Evidence map›Paper›PMID 42701175›Full record

ArticleMolecular diversity2026

PFOS exposure is linked to immune-metabolic disruption in MASLD: integrated population, computational, and experimental evidence.

Xulei Zuo, Shiyi Tan, Xiaoyu Hou, Cong Zhang, Yuxi Zhang, Juan Zhang

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In one paragraph

Article in Molecular diversity, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Xulei ZuoKey Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, 210096, China.
Shiyi TanKey Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, 210096, China.
Xiaoyu HouKey Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, 210096, China.
Cong ZhangKey Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, 210096, China.
Yuxi ZhangKey Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, 210096, China.
Juan ZhangKey Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, 210096, China. 101011288@seu.edu.cn.

Funding

SEU Innovation Capability Enhancement Plan for Doctoral Students CXJH_SEU 25218
6 · The paper itself

Abstract

Perfluorooctane sulfonate (PFOS), a persistent environmental pollutant, has been implicated in metabolic dysfunction-associated steatotic liver disease (MASLD), yet the underlying molecular mechanisms remain incompletely characterized. We constructed an integrated analytical framework combining population epidemiology, network toxicology, machine learning, transcriptomic analysis, single-cell mapping, molecular docking, and experimental validation. NHANES data (n = 1,834) were analyzed to assess the association between serum PFOS concentrations and FLI-defined MASLD. Machine-learning analyses using LASSO and SVM-RFE prioritized candidate genes from 874 overlapping PFOS-MASLD-associated genes. Single-cell RNA sequencing resolved cell-type-specific expression patterns, while molecular docking evaluated potential PFOS-protein interactions. A 12-week murine exposure model provided in vivo validation. Epidemiological analysis identified a nonlinear association between serum PFOS and MASLD odds (p < 0.001), with effects evident at background exposure levels (7.76 ng/mL). Convergent machine-learning analyses prioritized five candidate genes: CYP7A1, GRIA3, PHLDA1, SOCS2, and WNT5A. An exploratory five-gene model yielded an apparent AUC of 0.998 (95% CI 0.993-0.998) within the analyzed transcriptomic dataset. Single-cell analysis revealed cell-type specificity, with CYP7A1/PHLDA1 enriched in hepatocytes, SOCS2/WNT5A in hepatic stellate cells, and GRIA3 in T cells. Molecular docking predicted potential PFOS-protein interactions with the five candidate targets, with docking scores ranging from -6.3 to -9.3 kcal/mol. RT-qPCR analysis of PFOS-treated mouse liver showed transcriptional changes consistent with the computational predictions. PFOS-treated mice exhibited hepatic lipid accumulation, elevated liver injury markers, and lipid dysregulation. Together, these findings support an association between PFOS exposure and MASLD-related hepatic dysfunction and propose a hypothesis-generating immune-metabolic framework requiring prospective and direct mechanistic validation.

Indexed as

Machine learningMetabolic dysfunction-associated steatotic liver diseaseNetwork toxicologyPerfluorooctane sulfonateSingle-cell transcriptomics

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.