Unsaturated oxidative formaldehyde is a noxious aldehyde in cigarette smoke that causes edematous acute lung injury. However, the mechanistic effects of formaldehyde on lung fluid transport are still poorly understood. We examined how formaldehyde regulates human epithelial sodium channels (ENaC) in H441 and expressed in Xenopus oocytes and exposed mice in vivo. Our results showed that formaldehyde reduced mouse transalveolar fluid clearance in vivo. Formaldehyde caused a dose-dependent inhibition of amiloride-sensitive short-circuit Na+ currents in H441 monolayers and of αβγ-ENaC channel activity in oocytes. α-ENaC protein was reduced, whereas phosphorylation of the extracellular regulated protein kinases 1 and 2 (ERK1/2) increased significantly post exposure. Moreover, both α- and γ-ENaC transcripts were down-regulated. Reactive oxygen species (ROS) was elevated significantly by formaldehyde in addition to markedly augmented membrane permeability of oocytes. These data suggest that formaldehyde contributes to edematous acute lung injury by reducing transalveolar Na+ transport, through decreased ENaC activity and enhanced membrane depolarization, and by elevating ROS production over long-term exposure.

Formaldehyde has been discussed as a typical indoor pollutant for decades. To evaluate the current state-of-the-art in formaldehyde research and to identify the plethora of regulated and unregulated formaldehyde sources in indoor and outdoor spaces, an extensive literature search was carried out. The acquired data were analyzed with the aid of Monte-Carlo methods to calculate realistic formaldehyde concentration profiles and exposure scenarios under consideration of aging, source/sink behavior and diffusion effects. Average concentrations of formaldehyde are within 20-30 µg/m³ for European households under residential-typical conditions. The assumption of an average air exchange rate of 0.5 h-1 is also plausible. Formaldehyde emission rates of materials and products for indoor use are widely spread and range from non-detectable to > 1000 µg/h. However, processes like combustion, cleaning activities, operation of air purifiers and indoor chemistry were identified as temporary but relevant formaldehyde sources, which might cause high peak concentrations.

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Normal cellular processes give rise to toxic metabolites that cells must mitigate. Formaldehyde is a universal stressor and potent metabolic toxin that is generated in organisms from bacteria to humans. Methylotrophic bacteria such as Methylorubrum extorquens face an acute challenge due to their production of formaldehyde as an obligate central intermediate of single-carbon metabolism. Mechanisms to sense and respond to formaldehyde were speculated to exist in methylotrophs for decades but had never been discovered. Here, we identify a member of the DUF336 domain family, named efgA for enhanced formaldehyde growth, that plays an important role in endogenous formaldehyde stress response in M. extorquens PA1 and is found almost exclusively in methylotrophic taxa. Our experimental analyses reveal that EfgA is a formaldehyde sensor that rapidly arrests growth in response to elevated levels of formaldehyde. Heterologous expression of EfgA in Escherichia coli increases formaldehyde resistance, indicating that its interaction partners are widespread and conserved. EfgA represents the first example of a formaldehyde stress response system that does not involve enzymatic detoxification. Thus, EfgA comprises a unique stress response mechanism in bacteria, whereby a single protein directly senses elevated levels of a toxic intracellular metabolite and safeguards cells from potential damage.

Aldehyde dehydrogenase class 3, encoded by ADH5 in humans, catalyzes the glutathione dependent detoxification of formaldehyde. Here we show that ADH5 deficient cells turn over formaldehyde using alternative pathways starting from the reaction of formaldehyde with free amino acids. When mammalian cells are exposed to formaldehyde, the levels of the reaction products of formaldehyde with the amino acids cysteine and histidine - timonacic and spinacine - are increased. These reactions take place spontaneously and the formation of timonacic is reversible. The levels of timonacic are higher in the plasma of Adh5-/- mice relative to controls and they are further increased upon administration of methanol. We conclude that mammals possess pathways of cysteine and histidine dependent formaldehyde metabolism and that timonacic is a formaldehyde reservoir.

Formaldehyde (HCHO), a chemical compound used in the fabrication process of a broad range of household products, is present indoors as an airborne pollutant due to its high volatility caused by its low boiling point ( T = - 19 °C). Miniaturization of analytical systems towards palm-held devices has the potential to provide more efficient and more sensitive tools for real-time monitoring of this hazardous air pollutant. This work presents the initial steps and results of the prototyping process towards on-chip integration of HCHO sensing, based on the Hantzsch reaction coupled to the fluorescence optical sensing methodology. This challenge was divided into two individually addressed problems: (1) efficient airborne HCHO trapping into a microfluidic context and (2) 3,5-diacetyl-1,4-dihydrolutidine (DDL) molecular sensing in low interrogation volumes. Part (2) was addressed in this paper by proposing, fabricating, and testing a fluorescence detection system based on an ultra-low light Complementary metal-oxide-semiconductor (CMOS) image sensor. Two three-layer fluidic cell configurations (quartz-SU-8-quartz and silicon-SU-8-quartz) were tested, with both possessing a 3.5 µL interrogation volume. Finally, the CMOS-based fluorescence system proved the capability to detect an initial 10 µg/L formaldehyde concentration fully derivatized into DDL for both the quartz and silicon fluidic cells, but with a higher signal-to-noise ratio (SNR) for the silicon fluidic cell ( S N R s i l i c o n = 6.1 ) when compared to the quartz fluidic cell ( S N R q u a r t z = 4.9 ). The signal intensity enhancement in the silicon fluidic cell was mainly due to the silicon absorption coefficient at the excitation wavelength,   a ( λ a b s = 420   nm ) = 5 × 10 4   cm - 1 , which is approximately five times higher than the absorption coefficient at the fluorescence emission wavelength, a ( λ e m = 515   nm ) = 9.25 × 10 3   cm - 1 .

Studies suggest that patch testing with formaldehyde releasers (FRs) gives significant additional information to formaldehyde 1% aq. and should be considered for addition to the European baseline series (EBS). It is not known if this is also true for formaldehyde 2% aq.

The group of neurodegenerative diseases, Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) all exhibit inclusions containing amyloid-type α-synuclein (α-syn) aggregates within degenerating brain cells. α-syn also exists as soluble oligomeric species that are hypothesized to represent intermediates between its native and aggregated states. These oligomers are present in brain extracts from patients suffering from synucleinopathies and hold great potential as biomarkers. Although easily prepared in vitro, oligomers are metastable and dissociate over time, thereby complicating α-syn oligomer research. Using the small amine-reactive cross-linker, formaldehyde (FA), we successfully stabilized α-syn oligomers without affecting their size, overall structure or antigenicity towards aggregate-conformation specific α-syn antibodies FILA and MJFR-14-6-4-2. Further, cross-linked α-syn oligomers show resistance towards denaturant like urea and SDS treatment and remain fully functional as internal standard in an aggregation-specific enzyme-linked immunosorbent assay (ELISA) despite prior incubation with urea. We propose that FA cross-linked α-syn oligomers could serve as important calibrators to facilitate comparative and standardized α-syn biomarker studies going forward.

The adsorption technique is widely used in water purification, and its efficiency can be significantly improved by target-specific adsorbent design. Research on iodine and its ion removal from water has attracted a great deal of interest due to increased concentrations in the environment and acute toxic effects, e.g., in human thyroid cells. In this work, the iodide removal performance of two high-surface-area resorcinol-formaldehyde-based carbon aerogels was studied under acidic conditions. The BET surface area was 790 m2/g (RF_ac) and 375 m2/g (RMF-GO), with a corresponding micropore ratio of 36 and 26%, respectively. Both aerogels showed outstanding adsorption capacity, exceeding the reported performance of other carbons and Ag-doped materials. Owing to its basic nature, the RMF-GO carbon aerogel showed higher I- capacity, up to 97 mg/g, than the acidic RF_ac, which reached a capacity of 82 mg/g. The surface chemistry of the aerogels also played a distinct role in the removal. In terms of kinetics, RF_ac removed 60% of the iodide ions and RMF-GO 30% within 8 h. The removal kinetics was of the first order, with a half-life of 1.94 and 1.70 h, respectively.

Low-cost urea formaldehyde resin (UF)/reactive halloysite nanotubes (HNTs) nanocomposite adhesive was prepared successfully via in situ polymerization. The HNTs were modified to improve its compatibility with polymer. The XRD and FTIR results showed that physical and chemical interaction between the HNTs and polymer resin influenced the structure of UF owing to the functional groups on the HNTs. It is found from SEM images that the modified HNTs could be dispersed uniformly in the resin and the nanocomposite particles were spherical. The performance experiment confirmed that thermal stability of nanocomposite increased largely, formaldehyde emission of UF wood adhesive reduced 62%, and water resistance of UF wood adhesive improved by 84%. Meanwhile, the content of HNTs on the nanocomposites could be up to 60 wt %. The mechanism of the nanocomposites based on the reactive HNTs was proposed. The approach of the preparation could supply an idea to prepare other polymer/clay nanocomposites.

Folate enzyme cofactors and their derivatives have the unique ability to provide a single carbon unit at different oxidation levels for the de novo synthesis of amino-acids, purines, or thymidylate, an essential DNA nucleotide. How these cofactors mediate methylene transfer is not fully settled yet, particularly with regard to how the methylene is transferred to the methylene acceptor. Here, we uncovered that the bacterial thymidylate synthase ThyX, which relies on both folate and flavin for activity, can also use a formaldehyde-shunt to directly synthesize thymidylate. Combining biochemical, spectroscopic and anaerobic crystallographic analyses, we showed that formaldehyde reacts with the reduced flavin coenzyme to form a carbinolamine intermediate used by ThyX for dUMP methylation. The crystallographic structure of this intermediate reveals how ThyX activates formaldehyde and uses it, with the assistance of active site residues, to methylate dUMP. Our results reveal that carbinolamine species promote methylene transfer and suggest that the use of a CH2O-shunt may be relevant in several other important folate-dependent reactions.

A promising strategy for the prevention of Alzheimer's disease (AD) is the identification of age-related changes that place the brain at risk for the disease. Additionally, AD is associated with chronic dehydration, and one of the significant changes that are known to result in metabolic dysfunction is an increase in the endogenous formaldehyde (FA) level. Here, we demonstrate that the levels of uric formaldehyde in AD patients were markedly increased compared with normal controls. The brain formaldehyde levels of wild-type C57 BL/6 mice increased with age, and these increases were followed by decreases in their drinking frequency and water intake. The serum arginine vasopressin (AVP) concentrations were also maintained at a high level in the 10-month-old mice. An intravenous injection of AVP into the tail induced decreases in the drinking frequency and water intake in the mice, and these decreases were associated with increases in brain formaldehyde levels. An ELISA assay revealed that the AVP injection increased both the protein level and the enzymatic activity of semicarbazide-sensitive amine oxidase (SSAO), which is an enzyme that produces formaldehyde. In contrast, the intraperitoneal injection of formaldehyde increased the serum AVP level by increasing the angiotensin II (ANG II) level, and this change was associated with a marked decrease in water intake behavior. These data suggest that the interaction between formaldehyde and AVP affects the water intake behaviors of mice. Furthermore, the highest concentration of formaldehyde in vivo was observed in the morning. Regular water intake is conducive to eliminating endogenous formaldehyde from the human body, particularly when water is consumed in the morning. Establishing good water intake habits not only effectively eliminates excess formaldehyde and other metabolic products but is also expected to yield valuable approaches to reducing the risk of AD prior to the onset of the disease.

Formaldehyde crosslinking is in widespread use as a biological fixative for microscopy and molecular biology. An assumption behind its use is that most biologically meaningful interactions are preserved by crosslinking, but the minimum length of time required for an interaction to become fixed has not been determined.

Most organisms are exposed to the genotoxic chemical formaldehyde, either from endogenous or environmental sources. Therefore, biology has evolved systems to perceive and detoxify formaldehyde. The frmRA(B) operon that is present in many bacteria represents one such system. The FrmR protein is a transcriptional repressor that is specifically inactivated in the presence of formaldehyde, permitting expression of the formaldehyde detoxification machinery (FrmA and FrmB, when the latter is present). The X-ray structure of the formaldehyde-treated Escherichia coli FrmR (EcFrmR) protein reveals the formation of methylene bridges that link adjacent Pro2 and Cys35 residues in the EcFrmR tetramer. Methylene bridge formation has profound effects on the pattern of surface charge of EcFrmR and combined with biochemical/biophysical data suggests a mechanistic model for formaldehyde-sensing and derepression of frmRA(B) expression in numerous bacterial species.

Formaldehyde is a highly reactive compound that participates in multiple spontaneous reactions, but these are mostly deleterious and damage cellular components. In contrast, the spontaneous condensation of formaldehyde with tetrahydrofolate (THF) has been proposed to contribute to the assimilation of this intermediate during growth on C1 carbon sources such as methanol. However, the in vivo rate of this condensation reaction is unknown and its possible contribution to growth remains elusive. Here, we used microbial platforms to assess the rate of this condensation in the cellular environment. We constructed Escherichia coli strains lacking the enzymes that naturally produce 5,10-methylene-THF. These strains were able to grow on minimal medium only when equipped with a sarcosine (N-methyl-glycine) oxidation pathway that sustained a high cellular concentration of formaldehyde, which spontaneously reacts with THF to produce 5,10-methylene-THF. We used flux balance analysis to derive the rate of the spontaneous condensation from the observed growth rate. According to this, we calculated that a microorganism obtaining its entire biomass via the spontaneous condensation of formaldehyde with THF would have a doubling time of more than three weeks. Hence, this spontaneous reaction is unlikely to serve as an effective route for formaldehyde assimilation.

Exposure to Formaldehyde (FA) results in many pathophysiological symptoms, however the underlying mechanisms are not well understood. Given the complicated modulatory role of intestinal microbiota on human health, we hypothesized that interactions between FA and the gut microbiome may account for FA's toxicity. Balb/c mice were allocated randomly to three groups: a control group, a methanol group (0.1 and 0.3 ng/mL MeOH subgroups), and an FA group (1 and 3 ng/mL FA subgroups). Groups of either three or six mice were used for the control or experiment. We applied high-throughput sequencing of 16S ribosomal RNA (rRNA) gene approaches and investigated possible alterations in the composition of mouse gut microbiota induced by FA. Changes in bacterial genera induced by FA exposure were identified. By analyzing KEGG metabolic pathways predicted by PICRUSt software, we also explored the potential metabolic changes, such as alpha-Linolenic acid metabolism and pathways in cancer, associated with FA exposure in mice. To the best of our knowledge, this preliminary study is the first to identify changes in the mouse gut microbiome after FA exposure, and to analyze the relevant potential metabolisms. The limitation of this study: this study is relatively small and needs to be further confirmed through a larger study.

Formaldehyde (HCHO), the simplest and most abundant carbonyl in the atmosphere, contributes to particulate matter (PM) formation via two in-cloud processing pathways. First, in a catalytic pathway, HCHO reacts with hydrogen peroxide (H2O2) to form hydroxymethyl hydroperoxide (HMHP), which rapidly oxidizes dissolved sulfur dioxide (SO2,aq) to sulfate, regenerating HCHO. Second, HCHO reacts with dissolved SO2,aq to form hydroxymethanesulfonate (HMS), which upon oxidation with the hydroxyl radical (OH) forms sulfate and also reforms HCHO. Chemical transport model simulations using rate coefficients from laboratory studies of the reaction rate of HMHP with SO2,aq show that the HMHP pathways reduce the SO2 lifetime by up to a factor of 2 and contribute up to ∼18% of global sulfate. This contribution rises to >50% in isoprene-dominated regions such as the Amazon. Combined with recent results on HMS, this work demonstrates that the one-carbon molecules HMHP and HCHO contribute significantly to global PM, with HCHO playing a crucial catalytic role.

The objectives of the systematic review were to: identify the work sectors at risk for exposure to formaldehyde; investigate the procedures applied to assess occupational exposure; evaluate the reported exposure levels among the different settings. An electronic search of Pubmed, Scopus, Web of Science and ToxNet was carried out for collecting all the articles on the investigated issue published from January 1, 2004 to September 30, 2019. Forty-three papers were included in the review, and evidenced a great number of occupational scenarios at risk for formaldehyde exposure. All the included studies collected data on formaldehyde exposure levels by a similar approach: environmental and personal sampling followed by chromatographic analyses. Results ranged from not detectable values until to some mg m-3 of airborne formaldehyde. The riskiest occupational settings for formaldehyde exposure were the gross anatomy and pathology laboratories, the hairdressing salons and some specific productive settings, such as wooden furniture factories, dairy facilities and fish hatcheries. Notice that formaldehyde, a well-known carcinogen, was recovered in air at levels higher than outdoor in almost all the studied scenarios/activities; thus, when formaldehyde cannot be removed or substituted, targeted strategies for exposure elimination or mitigation must be adopted.

Formaldehyde is a known human carcinogen and an important indoor and outdoor air pollutant. However, current strategies for formaldehyde measurement, such as chromatographic and optical techniques, are expensive and labor intensive. Low-cost gas sensors have been emerging to provide effective measurement of air pollutants. In this study, we evaluated eight low-cost electrochemical formaldehyde sensors (SFA30, Sensirion®, Staefa, Switzerland) in the laboratory with a broadband cavity-enhanced absorption spectroscopy as the reference instrument. As a group, the sensors exhibited good linearity of response (R2 > 0.95), low limit of detection (11.3 ± 2.07 ppb), good accuracy (3.96 ± 0.33 ppb and 6.2 ± 0.3% N), acceptable repeatability (3.46% averaged coefficient of variation), reasonably fast response (131-439 s) and moderate inter-sensor variability (0.551 intraclass correlation coefficient) over the formaldehyde concentration range of 0-76 ppb. We also systematically investigated the effects of temperature and relative humidity on sensor response, and the results showed that formaldehyde concentration was the most important contributor to sensor response, followed by temperature, and relative humidity. The results suggest the feasibility of using this low-cost electrochemical sensor to measure formaldehyde concentrations at relevant concentration ranges in indoor and outdoor environments.

Numerous mammalian viruses are routinely analyzed in clinical diagnostic laboratories around the globe or serve as indispensable model systems in viral research. Potentially infectious viral entities are handled as blood, biopsies, or cell and tissue culture samples. Countless protocols describe methods for virus fixation and inactivation, yet for many, a formal proof of safety and completeness of inactivation remains to be shown. While modern nucleic acid extraction methods work quite effectively, data are largely lacking on possible residual viral infectivity, e.g., when assessed after extended culture times, which maximizes the sensitivity for low levels of residual infectiousness. Therefore, we examined the potency and completeness of inactivation procedures on virus-containing specimens when applying commonly used fixatives like formaldehyde or nucleic acid extraction/lysis buffers. Typical representatives of different virus classes, including RNA and DNA viruses, enveloped and non-enveloped, such as adenovirus, enterovirus, lentivirus, and coronavirus, were used, and the reduction in the in vitro infectiousness was assessed for standard protocols. Overall, a 30-minute incubation with formaldehyde at room temperature effectively inactivated all tested enveloped and non-enveloped viruses. Full inactivation of HIV-1 and ECHO-11 was also achieved with all buffers in the test, whereas for SARS-CoV-2 and AdV-5, only five of the seven lysis buffers were fully effective under the tested conditions.