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Dehalperoxidase (DHP) has diverse catalytic activities depending on the substrate binding conformation, pH, and dynamics in the distal pocket above the heme. According to our hypothesis, the molecular structure of the substrate and binding orientation in DHP guide enzymatic function. Enzyme kinetic studies have shown that the catalytic activity of DHP B is significantly higher than that of DHP A despite 96% sequence homology. There are more than 30 substrate-bound structures with DHP B, each providing insight into the nature of enzymatic binding at the active site. By contrast, the only X-ray crystallographic structures of small molecules in a complex with DHP A are phenols. This study is focused on investigating substrate binding in DHP A to compare with DHP B structures. Fifteen substrates were selected that were known to bind to DHP B in the crystal to test whether soaking substrates into DHP A would yield similar structures. Five of these substrates yielded X-ray crystal structures of substrate-bound DHP A, namely, 2,4-dichlorophenol (1.48 Å, PDB: 8EJN), 2,4-dibromophenol (1.52 Å, PDB: 8VSK), 4-nitrophenol (2.03 Å, PDB: 8VKC), 4-nitrocatechol (1.40 Å, PDB: 8VKD), and 4-bromo-o-cresol (1.64 Å, PDB: 8VZR). For the remaining substrates that bind to DHP B, such as cresols, 5-bromoindole, benzimidazole, 4,4-biphenol, 4.4-ethylidenebisphenol, 2,4-dimethoxyphenol, and guaiacol, the electron density maps in DHP A are not sufficient to determine the presence of the substrates, much less their orientation. In our hands, only phenols, 4-Br-o-cresol, and 4-nitrocatechol can be soaked into crystalline DHP A. None of the larger substrates were observed to bind. A minimum of seven hanging drops were selected for soaking with more than 50 crystals screened for each substrate. The five high-quality examples of direct comparison of modes of binding in DHP A and B for the same substrate provide further support for the hypothesis that the substrate-binding conformation determines the enzyme function of DHP.
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Peroxidasas , Cristalografía por Rayos X , Especificidad por Sustrato , Sitios de Unión , Peroxidasas/química , Peroxidasas/metabolismo , Dominio Catalítico , Modelos Moleculares , Conformación Proteica , Animales , CinéticaRESUMEN
Compared to pathogens Pseudomonas aeruginosa and P. putida, P. donghuensis HYS has stronger virulence towards Caenorhabditis elegans. However, the underlying mechanisms haven't been fully understood. The heme synthesis system is essential for Pseudomonas virulence, and former studies of HemN have focused on the synthesis of heme, while the relationship between HemN and Pseudomonas virulence were barely pursued. In this study, we hypothesized that hemN2 deficiency affected 7-hydroxytropolone (7-HT) biosynthesis and redox levels, thereby reducing bacterial virulence. There are four hemN genes in P. donghuensis HYS, and we reported for the first time that deletion of hemN2 significantly reduced the virulence of HYS towards C. elegans, whereas the reduction in virulence by the other three genes was not significant. Interestingly, hemN2 deletion significantly reduced colonization of P. donghuensis HYS in the gut of C. elegans. Further studies showed that HemN2 was regulated by GacS and participated in the virulence of P. donghuensis HYS towards C. elegans by mediating the synthesis of the virulence factor 7-HT. In addition, HemN2 and GacS regulated the virulence of P. donghuensis HYS by affecting antioxidant capacity and nitrative stress. In short, the findings that HemN2 was regulated by the Gac system and that it was involved in bacterial virulence via regulating 7-HT synthesis and redox levels were reported for the first time. These insights may enlighten further understanding of HemN-based virulence in the genus Pseudomonas.
RESUMEN
Dehaloperoxidase (DHP) is a multifunctional hemeprotein with a functional switch generally regulated by the chemical class of the substrate. Its two isoforms, DHP-A and DHP-B, differ by only five amino acids and have an almost identical protein fold. However, the catalytic efficiency of DHP-B for oxidation by a peroxidase mechanism ranges from 2- to 6-fold greater than that of DHP-A depending on the conditions. X-ray crystallography has shown that many substrates and ligands have nearly identical binding in the two isoenzymes, suggesting that the difference in catalytic efficiency could be due to differences in the conformational dynamics. We compared the backbone dynamics of the DHP isoenzymes at pH 7 through heteronuclear relaxation dynamics at 11.75, 16.45, and 19.97 T in combination with four 300 ns MD simulations. While the overall dynamics of the isoenzymes are similar, there are specific local differences in functional regions of each protein. In DHP-A, Phe35 undergoes a slow chemical exchange between two conformational states likely coupled to a swinging motion of Tyr34. Moreover, Asn37 undergoes fast chemical exchange in DHP-A. Given that Phe35 and Asn37 are adjacent to Tyr34 and Tyr38, it is possible that their dynamics modulate the formation and migration of the active tyrosyl radicals in DHP-A at pH 7. Another significant difference is that both distal and proximal histidines have a 15-18% smaller S2 value in DHP-B, thus their greater flexibility could account for the higher catalytic activity. The distal histidine grants substrate access to the distal pocket. The greater flexibility of the proximal histidine could also accelerate H2O2 activation at the heme Fe by increased coupling of an amino acid charge relay to stabilize the ferryl Fe(IV) oxidation state in a Poulos-Kraut "push-pull"-type peroxidase mechanism.
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Histidina , Poliquetos , Animales , Histidina/química , Isoenzimas/metabolismo , Peróxido de Hidrógeno/metabolismo , Hemoglobinas/química , Peroxidasas/química , Peroxidasa/química , Poliquetos/química , Poliquetos/metabolismo , Cristalografía por Rayos XRESUMEN
Oxytocin (OXT), a neuropeptide consisting of only nine amino acids, is synthesized in the paraventricular and supraoptic nuclei of the hypothalamus. Although OXT is best known for its role in lactation and parturition, recent research has shown that it also has a significant impact on social behaviors in mammals. However, a comprehensive review of this topic is still lacking. In this paper, we systematically reviewed the effects of OXT on social behavior in mammals. These effects of OXT from the perspective of five key behavioral dimensions were summarized: parental behavior, anxiety, aggression, attachment, and empathy. To date, researchers have agreed that OXT plays a positive regulatory role in a wide range of social behaviors, but there have been controversially reported results. In this review, we have provided a detailed panorama of the role of OXT in social behavior and, for the first time, delved into the underlying regulatory mechanisms, which may help better understand the multifaceted role of OXT. Levels of OXT in previous human studies were also summarized to provide insights for diagnosis of mental disorders.
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Oxitocina , Conducta Social , Oxitocina/metabolismo , Oxitocina/fisiología , Animales , Humanos , Neuropéptidos/metabolismo , Mamíferos/metabolismo , Ansiedad/metabolismo , Ansiedad/psicología , Agresión/fisiología , Empatía/fisiología , Femenino , Conducta Materna/fisiologíaRESUMEN
Folate receptor autoantibody (FRAA) has caught increasing attention since its discovery in biological fluids of patients with autism spectrum disorder (ASD), but quantification and understanding of its function are still in their infancy. In this study, we aimed to quantify serum binding-FRAA and explore its relation with serum folate, vitamin B12 (VB12) and ferritin. We quantitated serum binding-FRAA in 132 ASD children and 132 typically-developing (TD) children, as well as serum levels of folate, VB12 and ferritin. The results showed that serum binding-FRAA in the ASD group was significantly lower than that in the TD group (p < 0.0001). Further analysis showed that the difference between these two groups was attributed to boys in each group, not girls. There was no statistically significant difference in folate levels between the ASD and TD groups (p > 0.05). However, there was significant difference in boys between these two groups, not girls. Additionally, the combination of nitrite and binding-FRAA showed potential diagnostic value in patients with ASD (AUC > 0.7). Moreover, in the ASD group, the level of folate was consistent with that of binding-FRAA, whereas in the TD group, the binding-FRAA level was high when the folate level was low. Altogether, these differences revealed that the low serum FRAA in autistic children was mediated by multiple factors, which deserves more comprehensive investigation with larger population and mechanistic studies.
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Trastorno del Espectro Autista , Trastorno Autístico , Masculino , Niño , Humanos , Ácido Fólico , Trastorno del Espectro Autista/epidemiología , Autoanticuerpos , FerritinasRESUMEN
Sound vibration is one of natural stimuli trigging physiological changes in plants. Recent studies showed that sound waves stimulated production of a variety of plant secondary metabolites, including flavonoids, in order to enhance seed germination, flowering, growth or defense. In this review, we examine the potential role of sound stimulation on the biosynthesis of secondary metabolites and the followed cascade of physiological changes in plants, from the perspective of transcriptional regulation and epigenetic regulation for the first time. A systematic summary showed that a wide range of factors may regulate the production of secondary metabolites, including plant species, growth stage, sound types, sound frequency, sound intensity level and exposure time, etc. Biochemical and physiological changes due to sound stimulation were thoroughly summarized as well, for secondary metabolites can also act as a free radical scavenger, or a hormone signaling molecule. We also discussed the limits of previous studies, and the future application of sound waves in biosynthesis of plant secondary metabolites.
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Highly persistent, drug-resistant and transmissible healthcare pathogens such as Clostridioides difficile (C. difficile) and Candida auris (C. auris) are responsible for causing antibiotic-associated fatal diarrhea and invasive candidiasis, respectively. In this study, we demonstrate that these potentially lethal gastrointestinal microbes can be rapidly inactivated on the solid surface of a self-disinfecting anionic block polymer that inherently generates a water surface layer that is highly acidic (pH < 1) upon hydration. Due to thermodynamic incompatibility between its chemical sequences, the polymer spontaneously self-organizes into a nanostructure that enables proton migration from the interior of a film to the surface via contiguous nanoscale hydrophilic channels, as discerned here by scanning electron and atomic force microscopies, as well as X-ray photoelectron spectroscopy. Here, we report that two strains of C. difficile in the vegetative state and two species of Candida, Candida albicans (C. albicans) and C. auris, are, in most cases, inactivated to the limit of minimum detection. Corresponding electron and optical microscopy images reveal that, upon exposure to the hydrated polymer, the outer microbial membranes display evidence of damage and intracellular material is expelled. Combined with our previous studies of rapid bacterial and viral inactivation, these antimicrobial results are highly encouraging and, if translatable to clinical conditions in the form of self-standing polymer films or coatings, are expected to benefit the welfare of patients in healthcare facilities by continuously preventing the spread of such potentially dangerous microbes.
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Candidiasis , Clostridioides difficile , Humanos , Candida , Candida albicans , AntifúngicosRESUMEN
The urgent demand for scalable, potent, color variable, and comfortable antimicrobial textiles as personal protection equipment (PPE) to help reduce infection transmission in hospitals and healthcare facilities has significantly increased since the start of the COVID-19 pandemic. Here, we explored photodynamic antimicrobial polyethylene terephthalate/cotton (TC) blended fabrics comprised of photosensitizer-conjugated cotton fibers and polyethylene terephthalate (PET) fibers dyed with disperse dyes. A small library of TC blended fabrics was constructed wherein the PET fibers were embedded with traditional disperse dyes dominating the fabric color, thereby enabling variable color expression, while the cotton fibers were covalently coupled with the photosensitizer thionine acetate as the microbicidal agent. Physical (SEM, CLSM, TGA, XPS and mechanical strength) and colorimetric (K/S and CIELab values) characterization methods were employed to investigate the resultant fabrics, and photooxidation studies with DPBF demonstrated the ability of these materials to generate reactive oxygen species (i.e., singlet oxygen) upon visible light illumination. The best results demonstrated a photodynamic inactivation of 99.985% (~ 3.82 log unit reduction, P = 0.0021) against Gram-positive S. aureus, and detection limit inactivation (99.99%, 4 log unit reduction, P ≤ 0.0001) against Gram-negative E. coli upon illumination with visible light (60 min; ~ 300 mW/cm2; λ ≥ 420 nm). Enveloped human coronavirus 229E showed a photodynamic susceptibility of ~ 99.99% inactivation after 60 min illumination (400-700 nm, 65 ± 5 mW/cm2). The presence of the disperse dyes on the fabrics showed no significant effects on the aPDI results, and furthermore, appeared to provide the photosensitizer with some measure of protection from photobleaching, thus improving the photostability of the dual-dyed fabrics. Taken together, these results suggest the feasibility of low cost, scalable and color variable thionine-conjugated TC blended fabrics as potent self-disinfecting textiles.
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Antiinfecciosos , COVID-19 , Humanos , Tereftalatos Polietilenos , Colorantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Staphylococcus aureus , Escherichia coli , Pandemias , TextilesRESUMEN
Biomass carbon dots (CDs) derived from natural plants possess the advantages of low cost, photostability, and excellent biocompatibility, with potential applications in chemical sensing, bioimaging, and nanomedicine. However, the development of biomass CDs with excellent antioxidant activity and good biocompatibility is still a challenge. Herein, we propose a hypothesis for enhancing the antioxidant capacity of biomass CDs based on precursor optimization, extraction solvent, and other conditions with broccoli as the biomass. Compared to broccoli water extracts, broccoli powders, and broccoli organic solvent extracts, CDs derived from broccoli water extracts (BWE-CDs) have outstanding antioxidant properties due to the abundant CâC, carbonyl, and amino groups on their surface. After optimization of the preparation condition, the obtained BWE-CDs exhibit excellent free-radical scavenging activity with an EC50 of 68.2 µg/mL for DPPH⢠and 22.4 µg/mL for ABTSâ¢+. Cytotoxicity and zebrafish embryotoxicity results indicated that BWE-CDs have lower cytotoxicity and better biocompatibility than that of CDs derived from organic solvents. In addition, BWE-CDs effectively scavenged reactive oxygen species (ROS) in A549 cells, 293T cells, and zebrafish, as well as eliminating inflammation in LPS-stimulated zebrafish. Mechanistic studies showed that the anti-inflammatory effect of BWE-CDs was dependent on the direct reaction of CDs with free radicals, the regulation of NO levels, and the upregulation of the expression of SOD and GPX-4. This work indicates that the antioxidant activity of CDs could be enhanced by using solvent extracts of biomass as precursors, and the obtained BWE-CDs exhibit characteristics of greenness, low toxicity, and excellent antioxidant and anti-inflammatory activities, which suggests the potential promising application of BWE-CDs as an antioxidant nanomedicine for inflammatory therapy.
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Antioxidantes , Brassica , Animales , Pez Cebra , Carbono/química , Agua , Antiinflamatorios/química , SolventesRESUMEN
Dehaloperoxidase (DHP) from the marine polychaete Amphitrite ornata is a multifunctional enzyme that possesses peroxidase, peroxygenase, oxidase and oxygenase activities. Herein, we investigated the reactivity of DHP B with bisphenol A (BPA) and related compounds (bisphenol E, bisphenol F, tetrachlorobisphenol A, 2,2'-biphenol, 3,3'-biphenol, 4,4'-biphenol, and 3,3'-dibromo-4,4'-biphenol). As a previously unknown substrate for DHP B, BPA (as a representative substrate) is an endocrine disruptor widely used in polycarbonate and epoxy resins, thus resulting in human exposure. Reactivity studies with these substrates were investigated using high performance liquid chromatography (HPLC), and their corresponding oxidation products were determined by mass spectrometry (GC-MS/ LC-MS). BPA undergoes oxidation in the presence of DHP B and hydrogen peroxide yielding two cleavage products (4-isopropenylphenol and 4-(2-hydroxypropan-2-yl)phenol), and oligomers with varying degrees of oxidation. 18O-labeling studies confirmed that the O-atom incorporated into the products was derived exclusively from water, consistent with substrate oxidation via a peroxidase-based mechanism. The X-ray crystal structures of DHP bound with bisphenol E (1.48 Å), bisphenol F (1.75 Å), 2,2'-biphenol (1.90 Å) and 3,3'-biphenol (1.30 Å) showed substrate binding sites are in the distal pocket of the heme cofactor, similar to other previously studied DHP substrates. Stopped-flow UV-visible spectroscopy was utilized to investigate the mechanistic details and enzyme oxidation states during substrate turnover, and a reaction mechanism is proposed. The data presented here strongly suggest that DHP B can catalyze the oxidation of bisphenols and biphenols, thus providing evidence of how infaunal invertebrates can contribute to the biotransformation of these marine pollutants.
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Hemoglobinas , Peroxidasas , Fenoles , Poliquetos , Hemoglobinas/química , Oxidorreductasas , Peroxidasas/metabolismo , Poliquetos/enzimologíaRESUMEN
In order to extract sulforaphane (SFN) from broccoli via green and efficient ways, a novel method based on salting-out assisted deep eutectic solvent (DES) has been developed. Compared to known organic solvent- (such as dichloromethane, ethyl acetate, n-hexane, etc.) based liquid-liquid extraction, this new N8881Cl-based DES method exhibited excellent extraction efficiency for SFN, including a significant improvement due to the salting-out effect of KH2PO4. Under optimal conditions, 97.77 % of SFN was extracted by N8881Cl-EG DES and more than 82.5 % of SFN was recovered by activated carbon from DES. In addition, further studies with Kamlet-Taft parameters and density functional theory showed that the H-bond accepting capacity of hydrophobic DES, the existing vdW interaction, and the electrostatic interaction between N8881Cl-EG DES all contributed to efficient extraction of SFN. This is the first time that the underlying mechanism for SFN extraction by DES was revealed.
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Brassica , Brassica/química , Disolventes Eutécticos Profundos , Sulfóxidos , Isotiocianatos , Solventes/química , Cloruro de SodioRESUMEN
As bacterial infections continue to pose a significant challenge to healthcare globally, new therapeutic strategies, interventions, and complementary approaches that address both infection prevention and treatment are needed. As one such strategy, photothermal therapy (PTT) as a non-chemotherapeutic approach is considered a safe and potentially efficient strategy to combat bacterial infections, particularly for antibiotic-resistant pathogens given that PTT operates via a temperature-dependent process against which the development of bacterial resistance is unlikely. Here, we prepared Au@CDs composite nanoparticles (Au@CD) comprised of gold nanoparticles (AuNPs) and carbon dots (N,S-CDs), and investigated their use as a photothermal agent in PTT. The presence of the CDs as surface decorations conferred improved photothermal conversion efficiency, photostability, and biocompatibility to the Au@CD when compared to the parent AuNPs. To investigate if the Au@CD could serve as a PTT wound dressing and accelerate tissue repair, they were embedded within a PVA membrane via electrospinning. The resultant Au@CD membrane exhibited excellent biocompatibility and photothermal antimicrobial activity. In vitro photothermal antibacterial inactivation studies confirmed their efficacy against S. aureus and E. coli (99 + % inactivation of both pathogens under NIR irradiation). Moreover, in vivo studies employing Kunming male mice with S. aureus-infected wounds on their backs were chosen as a trauma model, with the Au@CD membranes serving as wound dressings. The results showed that a local temperature increased up to 50 °C upon NIR irradiation could effectively eradicate bacteria at the wound site, reduce the risk of bacterial infection, suppress inflammation as well as improve collagen deposition and angiogenesis, all of which together facilitated wound closure and resulted in a better therapeutic effect than the controls. Taken together, this work confirms that NIR-irradiated Au@CD-based membranes and related materials are promising photothermal antimicrobial platforms for wound dressings and related healthcare applications.
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Oro , Nanopartículas del Metal , Masculino , Ratones , Animales , Oro/farmacología , Staphylococcus aureus , Nanopartículas del Metal/uso terapéutico , Terapia Fototérmica , Escherichia coli , Carbono/farmacología , Antibacterianos/farmacologíaRESUMEN
Room-temperature macromolecular crystallography allows protein structures to be determined under close-to-physiological conditions, permits dynamic freedom in protein motions and enables time-resolved studies. In the case of metalloenzymes that are highly sensitive to radiation damage, such room-temperature experiments can present challenges, including increased rates of X-ray reduction of metal centres and site-specific radiation-damage artefacts, as well as in devising appropriate sample-delivery and data-collection methods. It can also be problematic to compare structures measured using different crystal sizes and light sources. In this study, structures of a multifunctional globin, dehaloperoxidase B (DHP-B), obtained using several methods of room-temperature crystallographic structure determination are described and compared. Here, data were measured from large single crystals and multiple microcrystals using neutrons, X-ray free-electron laser pulses, monochromatic synchrotron radiation and polychromatic (Laue) radiation light sources. These approaches span a range of 18 orders of magnitude in measurement time per diffraction pattern and four orders of magnitude in crystal volume. The first room-temperature neutron structures of DHP-B are also presented, allowing the explicit identification of the hydrogen positions. The neutron data proved to be complementary to the serial femtosecond crystallography data, with both methods providing structures free of the effects of X-ray radiation damage when compared with standard cryo-crystallography. Comparison of these room-temperature methods demonstrated the large differences in sample requirements, data-collection time and the potential for radiation damage between them. With regard to the structure and function of DHP-B, despite the results being partly limited by differences in the underlying structures, new information was gained on the protonation states of active-site residues which may guide future studies of DHP-B.
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The multifunctional catalytic globin dehaloperoxidase (DHP) from the marine worm Amphitrite ornata was shown to catalyze the H2O2-dependent oxidation of 2,4- and 2,6-dihalophenols (DXP; X = F, Cl, Br). Product identification by LC-MS revealed multiple monomeric products with varying degrees of oxidation and/or dehalogenation, as well as oligomers with n up to 6. Mechanistic and 18O-labeling studies demonstrated sequential dihalophenol oxidation via peroxidase and peroxygenase activities. Binding studies established that 2,4-DXP (X = Cl, Br) have the highest affinities of any known DHP substrate. X-ray crystallography identified different binding positions for 2,4- and 2,6-DXP substrates in the hydrophobic distal pocket of DHP. Correlation between the number of halogens and the substrate binding orientation revealed a halogen-dependent binding motif for mono- (4-halophenol), di- (2,4- and 2,6-dihalophenol) and trihalophenols (2,4,6-trihalopenol). Taken together, the findings here on dihalophenol reactivity with DHP advance our understanding of how these compounds bridge the inhibitory and oxidative functions of their mono- and trihalophenol counterparts, respectively, and provide further insight into the protein structure-function paradigm relevant to multifunctional catalytic globins in comparison to their monofunctional analogs.
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Hemoglobinas , Poliquetos , Animales , Halógenos , Hemoglobinas/química , Peróxido de Hidrógeno/química , Peroxidasas/metabolismoRESUMEN
Dehaloperoxidase (DHP) is a multi-functional catalytic globin from the marine worm A. ornata, whose physiological functions include oxygen transport and oxidation of toxic substrates present in its habitat. In the Fe(III) state, DHPA has an isomer shift of 0.42 mm/s, characteristic for high-spin heme proteins. Changes in pH have subtle effects on the electronic structure of DHP in the Fe(III) state detectable in the high-field spectra, which show a pH-dependent mixture of species with different zero-field splittings between 5 and 18 cm-1. The short-lived intermediate obtained by direct reaction of the Fe(III) enzyme with H2O2 has an isomer shift of 0.10 mm/s, indicative of an Fe(IV)-oxo state and of an S = 1 electronic ground state confirmed by variable field studies. The O2-bound state of DHP has an isomer shift of 0.28 mm/s and a high-field spectrum characteristic for diamagnetic heme complexes, similarly to other haemoglobins. Overall, the isomer shift and quadrupole splitting of DHP in the four states studied are expectedly similar to both peroxidases and to myoglobin. The differences in electronic structure between DHP and other heme proteins and enzyme are observed in the high-field Mössbauer spectra of the ferric state, which show pH-dependent zero-field splittings suggesting a heme site in which the ligand field strength at the iron ion is tuned by pH. This tunability is correlated with variable electron-donating properties of the iron, which can perform multiple functions.
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Peróxido de Hidrógeno , Poliquetos , Animales , Compuestos Férricos/química , Hemo/química , Hemoglobinas/química , Peróxido de Hidrógeno/química , Hierro/química , Mioglobina/química , Peroxidasas/metabolismo , Espectroscopía de MossbauerRESUMEN
For the purpose of developing multifunctional water purification materials capable of degrading organic pollutants while simultaneously inactivating microorganisms from contaminated wastewater streams, we report here a facile and eco-friendly method to immobilize molybdenum disulfide into bacterial cellulose via a one-step in-situ biosynthetic method. The resultant nanocomposite, termed BC/MoS2, was shown to possess a photocatalytic activity capable of generating â¢OH from H2O2, while also exhibiting photodynamic/photothermal mechanisms, the combination of which exhibits synergistic activity for the degradation of pollutants as well as for bacterial inactivation. In the presence of H2O2, the BC/MoS2 nanocomposite exhibited excellent antibacterial efficacy upwards of 99.9999% (6 log units) for the photoinactivation of both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus upon infrared (IR) lamp illumination (100 W, 760 nm ≤ λ ≤ 5000 nm, 15 cm vertical distance; 5 min). Mechanistic studies revealed synergistic pathogen inactivation resulting from the combination of photocatalytically generated â¢OH and hyperthermia induced by the photothermal conversion of the near-IR light. In addition, the BC/MoS2 nanocomposite also showed excellent photodegradation activity for common aqueous contaminants in the presence of H2O2, including malachite green (a textile dye), catechol violet (a phenol) and formaldehyde. Taken together, our findings demonstrate that sustainable materials such as BC/MoS2 have potential applications in wastewater treatment and microorganism disinfection.
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Antibacterianos/farmacología , Celulosa/farmacología , Disulfuros/farmacología , Escherichia coli/efectos de los fármacos , Molibdeno/farmacología , Staphylococcus aureus/efectos de los fármacos , Aguas Residuales/microbiología , Antibacterianos/química , Celulosa/química , Disulfuros/química , Pruebas de Sensibilidad Microbiana , Molibdeno/química , Purificación del AguaRESUMEN
Nitric oxide (NO) plays an important role in cardiovascular and immune systems. Quantification of blood nitrite and nitrate, two relatively stable metabolites of NO (generally as NOx), has been acknowledged, in part, representing NO bioactivity. Dysregulation of NOx had been reported in SARS-CoV-2 infected populations, but whether patients recovered from COVID-19 disease present with restored NOx is unknown. In this study, serum NO2- and NO3- were quantified and analyzed among 109 recovered adults in comparison to a control group of 166 uninfected adults. Nitrite or nitrate levels were not significantly different among mild-, common-, severe- and critical-type patients. However, these recovered patients had dramatically lower NO2- and NO2-/NO3- than the uninfected group (p < 0.0001), with significantly higher NO3- levels (p = 0.0023) than the uninfected group. Nitrate and nitrite/nitrate were positively and negatively correlated with patient age, respectively, with age 65 being a turning point among recovered patients. These results indicate that low NO2-, low NO2-/NO3- and high NO3- may be potential biomarkers of long-term poor or irreversible outcomes after SARS-CoV-2 infection. It suggests that NO metabolites might serve as a predictor to track the health status of recovered COVID-19 patients, highlighting the need to elucidate the role of NO after SARS-CoV-2 infection.
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COVID-19 , Nitritos , Adulto , Anciano , Biomarcadores , Humanos , Nitratos , Óxido Nítrico , SARS-CoV-2RESUMEN
The dual threats posed by the COVID-19 pandemic and hospital-acquired infections (HAIs) have emphasized the urgent need for self-disinfecting materials for infection control. Despite their highly potent antimicrobial activity, the adoption of photoactive materials to reduce infection transmission in hospitals and related healthcare facilities has been severely hampered by the lack of scalable and cost-effective manufacturing, in which case high-volume production methods for fabricating aPDI-based materials are needed. To address this issue here, we examined the antimicrobial efficacy of a simple bicomponent spray coating composed of the commercially-available UV-photocrosslinkable polymer N-methyl-4(4'-formyl-styryl)pyridinium methosulfate acetal poly(vinyl alcohol) (SbQ-PVA) and one of three aPDI photosensitizers (PSs): zinc-tetra(4-N-methylpyridyl)porphine (ZnTMPyP4+), methylene blue (MB), and Rose Bengal (RB). We applied these photodynamic coatings, collectively termed SbQ-PVA/PS, to a variety of commercially available materials. Scanning electron microscopy (SEM) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) confirmed the successful application of the coatings, while inductively coupled plasma-optical emission spectroscopy (ICP-OES) revealed a photosensitizer loading of 0.09-0.78 nmol PS/mg material. The antimicrobial efficacy of the coated materials was evaluated against methicillin-susceptible Staphylococcus aureus ATCC-29213 and human coronavirus strain HCoV-229E. Upon illumination with visible light (60 min, 400-700 nm, 65 ± 5 mW/cm2), the coated materials inactivated S. aureus by 97-99.999% and HCoV-229E by 92-99.999%, depending on the material and PS employed. Photobleaching studies employing HCoV-229E demonstrated detection limit inactivation (99.999%) even after exposure for 4 weeks to indoor ambient room lighting. Taken together, these results demonstrate the potential for photodynamic SbQ-PVA/PS coatings to be universally applied to a wide range of materials for effectively reducing pathogen transmission.