A systematic exposure‐wide framework leveraging machine learning to identify multidomain exposure factors and their joint influence on cognitive function: Evidence from a neurological cohort

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(2)

Published: Feb. 1, 2025

Abstract INTRODUCTION Cognitive decline has become a growing public concern, yet large‐scale exposure data identifying the contributing factors remain limited. METHODS We conducted an exposure‐wide association study involving 1142 participants and 207 exposures, using machine learning to assess relative contribution joint effects of key factors. Cluster analysis intervention simulation trials helped identify high‐risk subpopulations potential benefits targeted interventions. RESULTS In adjusted mixed models, socioeconomic status domain emerged as strongest predictor longitudinal global cognitive score ( β = 2.91, p < 0.0001, q 0.0001), while dietary also played important role in memory function. The cluster found that “unfavorable lifestyle” dominated phenotype was associated with poorest outcomes. Simulation indicated scores could improve by shifting individuals from unfavorable favorable phenotypes. DISCUSSION health requires multidomain interventions, particularly fields, necessitates collaboration between government individuals. Highlights design, which assesses broad range is used novel variables understand their contributions findings indicate most significant contributor function, diet plays largest Increasing proportion phenotypes through interventions can significantly enhance health.

Language: Английский

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Abnormal epigenetic modification of lysosome and lipid regulating genes in Alzheimer’s disease

Journal of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: unknown

Published: March 28, 2025

Background Abnormal lipid metabolism has been identified as a potential pathogenic mechanism of Alzheimer's disease (AD), which might be epigenetically regulated. Lysosomes are critical organelles for metabolism. However, the epigenetic modifications lysosome and regulating genes remain unclear in AD patients. Objective Explore role abnormal modifications, especially methylation metabolism-related AD. Methods Methylation beadchip MALDI-TOF mass spectrometry were used to detect genome-wide DNA levels validate key gene methylation, respectively. Clinical data collected from all participants. Associations between clinical biochemical characteristics altered patients analyzed, risk factor model was established. Results 41 differentially methylated positions (DMPs) corresponding 33 patients, with 18 hypermethylated 23 hypomethylated positions. Significant alterations observed ( CTNNB1, DGKQ, SLC27A1 ) lysosomal transmembrane TMEM175 ). analysis revealed that TP, ALB, IB, ADA, ALP, HCY, GLU, TC, BUN, HDL-C, LDL-C, APOA1 significantly higher whereas A/G DB lower. hypermethylation further verified found correlate APOA1, HCY. The AUC model, integrated markers reached 0.9519 p < 0.0001). Conclusions regulation dyshomeostasis high-risk factors processes pathogenesis.

Language: Английский

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A column-switching two-dimensional liquid chromatography - high resolution/triple quadrupole dual mass spectrometry system for simultaneously untargeted metabolome and targeted exposome analyses

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

Metabolome-exposome association studies (mEWAS) demands high-coverage and high-sensitivity analytical methods for metabolites exposures with diverse chemical properties concentrations. Here, we present an integrated column-switching two-dimensional liquid chromatography (2DLC) - high resolution/triple quadrupole dual mass spectrometry (MS) method, achieving simultaneously untargeted metabolome targeted exposome analyses including 598 in a single run. Polar non-polar compounds log P ranging from -8 to 15 were separated without unretained the dead time. Benchmarked against biological matrices, analyte coverage increased by 35-104% over one-dimensional LC method. Highly sensitive limits of detection 0.001-1 μg/mL >90% ng/mL obtained, matching concentration difference between human blood. The method was demonstrated patients chronic diseases, showing feasibility establishing mEWAS integrating 2DLC-dual MS techniques.

Language: Английский

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Detection and screening of organophosphate esters in infant formula from Shanghai, China: distribution characteristics and risk evaluation

Food Additives & Contaminants Part A, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 14

Published: Feb. 6, 2025

Organophosphate esters (OPEs) have raised great concerns in recent years. However, information regarding their occurrence infant formula remains limited. Thus, thirty-two OPEs were measured sold Shanghai, China 2023. The results showed that OPE was widespread. median concentrations of organophosphate diesters, triesters, and total 2.28, 5.20, 8.63 ng/g, respectively. Tris(2-chloroisopropyl) phosphate (TCPP) the highest concentration (1.95 ng/g), followed by triethyl phosphate, bis(1-chloro-2-propyl) (BCPP), tri-isobutyl triphenyl (0.532-0.581 ng/g). dominant chloro-OPEs (TCPP BCPP) regional-specific. Compared to corresponding diester often lower, except for bis(2-butoxyethyl) tributoxyethyl phosphate. Additionally, five novel with phenyl groups identified, showing high detection frequencies comparable TCPP. Raw materials food processing methods might affect individual OPEs. estimated daily intakes (EDIs) ranged from 62.3 355 ng/kg bw/day. EDI occurred infants 0-6 months age but posed no obvious health risk toddlers. Further studies are still needed evaluate possible implications arising metabolites, as well potentially synergistic effects.

Language: Английский

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A Bigger Big Picture: Insights on Environmental Chemicals and Dyslipidemia through Combined “Omic” Analyses

Environmental Health Perspectives, Journal Year: 2024, Volume and Issue: 132(10)

Published: Oct. 1, 2024

Exposures to chemicals, including phthalates, triphenyl phosphate, and dibutyl have been associated with increased levels of lipid markers, such as elevated low-density lipoprotein.

Language: Английский

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