Production Of Adducts Research Articles

Quantitative Determination of Volatile N-Nitrosamines in Meat Products Using Gas Chromatography Coupled to an Ion Mobility Spectrometer with an Ammonia Dopant.

Herein, we develop a novel method using gas chromatography-ion mobility spectrometry (IMS) with an ammonia dopant for the determination of volatile N-nitrosamines in meat products. The IMS system was implemented with Fourier deconvolution multiplexing to simultaneously improve the resolving power and sensitivity. The ammonia dopant mitigated the formation of N-nitrosamine dimer ions, suppressing the ionization of interferents and shifting the reactant peak from hydrated protons to hydrated ammonium ions. The ammonium adduct product ions of N-nitrosamines were confirmed using time-of-flight mass spectrometry. The instrument limits of detection and quantitation for nitrosamines were 0.78-1.79 and 2.60-5.82 ng/mL, respectively, with recoveries between 71.39% and 110.59% using a simple water distillation method. The developed method showed satisfactory performance when applied to the detection of nitrosamines in various meat products.

Multi-defense Pathways against Electrophiles through Adduct Formation by Low Molecular Weight Substances with Sulfur Atoms.

There is a variety of electrophiles in the environment. In addition, there are precursor chemicals that undergo metabolic activation by enzymes and conversion to electrophiles in the body. Although electrophiles covalently bind to protein nucleophiles, they also form adducts associated with adaptive or toxic responses. Low molecular weight compounds containing sulfur are capable of blocking such adduct formation by capturing the electrophiles. In this review, we present out findings on the capture and inactivation of electrophiles by 1) intracellular glutathione, 2) reactive sulfur species and 3) extracellular cysteine (formed during the production of sulfur adducts). These actions not only substantially suppress electrophilic activity but also regulate protein adduct formation.

Exogenous Reactive Oxygen Species Augments SMAD4 Expression And TGF-β Paradox in Human Breast Cancer

Background: The Transforming growth factor-β (TGF-β) functions to induce apoptosis, cell cycle arrest, and differentiation is central to sustaining tissue homeostasis and maintaining genomic stability. TGF-β normally, an effective tumor-suppressor that restricts the uncontrolled division of cells augments the development and progression of human malignancies when cytostatic activities of TGF-β are resisted by genetic and epigenetic events caused by tumorigenesis. This dichotomic nature of TGF-β during oncogenesis termed as “TGF-β Paradox,” persists to be the most crucial and puzzling query regarding its physio-pathological function and the role of cellular antioxidant status is highly interrelated which warrants more studies on the role of endogenous reactive oxygen species (ROS) in deciding epithelial-mesenchymal transition (EMT) process. The objective of the study was to check whether enhanced ROS augments the TGF-β pathway facilitating EMT. Methods: In vitro toxicity assay was performed to assess the appropriate concentration of hydrogen peroxide (H2O2) imparting oxidative stress. Comet assay and 8-OHdG (8-hydroxy-2’-deoxyguanosine) enzyme-linked immunosorbent assay (ELISA) were performed to check the extent of DNA damage and adduct production respectively. Mitogen-activated protein kinase (MAPK) p38 ELISA and mRNA gene expression analysis of TGF-β and SMAD were done to verify the effect of H2O2 on these signaling. Results: The objective of the study was to check whether enhanced ROS augments the TGF-β pathway facilitating EMT. Along with morphological alterations, a dose-dependent decrease in cell viability was seen at 300µM of H2O2 compared to 75µM. DCFDA labeling discovered the dose-dependent gradation of intracellular ROS generation and this was correlated to increased cellular DNA damage and DNA adduct production which was increased linearly with increasing H2O2 as evident with comet test and 8-OHdG ELISA. Significantly reduced MAPK p38 activity revealed by indirect ELISA analysis suggests lessened suppression of cell growth. Conclusions: The study establishes that higher intracellular ROS will facilitate the TGF-β paradox leading to epithelial mesenchymal transition which can adversely affect therapeutic strategies targeting EMT

Mass Spectrometry Imaging for the Characterization of C═C Localization in Unsaturated Lipid Isomers at the Single-Cell Level.

Unsaturated lipids with carbon-carbon double bonds (C═C) have been implicated in the pathogenesis of various diseases. While mass spectrometry imaging (MSI) has been employed to map the distribution of lipid isomers in tissue sections, the identification of lipid C═C positional isomers at the single-cell level using MSI poses a significant challenge. In this study, we developed a novel approach utilizing ToF-SIMS in conjunction with the Paternò-Büchi (P-B) photochemical reaction to characterize the C═C localization in unsaturated lipid isomers at the single-cell level. The P-B reaction was employed to produce adduct products, which were subsequently subjected to collision-induced dissociation by the primary ion beam of ToF-SIMS to generate characteristic ion pairs indicative of the presence of C═C bonds. Utilizing this approach, lipid isomers in brain and skeletal tissues from mice, as well as different cell lines, were visualized at single-cell resolution. Furthermore, distinct variations in the composition of FA 18:1 isomers across different microregions and cell types were revealed. Our P-B ToF-SIMS approach enables the accurate identification and characterization of complex lipid structures with remarkable spatial resolution and can be helpful in understanding the physiological role of these C═C positional isomers.

Antigen Presenting Cell activator protein 1 (AP-1) complex contributes to Salt-sensitive Blood Pressure

Salt-sensitivity of blood pressure (SSBP) affects 50% of the hypertensive and 25% of the normotensive population and is a major independent risk factor for cardiovascular morbidity and mortality. We previously found that SSBP is associated with activation of the NLRP3 inflammasome in antigen presenting cells (APCs) via increased oxidated stress and isolevuglandin (IsoLG) formation, but the underlying mechanisms are unknown. The activator protein 1 (AP-1) (FOS/JUN) has been implicated in activation of the NLRP3 inflammasome but its role in SSBP is not known. We hypothesized that AP-1 transcription factor in APCs senses elevated sodium and contributes to SSBP. We further hypothesize that antioxidant flavonoid, diosmetin prevents AP-1 activation and SSBP. Using bulk RNA-sequencing in human monocytes, we found elevated sodium increases expression of the AP-1 gene family when compared to normal sodium concentration, including cFOS (2378.18 ± 480.7 vs 6494.09 ± 945.55, p= 0.0009), FOSB (53.63 ± 17. 55 vs 131.06 ± 10.30, p= 0.397), cJUN (7313.90 ± 984.93 vs 11370.09 ± 1286.35, p= 0.2563) JUNB (4218.4.36 ± 199.17 vs 570.45 ± 200.91, p= 0.0445) and JUND (3309. 63 ± 270.64 vs 8057.90 ± 1043.05, p= 0.00006). In additional experiments, we enrolled people with hypertension and phenotype them for SSBP using an established in-patient protocol of salt-loading/depletion and performed single-cell transcriptomic analyses in vivo on peripheral blood mononuclear cells (PBMCs). We found that expression of the FOSB and JUNB genes are more sensitive in concert with blood pressure in salt-sensitive (SS) but not salt-resistant (SR) humans. Moreover, diosmetin attenuated high salt-induced hypertension, 123.5 ± 4.1 vs 146.8 ± 2.5 mm Hg in controls, **p< 0.01). In addition, diosmetin also reduced high salt-induced inflammation including APC production of IsoLG-protein adducts, IL-1β, and NLRP3 inflammasome expression. These findings reveal a role for immune cell AP-1 (FOS/JUN) signaling in salt-sensitive hypertension and diosmetin may provide a potential therapeutic target for treatment of SSBP. 1R01HL144941-01A1. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

UiO-66 metal-organic frameworks as aldol condensation catalyst: Impact of defects, solvent, functionality on the catalytic activity and selectivity

Defected and amine-loaded zirconium-based metal–organic frameworks (MOF) UiO-66(Zr) have been characterized and chemically assessed in a condensation reaction of acetone and 4-nitrobenzaldehyde. The present work focuses primarily on the production of the aldol adduct as the main product while minimizing the formation of the enone adduct as a side product. Four analogues with varying numbers of missing linkers in the hexanuclear secondary building units, from one to four out of a total of 12, were synthesized. Thorough characterization showed that an increased number of defects results in an enhanced acidity, a higher internal surface area, and an increased accessibility of coordinatively unsaturated Zr-sites. The catalytic performance assessment revealed that defects, to a certain extent, positively affect the selectivity towards the aldol adduct, i,e. the catalyst, which is missing 3 of the 12 linkers, exhibits the highest activity in a solvent-free environment with a turnover frequency (TOF) amounting to 8.03 10-3 s−1. This TOF value is approximately double of the catalyst with 1.4 defects, which exhibited a TOF of only 4.41 10-3 s−1. Excluding more than three linkers more likely leads to 'missing cluster defects' and causes a decrease in the reaction rate towards the aldol adduct. A reduction in overall catalytic activity was observed upon functionalization with amine groups (UiO-66-NH2). Functionalization with L-proline (UiO-66Lpr) resulted in a shift from an acid to a basic reaction mechanism which was reflected by an improved selectivity towards the aldol adduct while maintaining a reasonable overall activity level. The best performances were obtained working solvent-free or with hexane as a solvent, while polar/semi-polar solvents hindered the catalyst performance. An 18-hour stability test demonstrated the robustness of defected and functionalized UiO-66.

Reversible O-H Bond Activation by Tripodal tris(Nitroxide) Aluminum and Gallium Complexes.

Herein, we report the preparation and characterization of the Group 13 metal complexes of a tripodal tris(nitroxide)-based ligand, designated (TriNOx3-)M (M = Al (1), Ga (2), In (3)). Complexes 1 and 2 both activate the O-H bond of a range of alcohols spanning a ∼10 pKa unit range via an element-ligand cooperative pathway to afford the zwitterionic complexes (HTriNOx2-)M-OR. Structures of these alcohol adduct products are discussed. We demonstrate that the thermodynamic and kinetic aspects of the reactions are both influenced by the identity of the metal, with 1 having higher reaction equilibrium constants and proceeding at a faster rate relative to 2 for any given alcohol. These parameters are also influenced by the pKa of the alcohol, with more acidic alcohols reacting both to more completion and faster than their less acidic counterparts. Possible mechanistic pathways for the O-H activation are discussed.

Selective enhancement of (6-4) photoproduct formation in dithymine dinucleotides driven by specific sugar puckering.

Four dinucleotide analogs of thymidylyl(3'-5')thymidine (TpT) have been designed and synthesized with a view to increase the selectivity, with respect to CPD, of efficient UV-induced (6-4) photoproduct formation. The deoxyribose residues of these analogs have been modified to increase north and south conformer populations at 5'- and 3'-ends, respectively. Dinucleotides whose 5'-end north population exceeds ca. 60% and whose 3'-end population is almost completely south display a three-fold selective enhancement in (6-4) adduct production when exposed to UV radiation, compared to TpT. These experimental results undoubtedly provide robust foundations for studying the singular ground-state proreactive species involved in the (6-4) photoproduct formation mechanism.

Estrogen genotoxicity causes preferential development of Fuchs endothelial corneal dystrophy in females

Fuchs endothelial corneal dystrophy (FECD) is a genetically complex, age-related, female-predominant disorder characterized by loss of post-mitotic corneal endothelial cells (CEnCs). Ultraviolet-A (UVA) light has been shown to recapitulate the morphological and molecular changes seen in FECD to a greater extent in females than males, by triggering CYP1B1 upregulation in females. Herein, we investigated the mechanism of greater CEnC susceptibility to UVA in females by studying estrogen metabolism in response to UVA in the cornea. Loss of NAD(P)H quinone oxidoreductase 1 (NQO1) resulted in increased production of estrogen metabolites and mitochondrial-DNA adducts, with a higher CEnC loss in Nqo1−/− female compared to wild-type male and female mice. The CYP1B1 inhibitors, trans-2,3′,4,5′-tetramethoxystilbene (TMS) and berberine, rescued CEnC loss. Injection of wild-type male mice with estrogen (E2; 17β-estradiol) increased CEnC loss, followed by increased production of estrogen metabolites and mitochondrial DNA (mtDNA) damage, not seen in E2-treated Cyp1b1−/−male mice. This study demonstrates that the endo-degenerative phenotype is driven by estrogen metabolite-dependent CEnC loss that is exacerbated in the absence of NQO1; thus, explaining the mechanism accounting for the higher incidence of FECD in females. The mitigation of estrogen-adduct production by CYP1B1 inhibitors could serve as a novel therapeutic strategy for FECD.

Polyamine-Derived Aminoaldehydes and Acrolein: Cytotoxicity, Reactivity and Analysis of the Induced Protein Modifications.

Polyamines participate in the processes of cell growth and development. The degradation branch of their metabolism involves amine oxidases. The oxidation of spermine, spermidine and putrescine releases hydrogen peroxide and the corresponding aminoaldehyde. Polyamine-derived aminoaldehydes have been found to be cytotoxic, and they represent the subject of this review. 3-aminopropanal disrupts the lysosomal membrane and triggers apoptosis or necrosis in the damaged cells. It is implicated in the pathogenesis of cerebral ischemia. Furthermore, 3-aminopropanal yields acrolein through the elimination of ammonia. This reactive aldehyde is also generated by the decomposition of aminoaldehydes produced in the reaction of serum amine oxidase with spermidine or spermine. In addition, acrolein is a common environmental pollutant. It causes covalent modifications of proteins, including carbonylation, the production of Michael-type adducts and cross-linking, and it has been associated with inflammation-related diseases. APAL and acrolein are detoxified by aldehyde dehydrogenases and other mechanisms. High-performance liquid chromatography, immunochemistry and mass spectrometry have been largely used to analyze the presence of polyamine-derived aminoaldehydes and protein modifications elicited by their effect. However, the main and still open challenge is to find clues for discovering clear linkages between aldehyde-induced modifications of specific proteins and the development of various diseases.

Sesamin Protects against APAP-Induced Acute Liver Injury by Inhibiting Oxidative Stress and Inflammatory Response via Deactivation of HMGB1/TLR4/NFκB Signal in Mice.

Acetaminophen (APAP) overdose would lead to liver toxicity and even acute liver failure in severe cases by triggering an inflammatory response and oxidative stress. Sesamin has been reported to possess anti-inflammatory and antioxidant actions in several animal disease models. In the present study, the effects and mechanisms of sesamin on APAP-induced acute liver injury (ALI) were explored. The results showed that pretreatment with sesamin significantly alleviated APAP-induced ALI, as indicated by decreased serum aminotransferase activities, hepatic pathological damages, and hepatic cellular apoptosis. But sesamin has no significant effects on the expression of cytochrome P450 2E1 (CYP2E1), APAP-cysteine adducts (APAP-CYS) production, and glutathione content in the liver of APAP-administered mice. Moreover, APAP-induced liver oxidative stress and inflammatory response also were remarkedly attenuated by sesamin, including reducing hepatic reactive oxygen species levels, promoting antioxidant generation, and inhibiting the expression of TNF-α and IL-1β, as well as decreasing inflammatory cell recruitment. Notably, sesamin inhibited serum high-mobility group box 1 (HMGB1) releases and blocked hepatic activation of Toll-like receptor 4 (TLR4)-interleukin 1 receptor-associated kinase 3-nuclear factor kappa B (NF-κB) signaling pathway in APAP-administered mice. These findings indicated that sesamin could mitigate APAP-induced ALI through suppression of oxidative stress and inflammatory response, which might be mediated by the deactivation of HMGB1/TLR4/NF-κB signaling in mice.

Glycyrrhetinic acid ameliorates diosbulbin B-induced hepatotoxicity in mice by modulating metabolic activation of diosbulbin B.

Exposure to diosbulbin B (DBB), the primary component of the herbal medicine Dioscorea bulbifera L. (DB), can cause liver injury in humans and experimental animals. A previous study found DBB-induced hepatotoxicity was initiated by CYP3A4-mediated metabolic activation and subsequent formation of adducts with cellular proteins. The herbal medicine licorice (Glycyrrhiza glabra L.) is frequently combined with DB used in numerous Chinese medicinal formulas in an effort to protect against DB-elicited hepatotoxicity. Importantly, glycyrrhetinic acid (GA), the major bioactive ingredient in licorice, inhibits CYP3A4 activity. The study aimed to investigate the protection of GA against DBB-induced hepatotoxicity and the underlying mechanism. Biochemical and histopathological analysis showed GA alleviated DBB-induced liver injury in a dose-dependent manner. In vitro metabolism assay with mouse liver microsomes (MLMs) indicated that GA decreased the generation of metabolic activation-derived pyrrole-glutathione (GSH) conjugates from DBB. Toxicokinetic studies demonstrated that GA increased maximal serum concentration (Cmax ) and area under the serum-time curve (AUC) of DBB in mice. In addition, GA attenuated hepatic GSH depletion caused by DBB. Further mechanistic studies showed that GA reduced the production of DBB-derived pyrroline-protein adducts in a dose-dependent manner. In conclusion, our findings demonstrated that GA exerted protective effect against DBB-induced hepatotoxicity, mainly correlated with suppressing the metabolic activation of DBB. Therefore, the development of a standardized combination of DBB with GA may protect patients from DBB-induced hepatotoxicity.

Skullcapflavone II, a novel NQO1 inhibitor, alleviates aristolochic acid I-induced liver and kidney injury in mice.

Aristolochic acid I (AAI) is a well established nephrotoxin and human carcinogen. Cytosolic NAD(P)H quinone oxidoreductase 1 (NQO1) plays an important role in the nitro reduction of aristolochic acids, leading to production of aristoloactam and AA-DNA adduct. Application of a potent NQO1 inhibitor dicoumarol is limited by its life-threatening side effect as an anticoagulant and the subsequent hemorrhagic complications. As traditional medicines containing AAI remain available in the market, novel NQO1 inhibitors are urgently needed to attenuate the toxicity of AAI exposure. In this study, we employed comprehensive 2D NQO1 biochromatography to screen candidate compounds that could bind with NQO1 protein. Four compounds, i.e., skullcapflavone II (SFII), oroxylin A, wogonin and tectochrysin were screened out from Scutellaria baicalensis. Among them, SFII was the most promising NQO1 inhibitor with a binding affinity (KD = 4.198 μmol/L) and inhibitory activity (IC50 = 2.87 μmol/L). In human normal liver cell line (L02) and human renal proximal tubular epithelial cell line (HK-2), SFII significantly alleviated AAI-induced DNA damage and apoptosis. In adult mice, oral administration of SFII dose-dependently ameliorated AAI-induced renal fibrosis and dysfunction. In infant mice, oral administration of SFII suppressed AAI-induced hepatocellular carcinoma initiation. Moreover, administration of SFII did not affect the coagulation function in short term in adult mice. In conclusion, SFII has been identified as a novel NQO1 inhibitor that might impede the risk of AAI to kidney and liver without obvious side effect.

Design of supported organocatalysts from a biomass-derived difuran compound and catalytic assessment for lactose hydrolysis.

The engineered structures and active sites of enzyme catalysts give rise to high catalytic activity and selectivity toward desired reactions. We have employed a biomass-derived difuran compound to append N-substituted maleimides with amino acid (glutamic acid) substitution by Diels-Alder reaction to mimic the chemical functional groups that comprise the active site channels in enzyme catalysts. The difunctionality of the biomass-derived difuran allows production of Diels-Alder adducts by appending two amino acid moieties to form a difunctional organocatalyst. The catalytic activity of the organocatalyst can be improved by immobilizing the organocatalyst on solid supporting materials. Accordingly, the structures of these immobilized organocatalysts can be engineered to mimic enzymatic active sites and to control the interaction between reactants, products, and transition states of catalytic reactions. Lactose hydrolysis was carried out to provide an example of industrial application of this approach to design and fabricate new supported organocatalysts as artificial enzymes.

Engineered multivalent DNA capsules for multiplexed detection of genotoxicants via versatile controlled release mechanisms

Assessing the risks associated with genotoxic compounds is challenging because of their complex genotoxicity and the difficulty in the dynamic monitoring of coexisting hazards. In this paper, DNA-assembly-based multistimulus responsive capsules that can detect multiple genotoxic agents simultaneously are presented. By exploiting the sequence- and reactivity-editable properties of DNA, DNA sequences in a DNA shell are designed to exhibit multivalent susceptibility against ultraviolet B radiation, aflatoxin B1, and styrene oxide. Upon exposure to genotoxicants, the developed DNA capsules dissociate because of the production of DNA adducts or aptamer–ligand complex-activated dehybridization, which results in the release of encapsulated fluorophores for a measure of the genotoxicant level. The fluorophore release kinetics for each genotoxicant is investigated. Moreover, the destruction behaviors of the developed capsules are evaluated in binary and ternary toxin mixtures. Multiple linear regression indicates the existence of a strong relationship between the fluorescent response and the genotoxicant level; the result highlights the significance of particular genotoxicant and the antagonistic effect of interacting genotoxic substances on capsule destruction. This DNA architecture allows the monitoring of human exposure to genotoxic agents, which enables the timely adoption of remedial measures, and benefits development of an endogenous genotoxin-responsive drug delivery system.

Variation of bioactive secondary metabolites in Ceylon cinnamon (<em>Cinnamomum zeylanicum</em> Blume) in different climatic conditions, maturity status and propagation types

This paper presents the variation of phytochemical quantities of leaves and bark of Cinnamomum zeylanicum Blume (Ceylon cinnamon) under different conditions such as ecological variation, maturity and physical state of the tree, and the propagation type. Among 49 climatic zones in Sri Lanka, six cinnamon growing zones including three wet zones (WL 1a, WL 2a, and WU 2b), two intermediate zones (IL 1a, IL 1b) and one dry zone (DL5) were selected for collecting cinnamon leaves and bark samples. The quantities of phytochemicals in leaves and bark extracts of Ceylon cinnamon according to the climatic difference, maturity stages (1-3, 3-5 and >5 y) and physical stage (flowering, fruiting, flushing), and seed and vegetative propagates (Sri Gamunu and Sri Wijaya) were evaluated. The results showed that climatic zones of WL 1a and IL 1a were the best climatic zones for obtaining high quantities of phytochemical classes in seeding and vegetative propagation types, respectively. Besides, the best phytochemical composition was observed in the leaves with >5 y and the bark of 3-5 y maturity of seed propagation varieties. Comparatively, bark from Sri Wijaya and leaves from Sri Gamunu which belonged to >5 y maturity contained better phytochemical composition in vegetative propagated varieties. According to the physical variations, the best phytochemical composition was observed in the bark samples which were collected in the flowering season, and the leaves samples collected in the fruiting season. Therefore, leaves in >5 y matured stage and bark in 3-5 y matured stage of seed propagation varieties of Ceylon cinnamon which are grown in WL 1a climatic zone are the best Cinnamon cultivar for the purpose of enhancing value chain and development cinnamon into different value adduct products.

Metabolomic Evaluation of N-Acetyl-p-Benzoquinone Imine Protein Adduct Formation with Therapeutic Acetaminophen Administration: Sex-based Physiologic Differences.

Acetaminophen (APAP)-associated transaminase elevation, induced by N-acetyl-p-benzoquinone imine (NAPQI) protein adduction, remains an area of research interest. Distinct from known genetic, physiologic, and dosage associations dictating severity of hepatic injury, no known factors predict an absence of protein adduct formation at therapeutic APAP dosing. Sex-based physiology is predictive of APAP-induced protein adduct formation and differential metabolite expression at therapeutic doses. This retrospective study interrogated serum samples collected for a prior study investigating fluctuations of alanine aminotransferase (ALT) over time with 4G daily APAP dosing for ≥ 16days in subjects from Denver, Colorado. Subjects were grouped by adduct formation (n = 184) vs no adducts (n = 20). Samples were run on ultra-high-performance liquid chromatography mass spectrometry from study days 0, 7, 16, and 31. Significant metabolite expressions were identified using t-tests with false discovery rate correction (FDR), partial least squares discriminant, and ANOVA simultaneous comparison analyses. Demographic and clinical data were explored using t-tests with FDR (age, weight, BMI, ALT) and Chi-square (sex, ethnicity, race) analyses. In pre-treatment samples, relative quantitation caprylic acid was expressed ninefold higher and 6-carboxyhexanoate was expressed threefold lower in subjects who did not develop adducts. Lactate had greater expression in the no adducts group (p = 0.001). Using absolute quantitation, glutathione was expressed 2.6-fold greater among no adduct subjects. Odds of males developing NAPQI protein adducts at therapeutic APAP dosing were 5.91 times lower than females (95% CI = 2.3-14.9; p = 0.0001). Multiple metabolites were differentially expressed based on adduct group and sex. Metabolites were identified unique to adduct development independent of sex. At therapeutic APAP dosing, males were less likely to develop APAP protein adducts. Further research into lipid biosynthesis and metabolism may provide further insight into physiology associated with adduct production.

A mechanistic view of the reaction between phosphine and fluorine atom: Insights into PH3F isomers

The aim of this study is to elucidate the reaction mechanism between phosphine and fluorine. Notwithstanding a hydrogen abstraction process is expected in the PH3 + F reaction yielding PH2 and HF as the most feasible pathway, the formation of a covalent bound structure (PH3F) among reactants leads to a different picture. Therefore, three PH3F isomers were characterized showing C1 (r1) and Cs (r2 and r3) symmetries, where the most stable one is in an energy well of 50 kcal mol−1 lower than the energy of the separated reactants. Thus, with the production of the PH3F adducts, a H-elimination route became the most favorable pathway forming PH2F + H products residing in an energy well of -30 kcal mol−1, while the transition state structure associated with H-abstraction showed a barrier height placed -5.8 kcal mol−1 relative to the separated reactants. Vibrational frequencies and isotropic hyperfine coupling constants of PH3F isomers were also perfomed here.

Dietary Resveratrol Alleviates AFB1-Induced Ileum Damage in Ducks via the Nrf2 and NF-κB/NLRP3 Signaling Pathways and CYP1A1/2 Expressions

The aim of this study was to explore the mechanism underlying the protective effects of resveratrol against Aflatoxin B1-induced ileum injury in ducks. A corn–soybean meal-basal diet and two test diets (500 mg/kg resveratrol +0.2 mg Aflatoxin B1/kg, 0.2 mg AFB1/kg) were used in a 10-wk design trial (n = 15 ducks/group). These results showed that the toxicity of Aflatoxin B1 significantly reduced the antioxidant capacity of duck ileum and induced inflammation, oxidative stress, mitochondrial dysfunction and DNA damage in ducks. The expression of genes, including CYP1A2, CYP2A6, and CYP3A4, at the mRNA level was significantly upregulated (p < 0.05) by AFB1. The level of Nrf2 was suppressed (p < 0.05) and the mRNA and protein level of NF-κB was activated (p < 0.05) in the AFB1 group. However, supplementation with 500 mg/kg dietary resveratrol in Aflatoxin B1-induced ducks significantly ameliorated these alterations and decreased the mRNA expression of CYP1A1 and CYP1A2 (p < 0.05) and the production of AFB1-DNA adducts (p < 0.05). The results proved that resveratrol alleviated ileum injury induced by AFB1, decreased the production of AFB1-DNA adducts by downregulating the expression of CYP1A1 and CYP1A2, and reduced DNA damage and oxidative stress via the Nrf2/ Keap1 and NF-κB/NLRP3 signaling pathways.

Raman spectroscopy signatures for monomeric, dimeric and trimeric zinc dimethoxide with tetrahydrofuran adduct and early hydrolysis-condensation products on Au(111) surface: theoretical and experimental approach

Raman spectroscopy signatures for monomeric, dimeric and trimeric zinc dimethoxide with tetrahydrofuran adduct and early hydrolysis-condensation products on Au(111) surface: theoretical and experimental approach