Acid Form Research Articles

Abstract 4136448: A Novel Cardiomyocyte Targeting Peptide Enhances Calcium Handling

Introduction: Intracellular calcium handling plays a central role in cardiac contractility and relaxation. Genes such as the Ca 2+ -ATPase pump (SERCA2a) and the Dihydropteridine reductase (DHPR) enzyme are especially important in the cycling of intracellular calcium. As prior research has established a link between treatment with our cardiac targeting peptide (CTP: a 12-amino acid, cardiomyocyte-specific cell penetrating peptide) and upregulation of calcium-handling genes such as SERCA2a and DHPR, we hypothesized that treatment with our novel hybrid cardiac targeting peptide (hCTP: positions #3 and 11 replaced with the D-enantiomer form of the amino acids) will improve intracellular calcium handling in human cardiomyocytes (CMCs) by increasing expression of key calcium handling genes instrumental in sequestering calcium in diastole and lowering cytosolic levels. Methods: To test hCTP’s calcium handling abilities, CMCs were plated on day 1 and allowed to settle for 24 hours, after which they received daily treatment with various concentrations of hCTP (1-25µM) for three days. On day 5, cells underwent either intracellular calcium measurements using the FLIPR 6 Calcium assay or were prepared for western blotting. Western blotting was performed to determine the protein concentrations of SERCA2a and DHPR, as compared to a GAPDH control. To test hCTP’s intrinsic calcium handling abilities, various concentrations of hCTP were mixed with a constant amount of elemental calcium dissolved in water. After 20 min at 37 o C, the concentration of free Ca 2+ was measured with an ABL90 Flex Plus radiometer. Results: In CMCs, treatment with hCTP led to a decrease in cytosolic calcium in a dose dependent fashion; concentrations as low as 1µM led to a significant decrease in cytosolic calcium (p< 0.0001 for all groups). Western blots performed on the treated CMCs revealed an increase in expression of both DHPR and SERCA2a, normalized to GAPDH control. Outside of the cellular environment, hCTP did not appear to display inherent calcium sequestring properties, suggesting that improvements in calcium handling are due to upregulation of gene expression. Conclusion: hCTP appears to lower cytosolic calcium and improve calcium handling through upregulation of SERCA2a and DHPR. Our data indicates that hCTP is worth pursuing as a stand-alone, cardio-selective therapy for cardiomyopathies involving calcium mishandling.

Phenolic Acids and Their Relationship to Nutritional and Technological Grain Parameters of Durum Wheat Under Variable Treatment Intensity in Central European Conditions

The objective of this two-year study was primarily the evaluation of the free and the bound forms of phenolic acids and phenolic aldehydes (PAAs) in grains of four selected cultivars of spring durum wheat subjected to three treatment intensities (GD—Green Deal, BT—Basic and IT—Intensive). All treatments included a common basic level and different spring production levels of nitrogen fertilisation (0 kg N in the case of GD; 30 kg N in the case of BT; and 60 kg N in the case of IT). Pesticide applications included herbicides and insecticides in both the BT and IT treatments, which were supplemented by combinations of fungicide and morphoregulator in the IT treatment. The GD treatment included only basic nitrogen, herbicide protection, and the application of a biostimulator (ExelGrow). The spring durum wheat cultivars subjected to testing were cultivated under Central European conditions, specifically in the Czech Republic’s central Bohemian region. UHPLC-ESI-MS/MS was used for the detection and accurate quantification of PAAs. In parallel, 12 other nutritional and basic technological parameters of the cereal were evaluated. Nine bound and seven free forms of PAAs were quantified in the analysed cereal samples. Bound forms of PAAs were dominant, accounting for 99.4% of total PAAs. Considering single PAAs, ferulic acid was the most abundant, accounting for 87% of the total bound PAAs. Interestingly, year and treatment intensity were the key factors in the variability of both free and bound PAAs, but these factors had different effects on bound PAAs. Under low nitrogen conditions, plants responded with an increase in free PAAs in particular, as well as in three bound PAAs. Unfavourable weather conditions, combined with the presence of biotic factors (e.g., Fusarium infections), significantly influenced the increase in both PAA groups, with the exception of free p-coumaric acid. PCA analysis confirmed close relationships between PAAs within both categories (free and bound). Subsequent correlation analysis further revealed that the immunoreactive gluten component (G12) exhibited a high negative correlation with the dominant ferulic acid (r = −0.70) and sinapic acid (r = −0.68). Additionally, moderate negative correlations were observed between four bound phenolic acids and grain hardness (r = −0.48–−0.60).

Sialic Acids and Cancer: Pathophysiological Association between Metastatic Progress and Treatment

Abstract: Neoplasm metastasis is a multi-step process with a high rate of cancer mortality (>60%). Several complex pathogenesis pathways and key therapeutic targets are unclear to us now. To change this scenario, effective drug targets and underlying mechanisms should be found, and high-quality metastasis treatment should be supported. Aberrant tumor sialylation was proposed as a putative drug target candidate to bridge the gaps between metastatic spread and drug responses (genetic, molecular, and animal models). More recently, several promising therapeutic mechanisms and benefits against neoplasm metastasis have been observed by potential association for the target of higher levels and diverse forms of sialic acids (sia) analogues, antigens, glycan, sialylation enzymes, and conjugates. Subsequently, sia-related pathophysiology in cancer diagnosis, prognosis, and therapeutic responses has been reviewed. New algorithms, computation, experimental evaluations, and modern technology might see breakthroughs in therapeutic targets, responses, and immune regulation via sialylation enzymes, associated genes, different glycol conjugates, and other hallmarks of cancer.

PHARMACOKINETIC STUDY OF HY-FOLIC® AND FOLIC ACID IN HEALTHY VOLUNTEERS

Objective: HY-FOLIC® is the active form of Folic Acid (FA) produced by PT Simex Pharmaceutical Indonesia containing (6S)-5-Methyltetrahydrofolate (5-MTHF). We evaluated the pharmacokinetic profiles of HY-FOLIC® versus FA after single oral administration in healthy volunteers. Methods: A randomized, open-label, 2-way crossover, single-dose design was conducted on 12 healthy subjects with two steps. In the first step, 6 subjects were given 1100 mcg of HY-FOLIC®(1.3 μmol), and 6 subjects were given an equimolar dose of 600 mcg of FA (1.3 μmol) in a fasting condition. Blood samples were taken before, and at 1, 2, 3, 4, 5, 6, 7, and 8 h after administration of products for measurement of peak concentration (Cmax), the Area Under the Curve at t-time (AUCt) and infinite time (AUCinf). After a washout period of 14 d, the same procedure was repeated in which the first 6 subjects received FA, and the second 6 subjects received HY-FOLIC®. Pharmacokinetic data of 5-MTHF and Unmetabolized Folic Acid (UMFA) were compared with paired t-tests. Results: Cmax of 5-MTHF (mean±SD) following administration of HY-FOLIC®and FA were 46.91+28.16 vs 22.61+15.73 nmol/l, respectively (p=0.000); the AUCt were 214.47+183.46 vs 112.93+112.11 h. mmol/l (p=0.001). Conversely, Cmax of UMFA were 9.49+7.89 vs 21.97+14.79 nmol/l (p=0.003); AUCt 33.29+39.34 vs 78.16+58.93 h. nmol/l (p=0.001). Conclusion: HY-FOLIC®is much more bioavailable than FA as indicated by much higher Cmax and AUCt of the active form of 5-MTHF.

Diammonium glycyrrhizinate alleviates iron overload-induced liver injury in mice via regulating the gut-liver axis

BackgroundEvidence indicates a close association between iron overload (IO) and the pathogenesis of chronic liver diseases, highlighting the potential for interventions targeted at IO to impede or decelerate the progression of chronic liver diseases. Diammonium glycyrrhizinate (DG), the medicinal form of glycyrrhizic acid, a principal constituent of licorice, has been clinically employed as a hepatoprotective agent; however, its protective effect against IO-induced liver injury and underlying molecular mechanisms remain elusive. PurposeThe aim of the present study is to investigate the hepatoprotective effect of DG against IO-induced liver injury with a focus on the gut-liver axis. Study design and methodsAnimal models of IO-induced liver injury and DG treatment have been established in vivo. Iron deposition, liver injury, intestinal barrier damage, and liver inflammation were assessed in mice treated with iron dextran or DG. The microbiome composition in feces was analyzed using 16S rRNA full-length sequencing. Bile acids (BAs) profiles in feces were detected by UPLC-Q-TOF-MS technique, and the expression levels of receptors, enzymes or transporters involved in BAs metabolism were also determined. ResultsDG partially reduced the iron deposition and the levels of ferrous ion in the livers of mice with IO, thereby mitigating oxidative damage. DG also improved gut microbiota dysbiosis, repaired intestinal barrier damage, inhibited endotoxin translocation to the liver, and subsequently suppressed TLR4/NF-κB/NLRP3 pathway-mediated liver inflammation caused by IO. Moreover, DG modulated BAs metabolism disorder in IO mice, reducing the accumulation of BAs in the liver. ConclusionDG alleviates IO-induced liver injury in mice by regulating the gut-liver axis. This study provides novel insights into the underlying mechanisms through which DG ameliorates liver injury caused by IO.

Effects of Different Technological Forms of the Perilla frutescens in the Diet on Ruminal Fermentation, Milk and Plasma Fatty Acid Composition, Ruminal Biohydrogenation and Milk Quality in Dairy Goats.

Fatty acids can be protected by changing their structure or form against microbial activity, and the different forms of fatty acids can modulate the ruminal biohydrogenation rate and contribute to the desired fatty acid profile in milk fat. The study investigated the effects of perilla (Perilla frutescens) dietary supplementation in the diet in different technological forms (seed, oil and formaldehyde-treated oil) on milk, plasma and ruminal fatty acid composition, and milk quality in lactating goats. The four dietary treatments consisted of (1) no supplementation, basal diet (CON); (2) perilla supplementation as seed at 44.7g/kg (consisting of 20g/kg oil (PS)); (3) perilla supplementation as oil at 20g/kg (PO); (4) perilla supplementation as formaldehyde treated oil at 20g/kg (protected perilla oil [PPO]). The experiment was implemented in a double 4×4 Latin square trial design, and sampling was carried out for 7 days after 21 days of adaptation. Performance parameters were not affected by P. frutescens supplementation to the diet. PO decreased milk fat, whereas PPO increased milk fat. Milk cholesterol was not affected by P. frutescens dietary supplementation. Perilla oil supplementation in different forms to the diet did not affect ruminal pH, VFA and methane production. Perilla oil supplementation in different forms to the diet did not also affect the concentration of blood serum glucose, cholesterol and non-esterified fatty acids. Perilla supplementation to the diet increased the milk conjugated linoleic acid (CLA), C18:3n-3, C22:5n-3, C20:5n-3, C22:6n-3 and polyunsaturated fatty acid (PUFA) concentrations, and PPO group showed the greatest values. Ruminal palmitic (C16:0) acid was decreased, and in perilla groups, stearic acid (C18:0) concentration had the lowest, and ruminal c-9, t-11 CLA concentration had the highest value in PPO. It has been found that the most effective form of perilla oil in increasing milk quality is that with formaldehyde treatment (protected form). Perilla oil, which is a rich source of omega 3 in the diet, can be used to increase milk quality in goats without adversely affecting performance, ruminal fermentation and blood parameters.

Silver-Tungsten Induced Codeposition: Influence of pH and Carboxylic Acid Form in a DMH-based Electrolyte

Silver-tungsten coatings were successfully electrodeposited on platinum and copper substrates from a non-toxic 5.5-dimethylhydantoin electrolyte at low pH and two different carboxylic acid forms: citrate or tartrate. Tungsten contents remain at low levels compared to former works, but close to the values considered as optimal for functional properties without having to recourse to controversial substances such as thiourea. Electrochemical studies by linear sweep voltammetry allow to distinguish two typical behaviors and give interesting insight into the induced codeposition mechanism. Silver-tungsten codeposition only occurred at pH 2.0 and 3.5 using citrates and at pH 2.0 using tartrates, corresponding to the forms H3Cit, H2Cit-2, and H2Tar, respectively. No silver-tungsten reduction was possible with less than two protonated carboxyl groups on either tartrate or citrate ions. Separate silver and tungsten lattice are both present in the resulting alloy. Grain and crystallite sizes were observed by SEM. XPS investigations show that for our low W content alloys, silver is found to be metallic whereas tungsten is present in oxide form. The carbon peaks and also gaps between peaks when N is absent indicate that citrates are present in the coating, unlike DMH.

Multifunctional hybrid films made from CoT3OTx4 and CoFeT2OT4 nanoparticles inside a poly 3-hydroxybutyrate matrix and study of their impact in methyl orange photodegradation.

This work aims to produce hybrid materials with potential applications in dye photodegradation. Therefore, hybrid films were obtained by incorporating cobalt (II, III) oxide (Co3O4) or cobalt ferrite (CoFe2O4) nanoparticles (NPs) with 18 ± 1.6 nm and 26 ± 1.3 nm, respectively, into a poly 3-hydroxybutyrate (P3HB) polymeric matrix. The Co3O4@P3HB and CoFe2O4@P3HB hybrid films were fabricated by solvent casting in a ratio of 85 mg to 15 mg (P3HB-NPs). Different spectroscopic and microscopy techniques characterized the Co3O4 and CoFe2O4 NPs and the P3HB, Co3O4@P3HB and CoFe2O4@P3HB films. The optical band gap for Co3O4 and CoFe2O4 NPs was estimated from their diffuse reflectance spectra (DRS) around 2.5 eV. X-ray diffraction (XRD) of the hybrid films revealed that the nanometric sizes of the Co3O4 and CoFe2O4 nanoparticles incorporated into the P3HB are preserved. The magnetic hysteresis curve of CoFe2O4 nanoparticles and CoFe2O4@P3HB film showed a ferromagnetic behaviour at 300 K. Transmission electron microscopy (TEM) confirmed the formation of nanocrystals, and scanning electron microscopy (SEM) provided evidence for the successful incorporation of the NPs into the P3HB matrix. The surface roughness and hydrophilicity of the hybrid films are increased compared to the P3HB film. The impact of the nanoparticles and the hybrid films on the photodegradation of methyl orange (MO) in its acidic form was studied. The photodegradation tests were carried out by direct sunlight exposure. The CoFe2O4@P3HB hybrid film achieved 85% photodegradation efficiency of a methyl orange solution of 20 ppm after 15 minutes of exposure to sunlight. After 30 minutes of exposure to sunlight, the nanoparticles and the hybrid films reached about 90% of the MO degradation. The results suggest that combining nanoparticles with the polymer significantly enhances photodegradation compared to isolated nanoparticles.

Hays of Novel-Improved Legume Cultivars: Phytochemical Content and Nutritional Value.

The imperative need to produce safe foodstuffs using environmentally sustainable practices has highlighted the incorporation of legumes in human and animal diets as an emerging nutritional staple. Since legumes comprise a family of plants known to display an extensive agricultural diversity with significant bioactivities, we report herein the exploitation outcome of the nutritional and bio-functional content of hay, derived from the post-harvest aerial parts of eight novel-improved Greek cultivars belonging to the following six taxa: Larthyrus sativus L., Medicago sativa L., Cicer arietinum L., Pisum sativum L., Vicia faba L., and Phaseolus vulgaris L. In specific, the phytochemical content of their hay extracts was screened against the presence of 37 fatty acids and 67 polyphenols using, respectively, GC-FID and LC-MS/MS instruments, while the determination of their total phenolic and tannin contents was achieved with spectrophotometric methods. In this respect, the presence of 26 different fatty acids was detected of which the acids linoleic, linolenic and palmitic were traced in all extracts in concentrations exceeding the 10 mg/g, while the oleic acid was determined as the major component of C. arietinum (77.58 mg/g), V. faba (36.11 mg/g), and L. sativus (12.89 mg/g) extracts. In addition, 30 different phenolics were traced as extracts' components with the most abundant the molecule of isoquercetin, which was present in six extracts and isoliquiritigenin, calycosin, and chlorogenic acid which were detected in five extracts. Finally, the antioxidant properties of the extracts were evaluated by performing both DPPH• and FRAP assays, which highlighted the V. faba extract as the most potent in both tests, followed by the extracts of P. sativum and P. vulgaris. Results herein are indicative of the significant advances achieved, for the improvement of investigated plant cultivars with respect to their utilization as nutritional crops, since these novel cultivars hays have been found to contain significant amounts of essential nutrients in the form of fatty acids along with bioactive ingredients in the form of polyphenols, while simultaneously they were determined as deprived of tannins that constitute essential anti-nutritional factors.

Development and Validation of an optimized HPLC-UV analytical method for the quantification of 5-Methyltetrahydrofolate (Active Folate) in dietary Supplements: Application to commercial tablets and capsules

5-MTHF is the active form of folic acid, and it is provided as a dietary supplement in the market. Therefore, in this study we provide a new, simple and economic HPLC-UV analysis method to quantify 5-MTHF in dietary supplement. A new HPLC-UV method was developed and validated for the quantification of 5-methyltetrahydrofolate in dietary supplements. The method was optimized in terms of chromatographic conditions, including the mobile phase composition, chromatographic column, and the sample preparation diluent using ascorbic acid. A combination of ammonium acetate buffer with methanol (90:10) was the optimal mobile phase, achieving a retention time of approximately 11.4 min on C18 column with good column performance (N = 6786, Asymmetry = 1.03). The method was validated for selectivity, linearity, precision, accuracy, and robustness. The calibration curve was linear (r2 > 0.999) over the concentration range of 1.20 to 4.80 µg/mL. Precision was demonstrated with RSD% values ranging from 1.38 % to 2.90 % for intra-day precision and 0.96 % to 2.61 % for inter-day precision. Accuracy was confirmed with recovery values between 96.5 % and 110.6 % for spiked samples. To demonstrate the method’s applicability, ten brands of 5-MTHF dietary supplements were collected from local pharmacies. Assay results showed significant variability, with four brands having contents below the acceptable range (90–110 % of labeled contents) and two brands exceeding this range. The stability of 5-MTHF in these products appeared to be formula-dependent, emphasizing the need for regulatory revisions to mandate stability testing for dietary supplements.

Folates, bacteria and ageing: insights from the model organism C. elegans in the study of nutrition and ageing.

The relationship between nutrition and ageing is complex. The metabolism and synthesis of micronutrients within the gut microbiome can influence human health but is challenging to study. Furthermore, studying ageing in humans is time-consuming and difficult to control for environmental factors. Studies in model organisms can guide research efforts in this area. This review describes how the nematode Caenorhabditis elegans can be used to study how bacteria and diet influence ageing and inform follow-on studies in humans. It is known that certain bacteria accelerate ageing in C. elegans. This age-accelerating effect is prevented by inhibiting folate synthesis within the bacteria, and we propose that in the human microbiome, certain bacteria also accelerate ageing in a way that can be modulated by interfering with bacterial folate synthesis. Bacterial-derived folates do not promote ageing themselves; rather, ageing is accelerated by bacteria in some way, either through secondary metabolites or other bacterial activity, which is dependent on bacterial folate synthesis. In humans, it may be possible to inhibit bacterial folate synthesis in the human gut while maintaining healthy folate status in the body via food and supplementation. The supplement form of folic acid has a common breakdown product that can be used by bacteria to increase folate synthesis. Thus, supplementation with folic acid may not be good for health in certain circumstances such as in older people or those with an excess of proteobacteria in their microbiome. For these groups, alternative supplement strategies may be a safer way to ensure adequate folate levels.

Diammonium glycyrrhizinate ameliorates alcohol-induced liver injury by reducing oxidative stress, steatosis, and inflammation

Alcohol-induced liver injury (ALI) is a serious global health issue. Diammonium glycyrrhizinate (DG), a pharmaceutical form of glycyrrhizic acid, has been reported to have anti-inflammatory and anti-oxidative stress properties. We investigated the potential hepatoprotective effects of DG against ALI and explored the mechanisms of it. In vivo, C57BL/6J mice were used to investigate the protective effect of DG on ALI induced by chronic plus binge alcohol exposure. In vitro, AML-12 cells were applied to evaluate the role of DDX5 in the hepatic protection of DG and explore the possible mechanism of STAT1 activation regulated by DDX5. The results showed that DG significantly alleviated liver injury, inflammation, and lipid deposition in hepatocytes. It also beneficially influenced oxidative stress dysregulation. RNA-seq expression in mouse liver tissue indicated that Dead-box helicase 5 (DDX5) might be a potential target of DG. Compared with the control group, the expression of DDX5 decreased significantly in the ethanol-fed group, while DDX5 was restored in the DG treatment group. In addition, the protective effects of DG against ALI were impaired by DDX5 deficiency. DDX5 inhibited the phosphorylation of signal transducer and activator of transcription 1 (STAT1) by recruiting the protein inhibitor of activated STAT1 (PIAS1) to STAT1. The protective effect of DG against ALI associated with oxidative stress, steatosis, and inflammation was probably via regulating the DDX5/STAT1 axis.

Cellulose Acetates in Hydrothermal Carbonization: A Green Pathway to Valorize Residual Bioplastics.

Bioplastics possess the potential to foster a sustainable circular plastic economy, but their end-of-life is still challenging. To sustainably overcome this problem, this work proposes the hydrothermal carbonization (HTC) of residual bioplastics as an alternative green path. The focus is on cellulose acetate - a bioplastic used for eyewear, cigarette filters and other applications - showing the proof of concept and the chemistry behind the conversion, including a reaction kinetics model. HTC of pure and commercial cellulose acetates was assessed under various operating conditions (180-250 °C and 0-6 h), with analyses on the solid and liquid products. Results show the peculiar behavior of these substrates under HTC. At 190-210 °C, the materials almost completely dissolve into the liquid phase, forming 5-hydroxymethylfurfural and organic acids. Above 220 °C, intermediates repolymerize into carbon-rich microspheres (secondary char), achieving solid yields up to 23 %, while itaconic and citric acid form. A comparison with pure substrates and additives demonstrates that the amounts of acetyl groups and derivatives of the plasticizers are crucial in catalyzing HTC reactions, creating a unique environment capable of leading to a total rearrangement of cellulose acetates. HTC can thus represent a cornerstone in establishing a biorefinery for residual cellulose acetate.

P57Kip2 Phosphorylation Modulates Its Localization, Stability, and Interactions.

p57Kip2 is a member of the cyclin-dependent kinase (CDK) Interacting Protein/Kinase Inhibitory Protein (CIP/Kip) family that also includes p21Cip1/WAF1 and p27Kip1. Different from its siblings, few data are available about the p57Kip2 protein, especially in humans. Structurally, p57Kip2 is an intrinsically unstructured protein, a characteristic that confers functional flexibility with multiple transient interactions influencing the metabolism and roles of the protein. Being an IUP, its localization, stability, and binding to functional partners might be strongly modulated by post-translational modifications, especially phosphorylation. In this work, we investigated by two-dimensional analysis the phosphorylation pattern of p57Kip2 in different cellular models, revealing how the human protein appears to be extensively phosphorylated, compared to p21Cip1/WAF1 and p27Kip1. We further observed clear differences in the phosphoisoforms distributed in the cytosolic and nuclear compartments in asynchronous and synchronized cells. Particularly, the unmodified form is detectable only in the nucleus, while the more acidic forms are present in the cytoplasm. Most importantly, we found that the phosphorylation state of p57Kip2 influences the binding with some p57Kip2 partners, such as CDKs, LIMK1 and CRM1. Thus, it is necessary to completely identify the phosphorylated residues of the protein to fully unravel the roles of this CIP/Kip protein, which are still partially identified.

Formation and Applications of Typical Basic Protein-Based Heteroprotein Complex Coacervations.

Lactoferrin, lysozyme, and gelatin are three common basic proteins known for their ability to interact with acidic proteins (lactoglobulin, ovalbumin, casein, etc.) and form various supramolecular structures. Their basic nature makes them highly promising for interaction with other acidic proteins to form heteroprotein complex coacervation (HPCC) with a wide range of applications. This review extensively examines the structure, properties, and preparation methods of these basic proteins and delves into the internal and external factors influencing the formation of HPCC, including pH, ionic strength, mixing ratio, total protein concentration, temperature, and inherent protein properties. The applications of different HPCCs based on these three basic proteins are discussed, including the encapsulation of bioactive molecules, emulsion stabilization, protein separation and extraction, nanogel formation, and the development of formulas for infants. Furthermore, the challenges and issues that are encountered in the formation of heteroprotein complexes are addressed and summarized, shedding light on the complexities and considerations involved in utilizing HPCC technology in practical applications. By harnessing the basic proteins to interact with other proteins and to form complex coacervates, new opportunities arise for the development of functional food products with enhanced nutritional profiles and functional attributes.

Orthosilicic acid inhibits human osteoclast differentiation and bone resorption.

Silicon (Si), which is present in the diet in the bioavailable form of orthosilicic acid (OSA) and is detected as a dissolution product of certain bone-substitute materials, is suggested to promote bone health, and enhance bone healing, respectively. Silicon has been shown to stimulate osteoblastic cell differentiation and function, although the effect of Si on human osteoclasts is unclear. The present study investigated the direct effects of Si on human osteoclast differentiation, gene expression, and bone resorption. Human CD14+ monocytes were isolated from buffy coats and cultured with M-CSF and RANKL in medium without or with Si (50 μg/ml; constituting 75% OSA). The effects of Si on osteoclast differentiation were evaluated by TRAP-staining and the expression levels of CtsK, CalcR, TRAP, and DC-STAMP measured by RT-qPCR. The effect of Si on the expression level of AQP9, which encodes a potential Si transporter, was also analyzed. Bone resorption was determined based on the number of resorption pits formed when the RANKL-stimulated monocytes were cultured on bone slices, and by the levels of type I collagen fragments released into the cell culture medium. Silicon significantly inhibited the number of TRAP+ multinucleated cells and the expression of osteoclast related genes but increased the late expression of AQP9. Furthermore, Si significantly inhibited the number of resorption pits and the amount of collagen fragments in the medium when cells were cultured on bone slices. Our results demonstrate that OSA inhibits RANKL-stimulated human osteoclast differentiation, gene expression of osteoclast phenotypic markers, and bone resorption.

Neural network cognitive analysis of accumulation metals by marigold

The article presents the results of studies to assess the effect of humic acids, taken at a concentration of 250 ppm, on the process of induced phytoextraction of heavy metals from soils selected near Norilsk. Phytoxtraction was carried out by different types of marigold plants: Tagetes patula and Tagetes erecta. The studies were carried out in greenhouse conditions under controlled spectral illumination (light culture). The duration of the experiment was 21 days. A short vegetation period was chosen based on the conditions of a short summer period typical for this region, where it is more rational to keep records of the systemic removal of toxicants from contaminated soils by several cycles of their sowing/cutting per season, already at the juvenile phase of ontogenesis. For elemental analysis, the method of atomic emission spectrometry with inductively coupled plasma was used. To assess the level of efficiency of metal accumulation, the authors developed and used the original computing neural network CompNN, which allows calculating the cognitive significance index (CSI) based on empirical data on the accumulation of toxicants, both in shoots and roots of plants. The results of the study showed that the introduction of an organic additive in the form of humic acids into the soil led to inhibition of the growth of the above-ground part of T. patula. As for T. erecta, the rate of accumulation of green plant biomass did not change when humic acids were added. The decrease in the biomass of shoots of T. patula plants is explained by an increase in the accumulation of metals in them by an average of 91.6% for the variants. The content of metals in the shoots of T. erecta under the influence of humic acids, on the contrary, decreased by 17.3% on average. A similar result was observed in relation to the root zone: the trend of change in the fixation of metals for both plant species here was 40.8 and 10.8%, respectively. Calculation of CSI indices also showed that the addition of humic acids in T. patula increases the intensity of metal accumulation from the soil in its biomass in all variants, while in T. erecta, on the contrary, it decreases. The performed cluster analysis demonstrated the fixation of metals in the main buffer zone of plants, and also made it possible to isolate nickel into a separate homogeneous series. With regard to the distribution of this element in the shoots by variants, experience has shown that it has demonstrated here the proximity of convergence with copper. The correlation coefficients of their accumulation with the CSI index in the shoots of both plants were r = 0.82; 0.87 for Cu and r = 0.87; 0.83 for Ni. The proximity of these values indicates the priority nature of the accumulation of these metals in the plant biomass of marigolds, and also characterizes the manifestation of certain interactions between them in contaminated soil by the type of antagonism or synergism.

DFT modeling of the oxygen electroreduction reaction on SiN3-doped carbon nanotubes

The thermodynamic features and mechanism of the electrocatalytic oxygen reduction reaction were studied using the revPBE0-D3(BJ)/Def2-TZVP method on the example of (6,6)-armchair carbon nanotube doped with a tricoordinated silicon atom and nitrogen atoms of pyridinic and graphitic nature. Irreversible oxidation of the silicon center as a result of the formation of stable oxygen-containing adsorbates was shown. It was found that Si-poisoned structures are capable of participating in the catalysis of the target reaction along two- and four-electron routes at high overpotentials. For a nanotube doped simultaneously with pyridinic and graphitic nitrogens the potential possibility of eliminating the silicon atom from the catalyst composition in the form of orthosilicic acid and the participation of a silicon-free nitrogen-doped framework in the oxygen electroreduction reaction, for which the stage of tautomerization of pyridin-2(1H)-one to pyridin-2-ol is the limiting step was shown.

Vapor Phase Electrochemistry 2: Spherical and Spheroidal Air Plasmas

Among the rare meteorological phenomena that exist are long-lived spheroidal air plasmas. Of these, lightning balls are best characterized. Closely related are earth-lights, tornadic lights and Unpredictable Flying Objects (UFOs). Early physicists took all such phenomena to be plasmas and would refer to them as electric fire or fireballs. Many physicists today do not accept that these light emitting objects are plasmas because they neglect a variety of influences that result from chemical change. Stability results mainly from entropy production as an ionized, metastable form of nitrous acid, produced at an air plasma surface, refrigerates the surface through its conversion to the stable acid. It is then oxidized to nitric acid in an aerosol form, which restricts the inflow of air to the plasma surface. This can explain the “ surface tension” of lightning balls early, as hypothesized by Stakhanov (1979). Studies of earth-lights (Teodorani, 2004) imply that these are plasma balls held together by the same forces as those providing mechanical stability to lightning balls. Studies of flame balls in space support this view. UFOs and earth-lights are structured similarly but the plasma components of UFOs can be held together by far stronger forces. Potentially, air plasmas have important technological implications since they are all powered by extracting and using chemical energy from the air. Crucially, this energy can only be extracted from air whose temperature is below 150 C. If air plasmas could be prepared artificially, they would prove invaluable in supplying ample carbon-free electrical energy.

Unveiling the Potential of Phytocannabinoids: Exploring Marijuana’s Lesser-Known Constituents for Neurological Disorders

Cannabis sativa is known for producing over 120 distinct phytocannabinoids, with Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) being the most prominent, primarily in their acidic forms. Beyond Δ9-THC and CBD, a wide array of lesser-known phytocannabinoids, along with terpenes, flavonoids, and alkaloids, demonstrate diverse pharmacological activities, interacting with the endocannabinoid system (eCB) and other biological pathways. These compounds, characterized by phenolic structures and hydroxyl groups, possess lipophilic properties, allowing them to cross the blood–brain barrier (BBB) effectively. Notably, their antioxidant, anti-inflammatory, and neuro-modulatory effects position them as promising agents in treating neurodegenerative disorders. While research has extensively examined the neuropsychiatric and neuroprotective effects of Δ9-THC, other minor phytocannabinoids remain underexplored. Due to the well-established neuroprotective potential of CBD, there is growing interest in the therapeutic benefits of non-psychotropic minor phytocannabinoids (NMPs) in brain disorders. This review highlights the emerging research on these lesser-known compounds and their neuroprotective potential. It offers insights into their therapeutic applications across various major neurological conditions.