ALDH2 as an immunological and prognostic biomarker: Insights from pan-cancer analysis.

Aldehyde dehydrogenase 2 (ALDH2) plays a critical role in safeguarding cells against acetaldehyde toxicity and is closely linked to human metabolism. Nevertheless, the involvement of ALDH2 in cancer remains enigmatic. This investigation seeks to comprehensively assess ALDH2's significance in pan-cancer. We conducted an all-encompassing analysis of pan-cancer utilizing multiple databases, including TCGA, linkedomicshs, UALCAN, and Kaplan-Meier plotter. We employed diverse algorithms such as EPIC, MCPCOUNTER, TIDTIMER, xCell, MCP-counter, CIBERSORT, quanTIseq, and EPIC to examine the connection between ALDH2 expression and immune cell infiltration. Single-cell sequencing analysis furnished insights into ALDH2's functional status in pan-cancer. Immunohistochemical staining was performed to validate ALDH2 expression in cancer tissues. In a comprehensive assessment, we observed that tumor tissues demonstrated diminished ALDH2 expression levels compared to normal tissues across 16 different cancer types. ALDH2 expression exhibited a significant positive correlation with the infiltration of immune cells, including CD4 + T cells, CD8 + T cells, neutrophils, B cells, and macrophages, in various tumor types. Moreover, this study explored the association between ALDH2 and patient survival, examined the methylation patterns of ALDH2 in normal and primary tumor tissues, and delved into genetic variations and mutations of ALDH2 in tumors. The findings suggest that ALDH2 could serve as a valuable prognostic biomarker in pan-cancer, closely linked to the tumor's immune microenvironment.

Ethanol, acetaldehyde, and methanol in the gas phase and rainwater in different biomes and urban regions of Brazil.

In the context of the increasing global use of ethanol biofuel, this work investigates the concentrations of ethanol, methanol, and acetaldehyde, in both the gaseous phase and rainwater, across six diverse urban regions and biomes in Brazil, a country where ethanol accounts for nearly half the light-duty vehicular fuel consumption. Atmospheric ethanol median concentrations in São Paulo (SP) (12.3 ± 12.1 ppbv) and Ribeirão Preto (RP) (12.1 ± 10.9 ppbv) were remarkably close, despite the SP vehicular fleet being ∼13 times larger. Likewise, the rainwater VWM ethanol concentration in SP (4.64 ± 0.38 µmol L-1) was only 26 % higher than in RP (3.42 ± 0.13 µmol L-1). This work demonstrated the importance of evaporative emissions, together with biomass burning, as sources of the compounds studied. The importance of biogenic emissions of methanol during forest flooding was identified in campaigns in the Amazon and Atlantic forests. Marine air masses arriving at a coastal site led to the lowest concentrations of ethanol measured in this work. Besides vehicular and biomass burning emissions, secondary formation of acetaldehyde by photochemical reactions may be relevant in urban and non-urban regions. The combined deposition flux of ethanol and methanol was 6.2 kg ha-1 year-1, avoiding oxidation to the corresponding and more toxic aldehydes. Considering the species determined here, the ozone formation potential (OFP) in RP was around two-fold higher than in SP, further evidencing the importance of emissions from regional distilleries and biomass burning, in addition to vehicles. At the forest and coastal sites, the OFP was approximately 5 times lower than at the urban sites. Our work evidenced that transition from gasoline to ethanol or ethanol blends brings the associated risk of increasing the concentrations of highly toxic aldehydes and ozone, potentially impacting the atmosphere and threatening air quality and human health in urban areas.

Substitution of both histidines in the active site of yeast alcohol dehydrogenase 1 exposes underlying pH dependencies.

Histidine residues 44 and 48 in yeast alcohol dehydrogenase (ADH) bind to the coenzymes NAD(H) and contribute to catalysis. The individual H44R and H48Q substitutions alter the kinetics and pH dependencies, and now the roles of other ionizable groups in the enzyme were studied in the doubly substituted H44R/H48Q ADH. The substitutions make the enzyme more resistant to inactivation by diethyl pyrocarbonate, modestly improve affinity for coenzymes, and substantially decrease catalytic efficiencies for ethanol oxidation and acetaldehyde reduction. The pH dependencies for several kinetic parameters are shifted from pK values for wild-type ADH of 7.3-8.1 to values for H44R/H48Q ADH of 8.0-9.6, and are assigned to the water or alcohol bound to the catalytic zinc. It appears that the rate of binding of NAD+ is electrostatically favored with zinc-hydroxide whereas binding of NADH is faster with neutral zinc-water. The pH dependencies of catalytic efficiencies (V/EtKm) for ethanol oxidation and acetaldehyde reduction are similarly controlled by deprotonation and protonation, respectively. The substitutions make an enzyme that resembles the homologous horse liver H51Q ADH, which has Arg-47 and Gln-51 and exhibits similar pK values. In the wild-type ADHs, it appears that His-48 (or His-51) in the proton relay systems linked to the catalytic zinc ligands modulate catalytic efficiencies.

Preparation, assay, and application of 4-fluorothreonine transaldolase from Streptomyces sp. MA37 for ß-hydroxyl amino acid derivatives.

ß-Hydroxy-α-amino acids (ßHAAs) are an essential class of building blocks of therapeutically important compounds and complex natural products. They contain two chiral centers at Cα and Cß positions, resulting in four possible diastereoisomers. Many innovative asymmetric syntheses have been developed to access structurally diverse ßHAAs. The main challenge, however, is the control of the relative and absolute stereochemistry of the asymmetric carbons in a sustainable way. In this respect, there has been considerable attention focused on the chemoenzymatic synthesis of ßHAAs via a one-step process. Nature has evolved different enzymatic routes to produce these valuable ßHAAs. Among these naturally occurring transformations, L-threonine transaldolases present potential biocatalysts to generate ßHAAs in situ. 4-Fluorothreonine transaldolase from Streptomyces sp. MA37 (FTaseMA) catalyzes the cross-over transaldolation reaction between L-Thr and fluoroacetaldehyde to give 4-fluorothreonine and acetaldehyde (Ad). It has been demonstrated that FTaseMA displays considerable substrate plasticity toward structurally diverse aldehyde acceptors, leading to the production of various ßHAAs. In this chapter, we describe methods for the preparation of FTaseMA, and the chemoenzymatic synthesis of ßHAAs from various aldehydes and L-Thr using FTaseMA.

1H NMR based sulfonation reaction kinetics of wine relevant thiols in comparison with known carbonyls.

Sulfite addition is a common tool for ensuring wines' oxidative stability via the activity of its free and weakly bound molecular fraction. As a nucleophile, bisulfite forms covalent adducts with wine's most relevant electrophiles, such as carbonyls, polyphenols, and thiols. The equilibrium in these reactions is often represented as dissociation rather than formation. Recent studies from our laboratory demonstrate, first, the acetaldehyde sulfonate dissociation, and second, the chemical stability of cysteine and epicatechin sulfonates under wine aging conditions. Thus, the objective of this study was to monitor by 1H NMR the binding specificity of known carbonyl-derived SO2 binders (acetaldehyde and pyruvic acid) in the presence of S-containing compounds (cysteine and glutathione). We report that during simulated wine aging, the sulfur dioxide that is rapidly bound to carbonyl compounds will be released and will bind to cysteine and glutathione, demonstrating the long-term sulfur dioxide binding potential of S-containing compounds. These results are meant to serve as a complement to existing literature reviews focused on molecular markers related to wines' oxidative stability and emphasize once more the importance of S-containing compounds in wine aging chemical mechanisms.

Potent Inhibition of E. coli DXP Synthase by a gem-Diaryl Bisubstrate Analog.

New antimicrobial strategies are needed to address pathogen resistance to currently used antibiotics. Bacterial central metabolism is a promising target space for the development of agents that selectively target bacterial pathogens. 1-Deoxy-d-xylulose 5-phosphate synthase (DXPS) converts pyruvate and d-glyceraldehyde 3-phosphate (d-GAP) to DXP, which is required for synthesis of essential vitamins and isoprenoids in bacterial pathogens. Thus, DXPS is a promising antimicrobial target. Toward this goal, our lab has demonstrated selective inhibition of Escherichia coli DXPS by alkyl acetylphosphonate (alkylAP)-based bisubstrate analogs that exploit the requirement for ternary complex formation in the DXPS mechanism. Here, we present the first DXPS structure with a bisubstrate analog bound in the active site. Insights gained from this cocrystal structure guided structure-activity relationship studies of the bisubstrate scaffold. A low nanomolar inhibitor (compound 8) bearing a gem-dibenzyl glycine moiety conjugated to the acetylphosphonate pyruvate mimic via a triazole-based linker emerged from this study. Compound 8 was found to exhibit slow, tight-binding inhibition, with contacts to E. coli DXPS residues R99 and R478 demonstrated to be important for this behavior. This work has discovered the most potent DXPS inhibitor to date and highlights a new role of R99 that can be exploited in future inhibitor designs toward the development of a novel class of antimicrobial agents.

Enhanced chaotrope tolerance and (S)-2-hydroxypropiophenone production by recombinant Pseudomonas putida engineered with Pprl from Deinococcus radiodurans.

Pseudomonas putida is a soil bacterium with multiple uses in fermentation and biotransformation processes. P. putida ATCC 12633 can biotransform benzaldehyde and other aldehydes into valuable α-hydroxyketones, such as (S)-2-hydroxypropiophenone. However, poor tolerance of this strain toward chaotropic aldehydes hampers efficient biotransformation processes. To circumvent this problem, we expressed the gene encoding the global regulator PprI from Deinococcus radiodurans, an inducer of pleiotropic proteins promoting DNA repair, in P. putida. Fine-tuned gene expression was achieved using an expression plasmid under the control of the LacIQ /Ptrc system, and the cross-protective role of PprI was assessed against multiple stress treatments. Moreover, the stress-tolerant P. putida strain was tested for 2-hydroxypropiophenone production using whole resting cells in the presence of relevant aldehyde substrates. P. putida cells harbouring the global transcriptional regulator exhibited high tolerance toward benzaldehyde, acetaldehyde, ethanol, butanol, NaCl, H2 O2 and thermal stress, thereby reflecting the multistress protection profile conferred by PprI. Additionally, the engineered cells converted aldehydes to 2-hydroxypropiophenone more efficiently than the parental P. putida strain. 2-Hydroxypropiophenone concentration reached 1.6 g L-1 upon a 3-h incubation under optimized conditions, at a cell concentration of 0.033 g wet cell weight mL-1 in the presence of 20 mM benzaldehyde and 600 mM acetaldehyde. Product yield and productivity were 0.74 g 2-HPP g-1 benzaldehyde and 0.089 g 2-HPP g cell dry weight-1 h-1 , respectively, 35% higher than the control experiments. Taken together, these results demonstrate that introducing PprI from D. radiodurans enhances chaotrope tolerance and 2-HPP production in P. putida ATCC 12633.

Exocyclic DNA adducts and oxidative stress parameters: useful tools for biomonitoring exposure to aldehydes in smokers.

CONTEXT: Exocyclic DNA adducts have been shown to be potential biomarkers of cancer risk related to oxidative stress and exposure to aldehydes in smokers. In fact, aldehydes potentially arise from tobacco combustion directly and endogenously through lipid peroxidation. OBJECTIVE: This study aims to investigate the relationship between a profile of nine aldehydes-induced DNA adducts and antioxidant activities, in order to evaluate new biomarkers of systemic exposure to aldehydes. METHODS: Using our previously published UPLC-MS/MS method, adducts levels were quantified in the blood DNA of 34 active smokers. The levels of antioxidant vitamins (A, C and E), coenzyme Q10, ß-carotene, superoxide dismutase (SOD) and autoantibodies against oxidized low-density lipoprotein were measured. RESULTS: Adducts induced by tobacco smoking-related aldehydes were quantified at levels reflecting an oxidative production from lipid peroxidation. A significant correlation between SOD and crotonaldehyde-induced adducts (p = 0.0251) was also observed. ß-Carotene was negatively correlated with the adducts of formaldehyde (p = 0.0351) and acetaldehyde (p = 0.0413). Vitamin C tended to inversely correlate with acetaldehyde-induced adducts (p = 0.0584). CONCLUSION: These results are promising, and the study is now being conducted on a larger cohort with the aim of evaluating the impact of smoking cessation programs on the evolution of adducts profile and antioxidants activities.

Novel hydrocolloids synthesized by polyphenols grafted onto chitosan: A promising coating to inhibit PhIP formation during pan-frying of golden pompano fillets.

Hydrocolloids synthesized by gallic acid (GA) and ferulic acid (FA) grafting onto chitosan (CS) were characterized, and their effects on PhIP formation in pan-fried golden pompano were investigated. Spectrograms including nuclear magnetic resonance, Fourier transform infrared spectroscopy and ultraviolet-visible confirmed that GA and FA were successfully grafted onto CS via covalent bonds, with grafting degree of 97.06 ± 2.56 mg GA/g and 93.56 ± 2.76 mg FA/g, respectively. The CS-g-GA and CS-g-FA exerted better solubility and antioxidant activities than CS. For the 8-min pan-fried golden pompano fillets, CS-g-GA and CS-g-FA (0.5 %, m/v) significantly reduced the PhIP formation by 61.71 % and 81.64 %, respectively. Chemical models revealed that CS-g-GA and CS-g-FA inhibited PhIP formation mainly by decreasing the phenylacetaldehyde contents from Maillard reaction and competing with creatinine to react with phenylacetaldehyde. Therefore, it was suggested that CS-g-phenolic acids emerge as novel coating for aquatic products during processing and inhibit heterocyclic amines generation.

Investigating inhibitors of 1-deoxy-d-xylulose 5-phosphate synthase in a mouse model of UTI.

The rising rate of antimicrobial resistance continues to threaten global public health. Further hastening antimicrobial resistance is the lack of new antibiotics against new targets. The bacterial enzyme, 1-deoxy-d-xylulose 5-phosphate synthase (DXPS), is thought to play important roles in central metabolism, including processes required for pathogen adaptation to fluctuating host environments. Thus, impairing DXPS function represents a possible new antibacterial strategy. We previously investigated a DXPS-dependent metabolic adaptation as a potential target in uropathogenic Escherichia coli (UPEC) associated with urinary tract infection (UTI), using the DXPS-selective inhibitor butyl acetylphosphonate (BAP). However, investigations of DXPS inhibitors in vivo have not been conducted. The goal of the present study is to advance DXPS inhibitors as in vivo probes and assess the potential of inhibiting DXPS as a strategy to prevent UTI in vivo. We show that BAP was well-tolerated at high doses in mice and displayed a favorable pharmacokinetic profile for studies in a mouse model of UTI. Further, an alkyl acetylphosphonate prodrug (homopropargyl acetylphosphonate, pro-hpAP) was significantly more potent against UPEC in urine culture and exhibited good exposure in the urinary tract after systemic dosing. Prophylactic treatment with either BAP or pro-hpAP led to a partial protective effect against UTI, with the prodrug displaying improved efficacy compared to BAP. Overall, our results highlight the potential for DXPS inhibitors as in vivo probes and establish preliminary evidence that inhibiting DXPS impairs UPEC colonization in a mouse model of UTI.IMPORTANCENew antibiotics against new targets are needed to prevent an antimicrobial resistance crisis. Unfortunately, antibiotic discovery has slowed, and many newly FDA-approved antibiotics do not inhibit new targets. Alkyl acetylphosphonates (alkyl APs), which inhibit the enzyme 1-deoxy-d-xylulose 5-phosphate synthase (DXPS), represent a new possible class of compounds as there are no FDA-approved DXPS inhibitors. To our knowledge, this is the first study demonstrating the in vivo safety, pharmacokinetics, and efficacy of alkyl APs in a urinary tract infection mouse model.

Synergistic inhibition against heterocyclic amines in beef patties: Caused by carbonyl-trapping and toxicity-reducing of amino acid combinations.

The inhibitory effects of amino acids and their combinations on the formation of heterocyclic amines were investigated in this study. The great potential in the inhibition of HAs was observed in amino acid combinations compared with that of single agents. At a mass ratio of 1:1, a His-Pro combination achieved a maximum inhibitory rate of 80 %, and the total HAs content decreased to 4.70 ± 0.18 ng/g relative to the control (24.49 ± 2.18 ng/g). However, the inhibitory rate of triple combinations showed no obvious increase compared with the binary combinations. Benzaldehyde, phenylacetaldehyde, methylglyoxal, and glyoxal were positively correlated with HAs formation, and His-Pro combination (1:4) led to a significant reduction of benzaldehyde and phenylacetaldehyde at scavenging rates of 79 % and 92 %. Thus, the synergistic inhibition was achieved by simultaneously scavenging these aldehyde intermediates, and other inhibitory target, such as competition with precursors and elimination of final products can serve as supporting factors. These results provide a new perspective for approaches to enhance the suppression of HAs and control the formation of flavor compounds.

A primary study of ethanol production in postmortem liver and muscle tissue of rats.

OBJECTIVE: To study the characteristics of postmortem ethanol production and its relation with alcohol congeners in postmortem rat liver and muscle tissues. METHOD: Postmortem liver and muscle tissues in Sprague-Dawley rats, from postmortem time interval (PMI) day 0-20, were analyzed via headspace gas chromatograph flame ionization detection to observe production of postmortem ethanol and 5 selected alcohol congeners. RESULT: 1. Putrid ethanol production increased gradually to a peak and then decreased with the prolongation of PMI; 2. Acetaldehyde, 1-propanol, and 3-methyl-butyraldehyde were produced along with postmortem ethanol; 1-butanol was only detected from day 11-20; 3. The concentrations of acetaldehyde, 1-propanol and 3-methyl-butyraldehyde was related with ethanol production. Fifteen mathematical models were constructed for putrid ethanol production based on acetaldehyde, 1-propanol, and 3-methyl-butyraldehyde. CONCLUSION: A peak in postmortem ethanol production was identified. The production trends of acetaldehyde, 1-propanol, and 3-methyl-butyraldehyde in the liver, and of 1-propanol in muscle, were consistent with those of ethanol, and could potentially to be used as biomarkers of postmortem ethanol production. Further human samples and data analysis are needed to verify this.

Comparison of the properties of phenolic resin synthesized from different aldehydes and evaluation of the release and health risks of VOCs.

Different amounts of glyoxal and paraformaldehyde were used to synthesize phenol-glyoxal (PG) and phenol-paraformaldehyde (PPF) resins, which were compared with conventional phenol-formaldehyde (PF) resins. Glyoxal oxidation leads to a pH value of 9.83 for PG 2.2. With the addition of polyformaldehyde, PPF 2.2 exhibited the highest viscosity at 17333.33 mPa s. The PPF 2.0 plywood has a maximum bonding strength of 1.94 MPa. The formaldehyde emission of PG 1.8 plywood is found to have a minimum value of 0.025 mg/m3, reaching the ENF limit (≤0.025 mg/m3). Acetaldehyde is found only in volatile organic compound (VOC) emissions from PG plywood and is associated with increased glyoxal. PPF plywood emitted more aromatic and total VOC (TVOC) than the other two plywood types. The measured TVOC for PPF 2.2 is 196.07 µg/m3. The results showed that the total cancer risk (TCR) values of PPF 1.8, PPF 2.0, and PG 1.8 were above the threshold of 1.00E-4, indicating a definite carcinogenic risk. Acetaldehyde in the PG plywood exceeded the safety threshold for noncarcinogenic risk. The use of paraformaldehyde in the wood-based panel production is been considered a possible means of improving the bonding strength of plywood. Glyoxal has also been shown to be a viable method for lowering the formaldehyde emissions from plywood. The VOC emissions from plywood changed significantly depending on the aldehyde used. Limiting VOCs that present high health hazards is crucial for reducing the negative impact of plywood on both indoor environments and human health.

A Versatile Aldehyde: Ferredoxin Oxidoreductase from the Organic Acid Reducing Thermoanaerobacter sp. Strain X514.

Aldehyde:ferredoxin oxidoreductases (AORs) have been isolated and biochemically-characterized from a handful of anaerobic or facultative aerobic archaea and bacteria. They catalyze the ferredoxin (Fd)-dependent oxidation of aldehydes to acids. Recently, the involvement of AOR in the reduction of organic acids to alcohols with electrons derived from sugar or synthesis gas was demonstrated, with alcohol dehydrogenases (ADHs) carrying out the reduction of the aldehyde to the alcohol (AOR-ADH pathway). Here, we describe the biochemical characterization of an AOR of the thermophilic fermentative bacterium Thermoanaerobacter sp. strain X514 (AORX514). The putative aor gene (Teth514_1380) including a 6x-His-tag was introduced into the genome of the genetically-accessible, related species Thermoanaerobacter kivui. The protein was purified to apparent homogeneity, and indeed revealed AOR activity, as measured by acetaldehyde-dependent ferredoxin reduction. AORX514 was active over a wide temperature (10 to 95 °C) and pH (5.5 to 11.5) range, utilized a wide variety of aldehydes (short and branched-chained, aliphatic, aromatic) and resembles archaeal sensu stricto AORs, as the protein is active in a homodimeric form. The successful, recombinant production of AORX514 in a related, well-characterized and likewise strict anaerobe paves the road towards structure-function analyses of this enzyme and possibly similar oxygen-sensitive or W/Mo-dependent proteins in the future.

Molluscicidal activity of calcium borate nanoparticles with kodom ball-flower structure on hematological, histological and biochemical parameters of Eobania vermiculata snails.

Land snails are the most harmful pests in agricultural fields. Eobania vermiculata is a widespread snail species that causes massive damage to all agricultural crops. Thus, the molluscicidal activity of calcium borate nanoparticles (CB-NPs) against Eobania vermiculata was evaluated and compared with metaldehyde (Gastrotox® E 5% G). The amorphous phase of CB-NPs was obtained after thermal treatment at a low temperature (500 °C) which conformed by X-ray diffraction (XRD) analysis. CB-NPs are composed of aggregated nano-sheets with an average thickness of 54 nm which enhanced their molluscicidal activity. These nano-sheets displayed meso-porous network architecture with pore diameters of 13.65 nm, and a 9.46 m2/g specific surface area. CB-NPs and metaldehyde (Gastrotox® E 5% G) exhibited molluscicidal effects on Eobania vermiculata snails with median lethal concentrations LC50 of 175.3 and 60.5 mg/l, respectively, after 72 h of exposure. The results also showed significant reductions of Eobania vermiculata snails hemocytes' mean total number, the levels of Testosterone (T) and Estrogen (E), alkaline phosphatase, acid phosphatase, albumin, and protein concentrations, succinate dehydrogenase, glucose, triglycerides and phospholipids levels, while significant increases in the phagocytic index and mortality index, both transaminases (ALT and AST) and glycogen phosphorylase concentration were observed after the exposure to LC50 of CB-NPs or metaldehyde (Gastrotox® E 5% G) compared to the control group. Therefore, CB-NPs could be used as an alternative molluscicide for controlling Eobania vermiculata, but further studies are needed to assess their effects on non-target organisms.

Determination and Quantification of Acetaldehyde, Acetone, and Methanol in Hand Sanitizers Using Headspace GC/MS: Effect of Storage Time and Temperature.

Accurate determination of the concentration of alcohols and their metabolites is important in forensics and in several life science areas. A new headspace gas chromatography-mass spectrometry method has been developed to quantify alcohols and their oxidative products using isotope-labeled internal standards. The limit of detection (LOD) of the analytes in the developed method was 0.211 µg/mL for methanol, 0.158 µg/mL for ethanol, 0.157 µg/mL for isopropanol, 0.010 µg/mL for n-propanol, 0.157 µg/mL for acetone, and 0.209 µg/mL for acetaldehyde. The precision and accuracy of the method were evaluated, and the relative standard deviation percentages were found to be less than 3%. This work demonstrates the application of this method, specifically in quantifying the concentration of oxidative products of alcohol and other minor alcohols found in hand sanitizers, which have become an essential household item since the COVID-19 pandemic. Apart from the major components, the minor alcohols found in hand sanitizers include methanol, isopropanol, and n-propanol. The concentration range of these minor alcohols found in ethanol-based hand sanitizer samples was as follows: methanol, 0.000921-0.0151 mg/mL; isopropanol, 0.454-13.8 mg/mL; and n-propanol, 0.00474-0.152 mg/mL. In ethanol-based hand sanitizers, a significant amount of acetaldehyde (0.00623-0.231 mg/mL) was observed as an oxidation product, while in the isopropanol-based hand sanitizer, acetone (0.697 mg/mL) was observed as an oxidation product. The concentration of acetaldehyde in ethanol-based hand sanitizers significantly increased with storage time and temperature, whereas no such increase in acetone concentration was observed in isopropanol-based hand sanitizers with storage time and temperature. In two of the selected hand sanitizers, the acetaldehyde levels increased by almost 200% within a week when stored at room temperature. Additionally, exposing the hand sanitizers to a temperature of 45 °C for 24 h resulted in a 100% increase in acetaldehyde concentration. On the contrary, the acetone level remained constant upon the change in storage time and temperature.

Effect of Smoke Evacuator on Reduction of Volatile Organic Compounds and Particles in Surgical Smoke: A Randomized Controlled Trial.

BACKGROUND: Surgical smoke is an occupational health problem and is increasingly recognized as a potential source of virus transmission. Dedicated smoke evacuators are used to protect against surgical smoke exposure. We tested the hypothesis that using smoke evacuators would reduce volatile organic compounds and the number of particles in surgical smoke during the laparotomy procedure. STUDY DESIGN: A randomized, double-blind clinical trial was conducted in patients undergoing laparotomy from June 11, 2021, to March 30, 2022, to compare the effectiveness of smoke evacuators with a control (registration, UMIN000044250). The primary outcome was a change in the acetaldehyde level. Secondary outcomes were changes in the formaldehyde level and particle count assessed by the particle size of 0.3, 0.5, 1.0, and 5.0 nm. RESULTS: A total of 42 patients were randomized and assessed (smoke evacuator group, n = 22 vs control group, n = 20). The acetaldehyde level was significantly lower in the smoke evacuator group than in the control group: mean (95% CI), 10.6 (3.7 to 17.5) vs 47.2 (19.9 to 74.5) µg/m 3 , p < 0.001. Similarly, the formaldehyde level was 72.2% lower in the smoke evacuator group than in the control group. Particle counts by each particle size category were 80% to 95% lower in the smoke evacuator group than in the control group (all, p < 0.001). CONCLUSIONS: Dedicated smoke evacuators reduced the level of acetaldehyde and formaldehyde, and the number of particles in surgical smoke, minimizing the potential exposure to volatile organic compounds and particle matters during surgery.

Alcohol metabolism in alcohol use disorder: a potential therapeutic target.

Ethanol metabolism plays an essential role in how the body perceives and experiences alcohol consumption, and evidence suggests that modulation of ethanol metabolism can alter the risk for alcohol use disorder (AUD). In this review, we explore how ethanol metabolism, mainly via alcohol dehydrogenase and aldehyde dehydrogenase 2 (ALDH2), contributes to drinking behaviors by integrating preclinical and clinical findings. We discuss how alcohol dehydrogenase and ALDH2 polymorphisms change the risk for AUD, and whether we can harness that knowledge to design interventions for AUD that alter ethanol metabolism. We detail the use of disulfiram, RNAi strategies, and kudzu/isoflavones to inhibit ALDH2 and increase acetaldehyde, ideally leading to decreases in drinking behavior. In addition, we cover recent preclinical evidence suggesting that strategies other than increasing acetaldehyde-mediated aversion can decrease ethanol consumption, providing other potential metabolism-centric therapeutic targets. However, modulating ethanol metabolism has inherent risks, and we point out some of the key areas in which more data are needed to mitigate these potential adverse effects. Finally, we present our opinions on the future of treating AUD by the modulation of ethanol metabolism.