Internal stimuli-responsive nanocarriers for controlled anti-cancer drug release: a review.

Cancer disease is one of the most frequent life-threatening, with a high fatality rate worldwide. However, recent immunotherapy studies in various tumours have yielded unsatisfactory outcomes, with just a few individuals experiencing long-term responses. To overcome these issues, nowadays internal stimuli-responsive nanocarriers have been widely exploited to transport a wide range of active substances, including peptides, genes and medicines. These nanosystems could be chemically adjusted to produce target-based drug release at the target location, minimizing pathological and physiological difficulties while increasing therapeutic efficiency. This review highlights the various types of internal stimuli-responsive nanocarriers and applications in cancer diagnosis. This study can provide inspiration and impetus for exploiting more promising internal stimuli-responsive nanosystems for drug delivery.

A comprehensive modelling approach to estimate the transmissibility of coronavirus and its variants from infected subjects in indoor environments.

A central issue in assessing the airborne risk of COVID-19 infections in indoor spaces pertains to linking the viral load in infected subjects to the lung deposition probability in exposed individuals through comprehensive aerosol dynamics modelling. In this paper, we achieve this by combining aerosol processes (evaporation, dispersion, settling, lung deposition) with a novel double Poisson model to estimate the probability that at least one carrier particle containing at least one virion will be deposited in the lungs and infect a susceptible individual. Multiple emission scenarios are considered. Unlike the hitherto used single Poisson models, the double Poisson model accounts for fluctuations in the number of carrier particles deposited in the lung in addition to the fluctuations in the virion number per carrier particle. The model demonstrates that the risk of infection for 10-min indoor exposure increases from 1 to 50% as the viral load in the droplets ejected from the infected subject increases from 2 × 108 to 2 × 1010 RNA copies/mL. Being based on well-established aerosol science and statistical principles, the present approach puts airborne risk assessment methodology on a sound formalistic footing, thereby reducing avoidable epistemic uncertainties in estimating relative transmissibilities of different coronavirus variants quantified by different viral loads.

Characterization of Mungbean yellow mosaic India virus genome with a recombinant DNA-B in Southern Peninsular India.

BACKGROUND: Mungbean yellow mosaic India virus (MYMIV) is a representative of the genus begomovirus/Begomoviridae, which is prevalent in the northern part of Indian subcontinent causing yellow mosaic disease (YMD). This virus is rapidly evolving and breaking the resistance in the advanced lines causing huge economic losses in the pulse production. In this context, the present investigation on characterization of the causal organism of YMD was undertaken METHODS AND RESULTS: A novel recombinant isolate (YMV-BG-BPT) causing YMD was identified from blackgram in Andhra Pradesh, southern peninsular region of India. The association of a bipartite begomovirus with the disease was done by sequence analyses of the cloned full-length genome. The full length genome sequences were submitted in NCBI GenBank with accession numbers MZ235792 (DNA-A) and MZ356197 (DNA-B). The sequence analysis of DNA-A of YMV-BG-BPT showed maximum of 99.12% similarity at nucleotide level with Mungbean yellow mosaic India virus (MYMIV) isolate reported from Tamil Nadu (KC911719), India which is also confirmed by clustering pattern in phylogenic analysis and DNA-B showed 95.79% with Mungbean yellow mosaic virus (MYMV) isolate reported from Tamil Nadu (KP319016) and 95.05% with MYMIV isolate reported from Karnataka (MT027037). The huge variation in DNA-B lead us to suspect a recombination in DNA-B, where a recombination event in the CR, region coding for nuclear shuttle protein and movement protein of DNA B was detected in which MYMV-BG-AP-IND (KF928962) and MYMIV-GG-CH-IND (MN020536) have been identified as major and minor parents, respectively. CONCLUSION: Overall, the present study revealed occurrence of MYMIV with recombinant DNA B component in southern peneinsular India.

Green Synthesis of Cu Nanoparticles in Modulating the Reactivity of Amine-Functionalized Composite Materials towards Cross-Coupling Reactions.

Control over both dispersion and the particle size distribution of supported metal particles is of paramount importance for the catalytic activity of composite materials. We describe the synthesis of materials with Cu nanoparticles well-dispersed on different amine-functionalized supports, using the extract of Wallich Spurge as a green, reducing agent. Graphene oxide (GO), mesoporous silica (MCM-41), mesoporous zirconia, and reduced graphene oxide-mesoporous silica (RGO-MCM-41) were explored as supports. Cu nanoparticles were better stabilized on RGO-MCM-41 compared to other supports. The novel composite materials were characterized by X-ray diffraction (XRD), Raman spectra, Scanning electron microscope (SEM), Transmission electron microscopy analysis and HR-TEM. SEM and EDX techniques. High angle XRD confirmed the conversion of graphene oxide to reduced graphene oxide (RGO) with plant extract as a reducing agent. Both XRD and TEM techniques confirmed the Cu nanoparticle formation. The catalytic activity of all the prepared materials for the Ullmann coupling reactions of carbon-, oxygen-, and nitrogen-containing nucleophiles with iodobenzene was evaluated. From the results, 5 wt% Cu on amine-functionalized reduced graphene oxide/mesoporous silica nanocomposite (5 wt%Cu(0)-AAPTMS@RGO-MCM-41) exhibited excellent efficiency with 97% yield of the C-C coupling product in water at 80 °C in 5 h. The activity remained unaltered almost up to the fourth cycle. The Cu nanoparticles stabilized by organic amine group on RGO hybrid facilitated sustained activity.

Cytotoxic activity of the bioactive principles from Ficus burtt-davyi.

Ficus burtt-davyi (Moraceae) is a medicinal plant species indigenous to Southern Africa. In this study, a phytochemical and cytotoxic investigation on F. burtt-davyi was conducted to evaluate its ethno-medicinal use. The phytochemical study of the fruits yielded triterpenoids (lupeol and α-amyrin). The cytotoxic evaluation was done on the methanolic extracts and selected compounds, lupeol, α-amyrin, lupeol acetate and (+)-catechin isolated from F. burtt-davyi stem bark and fruits. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay was carried out against two human cancer cell lines, breast adenocarcinoma (MCF-7) and colorectal adenocarcinoma (Caco-2), and normal human embryonic kidney cells (HEK293). The methanol extract from the stem bark was significantly cytotoxic to MCF-7 and Caco-2 cell lines (p < 0.05) in a concentration-dependent manner with IC50 values of 6.6 and 8.1 µg mL-1, respectively relative to the control. Lupeol and (+)-catechin showed cytotoxic activity against MCF-7 cell lines with IC50 values of 22.6 and 29.8 µg mL-1, respectively and greater cytotoxic activity against Caco-2 cell lines with IC50 values of 10.7 and 9.0 µg mL-1, respectively. Data from this study suggests that F. burtt-davyi exhibits cytotoxicity with no significant inhibitory effects against HEK293. The results also indicate that (+)-catechin and lupeol, the most abundant bioactive principles in the stem bark, are responsible for the synergistic cytotoxic effects against tested human cancer cell lines. This study provides evidence on the pharmaceutical potential of the medicinal plant, F. burtt-davyi, as a chemotherapeutic agent against cancer.

Ventilation dependence of concentration metrics of Ultra-fine Particles in a coagulating household smoke.

Role of Ultra-fine Particles (UFPs) in causing adverse health effects among large population across the world, attributable to household smoke, is being increasingly recognized. However, there is very little theoretical perspective available on the complex behavior of the UFP metrics with respect to controlling factors, such as ventilation rate and particle emission rate from the combustion sources. This numerical study examines through coagulation dynamics, the dependence of UFP metrics, viz., number (PN), mass (PM(0.1)) and surface area (PA(0.1)) concentrations below 0.1 µm diameter, on ventilation and the number emission rate from household smoke. For strong sources, the steady-state concentrations of these metrics are found to increase initially with increasing Air Exchange Rate (AER), reach a peak value and then decrease. Counter correlations are seen between UFP metric and PM(2.5) concentrations. The concepts of Critical Air Exchange Rate (CAER) and Half-Value Air Exchange Rate (HaVAER) have been introduced which indicate a feasibility of mitigation of PM(0.1) and PA(0.1), unlike PN, by ventilation techniques. The study clearly brings forth complex differential behavior of the three UFP metrics. The results are further discussed.

Structure and antioxidant activity of phenolic compounds isolated from the edible fruits and stem bark of Harpephyllum caffrum.

Antioxidant activity in edible fruits is an important characteristic in the choice of fruits for human consumption, and has profound influence on nutrition and health. Two pharmacologically active triterpenoids, ß-sitosterol and lupeol, and the powerful flavan-3-ol antioxidant, (+)-catechin, were isolated from the edible fruits of Harpephyllum caffrum while a mixture of cardanols, an alkyl p-coumaric acid ester, and (+)-catechin were isolated from the stem bark. This is the first report of these compounds being isolated from this plant. The antioxidant capacity of (+)-catechin was higher than the other isolated compounds as well as the known antioxidant, ascorbic acid.

Elemental uptake and distribution of nutrients in avocado mesocarp and the impact of soil quality.

The distribution of 14 elements (both essential and non-essential) in the Hass and Fuerte cultivars of avocados grown at six different sites in KwaZulu-Natal, South Africa, was investigated. Soils from the different sites were concurrently analysed for elemental concentration (both total and exchangeable), pH, organic matter and cation exchange capacity. In both varieties of the fruit, concentrations of the elements Cd, Co, Cr, Pb and Se were extremely low with the other elements being in decreasing order of Mg > Ca > Fe > Al > Zn > Mn > Cu > Ni > As. Nutritionally, avocados were found to be a good dietary source of the micronutrients Cu and Mn. In soil, Pb concentrations indicated enrichment (positive geoaccumuluation indices) but this did not influence uptake of the metal by the plant. Statistical analysis was done to evaluate the impact of soil quality parameters on the nutrient composition of the fruits. This analysis indicated the prevalence of complex metal interactions at the soil-plant interface that influenced their uptake by the plant. However, the plant invariably controlled metal uptake according to metabolic needs as evidenced by their accumulation and exclusion.

Oxyhalogen-sulfur chemistry: kinetics and mechanism of oxidation of chemoprotectant, sodium 2-mercaptoethanesulfonate, MESNA, by acidic bromate and aqueous bromine.

The oxidation of a well-known chemoprotectant in anticancer therapies, sodium 2-mercaptoethanesulfonate, MESNA, by acidic bromate and aqueous bromine was studied in acidic medium. Stoichiometry of the reaction is: BrO3(-) + HSCH2CH2SO3H → Br(-) + HO3SCH2CH2SO3H. In excess bromate conditions the stoichiometry was deduced to be: 6BrO3(-) + 5HSCH2CH2SO3H + 6H(+) → 3Br2 + 5HO3SCH2CH2SO3H + 3H2O. The direct reaction of bromine and MESNA gave a stoichiometric ratio of 3:1: 3Br2 + HSCH2CH2SO3H + 3H2O → HO3SCH2CH2SO3H + 6Br(-) + 6H(+). This direct reaction is very fast; within limits of the mixing time of the stopped-flow spectrophotometer and with a bimolecular rate constant of 1.95 ± 0.05 × 10(4) M(-1) s(-1). Despite the strong oxidizing agents utilized, there is no cleavage of the C-S bond and no sulfate production was detected. The ESI-MS data show that the reaction proceeds via a predominantly nonradical pathway of three consecutive 2-electron transfers on the sulfur center to obtain the product 1,2-ethanedisulfonic acid, a well-known medium for the delivery of psychotic drugs. Thiyl radicals were detected but the absence of autocatalytic kinetics indicated that the radical pathway was a minor oxidation route. ESI-MS data showed that the S-oxide, contrary to known behavior of organosulfur compounds, is much more stable than the sulfinic acid. In conditions where the oxidizing equivalents are limited to a 4-electron transfer to only the sulfinic acid, the products obtained are a mixture of the S-oxide and the sulfonic acid with negligible amounts of the sulfinic acid. It appears the S-oxide is the preferred conformation over the sulfenic acid since no sulfenic acids have ever been stabilized without bulky substituent groups. The overall reaction scheme could be described and modeled by a minimal network of 18 reactions in which the major oxidants are HOBr and Br2(aq).

Elemental composition and nutritional value of the edible fruits of Harpephyllum caffrum and impact of soil quality on their chemical characteristics.

Harpephyllum caffrum is a medicinal plant and common street tree distributed throughout the eastern part of South Africa. The elemental concentration in the edible fruit of H. caffrum was determined to assess for nutritional value and health impact. Concentrations of metals in the fruit and growth soil were determined from samples acquired from eight different sites in eastern KwaZulu-Natal, South Africa, to evaluate the impact of soil parameters on elemental distribution in the fruit. Typical elemental concentrations (µg g⁻¹, dry mass) in soil (Exchangeable/Total) and fruit samples, at Umhlanga, north of Durban, were Ca (1221/696 and 3333), Co (2.5/2.1 and 0.16), Cr (35/0.8 and 5.8), Cu (14/9 and 21), Fe (9424/394 and 116), Mg (199/139 and 915), Mn (268/187 and 13), Ni (2.8/0.51 and 3.4), Pb (36/32 and 1.2), and Zn (26/21 and 15). The analytical results showed that metal interactions in soil influenced their availability, but uptake was to a greater extent controlled by the plant. The concentrations of elements in the fruits were found to be in the order of Ca > Mg > Fe > Cu > Zn > Mn > Cr > Ni > Pb > Co. The concentrations of toxic metals, arsenic and lead were low. The fruits can contribute to the health and nutritional needs of individuals for most elements. It has potential to improve the Fe status and contribute towards a balanced diet.

Ozone facilitated dechlorination of 2-chloroethanol and impact of organic solvents and activated charcoal.

The ozone-initiated oxidation of 2-chloroethanol was followed by monitoring the consumption of the halogenated organic substrate. Gas chromatographic analysis of the ozonated products showed an increase in conversion from about 1 % after 3 h of ozone treatment to about 22 % after 12 h. The yields of major ozonated products identified and quantified namely acetaldehyde, acetic acid, and chloride ion increased proportionately as a function of ozone treatment time. The percent conversion of 2-chloroethanol in the presence of acetic acid or ethyl acetate were found to be higher than those under solvent-free conditions with similar products obtained. The use of activated charcoal during the ozonolyis of 2-chloroethanol showed a significant increase in the percent conversion of the substrate compared to solvent free ozonation. Based on the experimental findings, the overall mechanism for the reaction between 2-chloroethanol and ozone is described.

Elemental composition and fatty acid profile of the edible fruits of Amatungula (Carissa macrocarpa) and impact of soil quality on chemical characteristics.

The Amatungula fruit, from Carissa macrocarpa, is commonly consumed by the local people of KwaZulu-Natal (KZN), South Africa. Levels of elements in the fruit were determined to assess if they conform to recommended dietary allowances (RDAs) and to assess for potential toxicities. Soils and fruit samples from nine sites in eastern KZN were investigated. Concentrations of elements in the fruit were found to be in the order of Ca>Mg>Fe>Mn≈Cu≈Pb>Se>Cr>Ni>Zn. For the elements in focus, except for Pb, all of the elements found in the fruit contribute significantly towards the RDAs. Lipid profiling was also done to determine the fruits potential as a source of essential fatty acids. The fruit was rich in monounsaturated and essential fatty acids with the linoleic acid to α-linolenic acid ratio conforming to the recommended range for cardiac health. Concentrations of elements in soil had no significant effect on plant concentrations, but competition between elements in soil influenced their availability. Total soil concentrations of most metals studied have significantly correlated Pb availability, indicating the impact of these metals on Pb availability. The Amatungula fruit showed tendency to accumulate Pb, with Pb levels in fruit at all sites being toxic to human health. Site location had a major effect on plant concentrations however uptake and distribution was primarily dependent on the plants inherent controls, as evidenced by the accumulation and exclusion of elements, to meet its physiological requirements.

Fatty acid profile and elemental content of avocado (Persea americana Mill.) oil--effect of extraction methods.

Interest in vegetable oil extracted from idioblast cells of avocado fruit is growing. In this study, five extraction methods to produce avocado oil have been compared: traditional solvent extraction using a Soxhlet or ultrasound, Soxhlet extraction combined with microwave or ultra-turrax treatment and supercritical fluid extraction (SFE). Traditional Soxhlet extraction produced the most reproducible results, 64.76 ± 0.24 g oil/100 g dry weight (DW) and 63.67 ± 0.20 g oil/100 g DW for Hass and Fuerte varieties, respectively. Microwave extraction gave the highest yield of oil (69.94%) from the Hass variety. Oils from microwave extraction had the highest fatty acid content; oils from SFE had wider range of fatty acids. Oils from Fuerte variety had a higher monounsaturated: saturated FA ratio (3.45-3.70). SFE and microwave extraction produced the best quality oil, better than traditional Soxhlet extraction, with the least amount of oxidizing metals present.

Cu(II) and Mn(II) complexes containing macroacyclic ligand: synthesis, DNA binding, and cleavage studies.

The two new metal complexes of Cu(II) and Mn(II) containing macroacyclic ligand of the type [Cu(hpn)](PF(6))(2) (1) and [Mn(hpn)](PF(6))(2) (2) [where hpn = [1-{[2-{[2-hydroxynaphthalen-1-yl)methylidine]amino}phenyl)imino]methyl}naphthalene-2-ol]] have been synthesized and characterized by employing analytical and spectral methods. The DNA binding properties of the complexes with calf thymus-DNA were studied by using absorption spectra and viscosity measurements, as well as thermal denaturation experiments. The absorption spectra indicated that the complexes intercalate tightly between the base pairs of the DNA with intrinsic DNA binding constants of 1.8 × 10(4) M(-1) for (1) and 3.7 × 10(4) M(-1) for (2) in 5 mM Tris-HCl/50 mM NaCl buffer at pH 7.2, respectively. The enhancement in the relative viscosity of DNA on binding to the ligand supports the proposed DNA binding modes. The oxidative cleavage activity of complexes (1) and (2) were carried out on double-stranded pUC19 circular plasmid DNA using gel electrophoresis. The complexes show significant nuclease activity.

Kinetics of ozone-initiated oxidation of textile dye, Amaranth in aqueous systems.

The ozone facilitated oxidation mechanism of water soluble azo anionic dye, amaranth (Am) was investigated monitoring the depletion kinetics of the dye spectrometrically at 521 nm. The oxidation kinetics of the dye by ozone was studied under semi-batch conditions, by bubbling ozone enriched oxygen through the aqueous reaction mixture of dye, as function of flow rate, ionic strength, [O(3)] and pH variations. With excess concentration of ozone and other reagents and low [amaranth], reaction followed pseudo-first-order kinetics with respect to the dye. Added neutral salts had marginal effect on the reaction rate and the variation of pH from 7 to 2 and 7 to 12 exerted only small increases in the reaction rate suggesting molecular ozone possibly is the principle reactive species in oxidation of dye. The reaction order with respect ozone was near unity and it varied slightly with pH and flow rate variations. The overall second-order rate constant for the reaction was (105 ± 4) M(-1) min(-1). The main oxidation products immediately after amaranth decolorization were identified. The reaction mechanism and overall rate law were proposed. After spiking the seawater, river water and wastewaters with Amaranth dye, the reaction rates and trends in BOD and COD under control and natural conditions were investigated. The rate of depletion of the dye in natural waters was relatively lower, but the ozonation process significantly decreased both the BOD and COD levels.

Impact of soil quality on elemental uptake by, and distribution in, Colocasia esculenta (Amadumbe), an edible root.

In this study the elemental distribution of selected essential (Ca, Mg, Al, Mn, Cu, Fe, Co, Cr, Zn, Ni and Se) and the non-essential (Pb, Hg and As) elements were determined in the bulb and peel of Amadumbe (Colocasia esculenta) samples from eight different sites in KwaZulu-Natal, South Africa. The concentration of Se and As in the soil and in the Amadumbe bulbs were below the detection limit of 0.09 µg g⁻¹. The total and bioavailable concentrations of the elements in conjunction with pH, soil organic matter (SOM) and cation exchange capacity (CEC) were determined in the soil samples from the eight sites. Statistical analysis was done to evaluate the impact of soil quality parameters on the chemical composition of the Amadumbe root. The results show accumulation or exclusion of certain elements by the bulb as evidenced by the noticeable increase or decrease of the concentrations of elements, respectively. Ca and Mg were found to be major elements in the range (2000-12000 µg g⁻¹), whilst Mn, Zn, Fe and Al were found to be minor elements in the range (20-400 µg g⁻¹). A general trend observed was that the plant favours the absorption of Zn over Cu. A positive correlation between Mg & Ca, Cu & Fe and Co & Ni was also observed. Statistical analysis revealed that the plant tended to accumulate Mg, Ca, Co, Cr and Pb whilst it excluded Hg and Fe, to a lesser extent.

Synthesis, DNA binding, and oxidative cleavage studies of Fe(II) and Co(III) complexes containing bioactive ligands.

The two complexes containing bioactive ligands of the type and [Fe(L)] (PF(6))(2) (1) (where L = [1-{[2-{[2-hydroxynaphthalen-1-yl)methylidine]amino}phenyl)imino] methyl}naphthalene-2-ol]) and [Co(L(1)L(2))] (PF(6))(3) (2) (where L(1)L(2) = mixed ligand of 2-seleno-4-methylquinoline and 1,10-phenanthroline in the ratio 1:2, respectively) were synthesized and structurally characterized. The DNA binding property of the complexes with calf thymus DNA has been investigated using absorption spectra, viscosity measurements, and thermal denaturation experiments. Intrinsic binding constant K(b) has been estimated at room temperature. The absorption spectral studies indicate that the complexes intercalate between the base pairs of the CT-DNA tightly with intrinsic DNA binding constant of 2.8 × 10(5) M(-1) for (1) and 4.8 × 10(5) M(-1) for (2) in 5 mM Tris-HCl/50 mM NaCl buffer at pH 7.2, respectively. The oxidative cleavage activity of (1) and (2) were studied by using gel electrophoresis and the results show that complexes have potent nuclease activity.

Oxidation of toluidine blue by chlorite in acid and mechanisms of the uncatalyzed and Ru(III)-catalyzed reactions: a kinetic approach.

The complex mechanism of the uncatalyzed and Ru(III)-catalyzed oxidation of toluidine blue [(7-amino-8-methylphenothiazin-3-ylidene)dimethyl ammonium chloride, TB(+)Cl(-)] (λ(max) = 626 nm) by acidic chlorite is elucidated by a kinetic approach. Both the uncatalyzed and catalyzed reactions had a first-order dependence on the initial ClO(2)(-) and H(+) concentrations ([ClO(2)(-)](0) and [H(+)](0), respectively). The catalyzed reaction had a first-order dependence on the initial Ru(III) concentration ([Ru(III)](0)). The overall reaction of toluidine blue and chlorite ion was as follows: TB(+) + 5ClO(2)(-) + H(+) = P + 2ClO(2) + 2HCOOH + 3Cl(-) + H(2)O, where P is (7-amino-8-methyl-5-sulfoxophenothiazin-3-ylidene)amine. Consistent with the experimental results, the pertinent reaction mechanisms are proposed.

Titrimetric and photometric methods for determination of hypochlorite in commercial bleaches.

Two methods, simple titration and photometric methods for determination of hypochlorite are developed, based its reaction with hydrogen peroxide and titration of the residual peroxide by acidic permanganate. In the titration method, the residual hydrogen peroxide is estimated by titration with standard permanganate solution to estimate the hypochlorite concentration. The photometric method is devised to measure the concentration of remaining permanganate, after the reaction with residual hydrogen peroxide. It employs 4 ranges of calibration curves to enable the determination of hypochlorite accurately. The new photometric method measures hypochlorite in the range 1.90 x 10(-3) to 1.90 x 10(-2) M, with high accuracy and with low variance. The concentrations of hypochlorite in diverse commercial bleach samples and in seawater which is enriched with hypochlorite were estimated using the proposed method and compared with the arsenite method. The statistical analysis validates the superiority of the proposed method.

Ozone-initiated disinfection kinetics of Escherichia coli in water.

The effect of ozonation on the rate of disinfection of Escherichia coli was investigated as a function of ozone concentration, ozonation duration and flow rates. Ozone was generated in situ using Corona discharge method using compressed oxygen stream and depending on the oxygen flux the ozone concentrations ranged from 0.91-4.72 mg/L. The rate of disinfection of all the three microbes followed pseudo-first-order kinetics with respect to the microbe count and first order with respect to ozone concentration. The influence of pH and temperature the aqueous systems on the rate of ozone initiated disinfection of the microbe was investigated. The inactivation was faster at lower pH than at basic pH. Molecular ozone is found more effective in disinfection than hydroxyl radicals. Two reported mechanisms for antimicrobial activity of ozone in water systems from the literature are discussed. Based on the experimental findings a probable rate law and mechanism are proposed. Ozonation of natural waters significantly decreased the BOD levels of the control and microbe contaminated waters.