LncRNA TUG1 regulates miR-34a-5p / SIRT6 to participate in benzene-induced hematotoxicity through PI3K / AKT /mTOR signaling pathway.

LncRNA TUG1 plays pivotal roles in various diseases. However, its exact roles in benzene - induced hematotoxicity remain unclear. Herein, we aimed to investigate the role and mechanism of TUG1 in hematoxic injuries caused by benzene. In the current study, TUG1 was found dramatically decreased in WBCs of benzene exposure workers and negatively correlated with benzene exposure duration and urine SPMA. In vitro assays demonstrated that TUG1 overexpression attenuated 1,4-BQ-caused suppression of cell viability and proliferation, and promotion of ROS generation and apoptosis via PI3K /AKT /mTOR pathway. Bioinformatic prediction and molecular assay validated miR-34a-5p was negatively regulated by TUG1. The miR-34a-5p was upregulated in 1,4-BQ treated cells and downregulated in TUG1 overexpression cells. Moreover, miR-34a-5p upregulation partially reversed the protective effects of TUG1 overexpression on 1,4-BQ - caused cytotoxicity. Furthermore, SIRT6 was a downstream target gene of miR-34a-5p, whose expression was reduced in miR-34a-5p upregulation cells and elevated in TUG1 overexpression cells. Upregulated SIRT6 could counteract accelerated cytotoxicity mediated by miR-34a-5p upregulation after 1,4-BQ treatment. Taken together, our study revealed that the critical role of the TUG1 / miR-34a-5p / SIRT6 axis in benzene-caused hematotoxicity, and provided scientific basis for further understanding the epigenetic regulatory mechanisms underlying benzene hematotoxicity.

A sustainable approach towards extraction of diosgenin from fenugreek seeds using polystyrene/divinyl benzene resin.

Diosgenin, a bioactive molecule; is one of the deeply explored saponin with a wide spectrum of benefits against various ailments. The extraction and yield enhancement of diosgenin from a wide range of naturally occurring medicinal products has always been a challenging task for its commercial usage. The current research work envisages the use of a novel resin to maximize the yield of diosgenin. The extracted diosgenin was characterized using modern techniques. The current method qualifies for the extraction of diosgenin at a large scale making it a commercially viable technique.

Discovery of ß-nitrostyrene derivatives as potential quorum sensing inhibitors for biofilm inhibition and antivirulence factor therapeutics against Serratia marcescens.

Quorum sensing (QS) inhibition has emerged as a promising target for directed drug design, providing an appealing strategy for developing antimicrobials, particularly against infections caused by drug-resistant pathogens. In this study, we designed and synthesized a total of 33 ß-nitrostyrene derivatives using 1-nitro-2-phenylethane (NPe) as the lead compound, to target the facultative anaerobic bacterial pathogen Serratia marcescens. The QS-inhibitory effects of these compounds were evaluated using S. marcescens NJ01 and the reporter strain Chromobacterium violaceum CV026. Among the 33 new ß-nitrostyrene derivatives, (E)-1-methyl-4-(2-nitrovinyl)benzene (m-NPe, compound 28) was proven to be a potent inhibitor that reduced biofilm formation of S. marcescens NJ01 by 79%. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) results revealed that treatment with m-NPe (50 µg/ml) not only enhanced the susceptibility of the formed biofilms but also disrupted the architecture of biofilms by 84%. m-NPe (50 µg/ml) decreased virulence factors in S. marcescens NJ01, reducing the activity of protease, prodigiosin, and extracellular polysaccharide (EPS) by 36%, 72%, and 52%, respectively. In S. marcescens 4547, the activities of hemolysin and EPS were reduced by 28% and 40%, respectively, outperforming the positive control, vanillic acid (VAN). The study also found that the expression levels of QS- and biofilm-related genes (flhD, fimA, fimC, sodB, bsmB, pigA, pigC, and shlA) were downregulated by 1.21- to 2.32-fold. Molecular dynamics analysis showed that m-NPe could bind stably to SmaR, RhlI, RhlR, LasR, and CviR proteins in a 0.1 M sodium chloride solution. Importantly, a microscale thermophoresis (MST) test revealed that SmaR could be a target protein for the screening of a quorum sensing inhibitor (QSI) against S. marcescens. Overall, this study highlights the efficacy of m-NPe in suppressing the virulence factors of S. marcescens, identifying it as a new potential QSI and antibiofilm agent capable of restoring or improving antimicrobial drug sensitivity.

Confined Cu Single Sites in ZSM-5 for Photocatalytic Hydroxylation of Benzene to Phenol.

Zeolites with band-like charge transport properties have exhibited their potential activities in sensing, optics, and electronics. Herein, a precisely designed Cu@ZSM-5 catalyst is presented with an ultra-wide bandgap of 4.27 eV, showing excellent photocatalytic activity in hydroxylation of benzene with benzene conversion 27.9% and phenol selectivity 97.6%. The SXRD and Rietveld refinement results illustrate that Cu@ZSM-5 has an average of 0.8 Cu atoms per unit cell and the single Cu atoms located in the cross-section of the sinusoidal and straight channels. XANES and EXAFS further demonstrate that the Cu atoms have an oxidation state of +2, coordinated with three OMFI-framework atoms and one ─OH group. Detailed characterizations demonstrate that the Cu@ZSM-5 with tailored bandgap is able to enhance the photoinduced electron-hole separation and hence promote selective hydroxylation of benzene to phenol via the superoxide radical route. This work may open a new way for designing electrically conductive zeolite-supported photocatalysts.

Benzene metabolism and health risk evaluation: insights gained from biomonitoring.

Metabolic conversion of benzene (Bz) is thought to be required for the hematotoxic effects observed following Bz exposures. Most safe exposure limits set for Bz utilize epidemiology data on the hematotoxic effects of Bz for the dose-response assessments. These hematotoxic effects occurred among workers exposed to elevated Bz levels, thus dose extrapolation is required for assessing relevant risks for populations exposed orders of magnitude lower. Thus, understanding how Bz is metabolized over a wide range of air Bz levels is an important topic for risk assessments for Bz. Here, we analyze biomonitoring data for workers exposed to Bz to make evaluations of how the metabolism of Bz varies across a wide range of exposures. Our analysis indicates that the presence of metabolites derived from exposures to sources other than Bz (nonspecific metabolites of Bz) are significant confounders among biomonitoring studies and this precludes making any assessments of how Bz metabolism differs below approximately 3 ppm air Bz exposures using such nonspecific metabolites.

Data-driven machine learning models for predicting the maximum absorption and emission wavelengths of single benzene fluorophores.

Single benzene fluorophores (SBFs) have garnered significant research attention due to their ease of preparation, seamless diffusion into biological samples, and low molecular weight. Accurately predicting the molecular photophysical properties, specifically the maximum absorption and emission wavelengths, is pivotal in advancing functional SBFs. In this study, we introduce a machine-learning model to estimate the maximum absorption and emission wavelengths of SBFs precisely. This model leverages a Full Connect Neural Network and computational chemistry and is tailored to address the challenges associated with a relatively small dataset (81 SBFs). Remarkably, our model (SBFs-ML) demonstrates impressive accuracy, yielding a mean relative error of 1.54 % and 2.93 % for SBFs' maximum absorption and emission wavelengths, respectively. Importantly, the SBFs-ML was bullied based on only three descriptors, resulting in strong interpretability. Experimental results have strongly corroborated these predictions. Our prediction methods are poised to facilitate significantly the efficient design and creation of SBFs.

Carcinogenic industrial air pollution and postmenopausal breast cancer risk in the National Institutes of Health AARP Diet and Health Study.

BACKGROUND: Chemicals emitted from industrial facilities include known or suspected mammary carcinogens and endocrine disruptors, but epidemiologic studies are limited. We evaluated associations between air emissions of multiple carcinogenic chemicals and postmenopausal breast cancer risk in a large prospective U.S. METHODS: We used the U.S. Environmental Protection Agency's Toxics Release Inventory to estimate historical airborne emissions (1987-1995) of 19 known and probable carcinogens for participants enrolled (1995-1996) in the NIH-AARP Diet and Health Study. Among 170,402 women, 15,124 breast cancers were diagnosed through 2018. We constructed inverse distance- and wind-weighted average emissions metrics within 1, 2, 5, and 10 km of the enrollment address for each chemical. We estimated multivariable adjusted HRs and 95 % CIs for categories (quartiles, tertiles, medians) of each chemical in association with breast cancer overall and separately by type (invasive, ductal carcinoma in situ) and estrogen receptor (ER) status. RESULTS: We observed an association between benzene emissions and breast cancer risk that was strongest at 1 km (HRQ4 vs. non-exposed = 2.06, 95 %CI: 1.34-3.17; p-trend = 0.001). The magnitude of the association weakened with increasing distance (2 km HRQ4 vs. non-exposed = 1.17, 95 %CI=0.92-1.49; p-trend = 0.19; 5 km HRQ4 vs. non-exposed = 1.05, 95 %CI=0.94-1.16; p-trend = 0.37; 10 km HRQ4 vs. non-exposed = 0.95, 95 %CI=0.89-1.02; p-trend = 0.19) and appeared to be most relevant for invasive rather than intraductal disease. Overall risk was also elevated for vinyl chloride at 5 km (HR≥median vs. non-exposed = 1.20, 95 %CI=1.01-1.43; p-trend = 0.04), but not 2 km or 10 km. We observed suggestive associations for asbestos, trichloroethylene, and styrene in different subgroup analyses, but risk patterns were not clear across distances. Associations with other chemicals were generally null, with limited evidence of heterogeneity by disease type or ER status. CONCLUSIONS: An increased risk of breast cancer associated with relatively high levels of industrial benzene emissions warrants additional study, particularly among participants with diverse sociodemographic characteristics that live in areas with higher density of industrial facilities.

A Fluorescence-Based Assay for Measuring Polyamine Biosynthesis Aminopropyl Transferase-Mediated Catalysis.

Polyamines are polycationic molecules that are crucial in a wide array of cellular functions. Their biosynthesis is mediated by aminopropyl transferases (APTs), which are promising targets for antimicrobial, antineoplastic and antineurodegenerative therapies. A major limitation in studying APT enzymes, however, is the lack of high-throughput assays to measure their activity. We have developed the first fluorescence-based assay, DAB-APT, for the measurement of APT activity using 1,2-diacetyl benzene (DAB), which forms fluorescent conjugates with putrescine, spermidine, and spermine, with fluorescence intensity increasing with the carbon chain length. The assay has been validated using APT enzymes from Saccharomyces cerevisiae and Plasmodium falciparum, and the data further validated by mass spectrometry and thin-layer chromatography. Using mass spectrometry analysis, the structures of the fluorescent putrescine, spermidine and spermine 1,2-DAB adducts were determined to be substituted 1,3-dimethyl isoindoles. The DAB-APT assay is optimized for high-throughput screening, facilitating the evaluation of large chemical libraries. Given the critical roles of APTs in infectious diseases, oncology, and neurobiology, the DAB-APT assay offers a powerful tool with broad applicability, poised to drive advancements in research and drug discovery.

Data-driven approaches to study the spectral properties of chemical structures.

The molecular energy, which is the sum of all eigenvalues, is crucial in determining the total π-electron energy of conjugated hydrocarbon molecules. We used machine learning techniques to calculate the energy, inertia, nullity, signature, and Estrada index of molecular graphs for bismuth tri-iodide and benzene rings embedded in P-type surfaces within 2D networks. We applied MATLAB to extract the actual eigenvalues from the data and developed general equations for these molecular properties. We then used these equations to estimate the values and compared them to the actual values through graphical analysis. Our results demonstrate the potential of data-driven techniques in predicting molecular properties and enhancing our understanding of spectral theory.

Anaerobic benzene oxidation in Geotalea daltonii involves activation by methylation and is regulated by the transition state regulator AbrB.

Benzene is a widespread groundwater contaminant that persists under anoxic conditions. The aim of this study was to more accurately investigate anaerobic microbial degradation pathways to predict benzene fate and transport. Preliminary genomic analysis of Geotalea daltonii strain FRC-32, isolated from contaminated groundwater, revealed the presence of putative aromatic-degrading genes. G. daltonii was subsequently shown to conserve energy for growth on benzene as the sole electron donor and fumarate or nitrate as the electron acceptor. The hbs gene, encoding for 3-hydroxybenzylsuccinate synthase (Hbs), a homolog of the radical-forming, toluene-activating benzylsuccinate synthase (Bss), was upregulated during benzene oxidation in G. daltonii, while the bss gene was upregulated during toluene oxidation. Addition of benzene to the G. daltonii whole-cell lysate resulted in toluene formation, indicating that methylation of benzene was occurring. Complementation of σ54- (deficient) E. coli transformed with the bss operon restored its ability to grow in the presence of toluene, revealing bss to be regulated by σ54. Binding sites for σ70 and the transition state regulator AbrB were identified in the promoter region of the σ54-encoding gene rpoN, and binding was confirmed. Induced expression of abrB during benzene and toluene degradation caused G. daltonii cultures to transition to the death phase. Our results suggested that G. daltonii can anaerobically oxidize benzene by methylation, which is regulated by σ54 and AbrB. Our findings further indicated that the benzene, toluene, and benzoate degradation pathways converge into a single metabolic pathway, representing a uniquely efficient approach to anaerobic aromatic degradation in G. daltonii. IMPORTANCE: The contamination of anaerobic subsurface environments including groundwater with toxic aromatic hydrocarbons, specifically benzene, toluene, ethylbenzene, and xylene, has become a global issue. Subsurface groundwater is largely anoxic, and further study is needed to understand the natural attenuation of these compounds. This study elucidated a metabolic pathway utilized by the bacterium Geotalea daltonii capable of anaerobically degrading the recalcitrant molecule benzene using a unique activation mechanism involving methylation. The identification of aromatic-degrading genes and AbrB as a regulator of the anaerobic benzene and toluene degradation pathways provides insights into the mechanisms employed by G. daltonii to modulate metabolic pathways as necessary to thrive in anoxic contaminated groundwater. Our findings contribute to the understanding of novel anaerobic benzene degradation pathways that could potentially be harnessed to develop improved strategies for bioremediation of groundwater contaminants.

LaCoO3 is a promising catalyst for the dry reforming of benzene used as a surrogate of biomass tar.

Tar build-up is one of the bottlenecks of biomass gasification processes. Dry reforming of tar is an alternative solution if the oxygen chemical potential on the catalyst surface is at a sufficient level. For this purpose, an oxygen-donor perovskite, LaCoO3, was used as a catalyst for the dry reforming of tar. To circumvent the complexity of the tar and its constituents, the benzene molecule was chosen as a model compound. Dry reforming of benzene vapor on the LaCoO3 catalyst was investigated at temperatures of 600, 700, and 800 °C; at CO2/C6H6 ratios of 3, 6, and 12; and at space velocities of 14,000 and 28,000 h-1. The conventional Ni(15 wt.%)/Al2O3 catalyst was also used as a reference material to determine the relative activity of the LaCoO3 catalyst. Different characterization techniques such as X-ray diffraction, N2 adsorption-desorption, temperature-programmed reduction, and oxidation were used to determine the physicochemical characteristics of the catalysts. The findings demonstrated that the LaCoO3 catalyst has higher CO2 conversion, higher H2 and CO yields, and better stability than the Ni(15 wt.%)/γ-Al2O3 catalyst. The improvement in activity was attributed to the strong capacity of LaCoO3 for oxygen exchange. The transfer of lattice oxygen from the surface of the LaCoO3 catalyst facilitates the oxidation of carbon and other surface species and leads to higher conversion and yields.

Amino-Terephthalonitrile and Amino-Terephthalate-Based Single Benzene Fluorophores - Compact Color Tunable Molecular Dyes for Bioimaging and Bioanalysis.

This review article discusses the emerging amino-terephthalonitrile (Am-TN) and amino terephthalate-based single benzene fluorophores (SBFs) for their highly emissive nature and potential for numerous technical applications. Am-TN-SBFs are a new class of SBFs having amine as the electron donating (EDG) and dinitrile as the electron withdrawing group (EWG). The beauty of these Am-TN-SBFs lies in excellent intramolecular charge transfer between the EDG and EWG. The placement of two nitrile groups in para-position on the benzene ring allows better charge transfer from the donating amines to the linear nitrile group leading to the strongly emissive nature. We also outline here the latest developments in the well-known family of amino terephthalate SBFs reported in the last 2 to 3 years. Amino terephthalate SBFs have esters as the EWG and amine as the EDG. These have intramolecular H-bonding between the EDG and EWG which is responsible for their emissive behavior.

Metagenomic and genomic sequences from a nitrate-reducing benzene-degrading enrichment culture.

Metagenome-assembled genomes (MAGs) were recovered from metagenomic assemblies from a nitrate-reducing benzene-degrading enrichment culture. Ten MAGs of high quality or functional interest to benzene degradation are reported, seven of which are single contig genomes.

Occupational exposure to benzene and risk of non-Hodgkin lymphoma in an extended follow-up of two population-based prospective cohorts of Chinese men and women.

The carcinogenicity of benzene was reevaluated by the International Agency for Research on Cancer in 2017, with the Working Group reaffirming positive yet inconclusive associations with non-Hodgkin lymphoma (NHL). To extend our previous observation of a significant exposure-response for cumulative occupational benzene exposure and NHL risk among Chinese women in a population-based cohort in Shanghai, we extended follow-up of this cohort and pooled the data with a similarly designed population-based cohort of men in Shanghai. Cumulative exposure estimates were derived for 134,449 participants in the pooled analysis by combining ordinal job-exposure matrix intensity ratings with quantitative benzene measurements from an inspection database of Shanghai factories. Associations between benzene exposure metrics and NHL (n = 363 cases including multiple myeloma [MM]) were assessed using Cox proportional hazard models. Ever occupational exposure to benzene in the pooled population was associated with NHL risk (HR = 1.5, 95% CI = 1.2-2.0), and exposure-response relationships were observed for increasing duration (ptrend = .003) and cumulative exposure (ptrend = .003). Associations with ever exposure, duration, and cumulative exposure were similar for NHL with and without MM in the case definition, including lifetime cumulative exposures in the highest quartile (HR = 1.6, 95% CI = 1.1-2.4 with MM included; HR = 1.7, 95% CI = 1.1-2.7 with MM excluded). An elevated risk of the chronic lymphocytic leukemia subtype was suggested in the pooled analyses (HR for ever vs. never exposure = 2.3, 95% CI = 0.9-5.6). These observations provide additional support for a plausible association between occupational benzene exposure and risk of NHL.

Occupational benzene exposure and risk of head and neck cancer: A systematic review and meta-analysis.

INTRODUCTION: Benzene, an aromatic hydrocarbon, is a well-known leukemogen. To date, the link between benzene exposure and solid cancers is under examination. Our objective is to perform a systematic review and meta-analysis to evaluate if the occupational exposure to benzene is associated with the incidence and mortality of head and neck cancers (HNCs). METHODS: We systematically reviewed the literature for pertinent cohort studies mentioned in the most recent IARC Monograph on benzene working exposure and other cohorts and case-controls identified via a literature search performed in PubMed, Scopus, and Embase, from their inception to March 2024. Stratified multilevel meta-analyses according to study design, cancer type, industrial sector, quality score of the articles, geographic region and risk of exposure bias were conducted. RESULTS: A total of 29 independent studies were included in our review and multilevel meta-analysis. The findings revealed a bordeline association between exposure to occupational benzene and incidence of HNCs RR = 1.27, 95% CI = 1.00-1.64, I2 level2 = 0%, I2level3 = 43.30%, P < 0.05). In addition, we found a significant increased overall risk of HNCs in females (RR = 1.68, 95% CI = 1.07-2.61; I2level2 = 0%, I2level3 = 0%, P = 0.433). Stratification analysis according to cancer sites showed a significant increase in risk of nose & sinuses cancers (RR = 3.72, 95% CI = 2.07-6.68; I2level2 = 34.13%, I2level3 = 0%, P = 0.17). European cohorts (RR = 1.31, 95% CI = 1.08-1.59, p < 0.01) and lower quality studies (RR = 1.39, 95% CI = 1.00-1.91; I2level2 = 0%, I2level3 = 45.94%, P < 0.001). No evidence of publication bias was found (Egger test P = 0.103). CONCLUSIONS: In conclusion, this systematic review and meta-analysis provide evidence that workers with occupational exposure to benzene might be at increased risk of HNCs, in particular for nose & sinuses cancer. However, it is essential to consider the limitations of the studies, particularly residual confounding, and the areas that need further study to improve our understanding of the subject.

Moderate BMI accumulation modified associations between blood benzene, toluene, ethylbenzene and xylene (BTEX) and phenotypic aging: mediating roles of inflammation and oxidative stress.

The associations between blood benzene, toluene, ethylbenzene, and xylenes (BTEX) and biological aging among general adults remain elusive. The present study comprised 5780 participants from the National Health and Nutrition Examination Survey 1999-2010. A novel measure of biological aging, phenotypic age acceleration (PhenoAge.Accel), derived from biochemical markers was calculated. Weighted generalized linear regression and weighted quantile sum regression (WQS) were utilized to assess the associations between BTEX components and mixed exposure, and PhenoAge.Accel. The mediating roles of systemic immune-inflammation index (SII) and oxidative stress indicators (serum bilirubin and gamma-glutamyl transferase), along with the modifying effects of body mass index (BMI) were also examined. In the single-exposure model, the highest quantile of blood benzene (b = 0.89, 95%CI: 0.58 to 1.20), toluene (b = 0.87, 95%CI: 0.52 to 1.20), and ethylbenzene (b = 0.80, 95%CI: 0.46 to 1.10) was positively associated with PhenoAge.Accel compared to quantile 1. Mixed-exposure analyses revealed a consistent positive association between BTEX mixed exposure and PhenoAge.Accel (b = 0.88, 95%CI: 0.56 to 1.20), primarily driven by benzene (92.78%). The association between BTEX and PhenoAge.Accel was found to be partially mediated by inflammation and oxidative stress indicators (ranging from 3.2% to 13.7%). Additionally, BMI negatively modified the association between BTEX mixed exposure and PhenoAge.Accel, with a threshold identified at 36.2 kg/m^2. Furthermore, BMI negatively moderated the direct effect of BTEX mixed exposure on PhenoAge.Accel in moderated mediation models, while positively modified the link between SII and PhenoAge.Accel in the indirect path (binteraction = 0.04, 95%CI: 0.01 to 0.06). Overall, BTEX mixed exposure was associated with PhenoAge.Accel among US adults, with benzene may have reported most contribution, and inflammation and oxidative damage processes may partially explain this underlying mechanism. The study also highlighted the potential benefits of appropriate BMI increased. Additional large-scale cohort studies and experiments were necessary to substantiate these findings.

The short-term toxicity and metabolome of Benzene.

A 14-day rat study with plasma metabolomics was conducted to evaluate the toxicity of Benzene. Wistar rats were orally administered Benzene daily at doses of 0, 300 and 1000 mg/kg bw. The study identified liver and kidneys as target organs of Benzene toxicity and found reductions in total white blood cells, absolute lymphocyte and eosinophil cell counts, and increased relative monocyte counts suggesting bone marrow as a target organ. The study also confirmed liver as a target organ using metabolomics, which showed indications of a stress reaction in rats and changes in metabolites suggestive of a metabolic disorder. The metabolomics investigations did not find any other toxicologically relevant modes of action, and the observed metabolite changes were not associated with markers for mitochondrial dysfunction. The study concludes that integration of omics technologies, such as metabolomics, in regulatory toxicity studies is possible, confirms existing knowledge and adds additional information that can be used for mechanistic understanding of observed toxicity.

Benzene exposure and pediatric leukemia: From molecular clues to epidemiological insights.

According to the International Agency for Research on Cancer, leukemia ranks 14th in incidence and 11th in mortality and has a 5-year prevalence of approximately 1300,000 cases. Acute lymphoblastic leukemia is the most common hematopoietic syndrome in children during the first 5 years of life and represents approximately 75 % of all neoplasms among the pediatric population. The development of leukemia is strongly governed by DNA alterations that accelerate the growth of bone marrow cells. Currently, the most examined factor in pediatric leukemia is exposure to multiple compounds, such as hydrocarbons. Benzene, an aromatic hydrocarbon, can cause health challenges and is categorized as a carcinogen. Benzene toxicity has been widely associated with occupational exposure. Importantly, studies are underway to generate evidence that can provide clues regarding the risk of environmental benzene exposure and hematological problems in children. In this review, we summarize the existing evidence regarding the effects of benzene on pediatric leukemia, the associations between the effect of benzene on carcinogenesis, and the presence of certain molecular signatures in benzene-associated pediatric leukemia. Although there is sufficient evidence regarding the effects of benzene on carcinogenesis and leukemia, epidemiological research has primarily focused on occupational risk. Moreover, most benzene-induced molecular and cytogenetic alterations have been widely described in adults but not in the pediatric population. Thus, epidemiological efforts are crucial in the pediatric population in terms of epidemiological, clinical, and biomedical research.

Application of the CIEMAT/NIST method to 14C low-level measurements.

Radiocarbon dating of samples from benzene synthesis by low-level Liquid Scintillation Counting (LSC) method requires the availability of 14C standards in benzene, which are difficult to obtain, or the use of an absolute measurement which is out of reach for most analytical laboratories. This paper describes how the CIEMAT/NIST method can help to solve this issue and presents the measurements of low activity concentrations performed in the LRI-D using two different benzene base scintillator cocktails.

Hydroquinone impairs trophoblast migration and invasion via AHR-twist-IFITM1 axis.

INTRODUCTION: Embryo implantation is a tightly regulated process, critical for a successful pregnancy. After attachment of the blastocyst to the surface epithelium of the endometrium trophoblast migrate from the trophectoderm and invade into the stromal component of endometrium. Alterations on either process will lead to implantation failure or miscarriage. Volatile organic compounds (VOCs) such as benzene induce pregnancy complications, including preterm birth and miscarriages. The mechanism of this effect is unknown. The objective of this study was to elucidate the impact of benzene metabolite, Hydroquinone, on trophoblast function. We tested the hypothesis that Hydroquinone activates the Aryl hydrocarbon receptor (AhR) pathway modulating trophoblast migration and invasion. METHODS: First-trimester trophoblast cells (Sw.71) were treated with hydroquinone (6 and 25 µM). Trophoblast migration and invasion was evaluated using a 3D invasion/migration model. Gene expression was quantified by q-PCR and Western blot analysis. RESULTS: Hydroquinone impairs trophoblast migration and invasion. This loss is associated with the activation of the AhR pathway which reduced the expression of Twist1and IFITM1. IFITM1 overexpression can rescue impaired trophoblast migration. DISCUSSION: Our study highlights that hydroquinone treatment induces the activation of the AhR pathway in trophoblast cells, which impairs trophoblast invasion and migration. We postulate that activation of the AhR pathway in trophoblast suppress Twist1 and a subsequent IFITM1. Thus, the AhR-Twist1-IFITM1 axis represent a critical pathway involved in the regulation of trophoblast migration and it is sensitive to benzene exposure. These findings provide crucial insights into the molecular mechanisms underlying pregnancy complications induced by air pollution.