The effect of Limosilactobacillus fermentum 2i3 and 0.6% addition of humic substances on production parameters and the immune system of broilers.

The widespread use of antibiotics in the poultry industry as growth promoters has led to the emergence of bacterial resistance, which poses a significant health risk to humans and animals. Substances of natural origin, such as probiotic bacteria and humic substances, can be a promising solution. The aim of this experiment was to study the effect of the administration of a probiotic strain of Limosilactobacillus fermentum 2i3 and/or a new formula of humic substances specifically designed for detoxification on the production parameters, including gene expression of myogenic growth factors and selected parameters of the immune response. We found that production parameters such as feed conversion ratio and weekly weight gain, as well as gene expression of mucin-2 and immunoglobulin A, were positively influenced mainly by the administration of L. fermentum 2i3. Similarly, the percentage of active phagocytes and their absorption capacity as well as the proportions of CD8+ and CD4+CD8+ T-lymphocyte subpopulations were significantly increased. The addition of humic substances, either alone or in combination with probiotics, significantly reduced the aforementioned parameters compared to the control. On the other hand, the relative gene expression for all myogenic growth factors was the highest in the humic group alone. Based on the results obtained, we can confirm the immunostimulating effect of L. fermentum 2i3 administered in drinking water, which also had an impact on important production parameters of broiler meat. On the other hand, in the combined group there was no expected potentiation of the positive effects on the observed parameters.

Gaining insight into the effect of laccase expression on humic substance formation during lignocellulosic biomass composting.

The aim is to enhance lignin humification by promoting laccase activities which can promote lignin depolymerization and reaggregation during composting. 1-Hydroxybenzotriazole (HBT) is employed to conduct laccase mediator system (LMS), application of oxidized graphene (GO) in combination to strengthen LMS. Compared with control, the addition of GO, HBT, and GH (GO coupled with HBT) significantly improved laccase expression and activities (P < 0.05), with lignin humification efficiency also increased by 68.6 %, 36.7 %, and 107.8 %. GH treatment induces microbial expression of laccase by increasing the abundance and synergy of core microbes. The unsupervised learning model, vector autoregressive model and Mantel test function were combined to elucidate the mechanism of action of exogenous materials. The results showed that GO stabilized the composting environment on the one hand, and acted as a support vector to stabilize the LMS and promote the function of laccase on the other. In GH treatment, degradation of macromolecules and humification of small molecules were promoted simultaneously by activating the dual function of laccase. Additionally, it also reveals the GH enhances the humification of lignocellulosic compost by converting phenolic pollutants into aggregates. These findings provide a new way to enhance the dual function of laccase and promote lignin humification during composting. It could effectively achieve the resource utilization of organic solid waste and reduce composting pollution.

Humic substances mediated superior photochemical pollutant conversion on defective TiO2 in environmentally relevant matrices: The key roles of oxygen vacancy in surface interactions, oxidant activation and radical generation.

Ubiquitous humic substances usually exhibit strong interfering effects on target pollutant removal in advanced water purification. This work aims to develop a photochemical conversion system on the nonstoichiometric TiO2 for pollutant removal in environmentally relevant matrices. In this synergistic reaction system, the redox-reactive humic substances and defective oxygen vacancies can serve as the organic electron transfer mediator and the key surface reactive sites, respectively. This system achieves a superior pollutant degradation in real surface water at low oxidant concentrations. Reactive oxygen vacancies on the TiO2 surface and sub-surface are of considerable interest for this photochemical reaction system. By engineering defective oxygen vacancies on high-energy {001} polar facet, the surface and electronic interactions between tailored TiO2 and humic substances are greatly strengthened for the promoted electron transfer and oxidant activation. Rendered by the strong surface affinity and molecular activation, defective oxygen vacancies thermodynamically and dynamically promote reactive chain reactions for free radical formation, including the selective O2 reduction to ·O2- and the H2O2 activation to ·OH. Our findings take new insights into environmental geochemistry, and provide an effective strategy to in-situ boost the humic substances-mediated water purification without secondary pollution. ENVIRONMENTAL IMPLICATION: Humic substances are widely distributed in aquatic environment, thus playing important roles in environmental geochemistry. For example, humic substances can achieve good surface adsorption through electrostatic adsorption, ligand exchange and electronic interactions with typical TiO2 to form reactive ligand-metal charge transfer complexes for pollutant degradation. Inspired by the unique properties of surface and sub-surface oxygen vacancies, the defective TiO2 was designed to refine the humic substances-mediated photochemical reactions. A superior reactivity was measured for pollutant degradation. Our findings provide an effective strategy to boost naturally photochemical decontamination in environmentally relevant matrices.

Using landfill leachate to indicate the chemical and biochemical activities in elevated temperature landfills.

Landfill leachate properties contain important information and can be a unique indicator for the chemical and biochemical activities in landfills. In the recent decade, more landfills are experiencing elevated temperature, causing an imbalance in the decomposition of solid waste and affecting the properties of the landfill leachate. This study analyzes the properties of leachate from two landfills that were experiencing elevated temperature (ETLFs), samples were collected from both elevated temperature impacted and non-impacted areas in each landfill. The accumulation of volatile fatty acids (VFA) in leachates from elevated temperature impacted areas of both landfill sites revealed that methanogenesis was inhibited by the elevated temperature, which was further confirmed by the more acidic pH, higher H/C elemental ratio, and lower degree of aromaticity of the elevated temperature impacted leachates. Also, carbohydrates depletion indicated possible enhancement of hydrolysis and acidogenesis by elevated temperature, which was supported by compositional comparison of isolated acidic species by negative-ion electrospray ionization (ESI) Fourier transform ion cyclotron resonance mass spectrometry (FT-ICRMS) at 21 T derived from both elevated temperature impacted and non-impacted areas in the same landfill site. Furthermore, leachate organics fractionation showed that leachates not impacted by elevated temperature contain less hydrophilic fraction and more humic fraction than elevated temperature-impacted leachates for both ETLFs.

Efficacy of water application of a humic substance, butyric acid, vitamins C, D, and E and/or electrolytes on performance and mortality in health-challenged nursery pigs¹.

Health challenges continue to be rampant in nursery pigs which has led to increased industry-wide mortality trends. Therefore, the objective of these three studies was to evaluate a water supplement (HV; HydraVantage, Kent Nutrition Group, Muscatine, IA) which is a proprietary blend of a humic substance, butyric acid, and vitamins C, D, and E, as well as an electrolyte blend on nursery pig performance and mortality. Experiment 1 consisted of 196 crossbred weanling pigs (7 pigs per pen with 14 pens per treatment) which were randomly allotted by BW to two treatments consisting of control (water for 33 d) or HV at 15 g/L of stock solution and proportioned through a medicator (1:128) for 11 d followed by water for 22 d. There were no performance differences. However, mortality was reduced (P < 0.01) from 6.12% for the control to 0.00% for HV. In experiment 2, there were 488 weanling pigs (6 to 10 pigs/pen with 14 pens per treatment) which were randomly allotted by BW to four treatments in a 34-d trial. Treatment 1 was control (water), and treatments 2 and 4 were HV at 15 g/L of stock solution for 11 and 34 d, respectively. Treatment 3 utilized HV at 15 g/L stock solution during days 0 to 11 with 7.5 g HV/L stock solution utilized during days 11 to 21 followed by water. No performance differences were observed among the four treatments. Mortality was 10.89%, 4.82%, 5.54%, and 7.26% for treatments 1 to 4, respectively, with treatment 1 having a higher mortality (P < 0.05) compared to treatments 2 to 4. In experiment 3, a 2 × 2 factorial study was conducted (7 pigs per pen with 14 pens per treatment) in which the treatments were: 1) water; 2) HV at 15 g/L stock solution for 34 d; 3) electrolytes at 241 g/L stock solution for 34 d; and 4) HV at 15 g/L of stock solution and electrolytes at 226 g/L of stock for 34 d. Overall pen gain tended to be improved (P = 0.09) with supplemental HV. Moreover, mortality was reduced (P = 0.06) by 36% (16.86% mortality for treatments 1 and 3 vs. 10.73% mortality for treatments 2 and 4). Supplemental electrolytes had no effect on mortality. These data suggest that HV has a positive effect by reducing mortality in nursery pigs undergoing health challenges.

The humic substance analogue antraquinone-2, 6-disulfonate (AQDS) enhanced zero-valent iron based autotrophic denitrification: Performances and mechanisms.

Zero-valent iron based autotrophic denitrification (ZVI-AD) has attracted increasing attentions in nitrate removal due to saving organic carbon budget in wastewater treatment, but limited by the low reaction speed, poor electron transfer efficiency as well as the compaction/blocking by iron hydrolysis products. Humic substances (HS) were promising to regulate iron cycle and accelerate electron transfer by serving as electron mediators. In this study, HS analogue, antraquinone-2, 6-disulfonate (AQDS), was added to enhance ZVI-AD process. Results showed that the dosage of AQDS led to a NO3--N removal efficiency of 83.37 ± 3.98% within 96 h, which was 32.28 ± 1.25% higher than that in ZVI-AD system. The corrosion of ZVI and microbially nitrate reduction were both improved at the presence of AQDS. The addition of AQDS enriched the functional species, including autotrophic denitrobacteria namely Thauera and Hydrogenophaga, iron redox-related species namely Ferruginibacter and HS respiration related species namely Flavobacterium. The genes napA and napB related to electron transfer, nirK and nosZ related to the accumulation of intermediate products were also enriched by the addition of AQDS. AQDS addition boosted the electrons flowing to both abiotic and biotic nitrate reduction. Nitrate removal mechanism involved in ZVI-AQDS coupled system was proposed. This study provided an alternative strategy for improving ZVI-AD by HS.

Light-Driven Electron Uptake from Nonfermentative Organic Matter to Expedite Nitrogen Dissimilation by Chemolithotrophic Anammox Consortia.

Nonphotosynthetic microorganisms are typically unable to directly utilize light energy, but light might change the metabolic pathway of these bacteria indirectly by forming intermediates such as reactive oxygen species (ROS). This work investigated the role of light on nitrogen conversion by anaerobic ammonium oxidation (anammox) consortia. The results showed that high intensity light (>20000 lx) caused ca. 50% inhibition of anammox activity, and total ROS reached 167% at 60,000 lx. Surprisingly, 200 lx light was found to induce unexpected promotion of the nitrogen conversion rate, and ultraviolet light (<420 nm) was identified as the main contributor. Metagenomic and metatranscriptomic analyses revealed that the gene encoding cytochrome c peroxidase was highly expressed only under 200 lx light. 15N isotope tracing, gene abundance quantification, and external H2O2 addition experiments showed that photoinduced trace H2O2 triggered cytochrome c peroxidase expression to take up electrons from extracellular nonfermentative organics to synthesize NADH and ATP, thereby expediting nitrogen dissimulation of anammox consortia. External supplying reduced humic acid into a low-intensity light exposure system would result in a maximal 1.7-fold increase in the nitrogen conversion rate. These interesting findings may provide insight into the niche differentiation and widespread nature of anammox bacteria in natural ecotopes.

Humic acids alleviate aflatoxin B1-induced hepatic injury by reprogramming gut microbiota and absorbing toxin.

Aflatoxin B1 (AFB1) is a hepatotoxic fungal metabolite that is widely present in food and can cause liver cancer. As a potential detoxifier, naturally occurring humic acids (HAs) may be able to reduce inflammation and restructure the gut microbiota composition; however, little is known about the mechanism of HAs detoxification as applied to liver cells. In this study, HAs treatment alleviated AFB1-induced liver cell swelling and the infiltration of inflammatory cells. HAs treatment also reinstated various enzyme levels in the liver disturbed by AFB1 and substantially alleviated AFB1-caused oxidative stress and inflammatory responses by enhancing immune functions in mice. Moreover, HAs increased the length of the small intestinal and villus height to restore intestinal permeability, which is impaired by AFB1. In addition, HAs reconstructed the gut microbiota, increasing the relative abundance of Desulfovibrio, Odoribacter, and Alistipes. In vitro and in vivo assays demonstrated that HAs could efficiently remove AFB1 by absorbing the toxin. Therefore, HAs treatment can ameliorate AFB1-induced hepatic injury by enhancing gut barrier function, regulating gut microbiota, and adsorbing toxin.

The reverse function of lignin-degrading enzymes: The polymerization ability to promote the formation of humic substances in domesticated composting.

This study aimed to confirm the ability of lignin peroxidase (LiP) and manganese peroxidase (MnP) in promoting the formation of humic substances (HS) during domesticated composting. Three raw materials with different lignin types were used for composting, including rice straw, tree branches, and pine needles. Results suggested that LiP and MnP activity increased during domesticated composting. But HS formation was only promoted by LiP. The effect of MnP was insignificant, which might be caused by the lack of enzyme cofactors like Mn2+. Meanwhile, bacteria highly associated with LiP and MnP production were identified as core bacteria. Function prediction of 16S-PICRUSt2 showed that the function of core bacteria was consistent with total bacterial functions which mainly promoted compost humification. Therefore, it speculated that LiP and MnP had the ability to promote HS formation during composting. Accordingly, it is a new understanding of the role of biological enzymes in composting.

A data-driven approach for understanding the structure dependence of redox activity in humic substances.

Humic substances (HS) can facilitate electron transfer during biogeochemical processes due to their redox properties, but the structure-redox activity relationships are still difficult to describe and poorly understood. Herein, the linear (Partial Least Squares regressions; PLS) and nonlinear (artificial neural network; ANN) models were applied to monitor the structure dependence of HS redox activities in terms of electron accepting (EAC), electron donating (EDC) and overall electron transfer capacities (ETC) using its physicochemical features as input variables. The PLS model exhibited a moderate ability with R2 values of 0.60, 0.53 and 0.65 to evaluate EAC, EDC and ETC, respectively. The variable influence in the projection (VIP) scores of the PLS identified that the phenols, quinones and aromatic systems were particularly important for describing the redox activities of HS. Compared with the PLS model, the back-propagation ANN model achieved higher performance with R2 values of 0.81, 0.65 and 0.78 for monitoring the EAC, EDC and ETC, respectively. Sensitivity analysis of the ANN separately identified that the EAC highly depended on quinones, aromatics and protein-like fluorophores, while the EDC depended on phenols, aromatics and humic-like fluorophores (or stable free radicals). Additionally, carboxylic groups were the best indicator for evaluating both the EAC and EDC. Good model performances were obtained from the selected features via the PLS and sensitivity analysis, further confirming the accuracy of describing the structure-redox activity relationships with these analyses. This study provides a potential approach for identifying the structure-activity relationships of HS and an efficient machine-learning model for predicting HS redox activities.

Enhanced removal of arsenic and cadmium from contaminated soils using a soluble humic substance coupled with chemical reductant.

Soil washing is an efficient, economical, and green remediation technology for removing several heavy metal (loid)s from contaminated industrial sites. The extraction of green and efficient washing agents from low-cost feedback is crucially important. In this study, a soluble humic substance (HS) extracted from leonardite was first tested to wash soils (red soil, fluvo-aquic soil, and black soil) heavily contaminated with arsenic (As) and cadmium (Cd). A D-optimal mixture design was investigated to optimize the washing parameters. The optimum removal efficiencies of As and Cd by single HS washing were found to be 52.58%-60.20% and 58.52%-86.69%, respectively. Furthermore, a two-step sequential washing with chemical reductant NH2OH•HCl coupled with HS (NH2OH•HCl + HS) was performed to improve the removal efficiency of As and Cd. The two-step sequential washing significantly enhanced the removal of As and Cd to 75.25%-81.53% and 64.53%-97.64%, which makes the residual As and Cd in soil below the risk control standards for construction land. The two-step sequential washing also effectively controlled the mobility and bioavailability of residual As and Cd. However, the activities of soil catalase and urease significantly decreased after the NH2OH•HCl + HS washing. Follow-up measures such as soil neutralization could be applied to relieve and restore the soil enzyme activity. In general, the two-step sequential soil washing with NH2OH•HCl + HS is a fast and efficient method for simultaneously removing high content of As and Cd from contaminated soils.

Modified biochar/humic substance/fertiliser compound soil conditioner for highly efficient improvement of soil fertility and heavy metals remediation in acidic soils.

Fertile and uncontaminated soil with appropriate pH is crucial in terms of the agricultural sustainable development. Herein, a compound soil conditioner containing chitosan modified straw biochar (CBC), kitchen waste compost product-derived humic substance (HS), NPK compound fertiliser (NPK-CF) was prepared to simultaneously adjust acidic soil pH, improve fertility, and immobilize heavy metal. The results exhibited that the best Pb and NH4+ adsorption performance was obtained in CBC with chitosan:biochar of 1:5. Then, the acid soil pH was improved from 5.03 to 6.66 in the presence of CBC/HS (5:5) with 3% addition weight (the mass ratio of conditioner to soil). Meanwhile, compared with the control, the contents of organic matter, available nitrogen, and available phosphorus significantly increased by 52.4%, 92.6%, and 136.3%, respectively. Moreover, Pb was highly efficient immobilised by CBC, and the concentration of Pb in the soil was decreased by 55.2%. The optimal growth trend of ryegrass was obtained in the presence of 3% addition weight (the mass ratio of conditioner to soil) CBC/HS (CBC:HS = 5:5) combined with 60% of the recommended NPK-CF application weight, which was mainly contributed by the improvement of the soil microbial abundance and community structure diversity. The addition of CBC/HS could effectively reduce the addition of NPK-CF and contribute to simultaneous controlling nitrogen loss, releasing phosphorus, immobilising Pb, adjusting pH, improving soil quality and controlling nonpoint pollution.

Ability of aerated compost tea to increase the mobility and phytoextraction of copper in vineyard soil.

Aerated compost tea (ACT) contains soluble humic substances (SHS) that are expected to alter the dynamics and ecotoxicity of Cu in soil. This study investigated the efficiency of ACT in enhancing the mobility and phytoextraction of Cu in vineyard soil. Crimson clover (Trifolium incarnatum L.) was grown on a vineyard soil at three concentrations of Cu (90, 261 and 432 mg kg-1), and supplied (or not) with ACT, then sampled after 56 days to determine the amount of Cu phytoextracted. Soil was extracted with 0.01 M KCl and potentiometric analyses were performed to measure the impact of ACT on the speciation of Cu in the extraction solution. ACT was found to increase the mobility of Cu in the soil by a factor of 3-14 depending on the soil Cu content and on the soil extraction date. The increase in Cu mobility was associated with an increase in absorbance at 254 nm and with a decrease in the free ionic fraction of Cu in the KCl extract, suggesting that Cu was mainly mobilized by the SHS present in the compost tea, and through a ligand-controlled dissolution process. ACT increased Cu phytoextraction at Cu90 and Cu261 by on average 80% thanks to its positive impact on plant growth, and on Cu accumulation in plant shoots, whereas it reduced Cu phytoextraction at Cu432 due to its deleterious effect on plant growth at this soil Cu content. ACT is thus an efficient way to increase the phytoavailability of Cu in soil, but probably should not be used in vineyard soils that are highly contaminated by Cu. To obtain Cu phytoextraction yields in line with the needs of the wine sector, the use of ACT needs to be associated with the cultivation of a Cu-accumulating plant.

Improving the Properties of Magnetite Green Pellets with a Novel Organic Composite Binder.

A novel composite binder (humic acid modified bentonite, HAMB) and two other binders (bentonite and Modified humic acid, MHA) were used to explore the effects of binders on the properties of magnetite green pellets in this study. The results of green pellet properties and drying tests show that the low doses of a humic substance-based binder can achieve the same effect as high doses of bentonite binder. A humic substance-based binder could be a promising organic binder to replace bentonite. Meanwhile, the influence mechanism of adding different binders on the strength of green pellet was discussed, and the relationship between moisture content in the pellet and the compression strength of three binders was determined. A TG-DSC analysis found that the novel composite binder (HAMB) was not a simple mix of humic acid and bentonite, in which a humic substance could change the structure of bentonite and reduce the thermal stability of bentonite, causing the HAMB composite binder to have a high decomposition temperature.

Evaluating differences in humic substances formation based on the shikimic acid pathway during different materials composting.

This study aimed to evaluate differences in humic substance (HS) formation based on the shikimic acid pathway (SAP) during five different materials composting. The results showed that compared with other three materials, gallic acid, protocatechuic acid and shikimic acid of the SAP products in lawn waste (LW) and garden waste (GW) compost decreased significantly. Furthermore, as important indicators for evaluating humification, humic acid and degree of polymerization increased by 39.4%, 79.5% and 21.8%, 87.9% in LW and GW, respectively. Correlation analysis showed that SAP products were strongly correlated with HS fractions in LW and GW. Meanwhile, network analysis indicated that more core bacteria associated with both SAP products and HS were identified in LW and GW. Finally, the structural equation model proved that SAP had more significant contribution to humification improvement in LW and GW. These findings provided theoretical foundation and feasible actions to improve compost quality by the SAP.

Promotion of Nitrogen Fixation of Diverse Heterotrophs by Solid-Phase Humin.

Although biological nitrogen fixation (BNF) proceeds under mild conditions compared to the energy-intensive Haber-Bosch process, the slow kinetics of BNF necessitate the promotion of BNF activity in its practical application. The BNF promotion using purified nitrogenases and using genetically modified microorganisms has been studied, but these enzymes are unstable and expensive; moreover, designing genetically modified microorganisms is also a difficult task. Alternatively, the BNF promotion in non-modified (wild-type) microorganisms (enriched consortia) with humin has been shown, which is a humic substance insoluble at any pH and functions as an extracellular electron mediator. However, the taxonomic distribution of the diazotrophs promoted by humin, the levels of BNF promotion, and the underlying mechanism in BNF promotion with humin remain unknown. In this study, we show that taxonomically diverse heterotrophic diazotrophs, harboring nifH clusters I, II, and III, promoted their BNF by accepting extracellular electrons from humin, based on the characterization of the individual responses of isolated diazotrophs to humin. The reduced humin increased the acetylene reduction activity of the diazotrophs by 194-916% compared to the level achieved by the organic carbon source, causing adenosine triphosphate (ATP) synthesis in the diazotroph cells without increase in the CO2 production and direct electron donation to the MoFe protein of the nitrogenase in the cells without relying on the biological electron transfer system. These would result in BNF promotion in the wild-type diazotroph cells beyond their biochemical capacity. This significant promotion of BNF with humin would serve as a potential basis for sustainable technology for greener nitrogen fixation.

New insights into the distribution and interaction mechanism of microplastics with humic acid in river sediments.

Information on the distribution and interaction of microplastics (MPs) and humic acids (HAs) in river sediment has not been fully explored. This study assessed the distribution and interaction of MPs with HAs at different depths in river sediments. The results delineated that the average abundance of MPs in the 0-10 cm layer (190 ± 20 items/kg) was significantly lower than that in the 11-20 cm and 21-30 cm layers (211 ± 10 items/kg and 238 ± 18 items/kg, respectively). Likewise, the large MP particles mainly existed in the 0-10 cm layer (31.53%-37.87%), while small MP particles were found in the 21-30 cm layers (73.23%-100%). Moreover, HAs in MPs showed a transformation from low molecular weight to high molecular weight with an increase in depth from 0-10 cm to 21-30 cm, which may contribute to the distribution of MPs in the river sediments. These results provide new insight into the migration of MP pollution in river sediments, but further research needs to assess the interaction of MP with HA for mitigating MP pollution in river sediment.

Phosphorus sorption capacity of various iron-organic matter associations in peat soils.

This study was carried out to evaluate the contribution of different types of iron-organic matter associations (Fe-OM) to the phosphorus sorption capacity of peatland. Humic substance (HS) and particulate organic matter (POM) were isolated from peat soils, and different types of iron-organic matter associations (Fe-HS and Fe-POM) were prepared. Then, isothermal adsorption experiments were carried out on the synthesized Fe-OM and iron-contained peat soils. The morphology structure of Fe-HS associations is amorphous like that of ferrihydrite. The theoretical maximum adsorption capacity (Qmax) of Fe-HS associations can reach 36.90 mg/g, which is approximately two times higher than that of ferrihydrite (19.23 mg/g) and ten times higher than that of hematite (3.26 mg/g) and goethite (2.08 mg/g). Both peat soils and POM can strongly complex ferric ions, resulting in improved phosphorus sorption capacity. The Qmax of original peat soil and POM is 2.83 mg/g and 4.31 mg/g, which increased to 7.36 mg/g and 5.89 mg/g, respectively, after complexing ferric ions. Compared to inorganic Fe minerals, the associations of iron and organic matter (HS and POM) contribute more to the phosphorus retention ability of peat soils. However, the formation of Fe-OM associations could not fully explain why the addition of iron increases the phosphorus sorption capacity of peat soil by so much. Iron should also participate in other phosphorus retention processes, which need further exploration and research.

Second-Order Scattering Quenching in Fluorescence Spectra of Natural Humates as a Tracer of Formation Stable Supramolecular System for the Delivery of Poorly Soluble Antiviral Drugs on the Example of Mangiferin and Favipiravir.

In the present work, the methods of dynamic light scattering and fluorescence spectroscopy were applied to study the optical properties of aqueous dilutions of the humic substances complex (HC) as a potential drug delivery system. The supramolecular structures in the humate solution were characterized as monodisperse systems of the submicron range with a tendency to decrease in particle size with a decrease in the dry matter concentration. The slightly alkaline medium (8.3) of the studied aqueous dilutions of HC causes the absence of a pronounced fluorescence maximum in the region from 400 to 500 nm. However, the presence of an analytically significant, inversely proportional to the concentration second-order scattering (SOS) signal at 2λex = λem was shown. In the examples of the antiviral substances mangiferin and favipiravir, it was shown that the use of the humic complex as a drug carrier makes it possible to increase the solubility by several times and simultaneously obtain a system with a smaller particle size of the dispersed phase. It has been shown that HC can interact with mangiferin and favipiravir to form stable structures, which lead to a significant decrease in SOS intensities on HC SOS spectra. The scattering wavelengths, λex/λem, were registered at 350 nm/750 nm for mangiferin and 365 nm/730 nm for favipiravir, respectively. The increments of the scattering intensities (I0/I) turned out to be proportional to the concentration of antiviral components in a certain range of concentrations.

Species-dependent interaction of Gd-based contrast agents with humic substances.

In this study, model experiments regarding species-dependent differences in the interaction of gadolinium-based contrast agents (GBCAs) with humic acids as potential binding partners in the aquatic environment are conducted. For this, the Gd content of different weight fractions obtained via ultracentrifugation of incubation solutions of humic acids with a linear (gadodiamide) and a macrocyclic GBCA (gadobutrol) were analyzed via inductively coupled plasma-mass spectrometry (ICP-MS). This enabled the fractionation of Gd-humic acid adducts and intact GBCAs, since Gd bound to macromolecules would be present in the macromolecular fraction of the filter residue while the low molecular weight Gd species can pass the filter with the filtrate. The Gd concentration in the different weight fractions was determined and a different reaction behavior for the examined GBCAs was observed. 73% of the total Gd amount was present in the macromolecular fraction of the linear GBCA compared to 0.41% in case of the macrocyclic GBCA. Speciation analysis of the macromolecular fractions by size exclusion chromatography-UV-ICP-MS confirmed that Gd-humic acid adducts were formed in case of the linear gadodiamide, but not with the macrocyclic gadobutrol. The findings of this study suggest that humic substance was able to react with the linear GBCA while the macrocyclic GBCA remained stable. Since free Gd ions are toxic, the question remains whether the humic acid bound Gd can be remobilized or if subsequent reactions with other molecules can take place. Furthermore, the persistence of macrocyclic GBCAs towards the humic substances indicates the potential accumulation of these compounds in the environment. However, more experiments regarding other binding partners and long term studies are needed to assess their ultimate fate after their release into the environment.