Heterogeneous hydrochlorination of lipids mediated by fatty acids in an indoor environment.

Fatty acids from cooking fumes and hypochlorous acid (HOCl) released from indoor cleaning adversely affect respiratory health, but the molecular-level mechanism remains unclear. Here, the effect of cooking oil fumes [palmitic acid (PA), oleic acid (OA), and linoleic acid (LA)] on lung model phospholipid (POPG) hydrochlorination mediated by HOCl at the air-water interface of the hanged droplets was investigated. Interfacial hydrochlorination of POPG was impeded by OA and LA, while that of POPG was facilitated by PA. The effect on POPG hydrochlorination increased with the decrease in oil fume concentration. A potential mechanism with respect to the chain length of these oil fumes, regardless of their saturation, was proposed. PA with a short carbon chain looses the POPG packing and leads to the exposure of the C=C double bonds of POPG, whereas OA and LA with a long carbon chain hinder HOCl from reaching the C=C bonds of POPG. These results for short chain and low concentration dependence suggest that the decay of oil fumes or the conversion of short-chain species by indoor interfacial chemistry might be adverse to lung health. These results provide insights into the relationship between indoor multicomponent pollutants and the respiratory system.

Multidisciplinary expert consensus statements and recommendations for use of hypochlorous acid as a solution for negative pressure wound therapy with instillation.

BACKGROUND: HOCl (eg, pHAp) preserved solutions have antimicrobial properties and are considered safe and effective for wound management. NPWTi-d (or NPWTi) is an established adjunctive wound modality for a variety of wound etiologies in various anatomic locations in which an instillate solution dwells on the surface of the wound to assist in wound bed preparation. A variety of solutions have been used, including 0.9% normal saline wound cleansers and antiseptics. pHAp is growing in popularity as the solution of choice for NPWTi-d. OBJECTIVE: To evaluate consensus statements on the use of NPWTi-d with pHAp. METHODS: A 15-member multidisciplinary panel of expert clinicians in the United States, Canada, and France convened in person in April 2023 in Washington, D.C. and/or corresponded later to discuss 10 statements on the use of pHAp with NPWTi-d. The panelists then replied "agree" or "disagree" to each statement and had the option to provide comments. RESULTS: Ten consensus statements are presented, along with the proportion of agreement or disagreement and summary comments. Although agreement with the statements on NPWTi-d with pHAp varied, the statements appear to reflect individual preferences for use rather than concerns about safety or efficacy. CONCLUSION: The consensus indicates that NPWTi-d with pHAp can have a beneficial effect in wound care.

The therapeutic potential of thiocyanate and hypothiocyanous acid against pulmonary infections.

Hypothiocyanous acid (HOSCN) is an endogenous oxidant produced by peroxidase oxidation of thiocyanate (SCN-), an ubiquitous sulfur-containing pseudohalide synthesized from cyanide. HOSCN serves as a potent microbicidal agent against pathogenic bacteria, viruses, and fungi, functioning through thiol-targeting mechanisms, independent of currently approved antimicrobials. Additionally, SCN- reacts with hypochlorous acid (HOCl), a highly reactive oxidant produced by myeloperoxidase (MPO) at sites of inflammation, also producing HOSCN. This imparts both antioxidant and antimicrobial potential to SCN-. In this review, we discuss roles of HOSCN/SCN- in immunity and potential therapeutic implications for combating infections.

Visualization of Endogenous Hypochlorite in Drug-Induced Liver Injury Mice via a Bioluminescent Probe Combined with Firefly Luciferase mRNA-Loaded Lipid Nanoparticles.

Drug-induced liver injury (DILI) is a common liver disease with a high rate of morbidity, and its pathogenesis is closely associated with the overproduction of highly reactive hypochlorite (ClO-) in the liver. However, bioluminescence imaging of endogenous hypochlorite in nontransgenic natural mice remains challenging. Herein, to address this issue, we report a strategy for imaging ClO- in living cells and DILI mice by harnessing a bioluminescent probe formylhydrazine luciferin (ClO-Luc) combined with firefly luciferase (fLuc) mRNA-loaded lipid nanoparticles (LNPs). LNPs could efficiently deliver fLuc mRNA into living cells and in vivo, expressing abundant luciferase in the cytoplasm in situ. In the presence of ClO-, probe ClO-Luc locked by formylhydrazine could release cage-free d-luciferin through oxidation and follow-up hydrolysis reactions, further allowing for bioluminescence imaging. Moreover, based on the luciferase-luciferin system, it was able to sensitively and selectively detect ClO- in vitro with a limit of detection of 0.59 µM and successfully monitor the endogenous hypochlorite generation in the DILI mouse model for the first time. We postulate that this work provides a new method to elucidate the roles of ClO- in related diseases via bioluminescence imaging.

A G-quadruplex/thioflavin T-based label-free biosensor to detect ClO- in stress-induced hypertension.

Hypochlorous acid (HClO), as an essential reactive oxygen species (ROS) in biological systems, plays a pivotal role in processes of physiology and pathology. Abnormal fluctuations in HClO concentration can lead to various diseases, such as inflammation, cardiovascular diseases, and neurodegeneration. Therefore, developing an approach to rapidly and sensitively quantify ClO- content is vital to biomedicine development and bioassays. Herein, we fabricated a novel "turn-on" label-free fluorescence DNA probe to specifically detect hypochlorite ion (ClO-) based on G-quadruplex formation. To this end, we designed a G-rich signal DNA sequence (S-DNA) and a block DNA sequence (B-DNA), followed by the introduction of ClO--responsive phosphorothioate (PS) into B-DNA. In the absence of ClO-, B-DNA hybridized with S-DNA, preventing G-quadruplex formation from S-DNA; this resulted in the relatively low fluorescence intensity of ThT. Once ClO- was added, the hydrolysis between PS and ClO- split the B-DNA into two fragments, resulting in B-DNA breaking away from S-DNA, allowing G-quadruplex formation from S-DNA and increasing the fluorescence intensity of ThT. Using this method, we can detect ClO- without the interference of additional reactive oxygen species. The detection limit of ClO- was as low as 10 nM. Furthermore, this method facilitates the detection of ClO- within the tissues of rats with stress-induced hypertension.

Detection and application of hypochlorous acid in both aqueous environments and living organisms.

The scarcity of water resources has raised concerns regarding drinking water safety. Excessive addition of hypochlorous acid (OCl-) as a disinfectant in drinking water can result in severe consequences. Moreover, abnormal levels of OCl- within the human body can lead to various diseases. Employing fluorescence analysis, the design and synthesis of specific fluorescent probes for simultaneous detection of OCl- in water environments and living organisms holds strategic significance in ensuring the safety of drinking water and mitigating potential risks caused by its abnormal concentrations. This article utilizes naphthalimide as a precursor to develop a novel probe enabling highly sensitive detection of OCl- in water environments and at the organelle level within living organisms. This endeavor serves to provide assurance for drinking water safety and offers health alerts.

Ratiometric Near-Infrared Fluorescent Probe Monitors Ferroptosis in HCC Cells by Imaging HClO in Mitochondria.

Hypochlorous acid (HClO) is a typical endogenous ROS produced mainly in mitochondria, and it has strong oxidative properties. Abnormal HClO levels lead to mitochondrial dysfunction, strongly associated with various diseases. It has been shown that HClO shows traces of overexpression in cells of both ferroptosis and hepatocellular carcinoma (HCC). Therefore, visualization of HClO levels during ferroptosis of HCC is important to explore its physiological and pathological roles. So far, there has been no report on the visualization of HClO in ferroptosis of HCC. Thus, we present a ratiometric near-infrared (NIR) fluorescent probe Mito-Rh-S which visualized for the first time the fluctuation of HClO in mitochondria during ferroptosis of HCC. Mito-Rh-S has an ultrafast response rate (2 s) and large emission shift (115 nm). Mito-Rh-S was constructed based on the PET sensing mechanism and thus has a high signal-to-noise ratio. The cell experiments of Mito-Rh-S demonstrated that Fe2+- and erastin-induced ferroptosis in HepG2 cells resulted in elevated levels of mitochondrial HClO and that high concentration levels of Fe2+ and erastin cause severe mitochondrial damage and oxidative stress and had the potential to kill HepG2 cells. By regulating the erastin concentration, erastin induction time, and treatment of the ferroptosis model, Mito-Rh-S can accurately detect the fluctuation of mitochondrial HClO levels during ferroptosis in HCC.

Virucidal efficacy of hypochlorous acid water for aqueous phase and atomization against SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) is an infectious viral disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged at the end of 2019. SARS-CoV-2 can be transmitted through droplets, aerosols, and fomites. Disinfectants such as alcohol, quaternary ammonium salts, and chlorine-releasing agents, including hypochlorous acid, are used to prevent the spread of SARS-CoV-2 infection. In the present study, we investigated the efficacy of ionless hypochlorous acid water (HOCl) in suspension and by spraying to inactivate SARS-CoV-2. The virucidal efficacy of HOCl solution in tests against SARS-CoV-2 was evaluated as 50% tissue culture infectious dose. Although the presence of organic compounds influenced the virucidal efficacy, HOCl treatment for 20 s was significantly effective to inactivate Wuhan and Delta strains in the suspension test. HOCl atomization for several hours significantly reduced the SARS-CoV-2 attached to plastic plates. These results indicate that HOCl solution with elimination containing NaCl and other ions may have high virucidal efficacy against SARS-CoV-2. This study provides important information about the virucidal efficacy and use of HOCl solution.

Antimicrobial action, cytotoxicity and erosive potential of hypochlorous acid obtained from an electrolytic device compared with sodium hypochlorite.

OBJECTIVES: This study aimed to compare the antimicrobial action, cytotoxicity, cleaning ability, and erosion of dentine of hypochlorous acid (HClO) obtained from an electrolytic device at two different concentrations (Dentaqua) and three concentrations of sodium hypochlorite (NaOCl). METHODS: Microbiological test-The root canals of sixty single-rooted extracted human teeth were inoculated with Enterococcus faecalis and divided into 6 groups (n = 10), according to decontamination protocol: DW (control); 1% NaOCl; 2.5% NaOCl; 5.25% NaOCl; 250 ppm HClO and 500 ppm HClO. The colony-forming units were counted to evaluate the decontamination potential of each group, calculating the reduction in bacterial percentage. Cytotoxicity test-Cytotoxicity was evaluated after inoculation of the same tested protocols in fibroblastic cells for 3 min, calculating the cell viability percentages. Specifical statistical analysis was performed (α = 5%). Cleaning ability and erosion-Fifty-six single-rooted bovine lower incisors were divided into seven groups of 8 roots each, being the test groups 1% NaOCl; 2.5% NaOCl; 5,25% NaOCl; 250 ppm HClO and 500 ppm HClO, and a negative and positive control. Negative control was not contaminated, and the other groups were inoculated with Enterococcus faecalis. SEM images were ranked as from the cleanest to the least clean. Erosion was also assessed, being ranked from the least to the most eroded dentine. RESULTS: The highest bacterial reduction was observed in experimental groups, with no statistical differences between them (p > 0.05). The highest number of viable cells was observed in control group, followed by 250 ppm HClO and 500 ppm HClO groups, with statistical differences between them (p < 0.05). 1% NaOCl; 2.5% NaOCl; 5.25% NaOCl and 500 ppm HClO displayed the cleanest areas. All sodium hypochlorite groups displayed erosion with higher ranks with greater concentration, while hypochlorous acid did not display any erosion regardless the concentration. CONCLUSIONS: It is possible to conclude that HClO obtained from an electrolytic device presented high antimicrobial activity and low cytotoxicity in both tested concentrations. 500 ppm HClO did not display erosion and showed great cleaning ability. CLINICAL RELEVANCE: The use of 500 ppm hypochlorous acid may reduce unfavorable behavior of sodium hypochlorite whilst maintaining its antimicrobial action.

Taming Janus-Faced Quinoline-Derived Fluorescent Probes for Dual-Channel Distinguishable Visualization of HSO3- and HClO in Dried Foods and Living Cells.

With the booming development of food manufacturing, developing ideal analytical tools to precisely quantify food additives is highly sought after in the food science field. Herein, a new series of quinoline-derived multifunctional fluorescent probes has been synthesized. Bearing double reactive sites, these compounds display fluorescence response toward both bisulfite (HSO3-) and hypochlorous acid (HClO). Among these compact structures, compound ethyl-2-cyano-3-(6-(methylthio)quinolin-2-yl)acrylate (QTE) was screened out. Probe QTE not only shows ratiometric variation toward HSO3- with little cross talk but also performs turn-off signal toward HClO. In addition, probe QTE has been utilized for bioimaging of HClO in living cells. Furthermore, the HSO3- content in dried food samples has been appraised by QTE with satisfactory results. Meanwhile, relying on the apparent chromaticity change, a flexible dark-box device has been elaborated for chromatic analysis, promoting visualization of HSO3- in the field.

Design, synthesis, and biological application of A-D-A-type boranil fluorescent dyes.

For the first time, three acceptor-donor-acceptor (A-D-A)-type boranil fluorescent dyes, CSU-BF-R (R = H, CH3, and OCH3), featuring phenothiazine as the donor, were designed and synthesized. CSU-BF-R exhibited remarkable photophysical characteristics, including large Stokes shifts (>150 nm), high fluorescence quantum yields (up to 40%), long-wavelength emissions, and strong red solid-state fluorescence. Moreover, these CSU-BF-R fluorescent dyes were demonstrated to function as highly selective and sensitive ratiometric fluorescent probes for detecting hypochlorous acid (HClO). The preliminary biological applications of CSU-BF-OCH3 for sensing intracellular HClO in living cells and zebrafish were demonstrated. Therefore, CSU-BF-R possess the potential to further explore the physiological and pathological functions associated with HClO and provide valuable insights into the design of high-performance A-D-A-type fluorescent dyes.

Antimicrobial action and cytotoxicity of hypochlorous acid obtained from an innovative electrolytic device - An in vitro study.

OBJECTIVE: This study evaluated the antimicrobial effect and cytotoxicity of hypochlorous acid(HClO) obtained from an innovative electrolytic device. DESIGN: The root canals of fifty extracted human teeth were inoculated with Enterococcus faecalis and divided into 5 groups (n = 10): DW (control); 2% chlorhexidine gel(CHX); 2.5% sodium hypochlorite(NaOCl); 250 ppm HClO and 500 ppm HClO. The counting of colony forming units evaluated the decontamination potential of each group. Cytotoxicity was evaluated after inoculation of tested protocols in fibroblastic cells for 3 min, calculating the cell viability. Specific statistical analysis was performed (α = 5%). RESULTS: The highest bacterial reduction was observed in experimental groups, with no statistical differences from each other (p > 0.05). The highest number of viable cells was observed in control group, followed by 250 ppm HClO and 500 ppm HClO groups, with statistical differences from each other (p < 0.05). CONCLUSIONS: It could be concluded that HClO presented high antimicrobial activity and low cytotoxicity at both tested concentrations.

Quantifying sodium hypochlorite content in hypochlorite-based disinfectants via phase-conversion headspace technique.

In this work, a novel and efficient approach for sodium hypochlorite analysis is proposed via phase-conversion headspace technique, which is based on the gas chromatography (GC) detection of generated carbon dioxide (CO2) from the redox reaction of sodium hypochlorite with sodium oxalate. The data obtained by the proposed method suggest the high detecting precision and accuracy. In addition, the method has low detection limits (limit of quantification (LOQ) = 0.24 µg/mL), and the recoveries of added standard ranged from 98.33 to 101.27 %. The proposed phase-conversion headspace technique is efficient and automated, thereby offering an efficient strategy for highly efficient analysis of sodium hypochlorite and related products.

Persistent Luminescence Lifetime-Based Near-Infrared Nanoplatform via Deep Learning for High-Fidelity Biosensing of Hypochlorite.

In light of deep tissue penetration and ultralow background, near-infrared (NIR) persistent luminescence (PersL) bioprobes have become powerful tools for bioapplications. However, the inhomogeneous signal attenuation may significantly limit its application for precise biosensing owing to tissue absorption and scattering. In this work, a PersL lifetime-based nanoplatform via deep learning was proposed for high-fidelity bioimaging and biosensing in vivo. The persistent luminescence imaging network (PLI-Net), which consisted of a 3D-deep convolutional neural network (3D-CNN) and the PersL imaging system, was logically constructed to accurately extract the lifetime feature from the profile of PersL intensity-based decay images. Significantly, the NIR PersL nanomaterials represented by Zn1+xGa2-2xSnxO4: 0.4 % Cr (ZGSO) were precisely adjusted over their lifetime, enabling the PersL lifetime-based imaging with high-contrast signals. Inspired by the adjustable and reliable PersL lifetime imaging of ZGSO NPs, a proof-of-concept PersL nanoplatform was further developed and showed exceptional analytical performance for hypochlorite detection via a luminescence resonance energy transfer process. Remarkably, on the merits of the dependable and anti-interference PersL lifetimes, this PersL lifetime-based nanoprobe provided highly sensitive and accurate imaging of both endogenous and exogenous hypochlorite. This breakthrough opened up a new way for the development of high-fidelity biosensing in complex matrix systems.

Dicyanoisophorone-based near-infrared fluorescent probe with large Stokes shift for the monitoring and bioimaging of hypochlorite.

Hypochlorite (ClO-), as one of reactive oxygen species (ROS), is closely linked to various illnesses and is essential for the proper functioning of immune system. Hence, monitoring and assessing ClO- levels in organisms are extremely important for the clinical diagnosis of ClO--related disorders. In this study, a novel ClO--selective fluorescent probe, DCP-ClO, was synthesized with dicyanoisophorone-xanthene unit as parent fluorophore, which displayed excellent selectivity towards ClO-, near-infrared emission (755 nm), large Stokes shift (100 nm), real-time response to ClO-, high sensitivity (LOD = 3.95 × 10-8 M), and low cytotoxicity. The recognition mechanism of DCP-ClO towards ClO- was confirmed to be a typical ICT process by HPLC-MS, HR-MS, 1H NMR and theoretical calculations. Meanwhile, DCP-ClO demonstrated remarkable efficacy in monitoring ClO- levels in water samples and eye-catching ability in imaging endogenous/exogenous ClO- in living organisms, which verified its potential as a powerful tool for the recognition of ClO- in complex biological systems.

A lysosome-targeted fluorescent probe for fluorescence imaging of hypochlorous acid in living cells and in vivo.

Lysosomes, as crucial acidic organelles in cells, play a significant role in cellular functions. The levels and distribution of hypochlorous acid (HOCl) within lysosomes can profoundly impact their biological functionality. Hence, real-time monitoring of the concentration of HOCl in lysosomes holds paramount importance for further understanding various physiological and pathological processes associated with lysosomes. In this study, we developed a bodipy-based fluorescent probe derived from pyridine and phenyl selenide for the specific detection of HOCl in aqueous solutions. Leveraging the probe's sensitive photoinduced electron transfer effect from phenyl selenide to the fluorophore, the probe exhibited satisfactory high sensitivity (with a limit of detection of 5.2 nM and a response time of 15 s) to hypochlorous acid. Further biological experiments confirmed that the introduction of the pyridine moiety enabled the probe molecule to selectively target lysosomes. Moreover, the probe successfully facilitated real-time monitoring of HOCl in cell models stimulated by N-acetylcysteine (NAC) and lipopolysaccharide (LPS), as well as in a normal zebrafish model. This provides a universal method for dynamically sensing HOCl in lysosomes.

Inhalation of gaseous hypochlorous acid and its effect on human respiratory epithelial cells in laboratory model systems.

During the disinfection of indoor spaces using gaseous hypochlorous acid (HOCl(g)), inhalation is the most common route of exposure for humans. In this study, an artificial human respiratory tract model was exposed to 12-140 ppb HOCl(g) at an aspiration flow rate of 800 mL/s for 15 h in a 1 m3 chamber. The respiratory tract model was equipped with 5th order bronchi and all gas-contact parts were made of silicone rubber with no other chlorine-consuming substances. The concentration of HOCl(g) reaching the lung pseudo-space was approximately 47.4% of the HOCl(g) concentrations in the chamber and was calculated to be very close to zero when the chamber concentration was less than 20.5 ppb. The disappearance of HOCl(g) during inhalation is likely due to the adsorption of HOCl(g) on the gas-contact silicone rubber surfaces. The cytotoxicity of HOCl(g) on respiratory epithelial cells was also examined using human air-liquid-interface airway tissue models. Human nasal epithelium and bronchiolar epithelium were exposed to 100 ppb and 500 ppb HOCl(g) for 8 h and 5 d, respectively. No significant effects of HOCl(g) on cell viability and ciliary activity were observed in any cell type, indicating that low concentrations of HOCl(g）, less than 500 ppb, had no cytotoxic effect.

A triphenylamine-based carbohydrazide hydrazone fluorescent probe for selective detection of hypochlorite and sensing acidic gases.

Hypochlorous acid and its hypochlorite are important reactive oxygen species in the body, and are involved in various physiological processes related to immunity; their rapid detection is of great significance. Here, we synthesized a fluorescent probe (TPAS) by condensation of 4-(diphenylamino)benzaldehyde, carbohydrazide, and salicylaldehyde, which can be used for the detection of ClO- in water and sensing of acidic gas in its solid state. The probe showed strong selective recognition of ClO- in acetonitrile and good tolerance to interference ions. There were good linear responses between the intensity of absorbance and fluorescence and the amount of ClO-. The TPAS solid and its paper strips can emit red fluorescence when exposed to volatile acidic vapours. After being treated with NH3, the red fluorescence can be restored to yellow. The response process of TPAS to ClO- and acid gases was characterized using nuclear magnetic resonance, electrospray ionisation mass spectrometry, transmission electron microscopy, and density functional theory calculations. Furthermore, it can be utilized in analyzing ClO- in commercially available bleaching products; the detection results were basically compatible with the labelled values. In addition, the probe is biocompatible and can be applied for imaging ClO- in zebrafish.

Hypochlorous acid derived from microglial myeloperoxidase could mediate high-mobility group box 1 release from neurons to amplify brain damage in cerebral ischemia-reperfusion injury.

Myeloperoxidase (MPO) plays critical role in the pathology of cerebral ischemia-reperfusion (I/R) injury via producing hypochlorous acid (HOCl) and inducing oxidative modification of proteins. High-mobility group box 1 (HMGB1) oxidation, particularly disulfide HMGB1 formation, facilitates the secretion and release of HMGB1 and activates neuroinflammation, aggravating cerebral I/R injury. However, the cellular sources of MPO/HOCl in ischemic brain injury are unclear yet. Whether HOCl could promote HMGB1 secretion and release remains unknown. In the present study, we investigated the roles of microglia-derived MPO/HOCl in mediating HMGB1 translocation and secretion, and aggravating the brain damage and blood-brain barrier (BBB) disruption in cerebral I/R injury. In vitro, under the co-culture conditions with microglia BV cells but not the single culture conditions, oxygen-glucose deprivation/reoxygenation (OGD/R) significantly increased MPO/HOCl expression in PC12 cells. After the cells were exposed to OGD/R, MPO-containing exosomes derived from BV2 cells were released and transferred to PC12 cells, increasing MPO/HOCl in the PC12 cells. The HOCl promoted disulfide HMGB1 translocation and secretion and aggravated OGD/R-induced apoptosis. In vivo, SD rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) plus different periods of reperfusion. Increased MPO/HOCl production was observed at the reperfusion stage, accomplished with enlarged infarct volume, aggravated BBB disruption and neurological dysfunctions. Treatment of MPO inhibitor 4-aminobenzoic acid hydrazide (4-ABAH) and HOCl scavenger taurine reversed those changes. HOCl was colocalized with cytoplasm transferred HMGB1, which was blocked by taurine in rat I/R-injured brain. We finally performed a clinical investigation and found that plasma HOCl concentration was positively correlated with infarct volume and neurological deficit scores in ischemic stroke patients. Taken together, we conclude that ischemia/hypoxia could activate microglia to release MPO-containing exosomes that transfer MPO to adjacent cells for HOCl production; Subsequently, the production of HOCl could mediate the translocation and secretion of disulfide HMGB1 that aggravates cerebral I/R injury. Furthermore, plasma HOCl level could be a novel biomarker for indexing brain damage in ischemic stroke patients.