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The study is the first to examine the combined use of blast-furnace sludge as a source of microelements and converter slag as a soil-deoxidizing agent in oat (Avena sativa L.) cultivation in sod-podzolic soils. It has been established that blast-furnace sludge is a highly dispersed waste, which contains about 50% iron, 7% zinc, and a small amount of calcium, silicon, magnesium, aluminum, and sulfur. Hazardous components such as lead, arsenic, etc., are not detected. Converter slag comprises porous granules up to 3 mm in size, consisting mainly of calcium compounds (CaO, Ca(CO)3, CaSiO3, CaFe2O4) and a small amount of Mn, Al, and Mg trace elements. In a laboratory experiment, blast-furnace sludge increased the germination of oats by 5–10%, regardless of the addition of a deoxidizer (slag), but at the same time suppressed the growth of stem length by a maximum of 18% at 1 g∙kg−1. The addition of slag raised substrate pH and increased the index by 8% at a sludge concentration of 0.1 g∙kg−1. Root length in deoxidizer-free variants increased by 50–60% and with the addition of slag by 27–47%. Root dry mass also increased under the addition of sludge by 85–98%; however, the addition of slag reduced the indicator to the control level. In a field experiment with the combined application of waste, an increase in yield by more than 30% was shown. When soil was treated with slag and sludge, the height of plants increased by an average of 18%. It should be noted that the introduction of waste did not affect the quality of the grain. The use of slag increased the lead content in the soil, which is probably due to the sorption properties of calcium compounds in the slag, since lead was not found in the analyzed waste. Presumably, lead is sorbed by slag from the lower soil horizons, concentrating and immobilizing it in the upper layer. This version is supported by the absence of lead accumulation in straw and oat grain. The zinc-containing sludge increased the content of this element by 33% in the soil, as well as by 6% in straw and by 14% in grain. Thus, we found that the studied metallurgical wastes can be used as nutrients for agriculture, both individually and jointly. Overall, the proposed approach will contribute both to reducing the amount of accumulated waste and to improving the efficiency and sustainability of agricultural production and CO2 sequestration. However, the features of the accumulation of heavy metals in soil and plants under the influence of the analyzed types of waste require more in-depth study, including within the framework of long-term field experiments.

Copper (II) oxide nanoparticles (CuO NPs) attract much attention as a promising antimicrobial agent. We studied the antibacterial properties of three types of CuO NPs against Escherichia coli bacteria: flake-shaped particles with a diameter of 50–200 nm and a thickness of 10–20 nm (CuO-CD synthesized by chemical deposition), spherical particles with a size of 20–90 nm (CuO-EE obtained by electrical explosion), and rod-shaped particles with a length of 100–200 nm and a diameter of 30 × 70 nm (CuO-CS commercial sample). We tested how the shape, size, and concentration of the NPs, and composition of the dispersion medium affected the properties of the CuO NPs. We prepared dispersions based on distilled water, a 0.9% NaCl solution, and the LB broth by Lennox and used Triton X-100 and sodium dodecyl sulfate (SDS) as stabilizers. The concentration of NPs was 1–100 mg L−1. We showed that the dispersion medium composition and stabilizer type had the greatest influence on the antibacterial effects of CuO NPs. We observed the maximum antibacterial effect for all CuO NP types dispersed in water without a stabilizer, as well as in LB broth with the SDS stabilizer. The maximum inhibition of culture growth was observed under the influence of CuO-EE (by 30%) and in the LB broth with the SDS stabilizer (by 1.3–1.8 times depending on the type of particles). In the saline solution, the antibacterial effects were minimal; in some cases, the CuO NPs even promoted bacterial culture growth. SDS increased the antibacterial effects of NPs in broth and saline but decreased them in water. Finally, among the particle types, CuO-CS turned out to be the most bactericidal, which is probably due to their rod-shaped morphology and small diameter. At the same time, the concentration and aggregation effects of CuO NPs in the colloidal systems we studied did not have a linear action on their antibacterial properties. These results can be used in the development of antibacterial coatings and preparations based on CuO NPs to achieve their maximum efficiency, taking into account the expected conditions of their use.

Plant tissue culture is an important tool for accelerated vegetative reproduction of woody plants. To increase the efficiency of this method, it is necessary to search for new growth stimulators and protectors of microshoots. Two-dimensional (2D) nanomaterials are highly promising for applications in medicine and biotechnologies. We have studied the effects of TiS3 nanoribbons with the following mean dimensions: thickness less than 100 nm, length 1–10 μm and width 0.4–1 μm upon poplar × aspen hybrid and downy birch microclones in plant tissue culture. We have found the effectiveness of this particular nanomaterial as a sterilizing and stimulating agent in the initial growth stage and as a rhizogenesis-activating agent in the rooting stage. We analyzed a wide range of TiS3 concentrations in the nutrient media and identified 1.5 and 3 μg/L as optimal. However, concentration-dependent toxic effects manifesting themselves through microclones viability suppression have been discovered in the groups exposed to 6 and 15 μg/L TiS3. We have established that plant reaction to TiS3 treatment is specific for different plant species, i.e., downy birch is generally more tolerant than poplar × aspen hybrid. Here, we propose that the protective and stimulating effects of titanium trisulfide as well as its toxicity in high concentrations can be explained by the release of hydrogen sulfide as a result of aqueous hydrolysis of nanoribbons and its effect on plants. Additional studies are required in order to assess all biological effects produced by TiS3 nanoribbons at further stages of ontogenetic development and to identify the mechanisms of their action.

Long-term recurrent stress is a common cause of neuropsychiatric disorders. Animal models are widely used to study the pathogenesis of stress-related psychiatric disorders. The zebrafish ( Danio rerio ) is emerging as a powerful tool to study chronic stress and its mechanisms. Here, we developed a prolonged 11-week chronic unpredictable stress (PCUS) model in zebrafish to more fully mimic chronic stress in human populations. We also examined behavioral and neurochemical alterations in zebrafish, and attempted to modulate these states by 3-week treatment with an antidepressant fluoxetine, a neuroprotective omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA), a pro-inflammatory endotoxin lipopolysaccharide (LPS), and their combinations. Overall, PCUS induced severe anxiety and elevated norepinephrine levels, whereas fluoxetine (alone or combined with other agents) corrected most of these behavioral deficits. While EPA and LPS alone had little effects on the zebrafish PCUS-induced anxiety behavior, both fluoxetine (alone or in combination) and EPA restored norepinephrine levels, whereas LPS + EPA increased dopamine levels. As these data support the validity of PCUS as an effective tool to study stress-related pathologies in zebrafish, further research is needed into the ability of various conventional and novel treatments to modulate behavioral and neurochemical biomarkers of chronic stress in this model organism.

Widespread, debilitating and often treatment-resistant, depression and other stress-related neuropsychiatric disorders represent an urgent unmet biomedical and societal problem. Although animal models of these disorders are commonly used to study stress pathogenesis, they are often difficult to translate across species into valuable and meaningful clinically relevant data. To address this problem, here we utilized several cross-species/cross-taxon approaches to identify potential evolutionarily conserved differentially expressed genes and their sets. We also assessed enrichment of these genes for transcription factors DNA-binding sites down- and up- stream from their genetic sequences. For this, we compared our own RNA-seq brain transcriptomic data obtained from chronically stressed rats and zebrafish with publicly available human transcriptomic data for patients with major depression and their respective healthy control groups. Utilizing these data from the three species, we next analyzed their differential gene expression, gene set enrichment and protein–protein interaction networks, combined with validated tools for data pooling. This approach allowed us to identify several key brain proteins (GRIA1, DLG1, CDH1, THRB, PLCG2, NGEF, IKZF1 and FEZF2) as promising, evolutionarily conserved and shared affective ‘hub’ protein targets, as well as to propose a novel gene set that may be used to further study affective pathogenesis. Overall, these approaches may advance cross-species brain transcriptomic analyses, and call for further cross-species studies into putative shared molecular mechanisms of affective pathogenesis.

The serotonergic system and in particular serotonin 1A receptor (5-HT1AR) are implicated in major depressive disorder (MDD). Here we demonstrated that 5-HT1AR is palmitoylated in human and rodent brains, and identified ZDHHC21 as a major palmitoyl acyltransferase, whose depletion reduced palmitoylation and consequently signaling functions of 5-HT1AR. Two rodent models for depression-like behavior show reduced brain ZDHHC21 expression and attenuated 5-HT1AR palmitoylation. Moreover, selective knock-down of ZDHHC21 in the murine forebrain induced depression-like behavior. We also identified the microRNA miR-30e as a negative regulator of Zdhhc21 expression. Through analysis of the post-mortem brain samples in individuals with MDD that died by suicide we find that miR-30e expression is increased, while ZDHHC21 expression, as well as palmitoylation of 5-HT1AR, are reduced within the prefrontal cortex. Our study suggests that downregulation of 5-HT1AR palmitoylation is a mechanism involved in depression, making the restoration of 5-HT1AR palmitoylation a promising clinical strategy for the treatment of MDD. Palmitoylation is a post translational modification that regulates GPCR activity. Here the authors show that palmitoylation of 5-HT1AR by the palmitoyltransferase enzyme ZDHHC21 contributes to depression-like behaviour in rodents and might be implicated in major depressive disorder.

Stress-related neuropsychiatric disorders are widespread, debilitating and often treatment-resistant illnesses that represent an urgent unmet biomedical problem. Animal models of these disorders are widely used to study stress pathogenesis. A more recent and historically less utilized model organism, the zebrafish ( Danio rerio ), is a valuable tool in stress neuroscience research. Utilizing the 5-week chronic unpredictable stress (CUS) model, here we examined brain transcriptomic profiles and complex dynamic behavioral stress responses, as well as neurochemical alterations in adult zebrafish and their correction by chronic antidepressant, fluoxetine, treatment. Overall, CUS induced complex neurochemical and behavioral alterations in zebrafish, including stable anxiety-like behaviors and serotonin metabolism deficits. Chronic fluoxetine (0.1 mg/L for 11 days) rescued most of the observed behavioral and neurochemical responses. Finally, whole-genome brain transcriptomic analyses revealed altered expression of various CNS genes (partially rescued by chronic fluoxetine), including inflammation-, ubiquitin- and arrestin-related genes. Collectively, this supports zebrafish as a valuable translational tool to study stress-related pathogenesis, whose anxiety and serotonergic deficits parallel rodent and clinical studies, and genomic analyses implicate neuroinflammation, structural neuronal remodeling and arrestin/ubiquitin pathways in both stress pathogenesis and its potential therapy.

Oak is an important tree species, playing a fundamental role in many forest ecosystems. Obtaining high-quality oak planting material is a actual issue in forest biotechnology. The most promising method for this, in vitro micropropagation, faces a number of problems that can be overcome using a nanobiotechnological approach. In our work, we obtained flaky copper oxide nanoparticles with a particle size of 50–200 nm in diameter and a thickness of 10–20 nm, which were used in the WPN medium at a concentration of 0.75, 1.5, 3, 6, and 15 μg L -1 at the stage of introducing the original red oak material into the in vitro tissue culture. The study demonstrated a dose-dependent antimicrobial effect: seedling sterility increased from 80% (+10% to the control) at 1.5 μg L -1 CuO to 100% at doses of 3 μg L -1 and higher. The maximum survival rate was observed at 3 μg L -1 – 43%, which is 23% higher than the control values. At the multiplication stage, nanoparticles significantly increased plant viability – twice as much in the variant with 3 μg L -1 CuO and 1.7 times when using nanoparticles and phytohormones. The combined use of nanoparticles and hormones increased the seedling height by 1.5 times and the number of additional shoots by 3 times. At the rooting stage, CuO nanoparticles did not show any rhizogenesis-stimulating effect. At the same time, phytohormones and nanoparticles stimulated root formation. At the adaptation stage, a fairly low percentage of surviving and adapted plants was observed in the control variant, while the addition of nanoparticles had a positive effect on plant adaptation. The number of surviving seedlings increased by 15%, the number of adapted ones by 10. Thus, our study showed the prospects of using CuO nanoparticles to improve the biotechnology of clonal micropropagation of red oak. In the future, these results can be used in breeding and obtaining high-quality planting material for this species.

Animal models are widely used to study stress-induced affective disorders and associated with them neuroinflammation and other neuroimmune processes. Here, we examined rat behavioral and hippocampal transcriptomic responses to prolonged chronic unpredictable stress (PCUS), as well as following a 4-week treatment with a classical antidepressant fluoxetine, an anti-inflammatory agent eicosapentaenoic acid (EPA), a pro-inflammatory agent lipopolysaccharide (LPS) and their combinations. Overall, PCUS evoked an anxiety-like behavioral phenotype in rats (corrected by chronic fluoxetine alone or combined with other drugs), EPA was anxiolytic and LPS promoted anxiety in this model. PCUS evoked pronounced transcriptomic responses in rat hippocampi, including >200 differentially expressed genes. While pharmacological manipulations did not affect hippocampal gene expression markedly, Gpr6, Drd2 and Adora2a were downregulated in stressed rats treated with fluoxetine+EPA, suggesting G protein-coupled receptor 6, dopamine D2 receptor and adenosine A2A receptor as potential evolutionarily conserved targets in chronic stress. Overall, these findings support the validity of rat PCUS paradigm as a useful tool to study stress-related affective pathologies and calls for further research probing how various conventional and novel drugs modulate behavioral and neurotranscriptomic biomarkers of chronic stress.Competing Interest StatementThe authors have declared no competing interest.Footnotes* Minor revisions for streamlining the text and improving explanation of specific details.* https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE205325

Serotonergic hallucinogenic drugs potently affect human brain and behavior, and have recently emerged as potentially promising agents in psychopharmacotherapy. Complementing rodent studies, zebrafish (Danio rerio) is a powerful animal model for screening neuroactive drugs, including serotonergic agents. Here, we test ten different N-Benzyl-2-phenylethylamine (NBPEA) derivatives with the 2,4- and 3,4-dimethoxy substitutions in the phenethylamine moiety and the -OCH3, -OCF3, -F, -Cl and -Br substitutions in the ortho position of phenyl ring of N-benzyl fragment, assessing their behavioral and neurochemical effects in adult zebrafish. Overall, substitutions in N-benzyl fragment primarily affected zebrafish locomotion, and in phenethylamine moiety - anxiety-like behavior, also modulating brain serotonin and/or dopamine turnover. We also identified several behavioral clusters, including anxiogenic/hypolocomotor (24H-NBF, 24H-NBOMe and 34H-NBF), behaviorally inert (34H-NBBr, 34H-NBCl and 34H-NBOMe), anxiogenic/hallucinogenic-like (24H-NBBr, 24H-NBCl and 24H-NBOMe(F)), and anxiolytic/hallucinogenic-like (34H-NBOMe(F)) agents. The 24H-NBOMe(F) and 34H-NBOMe(F) also reduced despair-like behavior in zebrafish. The artificial intelligence-driven phenotyping supports association of multiple compounds with NMDA antagonists and/or MDMA, supporting their potential hallucinogenic-like properties, as well as other valuable psychoactive effects. In silico functional molecular activity modelling also supports existing of similarities between studied NBOMes drugs, MDMA, and ketamine. Functional analysis implicates potential involvement of serotonin release stimulating activity, calcium channel (voltage-sensitive) activity, some serotonin receptors activity and variety of psychiatric and neurologic disorders treatments activities. Overall, we report potent neuroactive properties of several novel synthetic N-benzylphenylethylamines in an in vivo vertebrate model system (zebrafish), raising the possibility of their potential use in clinical practice. Competing Interest Statement The authors have declared no competing interest.