Formaldehyde and the Transient Receptor Potential Ankyrin-1 Contribute to Electronic Cigarette Aerosol-induced Endothelial Dysfunction in Mice.

Electronic Nicotine Delivery Systems (ENDS) aerosol exposures can induce endothelial dysfunction (ED) in healthy young humans and animals. Thermal degradation of ENDS solvents, propylene glycol and vegetable glycerin (PG: VG), generates abundant formaldehyde (FA) and other carbonyls. Because FA can activate the transient receptor potential ankyrin-1 (TRPA1) sensor, we hypothesized that FA in ENDS aerosols provokes TRPA1-mediated changes that include ED and 'respiratory braking' - biomarkers of harm. To test this, wild-type (WT) and TRPA1-null mice were exposed by inhalation to either filtered air, PG: VG-derived aerosol, or formaldehyde (FA, 5 ppm). Short-term exposures to PG: VG and FA induced ED in female WT but not in female TRPA1-null mice. Moreover, acute exposures to PG: VG and FA stimulated respiratory braking in WT but not in TRPA1-null female mice. Urinary metabolites of FA (ie, N  -1,3-thiazolidine-4-carboxylic acid, TCA; N  -1,3-thiazolidine-4-carbonyl glycine, TCG) and monoamines were measured by LC-MS/MS. PG: VG and FA exposures significantly increased urinary excretion of both TCA and TCG in both WT and TRPA1-null mice. To confirm that inhaled FA directly contributed to urinary TCA, mice were exposed to isotopic 13C-FA gas (1 ppm, 6 h).13C-FA exposure significantly increased the urine level of 13C-TCA in the early collection (0-3 h) supporting a direct relationship between inhaled FA and TCA. Collectively, these data suggest that ENDS use may increase CVD risk dependent on FA, TRPA1, and catecholamines, yet independently of either nicotine or flavorants. This study supports that levels of FA in ENDS-derived aerosols should be lowered to mitigate CVD risk in people who use ENDS.

Highly sensitive and selective electrochemical biosensor using odorant-binding protein to detect aldehydes.

Recently, various biosensors based on odorant-binding proteins (OBPs) were developed for the detection of odorants and pheromones. However, important data gaps exist regarding the sensitive and selective detection of aldehydes with various carbon numbers. In this work, an OBP2a-based electrochemical impedance spectroscopy (EIS) biosensor was developed by immobilizing OBP2a on a gold interdigital electrode, and was characterized by EIS and atomic force microscopy. EIS responses showed the OBP2a-based biosensor was highly sensitive to citronellal, lily aldehyde, octanal, and decanal (detection limit of 10-11 mol/L), and was selective towards aldehydes compared with interfering odorants such as small-molecule alcohols and fatty acids (selectivity coefficients lower than 0.15). Moreover, the OBP2a-based biosensor exhibited high repeatability (relative standard deviation: 1.6%-9.1 %, n = 3 for each odorant), stability (NIC declined by 3.6 % on 6th day), and recovery (91.2%-96.6 % on three real samples). More specifically, the sensitivity of the biosensor to aldehydes was positively correlated to the molecular weight and the heterocyclic molecule structure of the odorants. These results proved the availability and the potential usage of the OBP2a-based EIS biosensor for the rapid and sensitive detection of aldehydes in aspects such as medical diagnostics, food and favor analysis, and environmental monitoring.

Cobalt-Catalyzed Reduction of Aldehydes to Alcohols via the Hydroboration Reaction.

A method for the reduction of aldehydes with pinacolborane catalyzed by pincer cobalt complexes based on a triazine backbone is developed in this paper. The presented methodology allows for the transformation of several aldehydes bearing a wide range of electron-withdrawing and electron-donating groups under mild conditions. The presented procedure allows for the direct one-step hydrolysis of the obtained intermediates to the corresponding primary alcohols. A plausible reaction mechanism is proposed.

Determination of low carbon aldehydes and ketones in cigarette smoke by MXene membrane enrichment-liquid chromatography.

Low carbon aldehydes and ketones are typical substances harmful to human body produced during cigarette smoking. Their contents in cigarette smoke are important indicators for evaluating its toxicity and the filtration effect of cigarette filter tips, which provides important guidance for its rational design. In this work, MXene membrane with unique lamellar structure was synthesized and loaded onto glass fiber filters to achieve effective enrichment of low carbon aldehydes and ketones. Compared to commercial Cambridge filters, the MXene-loaded filters exhibited higher extraction efficiency towards low-carbon aldehydes and ketones, making viable the detection of butyraldehyde, which was not detected by that enriched with Cambridge filters. Therefore, a MXene-based membrane enrichment-HPLC method was developed for the determination of low-carbon aldehydes and ketones in cigarette smoke with detection limits ranging from 0.133 µg/mL to 0.285 µg/mL. The applicability of the method was verified by analyzing three different types of filter cigarettes with the concentration in the range of 0.5-140 µg/branch for all the analytes, which were in good agreement with the manufacturer's results. The method is accurate and sensitive, and can be used for the quantitative determination of low carbon aldehydes and ketones in cigarette smoke.

Development and evaluation of a liquid chromatography-tandem mass spectrometry method for simultaneous measurement of toxic aldehydes from brain tissue.

Reactive aldehydes are a class of electrophilic low molecular weight compounds that play an essential role in physiological function and lipid peroxidation. These molecules are implicated in many diseases, especially cardiovascular and neurodegenerative diseases, and are potential endogenous markers of lipid peroxidation. However, there are limited options to accurately quantify multiple reactive aldehydes in brain tissue. This study developed and validated a 3-nitrophenylhydrazine derivatization-based LC-MS/MS method to quantify four reactive aldehydes: malondialdehyde, acrolein, 4-hydroxy-2-hexenal and 4-hydroxy-2-nonenal. Method development involved comparing the sensitivity of detection between widely used derivatization reagents: 2,4-dinitrophenylhydrazine and 3-nitrophenylhydrazine. Our data showed that 3-nitrophenylhydrazine resulted in greater sensitivity. Additional method development included evaluation of hydrolysis sample pretreatment, selection of protein precipitation reagent, and optimization of derivatization conditions. The optimized conditions included no hydrolysis and use of 20 % trichloroacetic acid as the protein precipitation reagent. The optimized derivatization condition was 25 mM 3-nitrophenylhydrazine reacted at 20 °C for 30 min. The chromatographic conditions were optimized to reduce matrix effects, ion suppression, and efficient analysis time (<7-minute analytical run). The four aldehyde species were accurately quantified in brain tissue using stable-labeled internal standards. Application of this assay to a traumatic brain injury mouse model revealed significant accumulation of acrolein, 4-hydroxy-2-hexenal, and 4-hydroxy-2-nonenal at 28 days post injury. Overall, a validated method was developed to rapidly quantify the most prominent reactive aldehydes associated with lipid peroxidation during injury progression following acute brain trauma.

Effectiveness of different antioxidants in suppressing the evolution of thermally induced peroxidation products in hemp seed oil.

Several scientific studies have warned that the ingestion of dietary lipid oxidation products (LOPs) may initiate or exacerbate the development of several chronic non-communicable diseases in humans. Indeed, the constantly increasing consumption of culinary oils by larger global populations indicates the need for scientific techniques to suppress the evolution of LOPs in thermo-oxidised oils. This study employed a 600.13 MHz frequency NMR spectrometer in evaluating the effect of 10, 50, and 100 ppm concentrations of chemical compounds reported to have antioxidant properties in continuously-stirred and thermally stressed polyunsaturated fatty acid (PUFA)-rich hemp seed oil at a frying temperature of 180℃ for 180 min. Research data acquired showed that the antioxidants α- and γ-tocopherol, γ-oryzanol, ß-carotene, eugenol, resveratrol, ascorbyl palmitate, gentisic acid, and L-ascorbic acid all played a vital role in suppressing the evolution of secondary aldehydic lipid oxidation products in hemp seed oil. However, the most ineffective LOP-suppressing agent was L-lysine, an observation which may be accountable by its poor oil solubility. Nonetheless, trends deduced for compounds acting as antioxidants were mainly unique for each class of agent tested. Conversely, the antioxidant capacity of resveratrol was consistently higher, and this effect was found to be independent of its added amounts. This report provides a direct approach in developing scientific methods for the suppression of LOPs in thermo-oxidatively susceptible PUFA-rich cooking oils.

Plasmalogen oxidation induces the generation of excited molecules and electrophilic lipid species.

Plasmalogens are glycerophospholipids with a vinyl ether linkage at the sn-1 position of the glycerol backbone. Despite being suggested as antioxidants due to the high reactivity of their vinyl ether groups with reactive oxygen species, our study reveals the generation of subsequent reactive oxygen and electrophilic lipid species from oxidized plasmalogen intermediates. By conducting a comprehensive analysis of the oxidation products by liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS), we demonstrate that singlet molecular oxygen [O2 (1Δg)] reacts with the vinyl ether bond, producing hydroperoxyacetal as a major primary product (97%) together with minor quantities of dioxetane (3%). Furthermore, we show that these primary oxidized intermediates are capable of further generating reactive species including excited triplet carbonyls and O2 (1Δg) as well as electrophilic phospholipid and fatty aldehyde species as secondary reaction products. The generation of excited triplet carbonyls from dioxetane thermal decomposition was confirmed by light emission measurements in the visible region using dibromoanthracene as a triplet enhancer. Moreover, O2 (1Δg) generation from dioxetane and hydroperoxyacetal was evidenced by detection of near-infrared light emission at 1,270 nm and chemical trapping experiments. Additionally, we have thoroughly characterized alpha-beta unsaturated phospholipid and fatty aldehydes by LC-HRMS analysis using two probes that specifically react with aldehydes and alpha-beta unsaturated carbonyls. Overall, our findings demonstrate the generation of excited molecules and electrophilic lipid species from oxidized plasmalogen species unveiling the potential prooxidant nature of plasmalogen-oxidized products.

Fatty Acid Origin of Insect Pheromones.

Pheromones are utilized to a great extent in insects. Many of these pheromones are biosynthesized through a pathway involving fatty acids. This chapter will provide examples where the biosynthetic pathways of fatty acid-derived pheromones have been studied in detail. These include pheromones from Lepidoptera, Coleoptera, and Hymenoptera. Many species of Lepidoptera utilize fatty acids as precursors to pheromones with a functional group that include aldehydes, alcohols, and acetate esters. In addition, the biosynthesis of hydrocarbons will be briefly examined because many insects utilize hydrocarbons or modified hydrocarbons as pheromones.

Chromatographic Methods and Sample Pretreatment Techniques for Aldehydes, Biogenic Amine, and Carboxylic Acids in Food Samples.

This review paper critically examines the current state of research concerning the analysis and derivatization of aldehyde, aromatic hydrocarbons and carboxylic acids components in foods and drinks samples, with a specific focus on the application of Chromatographic techniques. These diverse components, as vital contributors to the sensory attributes of food, necessitate accurate and sensitive analytical methods for their identification and quantification, which is crucial for ensuring food safety and compliance with regulatory standards. In this paper, High-Performance Liquid Chromatography (HPLC) and Gas Chromatographic (GC) methods for the separation, identification, and quantification of aldehydes in complex food matrices were reviewed. In addition, the review explores derivatization strategies employed to enhance the detectability and stability of aldehydes during chromatographic analysis. Derivatization methods, when applied judiciously, improve separation efficiency and increase detection sensitivity, thereby ensuring a more accurate and reliable quantification of aldehyde aromatic hydrocarbons and carboxylic acids species in food samples. Furthermore, methodological aspects encompassing sample preparation, chromatographic separation, and derivatization techniques are discussed. Validation was carried out in term of limit of detections are highlighted as crucial elements in achieving accurate quantification of compounds content. The discussion presented by emphasizing the significance of the combined HPLC and GC chromatography methods, along with derivatization strategies, in advancing the analytical capabilities within the realm of food science.

ALDH2 mutations and defense against genotoxic aldehydes in cancer and inherited bone marrow failure syndromes.

Reactive aldehydes, for instance, formaldehyde and acetaldehyde, are important endogenous or environmental mutagens by virtue of their abilities to produce a DNA lesion called interstrand crosslink (ICL). Aldehyde-metabolizing enzymes such as aldehyde dehydrogenases (ALDHs) and the Fanconi anemia (FA) pathway constitute the main defense lines against aldehyde-induced genotoxicity. Biallelic mutations of genes in any one of the FA complementation groups can impair the ICL repair mechanism and cause FA, a heterogeneous disorder manifested by bone marrow failure (BMF), congenital abnormality and a strong predisposition to cancer. The defective ALDH2 polymorphism rs671 (ALDH2*2) is a known risk and prognostic factor for alcohol drinking-associated cancers. Recent studies suggest that it also promotes BMF and cancer development in FA, and its combination with alcohol dehydrogenase 5 (ADH5) mutations causes aldehyde degradation deficiency syndrome (ADDS), also known by its symptoms as aplastic anemia, mental retardation, and dwarfism syndrome. ALDH2*2 and another pathogenic variant in the alcohol-metabolizing pathway, ADH1B1*1, is prevalent among East Asians. Also, other ALDH2 genotypes with disease-modifying potentials have lately been identified in different populations. Therefore, it would be appropriate to summarize current knowledge of genotoxic aldehydes and defense mechanisms against them to shed new light on the pathogenic effects of ALDH2 variants together with other genetic and environmental modifiers on cancer and inherited BMF syndromes. Lastly, we also presented potential treatment strategies for FA, ADDS and cancer based on the manipulation of aldehyde-induced genotoxicity.

Dysregulation of cardiac mitochondrial aldehyde dehydrogenase 2: Studies in dogs with chronic heart failure.

Mitochondrial (MITO) dysfunction occurs in the failing heart and contributes to worsening of heart failure (HF). Reduced aldehyde dehydrogenase 2 (ALDH2) in left ventricular (LV) myocardium of diabetic hearts has been implicated in MITO dysfunction through accumulation of toxic aldehydes including and elevated levels of 4-hydroxy-2-nonenal (4HNE). This study examined whether dysregulation of MITO ALDH2 (mALDH2) occurs in mitochondria of the failing LV and is associated with increased levels of 4HNE. LV tissue from 7 HF and 7 normal (NL) dogs was obtained. Protein quantification of total mitochondrial ALDH2 (t-mALDH2), phosphorylated mALDH2 (p-mALDH2), total MITO protein kinase c epsilon (t-mPKCε), phosphorylated mPKCε (p-mPKCε) was performed by Western blotting, and total mALDH2 enzymatic activity was measured. Protein adducts of 4HNE-MITO and 4HNE-mALDH2 were also measured in MITO fraction by Western Blotting. Protein level of t-mALDH2 was decreased in HF compared with NL dogs (0.63 ± 0.07 vs 1.17 ± 0.08, p < 0.05) as did mALDH2 enzymatic activity (51.39 ± 3 vs. 107.66 ± 4 nmol NADH/min/mg, p < 0.05). Phosphorylated-mALDH2 and p-mPKCε were unchanged. 4HNE-MITO proteins adduct levels increased in HF compared with NL (2.45 ± 0.08 vs 1.30 ± 0.03 du, p < 0.05) as did adduct levels of 4HNE-mALDH2 (1.60 ± 0.20 vs 0.39 ± 0.08, p < 0.05). In isolated failing cardiomyocytes (CM) exposure to 4HNE decreased mALDH2 activity, increased ROS and 4HNE-ALDH2 adducts, and worsened MITO function. Stimulation of mALDH2 activity with ALDA-1 in isolated HF CMs compared to NL CMs improved ADP-stimulated respiration and maximal ATP synthesis to a greater extant (+47 % and +89 %, respectively). Down-regulation of mALDH2 protein levels and activity occurs in HF and contributes to MITO dysfunction and is likely caused by accumulation of 4HNE-mALDH2 adduct. Increasing mALDH2 activity (via ALDA-1) improved MITO function in failing CMs.

The TaCl5-Mediated Reaction of Dimethyl 2-Phenylcyclopropane-1,1-dicarboxylate with Aromatic Aldehydes as a Route to Substituted Tetrahydronaphthalenes.

It is found that the reaction of dimethyl 2-phenylcyclopropane-1,1-dicarboxylate with 2 equivalents each of aromatic aldehydes and TaCl5 in 1,2-dichloroethane at 23 °C for 24 h after hydrolysis gives substituted 4-phenyl-3,4-dihydronaphtalene-2,2(1H)-dicarboxylates in good yield. This represents a new type of reactions between 2-arylcyclopropane-1,1-dicarboxylates and aromatic aldehydes, yielding chlorinated tetrahydronaphthalenes with a cis arrangement of the aryl and chlorine substituents in the cyclohexene moiety. A plausible reaction mechanism is proposed.

Photoredox/Bismuth Relay Catalysis Enabling Reductive Alkylation of Nitroarenes with Aldehydes.

The effective transition metal-free photoredox/bismuth dual catalytic reductive dialkylation of nitroarenes with benzaldehydes has been reported. The nitroarene reduction through visible light-driven photoredox catalysis was integrated with subsequent reductive dialkylation of anilines under bismuth catalysis to enable the cascade reductive alkylation of nitroarenes with carbonyls. Salient features of this relay catalysis system include mild reaction conditions, no requirement for transition metal catalysts, easy handling, step-economy, and high selectivity.

Synthesis and Antitumor Activities of Novel 5-amino-3-(halophenyl)- 1- phenyl-1H-pyrazole-4-carbonitriles.

In this work, a series of novel 3-(halophenyl)-1-phenyl-1H-pyrazole moieties have been synthesized. Their structures were characterized by IR, NMR, and MS spectroscopy, and the corresponding antitumor properties were also studied. OBJECTIVES: This study aimed to synthesize a series of new 3-(halophenyl)-1-phenyl-1Hpyrazole moieties and survey the antitumor properties of these compounds. MATERIALS AND METHODS: 3-(halophenyl)-1-phenyl-1H-pyrazoles (4a-j) were prepared by reaction of phenyl hydrazine (3) with different halogen aromatic aldehydes (1a-j) and malononitrile (2) in C2H5OH and piperidine. The reaction took place under microwave irradiation settings for two minutes at140°C. RESULTS: Three human cancer cell lines were used as in vitro test subjects for compounds 4a - j. Three cell lines from mammals HeLa (a cell line for human cervical cancer), MCF-7 (a cell line for human breast cancer), and PC-3 (a cell line for human prostate cancer), all with 5- fluorouracil as the standard reference drug were used. CONCLUSION: A series of novel 3-(halophenyl)-1-phenyl-1H-pyrazoles were synthesized in this work. All substances had their anticancer properties assessed.

Engineering a Carotenoid Cleavage Oxygenase for Coenzyme-Free Synthesis of Vanillin from Ferulic Acid.

One-pot biosynthesis of vanillin from ferulic acid without providing energy and cofactors adds significant value to lignin waste streams. However, naturally evolved carotenoid cleavage oxygenase (CCO) with extreme catalytic conditions greatly limited the above pathway for vanillin bioproduction. Herein, CCO from Thermothelomyces thermophilus (TtCCO) was rationally engineered for achieving high catalytic activity under neutral pH conditions and was further utilized for constructing a one-pot synthesis system of vanillin with Bacillus pumilus ferulic acid decarboxylase. TtCCO with the K192N-V310G-A311T-R404N-D407F-N556A mutation (TtCCOM3) was gradually obtained using substrate access channel engineering, catalytic pocket engineering, and pocket charge engineering. Molecular dynamics simulations revealed that reducing the site-blocking effect in the substrate access channel, enhancing affinity for substrates in the catalytic pocket, and eliminating the pocket's alkaline charge contributed to the high catalytic activity of TtCCOM3 under neutral pH conditions. Finally, the one-pot synthesis of vanillin in our study could achieve a maximum rate of up to 6.89 ± 0.3 mM h-1. Therefore, our study paves the way for a one-pot biosynthetic process of transforming renewable lignin-related aromatics into valuable chemicals.

4-Hydroxybenzoic Acid-Based Hydrazide-Hydrazones as Potent Growth Inhibition Agents of Laccase-Producing Phytopathogenic Fungi That Are Useful in the Protection of Oilseed Crops.

The research on new compounds against plant pathogens is still socially and economically important. It results from the increasing resistance of pests to plant protection products and the need to maintain high yields of crops, particularly oilseed crops used to manufacture edible and industrial oils and biofuels. We tested thirty-five semi-synthetic hydrazide-hydrazones with aromatic fragments of natural origin against phytopathogenic laccase-producing fungi such as Botrytis cinerea, Sclerotinia sclerotiorum, and Cerrena unicolor. Among the investigated molecules previously identified as potent laccase inhibitors were also strong antifungal agents against the fungal species tested. The highest antifungal activity showed derivatives of 4-hydroxybenzoic acid and salicylic aldehydes with 3-tert-butyl, phenyl, or isopropyl substituents. S. sclerotiorum appeared to be the most susceptible to the tested compounds, with the lowest IC50 values between 0.5 and 1.8 µg/mL. We applied two variants of phytotoxicity tests for representative crop seeds and selected hydrazide-hydrazones. Most tested molecules show no or low phytotoxic effect for flax and sunflower seeds. Moreover, a positive impact on seed germination infected with fungi was observed. With the potential for application, the cytotoxicity of the hydrazide-hydrazones of choice toward MCF-10A and BALB/3T3 cell lines was lower than that of the azoxystrobin fungicide tested.

Malondialdehyde Assays in Higher Plants.

Malondialdehyde is a three-carbon dialdehyde produced as a byproduct of polyunsaturated fatty acid peroxidation widely used as a marker of the extent of lipid peroxidation in plants. There are several methodological approaches to quantify malondialdehyde contents in higher plants, ranging from the simplest, cheapest, and quickest spectrophotometric approaches to the more complex ones using tandem mass spectrometry. This chapter summarizes the advantages and limitations of approaches followed and provides brief protocols with some tips to facilitate the selection of the best method for each experimental condition and application.

Recent developments in enzymatic and microbial biosynthesis of flavor and fragrance molecules.

Flavors and fragrances are an important class of specialty chemicals for which interest in biomanufacturing has risen during recent years. These naturally occurring compounds are often amenable to biosynthesis using purified enzyme catalysts or metabolically engineered microbial cells in fermentation processes. In this review, we provide a brief overview of the categories of molecules that have received the greatest interest, both academically and industrially, by examining scholarly publications as well as patent literature. Overall, we seek to highlight innovations in the key reaction steps and microbial hosts used in flavor and fragrance manufacturing.

Complete Degradation of Polyolefin Plastic Wastes to High-Value Products.

Plastic wastes continuously accumulate, causing critical environmental issues. It is urgent to develop efficient strategies to convert them to valuable products. Very recently, two novel approaches for plastic recycling were reported by Huber et al. (Science, 2023, 381, 660-666) and Liu et al. (Science, 2023, 381, 666-671), where polyethylene (PE) and polypropylene (PP) plastics were converted into potentially valuable products, such as alcohols, aldehydes, surfactants, and detergents. The two processes achieved complete degradation, high selectivity of target products, as well as high values of products, showing economic feasibility for industrial scale-up. These breakthroughs for plastic recycling are highlighted in this article.

Lipid Peroxidation-Related Redox Signaling in Osteosarcoma.

Oxidative stress and lipid peroxidation play important roles in numerous physiological and pathological processes, while the bioactive products of lipid peroxidation, lipid hydroperoxides and reactive aldehydes, act as important mediators of redox signaling in normal and malignant cells. Many types of cancer, including osteosarcoma, express altered redox signaling pathways. Such redox signaling pathways protect cancer cells from the cytotoxic effects of oxidative stress, thus supporting malignant transformation, and eventually from cytotoxic anticancer therapies associated with oxidative stress. In this review, we aim to explore the status of lipid peroxidation in osteosarcoma and highlight the involvement of lipid peroxidation products in redox signaling pathways, including the involvement of lipid peroxidation in osteosarcoma therapies.