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.

The HOCl dry fog-is it safe for human cells?

This study aims to investigate if high-concentration HOCl fogging disinfection causes cytotoxicity and genotoxicity to cultured primary human skin fibroblasts. The cells were exposed to a dry fog of HOCl produced from solutions with a concentration of 300 ppm (5.72 mM) or 500 ppm (9.53 mM). After four times when fibroblasts were exposed to aerosolized HOCl at a concentration of 500 ppm for 9 minutes, significant cytotoxicity and genotoxicity effects were observed. Significant changes in the morphology of fibroblasts and cell death due to membrane disruption were observed, independent of the number of exposures. Flow cytometry analyses performed under these experimental conditions indicated a decrease in the number of cells with an intact cell membrane in the exposed samples compared to the sham samples, dropping to 49.1% of the total cells. Additionally, under the same conditions, the neutral comet assay results demonstrated significant DNA damage in the exposed cells. However, no analogous damages were found when the cells were exposed to aerosolized HOCl generated from a 300-ppm solution for 3 minutes, whether once or four times. Therefore, we have concluded that aerosolized HOCl in dry fog, with a concentration exceeding 300 ppm, can cause cytotoxic and genotoxic effects on human skin fibroblasts.

Fast and easy detection of hypochlorite by a smartphone-based fluorescent turn-on probe: Applications to water samples, zebrafish and plant imaging.

We have developed a fluorescent probe DBT-Cl ((E)-2-(2-(4-(diphenylamino)benzylidene) hydrazinyl)-N,N,N-trimethyl-2-oxoethan-1-aminium chloride) for ClO- with an aggregation-induced emission (AIE) strategy depending on solvent polarity. DBT-Cl possessed a prominent solvatochromic emission property with intramolecular charge transfer (ICT) from the TPA (triphenylamine) to the amide group, which was studied by spectroscopic analysis and DFT calculations. These unique AIE properties of DBT-Cl led to the recognition of ClO- with high fluorescent selectivity. DBT-Cl quickly detected ClO- in less than 1 sec with a fluorescent color change from green to cyan. DBT-Cl had a low detection limit of 9.67 µM to ClO-. Detection mechanism of DBT-Cl toward ClO- was illustrated to be oxidative cleavage of DBT-Cl by 1H NMR titrations, ESI-mass, and DFT calculations. We established the viability for dependable detection of ClO- in actual water samples, as well as zebrafish and plant imaging. In particular, DBT-Cl was capable of easily monitoring ClO- through a smartphone application. Therefore, DBT-Cl assured a promising approach for a fast-responsive and multi-applicable ClO- probe in environmental and living organism systems.

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 deficiency of DNASE1L3 does not affect systemic sclerosis pathogenesis in two inducible murine models of the disease.

We induced systemic sclerosis (SSc)-like disease in both wild-type and Dnase1l3-deficient mice using two distinct approaches involving bleomycin and hypochlorous acid injections. Our observations revealed that the deficiency in DNASE1L3 did not affect tissue fibrosis or inflammation caused by these treatments. Despite the association of single nucleotide polymorphisms in humans with SSc pathogenesis, our study demonstrates that DNASE1L3 is dispensable in two inducible murine models of SSc-like pathogenesis.

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.

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.

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.

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.

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.

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.

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.

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.

A role of methionines in the functioning of oxidatively modified fibrinogen.

Posttranslational modifications in fibrinogen resulting from induced oxidation or oxidative stress in the organism can have deleterious influence on optimal functioning of fibrinogen, causing a disturbance in assembly and properties of fibrin. The protective mechanism supporting the ability of fibrinogen to function in ROS-generating environment remains completely unexplored. The effects of very low and moderately low HOCl/-OCl concentrations on fibrinogen oxidative modifications, the fibrin network structure as well as the kinetics of both fibrinogen-to-fibrin conversion and fibrin hydrolysis have been explored in the current study. As opposed to 25 Μm, HOCl/-OCl, 10 µM HOCl/-OCl did not affect the functional activity of fibrinogen. It is shown for the first time that a number of Met residues, AαMet476, AαMet517, AαMet584, BßMet367, γMet264, and γMet94, identified in 10 µM HOCl/-OCl fibrinogen by the HPLC-MS/MS method, operate as ROS scavengers, performing an important antioxidant function. In turn, this indicates that the fibrinogen structure is adapted to the detrimental action of ROS. The results obtained in our study provide evidence for a protective mechanism responsible for maintaining the structure and functioning of fibrinogen molecules in the bloodstream under conditions of mild and moderate oxidative stress.

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.

Hypochlorite-mediated degradation and detoxification of sulfathiazole in aqueous solution and soil slurry.

Although various activated sodium hypochlorite (NaClO) systems were proven to be promising strategies for recalcitrant organics treatment, the direct interaction between NaClO and pollutants without explicit activation is quite limited. In this work, a revolutionary approach to degrade sulfathiazole (STZ) in aqueous and soil slurry by single NaClO without any activator was proposed. The results demonstrated that 100% and 94.11% of STZ could be degraded by 0.025 mM and 5 mM NaClO in water and soil slurry, respectively. The elimination of STZ was shown to involve superoxide anion (O2•-), chlorine oxygen radical (ClO•), and hydroxyl radical (•OH), according to quenching experiments and the analysis of electron paramagnetic resonance. The addition of Cl-, HCO3-, SO42-, and humic acid (HA) marginally impeded the decomposition of STZ, while NO3-, Fe3+, and Mn2+ facilitated the process. The NaClO process exhibited significant removal effectiveness at a neutral initial pH. Moreover, the NaClO facilitated application in various soil samples and water matrices, and the procedure was also successful in effectively eliminating a range of sulfonamides. The suggested NaClO degradation mechanism of STZ was based on the observed intermediates, and the majority of the products exhibited lower ecotoxicity than STZ. Besides, the experiment results by using X-ray diffraction (XRD) and a fourier transform infrared spectrometer (FTIR) indicated the negligible effects on the composition and structure of soil by the treatment of NaClO. Simultaneously, the experimental results also illustrated that the bioavailability of heavy metals and the physiochemical characteristics of the soil before and after the remediation did not change to a significant extent. Following the remediation of NaClO, the phytotoxicity tests showed reduced toxicity to wheat and cucumber seeds. As a result, treating soil and water contaminated with STZ by using NaClO was a reasonably practical and eco-friendly method.

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.

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.