BACKGROUND:Frailty has been increasingly recognized as a significant contributor to adverse cardiovascular outcomes. However, the metabolic mechanisms underlying this relationship remain unclear. This study aimed to identify metabolomic signatures of frailty and their mediating roles in cardiovascular disease (CVD) risk. METHODS:Using data from 95 770 UK Biobank participants, we applied elastic net regularized regression to construct a frailty-related metabolomic signature score comprising 43 plasma metabolites across lipids, amino acids, fatty acids, and energy metabolism. Cox proportional hazards models were used to assess the association between this metabolomic signatures score and incident CVD, coronary heart disease (CHD), and stroke over a median follow-up of 13.81 years. Mediation analysis under a counterfactual framework was conducted to quantify the extent to which the metabolomic signatures mediated the frailty-CVD association. RESULTS:High metabolomic signature scores were significantly associated with increased risks of CVD (hazard ratio [HR] = 1.44; 95% confidence interval [CI]: 1.36-1.53), CHD (HR = 1.50; 95% CI: 1.41-1.61), and stroke (HR = 1.45; 95% CI: 1.37-1.54). Mediation analysis indicated that the metabolomic signature accounted for 14.9% of the association between frailty and overall CVD, 16.0% for CHD, and 16.9% for stroke. Pathway enrichment analysis revealed 7 metabolic pathways significantly enriched in frailty, with the primary associations implicating carbohydrate and amino acid metabolism. CONCLUSIONS:This study highlights a distinct frailty-related metabolic profile that independently predicts cardiovascular risk and partially mediates the frailty-CVD association. These findings underscore the value of metabolomic profiling in guiding early detection and prevention strategies for frailty-related cardiovascular outcomes.

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BACKGROUND:The independent and interactive associations of abdominal obesity and fatty acids with the risk of microvascular diseases (MVDs) are still unclear. METHODS:We conducted a prospective cohort study of 88,571 participants aged 40-69 years from the UK Biobank. Plasma fatty acids were quantified at baseline using high-throughput nuclear magnetic resonance spectroscopy and were analyzed in quartiles, with the lowest quartile of each fatty acid subtype as the reference. Cox regression models were employed to assess the associations between fatty acid levels and incident MVDs, with adjustment for relevant covariates. RESULTS:Over a median follow-up of 13.7 years, higher levels of total polyunsaturated fatty acids (PUFAs), n-3 PUFAs, and n-6 PUFAs are associated with a significantly lower risk of MVDs. The hazard ratios (HRs) for the highest versus lowest quartile (Q4 vs. Q1) are 0.81 (95% CI: 0.75-0.87), 0.89 (95% CI: 0.83-0.96), and 0.85 (95% CI: 0.79-0.91), respectively. Conversely, higher levels of saturated and monounsaturated fatty acids are associated with a higher risk of MVDs. Furthermore, an antagonistic additive interaction is observed between n-3 PUFAs and abdominal obesity (RERI: -0.14, 95% CI: -0.25- -0.03). CONCLUSION:Higher plasma PUFAs are associated with a lower risk of MVDs. Furthermore, the association between n-3 PUFAs and a lower risk of MVDs is more pronounced among individuals with abdominal obesity. These findings contribute to the limited prospective evidence on the associations between plasma-specific fatty acids and MVDs.

BACKGROUND:Although human milk is known to support child development, the specific roles of its bioactive components, like human milk oligosaccharides (HMOs), are still being uncovered. Evidence for HMO benefits is mostly limited to the first 2 y of life, with their long-term impacts on developmental outcomes remaining largely unknown. OBJECTIVES:This study aimed to investigate the associations of human milk feeding duration and HMO composition with child development at 5 y. METHODS:A total of 17 HMOs were measured in 309 milk samples from 156 urban Chinese mothers during 0-5, 10-15, 40-45, 200-240, and 300-400 d postpartum. Human milk and formula feeding data were collected during infancy. Child development was assessed at ∼5 y using the Griffiths Mental Development Scales for China. Multivariable general linear models with cluster-robust standard errors were applied, accounting for repeated HMO measurements. RESULTS:Longer duration of human milk feeding without formula (≥12 mo compared with <6 mo) was associated with significantly higher Z-scores in personal-social and practical reasoning domains. The relative abundance of key HMOs, including 2'-fucosyllactose (2'-FL) and 3'-sialyllactose (3'-SL), remained relatively stable throughout lactation. Each SD increase in 2'-FL and 3'-SL relative abundance was associated with a 0.28-point [95% confidence interval (CI): 0.02, 0.54; P = 0.034] and 0.19-point (95% CI: 0.06, 0.33; P = 0.007) increase in locomotor Z-scores, respectively. These positive associations were modified by infant feeding practice, appearing significant only in the human milk and formula-fed group, not in their human milk-fed peers (Pdifference < 0.05). CONCLUSIONS:Feeding human milk beyond 12 mo was associated with improved developmental outcomes at 5 y. Notably, higher relative abundances of 2'-FL and 3'-SL were associated with modest improvements in locomotor skills only in infants receiving both human milk and formula. These findings suggest that HMOs, acting alongside other modifiable factors, may contribute to long-term child development.

Background: Based on our extensive cohort study, the Maternal Nutrition and Infant Investigation (MUAI), this research investigated the associations between human milk oligosaccharide (HMO) intake during the postnatal period and allergic disease development and gut microbiome composition in early childhood through long-term follow-up. Methods: Human breast milk (HBM) samples at five lactation stages and fecal samples of infants and young children were collected. Children aged 5 years included in this study were categorized into allergic and non-allergic groups via standardized allergen testing. Results: The findings indicated that higher HMO intake levels across five distinct lactation periods may be linked to a reduced incidence of allergies in children. The consumption of six major structurally representative HMOs was significantly associated with alterations in the gut microbiota profiles of young children. Moreover, there were notable differences in gut microbiota composition between allergic and non-allergic children. Specifically, beneficial bacteria such as Bifidobacterium, Akkermansia, and Ruminococcus were significantly enriched, in addition to the levels of metabolite propionic acid, a beneficial short-chain fatty acid, which were notably higher in the non-allergic group. To further validate the relationship between Bifidobacterium abundance and early HMO intake, the analysis revealed that a differential strain biomarker, Bifidobacterium adolescentis (B. adolescentis), exhibited significant correlations with specific HMOs at different lactation stages, particularly showing a strong positive correlation with 2 '-fucosyllactose (2 '-FL) content. Conclusions: These findings suggest that early-life HMO intake is associated with long-term differences in allergic outcomes, potentially through modulation of gut microbiota composition, particularly the enrichment of B. adolescentis.

SGLT-2 inhibitors are now used beyond type 2 diabetes (T2DM) in heart failure (HF) and chronic kidney disease (CKD), where glucose is monitored less routinely. Whether their established ketoacidosis signal-particularly euglycaemic diabetic ketoacidosis (euDKA)-is maintained as the indications expand, and whether it reproduces across independent reporting systems, is untested. We analysed the US FAERS (2020Q1-2026Q1) and Japanese JADER using one pipeline. Signals required consensus across four methods (ROR, PRR, IC, EBGM/EB05). Analyses were run overall, within report-level indication strata [T2DM, HF, CKD, off-label type 1 diabetes (T1DM)] and against an active comparator (DPP-4 inhibitors), with two pre-specified negative controls, time-to-onset modelling and sensitivity analyses. The DKA signal met four-method consensus within every indication stratum, including HF and CKD, and was highest in off-label T1DM; it was therefore maintained, not diluted, as indications expanded. Overall RORs were 67.4 (95% CI 65.7-69.2) in FAERS and 112.3 (104.8-120.3) in JADER. SGLT-2 inhibitors accounted for 85.8% (FAERS) and 91.7% (JADER) of all euDKA reports, though euDKA was only 4.1% and 7.8% of SGLT-2 inhibitor reports. Both negative controls were null in both databases. Median time-to-onset was 60 days (Weibull β=0.48, 95% CI 0.46-0.50). Across two independent reporting systems, the SGLT-2 inhibitor ketoacidosis signal was maintained across the expanding cardiorenal indications, with euDKA concentrated within this class and early onset. Ketone-based assessment is warranted when ketoacidosis is suspected, particularly soon after initiation. As a disproportionality analysis, these are hypothesis-generating signals that cannot establish incidence, relative risk, or causality.

AIMS:To explore the amount-response associations between the duration of physical activity (PA) at different intensities and the risks of microvascular diseases (MVDs), with a particular focus on identifying the optimal amount of vigorous-intensity PA (VPA). METHODS:In this prospective cohort study, PA of different intensities were measured using wrist-worn accelerometers. MVDs, including nephropathy, neuropathy, and retinopathy, were identified from hospital inpatient records. Cox models and restricted cubic splines were used to evaluate the associations. RESULTS:This prospective study included 92,275 participants (40,256 males and 52,019 females) with a mean (SD) age of 61.7 (7.8) years. During a median follow-up of 7.9 years, a total of 5,201 individuals were diagnosed with MVDs, including 2,385 with nephropathy, 512 with neuropathy, and 2,666 with retinopathy. An L-shaped amount-response association for VPA and overall MVDs was observed (P value for non-linearity < 0.001), with the optimal amount of 38 (95 % CI: 34, 44) minutes/week, corresponding to an HR of 0.71 (95 % CI: 0.64, 0.77). CONCLUSION:VPA of 34-44 min/week were associated with 23 %-36 % lower risks of overall MVDs, with a less pronounced decline in risk thereafter. These findings may have implications for the future revision of physical activity recommendations to better improve microvascular health.

This study explores the formation of advanced glycation end products (AGEs) in chicken breast during roasting, focusing on the analytical characterization and simulation of dynamic models for the content of carboxymethyllysine (CML) and carboxyethyllysine (CEL), two key AGEs. To systematically investigate the formation patterns of AGEs, the chicken breasts were subjected to five roasting temperatures ranging from 180 degrees C to 230 degrees C. At each temperature, samples were roasted to achieve five distinct core temperatures, from 60 degrees C to 100 degrees C. Dynamic models for CML and CEL content were constructed using multiple linear regression and partial least squares methods, with the best-fit models identified based on their R2 and RMSE values, with R2 values of 0.886 for CEL, 0.954 for CML, and RMSE values indicating minimal prediction error. Our research provides a robust framework for predicting AGEs formation during roasting with validation, offering valuable insights for optimizing cooking processes to balance product quality and safety.

Although public health programs among undergraduate students have been increasing and gaining popularity worldwide, few studies have focused on the needs and structure of public health courses for non-medical students. This study aimed to design a public health course as a general education elective for non-medical undergraduates at Nankai University, one of China’s leading multidisciplinary and research-oriented universities. Students’ feedback on the course was collected and analyzed after the completion of the elective course. We designed and developed the course under the general education elective course at Nankai University. The course includes four segments: (a) Public Health Fundamentals and Population Research Methods; (b) Chemical Safety and Health, (c) Diet, Nutrition, and Health, (d) Immunology, Microbiology, and Infectious Diseases, spanning 34 class hours (with 6 class hours designated for a flipped classroom format). The teaching content was divided into five parts: (1) Health and Medicine Knowledge, (2) Public Health Knowledge, (3) Public Health Methodology and Philosophy, (4) Proper View of Health Issues, and (5) Values Education. Students’ feedback after the course indicated that Diet, Nutrition, and Health was the most interesting segment, and the students considered basic biological or medical knowledge to be more important than other public health knowledge. A problem-based learning model was implemented for flipped classrooms, and we found that the problem-based learning questions were not only helpful for students’ knowledge construction but also for educators in understanding and managing the learning expectations of non-medical students. We believe that the lesson may guide other institutions in designing similar curricula.

BACKGROUND:To examine the independent, stratified, and joint associations of physical activity (PA) and adiposity with microvascular diseases (MVDs) in prediabetes. METHODS:This cohort study included 9063 prediabetic individuals from the UK Biobank. Total PA, light-intensity PA, moderate- to vigorous-intensity PA, and vigorous-intensity PA were measured by wrist-worn AX3 accelerometers and determined through a machine learning approach. Moderate- to vigorous-intensity PA was categorized by the guideline (≥150 min/wk), and the others were categorized by tertiles. Body fat percentage (BF) was measured by bioimpedance and divided into low and high groups according to sex-specific medians. Cox proportional hazards models were used. RESULTS:During a median follow-up of 8.0 years, 700 cases of MVDs were documented. Recommended moderate- to vigorous-intensity PA and high vigorous-intensity PA (median = 18 min/wk) were associated with reduced risks of MVDs across all BF levels, but the protective association of light-intensity PA was only observed in the low BF group (hazard ratio: 0.67; 95% CI, 0.49-0.91). Joint analyses showed that the lowest risks of MVDs were observed in combinations of low BF and high PAs. The findings had no substantial change using body mass index as an indicator of adiposity. CONCLUSIONS:The findings suggested that short-time vigorous-intensity PA (approximate 18 min/wk) may reduce the risk of MVDs in all strata of adiposity, whereas the protective role of high light-intensity PA was mainly prominent in those with low adiposity among prediabetes. These findings highlighted the need to personalize PA advice combined with adiposity management to improve microvascular health.

High-protein foods and physical activity are crucial for bone growth in early life. This study first examined whether a protein-rich multi-nutrient intervention combined with rope-skipping training could prevent bone loss during winter in prepubertal children. A 10 week randomized controlled trial involving 120 children aged 9-12 years in rural northwestern China was conducted. Participants were assigned to a treatment group (protein-rich multi-nutritional drink plus rope-skipping training) or a control group (rope-skipping training only). Forearm bone mineral density (BMD) was measured at the baseline and week 10 of the trial, along with serum calcium, parathyroid hormone (PTH), insulin-like growth factor 1 (IGF-1), and bone turnover biomarkers. Second, we estimated the effects of three protein sources enriched in the drink, milk protein concentrates (MPC), collagen peptides (CP), and whey protein hydrolysates (WPH), on zebrafish backbone development. In children, BMD decreased in both groups, but the treatment group showed a smaller reduction and a positive intervention effect (relative change: 0.023 g cm-2, P = 0.037). The treatment group also had a smaller increase in PTH (relative change: -8.53 ng L-1, P = 0.012) and a smaller decrease in IGF-1 (relative change: 20.75 ng mL-1, P = 0.076). No significant differences were found in bone turnover biomarkers. In zebrafish, MPC, CP, and WPH individually and synergistically promoted bone growth without adverse effects, as shown by dose-dependent increases in the backbone fluorescence intensity. These findings suggest that protein-rich multi-nutrient supplementation combined with rope-skipping training could prevent bone loss in prepubertal children during winter, potentially through changes in serum PTH and IGF-1, and highlight the synergistic effects of these proteins on bone development.

BACKGROUND:Metabolically healthy obesity (MHO) has been linked to an increased risk of cardiovascular disease, but its link to neurological and mental health remains unclear. This cohort study explored associations between metabolic-obesity phenotypes and multiple brain-related disorders. METHODS:This population-based prospective cohort study included 318,103 UK Biobank participants with a median follow-up of 13.2 years. MHO was defined as BMI ≥ 30 kg/m2 and at least four of six metabolic biomarkers. Outcomes included stroke, anxiety, depression, bipolar disorder, dementia, and Parkinson's disease (PD) that were defined by ICD-10 codes. Cox regression models were performed to examine associations of metabolic-obesity phenotypes with neurological and mental disorders. RESULTS:Compared to metabolically healthy non-obesity (MHN) individuals, MHO participants had significantly elevated risks of stroke (HR, 1.11; 95 % CI: 1.03-1.20), anxiety (HR, 1.16; 95 % CI: 1.08-1.23), and depression (HR, 1.43; 95 % CI: 1.34-1.52). Elevated stroke risks were also observed in metabolically unhealthy non-obese (MUN) and metabolically unhealthy obese (MUO) groups. Similar patterns were found for anxiety and depression. Furthermore, stratified analyses showed significantly increased dementia risk in MUN (HR, 1.35; 95 % CI: 1.18-1.55) and MUO (HR, 1.27; 95 % CI: 1.10-1.47) among participants aged under 65, but not in older individuals. CONCLUSIONS:The study found that MHO and MUO are significantly associated with elevated risks of brain-related disorders, including stroke, anxiety, and depression, while dementia risk is more likely linked to metabolically unhealthy states, irrespective of obesity. These findings highlight the importance of both metabolic health and normal weight to improve brain health.

Foodborne pathogens, such as Salmonella, are major factors that pose significant threats to global food safety and public health. Salmonella typhimurium is a prominent serotype contributing to non-typhoidal salmonellosis, which is a prevalent foodborne illness affecting humans and animals. Bacteriophages are considered one of the most environmentally friendly biocontrol agents, particularly in the food industry, owing to their high specificity and high safety. However, the emergency of phage-resistant mutants limits the biocontrol effect of phage treatment, leading to the requirement for a high diversity of lytic phages. Therefore, the study isolated and characterized two novel lytic Salmonella bacteriophages (SPYS_1 and SPYS_2) targeting S. typhimurium ATCC14028 and evaluated their effectiveness in reducing the contamination rates for milk and chicken tenders. Morphological and genomic analyses indicated that Salmonella phages SPYS_1 and SPYS_2 are novel species classified under the genus Skatevirus and the genus Berlinvirus, respectively. Both phages exhibited high stability across a broad range of thermal and pH conditions. The one-step growth curve result suggested that both phages had a short adsorption time and a large burst size in a single lytic cycle. The phage SPYS_1 demonstrated a noteworthy inhibition effect on the growth of S. typhimurium ATCC14028 in milk, resulting in a ~2-log reduction within the 2 to 4 h range. Overall, both phages have shown significant potential for application in food safety in the future.

Background Evidence on the association between multimorbidity and cognitive impairment in Chinese older population is limited. In addition, whether a healthy lifestyle can protect cognitive function in multimorbid older population remains unknown. Methods A total of 6116 participants aged ≥ 65 years from the Chinese Longitudinal Healthy Longevity Survey were followed up repeatedly. The number of coexisting chronic diseases was used for assessing multimorbidity and cardiometabolic multimorbidity. Three lifestyle statuses (unhealthy, intermediate, and healthy) were defined based on a lifestyle score covering smoking, alcohol drinking, body mass index, outdoor activities, and dietary pattern. Cognitive impairment was defined as the Mini-Mental State Examination score < 24. A modified Poisson regression model with robust error variance was used to assess the associations between multimorbidity, healthy lifestyle, and cognitive impairment. Results During a median follow-up period of 5.8 years, 1621 incident cases of cognitive impairment were identified. The relative risk (RR) of cognitive impairment associated with heavy multimorbidity burden (≥ 3 conditions) was 1.39 (95% confidence interval: 1.22–1.59). This association declined with age, with RRs being 3.08 (1.78–5.31), 1.40 (1.04–1.87), and 1.19 (1.01–1.40) in subjects aged < 70 years, ≥ 70 and < 80 years, and ≥ 80 years, respectively (P for interaction = 0.001). Compared to unhealthy lifestyle, a healthy lifestyle was related to an approximately 40% reduced risk of cognitive impairment regardless of multimorbidity burden. Among the 5 lifestyle factors assessed, daily outdoor activities and a healthy dietary pattern showed convincing protective effects on cognitive function. Conclusions The relationship between multimorbidity and cognitive impairment is age-dependent but remains significant in the population aged 80 years or older. A healthy lifestyle may protect cognitive function regardless of the multimorbidity burden. These findings highlight the importance of targeting individuals with heavy multimorbidity burden and promoting a heathy lifestyle to prevent cognitive impairment in Chinese older population.

OBJECTIVE:Interleukin-27 (IL-27), a potential mediator linking obesity to inflammatory diseases, is considered an important candidate for regulating obesity. The present study evaluated the relationship of IL-27 with obesity and insulin resistance (IR) and further investigated the changes in IL-27 levels after weight loss. METHODS:The study analyzed 405 participants, of whom 62 with overweight or obesity completed one year of lifestyle intervention. The body compositions, including percent of body fat (PBF), visceral fat area (VFA), skeletal muscle mass (SMM), and visceral fat area to skeletal muscle mass ratio (VSR), were assessed using the bioelectrical impedance analysis method. Serum IL-27 levels were measured using the enzyme-linked immunosorbent assay (ELISA). RESULTS:IL-27 levels increased significantly with the increase in body mass index (BMI) (P < 0.001). Moreover, IL-27 levels were positively correlated with PBF, VFA, and VSR. Homeostatic model assessment for insulin resistance (HOMA-IR), the inverse of hepatic insulin sensitivity (1/HISI), adipose tissue insulin resistance (Adipo-IR), and homeostasis model assessment-adiponectin (HOMA-AD) increased significantly with each quartile of IL-27 levels (all P < 0.001). IL-27 levels significantly decreased after weight loss (P < 0.001). CONCLUSIONS:IL-27 was positively correlated with obesity, HOMA-IR, 1/HISI, Adipo-IR, and HOMA-AD. IL-27 levels significantly decreased after weight loss.

BACKGROUND:While short sleep duration is linked to higher risk of non-alcoholic fatty liver disease (NAFLD), the combined effects of sleep timing and sleep duration on NAFLD are less explored. METHODS:In this cross-sectional study of 39,471 participants from Beijing-Tianjin-Hebei region of China, self-reported sleep information and ultrasonography-diagnosed NAFLD were obtained from Jan 2018 to Jan 2020. Sleep timing was categorized based on sleep midpoint: early-type (before 2:00 AM), intermediate-type (2:00-2:30 AM), and late-type (after 2:30 AM). We used multivariable logistic regression to explore the relationship between sleep timing, duration, and NAFLD. We analyzed sleep midpoint and duration categorically and continuously, and conducted stratification analyses by age, sex, body mass index, hypertension, diabetes, and dyslipidemia. RESULTS:Intermediate-type (OR: 1.15, 95% confidence interval: 1.05-1.26) and late-type sleep timing (OR: 1.08, 1.00-1.16) were associated with higher NAFLD risk compared to early-type. Additionally, longer sleep duration was linked to lower risk (OR: 0.92, 0.90-0.95 per hour increase). Notably, intermediate to late-type sleepers with normal sleep duration (7 to <8 h) exhibited a 20% higher NAFLD risk compared to early-type sleepers with the same duration (OR: 1.20, 1.04-1.39). The increased NAFLD risk associated with intermediate to late sleep timing was particularly evident in men, hypertension, and prediabetes or diabetes participants. CONCLUSIONS:Intermediate to late sleep timing, even with normal sleep duration, is associated with increased NAFLD risk. These findings underscore the importance of considering both sleep timing and sleep duration for NAFLD prevention, especially in men and individuals with cardiometabolic conditions.

Background There is limited longitudinal evidence on the hypertensive effects of long-term exposure to ambient O 3 . We investigated the association between long-term O 3 exposure at workplace and incident hypertension, diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse pressure (PP), and mean arterial pressure (MAP) in general working adults. Methods We conducted a cohort study by recruiting over 30,000 medical examination attendees through multistage stratified cluster sampling. Participants completed a standard questionnaire and comprehensive medical examination. Three-year ambient O 3 concentrations at each employed participant’s workplace were estimated using a two-stage machine learning model. Mixed-effects Cox proportional hazards models and linear mixed-effects models were used to examine the effect of O 3 concentrations on incident hypertension and blood pressure parameters, respectively. Generalized additive mixed models were used to explore non-linear concentration-response relationships. Results A total of 16,630 hypertension-free working participants at baseline finished the follow-up. The mean (SD) O 3 exposure was 45.26 (2.70) ppb. The cumulative incidence of hypertension was 7.11 (95% CI: 6.76, 7.47) per 100 person-years. Long-term O 3 exposure was independently, positively and non-linearly associated with incident hypertension (Hazard ratios (95% CI) for Q2, Q3, and Q4 were 1.77 (1.34, 2.36), 2.06 (1.42, 3.00) and 3.43 (2.46, 4.79), respectively, as compared with the first quartile (Q1)), DBP ( β (95% CI) was 0.65 (0.01, 1.30) for Q2, as compared to Q1), SBP ( β (95% CI) was 2.88 (2.00, 3.77), 2.49 (1.36, 3.61) and 2.61 (1.64, 3.58) for Q2, Q3, and Q4, respectively), PP ( β (95% CI) was 2.12 (1.36, 2.87), 2.03 (1.18, 2.87) and 2.14 (1.38, 2.90) for Q2, Q3, and Q4, respectively), and MAP ( β (95% CI) was 1.39 (0.76, 2.02), 1.04 (0.24, 1.84) and 1.12 (0.43, 1.82) for Q2, Q3, and Q4, respectively). The associations were robust across sex, age, BMI, and when considering PM 2.5 and NO 2 . Conclusions To our knowledge, this is the first cohort study in the general population that demonstrates the non-linear hypertensive effects of long-term O 3 exposure. The findings are particularly relevant for policymakers and researchers involved in ambient pollution and public health, supporting the integration of reduction of ambient O 3 into public health interventions.

Convincing evidence has suggested the health potentials of oolong tea (OT) on gut microbiota homeostasis; however, limited population-based studies exist regarding the effect of OT consumption on human gut microbial and metabolic profile. This pilot study explored gut microbial and metabolic changes in healthy adults with a 3-week oolong tea intake. Our findings showed that OT treatment significantly altered gut microbial diversity (Shannon index, 5.4±0.1 vs. 5.7±0.1 pre- and post-OT treatment), reorganized gut microbiota composition, enriched Bacteroides and Prevotella, decreased Megamonas, and improved gastrointestinal function. Also, gut microbes from overweight subjects with BMI >23.9 exhibited greater responses to OT treatment compared with normal-weight counterparts. Metabolomic analysis identified OT intake-induced 23 differential metabolites and 10 enriched metabolic pathways. This study may provide new insights into the association among OT intervention, host gut microbiome and metabolic profile, and improve the knowledge of clinical strategies and personalized nutrition.

Abstract Aims To construct a polygenic risk score (PRS) for coronary artery disease (CAD) and comprehensively evaluate its potential in clinical utility for primary prevention in Chinese populations. Methods and results Using meta-analytic approach and large genome-wide association results for CAD and CAD-related traits in East Asians, a PRS comprising 540 genetic variants was developed in a training set of 2800 patients with CAD and 2055 controls, and was further assessed for risk stratification for CAD integrating with the guideline-recommended clinical risk score in large prospective cohorts comprising 41 271 individuals. During a mean follow-up of 13.0 years, 1303 incident CAD cases were identified. Individuals with high PRS (the highest 20%) had about three-fold higher risk of CAD than the lowest 20% (hazard ratio 2.91, 95% confidence interval 2.43–3.49), with the lifetime risk of 15.9 and 5.8%, respectively. The addition of PRS to the clinical risk score yielded a modest yet significant improvement in C-statistic (1%) and net reclassification improvement (3.5%). We observed significant gradients in both 10-year and lifetime risk of CAD according to the PRS within each clinical risk strata. Particularly, when integrating high PRS, intermediate clinical risk individuals with uncertain clinical decision for intervention would reach the risk levels (10-year of 4.6 vs. 4.8%, lifetime of 17.9 vs. 16.6%) of high clinical risk individuals with intermediate (20–80%) PRS. Conclusion The PRS could stratify individuals into different trajectories of CAD risk, and further refine risk stratification for CAD within each clinical risk strata, demonstrating a great potential to identify high-risk individuals for targeted intervention in clinical utility.