Objectives: We aimed to develop a practical dietary quality score reflecting the Cantonese dietary pattern and evaluate its validity against established indices. Methods: The Cantonese Dietary Index (CDI, ) was constructed based on Cantonese dietary principles. Reliability was assessed using intraclass correlation coefficients (ICC) over 5-6 years in the GNHS. Validity was evaluated using Spearman correlations with dietary indices (aMed, DASH, and DBI) and by comparing associations with metabolic syndrome (MetS) across dietary indices using regression models. The CDI was developed from the Guangzhou Nutrition and Health Study cohort (GNHS) and validated in the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIH) cohort and the National Health and Nutrition Examination Survey (NHANES). Results: A total of 4025 (GNHS), 29,165 (TCLSIH), and 28,890 (NHANES) participants were included. Median CDI scores were 58.5, 51.0, and 49.0, respectively. The 5-6-year ICC was 0.33 (p < 0.001). The CDI was moderately correlated with dietary indices across the three studies (GNHS: from -0.55 [DBI-LBS] to 0.61 [DASH], TCLSIH: from -0.61 [DBI-DQD] to 0.71 [DASH], NHANES: from -0.33 [DBI-DQD] to 0.68 [DASH]). The odds ratios (95% CIs) of MetS for CDI, aMed, and DASH scores were 0.80 (0.74, 0.86), 0.91 (0.84,0.99), and 0.83 (0.77, 0.90) in GNHS, 0.95 (0.92, 0.98), 0.99 (0.96, 1.02), and 0.92 (0.89, 0.95) in TCLSIH, and 0.80 (0.77, 0.84), 0.80 (0.76, 0.84), and 0.72 (0.69, 0.76) in NHANES. Conclusions: The CDI demonstrated moderate validity and reliability in Chinese populations and was inversely associated with MetS.

BACKGROUND:The pathogenesis of liver fibrosis centres on the activation of hepatic stellate cells (HSCs). Adenosine-to-inosine RNA editing, primarily catalysed by adenosine deaminase acting on RNA1 (ADAR1), is the most prevalent post-transcriptional modification that increases transcriptome diversity. OBJECTIVE:This study aims to elucidate the role of ADAR1-imposed RNA editome in HSC activation and to determine the therapeutic potential of targeting ADAR1 for liver fibrosis. DESIGN:ADAR1 expression was measured in fibrotic human and mouse livers, as well as in primary human and mouse HSCs. Adar1 loss-of-function effect was evaluated in Adar1f/f /Cre-ER, Adar1△HSC and Adar1i△HSC mice, whereas viral infection with Ad-Adar1 was employed in gain-of-function studies. Adar1△HSCIfih1-/-- and Adar1△HSCIfnar△HSC mice were used for mechanistic studies. An ADAR1 inhibitor and HSC-selective RNAi were used for therapeutic evaluations. RESULTS:ADAR1 is decreased in human and mouse fibrotic livers and activated HSCs. HSC-specific ablation or pharmacological inhibition of ADAR1 ameliorated HSC activation and liver fibrosis. In contrast, forced expression of ADAR1, but not its editing-deficient mutant, exacerbated HSC activation. Mechanistically, ADAR1 ablation accumulated double-stranded RNA and activated HSC-intrinsic innate immunity in a melanoma differentiation-associated gene 5-dependent manner. Interferon-β was identified as a key antifibrotic effector via the activation of the JAK1/2 pathway. RNA editome analysis revealed the Col3a1 3' UTR as a novel ADAR1 editing target, leading to increased collagen production. CONCLUSION:ADAR1-imposed RNA editome suppresses HSC-intrinsic innate immunity and promotes collagen production, leading to aggravated HSC activation and liver fibrosis. Targeting ADAR1 with its pharmacological inhibitor or HSC-selective RNAi shows great promise in treating liver fibrosis.

Background:Insulin resistance and obesity are critical determinants of low muscle mass. The main goal was to determine whether the reduced muscle mass in people without diabetes is correlated with the insulin resistance index and obesity indicators. Method:The data from NHANES 2011 to 2018 were analyzed to explore how the TyG index and obesity indices relate to low muscle mass. Associations were conducted using weighted logistic regression, RCS analysis, sensitivity analyses, and subgroup evaluations. In addition, the prediction capability of these indices was evaluated using ROC curve analysis and the AUC. Result:The TyG index (OR = 1.86, 95% CI: 1.31-2.63, p = 0.001), TyG-WC (OR = 7.53, 95% CI: 5.49-10.30, p < 0.001), TyG-WHtR (OR = 10.40, 95% CI: 7.56-14.30, p < 0.001), and TyG-WWI (OR = 4.74, 95% CI: 3.41-6.57, p < 0.001) turned out to show a positive relationship with low muscle mass in nondiabetic adults. TyG-WHtR's higher discriminative performance has been proven by its AUC, which was 0.831 (95% CI: 0.814-0.848). The most appropriate threshold values were 4.932 for men and 5.031 for women aged ≥ 40 years, and 4.628 for men and 4.674 for women aged < 40 years. Conclusion:The risk of insufficient muscle mass is increased in nondiabetic adults with higher values of TyG-obesity indicators (TyG-WC, TyG-WHtR, and TyG-WWI). TyG-WHtR possessed the best discriminative ability than other indicators.

OBJECTIVE:To examine the association between environmental exposures and specific type 2 diabetes (T2D) subphenotypes. RESEARCH DESIGN AND METHODS:We categorized T2D participants from the KORA F4 (2006-2008) and FF4 (2013-2014) study waves into three phenotypes using k-means clustering: Cluster A (insulin deficiency); Cluster B (age-related diabetes); and Cluster C (higher insulin resistance). The annual averages of fine particulate matter (PM2.5) and PM2.5 absorbance (PM2.5abs), annual air temperature mean (Tm) and standard deviations (Tsd), and greenness (NDVI), were assessed at participants' residences. Covariate-adjusted mixed multinomial logistic regression models were fitted to examine the effects of environmental exposures on diabetes subphenotypes. We also calculated joint odds ratios (ORs) to estimate the additive effects of exposure mixtures. RESULTS:The longitudinal analysis showed that interquartile range (IQR) increases in PM2.5 (OR = 1.29, 95 % confidence interval [CI]: 1.01, 1.64) and PM2.5abs (OR = 1.30, 95 % CI: 1.01, 1.67) were associated with higher odds of being in T2D Cluster C, compared to normoglycemic individuals. Furthermore, we found that IQR increases in PM2.5 and Tsd, alongside with decreases in NDVI and Tm increased the odds of being in Cluster B (joint OR = 1.41, 95 % CI: 1.03, 1.93) and Cluster C (joint OR = 1.55, 95 % CI: 1.02, 2.36), while the combination of PM2.5abs with other exposures increased the odds of Cluster C (joint OR = 1.54, 95 % CI: 1.01, 2.33). CONCLUSIONS:Our study contributes to an enhanced understanding of the associations between environmental exposures and diabetes, indicating increased risks for age-related and insulin-resistant diabetes.

INTRODUCTION:Chronic kidney disease (CKD) is a major health burden, yet its underlying mechanisms and early predictors remain poorly understood. OBJECTIVES:This prospective study identified serum proteins associated with incident CKD and examined their upstream determinants related to inflammation and diet. METHODS:A total of 2,182 participants with baseline serum proteomic data and repeated measurements of estimated glomerular filtration rate (eGFR) over four 3-year intervals were included. Proteins associated with incident CKD were identified using multivariable-adjusted models, with internal validation from repeated measurements and external replication in the UK Biobank (UKB). Associations of CKD-related proteins with serum inflammatory markers, inflammation-related dietary indices, and serum carotenoids were also examined. RESULTS:Twenty-two proteins were associated with 9-year CKD risk (11 positively and 11 inversely; adjusted p < 0.05). A combined protein score predicted CKD with an area under the curve (AUC) of 0.75 in the discovery cohort, 0.76 in the internal validation using averaged protein data, and 0.70 in the UKB replication using 15 overlapping proteins. Standardized hazard ratios of CKD risk ranged from 1.31 to 1.66 for the top 4 risk proteins (PEDF, CFAD, RET4, APOH) and from 0.77 to 0.80 for the top 4 protective proteins (A1BG, A2AP, ENAM, GPX3) (all adjusted p < 0.01). Inflammatory markers (e.g., C-reactive protein) were positively associated with deleterious proteins and inversely associated with protective ones. Higher serum carotenoid concentrations and DASH diet scores were associated with lower inflammatory markers and more favorable CKD-related protein profiles. CONCLUSIONS:We identified 22 serum proteins associated with CKD incidence, supporting their potential for early prediction and mechanistic insight. Systemic inflammation was adversely associated with, whereas circulating carotenoids were beneficially associated with, CKD-related protein profiles.

BACKGROUND:Tea is a dietary source of flavan-3-ols, which may influence bone health, but prospective evidence linking tea intake and its circulating biomarkers with longitudinal bone mineral status remains limited. OBJECTIVES:To examine associations of tea consumption and its serum biomarkers with bone mineral status in Guangzhou Nutrition and Health Study. METHODS:In 1708 participants, whole-body, total hip, lumbar spine, and femoral neck bone mineral density (BMD) and bone mineral content (BMC) were measured using dual-energy X-ray absorptiometry at 4 repeated visits during a 13-y follow-up period. Baseline serum flavan-3-ols, including epicatechin, epigallocatechin gallate (EGCG), epicatechin gallate (ECG), epigallocatechin, and catechin, were quantified using ultra-high-performance liquid chromatography-tandem mass spectrometry. Tea consumption was categorized as non-, low-, moderate-, or high-frequency. Multivariable linear mixed-effects models, including exposure × visit interactions, were used to evaluate visit-averaged bone mineral measures and longitudinal trajectories. RESULTS:Among 1708 participants, significant tea consumption group × visit interactions were observed for whole-body, lumbar spine, and femoral neck BMD and whole-body BMC (P-interaction ranged from <0.001 to 0.022). Moderate-frequency tea drinkers generally had the highest visit-averaged adjusted marginal mean Z-scores, including 0.107 (95% CI: 0.025, 0.190) for whole-body BMD, 0.090 (0.012, 0.168) for lumbar spine BMD, and 0.108 (0.029, 0.187) for femoral neck BMD (P-diff ranged from <0.001 to 0.017). In analyses of serum tea biomarkers, higher biomarker categories were generally associated with more favorable bone mineral measures; however, the associations were not consistently linear, and several biomarkers showed nonmonotonic patterns. Visit-averaged differences were most extensive across ECG and EGCG categories. CONCLUSIONS:Moderate-frequency tea consumption and higher categories of selected circulating tea biomarkers were associated with more favorable bone mineral status.

BACKGROUND:The alternative pathway (AP) plays a crucial role in triggering complement activation and promoting chronic inflammation. This study aims to investigate the longitudinal association between AP and atherosclerosis, and explore the potential role of gut microbiota and inflammatory factors in their association. METHOD:This study was based on a 9-year prospective cohort of 3382 participants from Guangzhou, China (mean age±SD, 57.75±5.85 years; 68.8% female), with data on serum APACPs (AP-associated complement proteins) and carotid plaque (measured by ultrasound) repeatedly measured up to 3×. Baseline inflammatory markers were evaluated in 923 participants, and gut shotgun metagenome data were obtained from 1567 participants. Mendelian randomization analysis was performed using genome-wide significant genetic variants as instrumental variables to suggest potential causal associations. RESULTS:Both longitudinal and prospective analyses consistently demonstrated positive associations between carotid plaque and 3 complement components: C3 (complement C3; odds ratios [95% Cl] for the highest versus lowest quartiles, 1.36 [1.07-1.74] in longitudinal analysis and 1.29 [1.06-1.56] in prospective analysis), CFB (complement factor B; 1.36 [1.07-1.72] in longitudinal analysis and 1.39 [1.15-1.69] in prospective analysis), and CFH (complement factor H; 1.39 [1.10-1.76] in longitudinal analysis and 1.31 [1.07-1.61] in prospective analysis). Mendelian randomization analysis suggested a potential causal association between CFB and carotid plaque. Inflammatory factors (CRP [C-reactive protein] and IL-6 [interleukin-6]) and microbial species (Ruminococcus bromii, Roseburia hominis, Rothia mucilaginosa, Collinsella stercoris, Olsenella scatoligenes, and Bacteroides massiliensis) were significantly associated with both APACPs and carotid plaque (P<0.05). For example, butyrate-producing bacterium R bromii was inversely associated with CFB and carotid plaque (odds ratios [95% CI], 0.83 [0.79-0.88]) and may mediate the CFB-carotid plaque association (proportion mediated, 13.5%; P=0.005). Microbial risk score (weighted sum of selected microbial species; proportion mediated, 42.6%; P<0.001) and total immune factors (the sum of all inflammatory factors; proportion mediated, 19.0%; P=0.002) mediated the association between Total-APACPs (sum of standardized carotid plaque-related APACPs [C3, CFB, and CFH]) and carotid plaque. CONCLUSIONS:Our study showed a negative association between the AP and carotid plaque in a longitudinal cohort. Gut microbiota and inflammatory biomarkers may provide mechanistic insights into the association between the AP and atherosclerosis. Our findings pave the way for the development of new therapeutic targets for atherosclerosis.

Circulating proteomics acts as an intermediate phenotype linking genetic susceptibility to MASLD. However, current evidence rarely establishes a direct concordance between serum protein levels and hepatic gene expression. We aimed to perform a multi-cohort joint analysis of serum proteomics and transcriptomics to characterize essential molecular features for MASLD. For the serum proteomic analysis of simple steatosis (MASL), we conducted a cross-sectional investigation in an MRI-based cohort (N/cases: 1048/428) and further examined the prospective association between protein features and MASL incidence (N/cases: 2945/1947) ascertained by ultrasonography over a median 9.8-year follow-up in the Guangzhou Nutrition and Health Study (GNHS) cohort. In parallel, we characterized fibrosis and MASH-related transcriptional features using liver transcriptomics from the MASH cohort (N = 94) and validated these gene signatures for MASH in liver transcriptomes from the independent Japanese and German populations (N = 98 and 59). The serum proteomic analysis identified the C3, C9, F9, VTN, AFM, APOD, APOF, and SHBG proteins were significantly associated with MASL risk (P < 0.05). Liver transcriptomic analysis revealed a coordinated downregulation of C9, C4BPB, C1RL, APOF, and ITIH4 in the high NAS group, implicating dysregulated complement activation as a critical mechanism driving disease progression. Furthermore, SHBG, A2M, GSN, C7, LUM, IGHG3, and IGFALS were associated with liver fibrosis stages, and pathways related to extracellular exosomes and vesicles were implicated in fibrotic development. Consistently, in the Japanese and Germany cohorts, APOF, GSN, and LUM exhibited aberrant expression in both MASH patients and those with high NAS scores. The multi-cohort study identified specific serum protein signatures associated with MASL risk, which correspond to dysregulated gene expression patterns in hepatocytes. These findings bridge the gap between systemic circulatory changes and intrahepatic pathological progression, providing not only robust non-invasive biomarkers for early stratification but also potential mechanistically-driven therapeutic targets for halting the progression of MASLD.

The gut microbiome undergoes profound changes during aging, including shifts in the microbial antibiotic resistome: the collective repertoire of antibiotic resistance genes (ARGs). We developed a language model-based ARG explorer (LARGE), which used frozen ESM-2 and FGeneBERT encoders to embed protein sequences and three independent multilayer perceptron classifiers to predict resistance type, mechanism, and gene name. LARGE was trained on 34,008 ARG and 30,309 non-ARG sequences from the NCRD95 and UniProt databases and benchmarked against DeepARG, RGI, PLM-ARG, and ARGNet using F1-scores on multiple independent test sets. We applied LARGE to a longitudinal cohort (GNHS, n = 1078, mean baseline age 64.6 years), and validated key findings in independent cohorts (CHNS, n = 356; ZMSC, n = 1361). Linear mixed-effects models were used to assess age-related ARG trajectories, and logistic regression examined associations with 13 chronic diseases. In benchmark test, LARGE substantially outperformed all four tools, achieving superior F1-scores. In longitudinal cohorts, LARGE revealed declining ARG burdens in dominant resistance drug classes and identified 31 species with significant ARG changes. The ARGs of these 31 species are closely associated with multiple age-related chronic diseases, such as chronic kidney disease and coronary heart disease; a specific chronic kidney disease ARG score was consistently associated with disease risk in both discovery and validation cohorts. The findings highlight the pivotal role of aging in resistome evolution and potentially provide microbiome-targeted interventions to mitigate antibiotic resistance and promote healthy aging.

The genetic architecture of glycemic dynamic metrics derived from continuous-glucose monitoring (CGM) across different populations remains poorly understood. Here, we conducted a trans-ethnic genome-wide association study (GWAS) meta-analysis of 20 CGM-derived glycemic traits, building upon a previously established European-ancestry CGM dataset and extending it through the inclusion of additional cohorts, in up to 9677 individuals originating from 2051 Chinese, 901 Dutch, and 6725 Israelis. Across 20 glycemic traits, we identified 18 genome-wide significant associations, of which 9 met study-wide significance, and three variants were novel. These variants indicated a shared genetic basis for continuous glycemic regulation and exhibited consistent patterns with those of sequential fingerstick glucose tests. Our findings further demonstrated that the identified genetic variants were enriched in pathways related to the nervous system. These findings were further supported by observed associations with brain magnetic resonance imaging (MRI) metrics, high CGM-related gene expression and co-regulation of quantitative trait loci in brain tissues. Additionally, we observed a positive relationship between genetic liability for the coefficient of variation (CV) and total cholesterol and a bi-directional putative causal relationship between hyperglycemia and type 1 diabetes across trans-ethnic populations. Moreover, we established a polygenic risk score (PRS) for additional participants and reported that certain glycemic traits were significantly associated with the risk of diabetes or pre-diabetes. These variants constituting the PRS demonstrated high transferability across general populations and pregnant women. Overall, our study yields unique insights into the high trans-ethnic and generalizable genetic architecture of CGM-derived glycemic profiles, supporting improved characterization of interindividual differences in glycemic dynamics and underscoring the potential for more personalized glucose management.

Environmental exposures have been adversely associated with the risk of diabetes but their role in the remission and progression of prediabetes (impaired glucose tolerance [IGT] and/or impaired fasting glucose [IFG]), especially different phenotypes, is poorly understood. This study aimed to investigate the relationship between environmental exposures and remission or progression of prediabetes phenotypes. Data were derived from the KORA (Cooperative Health Research in the Region of Augsburg) cohort in Southern Germany (2006–2022). Glucose tolerance status was defined according to the 1999/2006 WHO criteria. We included annual values of particulate matter (PM), light at night (LAN), normalised difference vegetation index (NDVI), imperviousness (IMP) and air temperature variation (Tsd). We fitted complementary log–log regression models for associations between IQR changes in exposures and the incidence of prediabetes phenotypes (isolated impaired fasting glucose [iIFG], isolated impaired glucose tolerance [iIGT], or their combination [IFG+IGT]), remission to normal glucose tolerance (NGT) or progression to type 2 diabetes. We also applied Quantile g-computation regression models for joint association analysis. During the follow-up, 370/1618 participants developed prediabetes (124 iIFG, 199 iIGT and 47 IFG+IGT). Among participants with prediabetes, 136/367 (without medication) regressed to NGT and 133/420 progressed to type 2 diabetes. We observed consistent associations of air pollutants and the built environment with iIGT or IFG+IGT. For example, an IQR increase in PM2.5 (aerodynamic diameter ≤2.5 μm) showed an HR of 1.89 (95

The pivotal role of gut fungi (i.e., mycobiome) in host health is increasingly recognized. Diet is a critical determinant factor for both gut fungi and host metabolic health. This study aimed to investigate the associations of plasma n-3 polyunsaturated fatty acids (PUFAs), an important dietary lipid component, with gut mycobiome and explore the relationship of n-3 PUFA-related gut fungi with type 2 diabetes (T2D) and glycemic phenotypes. Here, we identified four fungal genera that were inversely associated with plasma total n-3 PUFA in the discovery cohort. Among these, Debaryomyces, Kodamaea, and Wickerhamomyces were consistently associated with total n-3 PUFA in the metaanalysis of 4 human cohorts (FDR-meta<0.1). We also found that Wickerhamomyces was positively associated with host fasting blood glucose and glycated hemoglobin (FDR<0.05). Moreover, we observed an interaction between n-3 PUFA and Kodamaea on T2D (P-interaction=0.02), which was confirmed in the mice study. In human and mice studies, the inverse associations between n-3 PUFA and glycemic phenotypes were only observed in the Kodamaea-free population. Additionally, the enrichment of specific primary bile acids, namely cholic acid and its conjugated forms, was associated with Kodamaea colonization. Our results indicate that n-3 PUFA is associated with specific gut fungal genera, which may, in turn, affect host glucose homeostasis.

Objective: Inflammation and nutrition are interrelated, and both are related to depression. This study explored the association between the C-reactive protein (CRP)-albumin-lymphocyte (CALLY) index, a novel immunonutrition scoring system, and depression in patients with type 2 diabetes mellitus (T2DM). Methods: We included 3517 patients with T2DM from the National Health and Nutrition Examination Survey 2005-2010 and 2015-2018. The Patient Health Questionnaire-9 was used to evaluate depression. The CALLY index was based on a comprehensive assessment of serum CRP, serum albumin, and the lymphocyte counts from whole blood. Weighted multivariate logistic regression models were used to examine the relationship between the CALLY index and depression. The restricted cubic spline was applied to explore the nonlinear relationship. Results: Compared with the non-depressed group, CALLY index and albumin in the depressed group were significantly reduced, while CRP and lymphocytes were significantly increased (P < 0.05). After adjusting for covariates, only the CALLY index significantly decreased (the highest quartile vs the lowest quartile, odds ratio = 0.58, 95 % confidence interval: 0.38-0.89, P = 0.014). The non-linear association between the CALLY index and depression was not significant (P for nonlinear=0.69). The results of subgroup analysis were basically consistent (P for interaction > 0.05). Conclusion: The CALLY index was significantly negatively correlated with depression in American patients with diabetes and served as a potential marker for early identification.

Prior research has highlighted the significant roles of circulating retinol, retinol-binding protein 4 (RBP4), and apolipoprotein C (ApoC) in metabolic health. This study investigates the joint association of retinol and RBP4 with metabolic syndrome (MetS) and examines the potential mediating role of ApoCs in these relationships. This prospective study included 3,009 and 2,724 participants with baseline serum retinol and RBP4 data, respectively. Over a 9-year follow-up among 2,621 participants, 1,136, 127, 696, and 662 were categorized into MetS-free, recovered, incident MetS, and persistent MetS groups, respectively. Midway through the study, ApoC1-4 levels were measured in 2316 participants. Adjusted odds ratios (95% CIs) for the highest (vs. lowest) tertile of retinol and RBP4 levels were 3.63 (2.69-4.92) and 5.64 (4.05-7.92) for 9-year persistent MetS, respectively. The corresponding hazard ratios (95% CIs) were 1.67 (1.39-2.01) and 1.67(1.38, 2.03) for incident MetS, and 0.65 (0.41-1.03) and 0.44 (0.28, 0.70) for recovered MetS (all P-trends<.05). A synergistic association of retinol and RBP4 with MetS risk was observed for persistent MetS. Higher levels of retinol or RBP4 were associated with increased concentrations of ApoC1-4, which were linked to a greater risk of incident and persistent MetS. A newly developed composite score (ApoCS), derived from ApoC1-4 levels, explained 30.5% and 24.5% of the association between retinol or RBP4 and MetS, with ApoC2 and ApoC3 contributing predominantly to this connection. Our study identified notable positive correlations between serum retinol and RBP4 levels and MetS progression, explained by increases in circulating ApoC2 and ApoC3 within a Chinese cohort.

Inflammatory bowel disease (IBD) arises from genetic-environmental interactions. Adenosine deaminases acting on RNA 1 (ADAR), an RNA-editing enzyme converting adenosine (A) to inosine (I), is essential for tissue homeostasis. Here we report that intestinal ADAR deficiency contributes to IBD pathogenesis in humans with reduced ADAR expression in patient intestinal crypts. Genetic or pharmacological inhibition of ADAR in mice causes spontaneous ileitis and colitis. Organoid studies show that ADAR loss leads to double-strand RNA (dsRNA) and endogenous retroviruses (ERVs) accumulation, disrupting intestinal homeostasis via melanoma differentiation-associated protein 5 (MDA5)-mediated dsRNA sensing and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling. Editome analyses identify Mda5 as an ADAR target, and edited Mda5 exhibits impaired dsRNA sensing. The human ADAR p.N173S mutation is a loss-of-function variant that fails to rescue IBD in intestinal Adar deficient mice, whereas JAK1/2 inhibitor Ruxolitinib attenuates IBD. We conclude that the ADAR-dsRNA/ERVs-MDA5-JAK/STAT axis is a potential therapeutic target for IBD.

This study aimed to investigate the prospective association of dairy biomarkers of odd-chain saturated fatty acids (OCFA) with incident carotid artery plaque (CAP) and to explore the potential role of gut microbiota and related metabolites in the above associations. In the Guangzhou Nutrition and Health Study (GNHS, n = 1211; baseline mean age: 58.7 ± 6.1 years), we investigated the associations of baseline plasma phospholipid OCFAs with CAP incidence and gut microbiota (16S rRNA sequencing) over a median follow-up period of 6.2 years. Westlake Precision Birth Cohort was used to evaluate the potential associations between OCFA and the identified gut microbiota features in a younger population. Associations of OCFAs with CAP, gut microbial alpha diversity, specific genera, and related metabolites were examined using Cox proportional hazards models or linear regression models, with adjustments of potential confounders. The total OCFA was inversely associated with the incidence of CAP in the GNHS, with a hazard ratio of 0.63 (quartile 4 versus 1: 95

BACKGROUND:Obese individuals exhibit considerable heterogeneity in developing cardiovascular diseases, yet the underlying molecular mechanisms remain unclear. We aimed to investigate the prospective associations between obesity phenotypes, serum proteomics, and carotid atherosclerosis (CAS) incidence. METHODS:This cohort study included 3162 participants from the Guangzhou Nutrition and Health Study, with 413 proteins profiled from 6803 serum samples collected at three time-points. Obesity phenotypes included metabolically healthy non-obesity (MHNO) and metabolically healthy/unhealthy obesity (MHO/MUO). FINDINGS:We identified 11 proteins influenced by MUO (vs. MHO) over time, with their combined score positively associated with incident CAS (HR: 1.16; 95% CI: 1.01-1.34). Additionally, 8 proteins were prospectively associated with MHO-to-MUO transition, which increased the performance of traditional risk factors in predicting this transition (P < 0.001). Among the 8 proteins, bidirectional mediation effects were observed between pigment epithelium-derived factor (PEDF) (36.8%; P = 0.025) and the MHO-to-MUO transition (20.5%; P = 0.010) on CAS incidence. The PEDF genetic risk score was positively associated with MHO-to-MUO transition (OR: 1.20; 95% CI: 1.00-1.43). Our main findings were validated in both the internal and external validation cohorts. INTERPRETATION:This population-scale proteomics study broadens our understanding of the mechanisms underlying obesity heterogeneity and CAS, providing potential targets for the prevention of CAS. FUNDING:This study was supported by the National Natural Science Foundation of China, the Key Research and Development Program of Guangzhou, "Pioneer" and "Leading goose" R&D Program of Zhejiang, and the 5010 Program for Clinical Researches of the Sun Yat-sen University.

Objective: This study investigated the association of circulating levels of 25-hydroxyvitamin D (25[OH]D) with the risk of metabolic syndrome (MetS) and its components in adults. Methods: This nationwide cohort involved 23,810 Chinese adults attending annual health evaluations. Serum 25(OH)D levels, MetS status, and covariates were determined at each examination. Among them, 8146, 3310, and 1971 completed two, three, and more than three evaluations, respectively. A hybrid mixed-effects and Cox regression model was employed to determine the cross-sectional and longitudinal relationships. Results: The odds ratios (ORs) and 95% confidence intervals (CIs) of MetS were significantly lower in individuals within quartile 4 (vs. 1) of serum 25(OH)D for both between-individual (0.43 [0.35, 0.52]) and within-individual comparisons (0.60 [0.50, 0.73]), respectively (all p-trends < 0.001). Among the MetS components, the corresponding ORs (95% CI) in between- and within-individual comparisons were 0.40 (0.29, 0.54) and 0.26 (0.19, 0.36) for abdominal obesity, 0.49 (0.41, 0.58) and 0.78 (0.66, 0.93) for high triglycerides, 0.70 (0.59, 0.82) and 0.75 (0.64, 0.87) for hypertriglyceridemia, 0.48 (0.39, 0.59) and 0.87 (0.71, 1.07) for low HDL cholesterol, and 0.92 (0.76, 1.12) and 0.49 (0.41, 0.59) for hypertension, respectively. Decreased hazard ratios (95% CIs) in quartile 4 (vs. 1) of 25(OH)D were found for MetS (0.80 [0.65, 1.00]), high triglycerides (0.76 [0.62, 0.92]), abdominal obesity (0.77 [0.63, 0.96]), and low HDL cholesterol (0.64 [0.50, 0.81]). Conclusions: Decreased concentrations of serum 25(OH)D correlate significantly to a heightened MetS risk and specific components. Our findings underscore the potential preventive function of circulating vitamin D concerning metabolic disorders.

Mapping gut microbial structural variants (SVs) during human aging may provide fundamental knowledge and mechanistic understanding of the gut microbiome’s relationship with healthy aging. We characterize gut microbial SVs from 3,230 Chinese participants, identifying key SVs associated with aging, healthy aging, and age-related chronic diseases. Our findings reveal a pattern of copy number loss in aging-related SVs, with 35 core SVs consistently detected. Additionally, eight SVs distinguish healthy from unhealthy aging, regardless of age. Notably, a 3-kbp deletion SV of Bifidobacterium pseudocatenulatum, encoding plant polysaccharide degradation, is regulated by plant-based diet and contributes to healthy aging through bile acid metabolism. Our analysis also connects SVs to age-related diseases, such as chronic kidney disease, via genes in the methionine-homocysteine pathway. This study deepens our understanding of the gut microbiome’s role in aging and could inform future efforts to enhance lifespan and healthspan.

(1) Background: With autistic children’s high pervasiveness of eating problems and inappropriate feeding behaviors by their caregivers, this study wanted to inspect the connection between caregivers’ pressure to eat and food neophobia in these children. (2) Methods: Cross-sectional overview of 160 guardians of kids aged 2 to 7 years. After one-on-one questioning by the researcher, the collected information on the socio-demographic characteristics of the children with autism, caregiver feeding behavior, and new food neophobia (FN) scores was entered into the Questionnaire Star system. (3) Results: The mean FN score was 25.56 ± 6.46. The caregiver’s pressure to eat positively related to children’s FN (β = 0.164 95% CI, 0.078, 2.163). In these children, we found a negative correlation between FN score and the frequency of vegetable intake (p ≤ 0.001), fruit intake (p ≤ 0.05), aquatic product intake (p ≤ 0.05), and dietary diversity score (p ≤ 0.01), and positively correlated with the frequency of snack intake (p ≤ 0.05). (4) Conclusions: Caregiver pressure to eat was positively associated with high levels of FN in Chinese kids with ASD, which in turn negatively impacted dietary quality. To improve eating habits, caregivers should reconsider their feeding strategies and avoid using forceful methods to ease food neophobia in these children.