Increase In Redox Potential Research Articles

Site-Directed Mutagenesis of Two-Domain Laccase ScaSL for Obtaining a Biocatalyst with Improved Characteristics

Analysis of the structure of two-domain laccase ScaSL from Streptomyces carpinensis VKM Ac-1300 (with a middle-redox potential) revealed determinants that could affect the increased potential of ScaSL. Site-directed mutagenesis of the ScaSL laccase was carried out, and mutants H286A, H286T, H286W, and F232Y/F233Y were obtained. Replacement of His 286 with Ala led to a decrease in redox potential (0.45 V) and an increase in stability at pH 9 and 11; replacement with Thr led to an increase in redox potential (0.51 V) but to a decrease in the thermal stability of the protein; replacement with Trp did not affect the enzyme properties. Replacement of Phe residues 232 and 233 with Tyr led to a shift in enzyme activity to the acidic pH range without changing the redox potential and a decrease in the thermostability and pH stability of the enzyme. All mutants more efficiently oxidized phenolic substrate 2,6-DMP and were able to participate in direct electron transfer (DET) with MWCNT-modified electrodes. The F232Y/F233/Y mutant was unable to degrade triphenylmethane dyes without a mediator but showed a greater degree of decolorization of azo dyes in the presence of the mediator. The crystal structure of laccase with the highest potential was determined with high resolution.

Potential for formation of methylated thioarsenates in geothermal environments

Geothermal waters typically have elevated arsenic (As) concentrations. Various As species have been identified, including methylated thioarsenates, which present a high environmental and health risk due to high mobility and toxicity. Upon discharge from hot springs, temperature and geogenic sulfide excess decrease, while redox potential increases. The combined effects of those parameters on activities of sulfate-reducing bacteria and methanogens and thereby on extent of As methylation versus thiolation is currently unknown. Here, we incubated sediments from alkaline hot springs and outflow channels at the Tengchong geothermal region in southwestern China, where inorganic and methylated thioarsenates had been detected, at temperatures between 20 to 90 °C with different initial aqueous As and sulfur species. Results from field samples and incubation experiments showed methylated thioarsenates, but no methylated oxyarsenates, implying quantitative thiolation even at low sulfide concentrations. Enrichment cultures derived from one sediment with quantitative formation of dimethyl-dithioarsenate (DMDTA) at 55 °C, showed a dominance of inorganic trithioarsenate at 35 °C and monomethylated thioarsenates at 55 °C when incubated with two other sediments. The rate-limiting step was microbially mediated As methylation from arsenite, which was not observed at 20 °C or >= 75 °C, in contrast to thiolation of already methylated arsenates. Addition of free sulfide and thiosulfate to incubation experiments promoted formation of inorganic or monomethylated high-thiolated arsenates, while sulfate promoted full methylation and formation of DMDTA, probably due to continuous low supply of microbially produced sulfide. Since DMDTA is more mobile and toxic than inorganic and monomethylated thioarsenates, understanding constraints to its formation is especially important for future risk assessment

Antimicrobial Activity of Cold Atmospheric Plasma on Bacterial Strains Derived from Patients with Diabetic Foot Ulcers.

Bacterial infections or their biofilms in diabetic foot ulcer (DFU) are a key cause of drug-resistant wounds and amputations. Cold atmospheric plasma (CAP) is well documented for its antibacterial effect and promoting wound healing. In the current study, we built an argon- based, custom CAP device and investigated its potential in eliminating laboratory and clinical bacterial strains derived from DFU. The CAP device performed as expected with generation of hydroxyl, reactive nitrogen species, and argon species as determined by optical emission spectroscopy. A dose-dependent increase in oxidation reduction potential (ORP) and nitrites in the liquid phase was observed. The CAP treatment eliminated both gram-positive (Staphylococcus aureus, Entrococcus faecalis) and negative bacteria (Pseudomonas aeruginosa, Proteus mirabilis) laboratory strains. Clinical samples collected from DFU patients exhibited a significant decrease in both types of bacteria, with grampositive strains showing higher susceptibility to the CAP treatment in an ex vivo setting. Moreover, exposure to CAP of polymicrobial biofilms from DFU led to a notable disruption in biofilm and an increase in free bacterial DNA. The duration of CAP exposure used in the current study did not induce DNA damage in peripheral blood lymphocytes. These results suggest that CAP could serve as an excellent tool in treating patients with DFUs.

Physical and chemical characteristics of plasma-activated water generated by hybrid dielectric barrier discharge and gliding arc discharge

This research explores the synergistic application of Dielectric Barrier Discharge (DBD) and Gliding Arc Plasma Jet (GAPJ) in a Hybrid Plasma Discharge (HPD) setup for enhanced water activation. The HPD system demonstrated balanced and sustained generation of reactive oxygen and nitrogen species (RONS), maintaining efficiency at higher specific input energy (SIE) values. Comparative analyses with DBD and GAPJ systems highlighted the superior performance of the HPD system in generating RONS and modifying water’s molecular structure. Key observations included a decrease in water’s pH and an increase in oxidation-reduction potential, total dissolved solids, and conductivity, stabilizing beyond 5 l min−1 airflow and 10 min of treatment. UV−Vis spectroscopy identified nitrites, nitrates, hydrogen peroxide, and nitrous acid, while Raman spectroscopy captured shifts in vibrational modes, particularly in librational and O–H stretching bands. These changes correlated with alterations in reactive species concentrations and pH levels. Overall, the HPD system emerged as a versatile and efficient approach for generating plasma-activated water, suitable for applications in microbial deactivation, surface sterilization, and electrocatalytic process optimization, offering stable and continuous production of reactive species across a range of SIE values.

Controlling Redox Potential of a Manganese(III)-Bis(hydroxo) Complex through Protonation and the Hydrogen-Atom Transfer Reactivity.

A series of mononuclear manganese(III)-hydroxo and -aqua complexes, [MnIII(TBDAP)(OH)2]+ (1), [MnIII(TBDAP)(OH)(OH2)]2+ (2) and [MnIII(TBDAP)(OH2)2]3+ (3), were prepared from a manganese(II) precursor and confirmed using various methods including X-ray crystallography. Thermodynamic analysis showed that protonation from hydroxo to aqua species resulted in increased redox potentials (E1/2) in the order of 1 (-0.15 V) < 2 (0.56 V) < 3 (1.11 V), while pKa values exhibited a reverse trend in the order of 3 (3.87) < 2 (11.84). Employing the Bordwell Equation, the O-H bond dissociation free energies (BDFE) of [MnII(TBDAP)(OH)(OH2)]+ and [MnII(TBDAP)(OH2)2]2+, related to the driving force of 1 and 2 in hydrogen atom transfer (HAT), were determined as 75.3 and 77.3 kcal mol-1, respectively. It was found that the thermodynamic driving force of 2 in HAT becomes greater than that of 1 as the redox potential of 2 increases through protonation from 1 to 2. Kinetic studies on electrophilic reactions using a variety of substrates revealed that 1 is only weakly reactive with O-H bonds, whereas 2 can activate aliphatic C-H bonds in addition to O-H bonds. The reaction rates increased by 1.4 × 104-fold for the O-H bonds by 2 over 1, which was explained by the difference in BDFE and the tunneling effect. Furthermore, 3, possessing the highest redox potential value, was found to undergo an aromatic C-H bond activation reaction under mild conditions. These results provide valuable insights into enhancing electrophilic reactivity by modulating the redox potential of manganese(III)-hydroxo and -aqua complexes through protonation.

Nitrate-induced mobilization of trace elements in reduced groundwater environments

Groundwater is an essential source for drinking water production. Nitrate infiltration into groundwater due to over-fertilization can cause a potential risk for groundwater quality. Pyrite and other geogenic minerals can be oxidized and trace metals consequently released into water, e.g., nickel and uranium.To achieve a better understanding of the nitrate-induced mobilization of metals, this study investigated the release of antimony, arsenic, chromium, cobalt, molybdenum, uranium, and vanadium from three different reduced sediments after nitrate addition. The experiments were conducted as batch and soil column tests under oxygen-free conditions. In addition to the ORP, the pH value was a relevant driver for the metal mobilization due to pH dependent adsorption and ion exchange processes. Uranium concentrations in the water increased with increasing redox potential. Also, antimony and, to a lesser extent, molybdenum showed higher mobilization at higher ORP as well as at higher pH values. On the contrary, arsenic and cobalt was immobilized with increasing redox potential. Pourbaix diagrams demonstrated very complex species distributions even in synthetic water. The mobilization of trace metals is expected to be also influenced by the type of surrounding rocks and water quality parameters such as dissolved organic carbon.

Experimental investigation of integrated systems of precooling and plasma‐activated water‐based bacterial inactivation

AbstractPlasma‐activated water (PAW) is produced by treating aqueous solution with cold plasma. PAW is rich in reactive oxygen and nitrogen species, making it a safe and efficient approach for the inactivation of pathogens. In this paper, two types of integrated systems of precooling and PAW‐based bacterial inactivation for fruits and vegetables were proposed. One is cold water precooling (CWP) and PAW, the other is differential pressure precooling (DPP) and PAW. The influencing factors of PAW preparation and the bacterial inactivation effect of PAW suspension were experimentally investigated. The results demonstrated that with the increase in preparation time, the pH decreased, with a concurrent increase in temperature, electrical conductivity, and redox potential. The physicochemical properties of PAW were affected by temperature, with the optimal temperature being about 17°C. As the preparation time and bacterial inactivation time increased, the decontamination effect of PAW against Escherichia coli increased in suspension bacterial inactivation. Conversely, with the decrease in PAW temperature, the bacterial inactivation effect weakened. Furthermore, PAW was applied through CWP and DPP combined with PAW for precooling snow peas. Soaking CWP showed a 2.1 log reduction of background bacteria after 10 days of storage. Spraying CWP showed a 1.1 log reduction of background bacteria after 5 days of storage. DPP showed a 0.8 log reduction of background bacteria after 10 days of storage, and the appearance of snow peas surpassed those of the control group. Integrated systems of precooling and PAW‐based bacterial inactivation indicated promising effects on maintaining the safety and quality of snow peas.Practical applicationsPAW is a sterilization method with the advantage of easy preparation, low cost, minimal chemical residue, and effective sterilization. PAW could be produced simply by discharge on the tap water, which is very practical for its up‐scale application. In this study, different parameters on the physicochemical properties of PAW were evaluated, which was helpful in designing industrial PAW‐producing equipment. Besides, integrated systems of precooling and PAW sterilization for fruits and vegetables were proposed, which showed prominent sterilization and good preservation effects. The integrated systems could maintain the freshness of fruits and vegetables and prevent bacterial contamination during precooling by combining PAW sterilization and precooling, which will help extend the shelf lives of fruits and vegetables. In addition, this combination will prevent agricultural product waste and maintain the safety of fruits and vegetables.

Study of sorption of platinum, palladium and rhodium ions on a carbon sorbent

The article is devoted to the sorption concentration of platinum (II,IV), palladium (II) and rhodium (III) ions from chloride media on a carbon synthetic sorbent. For the study of the sorption concentration of platinum group metals, the carbon synthetic sorbent Lewatit AF5 was chosen. This sorbent has high mechanical strength, high surface area, narrow pore size distribution, and low cost compared to silicate or polymer sorbents. Sorption concentration was carried out under static conditions from model chloride solutions. The concentration of analytes in the initial solutions ranged from 8 to 50 mmol/dm3. Equilibrium concentrations of metals in solutions were determined by inductively coupled plasma atomic emission spectrometry. The dependences of adsorption on contact time, free acidity and redox potential of the system were studied, and the limiting absorption values for each of the metals studied were determined. The study of the kinetic parameters of the sorption of Pt (IV), Pd (II) and Rh (III) ions was carried out from chloride solutions characterized by free acidity values of 0.01 mol/dm3. The time for establishing sorption equilibrium was determined, which was 4 hours for each of the ions. When studying the dependence of adsorption on free acidity and the oxidation-reduction potential of the system (ORP), it was revealed that with an increase in free acidity and redox potential, a decrease in sorption activity is observed, thus we can conclude that aquated complexes of platinum metals, in which metals present not in the highest oxidation state, involved in the sorption process. Processing of experimental data showed the applicability of the linear equation of the Langmuir isotherm for the description of the adsorption process, the limiting adsorption values were calculated, using which the sorption capacity of the sorbent was assessed. The sorption capacity for Pt (II, IV), Pd (II) and Rh (III) was 1.24 mmol/g; 1.16 mmol/g and 0.57 mmol/g, respectively. High values of sorption capacity, as well as a fairly short time to achieve sorption equilibrium without the use of means for the acceleration of the process, in combination with the mechanical characteristics of the sorbent, allow us to conclude that the Lewatit AF5 sorbent is promising for the concentration of platinum group metals from hydrochloric acid solutions.

Neuronal Calcium Sensor 1: a Zinc/Redox-Dependent Protein of Nervous System Signaling Pathways

Intracellular calcium signals play a key role in the regulation of nervous system structure and function. The control of neuronal excitability and plasticity by calcium ions underlies the mechanisms of higher nervous activity, and the mechanisms of this control are of particular interest to researchers. In recent decades, a family of highly specialized neuronal proteins that can translate the information contained in calcium signals into the regulation of channels, enzymes, receptors, and transcription factors has been described. The most abundant member of this family is neuronal calcium sensor-1 (NCS-1), which is intensively expressed in CNS neurons and controls such vital processes as neuronal growth and survival, reception, neurotransmission and synaptic plasticity. In addition to calcium ions, NCS-1 may bind intracellular ‘mobile’ zinc, increased concentration of which is a characteristic feature of cells under oxidative stress. Zinc coordination under these conditions stimulates NCS-1 oxidation to form a disulfide dimer (dNCS-1) with altered functional properties. The combined effect of mobile zinc and the increased redox potential of the medium can thus induce the aberrant NCS-1 activity involving signals for survival of neuronal cells or induction of their apoptosis and, as a consequence, the development of neurodegenerative processes. The review details the localization, regulation of expression, structure and molecular properties of NCS-1, as well as current data on its signaling activity in health and disease, including zinc-dependent redox-regulation cascades.

Fiber supplementation protects from antibiotic-induced gut microbiome dysbiosis by modulating gut redox potential

Antibiotic-induced gut dysbiosis (AID) is a frequent and serious side effect of antibiotic use and mitigating this dysbiosis is a critical therapeutic target. We propose that the host diet can modulate the chemical environment of the gut resulting in changes to the structure and function of the microbiome during antibiotic treatment. Gut dysbiosis is typically characterized by increases in aerobic respiratory bacterial metabolism, redox potential, and abundance of Proteobacteria. In this study, we explore dietary fiber supplements as potential modulators of the chemical environment in the gut to reduce this pattern of dysbiosis. Using defined-diets and whole-genome sequencing of female murine microbiomes during diet modulation and antibiotic treatment, we find that fiber prebiotics significantly reduced the impact of antibiotic treatment on microbiome composition and function. We observe reduced abundance of aerobic bacteria as well as metabolic pathways associated with oxidative metabolism. These metatranscriptomic results are corroborated by chemical measurements of eH and pH suggesting that fiber dampens the dysbiotic effects of antibiotics. This work indicates that fiber may act as a potential therapeutic for AID by modulating bacterial metabolism in the gut to prevent an increase in redox potential and protect commensal microbes during antibiotic treatment.

Dosing oxygen from the early stages of white winemaking: Effect on oxidation–reduction potential, browning stability, volatile composition, and sensory properties

This study investigated the effect of controlled oxygen addition during alcoholic fermentation (4 mg/L, at 2nd, 4th, 6th, 10th, 14th, 16th, 20th day) and aging on lees (2 mg/L, every 15 days for 3 months) in a stainless-steel tank for white wine production from a nearly neutral grape. Under less reductive conditions (Ox), alcoholic fermentation was completed in 27 days, whereas one extra week was required under more reductive conditions (no-Ox). The greatest amount of dissolved oxygen in Ox wine triggered the increase of redox potential (EH) starting from the end of alcoholic fermentation and throughout aging (169 and 150 mV in Ox and no-Ox wine, respectively), also improving the wine resistance to browning. Oxygen addition from the early stages of winemaking significantly modulated volatile composition and sensory attributes, which may contribute to the diversification of wine style.

Scholastic modeling of pH and redox potential changes in olive tree leaf alcohol and acids containing incubation media designed for the steady growth of Acetobacter aceti and Saccharomyces cerevisiae

Modeling of pH and redox potential changes was investigated instructionally in incubation media designed for a stable growth of Acetobacter aceti and Saccharomyces cerevisiae. Olive tree leaf, phosphoric acid, vinegar, acetic acid and ethyl alcohol were used in incubation for extraction and symbiotic purposes. Structure imaging of olive tree leaf powder was performed using the Field Emission Gun – Scanning Electron Microscope (FEG-SEM). The incubation experiments were carried out at initially lowest pH and high temperatures of 30oC and 35oC for eight days in liquid state fermentation process. A steady A. aceti and S. cerevisiae growth was observed during the incubation. Increase in pH value displayed increase in redox potential in water+ phosphoric acid, vinegar+A. aceti+phosphoric acid, S. cerevisiae+A. aceti+acetic acid+phosphoric acid and S. cerevisiae+A. aceti+phosphoric acid solution processes at 30oC, and acetic acid+phosphoric acid and vinegar+phosphoric acid solution processes at 35oC. Decrease in pH value displayed decrease in redox potential in A. aceti+alcohol+phosphoric acid, vinegar+phosphoric acid, S. cerevisiae+A. aceti+acetic acid+phosphoric acid and S. cerevisiae+A. aceti+phosphoric acid solution processes at 30oC, and vinegar+A. aceti+phosphoric acid, S. cerevisiae+A. aceti+acetic acid+phosphoric acid and S. cerevisiae+A. aceti+phosphoric acid solution processes at 35 oC.

Substratum Raking Can Restore Interstitial Habitat Quality in Swedish Freshwater Pearl Mussel Streams

Functional and oxygenated stream beds provide crucial habitat for multiple endangered stream taxa, including endangered freshwater mussels, fishes, and insect larvae. Stream bed restoration measures such as substrate raking are often applied to mitigate excess fine sediment introductions and stream bed colmation, yet such measures are controversial. In this study, we conducted a systematic experiment in which sites with stream bed raking and removal of macrophytes were monitored over two years and compared with before-treatment conditions and untreated reference sites in the Swedish Brånsån stream, which still contains a population of the endangered freshwater pearl mussel Margaritifera margaritifera. The stream bed restoration resulted in improved habitat quality, as evident from decreased substrate compaction, increased redox potential, and oxygen supply into the stream bed. In contrast to previous studies in Central European catchments with more intensive agricultural catchment uses, the effects of the restoration measure were much longer, extending over two years. Consequently, stream bed raking and macrophyte removal can be considered a useful and more long-lasting restoration measure than currently assumed, especially in streams where excess input of fine sediment has already been mitigated, where catchment land use is rather extensive, and where near-natural flow regimes still prevail.

Effects of attapulgite on the growth status of submerged macrophytes Vallisneria spiralis and sediment microenvironment

The effects of raw attapulgite clay and thermally modified attapulgite clay on the growth status of submerged plant Vallisneria Spiralis (V. spiralis) and the microenvironment of sediment were first explored. The results demonstrated that the attapulgite could effectively promote the development of V. spiralis and improve plant stress resistance by enhancing the activity of antioxidant enzymes. The 10% addition of attapulgite clay increased the biomass of V. spiralis by 27%∼174%, and the promoted rate of raw attapulgite clay was 2∼5 times of modified attapulgite clay. The attapulgite increased redox potential in sediment (P < 0.05) and provided proper niches for organism propagation, further promoting the degradation of organic matter and nutrient metabolism in sediment. The value of Shannon, Chao, and Ace was 9.98, 4865.15, 5029.08 in the 10% modified attapulgite group, and 10.12, 4856.85, 4947.78 in the 20% raw attapulgite group, respectively, indicating that the attapulgite could increase the microbial diversity and abundance in sediment. Additionally, the nutrient elements, such as Ca, Na, S, Mg, K, Zn, and Mo, that dissolved from attapulgite may also promote the V. spiralis growth. This study provided an environment-friendly approach to facilitating submerged macrophyte restoration in the eutrophic lake ecosystem.

Effects of electrochemical intervention on the remediation of black-odorous water: insights into microbial community dynamics and functional shifts in sediments.

Black-odorous water is a severe environmental issue that has received continuous attention. The major purpose of the present study was to propose an economical, practical, and pollution-free treatment technology. In this study, the in situ remediation of black-odorous water was conducted by applying different voltages (2.5, 5, and 10 V) to improve oxidation conditions of the surface sediments. The study investigated the effects of voltage intervention on water quality, gas emissions, and microbial community dynamics in surface sediments during the remediation process. The results indicated that the voltage intervention can effectively increase the oxidation-reduction potential (ORP) of the surface sediments and inhibit the emissions of H2S, NH3, and CH4. Moreover, the relative abundances of typical methanogens (Methanosarcina and Methanolobus) and sulfate-reducing bacteria (Desulfovirga) decreased because of the increase in ORP after the voltage treatment. The microbial functions predicted by FAPROTAX also demonstrated the inhibition of methanogenesis and sulfate reduction functions. On the contrary, the total relative abundances of chemoheterotrophic microorganisms (e.g., Dechloromonas, Azospira, Azospirillum, and Pannonibacter) in the surface sediments increased significantly, which led to enhanced biochemical degradability of the black-odorous sediments as well as CO2 emissions.

Prussian Blue Analogues with Optimized Crystal Plane Orientation and Low Crystal Defects toward 450 Wh kg−1 Alkali‐Ion Batteries

AbstractPrussian blue analogues (PBAs) have been regarded as promising cathode materials for alkali‐ion batteries owing to their high theoretical energy density and low cost. However, the high water and vacancy content of PBAs lower their energy density and bring safety issues, impeding their large‐scale application. Herein, a facile “potassium‐ions assisted” strategy is proposed to synthesize highly crystallized PBAs. By manipulating the dominant crystal plane and suppressing vacancies, the as‐prepared PBAs exhibit increased redox potential resulting in high energy density up to ≈450 Wh kg−1, which is at the same level of the well‐known LiFePO4 cathodes for lithium‐ion batteries. Remarkably, unconventional highly‐reversible phase evolution and redox‐active pairs were identified by multiple in situ techniques for the first time. The preferred guest‐ion storage sites and migration mechanism were systematically analysed through theoretical calculations. We believe these results could inspire the design of safe with high energy density.

Prussian Blue Analogues with Optimized Crystal Plane Orientation and Low Crystal Defects toward 450 Wh kg-1 Alkali-Ion Batteries.

Prussian blue analogues (PBAs) have been regarded as promising cathode materials for alkali-ion batteries owing to their high theoretical energy density and low cost. However, the high water and vacancy content of PBAs lower their energy density and bring safety issues, impeding their large-scale application. Herein, a facile "potassium-ions assisted" strategy is proposed to synthesize highly crystallized PBAs. By manipulating the dominant crystal plane and suppressing vacancies, the as-prepared PBAs exhibit increased redox potential resulting in high energy density up to ≈450 Wh kg-1 , which is at the same level of the well-known LiFePO4 cathodes for lithium-ion batteries. Remarkably, unconventional highly-reversible phase evolution and redox-active pairs were identified by multiple in situ techniques for the first time. The preferred guest-ion storage sites and migration mechanism were systematically analysed through theoretical calculations. We believe these results could inspire the design of safe with high energy density.

A high-voltage Zn-air battery based on an asymmetric electrolyte configuration

Rechargeable Zn-air batteries promise safe energy storage. However, they are limited by the redox potential of O2/O2- chemistry in an alkaline electrolyte, resulting in low operating voltages and therefore insufficient energy density to compete with lithium-ion batteries. The O2/O2- redox potential increases by 0.8 V in an acidic medium, hinting at a way to boost the voltage: an asymmetric electrolyte configuration decoupling acidic and alkaline electrolytes for the air cathode and zinc anode. Such configuration requires a thin and ionically conductive membrane to separate two mutually incompatible electrolytes. Here, we report a Zn ion-exchange membrane with high ionic conductivity of 1.1 mS cm-1, which prevents acid-base neutralization. The highly reversible O2/O2- reaction in the acid is made possible by compositing a cobalt-coordinated porphyrin-based polymeric framework with MXene as a bifunctional electrocatalyst. The asymmetric Zn-air battery operates at voltages up to 1.85 V and cycles for more than 200 h with a material-level energy density of 1350 Wh kg-1, projected to a high device-level energy density of 50 Wh kg-1 (coin cell diameter: 20 mm). The asymmetric configuration withstands pressure up to 4 MPa (∼1200 N), demonstrating excellent structural stability for production and practical applications.

Neuronal Calcium Sensor-1: A Zinc/Redox-Dependent Protein of Nervous System Signaling Pathways

Intracellular calcium signaling is involved in regulating the key functional mechanisms of the nervous system. The control of neuronal excitability and plasticity by calcium ions underlies the mechanisms of higher nervous activity, and the mechanisms of this control are of particular interest to researchers. A family of highly specialized neuronal proteins described in recent decades can translate the information contained in calcium signals into the regulation of channels, enzymes, receptors, and transcription factors. Neuronal calcium sensor-1 (NCS-1) is the most common member of the family, which is intensely expressed in central nervous system (CNS) cells; and controls several vital processes, such as neuronal growth and survival, reception, neurotransmission, and synaptic plasticity. In addition to calcium ions, NCS-1 can bind the so-called mobile, or signaling intracellular zinc, an increased concentration of which is a characteristic feature of cells in oxidative stress. Zinc coordination under these conditions stimulates NCS-1 oxidation to form a disulfide dimer (dNCS-1) with altered functional properties. A combined effect of mobile zinc and an increased redox potential of the medium can thus induce aberrant NCS-1 activity, including signals that promote survival of neuronal cells or induce their apoptosis and, consequently, the development of neurodegenerative processes. The review details the localization, expression regulation, structure, and molecular properties of NCS-1 and considers the current data on its signaling activity in health and disease, including zinc-dependent redox regulation cascades.

Indolin-2-one Nitroimidazole Antibiotics Exhibit an Unexpected Dual Mode of Action.

Nitroimidazoles such as metronidazole are used as anti-infective drugs against anaerobic bacteria. Upon in vivo reduction of the nitro group, reactive radicals damage DNA and proteins in the absence of oxygen. Unexpectedly, a recent study of nitroimidazoles linked to an indolin-2-one substituent revealed potent activities against aerobic bacteria. This suggests a different, yet undiscovered mode of action (MoA). To decipher this MoA, we first performed whole proteome analysis of compound-treated cells, revealing an upregulation of bacteriophage-associated proteins, indicative of DNA damage. Since DNA binding of the compound was not observed, we applied activity-based protein profiling (ABPP) for direct target discovery. Labeling studies revealed topoisomerase IV, an essential enzyme for DNA replication, as the most enriched hit in pathogenic Staphylococcus aureus cells. Subsequent topoisomerase assays confirmed the inhibition of DNA decatenation in the presence of indolin-2-one nitroimidazole with an activity comparable to ciprofloxacin, a known inhibitor of this enzyme. Furthermore, we determined significantly increased redox potentials of indolin-2-one nitroimidazoles compared to classic 5-nitroimidazoles such as metronidazole, which facilitates in vivo reduction. Overall, this study unravels that indolin-2-one-functionalized nitroimidazoles feature an unexpected dual MoA: first, the direct inhibition of the topoisomerase IV and second the classic nitroimidazole MoA of reductive bioactivation leading to damaging reactive species. Importantly, this dual MoA impairs resistance development. Given the clinical application of this compound class, the new mechanism could be a starting point to mitigate resistance.