Oxidative Conditions Research Articles

FePO4.2H2O recovery from acidic phosphate-rich waste streams

Phosphorous not only needs to be removed to prevent eutrophication of wastewater effluent receiving surface water bodies, but it also has to be recovered as a scarce finite reserve. Phosphorus chemical precipitation as NH4MgPO4·6H2O, Ca3(PO4)2, or Fe3(PO4)2 ·8H2O is the most common method of phosphorus recovery from phosphorus-rich streams. These minerals ideally form under neutral to alkaline pH conditions, making acidic streams problematic for their formation due to the need for pH adjustments. This study proposes FePO4 .2H2O (strengite-like compounds) recovery from acidic streams due to its simplicity and high efficiency, while also avoiding the need for pH-adjusting chemicals. The effect of initial pH, temperature, Fe (III) dosing rates, and Fe (II) dosage under different oxidation conditions (pO2 = 0.2, 1, 1.5 bar, different H2O2 dosing rates) on phosphorus recovery percentage and product settleability were evaluated in this study. The precipitates formed were analyzed using optical microscopy, SEM, XRD, SQUID, Raman, and ICP. Experiments showed that Fe (III) dosing achieved phosphorus recovery of over 95 % at an initial pH of 3 or higher, and the product exhibited poor settleability in all initial pH (1.5-5), and temperature (20–80 °C) tests. On the other hand, Fe (II) dosage instead of Fe (III) resulted in good product settleability but varying phosphorus recovery percentages depending on the oxidation conditions. The novelty of the study lies in revealing that the Fe (II) oxidation rate serves as a crucial process-design parameter, significantly enhancing product settleability without the requirement of carrier materials or crystallizers. The study proposes a novel strategy with controlled Fe2+-H2O2 dosing, identifying an Fe (II) oxidation rate of 4.7 × 10−4 mol/l/min as the optimal rate for achieving over 95 % total phosphorus recovery, along with excellent settleability with a volumetric index equal to only 8 ml/gP.

Towards the development of a safe, metal-catalyzed aerobic oxidation of 2-acetyl thiophene

Thiophene-2-carbonyl chloride (TCC) is a key raw material in the manufacture of active ingredients for agriculture. A new 3-step process for preparing TCC from commercial thiophene was recently developed that featured a metal-catalyzed aerobic oxidation of 2-acetylthiopehene (AcT). That process utilized pure oxygen in a flammable solvent, acetic acid, at elevated temperatures, which represented a hazardous condition by operating above the limiting oxygen concentration for the solvent and at a temperature above the flashpoint for the solvent. More recently, the same oxidation reaction has been achieved in an autoclave using diluted oxygen. Described in this Letter are details of our progress towards the identification of safe operating conditions for the aerobic oxidation of AcT.

Moderate to advanced periodontitis contributes to increased oxidative stress in cats: a case-control study

BackgroundPeriodontal diseases are the most frequently diagnosed problem in cats. It has been well-established that periodontal diseases could not only cause various oral health issues but could also contribute to systemic diseases. Oxidative stress is a possible link between systemic diseases and periodontitis. Our study aimed to illustrate the influence of periodontitis on oxidative stress development in cats. Furthermore, the changes in the bacterial flora of the gums were investigated.MethodsBased on the clinical and laboratory examinations, fifty cats were divided into two groups normal (n = 25) and moderate to advanced periodontitis (n = 25). Serum total antioxidant capacity (TAC), total oxidant status (TOS), reduced (GSH) and oxidized glutathione (GSSG) were measured. In addition, samples were taken from the subgingival plaques of all cats for bacterial culture.ResultsSerum TOS, GSSG, GSSG to GSH ratio, and oxidative stress index (OSI), calculated as the ratio of TOS to TAC in cats with periodontal disease were significantly higher, and TAC was significantly lower (p < 0.05) compared with controls. The results of bacterial culture indicated that the number of isolated bacterial colonies is higher in patients than in the control group. Additionally, the analysis of these data showed a positive association between periodontal index and oxidative stress.ConclusionsOur results revealed that periodontitis in cats is related to a main oxidative stress. Furthermore, oxidant factors such as TOS and OSI, compared to antioxidant factors, may better indicate the presence of oxidative stress conditions in patients with periodontitis.

Purification of carbon nanotubes for dissolution in chlorosulfonic acid

Carbon nanotubes (CNTs) can be scalably processed into high-performance fiber with a low environmental footprint by solution spinning from chlorosulfonic acid (CSA). CNTs are produced by numerous manufacturers, but CNTs typically need to undergo purification to improve solubility in CSA. For over two decades, oxidative techniques have been used to remove amorphous carbon species to improve CNT dissolution in acid. However, more recent work has attributed the improved solubility after single-walled carbon nanotube (SWCNT) oxidation to the inclusion of oxygen groups in the sidewall of the SWCNT. Here, we refute the recent claim that oxidation incorporates oxygen into the sidewall of CNTs to improve CNT dissolution to CSA. Instead, we provide experimental evidence in support of classical purification literature: at the appropriate time and temperature, oxidation removes amorphous carbon shells and defective SWCNTs without oxidizing the SWCNT sidewall. Once these amorphous carbon shells are removed, CSA can access and protonate the sp2-bonded carbon sites, which results in SWCNT dissolution. Additionally, we explore how oxidation conditions impact SWCNT aspect ratio (length of CNT divided by CNT diameter), which directly controls macroscale fiber properties.

Moderate-intensity Exercise Alleviates Rat's Systemic Inflammation Induced by Repeated Exposure to Lipopolysaccharide.

The protective impacts of physical activity against inflammatory and oxidative stress conditions have been demonstrated. In this study, the impacts of moderate-intensity exercise on oxidative stress-associated factors and proinflammatory cytokines levels as well as the count of white blood cells (WBC) were assessed in a lipopolysaccharide (LPS)-triggered model of inflammation. Wistar rats were randomized into these groups (8 rats in each): (1) control; (2) LPS; (3) moderate exercise (EX); and (4) moderate exercise + LPS (EX+LPS). Exercise groups were trained for 8 weeks (30 min, 6 days/week) at 15 m/min speed. During the final week of the experiment, 1 mg/kg/day of intraperitoneal LPS was administered for 5 days. On day 56, from the rats' hearts, peripheral blood was taken for biochemical evaluation. LPS enhanced serum levels of C-reactive protein (CRP), interleukin (IL)- 1β, tumor necrosis factor-α (TNF-α), metabolites of nitric oxide, and malondialdehyde (MDA), as well as the counts of total WBC, monocytes, neutrophils, and eosinophils, but decreased serum levels of thiol as well as superoxide dismutase (SOD) and catalase (CAT) activity versus the control rats. Moderate exercise reduced the levels of thiol, CAT, and SOD, but increased TNF-α level, and total WBC, neutrophils, eosinophils, and monocytes counts versus the control group. In the EX+LPS group, moderate exercise decreased cell counts and diminished MDA, TNF-α, IL-1β, and CRP levels, while increasing thiol level, CAT, and SOD versus the LPS group. In our study, exercise preconditioning reduced inflammation induced by LPS by ameliorating inflammatory cytokine levels, WBC counts, and oxidative damage, while improving antioxidant defenses.

UV aging assessment of asphalt binder: influence of duration, zinc oxide, and aging condition

ABSTRACT Ultraviolet radiation penetrates the atmosphere resulting in photo-oxidative aging of asphalt. The conventional long-term aging method, such as pressure-aging vessel, ages the asphalt considering thermo-oxidative principle. However, asphalt undergoes predominantly photo-oxidative aging (POA) in field. Giving due importance to UV aging method will result in resilient asphalt, which can negate the impact of climate change on asphalt pavements to a certain extent. In this study, asphalt was aged using UV rays, considering different aging durations; 7, 14, and 21 days, aging temperature (room temperature and 60°C), and modification with zinc oxide nanoparticles (ZnO) as experimental factors. Further, thin asphalt layers were also subjected to natural aging by exposing them to atmosphere to develop equivalencies between laboratory and natural aging. The rheological studies indicated significant aging occurred in the laboratory in the first 7 days, followed by a decreased rate. The naturally-aged specimens depicted significant cracks after 1-, 3-, and 6-months of aging, which was relatively less in specimens with ZnO indicating its anti-POA properties. The carbonyl index was reduced by 30–75% with ZnO compared to binders without ZnO. Zero shear viscosity (ZSV) indicated that one-month naturally-aged asphalt with ZnO resulted in similar ZSV as PAV-aged binder with ZnO.

Innovative Molecularly Imprinted Electrochemical Sensor for Selective Nanomolar Detection of the Anti-COVID-19 Medication Molnupiravir

For the first time, a green ecofriendly approach is applied, to develop a molecularly imprinted polymer (MIP) electrochemical for the assay of the oral anti-viral molnupiravir (MLN) in various matrices as confirmed by referring to analytical eco-scale, green analytical procedure index (GAPI), Raynie and Driver, analytical greenness metric (AGREE), and national environmental index (NEMI). AuNPs were chronoamperometry deposited on the glassy carbon electrode surface (GCE) using 0.01 gm ml−1 gold solution (HAuCl4.3H2O) in 0.5 M H2SO4 at a constant potential of −0.4 V for 60 s. Then, the MIP was created by electropolymerizing OPDA on the surface of AuNPs GCE using cyclic voltammetry in the potential range between −0.5 and +1 V for 15 cycles (scan rate: 50 mV.s−1). To optimize the sensor’s performance, factors such as number of electropolymerization cycles, template: monomer ratio, binding and rebinding time, pH of rebinding buffer, extraction solvent, deposition time of Au nanoparticles, order of deposition on the electrode; surface, as well as differential pulse voltammetry parameters including accumulation potential and time, and potential step, were all investigated. The detection limit was set at 0.00098 ng ml−1 (3 × 10−12M) and the linearity range of MLN was between 0.033 ng ml−1 and 164 ng ml−1 (1 × 10−10–5 × 10−7 M). The MIP sensor was employed for MLN determination in its pharmaceutical product (capsules), spiked human plasma, and human urine samples with mean recovery % ± mean relative standard deviation (RSD) (99.82% ± 0.53), (99.88% ± 0.62), and (97.90% ± 0.70), respectively. The investigated sensor provided good reproducibility, repeatability, and durability. Acceptable selectivity regarding MLN when mixed with structurally comparable compounds was proved with mean recovery % ± mean RSD (97.10% ± 0.03). Additionally, when molnupiravir was exposed to oxidative, hydrolytic, and thermal stress conditions, good results in stability-indicating studies served as an indicator of sensor selectivity. The developed electrode is coupled with a portable potentiostat, making it a promising point-of-care diagnostic platform for on-site measurements.

Aqueous sage leave extract attenuates inflammation and oxidant-induced genotoxicity in human peripheral blood mononuclear cells.

Traditional medicine has used sage (Salvia officinalis L.) preparations for centuries to prevent and treat various inflammatory and oxidative stress-induced conditions. The aim of this in vitro study was to determine the bioactive properties of a sage leave extract obtained with environmentally friendly aqueous extraction and lyophilisation in primary human peripheral blood cells. To that end we measured the total phenolic and flavonoid content (TPC and TFC, respectively) with gas chromatography-mass spectrometry (GC-MS). Non-cytotoxic concentrations determined with the trypan blue assay were used to assess the antioxidant (DPPH, ABTS, and PAB assay), antigenotoxic (CBMN assay), immunomodulatory (IL-1β and TNF-α), and neuroprotective effects (AChE inhibition). The extract contained high TPC (162 mg GAE/g of dry extract) and TFC (39.47 mg QE/g of dry extract) concentrations, while β-thujone content was unexpectedly low (below 0.9 %). Strong radical-scavenging activity combined with glutathione reductase activation led to a decrease in basal and H2O2-induced oxidative stress and DNA damage. A decrease in TNF-α and increase in IL-1β levels suggest complex immunomodulatory response that could contribute to antioxidant and, together with mild AChE inhibition, neuroprotective effects. Overall, this study has demonstrated that aqueous sage leave extract reduces the levels of thujone, 1,8-cineole, pinene, and terpene ketones that could be toxic in high concentrations, while maintaining high concentrations of biologically active protective compounds which have a potential to prevent and/or treat inflammatory and oxidative stress-related conditions.

Effect of cell sintering temperature on the performance of non-noble metal loaded cerium oxide SOEC anodes

Abstract Introducing methane oxidation reaction into the anode of the high-temperature solid oxide electrolysis cell (SOEC) can reduce the power consumption for water electrolysis. Compared to the traditional conditions of methane oxidation, the methane oxidation catalyst sintered at the SOEC anode, which is closely related to the cell sintering process. This study uses non-noble metals as active sites for methane oxidation, zirconia, and samarium oxides doped ceria as catalyst support and oxygen ion conductors. The effects of anode sintering temperature on the electrochemical performance of SOEC assisted by methane oxidation were investigated. The results indicate that the high-temperature sintering process promotes the performance of the SOEC anode with Ni as the active site, while high temperature harms the performance of the Co-loaded anode. The sintering temperature exhibits a poor effect on the Fe-loaded anode. The Ni exhibits good enhancement of methane oxidation on reducing the electrolysis voltage of SOEC, while Co only exhibits methane oxidation assistance at low-temperature sintering. Differently, Fe has almost no obvious methane oxidation assistance for SOEC, which mainly represents good oxygen evolution performance.

Development and validation of stability-indicating assay method and identification of force degradation products of glucagon-like peptide-1 synthetic analog Exenatide using liquid chromatography coupled with Orbitrap mass spectrometer.

Exenatide is a synthetic glucagon-like peptide 1 analog, widely used in the management of type 2 diabetes mellitus. The stability of pharmaceutical products is significantly impacted by various environmental stress conditions. The present study reports the development of a validated reverse-phase high-performance liquid chromatography (RP-HPLC) stability-indicating method for the identification of force degradation products (DPs) of synthetic glucagon-like peptide-1 analog Exenatide using UHPLC-Orbitrap fusionTM mass spectrometer. Force degradation studies were performed by subjecting Exenatide to various stress conditions, such as hydrolytic, oxidative, photolytic and thermal to investigate the stability indicating ability of the method. Significant degradation was observed during acidic, oxidative, photolytic and thermal stress conditions. Exenatide and its major DPs identification and characterization were demonstrated by employing LC-HRMS and MS/MS method. In total, five major stress DPs were characterized, and their fragmentation pathway was proposed using MS/MS studies. Finally, the proposed RP-HPLC method was validated as per ICH guidance.

Nutritional Value, Therapeutic Effects, Phytochemistry, and Toxicology of Lepisanthes fruticosa: A Review.

The multifaceted benefits of Lepisanthes fruticosa position it is not only as a promising agricultural commodity but also as a versatile resource with implications for health, biodiversity, and economic growth. Lepisanthes fruticosa has a rich history of traditional use for treating various ailments such as fever and diarrhea. Beyond its traditional uses, the plant's antioxidant properties suggest potential applications in combating oxidative stress-related conditions. Its antihyperglycemic properties indicate promise in managing elevated blood sugar levels, while its antibacterial and antiviral attributes hint at potential applications in infectious disease control. Furthermore, the plant's anticancer properties add to its appeal as a valuable resource in the realm of medical research. The plant also exhibits considerable potential in addressing a range of health concerns, including non-communicable diseases and infections, antidiarrheal, and antiviral properties. In essence, Lepisanthes fruticose emerges as more than just an agricultural asset. Its unique combination of nutritional richness, health benefits, and economic viability underscores its potential to become a valuable asset both locally and on the global stage. In this current review, we are discussed about the ethnopharmacology, nutritional value, therapeutic effects, phytochemistry, and toxicology of Lepisanthes fruticose.

Interplay between mistranslation and oxidative stress in Escherichia coli.

Mistakes in translation are mostly associated with toxic effects in the cell due to the production of functionally aberrant and misfolded proteins. However, under certain circumstances mistranslation can have beneficial effects and enable cells to preadapt to other stress conditions. Mistranslation may be caused by mistakes made by aminoacyl-tRNA synthetases, essential enzymes that link amino acids to cognate tRNAs. There is an Escherichia coli strain expressing isoleucyl-tRNA synthetase mutant variant with inactivated editing domain which produces mistranslated proteomes where valine (Val) and norvaline (Nva) are misincorporated into proteins instead of isoleucine. We compared this strain with the wild-type to determine the effects of such mistranslation on bacterial growth in oxidative stress conditions. When the cells were pre-incubated with 0.75 mmol/L Nva or 1.5 mmol/L Val or Nva and exposed to hydrogen peroxide, no beneficial effect of mistranslation was observed. However, when the editing-deficient strain was cultivated in medium supplemented with 0.75 mmol/L Val up to the early or mid-exponential phase of growth and then exposed to oxidative stress, it slightly outgrew the wild-type grown in the same conditions. Our results therefore show a modest adaptive effect of isoleucine mistranslation on bacterial growth in oxidative stress, but only in specific conditions. This points to a delicate balance between deleterious and beneficial effects of mistranslation.

Redox dynamics and surface structures of an active palladium catalyst during methane oxidation

Catalysts based on palladium are among the most effective in the complete oxidation of methane. Despite extensive studies and notable advances, the nature of their catalytically active species and conceivable structural dynamics remains only partially understood. Here, we combine operando transmission electron microscopy (TEM) with near-ambient pressure X-ray photoelectron spectroscopy (NAP-XPS) and density functional theory (DFT) calculations to investigate the active state and catalytic function of Pd nanoparticles (NPs) under methane oxidation conditions. We show that the particle size, phase composition and dynamics respond appreciably to changes in the gas-phase chemical potential. In combination with mass spectrometry (MS) conducted simultaneously with in situ observations, we uncover that the catalytically active state exhibits phase coexistence and oscillatory phase transitions between Pd and PdO. Aided by DFT calculations, we provide a rationale for the observed redox dynamics and demonstrate that the emergence of catalytic activity is related to the dynamic interplay between coexisting phases, with the resulting strained PdO having more favorable energetics for methane oxidation.

Development and evaluation of guar gum-coated nano-nutriosomes for cyanidin-3-O-glucoside encapsulation

Cyanidin-3-O-glucoside (C3G) is a type of water-soluble flavonoid compound that is abundantly found in fruits and vegetables. C3G possesses numerous biological activities, however, it is prone to breakdown under environmental conditions. To overcome these issues, we developed nano-nutriosome (NS) carriers created by vortex-mixing and probe-sonication techniques for C3G encapsulation in which the phospholipid and Nutriose® FB06 were chosen as carrier material, and guar gum (GG) as a coating material to formulate a unilamellar and multicompartment structure. This study aimed to develop and evaluate C3G-loaded nano-nutriosomes coated by GG (GG-C3G-NS) for improving physicochemical stability, antioxidant activity, cellular uptake, and controlled release properties. The C3G-NS and GG-C3G-NS are nanosized (143.47 to 154.13 nm), with high encapsulation efficiency (>93.31 %). The NS carriers successfully encapsulated C3G which was confirmed by transmission electron microscopy, differential scanning calorimetry, and Fourier transform infrared spectroscopy. C3G showed more stability in storage, thermal, pH, ionic, and oxidative conditions. Furthermore, the NS exhibited a better-controlled release of C3G in different food stimulant conditions and in vitro release study. Additionally, NS systems enhanced cellular uptake and showed no cytotoxicity. Overall, GG-NS could be a promising nanocarrier for improving the stability, controlled release, and antioxidant activity of bioactive compounds.

Stability of Plasmonic Mg-MgO Core-Shell Nanoparticles in Gas-Phase Oxidative Environments.

Magnesium is a recent addition to the plasmonic toolbox: nanomaterials that efficiently utilize photons' energy due to their ability to sustain localized surface plasmon resonances. Magnesium nanoparticles protected by a native oxide shell can efficiently absorb light across the solar spectrum, making them a promising photocatalytic material. However, their inherent reactivity toward oxidation may limit the number of reactions in which Mg-MgO can be used. Here, we investigate the stability of plasmonic Mg-MgO core-shell nanoplates under oxidative conditions. We demonstrate that the MgO shell stabilizes the metallic Mg core against oxidation in air at up to 400 °C. Furthermore, we show that the reactivity of Mg-MgO nanoplates with water vapor (3.5 vol % in N2) decreases with temperature, with no oxidation of the Mg core detected from 200 to 400 °C. This work unravels the potential of Mg-MgO nanoparticles for a broad range of catalytic transformations occurring in oxidative environments.

Ameliorative Effect of Pigeon Pea Leaves and Ginger Extract on Oxidative Stress Condition in Kidney and Liver of Experimental Diabetic Rats

Ameliorative Effect of Pigeon Pea Leaves and Ginger Extract on Oxidative Stress Condition in Kidney and Liver of Experimental Diabetic Rats

A novel stability indicating HPTLC method for comparative quantitative estimation of quercetin in herbal preparations

This research introduces a novel stability-indicating HPTLC (High-Performance Thin-Layer Chromatography) method for the comparative quantitative estimation of Quercetin in herbal preparations. Through extensive stability studies, the method is validated, providing a robust framework for evaluating Quercetin's stability in diverse herbal formulations. The developed method ensures accurate and reliable quantification of Quercetin, facilitating comparative analysis across various herbal preparations. Additionally, results reveal that Quercetin degraded under most tested conditions, such as acidic, alkaline, oxidative and neutral conditions underscoring the necessity for intervention by experts to eliminate such challenges and ensure product efficacy and quality in the herbal industry.

Identification and Characterization of Rotigotine Degradation Products by HPLC Coupled DAD and CAD Detectors and HRMS Through Q-Orbitrap and Electrospray Ionization

Rotigotine (RTG) is a dopamine agonist used in the treatment of Parkinson's disease. As it is susceptible to oxidation, stability studies must be carefully designed for the identification and characterization of all possible degradation products. Here, RTG degradation was evaluated according to the International Conference on Harmonization guidelines under various stress conditions, including acidic and basic hydrolysis, oxidative, metallic, photolytic, and thermal conditions. Additionally, more severe stress conditions were applied to induce RTG degradation. Significant degradation was only observed under oxidative and photolytic conditions. The samples were analyzed by high performance liquid chromatography coupled to photodiode array detectors, charged aerosol, and high-resolution mass spectrometry. Chromatographic analyses revealed the presence of eight substances related to RTG, four of which were already described and were qualified impurities (impurities B, C, K and E) and four new degradation products (DP-1 – DP-4), whose structures were characterized by high-resolution mass spectrometry through Q-Orbitrap and electrospray ionization. In the stress testing of the active pharmaceutical ingredient in solid form, significant RTG degradation was observed in the presence of the oxidative matrix. The results corroborate the literature that confirm the high susceptibility of RTG to oxidation and the importance of using different detectors to detect degradation products in forced degradation studies.

Effects of UV/Cl2 and UV/PDS advanced oxidation on chemical characteristics of typical organic matter in reclaimed water

In this research, humic acid was selected as a typical organic substance in reclaimed water, and the effects of higher oxidation of UV/Cl2 and UV/PDS on its chemical composition, including aromaticity, molecular weight and fluorescence characteristics were investigated. Results showed that under the same oxidation conditions, the UVA254 removal rate of UV/Cl2 was higher than that of UV/PDS, but with the increase of pH, the UVA254 removal rate of both decreased. Increasing the oxidant concentration could improve the UVA254 removal rate, but UVA254 would not continue to decrease after a certain concentration (Cl2 0.5mM, PDS 0.75mM). After oxidation, organics whose molecular weight &gt;6520 Da significantly decreased, molecular weight 350-1690 Da significantly increased, with increasing UV dose, the molecular weight of 350-1690 Da decreased in UV/Cl2, but continued to increase in UV/PDS. The fluorescent regions of fulic acids under different treatments were effectively degraded after oxidation. The degradation efficiency of UV/Cl2 and UV/PDS reached 87.6% and 83.3% respectively with 0.75mM oxidant and 1500 mJ/cm2 UV light.

Comprehensive Analysis of Novel Synergistic Antioxidant Formulations: Insights into Pharmacotechnical, Physical, Chemical, and Antioxidant Properties.

(1) Background: Oxidative stress plays a pivotal role in the pathogenesis of various diseases, including neurodegenerative disorders, cardiovascular diseases, cancer, and diabetes, highlighting the pressing need for effective antioxidant interventions. (2) Methods: In this study, we aimed to develop and characterise two novel antioxidant formulations, F3 and F4, as therapeutic interventions for oxidative stress-related conditions. (3) Results: The physicochemical characterisation, preformulation analysis, formulation, preparation of filling powders for capsules, capsule content evaluation, and antioxidant activity assessment of the two novel antioxidant formulations were assessed. These formulations comprise a combination of well-established antioxidants like quercetin, biotin, coenzyme Q10, and resveratrol. Through comprehensive testing, the formulations' antioxidant efficacy, stability, and potential synergistic interactions were evaluated. (4) Conclusions: The findings underscore the promising potential of these formulations as therapeutic interventions for oxidative stress-related disorders and highlight the significance of antioxidant interventions in mitigating their progression.