Associations between systemic inflammation indicators and nonalcoholic fatty liver disease: evidence from a prospective study.

Background: Although inflammation has been linked to nonalcoholic fatty liver disease (NAFLD), most studies have focused only on a single indicator, leading to inconsistent results. Therefore, a large prospective study that includes a variety of well-documented single and composite indicators of inflammation is needed. This study aimed to thoroughly investigate the potential associations between different systemic inflammatory indicators and NAFLD in the UK Biobank cohort. Methods: After excluding ineligible participants, 378,139 individuals were included in the study. Associations between systemic inflammatory indicators and hepatic steatosis were assessed using multivariate logistic regression. The relationships between systemic inflammatory indicators and nonalcoholic fatty liver disease were analysed using Cox proportional hazards models, and nonlinear associations were investigated using restricted cubic splines. Results: According to the cross-sectional analysis, systemic inflammatory indicators significantly correlated with hepatic steatosis. Over a median follow-up of 13.9 years, 4,145 individuals developed NAFLD. After sufficient adjustment for confounding factors, CRP levels were found to be nonlinearly positively associated with NAFLD risk (P<0.001), representing the strongest correlation among the tested relationships; lymphocyte count and the LMR showed an L-shaped correlation; monocyte count and neutrophil count showed a linear positive correlation (all P< 0.001); and the NLR, PLR, and SII showed a U-shaped correlation (all P<0.001). Conclusions: Multiple systemic inflammatory indicators are strongly associated with the development of NAFLD, and aggressive systemic inflammation management may have a favourable impact on reducing the burden of NAFLD; further randomized controlled studies are needed.

Intrinsic Capacity, Polygenic Risk Score, APOE Genotype, and Risk of Dementia: A Prospective Cohort Study Based on the UK Biobank.

BACKGROUND AND OBJECTIVES: The World Health Organization recently released a novel metric for healthy aging: intrinsic capacity (IC). The relationship between IC and the incidence of dementia, and its subtypes, is unknown. We aimed to analyze the relationship between IC and the incidence of dementia and its subtypes. Moreover, we tested whether genetic susceptibility to dementia could be modified by IC. METHODS: This cohort study involved 366,406 participants from the UK Biobank between 2006 and 2010. We analyzed 7 factors that reflected functional status across 4 IC domains to compute a comprehensive IC deficit score. Cox models were used to elucidate the relationship between the IC deficit score and the incidence of dementia. RESULTS: Among the 366,406 participants, 5,207 cases of dementia were documented, encompassing 2,186 and 1,175 cases of Alzheimer disease (AD) and vascular dementia (VD), respectively. Compared with participants with an IC score of 0, individuals with an IC score of 4+ had a markedly elevated risk of dementia (hazard ratio [HR] 2.17, 95% CI 1.92-2.45). In the joint analysis, for participants with a high polygenic risk score (PRS) and an IC score of 4 or more, the HR of all-cause dementia was 8.11 (95% CI 6.28-10.47) compared with individuals with a low PRS and an IC score of 0. Similar results were seen in the AD and VD groups. DISCUSSION: In summary, IC is associated with a higher risk of dementia, particularly in those combined with genetically predisposed to dementia.

Association between residential greenness and incident delirium: A prospective cohort study in the UK Biobank.

BACKGROUND: Contemporary environmental health investigations have identified green space as an emerging factor with promising prospects for bolstering human well-being. The incidence of delirium increases significantly with age and is fatal. To date, there is no research elucidating the enduring implications of green spaces on the occurrence of delirium. Therefore, we explored the relationship between residential greenness and the incidence of delirium in a large community sample from the UK Biobank. METHODS: Enrollment of participants spanned from 2006 to 2010. Assessment of residential greenness involved the land coverage percentage of green space within a buffer range of 300 m and 1000 m. The relationship between residential greenness and delirium was assessed using the Cox proportional hazards model. Further, we investigated the potential mediating effects of physical activity, particulate matter (PM) with diameters ≤2.5 (PM2.5), and nitrogen oxides (NOx). RESULTS: Of 232,678 participants, 3722 participants were diagnosed with delirium during a 13.4-year follow-up period. Compared with participants with green space coverage at a 300 m buffer in the lowest quartile (Q1), those in the highest quartile (Q4) had 15 % (Hazard ratio [HR] = 0.85, 95 % confidence interval [CI]: 0.77, 0.94) lower risk of incident delirium. As for the 1000 m buffer, those in Q4 had a 16 % (HR = 0.84, 95 % CI: 0.76, 0.93) lower risk of incident delirium. The relationship between green space in the 300 m buffer and delirium was mediated partially by physical activity (2.07 %) and PM2.5(49.90 %). Comparable findings were noted for the green space percentage within the 1000 m buffer. CONCLUSIONS: Our results revealed that long-term exposure to residential greenness was related to a lower risk of delirium. Air pollution and physical activity exerted a significant mediating influence in shaping this association.

Visceral adiposity associated with incidence and development trajectory of cardiometabolic diseases: A prospective cohort study.

BACKGROUND AND AIMS: There is a lack of literature concerning the effects of visceral adipose on the development of first cardiometabolic disease (FCMD) and its subsequent progression to cardiometabolic multimorbidity (CMM) and mortality. METHODS AND RESULTS: 423,934 participants from the UK Biobank with different baseline disease conditions were included in the analysis. CMM was defined as the simultaneous presence of coronary heart disease, T2D, and stroke. Visceral adiposity was estimated by calculating the visceral adiposity index (VAI). Multistate models were used to assess the effect of visceral adiposity on the development of CMM. During a median follow-up of 13.5 years, 50,589 patients had at least one CMD, 6131 were diagnosed with CMM, whereas 24,634 patients died. We observed distinct roles of VAI with respect to different disease transitions of CMM. HRs (95 % CIs) of high VAI were 2.35 (2.29-2.42) and 1.64 (1.50-1.79) for transitions from healthy to FCMD and from FCMD to CMM, and 0.97 (0.93-1.02) for all-cause mortality risk from healthy, FCMD and CMM, respectively. CONCLUSIONS: Our study provides the first evidence that visceral adipose may contribute to the development of FCMD and CMM in healthy participants. However, visceral adipose may confer resistance to all-cause mortality in participants with existing CMD or CMM. A better understanding of the relationship between visceral adipose and CMM can focalize further investigations on patients with CMD with high levels of visceral fat and help take targeted preventive measures to reduce the medical burden on individual patients and society.

Ultra-processed food consumption, mediating biomarkers, and risk of chronic obstructive pulmonary disease: a prospective cohort study in the UK Biobank.

Background: Ultra-processed food (UPF) is a popular supplement in the UK and other developed countries. However, whether and how UPF intake is associated with chronic obstructive pulmonary disease (COPD) remains unclear. Objective: We aimed to examine the association between UPF consumption and COPD incidence and explore the potential mediating effects of COPD-related biomarkers. Methods: This prospective cohort study included 207 002 participants without COPD at recruitment and completed 24-hour dietary recalls. UPF was defined according to the NOVA classification system. Incident COPD was ascertained using electronic hospital and mortality records. Cox regression models were used to estimate UPF consumption and the subsequent risk of COPD. Substitution analysis was performed to assess the risk of COPD by substituting UPF with an equivalent proportion of unprocessed or minimally processed food (UNPF). Mediation analyses were performed to evaluate the contribution of biomarkers related to the lipid profile, glucose metabolism, and systemic inflammation to the observed associations. Results: During a median follow-up of 13.1 (interquartile range: 12.5-13.9) years, 4670 COPD events were recorded. The adjusted hazard ratio (HR) of COPD in the highest quintile versus the lowest quintile of the UPF consumption proportion (weight percentage of the UPF) was 1.22 (95% confidence interval [CI]: 1.11-1.34). There was a 10% elevated risk of COPD incidence per SD increase in UPF intake (HR: 1.10; 95% CI: 1.08-1.13). Replacing 20% of the UNPF weight with the UPF was associated with a 13% decrease in COPD risk (95% CI: 0.84-0.91). In mediation analyses, biomarkers explained 1.0-10.1% of the association between UPF intake and COPD. Results from stratified and sensitivity analyses further support the robustness of these findings. Conclusions: Elevated UPF consumption was associated with a higher risk of COPD, and this association was primarily mediated by glucose, inflammation, and lipids, whereas substituting UNPF for UPF was associated with a decreased risk of COPD.

Association of ultra-processed food consumption with incident depression and anxiety: a population-based cohort study.

Background: Global ultra-processed food (UPF) consumption has risen rapidly. The development and prognosis of depression and anxiety remain unclarified. Herein, we aimed to examine the association between UPF consumption and the incidence and progression trajectory of depression and anxiety. Methods: In our study, participants were recruited between 2006 and 2010. UPF consumption was expressed as UPF servings, energy ratio, and weight ratio. The relationships between UPF consumption and depression or anxiety were assessed using the Cox proportional hazards model. Multi-state models were used to explore the association between UPF consumption and the risks of all transitions from a healthy state to depression or anxiety and then to all-cause mortality. Results: Among the 183 474 participants, 5453 were diagnosed with depression and 6763 with anxiety during the follow-up of 13.1 years. The participants in the highest quartile (Q4) of UPF servings, energy ratio, and weight ratio had an increased risk of depression compared to those in the lowest quartile (Q1), with hazard ratios (HRs) and 95% confidence intervals [CIs] of 1.22 (1.13-1.31), 1.13 (1.05-1.22), and 1.26 (1.17-1.36), respectively. Similarly, participants in Q4 of UPF consumption had a higher risk of anxiety, with HRs (95% CIs) of 1.13 (1.06-1.21), 1.13 (1.05-1.21), and 1.11 (1.04-1.19), compared to those in Q1. The study also found a significant association between UPF consumption and all-cause mortality, which disappeared for participants with depression or anxiety. Conclusions: Our findings revealed that UPF consumption is associated with depression or anxiety.

Engineering Pheromone-Mediated Quorum Sensing with Enhanced Response Output Increases Fucosyllactose Production in Saccharomyces cerevisiae.

Engineering dynamic control of gene expression is desirable because many engineered functions interfere with endogenous cellular processes that have evolved to facilitate growth and survival. Minimizing conflict between growth and production phases can therefore improve product titers in microbial cell factories. We developed an autoinduced gene expression system by rewiring the Saccharomyces cerevisiae pheromone response pathway. To ameliorate growth reduction due to the early onset response at low population densities, α-pheromone of Kluyveromyces lactis (Kα) instead of S. cerevisiae (Sα) was expressed in mating type "a" yeast. Kα-induced expression of pathway genes was further enhanced by the transcriptional activator Gal4p expressed under the control of the pheromone-responsive FUS1 promoter (Pfus1). As a demonstration, the engineered circuit combined with the deletion of the endogenous galactose metabolic pathway genes was applied to the production of human milk oligosaccharides, 2'-fucosyllactose (2'-FL) and 3-fucosllactose (3-FL). The engineered strains produced 3.37 g/L 2'-FL and 2.36 g/L 3-FL on glucose with a volumetric productivity of 0.14 and 0.03 g/L·h-1 in batch flask cultivation, respectively. These represented 147 and 153% increases over the control strains on galactose wherein the respective pathway genes are expressed under GAL promoters only. Further fed-batch fermentation achieved titers of 32.05 and 20.91 g/L for 2' and 3-FL, respectively. The genetic program developed here thus represents a promising option for implementing dynamic regulation in yeast and could be used for the production of biochemicals that may place a heavy metabolic burden on cell growth.

Purification, characterization and action mechanism of plantaricin JY22, a novel bacteriocin against Bacillus cereus produced by Lactobacillus plantarum JY22 from golden carp intestine.

A novel bacteriocin-producing strain, Lactobacillus plantarum JY22 isolated from golden carp intestine, was screened and identified by its physiobiochemical characteristics and 16S rRNA gene sequence analysis. This bacteriocin, named plantaricin JY22, was purified using ethyl acetate extraction and gel filtration. Its molecular weight was approximately 4.1 kDa by SDS-PAGE analysis. The partial amino acid sequence of plantaricin JY22 was DFGFDIPDEV. It was highly heat-stable and remained active at pH range from 2.5 to 5.5, but was sensitive to protease. Plantaricin JY22 had a bactericidal mode. Scanning electron microscope analysis indicated that plantaricin JY22 damaged the morphology of cells and spores for Bacillus cereus. Moreover, the plantaricin JY22 destroyed cell membrane integrity as confirmed by the leakage of electrolytes, the losses of Na+K+-ATP, AKP, nucleic acids (OD260nm) and proteins. SDS-PAGE of B. cereus proteins further demonstrated that plantaricin JY22 had a remarkable effect on bacterial proteins.