Serum urate levels and neurodegenerative outcomes: a prospective cohort study and mendelian randomization analysis of the UK Biobank.

BACKGROUND: Previous studies on the associations between serum urate levels and neurodegenerative outcomes have yielded inconclusive results, and the causality remains unclear. This study aimed to investigate whether urate levels are associated with the risks of Alzheimer's disease and related dementias (ADRD), Parkinson's disease (PD), and neurodegenerative deaths. METHODS: This prospective study included 382,182 participants (45.7% men) from the UK Biobank cohort. Cox proportional hazards models were used to assess the associations between urate levels and risk of neurodegenerative outcomes. In the Mendelian randomization (MR) analysis, urate-related single-nucleotide polymorphisms were identified through a genome-wide association study. Both linear and non-linear MR approaches were utilized to investigate the potential causal associations. RESULTS: During a median follow-up period of 12 years, we documented 5,400 ADRD cases, 2,553 PD cases, and 1,531 neurodegenerative deaths. Observational data revealed that a higher urate level was associated with a decreased risk of ADRD (hazard ratio [HR]: 0.93, 95% confidence interval [CI]: 0.90, 0.96), PD (HR: 0.87, 95% CI: 0.82, 0.91), and neurodegenerative death (HR: 0.88, 95% CI: 0.83, 0.94). Negative linear associations between urate levels and neurodegenerative events were observed (all P-values for overall < 0.001 and all P-values for non-linearity > 0.05). However, MR analyses yielded no evidence of either linear or non-linear associations between genetically predicted urate levels and the risk of the aforementioned neurodegenerative events. CONCLUSION: Although the prospective cohort study demonstrated that elevated urate levels were associated with a reduced risk of neurodegenerative outcomes, MR analyses found no evidence of causality.

Association of Life's Essential 8 with all-cause mortality and risk of cancer: a prospective cohort study.

BACKGROUND: No study has concentrated on the association of LE8 with cancer risk and death. We aim to examine the association of LE8 with death and cancer. METHODS: A total of 94733 adults aged 51.42 ± 12.46 years and 77551 participants aged 54.09±12.06 years were enrolled in longitudinal and trajectory analysis respectively. Baseline LE8 was divided into three groups based on the American Heart Association criteria and three trajectory patterns by latent mixture models. We reviewed medical records and clinical examinations to confirm incident cancer during the period from 2006 to 2020. Death information was collected from provincial vital statistics offices. Cox models were used. RESULTS: 12807 all-cause deaths and 5060 cancers were documented during a 14-year follow-up. Relative to participants with high LE8 at baseline, participants with lower levels of LE8 have a significantly increased risk of mortality and incident cancer. All these risks have an increasing trend with LE8 level decreasing. Meanwhile, the trajectory analysis recorded 7483 all-cause deaths and 3037 incident cancers after approximately 10 years. The associations of LE8 with death and cancer were identical to the longitudinal study. In the subtype cancer analysis, LE8 has a strong effect on colorectal cancer risk. Moreover, the cut point is 56.67 in the association between LE8 and death, while the cut point altered to 64.79 in the association between LE8 and incident cancers. These associations were enhanced among younger adults. CONCLUSIONS: There was a significant association of LE8 with death and cancer risk, especially for the young population.

Gender disparities in all-cause mortality among individuals with early-onset cardiovascular diseases.

BACKGROUND AND OBJECTIVE: Gender disparities in mortality among individuals with early-onset cardiovascular disease (CVD) remain uncertain. This study aimed to investigate gender differences in all-cause mortality and identify influencing factors. METHODS: Data extracted from the Kailuan Study, a prospective cohort study initiated in 2006, were analyzed. A total of 2,829 participants with early-onset CVD were included. Cox proportional hazard models were used to assess hazard ratios (HR) and 95% confidence intervals (CI) for gender disparities in all-cause mortality, adjusting for various factors. RESULTS: Males experienced a median follow-up duration of 7.54 years with 276 recorded deaths, and females had a median follow-up of 6.45 years with 105 recorded deaths. Gender disparities in all-cause mortality were observed, with men experiencing a higher all-cause mortality risk compared to women (HR: 1.42, 95% CI: 1.04, 1.92) in the fully adjusted model. Both in men and women with early-onset CVD, elevated hs-CRP levels and an eGFR < 60 mL/min/1.73m2 notably escalated the risk of all-cause mortality. Furthermore, the utilization of antiplatelet agents and successful blood glucose control might mitigate the risk of all-cause mortality. Smoking and eGFR decline modified the association between gender and all-cause death, women were more vulnerable to tobacco consumption and kidney misfunctioning than men (P-interaction = 0.019). CONCLUSION: The study highlights gender disparities in all-cause mortality among individuals with early-onset CVD, with men experiencing a higher risk of mortality compared to women. Addressing these disparities is important for improving outcomes in this population. Further research is needed to develop sex-specific interventions and strategies to reduce gender-related mortality disparities in early-onset CVD.

Global epidemiology of type 2 diabetes in patients with NAFLD or MAFLD: a systematic review and meta-analysis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD) shares common pathophysiological mechanisms with type 2 diabetes, making them significant risk factors for type 2 diabetes. The present study aimed to assess the epidemiological feature of type 2 diabetes in patients with NAFLD or MAFLD at global levels. METHODS: Published studies were searched for terms that included type 2 diabetes, and NAFLD or MAFLD using PubMed, EMBASE, MEDLINE, and Web of Science databases from their inception to December 2022. The pooled global and regional prevalence and incidence density of type 2 diabetes in patients with NAFLD or MAFLD were evaluated using random-effects meta-analysis. Potential sources of heterogeneity were investigated using stratified meta-analysis and meta-regression. RESULTS: A total of 395 studies (6,878,568 participants with NAFLD; 1,172,637 participants with MAFLD) from 40 countries or areas were included in the meta-analysis. The pooled prevalence of type 2 diabetes among NAFLD or MAFLD patients was 28.3% (95% confidence interval 25.2-31.6%) and 26.2% (23.9-28.6%) globally. The incidence density of type 2 diabetes in NAFLD or MAFLD patients was 24.6 per 1000-person year (20.7 to 29.2) and 26.9 per 1000-person year (7.3 to 44.4), respectively. CONCLUSIONS: The present study describes the global prevalence and incidence of type 2 diabetes in patients with NAFLD or MAFLD. The study findings serve as a valuable resource to assess the global clinical and economic impact of type 2 diabetes in patients with NAFLD or MAFLD.

Association of Cumulative Exposure to Cardiovascular Health Behaviors and Factors with the Onset and Progression of Arterial Stiffness.

AIM: This study aims to explore the association of cumulative exposure to cardiovascular health behaviors and factors with the onset and progression of arterial stiffness. METHODS: In this study, 24,110 participants were examined from the Kailuan cohort, of which 11,527 had undergone at least two brachial-ankle pulse wave velocity (baPWV) measurements. The cumulative exposure to cardiovascular health behaviors and factors (cumCVH) was calculated as the sum of the cumCVH scores between two consecutive physical examinations, multiplied by the time interval between the two. A logistic regression model was constructed to evaluate the association of cumCVH with arterial stiffness. Generalized linear regression models were used to analyze how cumCVH affects baPWV progression. Moreover, a Cox proportional hazards regression model was used to analyze the effect of cumCVH on the risk of arterial stiffness. RESULTS: In this study, participants were divided into four groups, according to quartiles of cumCVH exposure levels, namely, quartile 1 (Q1), quartile 2 (Q2), quartile 3 (Q3), and quartile 4 (Q4). Logistic regression analysis showed that compared with the Q1 group, the incidence of arterial stiffness in terms of cumCVH among Q2, Q3, and Q4 groups decreased by 16%, 30%, and 39%, respectively. The results of generalized linear regression showed that compared with the Q1 group, the incidence of arterial stiffness in the Q3 and Q4 groups increased by -25.54 and -29.83, respectively. The results of Cox proportional hazards regression showed that compared with the Q1 group, the incidence of arterial stiffness in cumCVH among Q2, Q3, and Q4 groups decreased by 11%, 19%, and 22%, respectively. Sensitivity analyses showed consistency with the main results. CONCLUSIONS: High cumCVH can delay the progression of arterial stiffness and reduce the risk of developing arterial stiffness.

Adherence to healthy lifestyle was associated with an attenuation of the risk of chronic kidney disease from metabolic dysfunction-associated fatty liver disease: Results from two prospective cohorts.

AIMS: Non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) are important risk factors of chronic kidney disease (CKD). Whether adherence to a healthy lifestyle can modify these effects remain unknown. This study aimed to evaluate the modification effects of healthy lifestyle on the associations among NAFLD, MAFLD, and the risk of CKD, with taking into the effect of genetic risk. METHODS: The Tianjin Chronic Low-grade Systemic Inflammation and Health Cohort Study (TCLSIH), the UK Biobank Study (UKB). The outcome was incident CKD. The exposures including NAFLD, MAFLD, healthy lifestyle, and a genetic risk score (GRS) for CKD. RESULTS: After 1,135,334 person-year follow-up, we documented 2975 incident CKD cases in the two cohorts. MAFLD and NAFLD were associated with a higher risk of CKD, particularly in patients with MAFLD. In the TCLSIH and UKB, the hazard ratios (95% confidence intervals) of incident CKD for MAFLD were 1.47 (1.30, 1.66) and 1.73 (1.57, 1.91), respectively. Adherence to a healthier lifestyle decreased the risk of CKD from MAFLD with significant interaction effects (TCLSIH: Pinteraction = 0.02; UKB: Pinteraction = 0.04). Participants with a lower CKD-GRS experienced a higher risk of CKD from MAFLD, but achieved two healthy lifestyles can significantly decreased the risk of CKD in patients with MAFLD. CONCLUSIONS: MAFLD and NAFLD are associated with a higher CKD risk, particularly MAFLD. Adherence to a healthier lifestyle was associated with a lower risk of CKD from MAFLD. These results highlight the important role of following a healthy lifestyle to prevent CKD.

Prevalence of Diabetes in Patients with Hyperuricemia and Gout: A Systematic Review and Meta-analysis.

PURPOSE OF REVIEW: To perform a systematic review and meta-analysis of the prevalence of diabetes in patients with hyperuricemia and gout. RECENT FINDINGS: Previous studies have confirmed that hyperuricemia and gout are associated with an increased risk of diabetes. A previous meta-analysis indicated that the prevalence of diabetes in patients with gout is 16%. Thirty-eight studies (458,256 patients) were included in the meta-analysis. The combined prevalence of diabetes among patients with hyperuricemia and gout were 19.10% (95% confidence interval [CI]: 17.60-20.60; I2 = 99.40%) and 16.70% (95% CI: 15.10-18.30; I2 = 99.30%), respectively. Patients from North America showed a higher prevalence of diabetes (hyperuricemia: 20.70% [95% CI: 16.80-24.60], gout: 20.70% [95% CI: 16.80-24.60]) than those from other continents. Older patients with hyperuricemia and those using diuretics showed a higher prevalence of diabetes than younger patients and those who were not using diuretics. Studies with a small sample size, case-control design, and low quality score had a higher prevalence of diabetes than studies with a large sample size, other designs, and a high quality score. The prevalence of diabetes among patients with hyperuricemia and gout is high. Controlling plasma glucose and uric acid levels of patients with hyperuricemia and gout is critical for the prevention of diabetes.

Research on the photoluminescence properties of Cu2+-doped perovskite CsPbCl3 quantum dots.

CsPbX3 (X = Cl, Br, and I) quantum dots (QDs) and Cu2+-doped CsPbCl3 QDs with different Cu-to-Pb molar ratios were synthesized via a solvent-based thermal synthesis method. The photoluminescence (PL) properties of these Cu2+-doped CsPbCl3 QDs were also investigated in this study. The results showed that with the increase in the Cl- concentration the surface defects of CsPb(Cl/Br)3 QDs increased, which resulted in an increase in the non-radiative recombination of excitons and weakened the PL intensity. Moreover, Cu2+-doped CsPbCl3 QDs maintained the cubic crystal structure of the initial phases. Owing to the doping of Cu2+ ions, the surface defects of CsPbCl3 QDs were effectively eliminated, which facilitated the excitonic recombination via a radiative pathway. The PL quantum yields (PLQYs) of Cu2+-doped CsPbCl3 QDs were increased to 51%, showing great photostability. From the results, it is believed that Cu:CsPbCl3 QDs can be widely used in optoelectronic devices.

[Construction and structural analysis of integrated cellular network of Corynebacterium glutamicum].

Corynebacterium glutamicum is one of the most important traditional industrial microorganisms and receiving more and more attention towards a novel cellular factory due to the recently rapid development in genomics and genetic operation toolboxes for Corynebacterium. However, compared to other model organisms such as Escherichia coli, there were few studies on its metabolic regulation, especially a genome-scale integrated cellular network model currently missing for Corynebacterium, which hindered the systematic study of Corynebacterium glutamicum and large-scale rational design and optimization for strains. Here, by gathering relevant information from a number of public databases, we successfully constructed an integrated cellular network, which was composed of 1384 reactions, 1276 metabolites, 88 transcriptional factors and 999 pairs of transcriptional regulatory relationships. The transcriptional regulatory sub-network could be arranged into five layers and the metabolic sub-network presented a clear bow-tie structure. We proposed a new method to extract complex metabolic and regulatory sub-network for product-orientated study taking lysine biosynthesis as an example. The metabolic and regulatory sub-network extracted by our method was more close to the real functional network than the simplex biochemical pathways. The results would be greatly helpful for understanding the high-yielding biomechanism for amino acids and the re-design of the industrial strains.