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Background: Error-corrected next-generation sequencing (ecNGS) technologies have enabled the direct evaluation of genome-wide mutations after exposure to mutagens. Previously, we reported an ecNGS methodology, Hawk-Seq™, and demonstrated its utility in evaluating mutagenicity. The evaluation of technical transferability is essential to further evaluate the reliability of ecNGS-based assays. However, cutting-edge sequencing platforms are continually evolving, which can affect the sensitivity of ecNGS. Therefore, the effect of differences in sequencing instruments on mutation data quality should be evaluated. Results: We assessed the performance of four sequencing platforms (HiSeq2500, NovaSeq6000, NextSeq2000, and DNBSEQ-G400) with the Hawk-Seq™ protocol for mutagenicity evaluation using DNA samples from mouse bone marrow exposed to benzo[a]pyrene (BP). The overall mutation (OM) frequencies per 106 bp in vehicle-treated samples were 0.22, 0.36, 0.46, and 0.26 for HiSeq2500, NovaSeq6000, NextSeq2000, and DNBSEQ-G400, respectively. The OM frequency of NextSeq2000 was significantly higher than that of HiSeq2500, suggesting the difference to be based on the platform. The relatively higher value in NextSeq2000 was a consequence of the G:C to C:G mutations in NextSeq2000 data (0.67 per 106 G:C bp), which was higher than the mean of the four platforms by a ca. of 0.25 per 106 G:C bp. A clear dose-dependent increase in G:C to T:A mutation frequencies was observed in all four sequencing platforms after BP exposure. The cosine similarity values of the 96-dimensional trinucleotide mutation patterns between HiSeq and the three other platforms were 0.93, 0.95, and 0.92 for NovaSeq, NextSeq, and DNBSeq, respectively. These results suggest that all platforms can provide equivalent data that reflect the characteristics of the mutagens. Conclusions: All platforms sensitively detected mutagen-induced mutations using the Hawk-Seq™ analysis. The substitution types and frequencies of the background errors differed depending on the platform. The effects of sequencing platforms on mutagenicity evaluation should be assessed before experimentation. [ABSTRACT FROM AUTHOR]

Background and Purpose: The analgesic action of paracetamol involves KV7 channels, and its metabolite N‐acetyl‐p‐benzo quinone imine (NAPQI), a cysteine modifying reagent, was shown to increase currents through such channels in nociceptors. Modification of cysteine residues by N‐ethylmaleimide, H2O2, or nitric oxide has been found to modulate currents through KV7 channels. The study aims to identify whether, and if so which, cysteine residues in neuronal KV7 channels might be responsible for the effects of NAPQI. Experimental Approach: To address this question, we used a combination of perforated patch‐clamp recordings, site‐directed mutagenesis, and mass spectrometry applied to recombinant KV7.1 to KV7.5 channels. Key Results: Currents through the cardiac subtype KV7.1 were reduced by NAPQI. Currents through all other subtypes were increased, either by an isolated shift of the channel voltage dependence to more negative values (KV7.3) or by such a shift combined with increased maximal current levels (KV7.2, KV7.4, KV7.5). A stretch of three cysteine residues in the S2‐S3 linker region of KV7.2 was necessary and sufficient to mediate these effects. Conclusion and Implication: The paracetamol metabolite N‐acetyl‐p‐benzo quinone imine (NAPQI) modifies cysteine residues of KV7 subunits and reinforces channel gating in homomeric and heteromeric KV7.2 to KV7.5, but not in KV7.1 channels. In KV7.2, a triple cysteine motif located within the S2‐S3 linker region mediates this reinforcement that can be expected to reduce the excitability of nociceptors and to mediate antinociceptive actions of paracetamol. [ABSTRACT FROM AUTHOR]

Food chemical and microbiological contamination are major global food safety issues. This study investigated the combined effects of the food‐borne pathogen Helicobacter pylori (H. pylori) and the pollutant benzo(a)pyrene (Bap) on atrophic gastritis and gut microbiota in Mongolian gerbils. The results demonstrated that simultaneous administration of H. pylori and Bap caused more severe weight loss, DNA damage, and gastritis in Mongolian gerbils compared with those exposed to H. pylori or Bap alone. The combination also significantly increased the serum level of proinflammatory cytokines, including IL‐1β (p < .05), IL‐6 (p < .0001), and TNF‐α (p < .05). Additionally, the H. pylori and Bap combination altered the composition of gut microbiota in Mongolian gerbils: the relative abundance of Lactobacillus and Ligilactobacillus at the genus level (p < .05) was significantly reduced while the relative abundance of Allobaculum and Erysipelotrichaceae enhanced (p < .0001, p < .05). Our study revealed that the synergy of H. pylori and Bap can boost the development of atrophic gastritis and lead to gut microbiota dysbiosis in Mongolian gerbils, which provides essential implications for preventing contaminated foods to sustain life and promote well‐being. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 helicase, non-structural protein 13 (Nsp13), plays an essential role in viral replication, translocating in the 5′ → 3′ direction as it unwinds double-stranded RNA/DNA. We investigated the impact of structurally distinct DNA lesions on DNA unwinding catalyzed by Nsp13. The selected lesions include two benzo[a]pyrene (B[a]P)-derived dG adducts, the UV-induced cyclobutane pyrimidine dimer (CPD), and the pyrimidine (6–4) pyrimidone (6–4PP) photolesion. The experimentally observed unwinding rate constants (kobs) and processivities (P) were examined. Relative to undamaged DNA, the kobs values were diminished by factors of up to ~15 for B[a]P adducts but only by factors of ~2–5 for photolesions. A minor-groove-oriented B[a]P adduct showed the smallest impact on P, which decreased by ~11% compared to unmodified DNA, while an intercalated one reduced P by ~67%. However, the photolesions showed a greater impact on the processivities; notably, the CPD, with the highest kobs value, exhibited the lowest P, which was reduced by ~90%. Our findings thus show that DNA unwinding efficiencies are lesion-dependent and most strongly inhibited by the CPD, leading to the conclusion that processivity is a better measure of DNA lesions' inhibitory effects than unwinding rate constants. [ABSTRACT FROM AUTHOR]

[Display omitted] • A green PMS activation catalyst (N -CG) was fabricated via impregnation calcination. • N -CG exhibited excellent degradation efficiency toward benzo(a)pyrene polluted soil. • Melamine increased the ratio of graphitic N and Pyridine N during thermal annealing. • The mechanism of N -doping in coal gangue for PMS activation was well proposed. Efficient degradation of organic pollutants in complex media via advanced oxidation processes (AOPs) is still critical and challenging. Herein, nitrogen (N)-doped coal gangue (CG) catalysts (N -CG) with economic competitiveness and environmental friendliness were successfully synthesized to activate peroxymonosulfate (PMS), exhibiting ultrafast degradation performance toward benzo(a)pyrene (BaP) with 100.00 % and 93.21 % in contaminated solution and soil under optimized condition, respectively. In addition, 0.4 N -CG possessed excellent reusability toward BaP degradation with over 80.00 % after five cycles. However, BaP removal efficiency was significantly affected by some co-existing anions (HCO 3 − and SO 4 2−) and humic acid (HA) in solution and soil, as well as inhibited under alkaline conditions, especially pH ≥ 9. According to the characterizations, N -doping could promote the generation of pyridinic N and graphitic N in N -CG via high-temperature calcination, which was conducive to produce hydroxyl radical (•OH), sulfate radical (SO 4 •−), superoxide radical (•O 2 −) and single oxygen (1O 2). In 0.4 N -CG/PMS system, 1O 2 and •O 2 − were proved to be the predominant reactive oxygen species (ROSs) in BaP degradation, as well as •OH and SO 4 •− made certain contributions. To sum up, this work provided a promising strategy for synthesis of CG-based catalysts by chemical inertness conversion of carbon fracture via N -doping for PMS activation and opened a novel perspective for environmental remediation of hydrophobic and hydrophilic contaminants pollution. [ABSTRACT FROM AUTHOR]

Data on the contents of eleven polycyclic aromatic hydrocarbons (PAHs) in soils of single-time and repeatedly burnt areas of different ages in taiga landscapes of the Khamar-Daban Ridge (southern Baikal region, Buryatia) are presented. Morphological soil features inherited from the fires are identified: charcoal layer (pyr), ash layer (Cpyr), charred forest litter, (Opyr) and pyrogenic humus horizon (Apyr). The post-fire variability of the soil cover within burnt areas is related to the presence of areas with six degrees of burning of litter material. The content of PAHs in soils decreases with increasing fire intensity, as well as in the case of repeated fires on the already burnt area. Background soils of forests not disturbed by fire have a higher content of PAHs compared to that in soils of 42-year-old burnt area and one-year-old intensely burnt area. Four groups of PAHs differing in their origin have been identified using factor analysis: polyarenes of pyrogenic autochthonous origin formed in situ (naphthalene, tetraphene, pyrene, chrysene, anthracene, naphthalene, to a lesser extent benzo(a)pyrene and benzo(ghi)perylene); polyarenes of pyrogenic allochthonous origin that accumulated in soils due to atmospheric transport of ash material (benzo(a)pyrene and benzo(ghi)perylene); polyarenes of biochemical origin (fluorene and biphenyl); and polyarenes of biochemical and petrogenic origin accumulating in the deep soil horizons (phenanthrene). [ABSTRACT FROM AUTHOR]

While field ionization (FI) and field desorption (FD) are established soft vacuum ionization methods in mass spectrometry (MS), the technique of atmospheric pressure field desorption (APFD) has only recently been added to the repertoire. Similar to FI and FD, APFD can yield both positive even-electron ions of highly polar or ionic compounds and positive molecular ions, M+•, e.g., of polycyclic aromatic compounds. Thus, a dedicated APFD source assembly has been constructed and demonstrated to allow for robust APFD operation. This device also enabled observation of the emitter during operation and allowed for resistive emitter heating, thereby speeding up the desorption of the analytes and expanding the range of analytes accessible to APFD. While initial work was done using a Fourier transform-ion cyclotron resonance (FT-ICR) mass spectrometer, the new APFD source offered the flexibility to also be used on a trapped ion mobility-quadrupole-time-of-flight (TIMS-Q-TOF) instrument, and thus, it would be possible to be mounted to any Bruker mass spectrometer featuring an atmospheric pressure (AP) interface. Operating an APFD source at a TIMS-Q-TOF instrument called for the exploration of the combined use of APFD and TIMS. Here, operation, basic properties, and capabilities of this new atmospheric pressure field desorption-trapped ion mobility-mass spectrometry (APFD-TIMS-MS) coupling are described. APFD-TIMS-MS is employed for the separation of individual components of oligomers and for the accurate determination of their collision cross section (CCS). This work describes the application of APFD-TIMS-MS on poly(ethylene glycol) forming [M + Na]+ ions by cationization and on an amine-terminated poly(propylene glycol) yielding [M + H]+ ions. Some compounds forming molecular ions, M+•, by field ionization such as [60]fullerene and a mixture of four polycyclic aromatic hydrocarbons (PAHs) are examined. In APFD-TIMS-MS, the limits of detection (LODs) of fluoranthene and benzo[a]pyrene M+• ions are determined as ≈100 pg and <1 pg, respectively. Finally, [60]fullerene is analyzed by negative-ion APFD-TIMS-MS where it yields a molecular anion, M−•. [ABSTRACT FROM AUTHOR]

DNA adduction in the model yeast Saccharomyces cerevisiae was investigated after exposure to the fungicide penconazole and the reference genotoxic compound benzo(a)pyrene, for validating yeasts as a tool for molecular toxicity studies, particularly of environmental pollution. The effect of the toxicants on the yeast's growth kinetics was determined as an indicator of cytotoxicity. Fermentative cultures of S. cerevisiae were exposed to 2 ppm of Penconazole during different phases of growth; while 0.2 and 2 ppm of benzo(a)pyrene were applied to the culture medium before inoculation and on exponential cultures. Exponential respiratory cultures were also exposed to 0.2 ppm of B(a)P for comparison of both metabolisms. Penconazole induced DNA adducts formation in the exponential phase test; DNA adducts showed a peak of 54.93 adducts/109 nucleotides. Benzo(a)pyrene induced the formation of DNA adducts in all the tests carried out; the highest amount of 46.7 adducts/109 nucleotides was obtained in the fermentative cultures after the exponential phase exposure to 0.2 ppm; whereas in the respiratory cultures, 14.6 adducts/109 nucleotides were detected. No cytotoxicity was obtained in any experiment. Our study showed that yeast could be used to analyse DNA adducts as biomarkers of exposure to environmental toxicants. [ABSTRACT FROM AUTHOR]

The object of this research was isolation of the two new benzoazepine alkaloids – 3,10,11,12-tetramethoxy-4-oxo-7,8-dihydrobenzo[d]cyclohepta[b]azepine-6(4H)-carbaldehyde (1) and 6-(hydroxymethyl)-3,10,11,12-tetramethoxy-7,8-dihydrobenzo[d]cyclohepta[b]azepine-4(6H)-one) (3) as well as the known colchicine (2). [ABSTRACT FROM AUTHOR]

Cancer, which is currently rated as the second-leading cause of mortality across the globe, is one of the most hazardous disease groups that has plagued humanity for centuries. The experiments presented here span over two decades and were conducted on a specific species of mice, aiming to neutralize a highly carcinogenic agent by altering its chemical structure when combined with certain compounds. A plethora of growth models, each of which makes use of distinctive qualities, are utilized in the investigation and explanation of the phenomena of chemically induced oncogenesis and prevention. The analysis ultimately results in the formalization of the process of locating the growth model that provides the best descriptive power based on predefined criteria. This is accomplished through a methodological workflow that adopts a computational pipeline based on the Levenberg–Marquardt algorithm with pioneering and conventional metrics as well as a ruleset. The developed process simplifies the investigated phenomena as the parameter space of growth models is reduced. The predictability is proven strong in the near future (i.e., a 0.61% difference between the predicted and actual values). The parameters differentiate between active compounds (i.e., classification results reach up to 96% in sensitivity and other performance metrics). The distribution of parameter contribution complements the findings that the logistic growth model is the most appropriate (i.e., 44.47%). In addition, the dosage of chemicals is increased by a factor of two for the next round of trials, which exposes parallel behavior between the two dosages. As a consequence, the study reveals important information on chemoprevention and the cycles of cancer proliferation. If developed further, it might lead to the development of nutritional supplements that completely inhibit the expansion of cancerous tumors. The methodology provided can be used to describe other phenomena that progress over time and it has the power to estimate future results.

Azabora[6]helicene as a new heterohelicene analogue was synthesized by a one-pot reaction of commercially available 2,6-diaminopyridine and benzo[c,d]indole-2(1H)-one and subsequent boron coordination. While the single-crystal X-ray diffraction analysis elucidated a helical structure in the solid state, a dynamic helicity inversion was observed in solution. [ABSTRACT FROM AUTHOR]

Increasing environmental genotoxic chemicals have been shown to induce epigenetic alterations. However, the interaction between genetics and epigenetics in chemical carcinogenesis is still not fully understood. Here, we constructed an in vitro human lung carcinogenesis model (16HBE-T) by treating human bronchial epithelial cells with a typical significant carcinogen benzo(a)pyrene (BaP). We identified a novel circular RNA, circ0087385, which was overexpressed in 16HBE-T and human lung cancer cell lines, as well as in lung cancer tissues and serum exosomes from lung cancer patients. The upregulated circ0087385 after exposure to BaP promoted DNA damage in the early stage of chemical carcinogenesis and affected the cell cycle, proliferation, and apoptosis of the malignantly transformed cells. Overexpression of circ0087385 enhanced the expression of cytochrome P450 1A1 (CYP1A1), which is crucial for metabolically activating BaP. Interfering with circ0087385 or CYP1A1 reduced the levels of ultimate carcinogen benzo(a)pyrene diol epoxide (BPDE) and BPDE-DNA adducts. Interfering with CYP1A1 partially reversed the DNA damage induced by high expression of circ0087385, as well as decreased the level of BPDE and BPDE-DNA adducts. These findings provide novel insights into the interaction between epigenetics and genetics in chemical carcinogenesis which are crucial for understanding the epigenetic and genetic toxicity of chemicals. [ABSTRACT FROM AUTHOR]

Podophyllotoxin, a cyclolignan natural product, has been the object of extensive chemomodulation to obtain better chemotherapeutic agents. Among the obtained podophyllotoxin derivatives, podophyllic aldehyde showed very interesting potency and selectivity against several tumoral cell lines, so it became our lead compound for further modifications, as described in this work, oriented toward the enlargement of the cyclolignan skeleton. Thus, modifications performed at the aldehyde function included nucleophilic addition reactions and the incorporation of the aldehyde carbon into several five-membered rings, such as thiazolidinones and benzo-fused azoles. The synthesized derivatives were evaluated against several types of cancer cells, and although some compounds were cytotoxic at the nanomolar range, most of them were less potent and less selective than the parent compound podophyllic aldehyde, with the most potent being those having the lactone ring of podophyllotoxin. In silico ADME evaluation predicted good druggability for most of them. The results indicate that the γ-lactone ring is important for potency, while the α,β-unsaturated aldehyde is necessary to induce selectivity in these cyclolignans. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer death worldwide. Polycyclic aromatic hydrocarbons (PAHs) are metabolized by the cytochrome P450 (CYP)1A and 1B1 to DNA-reactive metabolites, which could lead to mutations in critical genes, eventually resulting in cancer. Omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are beneficial against cancers. In this investigation, we elucidated the mechanisms by which omega-3 fatty acids EPA and DHA will attenuate PAH-DNA adducts and lung carcinogenesis and tumorigenesis mediated by the PAHs BP and MC. Adult wild-type (WT) (A/J) mice, Cyp1a1-null, Cyp1a2-null, or Cyp1b1-null mice were exposed to PAHs benzo[a]pyrene (BP) or 3-methylcholanthrene (MC), and the effects of omega-3 fatty acid on PAH-mediated lung carcinogenesis and tumorigenesis were studied. The major findings were as follows: (i) omega-3 fatty acids significantly decreased PAH-DNA adducts in the lungs of each of the genotypes studied; (ii) decreases in PAH-DNA adduct levels by EPA/DHA was in part due to inhibition of CYP1B1; (iii) inhibition of soluble epoxide hydrolase (sEH) enhanced the EPA/DHA-mediated prevention of pulmonary carcinogenesis; and (iv) EPA/DHA attenuated PAH-mediated carcinogenesis in part by epigenetic mechanisms. Taken together, our results suggest that omega-3 fatty acids have the potential to be developed as cancer chemo-preventive agents in people. [ABSTRACT FROM AUTHOR]

Domino reaction of benzo[d]thiazole‐2‐methylamine (S1) has been developed in the presence of MnCl2 ⋅ 4H2O, leading to tetrasubstituted pyrrole coordinated dinuclear Mn(II) complex 1 ([MnClP]2, P−=2,3,4,5‐tetrakis(benzo[d]thiazol‐2‐yl)pyrrol‐1‐ide). The reaction process has been studied by assigning a series of intermediates based on time‐dependent mass spectrometry, control experiments, crystallography, and density functional theory (DFT) theoretical calculation. A plausible mechanism involving an unprecedented divergent‐convergent domino sequence has been proposed. Compound S1 could be activated by MnCl2 ⋅ 4H2O via coordination, which divergently produces two intermediates imine II (1‐(benzo[d]thiazol‐2‐yl)‐N‐(benzo[d]thiazol‐2‐ylmethyl)methanimine) and alkene C (1,2‐bis(benzo[d]thiazol‐2‐yl)ethene) through oxidative self‐condensation and free radical coupling followed by elimination, respectively. They could then react with each other convergently via formal [3+2] cycloaddition to give deprotonated tetrasubstituted pyrrole coordinated intermediate [MnClP] after aromatization. Dimerization of [MnClP] produces the final product 1. Three C−C bonds and one C−N bond are formed through this six‐step domino sequence. The corresponding organic skeleton (HP: 2,2′,2′′,2′′′‐(1H‐pyrrole‐2,3,4,5‐tetrayl)tetrakis(benzo[d]thiazole)) has been obtained from 1 and shows a higher fluorescent quantum yield (52 %) than the reported 3,4‐diphenyl substituted analogue 2,2′‐(3,4‐diphenyl‐1H‐pyrrole‐2,5‐diyl)bis(benzo[d]thiazole) (DPB) (42 %). [ABSTRACT FROM AUTHOR]

More than eight million premature deaths annually can be attributed to air pollution, with 99% of the world's population residing in areas below recommended air quality standards. Hence, the present study aimed to examine the association between primary DNA damage and air pollution data among 123 participants enrolled between 2011 and 2015 in Zagreb, Croatia. While most measured air pollutants adhered to regulatory limits, benzo[a]pyrene concentrations bound to PM10 exceeded them. Factorial analysis narrowed down air pollution data to four exposure factors (particulate matter, two metal factors, and other pollutants). Despite the absence of significant positive associations between modeled air pollution exposure factors and comet assay descriptors (tail length, tail intensity, tail moment, and highly damaged nuclei), the critical health implications of air pollution warrant further investigations, particularly with biomarkers of exposure and different biomarkers of effect in populations facing air pollution exposure. [ABSTRACT FROM AUTHOR]

Cancer, which is currently rated as the second-leading cause of mortality across the globe, is one of the most hazardous disease groups that has plagued humanity for centuries. The experiments presented here span over two decades and were conducted on a specific species of mice, aiming to neutralize a highly carcinogenic agent by altering its chemical structure when combined with certain compounds. A plethora of growth models, each of which makes use of distinctive qualities, are utilized in the investigation and explanation of the phenomena of chemically induced oncogenesis and prevention. The analysis ultimately results in the formalization of the process of locating the growth model that provides the best descriptive power based on predefined criteria. This is accomplished through a methodological workflow that adopts a computational pipeline based on the Levenberg–Marquardt algorithm with pioneering and conventional metrics as well as a ruleset. The developed process simplifies the investigated phenomena as the parameter space of growth models is reduced. The predictability is proven strong in the near future (i.e., a 0.61% difference between the predicted and actual values). The parameters differentiate between active compounds (i.e., classification results reach up to 96% in sensitivity and other performance metrics). The distribution of parameter contribution complements the findings that the logistic growth model is the most appropriate (i.e., 44.47%). In addition, the dosage of chemicals is increased by a factor of two for the next round of trials, which exposes parallel behavior between the two dosages. As a consequence, the study reveals important information on chemoprevention and the cycles of cancer proliferation. If developed further, it might lead to the development of nutritional supplements that completely inhibit the expansion of cancerous tumors. The methodology provided can be used to describe other phenomena that progress over time and it has the power to estimate future results. [ABSTRACT FROM AUTHOR]

One of the important classes of aza-polycyclic compounds is Phenazine systems which are naturally present and synthetically derived. More than 6000 phenazine compounds are recognized; among them, pyran and chromene fused Benzo[α]phenazines have gained special attention due to their fascinating biological properties. In this regard, synthesizing these phenazinle derivatives by multicomponent reactions has gained much attention due to the advantages associated with the process. Hence seeing the contribution of pyran and chromene fused benzo phenazines to the pharmaceutical field, this review highlights the synthesis of these compounds by different catalytic conditions involving the use of nontoxic catalysts and solvents in a multicomponent system. This review evaluates studies reported since 2012 on the multicomponent green synthesis of pyran and chromene fused benzo phenazines. [ABSTRACT FROM AUTHOR]

Light and atmospheric pollution are both independently implicated in cancer induction and premature aging. Evidence has been growing more recently on the toxic synergy between light and pollutants. Polycyclic aromatic hydrocarbons (PAHs) originate from the incomplete combustion of organic matter. Some PAHs, such as the Benzo[a]pyrene (BaP), absorb ultraviolet A (UVA) wavelengths and can act as exogenous chromophores, leading to synergistic toxicity through DNA damage and cytotoxicity concomitant to ROS formation. In this study, we shed light on the mechanism underlying the toxic synergy between PAHs and UVA. Using dermal fibroblasts co-exposed to UVA and BaP, we have demonstrated that the photosensitization reaction causes mortality, which is most likely caused by ROS accumulation. We have shown that these ROS are concentrated in the lipids, which causes an important induction of lipid peroxidation and malondialdehyde, by-products of lipid peroxidation. We have also shown the accumulation of bulky DNA damage, most likely generated by these by-products of lipid peroxidation. To our knowledge, this study represents the first one depicting the molecular effects of photo-pollution on dermal skin. [ABSTRACT FROM AUTHOR]

This study examined the safety of meat products from north Serbia (Vojvodina), smoked in traditional conditions, from a PAH point of view, and assessed the possibility of their reduction in these types of products. Samples of dry cured meat products, bacons and dry fermented sausages smoked in six different chambers on the territory of Vojvodina were examined. The contents of 16 polycyclic aromatic hydrocarbons, from the United States Environmental Protection Agency list (16 US-EPA PAHs), and sensory quality of meat products were determined. The total content of 16 US-EPA PAHs in dry cured meat products was in the range from 99.73 μg/kg to 412.76 μg/kg; in bacons it was in the range from 36.43 μg/kg to 188.86 μg/kg; and in dry fermented sausages in the range from 47.23 μg/kg to 270.60 μg/kg. The lowest contents of 16 US-EPA PAHs compounds were determined in meat products smoked in traditional conditions during 3–5 days (3–4 h per day) at a distance of 2.5 m between the fire and products. Generally, it can be concluded that shortening of smoking process is justified, because products of good sensory quality and with decreased content of PAHs compounds were obtained. Benzo[a]pyrene, whose maximum allowed content in smoked meat products is 2 μg/kg, was below the limit of detection in all examined traditional meat products from Vojvodina. Also, contents of PAH4, sum of benz[a]anthracene, chrysene, benzo[a]pyrene and benzo[b]fluoranthene, were in the range from ND to 2.22 μg/kg, still greatly lower than the set maximum value. These results indicated the safety of dry cured meat products, bacons and dry fermented sausages from the territory of north Serbia (Vojvodina), as defined by EU Regulation 2023/915 criteria for PAHs contents. [ABSTRACT FROM AUTHOR]

Premature ovarian insufficiency (POI) is a condition in which the quantity of follicles and the quality of oocytes gradually decrease. This results in an estrogen secretion disorder and abnormal follicle development, which can lead to related diseases, early onset of menopause, sexual dysfunction, and an increased risk of cardiovascular issues, osteoporosis, and depression, among others. This disease significantly impacts the physical and mental health and overall quality of life of affected women. Factors such as genetic abnormalities, oophorectomy, radiotherapy for malignancy, idiopathic conditions, and an unhealthy lifestyle, including smoking, can accelerate the depletion of the follicular pool and the onset of menopause. Extensive research has been conducted on the detrimental effects of tobacco smoke on the ovaries. This article aims to review the advancements in understanding the impact of tobacco smoke on POI, both in vivo and in vitro. Furthermore, we explore the potential adverse effects of common toxicants found in tobacco smoke, such as polycyclic aromatic hydrocarbons (PAHs), heavy metals like cadmium, alkaloids like nicotine and its major metabolite cotinine, benzo[a]pyrene, and aromatic amines. In addition to discussing the toxicants, this article also reviews the complications associated with POI and the current state of research and application of treatment methods. These findings will contribute to the development of more precise treatments for POI, offering theoretical support for enhancing the long-term quality of life for women affected by this condition. [ABSTRACT FROM AUTHOR]

This paper's purpose was to evaluate the interaction between three imidazole derivatives, (2-methyl-1H-imidazol-1-yl)methanol (SAM3), 1,1′-methanediylbis(1H-benzimidazole (AM5) and (1H-benzo[d]imidazol-1-yl)methanol 1-hydroxymethylbenzimidazole (SAM5) on the one hand, and sodium dodecyl sulphate (SDS) on the other, as antifungal combinations against Candida spp. Inhibitory activity was assessed using the agar diffusion method and Minimal Inhibitory Concentration (MIC) and showed moderate inhibitory activity of single imidazole derivatives against Candida spp. The mean value of MIC ranged from 200 µg/mL (SAM3) to 312.5 µg/mL (SAM3), while for SDS the MIC was around 1000 µg/mL. When used in combination with SDS, the imidazole derivatives demonstrated an improvement in their antifungal activity. Their MIC decreased over five times for AM5 and over seven times for SAM3 and SAM5, respectively, and ranged from 26.56 µg/mL (SAM3) to 53.90 µg/mL (AM5). Most combinations displayed an additive effect while a clear synergistic effect was recorded in only a few cases. Thus, the FIC Index (FICI) with values between 0.311 and 0.375 showed a synergistic effect against Candida spp. when SDS was associated with SAM3 (three strains), SAM5 (two strains) and AM5 (one strain). The association of imidazole derivatives with SDS led to the increased release of cellular material as well as the intracellular influx of crystal violet (CV), which indicated an alteration of the membrane permeability of Candida spp. cells. This favored the synergistic effect via increasing the intracellular influx of imidazoles. [ABSTRACT FROM AUTHOR]

Benzo[a]pyrene (BaP) and 2,2′,4,4′-tetrabrominated diphenyl ether (BDE-47) are common contaminants in the environment, posing a threat to the ecosystems and human health. Currently, information on the microbial metabolism of BaP and BDE-47 as well as the correlated bacteria is still limited. This research aimed to study the degradation of BaP and BDE-47 by enriched cultures originated from an agricultural soil in Tianjin (North China) and characterize the bacteria involved in the degradation. Two sets of experiments were set up with BaP and BDE-47 (2 mg/L) as the sole carbon source, respectively. The degradation of BaP and BDE-47 occurred at rate constants of 0.030 /d and 0.026 /d, respectively. For BaP, the degradation products included benzo[a]pyrene-9,10-dihydrodiol or its isomers, ben-zo(a)pyrene-7,8-dihydrodiol-9,10-epoxide, and cis-4 (8-hydroxypyrenyl-7)-2-oxo-3-butenoic acid. For BDE-47, the degradation products included 2,2′,4-tribrominated diphenyl ether (BDE-17), 2,4-dibrominated diphenyl ether (BDE-7), and hydroxylated dibromodiphenyl ether. The bacterial community structures in the original soil, the BaP culture, and the BDE-47 culture were quite different. The richness and diversity of bacteria in the two cultures were much lower than that in the original soil, and the BaP culture had higher richness and diversity than the BDE-47 culture. In the BaP culture, multiple species such as Niabella (23.4%), Burkholderia-Caballeronia-Paraburkholderia (13.7%), Cupriavidus (8.3%), and Allorhizobi-um-Neorhizobium-Pararhizobium-Rhizobium (8.0%) were dominant. In the BDE-47 culture, an unassigned species in the Rhizobiaceae was dominant (82.3%). The results from this study provide a scientific basis for the risk assessment and bioremediation of BaP and/or BDE-47 in a contaminated environment. [ABSTRACT FROM AUTHOR]

Discovery of antibiotics is regarded as one of the critical moments in the history of medicine; however, irrational use caused the emergence of a phenomenon known as drug resistance. Once considered benign, Acinetobacter baumannii (A. baumannii) evolved to become a challenging pathogen threatening the current antibiotic era. In 2017, WHO appointed A. baumannii as the most critical pathogen towards which the development of novel antibiotics is keenly required. The current study intends to explore the silver nanoparticles (AgNPs) role in the weakening of virulence and biofilm through reducing the expression of outer membrane protein-A (OmpA), biofilm-associated protein (Bap), Acinetobacter baumannii autoinducer-I (abaI) and Acinetobacter baumannii receptor (abaR) genes in the multi-drug resistant (MDR) A. baumannii. All bacterial isolates were capable to form biofilm and exhibited high resistance levels to the antibiotics used including (ampicillin/sulbactam, ceftazidime, tobramycin, amikacin, gentamicin, levofloxacin, imipenem, ciprofloxacin, meropenem, piperacillin/tazobactam, cefepime, ceftriaxone, doxycycline, and trimethoprim/sulfamethoxazole). AgNPs were biologically synthesized by Pseudomonas aeruginosa (P. aeruginosa) (PA-AgNP) and characterized via FTIR, UV-vis, EDX, XRD, and SEM. Results of characterization tools supported the successful formation of crystalline AgNPs. Minimum-inhibitory concentrations of the harvested AgNPs were determined to study their antibiofilm and quorum quenching potential at subinhibitory concentrations (SIC). RT PCR was utilized to estimate the influence of PA-AgNPs on the quorum sensing (QS) and biofilm at level of gene expression. Exposure of the tested isolates to PA-AgNP at SIC values decreased their biofilm fabrication capacity and significantly downregulated candidate genes expression. The results show that P. aeruginosa can be used to bio-fabricate AgNPs capable of interrupting bacterial-growth and biofilm progress in the MDR A. baumannii through the downregulation of QS and biofilm-associated genes. [ABSTRACT FROM AUTHOR]

Benzopyrene (B[a]P) is a well-known carcinogen that can induce chronic inflammation and fibrosis in the liver, leading to liver disease upon chronic exposure. Nonalcoholic steatohepatitis (NASH) is a chronic liver condition characterized by fat accumulation, inflammation, and fibrosis, often resulting in hepatocellular carcinoma (HCC). In this study, we aimed to investigate the intricate connections between B[a]P exposure, NASH, and HCC. Through comprehensive bioinformatics analysis of publicly available gene expression profiles, we identified differentially expressed genes (DEGs) associated with B[a]P exposure, NASH, and liver cancer. Furthermore, network analysis revealed hub genes and protein–protein interactions, highlighting cellular metabolic dysfunction and disruption of DNA damage repair in the B[a]P-NASH-HCC process. Notably, HSPA1A and PPARGC1A emerged as significant genes in this pathway. To validate their involvement, we conducted qPCR analysis on cell lines and NASH mouse liver tissues and performed immunohistochemistry labeling in mouse and human HCC liver sections. These findings provide crucial insights into the potential regulatory mechanisms underlying benzopyrene-induced hepatotoxicity, shedding light on the pathogenesis of B[a]P-associated NASH and HCC. Moreover, our study suggests that HSPA1A and PPARGC1A could serve as promising therapeutic targets. Enhancing our understanding of their regulatory roles may facilitate the development of targeted therapies, leading to improved patient outcomes. [ABSTRACT FROM AUTHOR]

The structure–property relationship is always the focus when organic light-emitting materials are used mainly in the aggregated state in some fields, such as optoelectronic devices, sensors, and bioimaging. To clarify a clear structure–property relationship between the aggregate structure and the luminescent property, the intermolecular dimer, which represents the smallest aggregate in a number, is selected as an ideal research model. However, how to achieve an intermolecular dimer by a rational molecular design is rarely found in previous papers in this field. Here, we design and synthesize three pyrene derivatives, aiming at achieving the pyrene-based dimer in a solid state, by bridging pyrene and benzo[d]thiazole (BZT) in a different position on a phenylene. The pyrene and BZT groups are connected with each other in the ortho-, meta-, and para-positions of the phenylene to construct three molecules Py-oBZT, Py-mBZT, and Py-pBZT. Experimental and theoretical investigations demonstrate that only Py-oBZT shows pyrene-based dimer stacking with a discrete feature due to the large steric hindrance provided by the BZT group. Compared to individual pyrenes in the crystal, the pyrene-based dimer in the Py-oBZT crystal exhibits a different molecular orientation, which is verified by the presence of multiple potential wells of the pyrene dimer using a theoretical simulation of the potential energy surface. This work not only examines the effect of steric hindrance on the formation of the pyrene dimer packing, but also provides an understanding of the multiplicity of the pyrene dimer structures. [ABSTRACT FROM AUTHOR]

Herbal extracts represent a wide spectrum of biologically active ingredients with potential medical applications. By screening minor constituents of jasmine essential oil towards aryl hydrocarbon receptor (AhR) activity using a gene reporter assay (GRA), we found the antagonist effects of jasmone (3-methyl-2-[(2Z)-pent-2-en-1-yl]cyclopent-2-en-1-one). It inhibited 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-, benzo[a]pyrene (BaP)-, and 6-formylindolo[3,2-b]carbazole (FICZ)-triggered AhR-dependent luciferase activity in a concentration-dependent manner. However, the inhibition differed markedly between TCDD, BaP, and FICZ, with the latter being significantly less inhibited. The dose-response analysis confirmed an allosteric type of AhR antagonism. Furthermore, jasmone efficiently inhibited AhR activation by AhR agonists and microbial catabolites of tryptophan (MICTs). TCDD- and FICZ-inducible CYP1A1 expression in primary human hepatocytes was inhibited by jasmone, whereas in the human HepG2 and LS180 cells, jasmone antagonized only TCDD-activated AhR. Jasmone only partially displaced radiolabeled TCDD from its binding to mouse Ahr, suggesting it is not a typical orthosteric ligand of AhR. TCDD-elicited AhR nuclear translocation was not affected by jasmone, whereas downstream signaling events, including the formation of the AhR:ARNT complex and enrichment of the CYP1A1 promoter, were inhibited by jasmone. In conclusion, we show that jasmone is a potent allosteric antagonist of AhR. Such discovery may help to find and/or clarify the use of jasmone in pharmaco- and phytotherapy for conditions where AhR plays a key role. [ABSTRACT FROM AUTHOR]

The primary motivation of this paper is to report the effects of n-butanol addition (5, 20 and 35% by volume) to diesel fuel on regulated and polycyclic aromatic hydrocarbon (PAH) emissions of a diesel engine. PAH samples were quantified using rigorous analytical chemistry procedures to determine total PAHs, PAH dispersion and PAH toxicity. In comparison with diesel fuel, all n-butanol blends (DBu5, DBu20, and DBu35) reduced nitrogen oxides (NOx) emissions by 6.77%, 9.59%, and 20.08% and total PAH emissions by 66.86%, 75.33%, and 80.98%. In terms of the relative distribution of PAHs, a significant decrease was recorded in higher cyclic PAHs such as Pyrene, Benzo[a]anthracene, Chrysene, Benzo[k]floranthene, Benzo[a]pyrene for all blends. Similarly, the amount of the toxicity of the PAH emissions also decreased by 11.66%, 87.53%, and 67.28% with DBu5, DBu20 and DBu35 blends, respectively. With the addition of n-butanol to the diesel fuel, total PAH emissions were detected below the Occupational Safety and Health Administration's (OSHA)-Permissible Exposure Level. Overall, it was demonstrated that n-butanol addition to diesel fuel significantly reduced PAH formation which is helpful to prevent wet stacking, and prolong the operating time of the diesel engine especially at low loads or cold operating conditions. [ABSTRACT FROM AUTHOR]

Chemical bond cleavage by electron transfer to an organic molecule is a typical electro-initiated reaction; however, there are few examples of carbon—carbon bond cleavage. In this study, using cyclic voltammetry, chronoamperometry, controlled-potential electrolysis with chromatographic characterization of products, and ab initio quantum chemical calculations, it was shown that the electrochemical reduction of benzopinacol (1,1,2,2-tetra-phenyl-1,2-ethanediol) in aprotic solvents (DMF, MeCN, THF) in the presence of Bu4NClO4 as a supporting electrolyte is accompanied by cleavage of the central C–C bond, which follows the electron transfer. This initiates a chain reaction giving equimolar amounts of benzophenone and benzhydrol (diphenylmethanol). The decomposition is inhibited in the presence of medium-strength proton donors (phenol, benzoic and acetic acids, etc.) in the solution. A similar effect is attained by the addition of divalent metal salts, in particular Mg(ClO4)2. According to the results of quantum chemical calculations, the effective C–C bond cleavage in the benzopinacol radical anion to give a radical and an anion is due to a very low energy barrier (1.7 kcal mol−1) and is very thermodynamically favorable (ΔG°298 = −16.6 kcal mol−1). [ABSTRACT FROM AUTHOR]

Benzo[a]pyrene (BaP) is a common air pollutant that has been reported to cause oxidative stress and carcinogenesis. Wogonin, a flavonoid compound extracted from the roots of Scutellaria baicalensis, has been found to possess a variety of pharmacological activities, including anti‐inflammatory and anti‐cancer effects. The purpose of this study was to examine the ability of wogonin to alleviate the cytotoxicity induced by BaP in human airway epithelial cells and explore the corresponding mechanism. Our study found that wogonin treatment inhibited DNA damage and reactive oxygen species overproduction induced by BaP in human airway epithelial cells. In vitro enzyme assays showed that wogonin significantly inhibited the enzymatic activity of CYP1A1. In addition, wogonin decreased the basal level of CYP1A1 and inhibited the CYP1A1 overexpression induced by BaP, whereas overexpression of CYP1A1 partially reversed the effect of wogonin on BaP‐induced DNA damage. Meanwhile, a CYP1A1 inhibitor and CYP1A1 knockdown also showed these same effects. Further studies showed that wogonin regulates CYP1A1 expression by inhibiting CDK7 and CDK9 activity. The use of CDK7 or CDK9 inhibitors decreased BaP‐induced cytotoxicity and CYP1A1 expression. Finally, we found that the methoxy group of wogonin was crucial for its inhibitory activity. In conclusion, our data indicated that wogonin could effectively relieve BaP induced cytotoxicity, and its mechanism was related to the dual inhibition of CYP1A1 activity and expression. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) in urban environments have been globally concerned due to their significant health impacts on residents. However, little is known about potential risks of PAHs from centralized water source areas. In the present study, 326 soils samples from the main water source areas of Beijing were collected and the occurrence, source appointment, and risks of PAHs were systematically investigated based on the monitoring results from high-performance liquid chromatography (HPLC). The total PAHs (∑16 PAHs) concentrations ranged from 5.70 to 1512 ng/g with median value of 44.2 ng/g, in which 4-ring and 5-ring groups were the major components. PAHs concentrations in the cultivated land were significantly higher than other areas, which could reflect significant impact of soil organic matter and total nitrogen contents on the spatial variations of PAHs. Further source identifications through positive matrix factorization model (PMF) revealed that biomass (22.5%), coal (21.4%), gasoline (17.6%) and diesel (16.4%) combustion were dominant sources of soil PAHs in the study area. Moreover, the risk assessment indicated that total ecological and health risk of PAHs were negligible, but individual PAH, including pyrene and benzo(b)fluoranthene, should be concerned due to their potential risks in several monitored stations located in the secondary protection area of four reservoirs. Our study provided new insights into environmental risks of soils in main water source areas from PAHs and could be helpful for organic micropollutant controlling and drinking water safety in rapidly urbanizing cities. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus-type 1 (HIV-1) remains one of the leading contributors to the global burden of disease, and novel antiretroviral agents with alternative mechanisms are needed to cure this infection. Here, we describe an exploratory attempt to optimize the antiretroviral properties of benfluron, a cytostatic agent previously reported to exhibit strong anti-HIV activity likely based on inhibitory actions on virus transcription and Rev-mediated viral RNA export. After obtaining six analogs designed to modify the benzo[c]fluorenone system of the parent molecule, we examined their antiretroviral and toxicity properties together with their capacity to recognize the Rev Recognition Element (RRE) of the virus RNA and inhibit the RRE–Rev interaction. The results indicated that both the benzo[c] and cyclopentanone components of benfluron are required for strong RRE–Rev target engagement and antiretroviral activity and revealed the relative impact of these moieties on RRE affinity, RRE–Rev inhibition, antiviral action and cellular toxicity. These data provide insights into the biological properties of the benzo[c]fluorenone scaffold and contribute to facilitating the design of new anti-HIV agents based on the inhibition of Rev function. [ABSTRACT FROM AUTHOR]

We map the photochemical reactivity of two chromophores—a pyrene-chalcone and a methylene blue protected amine—from a one-pot reaction mixture based on their dynamic absorptivity changes upon light exposure, constructing a dual action plot. We employ the action plot data to determine a pathlength-independent λ-orthogonality window, allowing the orthogonal folding of distinct polymer chains into single chain nano-particles (SCNPs) from the same reaction mixture. [ABSTRACT FROM AUTHOR]

Approximately 252 mg of Sb-T-M, 240 mg of Sb-S-M, 304 mg of Sb-L-M, 176 mg of Sb-T-E, 224 mg of Sb-S-E, 288 mg of Sb-L-E, 128 mg of Sb-T-A, 196 mg of Sb-S-A, 324 mg of Sb-L-A, 184 mg of Sb-T-W, 272 mg of Sb-S-W, and 290 mg of Sb-L-W were obtained from 1000 mg of dried plant powder. The antibacterial and antioxidant properties of extracts and the isolated compounds from I S. hatschbachii i [48], I S. magnifica i [49], I S. aggregata i [50], I S. warmingii i [51], I S. mauroana i [44,52], and I S. reitzii i [53] have also been investigated experimentally. Furthermore, even using acetone as the extraction solvent, tuber extracts of I S. bullata i also had very low cytotoxic activities as compared to the leaf extract (Figure 3). Compounds isolated from I S. aggregata i [45], I S. reitzii i [46], and I S. leucotricha i [47] have been further analyzed in cytotoxic activities. [Extracted from the article]

Exposure to coal mining dust poses a substantial health hazard to individuals due to the complex mixture of components released during the extraction process. This study aimed to assess the oxidative potential of residual coal mining dust on human lymphocyte DNA and telomeres and to perform a chemical characterization of coal dust and urine samples. The study included 150 individuals exposed to coal dust for over ten years, along with 120 control individuals. The results revealed significantly higher levels of DNA damage in the exposed group, as indicated by the standard comet assay, and oxidative damage, as determined by the FPG-modified comet assay. Moreover, the exposed individuals exhibited significantly shorter telomeres compared to the control group, and a significant correlation was found between telomere length and oxidative DNA damage. Using the PIXE method on urine samples, significantly higher concentrations of sodium (Na), phosphorus (P), sulfur (S), chlorine (Cl), potassium (K), iron (Fe), zinc (Zn), and bromine (Br) were observed in the exposed group compared to the control group. Furthermore, men showed shorter telomeres, greater DNA damage, and higher concentrations of nickel (Ni), calcium (Ca), and chromium (Cr) compared to exposed women. Additionally, the study characterized the particles released into the environment through GC–MS analysis, identifying several compounds, including polycyclic aromatic hydrocarbons (PAHs) such as fluoranthene, naphthalene, anthracene, 7H-benzo[c]fluorene, phenanthrene, pyrene, benz[a]anthracene, chrysene, and some alkyl derivatives. These findings underscore the significant health risks associated with exposure to coal mining dust, emphasizing the importance of further research and the implementation of regulatory measures to safeguard the health of individuals in affected populations. [ABSTRACT FROM AUTHOR]

The long-distance migration of polycyclic aromatic hydrocarbons (PAHs) promotes their release into the marine environment, posing a serious threat to marine life. Studies have shown that PAHs have significant immunotoxicity effects on bivalves, but the exact mechanism of immunotoxicity remains unclear. This paper aims to investigate the effects of exposure to 0.4, 2, and 10 μg/L of benzo(a)pyrene (B[a]P) on the immunity of Chlamys farreri under environmental conditions, as well as the potential molecular mechanism. Multiple biomarkers, including phagocytosis rate, metabolites, neurotoxicity, oxidative stress, DNA damage, and apoptosis, were adopted to assess these effects. After exposure to 0.4, 2, and 10 μg/L B[a]P, obvious concentration-dependent immunotoxicity was observed, indicated by a decrease in the hemocyte index (total hemocyte count, phagocytosis rate, antibacterial and bacteriolytic activity). Analysis of the detoxification metabolic system in C. farreri revealed that B[a]P produced B[a]P-7,8-diol-9,10-epoxide (BPDE) through metabolism, which led to an increase in the expression of protein tyrosine kinase (PTK). In addition, the increased content of neurotransmitters (including acetylcholine, γ -aminobutyric acid, enkephalin, norepinephrine, dopamine, and serotonin) and related receptors implied that B[a]P might affect immunity through neuroendocrine system. The changes in signal pathway factors involved in immune regulation indicated that B[a]P interfered with Ca2+ and cAMP signal transduction via the BPDE-PTK pathway or neuroendocrine pathway, resulting in immunosuppression. Additionally, B[a]P induced the increase in reactive oxygen species (ROS) content and DNA damage, as well as an upregulation of key genes in the mitochondrial pathway and death receptor pathway, leading to the increase of apoptosis rate. Taken together, this study comprehensively investigated the detoxification metabolic system, neuroendocrine system, and cell apoptosis to explore the toxic mechanism of bivalves under B[a]P stress. [ABSTRACT FROM AUTHOR]

Toxic compounds such as heterocyclic amines (HAs) and polycyclic aromatic hydrocarbons (PAHs) can be produced during food processing, especially meat products. This study aims to monitor the formation of HAs and PAHs in fried pork fiber, a common meat product in Taiwan, at different processing conditions. A total of six experimental groups, including raw pork tenderloin, dried pork filaments, sesame oil-stir-fried pork at 160 °C for 15 min, sesame oil-stir-fried pork at 200 °C for 6 min, lard-stir-fried pork at 160 °C for 15 min, and lard-stir-fried pork at 200 °C for 6 min, were prepared and analyzed for formation of HAs via UPLC-MS/MS and PAHs via GC-MS/MS in triplicate. Frying in sesame oil or lard showed a greater content of total HAs in fried pork fiber processed at 160 °C for 15 min than at 200 °C for 6 min. However, in the same heating conditions, pork fiber fried in sesame oil produced a higher level of total HAs than that fried in lard. Of the various HAs in fried pork fiber, both Harman and Norharman were generated in the highest amount. The precursors, including reducing sugar, amino acid, and creatine/creatinine, played a vital role in HAs formation in fried pork fiber. For total PAHs, the highest level was shown for pork fiber fried in lard at 200 °C/6 min, followed by frying in sesame oil at 200 °C/6 min and 160 °C/15 min, and in lard at 160 °C/15 min. Like HAs, at the same heating condition, a greater content of total PAHs was produced in pork fiber fried in sesame oil than in lard. Notably, the highly toxic benzo[a]pyrene was undetected in fried pork fiber. The PAH precursor benzaldehyde was shown to generate at a much higher level than 2-cyclohexene-1-one and trans,trans-2,4-decadienal in fried pork fiber, and it should play a more important role in PAH formation. Principal component analysis (PCA) also revealed that the formation mechanism of HAs and PAHs in fried pork fiber was different. [ABSTRACT FROM AUTHOR]

1,3‐Disubstituted N‐aryl‐2H‐isoindoles have been synthesized by a cascade reaction of divinyl ethers, which are derived from easily available 4‐bromoisocoumarins, with substituted anilines in HFIP. This cascade reaction consists of a ring‐opening step through addition‐elimination mechanism and the following 5‐exo‐tet type ring‐closing step via the intramolecular nucleophilic substitution reaction. Thus obtained 2H‐isoindoles have been derivatized to high‐order nitrogen‐containing polycycles including less accessible benzo[a]ullazines. [ABSTRACT FROM AUTHOR]

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that plays an important role in gastrointestinal barrier function, tumorigenesis, and is an emerging drug target. The resident microbiota is capable of metabolizing tryptophan to metabolites that are AHR ligands (e.g., indole-3-acetate). Recently, a novel set of mutagenic tryptophan metabolites named indolimines have been identified that are produced by M. morganii in the gastrointestinal tract. Here, we determined that indolimine-200, -214, and -248 are direct AHR ligands that can induce Cyp1a1 transcription and subsequent CYP1A1 enzymatic activity capable of metabolizing the carcinogen benzo(a)pyrene in microsomal assays. In addition, indolimines enhance IL6 expression in a colonic tumor cell line in combination with cytokine treatment. The concentration of indolimine-248 that induces AHR transcriptional activity failed to increase DNA damage. These observations reveal an additional aspect of how indolimines may alter colonic tumorigenesis beyond mutagenic activity. [ABSTRACT FROM AUTHOR]

In this work, the capability of step1 and step2 of the synthesis reaction mechanism of the 2-phenyl-1H-benzo[d]imidazole as a rate-determining step (RDS) has been energetically and thermodynamically evaluated using theoretical methods. The results were profoundly compared to the experimental approaches. The role of population explosion resulting from the increased hydroxyl groups within the catalyst structure was considered using some models with different hydroxyl groups on the reaction. Herein, the theoretical rate constants were obtained using the potential energy surfaces (PESs) and the transition state theory (TST) at the M06-2X/6-31 + G(d,p) level of theory. The calculated results showed that the second step (step2) is an RDS. In step2, H2O elimination can be proceeded by effective participation of catalyst for making a four-membered ring structure of TS that is generated harder than a six-membered ring mechanism (Ea = 56.3 and Ea = 29.7 kcal mol−1, respectively). Moreover, the reaction rate (for step2 as the RDS) in the presence of a modified catalyst (similar to sucrose containing five hydroxyl groups) speeds up 100,000 times more than the simple catalyst such as methanol (involving one hydroxyl group) and ethylene glycol (with the two hydroxyl groups). Theoretical calculations exhibited that the catalyst enables to facilitate a proton transfer process in step4 to make a great facility for doing oxidation process easily in step5 as the fastest step. In addition, when the reaction was followed without assisted-catalyst, herein, activation energy for step4 increased up to 34.8 kcal mol−1 while it was 10.8 kcal mol−1 in the presence of a catalyst. [ABSTRACT FROM AUTHOR]

Exhaust emissions from ships have garnered significant attention because of their impact on global climate change, deterioration of air quality, and potential risks to human health. Consequently, it is necessary and urgent to quantify the gaseous and particulate emission factors (EFs) of ships in a local area. In order to supplement native EF profile data, an inland cargo ship in China was selected for measuring gaseous and particle pollutants under real-world operation modes. The fuel-based EFs of carbon dioxide, carbon monoxide (CO), nitrogen oxides, and hydrocarbons (THC) were 2965–3144 g/kg, 8.04–83.53 g/kg, 64.51–126.20 g/kg, and 3.90–23.35 g/kg, respectively. The maximum values of CO EF and THC EF were achieved under idling mode, which were 10.4 and 5.3 times those observed under cruising (500 rpm) mode, as extremely poor engine loads under idling mode can result in low temperature, low pressure, and uneven mixture of air and fuel. Organic carbon and element carbon were identified as the most abundant compositions of particulate matter (PM). Ions and elements were primarily dominated by SO42− and S, which can be attributed to the utilization of fuels with high sulfur content. Additionally, hopanes (dominated by 17α(H),21β(H)-Hopane and 17α(H),21β(H)-29-Norhopane) and fatty acids (dominated by n-Hexadecanoic acid and n-Octadecanoic acid) have the potential to serve as tracers for ship exhaust emissions. Pyrene and fluoranthene, two EPA priority polycyclic aromatic hydrocarbons (PAHs), were identified as the major constituents of PAHs and accounted for 50% of total PAHs. This finding also provides an explanation for the significant contribution of four-ring PAHs to the total PAHs mass. [ABSTRACT FROM AUTHOR]

The chemosensor selectivity of 3-oxo-3H-benzo[f]chromen-2-carboxylic acid (ABKK) toward Na+ metal ion has been successfully studied in silico using FMO (Frontier Molecular Orbital) analysis method. The geometry of the ABKK structure was optimized by the DFT (Density Functional Theory) method with a function/basis set: M06/6-31G (d, p). Afterward, the electronic properties of the ABKK structure before and after binding to sodium ion were analyzed and compared with the ABKK+other metal ion structures representing valence charges 1-3 and within the constraints of the basis set used. The results of geometry optimization showed that 1ABKK+Na+ has a more positive frequency/minima than 2ABKK+Na+ with interaction energies of 145 and 200.5 kcal/mol, respectively. Ignoring the role of solvents, FMO analysis revealed that the bandgap energy of fluorophore and receptor interactions (ΔE LUMO Fl-Rs 1ABKK+Na+) and (E HOMO Fl-Rs 2ABKK+Na+) were 0.631 and 0.336 eV, correspondingly. In addition, the bandgap energy of fluorophore/ΔE Fl 1ABKK+Na+ and 2ABKK+Na+ were calculated at 4.347 and 4.362 eV. Comparing those two types of bandgap energies with the bandgap belonging to ABKK+other metal ions, the excitation, and PET (Photoinduced Electron Transfer) processes were estimated to be relatively favorable experienced by 2ABKK+Na+. Finally, the selectivity of ABKK toward sodium metal ions from the computational calculations was relatively in agreement with the laboratory experimental results. [ABSTRACT FROM AUTHOR]

BACKGROUND: The association between alcohol and certain cancers is well established, yet beyond ethanol and its metabolite acetaldehyde, little is known about the presence of other carcinogenic compounds in alcoholic beverages, including polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (a Group I carcinogen). OBJECTIVES: We summarized the published literature on PAH levels in alcoholic beverages to identify potential gaps in knowledge to inform future research. Methods: Medline and Scopus were searched for primary research published from January 1966 to November 2023 that quantified PAH levels among various types of alcoholic beverages, including whisky, rum, brandy, gin, vodka, wine, and beer. Studies that were not primary literature were excluded; only studies that quantified PAH content in the specified alcoholic beverages were included. Results: Ten studies published from 1966 to 2019 met the criteria for review. Other than beverage type, no publication reported selection criteria for their samples of tested alcohol products. Studies used a variety of analytical methods to detect PAHs. Of the 10 studies, 7 were published after 2000, and 6 assessed DISCUSSION: PAHs are found in some alcohol products and appear to vary by beverage type. However, there is an incomplete understanding of their presence and levels among large, representative samples from the range of currently available alcohol products. Addressing this gap could improve understanding of alcohol-cancer relationships and may have important implications for public health and the regulation of alcohol products. In addition, novel methods, such as direct mass spectroscopy, may facilitate more thorough testing of samples to further investigate this relationship. https://doi.org/10.1289/EHP13506, Introduction Alcohol consumption in much of the world is widely seen as a social norm, but it has serious health, social, and economic impacts. (1) An area of great interest [...]

Benzo(a)pyrene (BaP), the earliest and most significant carcinogen among polycyclic aromatic hydrocarbons (PAHs), has been found in foods, tobacco smoke, and automobiles exhaust, etc. Exposure to BaP induced DNA damage directly, or oxidative stress-related damage, resulting in cell apoptosis and carcinogenesis in human respiratory system, digestive system, reproductive system, etc. Moreover, BaP triggered genome-wide epigenetic alterations by methylation, which might cause disturbances in regulation of gene expression, and thereby induced cancer. It has been proved that BaP reduced genome-wide DNA methylation, and activated proto-oncogene by hypomethylation in the promoter region, but silenced tumor suppressor genes by promoter hypermethylation, resulting in cancer initiation and progression. Here we summarized the changes in DNA methylation in BaP exposure, and revealed the methylation of DNA plays a role in cancer development. [ABSTRACT FROM AUTHOR]

AIM: To investigate the effects of 17β-estradiol （E2） and benzopyrene （BaP） on programmed death ligand 1 （PD-L1） expression in human lung adenocarcinoma A549 cells and their potential molecular mechanisms. METHODS: The A549 cells were treated with 1~1 000 nmol/L E2 and 0. 008~5 μmol/L BaP, and the optimal concentrations were identified. The cells were divided into control group, E2 group, BaP group, and E2+BaP group. Each set of experiments was repeated 3 times. RT-qPCR was used to determine the mRNA level of PD-L1. Western blot was used to detect the expression levels of PD-L1, aryl hydrocarbon receptor（ AHR） and hypoxia-inducible factor-1α（ HIF-1α）, as well as the phosphorylation levels of protein kinase B （PKB/AKT） and extracellular signal-regulated kinase 1/2 （ERK1/2）. The AKT-specific inhibitor LY294002 and ERK1/2-specific inhibitor PD98059 were used for reverse verification, and the changes in PD-L1 expression were observed. RESULTS: Compared with E2 group and BaP group, the mRNA and protein levels of PD-L1 in the A549 cells of E2+BaP group were significantly up-regulated （P<0. 05）. The protein levels of AHR, HIF-1α, p-AKT and p-ERK1/2 in E2+BaP group were significantly higher than those in other groups （P<0. 05） LY294002 and PD98059 reversed the up-regulation of PD-L1 induced by E2+BaP （P<0. 05）. CONCLUSION: E2 combined with BaP up-regulates PD-L1 expression in human lung adenocarcinoma A549 cells through abnormal activation of the AHR-AKT-ERK1/2 signaling pathway. [ABSTRACT FROM AUTHOR]

In this study, levels of benzo(a)pyrene and sum of PAH4 compounds (benzo(a)pyrene benzo(a)anthracene, chrysene and benzo(b)fluoranthene) in four types of dry fermented sausages (n=126) collected from market in Belgrade, Serbia, were analysed. The levels of benzo(a)pyrene and PAH4 compounds ranged < 0.2-0.6 μg/kg and < 0.2-2.7 μg/kg, respectively. The levels of benzo[a]pyrene and sum of PAH4 in all samples were < 2 μg/kg and < 12 μg/kg, respectively, which is the MRL in smoked meat and smoked meat products regulated both by Serbian and EU legislation. PC analysis showed that kulen and sremska sausage have a higher capacity for absorption of the analysed compounds during the process of meat smoking than do the other investigated sausages. [ABSTRACT FROM AUTHOR]

Benzo[a]pyrene is a widespread environmental pollutant and a strong carcinogen. It is important to understand its bio-toxicity and degradation mechanism. Herein, we studied the excited state dynamics of benzo[a]pyrene by using time-resolved fluorescence and transient absorption spectroscopic techniques. For the first time, it is identified that benzo[a]pyrene in its singlet excited state could react with oxygen, resulting in fluorescence quenching. Additionally, effective intersystem crossing can occur from its singlet state to the triplet state. Furthermore, the interaction between the excited benzo[a]pyrene and ct-DNA can be observed directly and charge transfer between benzo[a]pyrene and ct-DNA may be the reason. These results lay a foundation for further understanding of the carcinogenic mechanism of benzo[a]pyrene and provide insight into the photo-degradation mechanism of this molecule. [ABSTRACT FROM AUTHOR]