Integrated multi-omics analysis of zinc-finger proteins uncovers roles in RNA regulation.

RNA interactome studies have revealed that hundreds of zinc-finger proteins (ZFPs) are candidate RNA-binding proteins (RBPs), yet their RNA substrates and functional significance remain largely uncharacterized. Here, we present a systematic multi-omics analysis of the DNA- and RNA-binding targets and regulatory roles of more than 100 ZFPs representing 37 zinc-finger families. We show that multiple ZFPs are previously unknown regulators of RNA splicing, alternative polyadenylation, stability, or translation. The examined ZFPs show widespread sequence-specific RNA binding and preferentially bind proximal to transcription start sites. Additionally, several ZFPs associate with their targets at both the DNA and RNA levels. We highlight ZNF277, a C2H2 ZFP that binds thousands of RNA targets and acts as a multi-functional RBP. We also show that ZNF473 is a DNA/RNA-associated protein that regulates the expression and splicing of cell cycle genes. Our results reveal diverse roles for ZFPs in transcriptional and post-transcriptional gene regulation.

TRIBE-STAMP reveals new insights into the functions of RNA binding proteins.

RNA binding proteins (RBPs) are important players in RNA metabolism and gene regulation. In this issue of Genes & Development, Flamand and colleagues (pp. 1002-1015) developed a new method (TRIBE-STAMP) that detects binding events by two distinct RBPs on single mRNA molecules, which they first applied to the YTHDF family of N 6-methyladenosine (m6A) reader proteins. The investigators show that these RBPs largely share a common pool of bound transcripts and that an individual mRNA may be bound by multiple YTHDF proteins throughout its lifetime. This single-molecule technique is an exciting new method to study potential synergy and/or antagonism between different RBPs.

Single-molecule identification of the target RNAs of different RNA binding proteins simultaneously in cells.

RNA-binding proteins (RBPs) regulate nearly every aspect of mRNA processing and are important regulators of gene expression in cells. However, current methods for transcriptome-wide identification of RBP targets are limited, since they examine only a single RBP at a time and do not provide information on the individual RNA molecules that are bound by a given RBP. Here, we overcome these limitations by developing TRIBE-STAMP, an approach for single-molecule detection of the target RNAs of two RNA binding proteins simultaneously in cells. We applied TRIBE-STAMP to the cytoplasmic m6A reader proteins YTHDF1, YTHDF2, and YTHDF3 and discovered that individual mRNA molecules can be bound by more than one YTHDF protein throughout their lifetime, providing new insights into the function of YTHDF proteins in cells. TRIBE-STAMP is a highly versatile approach that enables single-molecule analysis of the targets of RBP pairs simultaneously in the same cells.

Inhibition of YTHDF2 triggers proteotoxic cell death in MYC-driven breast cancer.

RNA-binding proteins (RBPs) are critical regulators of post-transcriptional gene expression, and aberrant RBP-RNA interactions can promote cancer progression. Here, we interrogate the function of RBPs in cancer using pooled CRISPR-Cas9 screening and identify 57 RBP candidates with distinct roles in supporting MYC-driven oncogenic pathways. We find that disrupting YTHDF2-dependent mRNA degradation triggers apoptosis in triple-negative breast cancer (TNBC) cells and tumors. eCLIP and m6A sequencing reveal that YTHDF2 interacts with mRNAs encoding proteins in the MAPK pathway that, when stabilized, induce epithelial-to-mesenchymal transition and increase global translation rates. scRibo-STAMP profiling of translating mRNAs reveals unique alterations in the translatome of single cells within YTHDF2-depleted solid tumors, which selectively contribute to endoplasmic reticulum stress-induced apoptosis in TNBC cells. Thus, our work highlights the therapeutic potential of RBPs by uncovering a critical role for YTHDF2 in counteracting the global increase of mRNA synthesis in MYC-driven breast cancers.

Laser-driven noncontact bubble transfer printing via a hydrogel composite stamp.

Transfer printing that enables heterogeneous integration of materials into spatially organized, functional arrangements is essential for developing unconventional electronic systems. Here, we report a laser-driven noncontact bubble transfer printing via a hydrogel composite stamp, which features a circular reservoir filled with hydrogel inside a stamp body and encapsulated by a laser absorption layer and an adhesion layer. This composite structure of stamp provides a reversible thermal controlled adhesion in a rapid manner through the liquid-gas phase transition of water in the hydrogel. The ultrasoft nature of hydrogel minimizes the influence of preload on the pick-up performance, which offers a strong interfacial adhesion under a small preload for a reliable damage-free pick-up. The strong light-matter interaction at the interface induces a liquid-gas phase transition to form a bulge on the stamp surface, which eliminates the interfacial adhesion for a successful noncontact printing. Demonstrations of noncontact transfer printing of microscale Si platelets onto various challenging nonadhesive surfaces (e.g., glass, key, wrench, steel sphere, dry petal, droplet) in two-dimensional or three-dimensional layouts illustrate the unusual capabilities for deterministic assembly to develop unconventional electronic systems such as flexible inorganic electronics, curved electronics, and micro-LED display.

Volatile-compound fingerprinting and discrimination of positional isomers in stamp-pad ink tracing using HS-GC-IMS combined with multivariate statistical analysis.

The rising crime rate associated with document forgery has a significant impact on public safety and social stability. In document fraud cases, determining the origin of a particular stamp-pad ink is the most important objective. In this study, a comprehensive analysis of the volatile compounds in quick-drying stamp-pad inks from six commonly used brands were performed for the first time, utilizing a combination of headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) and multivariate statistical analysis methods. Visual and comparative analysis of the differential volatile components among different stamp-pad ink samples was conducted using fingerprints and volcano plots. A total of 127 volatile compounds were accurately identified, with ketones, esters, alcohols, and aldehydes being the most abundant compounds in the stamp-pad inks. Hierarchical clustering analysis (HCA), including dendrograms and clustering heatmaps, was utilized to explore the correlations between these compounds and the samples. Additionally, the precise identification of positional isomers and functional group isomers of aliphatic compounds was achieved. To achieve accurate discrimination of various stamp-pad ink samples, a multivariate statistical analysis method was utilized to establish a classification model for them. Based on the results obtained from HS-GC-IMS, effective discrimination among different brands of stamp-pad ink samples was achieved through principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). The model exhibited excellent performance, with the fit index of dependent variables (R2Y) and the predictive index of the model (Q2) values of 0.99 and 0.984, respectively. These results provided significant theoretical evidence for the application of HS-GC-IMS as an efficient technique in the analysis of volatile compounds, identification of positional isomers and functional group isomers, as well as tracing the origin of stamp-pad ink and analyzing the formation time of documents.

The malnutrition screening tool STRONGKIDS performed better than other screening tools for children hospitalised in Egypt.

AIM: To compare the accuracy of three different screening tools, namely, the Paediatric Yorkhill Malnutrition Score (PYMS), Screening Tool for the Assessment of Malnutrition in Paediatrics (STAMP), and Screening Tool for Risk on Nutritional Status and Growth (STRONGKIDS), in assessing malnutrition risk in hospitalised children. METHODS: A cross-sectional study was conducted on 300 children aged 6 months to 15 years at Alexandria University Children's Hospital, Egypt. The sensitivity and specificity of each tool were calculated to detect acute and chronic malnutrition, and an agreement test was conducted between the nutritional screening tools. The patients were classified into different nutritional risk groups, and their classification was compared with anthropometric measures and clinical variables, such as the length of hospital stay (LOS). RESULTS: The prevalence of stunting and wasting on admission was found to be 3% and 6.6%, respectively. Children categorised as high-risk on admission had a longer LOS than those at low risk. The agreement test between the STAMP score and STRONGKIDS score on admission showed the most significant agreement, and STRONGKIDS had the best accuracy in detecting acute and chronic malnutrition. CONCLUSION: The comparison of the three screening tools revealed that STRONGKIDS exhibited the best accuracy in detecting acute and chronic malnutrition.

Compressive modulus, translucency, and irradiance transmittance of clear PVS materials used for resin injection molding technique.

OBJECTIVES: To evaluate the compressive modulus, translucency, and light curing irradiance transmittance of four clear polyvinyl siloxane (PVS) materials used for the injection molding technique at varying thicknesses, and to assess the correlation between color parameters and irradiance transmittance. MATERIALS AND METHODS: Four clear PVS materials (Exaclear, Clear Bite Matrix, Affinity Crystal, and Memosil 2) were used in this study. Compressive modulus was measured by compressing cylindrical PVS specimens (n = 9; d = 10 mm; t = 6 mm) up to 30% strain using a universal testing machine. For the translucency analysis and irradiance transmittance, specimens (n = 5) were fabricated with five different thicknesses (d = 12 mm and t = 2, 4, 6, 8 and 10 mm). The L*, a, *b* values of specimens were obtained using a CIELab spectrophotometer (CMD-700, Konica Minolta) with calibrated white and black tiles; the translucency parameter was calculated. The same specimens were placed onto a spectrophotometer (MARC Light Collector) to measure irradiance transmitted through the specimens from a light curing unit (Valo Corded, Ultradent). Data were analyzed using analysis of variance (ANOVA) with Tukey post hoc test and the correlation between translucency and irradiance transmittance of materials for each thickness was evaluated using Pearson's correlation. RESULTS: Compressive modulus differences in PVS materials were significant (one-way ANOVA: df = 3, F = 76.27, p < 0.001); Affinity and Memosil 2 were highest with no significant difference between them (Tukey: t = -1.62; p = 0.382). Clear Bite was higher than Exaclear (Tukey: t = -3.70; p = 0.004). Exaclear was lowest. Translucency decreased with thickness (Two-way ANOVA: df = 3, F = 586.53, p < 0.001; thickness: df = 4, F = 1389.34, p < 0.001). Exaclear was most translucent at all thicknesses. L*, a*, b* values varied by material and thickness (L*: df = 3, F = 1213.32, p < 0.001; a*: df = 3, F = 10766.8, p < 0.001; b*: df = 3, F = 3260.42, p < 0.001). Memosil 2 had lowest b* values. Irradiance transmittance was affected by material and thickness (Two-way ANOVA: df = 4, F = 2388.86, p < 0.001). Exaclear had highest irradiance transmission, surpassing control at >6 mm. Violet/blue irradiance ratio decreased with thickness; Exaclear maintained a constant ratio, indicating preserved violet irradiance. There was a strong positive correlation between translucency and light irradiance (Pearson's r = 0.97, R2 = 0.86-0.96). Radiant exposure analysis suggests adjusting the curing time based on PVS thickness for optimal exposure (10 J/cm2) is achievable within 13-14 s for <2 mm and 21-30 s for 8-10 mm with Clear Bite, Affinity, and Memosil 2; whereas Exaclear requires less time. CONCLUSIONS: Compressive modulus in clear PVS materials varied by type; Affinity and Memosil 2 demonstrate higher modulus, offering more stability of the clear mold. Translucency and irradiance transmission through clear PVS materials decreased as their thickness increased, yet Exaclear exceled in maintaining high translucency and superior light transmission capabilities. Additionally, there is a strong positive linear correlation between translucency and light irradiance transmittance, offering a method to adjust curing times effectively based on material translucency. CLINICAL SIGNIFICANCE: The light curing time to adequately polymerize composite through clear impression material may need to be increased, particularly with thicker matrices or less translucent materials.

Testing the reliability of accident analysis methods: a comparison of AcciMap, STAMP-CAST and AcciNet.

Accident analysis methods are used to model the multifactorial cause of adverse incidents. Methods such as AcciMap, STAMP-CAST and recently AcciNet, are systemic approaches that support the identification of safety interventions across sociotechnical system levels. Despite their growing popularity, little is known about how reliable systems-based methods are when used to describe, model and classify contributory factors and relationships. Here, we conducted an intra-rater and inter-rater reliability assessment of AcciMap, STAMP-CAST and AcciNet using the Signal Detection Theory (SDT) paradigm. A total of 180 hours' worth of analyses across 360 comparisons were performed by 30 expert analysts. Findings revealed that all three methods produced a weak to moderate positive correlation coefficient, however the inter-rater reliability of STAMP-CAST was significantly higher compared to AcciMap and AcciNet. No statistically significant or practically meaningful differences were found between methods in the overall intra-rater reliability analyses. Implications and future research directions are discussed.

Practitioners who undertake accident analysis within their organisations should consider the use of STAMP-CAST due to the significantly higher inter-rater reliability findings obtained in this study compared to AcciMap and AcciNet, particularly if they tend to work alone and/or part of relatively small teams.

Managing the risks associated with technological disruption in the road transport system: a control structure modelling approach.

Road transport is experiencing disruptive change from new first-of-a-kind technologies. While such technologies offer safety and operational benefits, they also pose new risks. It is critical to proactively identify risks during the design, development and testing of new technologies. The Systems Theoretic Accident Model and Processes (STAMP) method analyses the dynamic structure in place to manage safety risks. This study applied STAMP to develop a control structure model for emerging technologies in the Australian road transport system and identified control gaps. The control structure shows the actors responsible for managing risks associated with first-of-a-kind technologies and the existing control and feedback mechanisms. Gaps identified related to controls (e.g. legislation) and feedback mechanisms (e.g. monitoring for behavioural adaptation). The study provides an example of how STAMP can be used to identify control structure gaps requiring attention to support the safe introduction of new technologies.

This paper considers emerging risks associated with new technologies in the road transport system. It demonstrates a novel approach using STAMP to identify gaps in control and feedback mechanisms within the existing control structure which should be addressed to mitigate risk.

Effect of asciminib and vitamin K2 on Abelson tyrosine-kinase-inhibitor-resistant chronic myelogenous leukemia cells.

BACKGROUND: Abelson (ABL) tyrosine kinase inhibitors (TKIs) are effective against chronic myeloid leukemia (CML); however, many patients develop resistance during ABL TKI therapy. Vitamin K2 (VK2) is a crucial fat-soluble vitamin used to activate hepatic coagulation factors and treat osteoporosis. Although VK2 has demonstrated impressive anticancer activity in various cancer cell lines, it is not known whether VK2 enhances the effects of asciminib, which specifically targets the ABL myristoyl pocket (STAMP) inhibitor. METHOD: In this work, we investigated whether VK2 contributed to the development of CML cell lines. We also investigated the efficacy of asciminib and VK2 by using K562, ponatinib-resistant K562 (K562 PR), Ba/F3 BCR-ABL, and T315I point mutant Ba/F3 (Ba/F3 T315I) cells. RESULTS: Based on data from the Gene Expression Omnibus (GEO) database, gamma-glutamyl carboxylase (GGCX) and vitamin K epoxide reductase complex subunit 1 (VKORC1) were elevated in imatinib-resistant patients (GSE130404). UBIA Prenyltransferase Domain Containing 1 (UBIAD1) was decreased, and K562 PR cells were resistant to ponatinib. In contrast, asciminib inhibited CML cells and ponatinib resistance in a dose-dependent manner. CML cells were suppressed by VK2. Caspase 3/7 activity was also elevated, as was cellular cytotoxicity. Asciminib plus VK2 therapy induced a significantly higher level of cytotoxicity than use of each drug alone. Asciminib and VK2 therapy altered the mitochondrial membrane potential. CONCLUSIONS: Asciminib and VK2 are suggested as a novel treatment for ABL-TKI-resistant cells since they increase treatment efficacy. Additionally, this treatment option has intriguing clinical relevance for patients who are resistant to ABL TKIs.

Improved Performance of All-Inorganic Perovskite Light-emitting Diodes via Nanostructured Stamp Imprinting.

Halide perovskites are emerging emitters with excellent optoelectronic properties. Contrary to the large grain fabrication goal in perovskite solar cells, perovskite light-emitting diodes (PeLEDs) based on small grain enable efficient radiative recombination because of relatively higher charge carrier densities due to spatial confinement. However, achieving small-sized grain growth with superior crystal quality and film morphology remains a challenge. In this work, we demonstrated a nanostructured stamp thermal imprinting strategy to boost the surface coverage and improve the crystalline quality of CsPbBr3 film, particularly confine the grain size, leading to the improvement of luminance and efficiency of PeLEDs. We improved the thermal imprinting process utilizing the nanostructured stamp to selectively manipulate the nucleation and growth in the nanoscale region and acquire small-sized grain accompanied by improved crystal quality and surface morphology of the film. By optimizing the imprinting pressure and the period of the nanostructures, appropriate grain size, high surface coverage, small surface roughness and improved crystallization could be achieved synchronously. Finally, the maximum luminance and efficiency of PeLEDs achieved by nanostructured stamp imprinting with a period of 320 nm are 67600 cd/m2 and 16.36 cd/A, respectively. This corresponds to improvements of 123 % in luminance and 100 % in efficiency, compared to that of PeLEDs without the imprinting.

Enhancing Evanescent Wave Coupling of Near-Surface Waveguides with Plasmonic Nanoparticles.

Evanescent field excitation is a powerful means to achieve a high surface-to-bulk signal ratio for bioimaging and sensing applications. However, standard evanescent wave techniques such as TIRF and SNOM require complex microscopy setups. Additionally, the precise positioning of the source relative to the analytes of interest is required, as the evanescent wave is critically distance-dependent. In this work, we present a detailed investigation of evanescent field excitation of near-surface waveguides written using femtosecond laser in glass. We studied the waveguide-to-surface distance and refractive index change to attain a high coupling efficiency between evanescent waves and organic fluorophores. First, our study demonstrated a reduction in sensing efficiency for waveguides written at their minimum distance to the surface without ablation as the refractive index contrast of the waveguide increased. While this result was anticipated, it had not been previously demonstrated in the literature. Moreover, we found that fluorescence excitation by waveguides can be enhanced using plasmonic silver nanoparticles. The nanoparticles were also organized in linear assemblies, perpendicular to the waveguide, with a wrinkled PDMS stamp technique, which resulted in an excitation enhancement of over 20 times compared to the setup without nanoparticles.

Proteomic Analyses Discern the Developmental Inclusion of Albumin in Pig Enamel: A New Model for Human Enamel Hypomineralization.

Excess albumin in enamel is a characteristic of the prevalent developmental dental defect known as chalky teeth or molar hypomineralization (MH). This study uses proteomic analyses of pig teeth to discern between developmental origin and post-eruptive contamination and to assess the similarity to hypomineralized human enamel. Here, the objective is to address the urgent need for an animal model to uncover the etiology of MH and to improve treatment. Porcine enamel is chalky and soft at eruption; yet, it hardens quickly to form a hard surface and then resembles human teeth with demarcated enamel opacities. Proteomic analyses of enamel from erupted teeth, serum, and saliva from pigs aged 4 (n = 3) and 8 weeks (n = 2) and human (n = 4) molars with demarcated enamel opacities show alpha-fetoprotein (AFP). AFP expression is limited to pre- and perinatal development and its presence in enamel indicates pre- or perinatal inclusion. In contrast, albumin is expressed after birth, indicating postnatal inclusion into enamel. Peptides were extracted from enamel and analyzed by nano-liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS) after tryptic digestion. The mean total protein number was 337 in the enamel of all teeth with 13 different unique tryptic peptides of porcine AFP in all enamel samples but none in saliva samples. Similarities in the composition, micro-hardness, and microstructure underscore the usefulness of the porcine model to uncover the MH etiology, cellular mechanisms of albumin inclusion, and treatment for demarcated opacities.

The hybrid systems method integrating STAMP and HFACS for the causal analysis of the road traffic accident.

The role of traditional analysis methods in improving complex socio-technical system safety has reached a ceiling, and thus systems theory has been utilised to support the investigations and countermeasures for road traffic accidents. As two widely applied systems accident analysis models, STAMP (systems theoretic accident model and process) and HFACS (human factors analysis and classification system) have their own advantages in accident analysis and safety improvement. Therefore, this study develops a new hybrid systems method integrating STAMP and HFACS for road traffic accident (SH-RTA), which can adopt HFACS to enhance the identification and analysis ability of STAMP for human factors and employ control concepts and elements of STAMP to cement the characteristic of HFACS. To illustrate the applicability of the hybrid method, a case study of '9·22' major road traffic accident in China is thoroughly analysed. Finally, preventive countermeasures and suggestions are presented.Practitioner Summary: This paper proposes a new hybrid systems method integrating STAMP and HFACS for road traffic accident. The new method reveals dysfunctional interactions within the parallel level and across levels, and identifies additional human and organisational factors. The recommendations for preventing road traffic accident are provided from higher levels of system.

A stakeholder analysis of the road transport system in Tanzania using a STAMP control structure.

The way the road transport system is developed in a country affects safety. This study aims to identify the roles and relationships of road transport stakeholders and to explore the understanding of control and feedback mechanisms and associated gaps influencing road safety. A System-Theoretic Accident Model and Processes (STAMP) model was applied to document and interview data (n = 30). Participants emphasised the hindrance of overlapping mandates among stakeholders on the road transport system's operations and underlined the roles of coalitions for road safety as system enablers. Further, the withdrawal of some controls by international agencies can increase system vulnerability. Most importantly, critical control and feedback gaps were shown to increase risks for safety within the road transport system. The findings underscore the complexity of the road transport system and add to the discussion on a system's approach to road safety.Practitioner summary: Using a STAMP methodology, we extensively studied the road transport system in Tanzania. Road transport stakeholders were identified through the review of documents, interviews were conducted, and the main findings were discussed. Control and feedback mechanisms and associated gaps were critically presented, recommendations were proposed, and policy implications were suggested.

[Next treatment for TKI-resistant CML].

Tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis of chronic myeloid leukemia (CML) in the chronic phase. However, only 50-60% of patients stay on the same TKI for 5 years, and the long-term progression-free survival rate is significantly reduced if an early molecular response is not achieved. Possible mechanisms of therapeutic resistance against BCR::ABL1 dependent clones include point mutations in the ABL1 kinase domain, BCR::ABL1 splicing variants, BCR::ABL1 overexpression, and altered pharmacokinetics by the ABC transporter. Ponatinib, the most potent inhibitor among TKIs, and the STAMP inhibitor asciminib are important drugs for overcoming BCR::ABL1-dependent resistance.

[A technique of using an individual occlusal stamp]. / Tekhnika primeneniya individual'nogo okklyuzionnogo shtampa.

THE AIM OF THE STUDY: Was to describe a step-by-step protocol for the use of an individually manufactured silicone stamp for the restoration of class II carious cavities. Restoration of a tooth using the «silicone key¼ method in carious defects on approximal surfaces has a number of features. Liquid cofferdam was used as a material for the manufacture of an individual occlusal stamp. This article presents clinical illustrations and a step-by-step description of the technique. When using this technique, the occlusal surface of the restoration fully corresponds to the occlusal surface of the tooth before treatment, that is, the anatomy and functions are restored in full. In addition, the modeling protocol is simplified, and the working time is reduced, which is undoubtedly more comfortable for the patient. When monitoring occlusal contacts after work using the technique of an individual occlusal stamp, the restoration is in perfect anatomical and functional interaction with the antagonist tooth.

Building Interpretable Machine Learning Models to Identify Chemometric Trends in Seabirds of the North Pacific Ocean.

Marine environmental monitoring efforts often rely on the bioaccumulation of persistent anthropogenic contaminants in organisms to create a spatiotemporal record of the ecosystem. Intercorrelation results from the origin, uptake, and transport of these contaminants throughout the ecosystem and may be affected by organism-specific processes such as biotransformation. Here, we explore trends that machine learning tools reveal about a large, recently released environmental chemistry data set of common anthropogenic pollutants measured in the eggs of five seabird species from the North Pacific Ocean. We modeled these data with a variety of machine learning approaches and found models that could accurately determine a range of taxonomic and spatiotemporal trends. We illustrate a general workflow and set of analysis tools that can be used to identify interpretable models which perform nearly as well as state-of-the-art "black boxes." For example, we found shallow decision trees that could resolve genus with greater than 96% accuracy using as few as two analytes and a k-nearest neighbor classifier that could resolve species differences with more than 94% accuracy using only five analytes. The benefits of interpretability outweighed the marginally improved accuracy of more complex models. This demonstrates how machine learning may be used to discover rational, quantitative trends in these systems.

Hepatic STAMP2 alleviates polychlorinated biphenyl-induced steatosis and hepatic iron overload in NAFLD models.

Polychlorinated biphenyls (PCBs) have been associated with neurotoxicity, hepatoxicity, oncogenicity, and endocrine-disrupting effects. Although the recent studies have demonstrated that PCB exposure leads to nonalcoholic fatty liver disease (NAFLD), the underlying mechanism has remained unsolved. In this study, we examined the hepatic effects of a PCB mixture, Aroclor 1260, whose composition mimics human bioaccumulation patterns, and PCB 126 in C57BL/6 mice. Male C57Bl/6 mice were fed a standard diet or a 60% high-fat diet and exposed to Aroclor 1260 (10 mg/kg or 20 mg/kg) or PCB 126 (1 mg/kg or 5 mg/kg) by intraperitoneal injection for a total of four injections (2, 3, 4, and 5 weeks) for 6 weeks. In mice, both Aroclor 1260 and PCB 126-induced liver damage, hepatic steatosis and inflammation. We also observed that PCB exposure-induced hepatic iron overload (HIO). We previously demonstrated that hepatic six transmembrane protein of prostate 2 (STAMP2) may represent a suitable therapeutic target for NAFLD patients. Thus, we further examined whether hepatic STAMP2 is involved in PCB-induced NAFLD. We observed that hepatic STAMP2 was significantly decreased in PCB-induced NAFLD models in vivo and in vitro. Furthermore, overexpression of hepatic STAMP2 using an adenoviral delivery system resulted in improvement of PCB-induced steatosis and HIO in vivo and in vitro. Our findings indicate that enhancing hepatic STAMP2 expression represents a potential therapeutic avenue for the treatment of PCB exposure-induced NAFLD.