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BACKGROUND: Currently, many emerging polycyclic aromatic hydrocarbons (PAHs) have been found to be widely present in the environment. However, little has been reported about their toxicity, particularly in relation to CYP1A1. OBJECTIVES: This study aimed to explore the toxicity of naphtho[2,1-a]pyrene (N21aP) and elucidate the mechanism underlying N21aP-induced expression of CYP1A1. METHODS: The concentration and sources of N21aP were detected and analyzed by gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS) and diagnostic ratio analysis. Then the effects of CYP1A1 on the toxicity of N21aP were conducted in male wild-type (WT) and Cyp1a1 knockout mice exposed to N21aP (0.02, 0.2, and 2 mg/kg) through intratracheal instillation. Further, the aryl hydrocarbon receptor (AhR) pathway was examined through luciferase and chromatin immunoprecipitation (ChIP) assays. [N.sup.6]-methyladenosine ([m.sup.6]A) modification levels were measured on global RNA and specifically on CYP1A1 mRNA using dot blotting and methylated RNA immunoprecipitation-quantitative real-time polymerase chain reaction (MeRIP qRT-PCR), with validation by [m.sup.6]A inhibitors, DAA and SAH. [m.sup.6]A sites on CYP1A1 were identified by bioinformatics and luciferase assays, and CYP1A1 mRNA's interaction with IGF2BP3 was confirmed by RNA pull-down, luciferase, and RNA binding protein immunoprecipitation (RIP) assays. RESULTS: N21aP was of the same environmental origin as benzo[a]pyrene (BaP) but was more stably present in the environment. N21aP could be metabolically activated by CYP1A1 to produce epoxides, causing DNA damage and further leading to lung inflammation. Importantly, in addition to the classical AhR pathway (i.e., BaP), N21aP also induced CYP1A1 expression with a posttranscriptional modification of [m.sup.6]A in CYP1A1 mRNA via the METTL14--IGF2BP3-CYP1A1 axis. Specifically, in the two recognition sites of METTL14 on the CYP1A1 mRNA transcript (position at 2700 and 5218), a methylation site (position at 5218) in the 3'-untranslated region (UTR) was recognized by IGF2BP3, enhanced the stability of CYP1A1 mRNA, and finally resulted in an increase in CYP1A1 expression. DISCUSSION: This study systematically demonstrated that in addition to AhR-mediated transcriptional regulation, N21aP, had a new additional mechanism of [m.sup.6]A-mediated posttranscriptional modification, jointly contributing to CYP1A1 expression. Given that PAHs are the metabolic substrates of CYP1A1, this study not only helps to understand the significance of environment-genetic interactions for the toxicity of PAHs but also helps to better understand the health risks of the emerging PAHs at environmental exposure levels. https://doi.org/10.1289/EHP14055, Introduction Polycyclic aromatic hydrocarbons (PAHs) are organic compounds primarily derived from natural processes, such as forest and brush fires, as well as anthropogenic activities, including outdoor industrial and vehicular emissions [...]

This month's column is a contribution from my daughter Glenna, who recently completed her PhD studies in environmental science from the University of Copenhagen in Denmark. Her article explores the [...]

Six sartan substances including telmisartan, losartan, valsartan, irbesartan, olmesartan, and candesartan were selected in this work. A simple and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated to simutaniously detect six drugs. Linearity, LOD, and LOQ were satisfied for routine quantitative and qualitative detection. The linearity ranged from 2 to 1000 ng/mL with the determination coefficient more than 0.98. The intra-day and inter-day precisions were all below 27.5%. All the recoveries were above 80%, and matrix effects were between 25 and 120%. Profiling detection of six sartan substances in human urine was also developed after administration. Irbesartan urinary metabolic pathway was firstly investigated by liquid chromatography quadruple time-of-flight mass spectrometry using full scan and targeted tandem mass spectrometry techniques. Fifteen urinary metabolites of irbesartan were identified and characterized, and ten of them were firstly reported., Author(s): Yu Hong [sup.1] [sup.2] , Genye He [sup.3] , Jianghai Lu [sup.1] , Youxuan Xu [sup.1] Author Affiliations: (1) https://ror.org/03nxed310, grid.506888.b, 0000 0004 6004 1007, Drug and food anti-doping [...]

Adsorbents based on various substrates-silica and a copolymer of styrene with divinylbenzene-are developed for the determination of amino acids by hydrophilic interaction liquid chromatography-mass spectrometry. The optimal version of the structure of the functional layer in two series of the obtained stationary phases was chosen, which provides the best hydrophilization for each substrate. Retention mechanisms were studied and the conditions for the mass-spectrometric detection, separation, and determination of 16 amino acids were chosen. The applicability of the obtained adsorbents and a method for determining amino acids for the analysis of soil extracts were estimated., Author(s): N. Yu. Chikurova [sup.1] , A. V. Gorbovskaia [sup.1] , A. N. Stavrianidi [sup.1] [sup.2] , E. S. Fedorova [sup.2] , A. O. Shemyakina [sup.1] , A. K. Buryak [...]

For the first time, an UPLC-QTOF-MS method was developed and validated to simultaneously estimate dronedarone (DDN) and its four unlisted pharmacopoeial impurities: DDN impurities A, B, C, and D. UPLC separation was performed for 6 min on a BEH C18 (50 x 2.1 mm, 1.7 [micro]m) columnwith 0.1% formic acid in water (A) and acetonitrile (B) as mobile phase delivered in gradient at a constant flow rate of 0.6 mL/min. Mass spectrometric detection was performed in ESI-QTOF-MS. The LOD and LOQ values for the analytes ranged from 0.5 to 10 and 0.8 to 75 ng/mL, respectively. The method was found to be linear for all analyte ranges with r.sup.2 values [greater than or equal to]0.9998. The method was precise with %RSD values [less than or equal to]6.5% and overall analyte recovery was found to be 99.8 ± 1.0%. A novel, sensitive, selective, specific, linear, and accurate UPLC-QTOF-MS method was developed and validated to simultaneously estimate DDN and its impurities which are not listed in the pharmacopoeia., Author(s): Menaka Thangaraj [sup.1] Ramya Kuber B. [sup.2] , Anoop Karthika [sup.3] Author Affiliations: (1) Department of Pharmaceutical Chemistry, Mallige College of Pharmacy, , Bengaluru, India (2) grid.444735.5, 0000 0000 [...]

1-Pyrenylboronic acid (1-PBA) is a type of a reactive matrix useful for the analysis of polyfunctional compounds by MALDI mass spectrometry. It exhibits conventional matrix properties (absorption and transfer of laser radiation energy) and acts as a derivatizing reagent capable of interacting with vicinal functional groups under mild conditions and forming covalent adducts. Pyrenyl group in its structure, which has high ability to absorb UV laser quanta, ensures the detection of analyte derivatives containing a 1-PBA residue as radical cations, which is untypical for MALDI. The effectiveness of its use was earlier proved for compounds containing 1,2-diol fragments. This work presents additional cases of using this reactive matrix in the analysis of practically significant compounds of this type, demonstrating that 1-PBA can also react with distant OH groups. Many examples show its applicability to the study of various [alpha]-hydroxy acids and vicinal aminols and capability of forming cyclic covalent adducts with 1,2-diamines., Author(s): M. D. Matveeva [sup.1] , M. E. Zimens [sup.1] , A. P. Topolyan [sup.1] [sup.2] , D. I. Zhilyaev [sup.1] [sup.3] , D. L. Voskressenskaya [sup.1] [sup.3] , M. [...]

A procedure for the determination of a group of perfluororganic compounds, promising for medical use, in whole blood and tissues of laboratory animals by gas-liquid chromatography-mass spectrometry was developed in in vitro experiments. The sample preparation procedure based on the liquid-liquid extraction of the target compounds from the biomaterial with heptane containing perfluorobenzene as an internal standard was optimized. The validation of the procedure and its testing in in vivo experiments was carried out on an example of perfluorodecalin. The time of the presence of the xenobiotic in the bloodstream and in various organs of small laboratory animals during the endotracheal route of administration was estimated., Author(s): I. K. Zhurkovich [sup.1] , V. A. Utsal' [sup.1] , E. V. Ostrovidova [sup.1] , V. A. Barinov [sup.1] , N. V. Lugovkina [sup.1] , E. Yu. Bonitenko [sup.1] [...]

Novel surface molecularly imprinted polymers (MIPs) combined to restricted access materials (RAMs) were prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization for selective and efficient determination of 17[beta]-estradiol (E2) in milk powder. TiO.sub.2 nanoparticles were coated by a MIP layer via RAFT polymerization and formed a core-shell structure. 3-Glycidoxypropyltrimethoxysilane was grafted on the surface of MIP and hydrolyzed to form hydroxyl group to block unspecific adsorption of macromolecules. RAM-MIPs were characterized by infrared, thermal analyzer, surface area and porosimeter analyzer, and others. RAM-MIP exhibited efficient adsorption performance for E2. E2 in milk powder was dissolved in water, cleaned up by RAM-MIP solid phase extraction cartridge, silanized by N-methyl-N-(trimethylsilyl)trifluoroacetamide, dithioerythritol, and trimethyliodosilane, and determined by gas chromatography-mass spectrometry. The limit of quantification for E2 in milk powder samples was 0.001 mg/kg. The recoveries and relative standard deviations of E2 spiked at 0.001-0.01 mg/kg were 82.0-107.5% and 2.9-5.8%, respectively. Thus, RAM-MIP can be successfully applied to the determination of E2 in milk powder samples., Author(s): Hai Gen Zuo [sup.1] , Xiao Yu Liu [sup.1] , Yong Qin Du [sup.1] , Shi Yu Xiong [sup.1] , Ren Qing Hao [sup.1] , Zhi Fang Huang [sup.1] [...]

Metabolic disturbance may be implicated in the pathogenesis of autism. This study aimed to investigate the gut metabolomic profiles of autistic children and to analyze potential interaction between gut metabolites with autistic symptoms and neurodevelopment levels. We involved 120 autistic and 60 neurotypical children. Autistic symptoms and neurodevelopment levels were assessed. Fecal samples were analyzed using untargeted liquid chromatography-tandem mass spectrometry methods. Our results showed the metabolic disturbances of autistic children involved in multiple vitamin and amino acid metabolism pathways, with the strongest enrichment identified for tryptophan metabolism, retinol metabolism, cysteine-methionine metabolism, and vitamin digestion and absorption. Differential gut metabolites were correlated to autistic symptoms and neurodevelopment levels. Our findings improved the understanding of the perturbations of metabolome networks in autism., Author(s): Jiang Zhu [sup.1] [sup.2] , Xueying Hua [sup.1] [sup.3] , Ting Yang [sup.1] [sup.2] , Min Guo [sup.1] [sup.2] , Qiu Li [sup.1] [sup.2] , Lu Xiao [sup.1] [sup.2] [...]

Background: For decades, the dopamine D2 receptor (D2R) has been known as the main target of antipsychotic medications, but the mechanism for antipsychotic effects beyond this pharmacological target remains unclear. Disrupted-in-schizophrenia 1 (DISCI) is a gene implicated in the etiology of schizophrenia, and we have found elevated levels of the D2R-DISC1 complex in the postmortem brain tissue of patients with schizophrenia. Methods: We used coimmunoprecipitation to measure D2R-DISC1 complex levels in peripheral blood samples from patients with schizophrenia and unaffected controls in 3 cohorts (including males and females) from different hospitals. We also used label-free mass spectrometry to conduct proteomic analysis of these samples. Results: Levels of the D2R-DISC1 complex were elevated in the peripheral blood samples of patients with schizophrenia from 3 independent cohorts, and were normalized with antipsychotic treatment. Proteomic analysis of the blood samples from patients with high D2R-DISC1 complex levels that were normalized with antipsychotic treatment revealed a number of altered proteins and pathways associated with D2R, DISC1 and the D2R-DISC1 complex. We identified additional proteins and pathways that were associated with antipsychotic treatment in schizophrenia, and that may also be novel targets for schizophrenia treatment. Limitations: Sample sizes were relatively small, but were sufficient to detect associations between D2R-DISC1 levels, schizophrenia and treatment response. The relevance of leukocyte changes to the symptoms of schizophrenia is unknown. The coimmunoprecipitation lanes included several nonspecific bands. Conclusion: Levels of the D2R-DISC1 complex were elevated in patients with schizophrenia and reduced with antipsychotic treatment. This finding reinforces the independent role of each protein in schizophrenia. Our results enhanced our understanding of the molecular pathways involved in schizophrenia and in antipsychotic medications, and identified novel potential molecular targets for treating schizophrenia., Introduction Schizophrenia is a chronic mental illness characterized by episodes of psychotic symptoms, with persistent cognitive and social impairments that emerge in early adulthood. Dopamine D2 receptors (D2Rs) are the [...]