrhythmia. Cox regression analysis was conducted on the basis of 491,117 participants free of cardiac arrhythmias from the UK Biobank. The 2-sample mendelian randomization (MR) and 1-sample MR were used to ensure a causal effect of genetically predicted daytime napping on the risk of arrhythmias. RESULTS: During a median follow-up of 11.91 years, 28,801 incident AF/Af cases, 4132 incident ventricular arrhythmias, and 11,616 incident bradyarrhythmias were documented. Compared with never/rarely napping, usually napping was significantly associated with higher risks of AF/Af (hazard ratio, 1.141; 95% CI, 1.083-1.203) and bradyarrhythmia (hazard ratio, 1.138; 95% CI, 1.049-1.235) but not ventricular arrhythmia after adjustment for various covariates. The 2-sample MR and 1-sample MR analysis showed that increased daytime napping frequency was likely to be a potential causal risk factor for AF/Af in FinnGen (odds ratio, 1.626; 95% CI, 1.061-2.943) and bradyarrhythmia in the UK Biobank (odds ratio, 1.005; 95% CI, 1.002-1.008). CONCLUSION: The results of this study add to the burgeoning evidence of an association between daytime napping frequency and an increased risk of cardiac arrhythmias including AF/Af, ventricular arrhythmia, and bradyarrhythmia.

Remnant cholesterol and risk of incident hypertension: a population-based prospective cohort study.

Remnant cholesterol (RC) has been associated with atherosclerotic cardiovascular disease, but its relationship with hypertension remains unclear. This prospective cohort study aimed to investigate the association between RC and subsequent hypertension risk. Data from the UK Biobank, comprising 295,062 participants initially free of hypertension, were analyzed. Cox proportional hazards regression assessed the association between RC quartiles and hypertension risk. Discordance analysis evaluated the risk of hypertension in discordant/concordant groups of RC and low-density lipoprotein cholesterol (LDL-C) using the difference in percentile units (>10 units). Restricted cubic spline curves were used to model the relationship between RC and hypertension risk. The mean ± SD age of participants was 55.1 ± 8.1 years, with 40.6% being men and 94.7% White. During a median follow-up of 12.8 years, 39,038 participants developed hypertension. Comparing extreme quartiles of RC, the hazard ratio (HR) for incident hypertension was 1.20 (95% CI: 1.17-1.24). After adjusting for traditional risk factors, each 1 mmol/L increase in RC levels was associated with a 27% higher risk of incident hypertension (HR: 1.27; 95% CI: 1.23-1.31). The discordant group with high RC/low LDL-C exhibited a higher risk of incident hypertension compared to the concordant group (HR: 1.06; 95% CI: 1.03-1.09). Spline curves further demonstrated a positive association between RC and the risk of incident hypertension. We concluded that elevated RC emerged as an independent risk factor of incident hypertension, extending beyond traditional risk factors. Monitoring RC levels and implementing interventions to lower RC may have potential benefits in preventing hypertension.

Age at job initiation and risk of coronary heart disease: findings from the UK biobank cohort study.

BACKGROUND: Commencing work at an early age has been linked to various risk factors for coronary heart disease (CHD), such as shift work and intensive job strain. However, the relationship between starting work too early and CHD risk remains largely unclear. We examined the association between age at job initiation and the risk of CHD. METHODS: UK Biobank participants aged 38 to 70 years without cardiovascular disease who provided data on their age at job initiation were included. The primary outcome was CHD, which was ascertained using hospital and death records. The hazard ratios (HRs) and 95% confidence interval (CIs) for the association between age at job initiation and CHD were calculated using multivariable Cox regression. RESULTS: Of the 501,971 participants, 114,418 eligible participants were included in the final analysis. The median age at job initiation was 19.0 years. During the mean follow-up of 12.6 years, 6,130 (5.4%) first CHD events occurred. We observed that age at job initiation was inversely associated with CHD (HR 0.98, 95% CI 0.97-0.99), and the association was potentially J-shaped. The HRs for the < 17-year, 17-18-year, and 19-21-year age groups were 1.29 (95%CI 1.18-1.41), 1.12 (95% CI 1.03-1.22) and 1.05 (95% CI 0.97-1.14), respectively, compared with those of the ≥ 22-year group. CONCLUSIONS: Age at job initiation was associated with incident CHD, which was independent of socioeconomic status. Participants who commenced employment before the age of 19 years exhibited a higher risk of developing CHD later in adulthood.

Serum albumin and risk of incident diabetes and diabetic microvascular complications in the UK Biobank cohort.

AIM: To examine the associations between serum albumin and the incidences of diabetes and diabetic microvascular complications in participants of the UK Biobank cohort. METHODS: There were 398,146 participants without diabetes and 30,952 patients with diabetes from the UK Biobank cohort included in this study. Multivariate-adjusted Cox proportional hazard models were used to analyze the association of albumin with the incidences of diabetes and diabetic microvascular complications. Mendelian randomization (MR) analysis was used to determine the genetic relationships between serum albumin and diabetes. RESULTS: After a median 12.90 years follow-up, 14,710 participants developed incident diabetes (58.83 ± 7.52 years, 56.10% male). After multivariate adjustment, serum albumin was inversely associated with incident diabetes: hazard ratio (HR) [95% confidence interval] per 10 g/l increase 0.88 [0.82;0.94]. MR analyses suggested a potential genetic influence of serum albumin on diabetes in both the UK Biobank and the FinnGen consortium: odds ratios (ORs) [95% confidence interval per 1 g/l increase 0.99 [0.98;1.00] and 0.78 [0.67;0.92], respectively. In patients with diabetes, higher serum albumin levels were significantly associated with lower risk for diabetic microvascular complications. Specifically, per 10 g/l increase in serum albumin, the HRs for diabetic nephropathy, ophthalmopathy, and neuropathy were 0.42 [0.30;0.58], 0.61 [0.52;0.72], and 0.67 [0.51;0.88], respectively. CONCLUSION: In this large prospective study, serum levels of albumin were inversely associated with the incidences of diabetes and diabetic microvascular complications. These findings underscore the importance of maintaining optimal nutrient status in reducing the risk of diabetes and its complications.

Circular RNA circSP5 promotes liver metastasis of colorectal cancer via SP5-mediated BAMBI transcription.

Liver metastasis of colorectal cancer (CRC) is a major cause of cancer morbidity and mortality. Circular RNAs (circRNAs) have been widely reported to be implicated in cancer metastasis. This study aims to investigate the effect of circSP5 (has_circ_0057010) on liver metastasis of CRC. Quantitative real-time PCR (RT-qPCR) analysis was performed to detect gene expression. The level of proteins was measured by western blot. The migration and invasion of CRC cells were assessed by wound healing assay and transwell assay. In vivo assays were performed after the construction of the CRC xenograft model and CRC model with liver metastasis. Mechanism analyses were performed via RNA-binding protein immunoprecipitation (RIP), RNA pulldown, luciferase reporter, chromatin immunoprecipitation (ChIP), and DNA pulldown assays. We found that circSP5 is significantly overexpressed in CRC with liver metastasis and its depletion suppresses the progression of CRC with liver metastasis in vitro and in vivo. Moreover, circSP5 enhances the expression of Sp5 transcription factor (SP5) via competitively sponging microRNA (miR)-1249-3p and could regulate BMP and activin membrane-bound inhibitor (BAMBI) via transcriptional activation. CircSP5 promotes the migration, invasion, and epithelial-mesenchymal transition (EMT) of CRC cells via BAMBI. In sum, circSP5 promotes liver metastasis of CRC by up-regulating SP5-mediated BAMBI transcription.

Weight self-perception and weight loss attempts in Chinese cardiovascular patients and non-cardiovascular patients: evidence from a population-based study.

BACKGROUND: Weight loss is a significant improvement for individuals with overweight or obesity, especially for cardiovascular patients. The driving effects of weight self-perception and attempts to lose weight are vital in weight management, yet weight misperception is a direct culprit for the undesirability of weight control and obesity prevention. This study aimed to investigate weight self-perception and misperception and weight loss attempts in Chinese adults, especially among cardiovascular and non-cardiovascular patients. METHODS: We collected data from China HeartRescue Global Evaluation Baseline Household Survey 2015. Questionnaires were used to assess self-reported weight and cardiovascular patients. We used kappa statistics to check the consistency between weight self-perception and BMI. Logistic regression models were fitted to identify risk factors associated with weight misperception. RESULTS: A total of 2690 participants were enrolled in the household survey, while 157 respondents were cardiovascular patients. According to questionnaire results, 43.3% of cardiovascular patients thought they were overweight and obese, while the percentage is 35.3% among non-cardiovascular patients. Kappa statistics indicated higher consistency of self-reported weight and actual weight among cardiovascular patients. Multivariate analysis showed weight misperception was significantly associated with gender, education level, and actual BMI. Lastly, 34.5% of non-cardiovascular patients and 35.0% of cardiovascular patients were trying to lose weight or keep weight. The majority of these people adopted combined strategies of controlling diet and exercise to lose or maintain weight. CONCLUSIONS: Weight misperception was highly prevalent among cardiovascular or non-cardiovascular patients. Obese respondents, women, and individuals with lower education levels were more vulnerable to make weight misperception. However, no difference in the purpose of weight loss attempts was indicated among cardiovascular and non-cardiovascular patients.

Biophysical cues to improve the immunomodulatory capacity of mesenchymal stem cells: The progress and mechanisms.

Mesenchymal stem cells (MSCs) can maintain immune homeostasis and many preclinical trials with MSCs have been carried out around the world. In vitro culture of MSCs has been found to result in the decline of immunomodulatory capacity, migration and proliferation. To address these problems, simulating the extracellular environment for preconditioning of MSCs is a promising and inexpensive method. Biophysical cues in the external environment that MSCs are exposed to have been shown to affect MSC migration, residency, differentiation, secretion, etc. We review the main ways in which MSCs exert their immunomodulatory ability, and summarize recent advances in mechanical preconditioning of MSCs to enhance immunomodulatory capacity and related mechanical signal sensing and transduction mechanisms.