Many children and adults who have suffered prenatal hypoxia at an early age develop many serious diseases. This disease is an actual problem of pediatric cardiology and little studied. The aim was to analyze the cardioprotective effect of L-arginine, Thiotriazoline, Angioline and Mildronate on the cardiovascular system of rats after prenatal hypoxia. Methods: The experiments were carried out on 50 female white rats; intraperitoneal sodium nitrite solution was administered daily to pregnant female rats after 16 days at a dose of 50 mg/kg. Control pregnant rats received saline. The offspring were divided into groups: 1 – intact; 2 – the control group of rat pups after PH, daily treated with physiological saline; 3 – 6 groups of rat pups after PH, treated daily from the 1st to the 30th day after birth. Heat shock protein HSP70 was determined by enzyme immunoassay, ST2 Nitrotyrosine, eNOS was observed by ELISA. Results: Angiolin showed a high cardioprotective effect even a month after discontinuation of the drug, and after introduction, the highest decrease in ST2, nitrotyrosine was revealed. Thiotriazoline and L-arginine have an antioxidant effect and a positive effect on eNOS expression. increased the concentration of HSP70. Mildronate increased the expression of eNOS and the concentration of HSP70 in the blood of experimental rats after a course of administration, but did not show an antioxidant effect and did not reduce the concentration of nitrotyrosine. The results obtained indicate the cardioprotective effect of modulators of the NO system with different mechanisms of action of drugs after experienced prenatal hypoxia.

Cabbage (Brassica oleracea L. var. capitata) plays a very important role in the annual national vegetable supply and export trade. In recent years, the cadmium content of agricultural soils has increased. As a result, cabbage yields and quality have declined significantly. Studies have shown that selenium can counteract the harmful effects of cadmium on plants and can alleviate the stress caused by cadmium during the growth of plants. However, the mechanism of exogenous selenium application in the alleviation of cadmium stress in cabbage seedlings has not been thoroughly investigated. In this study, exogenous selenium (10μMol/L) was applied under cadmium (25μMol/L) stress and the physiological mechanisms such as biomass, photosynthetic pigment, leaf stomata parameters, selenium and cadmium content, chloroplast ultrastructure, active oxygen accumulation, leaf membrane esterification and antioxidant enzyme activity were determined. The protective mechanism of exogenous selenium on cabbage seedlings under cadmium stress was investigated. The re-sults showed that exogenous application of selenium could effectively alleviate the decrease in growth, photosynthetic pigment and gas exchange characteristics of cabbage seedlings under cadmium stress, im-prove cabbage root vitality, reduce root leaf cadmium content and alleviate cadmium stress-induced damage. Ultrastructural observation showed that cadmium stress caused the disruption of the internal structure of chloroplasts of cabbage leaves, while exogenous selenium treatment alleviated the chloroplast damage to some extent, improved the stability of the inner capsule membrane and alleviated the cadmium stress-induced damage to photosynthetic organs. Cadmium stress also caused oxidative damage and ex-cessive accumulation of ROS in the leaves of cabbage seedlings as evidenced by significant accumulation of O2-, H2O2, MDA and electrolyte leakage. On the other hand, after exogenous selenium treatment, cadmium stress- induced oxidative damage could be reduced by up-regulating the activities of antioxidant enzymes SOD, POD and APX. At the same time, cadmium stress significantly increased GSH levels, and exogenous selenium treatment further increased GSH levels, thereby increasing the tolerance of cabbage to cadmium stress. In conclusion, by protecting the photosynthetic system, eliminating excessive accumulation of reactive oxygen species in cadmium-stressed cabbage seedlings, alleviating oxidative stress and reducing cadmium levels in the plant, exogenous selenium can further improve cadmium tolerance in cabbage seedlings.

The Douro Demarcated Region (DDR) has peculiar edaphoclimatic characteristics that provide a suitable terroir for premium wine production. As climate change effects continue to emerge, ensuring productivity and quality becomes increasingly important for viticulturists, as those directly determine their profits. Cultural approaches, such as the use of biostimulants, are actively being developed to mitigate abiotic stress. The main objective of this work was to assess the effect of foliar sprays of a seaweed (Ascophyllum nodosum) based extract (ANE) and glycine betaine (GB) on grape berry quality, bioactive compounds, and antioxidant activity. A trial was installed in a commercial vineyard (cv. Touriga Franca) in the Douro Superior (Upper Douro) sub-region of the Douro Demarcated Region. In 2020, a total of three foliar sprayings were performed during the growing season, namely at pea-size, bunch closure, and veraison. There was a positive effect of both biostimulants (ANE and GB) on the physiological and biochemical performance of cv. Touriga Franca exposed to summer stress. In general, the GB 0.2% spraying was the most promising treatment for this grape cultivar, as it increased berry quality, the concentration of bioactive compounds (total phenolics, flavonoids and ortho-diphenols), and the antioxidant activities. These results revealed the efficacy of biostimulants sprayings as sustainable viticultural practice, improving berry quality under summer stress conditions.

Plant-based extracts have been recently employed as sustainable tools to improve biotic and abiotic stress tolerance and increase grape quality. However, knowledge about the effect of these extracts on secondary metabolism compounds, that are fundamental for grape and wine quality, is still scarce. In this study, a trial was installed in an experimental vineyard with the variety Touriga Franca located at University of Trás-os-Montes e Alto Douro, Baixo Corgo sub-region of the Douro Demarcated Region, in two growing seasons: 2019 and 2020. Foliar sprayings with the natural products, nettle extract (NE) and Japanese knotweed extract (JKE), were tested to evaluate their effect on downy mildew incidence and severity, on grapevines bioactive compounds contents and antioxidant activity, at veraison and harvest. NE and JKE have stimulated an improvement in the concentration of total carotenoids in leaves and the concentration of total phenolics in berries along with an improved concentration of total phenolics and flavonoids in leaves and berries. Thus, it was verified that these extracts enhance grapevines bioactive compounds and antioxidant capacity and, consequently, the physiological performance of the plant and the quality of the berries. Considering the challenges posed by climate change in the Mediterranean basin viticulture sector, the use of plant extracts might represent a sustainable tool to mitigate the increasing severity of drought, often associated to heatwaves and high irradiation. Moreover, downy mildew incidence results suggest that an integrated disease management approach combining conventional control with alternative fungicides can be used in the future for a more sustainable viticulture.

Low nasal nitric oxide (nNO) is a typical feature in Primary Ciliary Dyskinesia (PCD). nNO is part of the PCD diagnostic algorithm due to its discriminative power against other lung diseases such cystic fibrosis (CF). However, the underlying pathomechanisms are elusive. To better understand NO dysregulation in PCD, the L-arginine/NO (Arg/NO) pathway in patients with PCD (pwPCD) and CF (pwCF) and in healthy control (HC) subjects was investigated. In a prospective, controlled study, we measured in 24 pwPCD, 25 age-matched pwCF, and 14 HC the concentrations of the NO precursors Arg and homoarginine (hArg), the arginase metabolite ornithine (Orn), the NO inhibitor asymmetric dimethylarginine (ADMA), and the major NO metabolites (nitrate, nitrite) in sputum, plasma and urine by validated methods. In comparison to HC, the sputum contents (in µmol/mg) of L-Arg (PCD 18.43 vs. CF 329.46 vs. HC 9.86, p < 0.001) and of ADMA (PCD 0.055 vs. CF 0.015 vs. HC 0.010, p < 0.001) were higher. In contrast, the sputum contents (in µmol/mg) of nitrate and nitrite were lower in PCD compared to HC (nitrite 4.54 vs. 9.26, p = 0.023; nitrate 12.86 vs. 40.33, p = 0.008), but higher in CF (nitrite 16.28, p <0.001; nitrate 56.83, p = 0.002). The metabolite concentrations in urine and plasma were similar in all groups. The results of our study indicate that PCD, unlike CF, is associated with impaired NO synthesis in the lung, presumably due to mechano-chemical uncoupling.

Vibrio splendidus is the main pathogen infect a wide range of hosts, especially sea cucumber Apostichopus japonicus. Our previous studies had shown that the level of L-glutamic acid (L-Glu) was significantly increased under heat stress and it was one of the best carbon sources that could be used by V. splendidus AJ01. In this study, the effects of exogenous L-Glu on the coelomocyte viability, tissue status and individual mortality of sea cucumbers were analyzed. The results showed that 10 mM L-Glu decreased coelomocyte viability and increased mortality, with tissue rupture and pyknosis, while 0.1 mM L-Glu slightly affected the survival of sea cucumbers without obvious damages at both cellular and tissue levels. Transcriptomic analysis showed that there were 343 upregulated and 206 downregulated genes regulated by exogenous L-Glu. GO analysis showed that differentially expressed genes (DEGs) were mainly enriched in signaling and membrane formation, while KEGG analysis showed that DEGs were significantly enriched in the upregulated endocytosis and downregulated lysosomal pathways. The coelomocyte viability further decreased 20% in the simultaneous presence of exogenous L-Glu and V. splendidus AJ01, compared to that of V. splendidus AJ01 infection alone. Consequently, a higher mortality of sea cucumber was also observed in the presence of exogenous L-Glu challenged by V. splendidus AJ01. Real time reverse transcriptase PCR showed that L-Glu specifically upregulated the expression of the fliC gene, conding the subunit protein of flagellar filament, with promoted swimming motility activity of V. splendidus. Our result indicated that L-Glu should be kept in a state of equilibrium, and the excess L-Glu in the host-pathogen interface would prompt the virulence of V. splendidus via increasing bacterial motility.

Drought poses a significant constraint on rice production, and in this study, we have discovered a novel drought-sensitive mutant, designated as dsm3, arising from the progenies of indica rice variety Zhonghui8015 treated with EMS. Under drought stress conditions, dsm3 exhibited characteristic withered leaf tips, accompanied by increased levels of MDA and H2O2, reduced Pn, and decreased activity of POD and SOD. Genetic analysis revealed that the withered leaf tip phenotype was governed by a single recessive gene, designated as Osdsm3.To begin with, Osdsm3 was initially mapped to the short arm of chromosome 1 through a cross involving dsm3 and 02428. Subsequently, utilizing a population of 2591 F2 individuals, we narrowed down the location of Osdsm3 to a 78Kb interval, encompassing 13 open reading frames (ORFs). Sequencing analysis unveiled a mutation (1275G→A) in the exon of the candidate gene (LOC_Os01g10680), leading to premature translation termination. Moreover, a quantitative RT-PCR assay demonstrated high expression of OsDSM3 in the panicle and sheath, with a significant upregulation of drought stress-related genes under drought conditions. Phylogenetic analyses indicated that Osdsm3 shares evolutionary homology with UNE1, an intracellular transport protein found in Arabidopsis thaliana. Subcellular studies further confirmed that OsDSM3 resides in the cytoplasm. In conclusion, the forthcoming cloning of Osdsm3 holds promise for delving deeper into the molecular mechanisms governing rice drought resistance.

Abstract: Sickle cell disease (SCD) is an autosomal recessive monogenic disorder caused by a homozygous mutation in the β-globin gene, which leads to erythrocyte sickling, hemolysis, vaso-occlusion and sterile inflammation. Oral l-glutamine administration has been shown to reduce the frequency of pain crisis in SCD patients, however, the long-term effect of l-glutamine in SCD remains to be determined. To understand the long-term effect of l-glutamine administration in SCD liver we used quantitative liver intravital microscopy and biochemical analysis in humanized SCD mice. We here show that chronic l-glutamine administration reduces hepatic hemoglobin-heme-iron level, but fails to ameliorate ischemic liver injury. Remarkably, we find that this failure in resolution of hepatobiliary injury and persistent liver fibrosis is associated with reduced expression of hepatic Kupffer cells post l-glutamine treatment. These findings establish the importance to investigate the long-term effects of l-glutamine therapy on liver pathophysiology in SCD patients.

Biofilm formation and lipopolysaccharide (LPS) are implicated in the pathogenesis of gastrointestinal (GI) diseases caused by Gram-negative such as Escherichia coli and Salmonella enterica serovar Typhimurium. Grape seeds, wine industry by-products, have antioxidant, antimicrobial, and anti-inflammatory activities. In the present study, the protective effect of procyanidin-rich grape seed extract (prGSE), from unfermented pomace of Vitis vinifera cv Bellone, on bacterial LPS-induced oxidative stress and epithelial barrier integrity damages has been studied in a model of Caco-2 cells. The in vitro activity of prGSE against formation of biofilm of S. Typhimurium and E. coli, has been investigated. In vivo, prGSE activity using infected Galleria mellonella larvae has been evaluated. The results showed that the prGSE, if administered with LPS, can significantly reduce the LPS-induced permeability alteration. Moreover, the ability of the extract to prevent Reactive Oxygen Species (ROS) production induced by LPS treatment of Caco-2 cells has been demonstrated. prGSE inhibited the biofilm formation of E. coli and S. Typhimurium. In in vivo activity, increased survival of infected G. mellonella larvae after treatment with prGSE has been demonstrated. In conclusion, grape seed extracts could be used in the reduction of GI damage caused by bacterial endotoxin and biofilm of Gram-negative bacteria.

The theory of electron spin has been proposed for a century, but the study of quantum effects in biological molecules is still in its infancy. Chirality-induced spin selectivity (CISS) is a very modern theory that can explain many biochemical phenomena. In this paper, we propose a new theoretical model based on CISS theory and quantum chemistry theory, which can well explain the theoretical explanation of the chiral selectivity of chiral proteins. Moreover, this theory can predict the spin state of corresponding chiral molecules. Taking L-DOPA and AADC enzyme as examples, this theoretical model solves the theoretical explanation of AADC enzyme's chiral catalysis selectivity problem and successfully predicts the spin state of L-DOPA and D-DOPA's valence electrons.

Bioinformatics analysis of the sequences of orthologous zinc-containing peptidases of the M15_C subfamily revealed the presence of a conserved tryptophan residue near the active site, which is not involved in the formation of the protein core. Site-directed mutagenesis of this Trp114/109 residue using two representatives of the family, L-alanoyl-D-glutamate peptidases of bacteriophages T5 (Calcium-activated EndoT5) and RB49 (EndoRB49, without ion regulation) as an example, and further analysis of the 1H NMR spectra of the mutants showed that a decrease in the volume of the W → F → A residue leads to changes in the hydrophobic core and active center of the protein, and also decreased affinity for regulatory Ca2+ in the EndoT5 mutants. The inactive T5W114A mutant lacks the ability to bind the substrate. In general, the conserved Trp114/109 residue, due to the spatial restrictions of its side chain, significantly affects the formation of the catalytically active form of the enzyme and is critical for catalysis.

Pearl millet (Pennisetum glaucum L.) is the second most important cereal grown in Eritrea after sorghum (Sorghum bicolor L.) grown under low input systems by small scale farmers. The crop utilizes soil moisture efficiently and has ability to tolerate soil toxicity and extreme temperatures than other cereals. It is a sustenance and food security crop important for its nutritive and cultural value and provides dietary energy and nutrition. However, despite the positive attributes and qualities of pearl millets for the present and future agriculture, production has been low. We attribute this to inadequate rainfall distribution, poor crop management by poorly resourced farmers, unavailability and high prices of farm inputs such as fertilizer and pesticides and low adoption of improved varieties by the farmers. This review outlines the constraints, interventions the government/ farmers have and can implement and the prospects of actions that can improve pearl millet production. As much as there have been efforts by the government and stakeholders to address these challenges and improve productivity of pearl millet, more needs to be done to meet the increasing demand of the increasing populations. This will enable farmers to intensify and diversify their agricultural systems and improve food security situation in the country. Unless a combined effort in soil fertility improvement, policies to promote use of modern varieties and conservation of and promotion of this crop biodiversity, the potential of this crop as famine and poverty alleviation among the rural poor will not be realized.

The largest gene families in plants were found to be Glutathione transferase (GSTs), which played significant roles in regulating plant growth, development, and stress response. Within the GSTs gene family, members were found to play a crucial role in the low-temperature response process of plants. A comprehensive study identified a total of 70 BraGSTs genes. Cluster analysis results demonstrated that the BraGSTs in Brassica rapa(B.rapa) could be categorized into eight sub-families and were unevenly distributed across ten chromosomes. The 39 BraGSTs genes were found to be organized into 15 tandem gene clusters, with the promoters containing multiple cis-elements associated with low-temperature response. Cold stress was observed to stimulate the expression of 15 genes, with the BraGSTF2 gene exhibiting the highest level of expression, sug-gesting its significant involvement in winter B.rapa's response to low-temperature stress. Sub-cellular localization analysis of the BraGSTF2 protein indicated its potential expression in both the cell membrane and nucleus. The analysis of stress resistance in BraGSTF2 transgenic Arabidopsis thaliana lines emon-strated that the over-expression of this gene resulted in significantly elevated levels of SOD, POD activity, and SP content compared to the wild type following exposure to low temperatures. These levels reached their peak after 24 hours of treatment. Conversely, the MDA content was lower in the transgenic plants compared to the wild type. Additionally, the survival rate of BraGSTF2 transgenic Arabidopsis thaliana was higher than that of the wild type, suggesting that the BraG-STF2 gene may play a crucial role in enhancing the cold stress tolerance of winter B. rapa. This study lay a foundation for further study on the role of BraGSTs gene in the molecular regulation of cold resistance in winter B.rapa.

Febuxostat (FBX), a selective xanthine oxidase inhibitor, belongs to BCS class II showing low solubility and high permeability with a moderate F value (< 49%). Recently, FBX/L-pyroglutamic acid cocrystal (FBX-PG) was developed with improving 4-fold increase of the FBX solubility. Nevertheless, in vivo pharmacokinetic property of FBX-PG has not been evaluated yet. Therefore, the pharmacokinetic feasibility of FBX in FBX and FBX-PG-treated rats and mice was compared in this study. The results showed that the F values of FBX were 210% and 159% in FBX-PG rats and mice, respectively. The 2.10-fold greater AUC of FBX was due to the increased absorption (i.e., 2.60-fold higher Cmax,1 at 15 min) and entero-hepatic circulation of FBX (i.e., 1.68-fold higher Cmax,2 at 600 min) in FBX-PG rats compared to the FBX rats. The 1.59-fold greater AUC of FBX was due to a 1.65-fold higher Cmax,1 at 5 min, and 1.15-fold higher Cmax,2 at 720 min of FBX in FBX-PG mice than those in FBX mice. FBX was highly distributed in the liver, stomach, small intestine, and lungs in both groups of mice, and the FBX distributions to the liver and lungs were increased in FBX-PG mice compared to FBX mice. The results suggest the FBX-PG has a suitable pharmacokinetic profile of FBX for improving its oral F value.

N-Acetyl-L-glutamate kinase (NAGK) catalyzes the rate-limiting step in the ornithine/arginine biosynthesis pathway in eukaryotic and bacterial oxygenic phototrophs. NAGK is the most highly conserved target of the PII signal transduction protein in Cyanobacteria and Archaeplastida (red algae and Chlorophyta). However, yet there is still much to be learnt on how NAGK is regulated in vivo. The use of unicellular green Chlamydomonas reinhardtii as a model system has already been instrumental in identifying several key regulation mechanisms that control nitrogen (N) metabolism. With a combination of molecular-genetic and biochemical approaches, we show the existence of the complex CrNAGK control at transcriptional level, which is dependent on N source and N availability. In growing cells, CrNAGK requires CrPII to properly sense the feedback inhibitor arginine. Moreover, we provided primary evidence that CrPII is only partly responsible for regulating CrNAGK activity to adapt to changing nutritional conditions. Collectively, our results suggest that in vivo CrNAGK is tuned at transcriptional and post-translational levels, and CrPII and additional as yet unknown factor(s) are integral parts of this regulation.

Abstract: This study aimed to evaluate the application of chemical defensives and long-life inoculant, in mixtures or not, under the nodulation process of plants and the quality of soy seeds during storage. The first was carried out in a greenhouse and completely randomized design was used, in an 8 x 2 factorial scheme, with three replications, and the treatments consisted of applications of seed treatments via industrial: (T1 - control; T2 - MaximAdvanced; T3 - Fortenza; T4 - long-life inoculant; T5 - MaximAdvanced + Fortenza); T6 - MaximAdvanced + long-life inoculant; T7 - Fortenza + long-life inoculant; T8 - MaximAdvanced + Fortenza + long-life inoculant), which were sown in pots containing soils from two cultivation areas; the second in the laboratory, using a completely randomized design, in a factorial scheme 8 x 7, with four replications, with treatments consisting of eight combinations of industrial seed treatment in the greenhouse, stored for two months. That seed treatment industrial with fungicide/insecticide/inoculant, applied in isolation or not, does not influence the soy nodulation process. Soy seeds, regardless of the type of treatment received with fungicide/insecticide/long-life inoculant products, in mixtures or in isolation, may be stored for a period of 40 days for commercial purposes.

Phenotypic plasticity is widely acknowledged as one of the most common solutions for coping with novel environmental conditions following climate change. However, it is less known wheth-er current amounts of trait plasticity, which is sufficient for matching with contemporary climate, will be adequate when global temperatures exceed historical levels. We addressed this issue by ex-ploring the responses of functional and structural leaf traits in Iris pumila clonal individuals to ex-perimentally increased temperature (~1.5°C), using an open top chamber (OTC) design. We de-termined phenotypic values of specific leaf area, leaf dry matter content, specific leaf water con-tent and leaf thickness in leaves sampled from the same clone inside and outside of the OTC de-ployed on it, over seasons and years within two natural populations. We analyzed the data by a repeated multivariate analysis of variance, which is primarily focused on profiles (reaction norms, RNs) of a variable gathered from the same individual at several different time points. We found that the mean RNs of all analyzed traits were parallel regardless of experienced temperatures, but differed in the level and the shape. The populations RNs were similar as well. Since the amount of plasticity in analyzed leaf trait was adequate for coping with elevated temperatures inside the OTCs, we predict that it will be also sufficient for responding to increased temperatures if they exceed the 1.5°C target.

The DnaA protein has long been considered to play the key role in the initiation of chromosome replication in modern bacteria. Many questions about this role, however, remain unanswered. Here, we raise these questions within a framework based on the dynamics of hyperstructures alias large assemblies of molecules and macromolecules that perform a function. In this dynamics, hyperstructures can (1) emit and receive signals or (2) fuse and separate from one another. We ask whether the DnaA-based initiation hyperstructure acts as a logic gate receiving information from the membrane, the chromosome and metabolism to trigger replication; we try to phrase some of these questions in terms of DNA supercoiling, strand opening, glycolytic enzymes, SeqA, ribonucleotide reductase, the Macromolecular Synthesis operon, post-translational modifications and metabolic pools. Finally, we ask whether, underpinning the regulation of the cell cycle, there is a physico-chemical clock inherited from the first protocells, and whether this clock emits a single signal that triggers both chromosome replication and cell division.

Pruning is an important part in controlling the branching, good fruit size, and prodctivity of fruit trees. and consequently, ‘Valencia’ orange trees were grown many years ago, the trees were suffering from a decline in productivity in the newly reclaimed lands after certain years of plantation. This study elucidated the effect of pruning severity on growth, yield and fruit quality of ‘Valencia’ orange trees. Four levels of pruning were applied on 35 years old ‘Valencia’ orange trees as follows: T1: Control (un-pruned), T2: Light pruning ( 25% of main branches were removed); T3: Moderate pruning (50% of main branches were removed) and T4: Heavy pruning: 75% of main branches were removed. The treatments were done in February 15th (for each season). The results indicated that pruning severity increased vegetative growth paraments such as shoot length and leaf area and decreased canopy volume of Valencia orange trees in comparison to control. Maximum yield was gained from 75% followed by 50% and 25% pruning severity treatment. The pruning treatments improve in fruit weight, size, firmness, juice content, TSS%, TSS/acid ratio and vitamin C content. In addition, pruning produced an increasing in fruit yield per tree as well as yield increasing %. Hence, it might be concluded that pruning at different severity applied in February can be used effectively on ‘Valencia’ orange trees to improve vegetative growth, fruit physical and chemical properties. Besides, increasing fruit yield by nearly 20% in comparison to control.

Many cancers utilize L-glutamine as a major energy source. This “L-glutamine addiction” involves a well-characterized pathway whereby L-glutamine is hydrolyzed by a glutaminase (GLS) to L-glutamate, which is then converted to α-ketoglutarate, the carbons of which enter the tricarboxylic acid (TCA) cycle. However, mammalian tissues/cancers possess a rarely mentioned alternative pathway (the glutaminase II pathway): L-Glutamine is transaminated to α-ketoglutaramate (KGM), followed by ω-amidase (ωA)-catalyzed hydrolysis of KGM to α-ketoglutarate. Uncertainty may prevail over the name glutaminase II which may be confused with the enzyme named glutaminase 2 (GLS2). Thus, we recently suggested a new name for the glutaminase II pathway, namely the glutamine transaminase-ω-amidase (GTωA) pathway. Herein, we 1) evaluate three recent articles that mention L-glutamine addiction, but not the GTωA pathway, 2) summarize the metabolic importance of the GTωA pathway, including its role in closing the methionine salvage pathway, and 3) as a source of anaplerotic α-ketoglutarate. An advantage of the GTωA pathway [i.e., L-glutamine + α-keto acid + H2O α-ketoglutarate + L-amino acid + +NH4] is that it is irreversible and that there is no net change in redox status, permitting α-ketoglutarate production during hypoxia. Finally, we discuss possible clinical benefits of GTωA pathway inhibitors.

Anastatica hierochuntica L. (Brassicaceae) has been claimed to treat various conditions including complicated childbirth. The principal objective of this research was to provide scientific evidence on the contractile effect of the aqueous and hydroethanolic extracts of the whole plant from A. hierochuntica during labor. Qualitative and quantitative methods helped identify and quantify the phytoconstituents in both extracts. The antioxidant activity was studied using four standard methods. The inhibitory power of the extracts on pro-inflammatory enzymes such as 15-lipoxygenase and phospholipase A2 was determined. The contractile effects of the extracts were evaluated using isolated pregnant mice uteri. Steroids, triterpenoids, flavonoids, tannins, coumarins, and reduced compounds were identified in both extracts. The extracts demonstrated the ability to reduce oxidative stress. The hydroethanolic extract displayed the most significant anti-lipoxygenase activity with an IC50 value of 55.82 ± 1.15 µg/mL. The lethal dose (LD50) of extracts was estimated to be superior to 2000 mg/kg bw. The ability of the samples to produce one cm amplitude of contraction at 50% effective concentrations (EC50) was 1.51 ± 0.08 mg/mL for aqueous extract and 3.57 ± 0.61 mg/mL for hydroethanolic extract. These findings could provide evidence for using Anastatica hierochuntica to augment labor.

Water stress is one of the main factors affecting the development of agricultural crops. An inno-vative alternative to improve tolerance to water stress is the application of biostimulants. In the present study, the efficacy and physiological and biochemical responses of different biostimulants were evaluated in beans under moderate and severe stress. The treatments consisted of three types of irrigation: FC100, without water stress, FC75, irrigation reduced by 25% (moderate water stress) and FC50, irrigation reduced by 50% (severe water stress). In the treatments with water deficit, foliar biostimulants were applied: zinc oxide nanoparticles plus chitosan, Codasil®, Osmoplant®, Stimplex® and salicylic acid. Foliar application of ZnO + chitosan nanoparticles benefited biomass accumulation and yield under moderate water stress (FC75) and Codasil® and Osmoplant® under severe water stress (FC50). Proline, free sugars and gas exchange were higher under the application of ZnO + chitosan nanoparticles under moderate water stress and under Codasil® and Osmoplant® under severe water stress. Depending on the severity of water stress, ZnO + chitosan nanoparticles, Codasil® and Osmoplant® are viable products to increase tolerance in green bean cv. Strike plants.

In the last decades, cultivation of chia (Salvia hispanica L.) has expanded around the world and the seeds have become well known due to their rich composition in nutrients and bioactive compounds. The aim of this work was to evaluate the physical, chemical and nutritional profile of eight chia seeds grown in different Latin-American countries (Argentina, Bolivia, Chile, Ecuador, Mexico, Paraguay and Peru). The results showed that several nutritional parameters such as the protein content and amino acid profile, dietary fiber content, lipid content, mineral composition and phytate present in the seeds depend on the location they were grown in. Other parameters such as ash content, fatty acid profile or physical parameters were uniform across locations (except for color parameters). The results support the notion that nutritional characteristics of seeds are determined by the seed's origin, further analysis is needed to define the exact mechanisms that control the changes in the seeds nutritional properties.

The rye (Secale cereale L.) crop shows a high potential to collaborate in the sustainability of high Andean livestock because it supports the agroclimatic conditions and acid soils in the Peruvian Andes. The production of green forage, hay, and grain of the rye crop in acid soils was studied with the use of different levels of phosphorus and potassium fertilization in four local rye ecotypes (CBI-001, CSM-001, CJS-001, and CCE-001). The green forage yield (FV) ranged from 32.35 to 53.62 t ha-1, dry matter from 6.05 to 8.56 t ha-1, and hay from 7.0 to 10.36 t ha-1; nutritional levels ranged from 9.02 % to 13.56 % protein and 6.50 to 7.75 % ash levels, mainly with differences between ecotypes (p<0.05). No differences existed between fertilization levels for the number of stems per plant, and flowering stems per plant, and grains per ear (p>0.05). Also, CBI-001 and CCE-001 were superior with 1868.4 and 1797.8 kg ha-1 of grain, respectively (p=0.0072); the use of 60 kg ha of Nitrogen, 120 kg ha-1 of P2O5 and 80 kg ha-1 of K2O gave higher grain and residue yields. The high nutritional value and yield of the rye ecotypes studied in acid soil conditions and without irrigation can be an alternative for livestock feeding and grain production in the rainy season in the Andes as a dual-purpose crop.

Drought and salinity are among the most important abiotic stress factors that limit the productivity in economically important plants. Although genes from wild relatives or unadapted germplasm have often been used for stress tolerance breeding, only few studies have examined wild relatives to understand the genetic and molecular basis of stress tolerance. In this study, we monitored the changes in gene expression profiles of leaf and root tissues of two wild barleys (Hordeum spontaneum L.) accessions from Israel after treatment with salt (NaCl) and drought (PEG) stress. We identified a total of 641 differentially expressed genes across 24 conditions (2 accessions, 2 stress conditions, 2 tissues and 3 time points). Our gene expression analyses revealed large numbers of differentially expressed genes in different accessions by different stress treatments. In addition, the number of genes altered in the leaves of stress-exposed plants of both genotypes was higher than those altered in the roots. Interestingly, there was a relatively little overlap between the leaf and the root stress-responsive gene expression patterns, suggesting that different stress-associated processes might be operating in these tissues during stress adaptation. Overall, our results revealed a number of candidate genes and plant processes associated with stress tolerance in wild barley. Wild barley would be a useful source of new genetic variation for drought and salt stress tolerance. Our results could provide new insights into the mechanisms of drought and salt stress tolerance in wild barley and should be useful for genetic improvement of salt-drought tolerance in cultivated barley.

Duchenne muscular dystrophy (DMD), the severest form of muscular dystrophy, is characterized by progressive muscle weakness with fatal outcome most often before the fourth decade of life. Despite recent addition of molecular treatments, DMD remains a disease without a cure, and the need persists for the development of supportive therapies aimed to help improve patients’ quality of life. This review focusses on the therapeutical potential of amino acid and derivative supplements, summarizing results obtained in preclinical studies in the murine disease model. Several promising compounds have come forward, with L-arginine, N-acetylcysteine and taurine featuring among the most intensively investigated. Beneficial effects include improved muscle function and reduced muscle fiber necrosis and reduced inflammatory and oxidative damage to muscle tissues, however mild side effects have also surfaced. In order to identify amino acid formulae that are safe and of true benefit to DMD patients, more explorative, placebo-controlled and long-term clinical trials need to be conducted, documenting therapeutic outcomes.

In addition to its use as a food additive, sesame is also very popular in conventional drugs because of its antifungal, anticancer, analgesic, antioxidant, and antiproliferative, vitamin B and E supplier, serum cholesterol and blood pressure-lowering, wound healing potential. In this study, the cytotoxicity, wound healing, and anticancer (antiproliferation) properties of the ex-tract obtained from in vitro cultures of Sesamum orientale L. cv. "Gökova" were investigated using in L929 fibroblast, MCF-7 breast, and A549 lung epithelial cell lines. In our study, the cisplatin was also used as a control group to compare the anticancer efficacy of our plant extract. The IC50 values obtained from cell treatments were 922.73 µg.ml-1 (plant extract) and 33.09 µg.ml-1 (cispla-tin) for A549 µg.ml-1, 1837.07 µg.ml-1 (plant extract) and 19.27 µg.ml-1 (cisplatin) for MCF-7, and 154.70 µg.ml-1 (plant extract) for L929, respectively. The subcytotoxic doses of the treated plant extract provided the healing of artificially created wounds on L929 fibroblast cell cultures within 48 hours. For the evaluation of the anticancer activity, it was also determined that transcriptomic analyzes of BCL-XL gene, which is negatively correlated with apoptotic pathway, and Cas3 and Cas9 genes, which are positively correlated with apoptotic pathway, showed a statistically sig-nificant increase in A549 and MCF-7 cell lines treated with plant extract or cisplatin. In the light of the results obtained from the present study, it was seen that sesame plant extract may have wound healing potential at decreasing doses and anticancer activity potential at increasing dos-es. The present study can be a useful resource for the development of a drug with wound healing and/or antiproliferative potential, with applications to be made in different cell lines in the future.

The basic helix-loop-helix (bHLH) transcription factor family is the second-largest transcription factor in plants. Members of this family are involved in the process of growth and development, secondary metabolic biosynthesis, signal transduction, and plant resistance. Loropetalum chinense var. rubrum is a critical woody plant with higher ornamental and economic values, which used as ornamental architecture and traditional Chinese herbal medicine plant. However, the bHLH transcription factor in the L. chinense var. rubrum (Loropetalum chinense var. Rubrum) have yet to be systematically demonstrated, and their role in anthocyanin biosynthesis remains secret. Here, we identified 165 potential LcbHLHs genes by two methods, and they were unequally distributed on chromosomes 1 to 12 of the L. chinense genome. Based on a phylogenetic comparison with proteins from Arabidopsis, these bHLH proteins were categorized into 21 subfamilies. Most LcbHLHs in a given subfamily had similar gene structures and conserved motifs. The gene ontology annotation and cis-elements predicted that the LcbHLHs had many molecular functions and were involved in plant growth processes, including flavonoid and anthocyanin biosynthetic processes, etc. Transcriptomic analysis revealed different expression patterns among different tissues and cultivars in L. chinense. Many LcbHLHs were expressed in leaves, and only a few genes were highly expressed in flowers. Six LcbHLH genes differentially expressed between species and periods in color variation, which may play a key role in anthocyanin synthesis. These further functional predictions of LcbHLHs were established by quantitative real-time PCR analysis and protein-protein interaction network. This study identified the six potential bHLH genes related to anthocyanin in L. chinense and created a solid framework for future research on the function and evolution of bHLHs.

The demand for dietary supplements containing collagen has been growing for years. The speciality and uniqueness of the dietary supplement (DS) examined in our study is the presence of L-arginine and hyaluronic acid alongside collagen and vitamin C. The individual mechanisms of action and physiological role of these compounds are understood, but they have not yet been tested in the combination and amounts of the dietary supplement used in this study. In this study, we investigated the effectiveness of the DS in elderly patients with musculoskeletal complaints. Somatometric, body composition, physiotherapy and laboratory tests were performed at the beginning and at the end of the study. The two-month study involved 30 people, randomly divided into two groups: a control group (CG) and an experimental group (EG). All subjects consumed 25 ml DS per day and EG members also participated in physiotherapy 3 times a week. Alongside the DS, blood lipid levels changed: LDL decreased, HDL increased, LDL/HDL ratio significantly decreased in both groups. For EG, the results improved more markedly. In 3 items of the body composition test, there was a significant improvement in both groups, which was attributed to the use of the dietary supplement. For the EG, there were significant changes in 5 additional test items, which we attribute to the addition of regular physical activity. Knee and hip joint range of motion (ROM) showed significant improvements in the study group, while in the CG the DS can cause significant improvements in joint range of motion in a passive condition as well.

In globe artichoke both the edible portion and the waste biomass are recognized as valuable sources of bioactive compounds. For this study, heads with 30 cm-long floral stems, including 2-3 leaves, were harvested from five genotypes which included two traditional vegetatively-propagated varietal types (‘Brindisino,’ and ‘Violetto di Foggia,’) and three "seed"-propagated hybrids (‘Tempo,’ ‘Opal,’ and ‘Madrigal’). The study aimed to determine the total and individual polyphenolic concentrations (measured spectrophotometrically and by HPLC) and antioxidant activity (AA) in different artichoke parts, namely the "hearts" (H), head waste (HW), stem waste (SW), and leaf waste (LW). ‘Brindisino’ SW exhibited the highest accumulation of luteolin (26,317 mg kg−1 F.W.), while ‘Tempo’ H displayed the highest cynarin content (190 mg kg−1 F.W.). ‘Tempo’ HW and H showed the highest levels of apigenin (640 mg kg−1 F.W.), and the greatest source of chlorogenic acid was found in the HW of ‘Opal’ and the H of ‘Brindisino’ (4,300 mg kg−1 F.W.). The hybrids generally exhibited lower total polyphenolic concentrations than the traditional genotypes, particularly evident in the LW. The SW demonstrated the highest concentration of total polyphenols (18,000 mg kg−1 F.W.), followed by the edible H and non-edible HW (12,000 mg kg−1 F.W.), while the LW exhibited the lowest concentration (2,000 mg kg−1 F.W.). Interestingly, the AA did not precisely align with the total polyphenolic concentration, showing slight variations between the examined parts and genotypes.

Many factors affect the quality of red meat. The aim of the study, carried out on 44 Polish Merino lambs, was analysis of physicochemical traits (pH, meat color, expressed juice, content of moisture, protein, fat, total collagen and fatty acid ) and content of carnosine, taurine, L-carnitine on fresh and meat aged for 7 and 14 d in the longissimus lumborum (LL) and gluteus medius (GM) muscles., Higher (p<0.05) redness value (a*), lower yellowness (b*) were recorded in meat after of aging in gluteus medius muscle. A lower value (p<0.05) of expressed juice was found in both LL and GM after 7 days of aging. The increase (p<0.05) in protein and fat content in both muscle and collagen content in LL was observed in aged meat. There was no difference in fatty acid groups and C18:2 c9, t11 content between GM and LL muscle and fresh and aging meat. A higher TBARS content (p<0.05) was recorded in meat after aging in both GM and LL. The meat aging process increased (p<0.05) the content of carnitine and taurine, while the content of carnosine decreased. In summary the processes that turn muscles into meat in different types of muscles affect the physicochemical characteristics and the content of bioactive ingredients.

The development of technology that combines supercapacitors and lithium-ion batteries by externally connecting them in parallel is ongoing. This study examines the correlation between the volume ratio and electrical characteristics of a cell made by internally connecting a battery capacitor with Li4Ti5O12 as the anode active material and a supercapacitor in parallel. It was found that increasing the volume occupied by the battery capacitor in the cell led to increased cell energy and resistance, resulting in decreased output characteristics. Conversely, increasing the volume occupied by the supercapacitor in the cell led to a decrease in the IR drop during discharge and cell temperature when evaluating cycle characteristics with a current of 20C. The study also examined the behavior of the current distributed during the charging and discharging process based on the volume ratio of the supercapacitor and the battery capacitor. Analyzing the correlation between the volume ratio and electrical characteristics of supercapacitors and battery capacitors could potentially lead to the development of a new type of energy storage device.

The olive wide genetic variability can be used to overcome some of the challenges faced by olive growing, including climate warming. One effect of climate warming in olive is the difficulty to fulfill the chilling requirements for flowering due to high winter temperatures. In the present work, we evaluate seven olive cultivars for their adaptation to high winter temperatures by comparing their flowering phenology in the standard Mediterranean climate of Cordoba, Southern Iberian Peninsula, with the Subtropical climate of Tenerife, Canary Islands. Flowering phenology in Tenerife was significantly earlier and longer than in Cordoba. However, genotype seems to have little influence on the effects of lack of winter chilling temperatures as in Tenerife. This even though the cultivars studied have a high genetic distance between them. In fact, all the cultivars tested in Tenerife flowered the three years under study but showing asynchronous flowering bud burst. Only ‘Arbequina’ showed an earlier day of full flowering than the rest of cultivars. The results observed here could be of interest to refine the phenological simulation models and including of the length of the flowering period. More genetic variability should be evaluated in warm winter conditions to look for adaptation to climate warming.

Advanced MRI methods and PET using radiolabeled amino acids provide valuable information in addition to conventional MR imaging for brain tumor diagnostics. These methods are particularly helpful in challenging situations such as the differentiation of malignant processes from benign lesions, the identification of non-enhancing glioma subregions, the differentiation of tumor progression from treatment-related changes, and the early assessment of response to anticancer therapy. The debate over which of the methods is preferable in which situation is ongoing and has been addressed in numerous studies. Currently, most radiology and nuclear medicine departments perform these examinations independently of each other leading to multiple examinations for the patient. The advent of hybrid PET/MRI allowed a convergence of the methods but to date simultaneous imaging has reached little relevance in clinical neuro-oncology. This is partly due to the limited availability of hybrid PET/MRI scanners, but is also due to the fact that PET is a second-line examination in brain tumors. PET is only required in equivocal situations, and spatial co-registration of PET examinations of the brain to previous MRI is possible without disadvantage. A key factor for the benefit of PET/MRI in neuro-oncology is a multimodal approach that provides decisive improvements in the diagnostics of brain tumors compared with a single modality. This systematic review focuses on studies that were able to demonstrate the additive value of amino acid PET and ‘advanced’ MRI in the diagnosis of brain tumors. Available studies suggest that the combination of amino acid PET and advanced MRI improves grading and the histomolecular characterization of newly diagnosed tumors. However, data concerning the delineation of tumor extent and biopsy guidance are of limited value. A clear additive diagnostic value of amino acid PET and advanced MRI can be achieved regarding the differentiation of tumor recurrence from treatment-related changes. Here, PET-guided evaluation of advanced MR methods seems to be helpful. In summary, there is growing evidence that a multimodal approach can achieve decisive improvements in the diagnostics of brain tumors, for which hybrid PET/MRI offers optimal conditions.

N-acetyl-L-cysteine (NAC), a sulfhydryl-containing compound, is mainly used as a mucolytic and as an antidote for acetaminophen overdose. Flow injection and sequential injection systems were designed and optimized with the aim of providing precise, accurate and reliable flow methods for NAC determination in pharmaceuticals with very low sample and reagent consumption. Proposed methods are based on a redox reaction wherein NAC reduces a complex of Cu(II) and bathocuproine disulfonate (BCS) to orange [Cu(BCS)2]3– complex, which absorption was measured at λmax = 483 nm. The optimized FIA and SIA configuration yielded a linear calibration curve with correlation coefficients (R2 = 0.9999 and R2 = 0.9996) in the concentration range of 3.0 × 10–7 – 3.0 × 10–5 mol L–1 and analytical frequency of 120 h–1 for the FIA method and 4.0 × 10–7 – 4.0 × 10–5 mol L–1, at sampling rate 60 h–1 for the SIA method. The proposed flow methods were successfully applied for the determination of NAC in pharmaceutical products, as the results showed good agreement with the standard method prescribed by Pharmacopoeia. Recoveries were in the range from 98.4% to 101.9% for the FIA method and from 97.2% to 101.8% for the SIA method.

Human induced pluripotent stem cell (hiPSC)-derived neural cells have been used at the preclinical stage of drug development. As previously reported, hiPSC-derived neurons exhibit greater tolerance to excitotoxicity than that of primary cultures of rodent neurons; however, the underlying mechanisms remain unknown. We therefore investigated the functions of L-glutamate (L-Glu) transporters, the most important machinery used to maintain low extracellular L-Glu concentrations, in hiPSC-derived neural cells. We also clarified the contribution of each L-Glu transporter subtype. At 63 days in vitro (DIV), we detected neuronal circuit functions in hiPSC-derived neural cells by a microelectrode array system (MEA). Exposure to 100 μM L-Glu for 24 hrs did not affect the viability of these 63 DIV neural cells. Pharmacological inhibition of excitatory amino acid transporter 1 (EAAT1) and EAAT2 blocked almost 100% of L-Glu uptake. In this condition, L-Glu exposure dramatically decreased cell viability. These results suggest that in hiPSC-derived neural cells, EAAT1 and EAAT2 are predominant L-Glu transporters, and their uptake potentials are stronger than those of primary cultures of rodent neurons. Furthermore, hiPSC-derived neural cells may be useful for screening drugs that target L-Glu transporters.

Achieving high-yield potential is always the ultimate objective of any breeding program. However, various abiotic stresses like salinity, drought, cold, flood, and heat hampered rice productivity tremendously. Salinity is one of the most important abiotic stresses that adversely affect rice grain yield. The present investigation was undertaken to dissect new genetic loci, which are responsible for salt tolerance at the early seedling stage in rice. A bi-parental mapping population (F2:3) was developed from the cross between BRRI dhan28/Akundi, where BRRI dhan28 (BR28) is a salt-sensitive irrigated (boro) rice mega variety and Akundi is a highly salinity tolerant Bangladeshi origin indica rice landrace that is utilized as a donor parent. We report stable QTLs for salt tolerance from a common donor (Akundi) irrespective of two different genetic backgrounds (BRRI dhan49/Akundi and BRRI dhan28/Akundi). A robust 1k-Rice Custom Amplicon (1k-RiCA) SNP marker genotyping platform was used to genotype this bi-parental population. After eliminating markers with high segregation distortion, 886 polymorphic SNPs built a genetic linkage map covering 1526.5 cM of whole rice genome with an average SNP density of 1.72 cM for the 12 genetic linkage groups. A total of 12 QTLs for nine different salt tolerance-related traits were identified using QGene and inclusive composite interval mapping of additive and dominant QTL (ICIM-ADD) under salt stress on seven different chromosomes. All of these 12 new QTLs found unique, as no other map from the previous study has reported these QTLs in the similar chromosomal location and found them different from extensively studied Saltol, SKC1, OsSalT and salT locus. Twenty-eight significant digenic/epistatic interactions identified between chromosomal regions linked to or unlinked to QTLs. Akundi acts like a new alternate donor source of salt tolerance except for other usually known donors like Nona Bokra, Pokkali, Capsule, and Hasawi used in salt tolerance genetic analysis and breeding programs worldwide, including Bangladesh. Integration of the seven novel and stable QTLs (qSES1, qSL1, qRL1, qSUR1, qSL8, qK8, qK1) reported in this investigation will expedite the cultivar development that is highly tolerant to salt stress.

Overuse and misuse of antibiotics can pose the risks of spreading mutant strains that show antimicrobial resistance (AMR), with negative impact on management of bacterial infections and economic implications on healthcare systems. Research and development of natural antibacterial agents could be a priority in the next years to improve number of effective antibacterial molecules and to reduce AMR phenomenon and its development. The present study identified the most effective concentration and contact time of Thymus vulgaris L. essential oil (TEO) to obtain bactericidal effect in vitro against different Gram + and Gram – bacterial strains. Six clinically isolated (wild types) bacterial strains, (Citrobacter freundii, Enterococcus feciorum, Proteus mirabilis, Acinetobacter cioffi, Pasteurella putrefaciens, Klebsiella pneumoniae) and two ATCC (Staphylococcus aureus and Streptococcus mutans) were tested after 1min, 3min and 5min of contact with TEO. Preliminary results on S. aureus after 24h incubation revealed a TEO concentration of 9.28mg/mL (w/v) that completely inhibited bacteria growth keeping cell viability. Total suppression of bacterial growth at all tested contact times was observed for all tested bacterial strains and the results were confirmed after 48h incubation. Bacterial growth suppression was confirmed even with presence of organic component. These preliminary results showed in vitro antimicrobial efficacy of TEO against different Gram+ and Gram- bacterial strains. Future studies are necessary to confirm the reproducibility of these results even on other strains and to define exactly the molecular mechanisms of EOs, in order to consider TEO as a valid alternative of classic antibiotic therapies and subsequently to reduce the occurrence of AMR.

In the present study the effects of Origanum onites L. extract and essential oil of O. onites L. on the antioxidant status of the liver and brain of mice were investigated. Due to certain disadvantages of essential oils, such as poor solubility, high volatility, sensitivity to UV light and heat, formulation of liposomes with Oregano essentials (OE) was optimized and used in this study. The results demonstrated that the best composition of the lipid carriers and Oregano essentials were conducted in terms of the PDI, mean particle size and EE. The LE4 formulation contained Lipoid S100 of 45 mg, Lipoid S75 of 45 mg and 90 mg of EO. The administration of O. onites L. extract to mice for 21 days significantly decreased glutathione (GSH) level in the liver and brain of mouse as well as malondialdehyde (MDA) concentration in the liver. In the brain of mice MDA level significantly increased after this extract consumption. Whereas liposomes with OE significantly decreased GSH concentration in mouse brain and MDA concentration in mouse liver but increased (p>0.05) GSH level in liver and MDA concentration in brain of mice compared with the control group. It was investigated that both, O. onites L. extract as well as liposomes with OE of this plant material make changes in the antioxidant status in the liver and brain of mice.

The botanical species Ceratonia siliqua L., commonly referred to as the Carob tree, and locally as “L’Kharrûb”, holds significance as an agro-sylvo-pastoral species, and is traditionally utilized in Morocco for treating a variety of ailments. This current investigation aims to ascertain the antioxidant, antimicrobial, and cytotoxic properties of the ethanolic extract of C. siliqua leaves (CSEE). Initially, we analyzed the chemical composition of CSEE through high-performance liquid chromatography with Diode-Array Detection (HPLC-DAD). Subsequently, we conducted various assessments, including DPPH scavenging capacity, β-carotene bleaching assay, ABTS scavenging, and total antioxidant capacity assays, to evaluate the antioxidant activity of the extract. In this study, we investigated the antimicrobial properties of CSEE against five bacterial strains (two gram-positive, Staphylococcus aureus, and Enterococcus faecalis; and three gram-negative bacteria, Escherichia coli, Escherichia vekanda, and Pseudomonas aeruginosa) and two fungi (Candida albicans, and Geotrichum candidum). Additionally, we evaluated the cytotoxicity of CSEE on three human breast cancer cell lines (MCF-7, MDA-MB-231, and MDA-MB-436) and assessed the potential genotoxicity of the extract using the comet assay. Through HPLC-DAD analysis, we determined that phenolic acids and flavonoids were the primary constituents of the CSEE extract. The results of the DPPH test indicated a potent scavenging capacity of the extract with an IC50 of 302.78 ± 7.55 µg/mL, which was comparable to that of ascorbic acid with an IC50 of 260.24 ± 6.45 µg/mL. Similarly, the β-carotene test demonstrated an IC50 of 352.06 ± 12.16 µg/mL, signifying the extract's potential to inhibit oxidative damage. The ABTS assay revealed IC50 values of 48.13 ± 3.66 TE µmol/mL, indicating a strong ability of CSEE to scavenge ABTS radicals, and the TAC assay demonstrated an IC50 value of 165 ± 7.66 µg AAE/mg. The results suggest that the CSEE extract had potent antioxidant activity. Regarding its antimicrobial activity, the CSEE extract was effective against all five tested bacterial strains, indicating its broad-spectrum antibacterial properties. However, it only showed moderate activity against the two tested fungal strains, suggesting it may not be as effective against fungi. The CSEE exhibited a noteworthy dose-dependent inhibitory activity against all the tested tumor cell lines in vitro. The extract did not induce DNA damage at the concentrations of 6.25, 12.5, 25, and 50 µg/ml, as assessed by the comet assay. However, the 100 µg/ml concentration of CSEE resulted in a significant genotoxic effect compared to the negative control. A computational analysis was conducted to determine the physicochemical and pharmacokinetic characteristics of the constituent molecules present in the extract. The Prediction of Activity Spectra of Substances (PASS) test was employed to forecast the potential biological activities of these molecules. Additionally, the toxicity of the molecules was evaluated using the Protox II webserver.

Weaning is a critical period in the pig’s life. Piglets are confronted with abrupt changes to their physical and social environment, as well as management and nutritional changes. Weaning was always associated with a growth check and was frequently accompanied by post-weaning diarrhea in piglets. However, rapid increases in litter size, in the last decade, has increased within-litter piglet weight variation, with piglets now generally lighter at weaning, making the challenges associated with weaning even greater. Many interventions can be employed during the suckling period to ease the weaning transition for piglets. Pre-weaning strategies such as supervised farrowing (assistance with suckling, oxytocin provision), provision of pain relief to sows around farrowing, split-suckling, early oral supplementation with glucose, bovine colostrum, fecal microbiota transplantation, feed additives, solid and liquid creep feeding (milk and liquid feed) have all been investigated. The objective of these strategies is to stimulate earlier maturation of the digestive tract, improve immunity, reduce latency to the first feed post-weaning and increase early post-weaning feed intake and growth. This review focuses in particular on: 1) pain relief provision to sows around farrowing, 2) split-suckling of piglets, 3) pre-weaning provision of supplementary milk and/or liquid feed, 4) other strategies to stimulate earlier enzyme production (e.g. enzyme supplementation) and 5) other nutritional strategies to promote improved gut structure and function (e.g. L-glutamine supplementation). Correctly implementing these strategies can not only increase post-weaning growth and reduce mortality but also maximize lifetime growth in pigs.

Ferroptosis is a unique variety of non-apoptotic cell death, driven by massive lipid oxidation in an iron-dependent manner. Since Ferroptosis was introduced as a concept in 2012, it was shown it's essential role in the pathogenesis in neurodegenerative diseases and an important role in therapy-resistant cancer cells. Thus, a detailed molecular understanding of both canonical and alternative ferroptosis pathways are required. There is a set of widely used chemical agents to modulate ferroptosis using different pathway targets: Erastin blocks cystine-glutamate antiporter, system xc-; ML210 directly inactivate GPX4; L-buthionine sulfoximine (BSO) inhibits γ-glutamylcysteine synthetase, an essential enzyme for glutathione synthesis de novo. Most studies were focused on lipidomic profiling of model systems undergoing death in a ferroptotic modality.

Sperm morphology can predict the reproductive male fertilizing potential. This study aimed to determine the morphological and morphometric spermatozoa characteristics from guinea pigs subjected to different photoperiodic stimulation. Thirty F1 guinea pigs were randomly assigned to three photoperiodic treatments: FT1 (photoperiod with 10L/14D LED light), FT2 (photoperiod with 10L/14D sunlight), and FT0 (room without direct light source). At 107 ± 9.8 days of age, sperm concentration and motility were higher in FT0 and FT1 (p<0.05); furthermore, there were no differences in nucleus length and ellipticity between FT0 and FT1, but FT1 was higher in perimeter and nuclear area, while FT0 was higher in roughness, regularity, midpiece length and tail (p<0.01). Expanding acrosome (Type 2) was more frequent in FT2, but there was variation in head measurements between all morphological categories. Pregnancy rate, calving age and mating age were higher in FT0, meanwhile FT1 initiated successful matings earlier (p<0.01). FT0 had a higher fertility rate, and FT1 age of mating and first calving were earlier than FT0 but no pregnancies were reported for FT2. The photoperiodic stimulation can increase the morphometric dimensions of guinea pig spermatozoa, favoring the reproductive characteristics, but sunlight could reduce their size due to heat stress.

Honey bees (Apis mellifera L.) express complex behavioral patterns (aggressiveness) to exhibit defensive mechanisms for their survival. Their phenotypic expression of aggressive behavior is influenced by internal and external stimuli. Knowledge of this behavior is recently important though beekeepers are still faced with the challenges of selecting aggressive and less-aggressive bred lines. Field evaluation of aggressiveness among bred lines of honey bees is required to overcome the challenges. Chemical cues (alarm pheromone and isopentyl acetate mixed with paraffin oil), physical and visual stimuli (dark leather suede, colony marbling and suede jiggling) were used to evaluate aggressiveness and orientation among five bred lines of honeybee colonies. Our results showed that both chemical assays recruited bees but the time of recruitment was significantly lower for alarm pheromone. Honeybees’ response to both assays culminated to stings which differed among bred lines for alarm pheromone and paraffin when colonies were marbled. Honeybee aggression varied among bred lines and was higher in more aggressive bred lines compared to less-aggressive bred lines. Our findings suggest that it is crucial to repeatedly evaluate orientation aggressiveness at the colony level and among bred lines when selecting breeding colonies.

L\'evy walks represent important modeling tools for variety of real life processes. Their natural scaling limits are known to be described by the so-called material fractional derivatives. So far these scaling limits were derived for spatially homogeneous walks, where Fourier and Laplace transforms represent natural tools of analysis. Here we derive the corresponding limiting equations in the case of position depending times and velocities of walks, where Fourier transforms cannot be effectively applied. In fact, we derive three different limits (specified by the way the process is stopped at an attempt to cross the boundary), leading to three different multi-dimensional versions of Caputo-Dzherbashian derivatives, which correspond to different boundary conditions for the generators of the related Feller semigroups and processes. Some other extensions and generalisations are analysed.

The addition of mineral-solubilizing microbial inoculums is a kind of biological measure for vegetation restoration of rock mining areas. Its function is to accelerate soil weathering, improve soil fertility, improve the ability of plants to fix soil. Through understanding the response of plant rhizosphere microbial community to the mineral-solubilizing microbial inoculums, it is helpful to popularize the use of mineral-solubilizing microbial inoculums. However, little is known about the changes of plant rhizosphere soil microbial communities after the addition of mineral-solubilizing microbial inoculums. Therefore, the purpose of this study was to reveal the pasthways through which different mineral-solubilizing microbial inoculums positively affect underground part of R. pseudoacacia. A pot experiment was conducted to investigate the responses of rhizosphere soil bacterial and fungal communities in R. pseudoacacia by taking 32 samples from four different mineral-solubilizing microbial inoculums treatments. The results showed that the effect of mineral-solubilizing microbial inoculums on the structure of fungal community was greater than that of bacterial community. But the relative abundance of Proteobacteria was increased, which had a strong positive correlation with root nodulation. In terms of microbial diversity, mineral-solubilizing microbial inoculums had a greater effect on the diversity and evenness of bacterial community. It is worth noting that correlation analysis showed that Proteobacteria and Verrucomicrobia in bacteria and Ascomycota and Zoopagomycota in fungi were positively correlated with soil enzyme activity and plant growth. RDA analysis showed that the relative abundance of these two phyla in bacteria also had positive effects on plant root nodulation. Our results showed that the addition of mineral-solubilizing microbial inoculums can optimize the rhizosphere soil microbial community structure, promote R. pseudoacacia root nodulation, and enhance the nitrogen fixation capacity of plants. In addition, this study can provide a theoretical basis for the application of mineral-solubilizing microbial inoculums to a wide range of slope ecological restoration.

At the time of tillage, properties of the soil change, thereby changing the conditions of crop development and ultimately their productivity and quality. The effect of non-inversion tillage or no till on faba bean development is stills not widely investigated. For this reason, investigations of tillage systems from deep and shallow ploughing, chiselling, disking to no tillage were tested in Vytautas Magnus University, Agriculture Academy, Lithuania. The results showed that different tillage methods had less influence on faba bean development than meteorological conditions during the growing seasons. Soil chiselling generally showed better faba bean canopy development rates than other treatments. Faba bean roots developed somewhat better in not tilled plots. Vegetative conditions had a significant influence on faba bean development indicators. The effects of vegetative conditions during all four years of the experimentation were significantly different from each other. This shows that, due to rapid climate change, the conditions of each vegetative season become unique and require precise attention.

Rapeseed (Brassica napus L.) is a globally important oilseed crop with various uses, including consumption of its succulent stems as a seasonal vegetable, but its uniaxial branching habit limits the stem yield. Therefore, developing a multi-stem rapeseed variety has become increasingly crucial. In this study, a nature mutant of wild type from germplasm resources with stable inheritance of the multi-stem trait (MS) was obtained and showed abnormal shoot apical meristem (SAM) development and increased main stem number compared to WT. Histological and scanning electron microscopy analyses revealed multiple SAMs in the MS mutant, while only a single SAM was found in WT. Compared to WT, the mutant exhibited increased accumulation of cytokinins (CKs), transcriptome and RT-qPCR analyses showed the expression of genes involved in CK biosynthesis and metabolism pathways were altered in MS mutant. These findings provide insight into the mechanism of multiple main stems formation in Brassica napus L. and lay a theoretical foundation for breeding multi-main stem rapeseed vegetable varieties.

Tomato is considered the most important vegetable crop worldwide. Improving the nutritional value of fruits must be based on sustainable production in terms of varieties and fertilization management. This study aimed to improve the nutritional value (total soluble solids, acidity, lycopene, β-carotene, polyphenols, macro and microelements) of two tomato varieties (‘Cristal’ and ‘Siriana’) under three fertilization types (NPK chemical fertilizer, chicken manure and biological fertilizer with microorganisms) for the greenhouse. Primary metabolism compounds do not vary significantly according to the type of fertilizer used. The results for the antioxidant compounds showed a better effect of biological fertilization compared to chemical fertilizer and control unfertilized. The tomato fruits from the local cultivar (‘Siriana’) are richer in nutritional compounds such as rutin, regardless of the type of fertilization, which denotes a good ability to adapt to crop conditions. Tomato cultivars reacted positively to microbiological fertilization compare to chemical, thus producing nutritious fruits under sustainable management. Tomato fruits were richer in the quality of microelement contents.

The excessive use of synthetic insecticides in modern agriculture has led to the contamination of the environment and the development of insect resistance. In this study, we evaluated the potential of tangerine (Citrus reticulata L.) peel essential oil (EO) as a natural insecticide against greenhouse whitefly (Trialeurodes vaporariorum W. (Homoptera: Aleyrodidae)), a common pest in greenhouse production. Petroleum ether (PET) and n-hexane (HEX) were used as solvents to extract essential oil (EO) from tangerine peels. The yield of EO was 1.59 % and 2.00 % (m/m) for PET and HEX, respectively. The insecticidal activity of EO was evaluated by measuring the mortality rate (MR) of greenhouse whiteflies at different time intervals. The results showed that PET and HEX extracts of tangerine EO effectively controlled the greenhouse whitefly. With both solvents, it was observed that with doses of 12.5% (v/v), similar results were achieved as with the positive control (corresponding to the commercial insecticide imidacloprid). Additionally, the FTIR analysis found that the EO contained d-limonene, which may be the source of its insecticidal properties. Therefore, tangerine peel essential oil is an excellent natural insecticide candidate for controlling greenhouse whiteflies effectively and sustainably.

The crystal structure of a polymorph of Glycyl-L-alanine HI.H2O was synthesized from chiral cyclic Glycyl-L-alanine dipeptide, known to show molecular flexibility in different environments. The space group is polar (P21) and therefore pyroelectricity and optical second harmonic generation properties are allowed by symmetry. We report a pyroelectric coefficient as high as 45 µC/m2K occurring at 345 K, one order of magnitude smaller than the semi-organic ferroelectric Triglycine Sulphate (TGS) crystal. Furthermore, the polymorph displays a nonlinear optical effective coefficient of 0.14 pm/V, around 14 times smaller than the value from a phase-matched inorganic Barium Borate (BBO) single crystal.

Clinical and histological similarities between sarcoidosis and tuberculosis have driven repeated investigations looking for a mycobacterial cause of sarcoidosis. Over 50 years ago “anonymous mycobacteria” were suggested to have a role in the etiology of sarcoidosis. Both tuberculosis and sarcoidosis have a predilection for lung involvement though each can be found in any area of the body. A key histopathologic feature of both sarcoidosis and tuberculosis is the granuloma – while the tuberculous caseating granuloma has an area of caseous necrosis with a cheesy consistency; the non-caseating granuloma of sarcoidosis does not have this feature. This article reviews and reiterates the complicity of the infectious agent, Mycobacterium avium ss. paratuberculosis (MAP) as a cause of sarcoidosis. MAP is involved in a parallel story as the putative cause of Crohn’s disease, another disease featuring noncaseating granulomas. MAP is a zoonotic agent infecting ruminant animals and is found in dairy products and in environmental contamination of water and air. Despite increasing evidence tying MAP to several human diseases, there is a continued resistance to embracing its pleiotropic roles. "Who Moved My Cheese" is a simple yet powerful book that explores the ways in which individuals react to change. Extending the metaphor, the “non-cheesy” granuloma of sarcoidosis actually contains the difficult-to-detect “cheese”, MAP; MAP did not move, it was there all along.

Plantago major L. is a worldwide available plant that has been used traditionally for several medical application due to its properties such as wound healing, anti-inflammatory, antimicrobial etc. This work aimed to develop and evaluate nanostructured PCL electrospun dressing with P. major extract encapsulated in nanofibers for application in wound healing. The extract from leaves was obtained by extraction in a mixture of water:ethanol= 1:1 of the freeze-dried extract presented a minimum inhibitory concentration (MIC) for Staphylococcus Aureus susceptible and resistant to methicillin of 5.3 mg/mL, a high antioxidant capacity, but a low content of total flavonoids. Electrospun mats without defects were successfully produced using two P. major extract concentrations based on MIC value. The extract incorporation in PCL nanofibers was confirmed by FTIR and contact angle measurements. The PCL/P. major extract was evaluated by DSC and TGA demonstrating that incorporation of the extract decreases the thermal stability of the mats as well as the degree of crystallinity of PCL-based fibers. The P. major extract incorporation on electrospun mats produced a significant swelling degree (more than 400%) and increased the capacity of adsorbing wound exudates and moisture, important characteristics for skin healing. The extract-controlled release evaluated by in vitro study in PBS (pH, 7.4) shows that P. major extract delivery from the mats occurs in the first 24 h, demonstrating their potential capacity to be used in wound healing.

Background: Combinatorial therapy- “nano antibiotics” is an emerging field in nanoscience. In this present investigation, we attempted to combine the green synthesized noble metal nanoparticle and the antibiotic Streptomycin to form bio-conjugated nanoparticles. The newly synthesized Nano antibiotics acted as the antibiotic carrier, functioned as cargo, and delivered the antibiotic. Methods: Comparative studies between the noble metal nanoparticles were attempted for the first time on the grounds of their antibacterial activity. The antibacterial activity of the three noble metal nanoparticles was assessed against Streptomycin-resistant Bacillus sp.; the results obtained proved that silver nanoparticles were a potent antibacterial agent. Still, no antibacterial activity was exerted by gold, and platinum nanoparticles were for the Streptomycin-resistant strain Bacillus sp. To our surprise, the gold and platinum fabricated/bio-conjugated nanoparticle with the antibiotic showed 100% antibacterial activity, whose antibacterial activity was zero when functioning as a nanoparticle alone. Results: The combinatorial therapy of two different clauses of drugs majorly increased antibacterial activity. It enhanced the antibiotic to overcome the resistance exhibited by the bacterial pathogen, and the possible mechanism is elucidated in the present study. Also, an attempt has been made to assess the nanotoxicity of the nano-bioconjugates on RBC and compare their hemocompatibility. The results obtained in the current investigation demonstrate the enhanced antibacterial activity of the green synthesized nanoparticles conjugated with the streptomycin; their efficacy for combinational therapy against resistance in pathogenic organisms highlights the novelty of the work and the comparative study of three different noble metals nanoparticles (Ag, Au, Pt) from single agro-waste for the first time.

Acute lymphoblastic leukemia (ALL) is the most common cancer among children worldwide, characterized by an overproduction of undifferentiated lymphoblasts in the bone marrow. The treatment of choice for this disease is the enzyme L-asparaginase (ASNase) from bacterial sources. ASNase hydrolyzes circulating L-asparagine in plasma, leading to starvation of leukemic cells. The ASNase formulations of E. coli and E. chrysanthemi present notorious adverse effects, especially the immunogenicity they generate, which undermines both their effectiveness as drugs and patient safety. In this study, we developed a humanized chimeric enzyme from E. coli L-asparaginase, which would reduce the immunological problems associated with current L-asparaginase therapy. For these, the immunogenic epitopes of E. coli L-asparaginase (PDB: 3ECA) were determined and replaced with those of the less immunogenic Homo sapiens asparaginase (PDB:4O0H). The structures were modeled using the Pymol software and the chimeric enzyme was modeled using the SWISS MODEL service. A humanized chimeric enzyme with four subunits similar to the template structure was obtained, and the presence of asparaginase enzymatic activity was predicted by protein-ligand docking.

Age-related macular degeneration is one of the most common causes of blindness, and the incidence exhibits profound racial bias, occurring most frequently in Caucasians. A primary cell type affected in the disease is the retinal pigment epithelium, but the etiology is unclear. The end 10% of the photoreceptor outer segments are shed each day, and the underlying retinal pigment epithelium engulfs, digests, and recycles molecules back to the sensory retina. In previous work, we showed that GPR143 signaling in response to L-DOPA may be effective in the prevention or delay of age-related macular degeneration. In this study, we explore a novel potential effector of GPR143 signaling, that of outer segment uptake and digestion. Using isolated outer segments, labelled with a pH-sensitive marker to fluoresce in lysosomes, we show that GPR143 signaling does not impact outer segment uptake, but does have a significant effect on subsequent degradation. Interestingly, GPR143 signaling did not affect the digestive capacity of the cells, marked by total proteolytic capacity and cathepsin D activity. Rather, our data suggest GPR143 improved endosomal trafficking efficiency of the phagocytosed outer segments to the lysosome. This result is similar to the effect we previously reported for GPR143 on exosome release from the endosomal compartment. Our data illustrate that GPR143 is active in endosomal traffic A single paragraph of about 200 words maximum. For research articles, abstracts should give a pertinent overview of the work. We strongly encourage authors to use the following style of structured abstracts, but without headings: (1) Background: Place the question addressed in a broad context and highlight the purpose of the study; (2) Methods: briefly describe the main methods or treatments applied; (3) Results: summarize the article’s main findings; (4) Conclusions: indicate the main conclusions or interpretations. The abstract should be an objective representation of the article and it must not contain results that are not presented and substantiated in the main text and should not exaggerate the main conclusions.

Background: Newer personalized medicine including targeted therapies such as PARP inhibitors and CDK 4/6 inhibitors have shown to improve survival of breast and gynaecological cancer patients. However, efficacy outcomes may be hampered by treatment discontinuation due to targeted therapy-related adverse drug reactions or resistance. Studies suggest that add-on mistletoe (Viscum album L., VA) improves quality of life and ameliorates cytotoxic side effects of standard oncological therapy in cancer patients. The primary objective of this real-world data study was to determine the safety profile of targeted therapy in combination with add-on Helixor® VA therapy in breast and gynecological cancer patients. Methods: The present study is a real-world data study utilizing demographic and treatment data from the accredited national Network Oncology (NO) registry. The study has received ethics approval. The safety profile of targeted with or without Helixor® VA therapy as well as safety - associated variables were evaluated by univariate and adjusted multivariable regression analyses. Results: All stage breast or gynecological cancer patients (n = 242) were on average 54.5±14.2 years old. One hundred and sixty patients (66.1%) were in the control (CTRL, targeted therapy) and 82 patients (33.9%) in the combinational (COMB, targeted plus Helixor® VA therapy) group. The addition of Helixor® VA did not hamper the safety profile (χ2 = 0.107, p-value = 0.99) of targeted therapy. Furthermore, no adverse events and a trend towards an improved targeted therapy adherence were observed in the COMB group. Conclusions: The present study is the first of its kind showing the applicability of Helixor® VA in combination with targeted therapies. The results indicate that add-on Helixor® VA does not negatively alter the safety profile of targeted therapies in breast and gynaecological cancer patients.

High resolution melting (HRM) analysis is a powerful detection method for fast, high-throughput post-PCR analysis. A two-step HRM marker system was developed for identification of the N-, S-, R- and T-cytoplasms of onion. In the first step for identification of N-, S-, and R-cytoplasms, one forward primer was designed to the identical sequences of both cox1 and orf725 genes and two reverse primers specific to the polymorphic sequences of cox1 and orf725 genes were used. For the second step breeding lines with N-cytoplasm were evaluated with primers developed from the orfA501 sequence to distinguish between N- and T-cytoplasms. An amplicon with primers to the mitocondrial atp9 gene was used as an internal control. The two-step HRM marker system was tested using 246 onion plants. HRM analysis showed that the most common source of CMS, often used by Russian breeders, is S-cytoplasm, the rarest type of CMS is R-cytoplasm, and the proportion of T-cytoplasm among the analyzed breeding lines was 20.5%.

Delineating chilling and forcing periods is one of the challenging topics in understanding how temperatures drive the timing of budburst and bloom in fruit tree species. Here, we investigated this question on olive trees, using flowering data collected over six years on 331 cultivars in the worldwide collection of Marrakech, Morocco. Using a Partial Least Squares approach on a long-term phenology (29 years) of ‘Picholine Marocaine’ cultivar, we showed that the relevance of delineating the chilling and forcing periods depends more on the variability of inter-annual temperatures than on the long-term datasets. In fact, chilling and forcing periods are similar between those delineated by using datasets of 29 years and those of only 6 years (2014–2019). We demonstrated that the variability of inter-annual temperatures is the main factor explaining this pattern. We then used the datasets of six years to assess the chill and heat requirements of 285 cultivars. We classified Mediterranean olive cultivars into four groups according to their chill requirements. Our results, using the Kriging interpolation method, indicated that flowering dates of most of these cultivars (92%) were governed by both chilling and forcing temperatures. Our investigations provided first insights to select adapted cultivars to global warming.

Over the last decade, Psidium guajava L. (guava) leaves have demonstrated their in vitro and in vivo effect against Diabetes mellitus (DM). However, there is a lack of literature concerning the effect of the individual phenolic compounds present in the leaves in DM disease. For this reason, the aim of the present work was the in silico evaluation of each phenolic compound. The identification of an 80% ethanol extract of guava leaves revealed the presence of 73 compounds. The in silico study carried out with the DIA-DB web server revealed that aldose reductase was the target protein with heterogeneous affinity. Naringenin exhibited the highest number of interactions with target proteins, and compounds like catechin, quercetin, naringenin and morin displayed similarities with known antidiabetic drugs. In conclusion, the computational workflow showed that guava leaves contain several compounds that can play a therapeutic role in the treatment of DM.

Autism Spectrum disorder (ASD) and intellectual disability (ID) are the most frequent develop-mental disorders with a prevalence between 3% and 5% of the population. In addition, both ASD and ID can be found in the same patient. Mutations in several genes involved in the epigenetic regulation of gene expression have been linked to different ID associated with ASD features including alterations of the ly-sine-acetyltransferase 6A (KAT6A) gene in KAT6A syndrome. KAT6A enzyme participates in a wide range of critical cellular functions such as chromatin remodeling, gene expression, protein synthesis, cell metabolism, and replication. In this manuscript, we examined the pathophysiolog-ical alterations in fibroblasts derived from three patients harboring KAT6A mutations. We ad-dressed survival in stress medium, histone acetylation, protein expression patterns and tran-scriptome analysis as well as cell bioenergetics. In addition, we evaluated the therapeutic effec-tiveness of epigenetic modulators and mitochondrial boosting agents such as pantothenate and L-carnitine in correcting the mutant phenotype. Pantothenate and L-carnitine treatment increased histone acetylation and corrected protein and transcriptomic expression patterns in mutant KAT6A cells. Furthermore, cell bioenergetics of mutant cells was significantly improved. Our results suggest that pantothenate and L-carnitine can significantly correct the mutant phe-notype in cellular models of KAT6A syndrome.

A dendrochronological investigation was undertaken on subfossil Scots pine (Pinus sylvestris L.) stumps following their discovered during conservation management activities at Wem Moss, a small (28ha) former raised mire in Shropshire, UK. Two ring-width chronologies were constructed from 14 of the 17 trees investigated spanning 198 and 208 years respectively. Whilst absolute dating was not possible, radiocarbon assays provided an estimated age for this mire-rooting woodland of between 3015 – 2505 years Cal BC, coinciding with the age traditionally associated with the widespread mortality of pine trees throughout much of the UK and Ireland, The Pine Decline (circa 4 ka radiocarbon years BP). Placed in a wider geographical context, the Wem Moss pines are located within the wider lowland area of the Meres and Mosses Region, where previous studies on subfossil pine have demonstrated protracted declines in mire-rooting trees. These have included tree mortality significantly post-dating The Pine Decline, notably at larger peatland sites exceeding 5.5 km2. This macrofossil evidence for the presence of Scots pine into the late Holocene is supported by continuous Pinus pollen representation at peatland sites in the Welsh Marches (English-Welsh border) suggesting the possible survival of native Scots pine trees in this area up to the present-day. This research highlights the incomplete and patchy nature of palaeo-vegetational records and also the potential for genetic research on living Scots pine in possible refugial areas in the UK and Ireland.

Human societies demand sustainable alternatives for goods and services. Plants are sustainable sources of important metabolites with beneficial impacts on human health. There are many reported methodologies and commercial suppliers for extract preparations from the plant Mucuna sp. They usually claim to be enriched in L-dopa, their distinctive metabolite. However, there are poor characterizations of the metabolite's components in that extracts. Here, we present the metabolite characterization of a Mucuna seed extract, emphasizing the L-dopa identification and quantification. To obtain the extracts, we follow a green and sustainable extraction protocol. The lyophilized extract was subject to liquid chromatography and mass spectrometry to identify its primary metabolites. Additionally, we follow thin-layer chromatography to identify some carbohydrates in the sample. The resultant extract has a 56% L-dopa. Other main components in the extract were arginine, stizolamine, and the fructooligosaccharides sucrose and nystose. The characterized Mucuna extract can be easily standardized as powder presentation and used in several biomedical applications.

Heavy Ion Beam Probing (HIBP) diagnostic is a powerful tool for electric field studies in hot dense plasma of modern day toroidal magnetic confinement devices. On the TUMAN-3M to-kamak, the HIBP have been used in regimes with improved plasma confinement to clear up the role of radial electric field in the transition to good confinement regimes. Recently, a moderni-zation of the TUMAN-3M HIBP diagnostics was performed aiming to reconfigure it for a work with a reversed plasma current direction and improvement of overall stability of the diagnostic. The results of first measurements of plasma potential in co-NBI scenario are reported and dis-cussed.

Estimating the parameters of statistical distributions generally involves solving a system of nonlinear equations or a nonlinear equation, being a technical difficulty in their usual application in hydrology. This article presents improved approximations and, in some cases, new approximations for the estimation with the method of ordinary moments and the method of linear moments, which are useful for the direct calculation of the parameters, because the errors in the approximate estimation are similar to the use of iterative numerical methods. Thirteen statistical distributions of two and three parameters frequently used in hydrology are presented, for which parameter estimation was laborious. Thus, the approximate estimation of the parameters by the two methods is simple but also precise and easily applicable by hydrology researchers. The approximate forms characterized by very small errors are the result of the research conducted within the Faculty of Hydrotechnics to update the romanian normative standards in the hydrotechnical field.

In this work, we explore the extreme searching of multidimensional functions by natural gradient descent based on Dirichlet and generalized Dirichlet distributions. The natural gradient is based on describing multidimensional surface with probability distributions, which allows us to reduce changing the accuracy of gradient and step-size. In this article, we propose an algorithm of natural gradient descent based on Dirichlet and generalized Dirichlet distributions. We demonstrate that the natural gradient descent with step-size adaptation with Dirichlet and generalized Dirichlet distributions has higher accuracy and does not take a large number of iterations for minimizing test functions than gradient descent and Adam.

This study proposed a spatially and temporally improving methodology adopting the Regional Frequency Analysis with L-moments approach to estimate rainfall quantiles from 22787 grids of radar rainfall in Taiwan for a 24-hour duration. Due to limited radar coverage in the eastern region, significant discordant grids were found in the coastal area of the eastern region. A K-means cluster analysis using scaled at-site characteristics was used to group the QPESUMS grids in Taiwan into 22 clusters/sub-regions based on their characteristics. Spatially, homogeneous subregions with QPESUMS data produce more detailed homogeneous subregions with clear and continuous boundaries, especially in the mountain range area where the number of rain stations is still very limited. According to the results of z-values and L-moment ratio diagrams, the Wakeby (WAK), Generalized Extreme Value (GEV), and Generalized Pareto (GPA) distributions of rainfall extremes fitted well for the majority of subregions. The Wakeby distribution was the dominant best-fitted distribution, especially in the central and eastern regions. The east of the northern part and southern part of Taiwan had the highest extreme rainfall for each return period. Both areas were frequently struck by typhoons. By using grid-based (at-site) as the basis for assessing regional frequency analysis, the results show that the regional approach in determining extreme rainfall is very suitable for large-scale applications and even better for smaller scales such as watershed areas. The spatial investigation was performed by establishing regions of interest in small subregions across the northern part. It showed that regionalization was correct and consistent.

Background: The use of medicinal plants and their effective compounds as natural sources that have antioxidant properties, has been considered by researchers. Antioxidants are compounds that effectively inhibit the reaction of oxygen and nitrogen-free radicals with biomolecules in a variety of ways, reducing damage or preventing cell death, cardiovascular diseases, and cancers. Objective: In this study, chemical compounds of Adiantum capillus-veneris essential oil were used to evaluate its antioxidant and antimicrobial activity using water distillation and gas chromatography. Methods: The whole plant was dried at room temperature at 25 ° C and the distillation method with water with modifications was used using a Clevenger device for essential oil extraction. Gas chromatography-mass spectrometry (GC/MS) was used to identify the resulting essential oil compounds and the antioxidant and antibacterial activity of the essential oil was evaluated. Results: The most important chemical constituents of Adiantum capillus-veneris essential oil were carvone (33.00%), carvacrol (15.05%), hexadecanoic acid (7.02%), hexahydrofarnesyl acetone (4.25%) and n-nonanal (4.2%). The antibacterial activity of Adiantum capillus-veneris essential oils (mg/ml) was calculated and the highest antibacterial activity was determined by Staphylococcus aureus (8.23±1.07), Streptococcus pyogenes (12.46±1.62), and Diphtheroid (11.37±1.36) at a concentration of 100 mg/ml of essential oils. Conclusion: The results of the present study showed that the essential oil of Adiantum capillus-veneris prevented the growth of three pathogenic bacteria. This antibacterial property is due to the presence of flavonoid compounds in Adiantum capillus-veneris has the capacity for therapeutic and medical uses.

Methylmercury is a neurotoxin present in fish tissues that permeates the blood-brain barrier after consumption. Previous research has shown that methylmercury is harmful to neurons, causing pH alterations, oxidative stress, excitotoxicity, and parenchymal damage. Methylmercury is a known factor of neurological disorders including Alzheimer's and Parkinson's. The method by which methylmercury passes through the blood-brain barrier is largely unknown. According to preliminary studies, one way methylmercury crosses the blood-brain barrier is by creating a complex with L-Cysteine, which facilitates its passage by the LATs system through mimicking another amino acid existing in the body. The human blood-brain barrier was studied using C. elegans as a model organism. It was hypothesized that if methylmercury passes through the blood-brain barrier of C. elegans faster with L-Cysteine present than without L-Cysteine present, the methylmercury's adverse effects (death and locomotive difficulty) will occur sooner. Each of the four experimental groups contained one C. elegans: the control, the L-Cysteine group, the methylmercury group, and the methylmercury and L-Cysteine combination group. The effects of L-Cysteine and methylmercury on C. elegans were studied using three metrics: viability, locomotive disability, and time for locomotive effects to occur. The group that received both methylmercury and L-Cysteine had reduced viability rates and a decreased time for locomotive difficulty to develop, supporting the hypothesis. These findings suggest that L-Cysteine aids methylmercury permeation through the blood-brain barrier. Because the experiment indicates how methylmercury penetrates the blood-brain barrier, these results aid in finding a therapeutic solution to reverse methylmercury neurotoxicity in the brain. Additionally, this study further opens channels into potential therapeutic and preventative measures for dementia, improving morbidity and mortality in neurodegenerative diseases.

Cells actively sense differences in topology, matrix elasticity and protein composition of the extracellular microenvironment and adapt their function and morphology. In this study, we focus on the cross-talk between matrix stiffness and protein coating density that regulate morphology and proliferation dynamics of single myocytes. For this, C2C12 myocytes were monitored on L-DOPA functionalized hydrogels of 22 different elasticity and fibronectin density compositions. Static images were recorded and statistically analyzed to determine morphological differences and to identify the optimized extracellular matrix (ECM). Using that information, selected ECMs were used to study the dynamics before and after cell proliferation by statistical comparison of distinct cell states. We observed a fibronectin density independent increase of the projected cell area until 12 kPa. Additionally, changes in the fibronectin density led to an area optimum at about 2.6 μg/cm, which was confirmed by an independent F-actin analysis, revealing a maximum actin filament to cell area ratio of 7.5 %. The proliferation evaluation showed an opposite correlation between cell spreading duration and speed to the matrix elasticity and protein density, which did not affect the cell cycle duration. In summary, we identified an optimized ECM composition, while independent matrix properties regulate distinct cell characteristics.

In plants, water flows are the major driving force behind the growth and play a crucial role in the life cycle. To study hydrodynamics, methods based on tracking small particles inside water flows occupy a special place. Due to these tools, it is possible to get information about the dynamics of the spatial distribution of the fluxes characteristics. In this paper, using contrast-enhanced MRI, we have shown that gadolinium chelate, used as an MRI contrast agent, marks the structural characteristics of xylem bundles of maize stem nodes and internodes. Supplementing MRI data, a high-precision visualization of xylem vessels by laser scanning microscopy was used to reveal structural and dimensional characteristics of the stem vascular system. In addition, we proposed the concept of using the prototype "Y-type xylem vascular bundles" as a model of the elementary connection of vessels within the vascular system. A Reynolds number can match the microchannel model with the real xylem vessels.

L-asparaginase (ASNase) is an aminohydrolase currently used in the pharmaceutical and food industries. Enzyme immobilization is an exciting option for both applications, allowing a more straightforward recovery and increased stability. High surface area and customizable porosity make carbon xerogels (CXs) promising materials for ASNase immobilization. This work describes the influence of contact time, pH, and ASNase concentration on the immobilization yield (IY) and relative recovered activity (RRA) using Central Composite Design methodology. The most promising results were obtained using CX with an average pore size of 4 nm (CX-4), reaching IY and RRA of 100%. At the optimal conditions, the ASNase-CXs biocomposite was characterized and evaluated in terms of kinetic properties and operational, thermal and pH stabilities. The immobilized ASNase onto CX-4 retained 71% of its original activity after six continuous reaction cycles, showed a good thermal stability at 37 °C (RRA of 91% after 90 min) and was able to adapt to both acidic and alkaline environments. Finally, the results indicated a 3.9-fold increase in the immobilized ASNase affinity for the substrate, confirming the potential of CXs as a support for ASNase and as a cost-effective tool for subsequent use in the therapeutic and food sectors.

Background: Continuous subcutaneous apomorphine infusion (CSAI), levodopa-carbidopa intestinal gel infusion (LCIG), and deep brain stimulation of the subthalamic nucleus (STN-DBS) have markedly changed the treatment landscape of advanced Parkinson’s disease (aPD). Despite a similar outcome of all device-aided therapies (DATs), some patients switch or combine DATs. The aim of this retrospective study was to explore the frequency and reasons for switching between or combining DATs in two movement disorders centres in Slovenia and Israel. Methods: We collected and analysed demographic and clinical data from aPD patients who switched between or combined DATs. Motor and non-motor reasons and their frequency for switching/combining were examined, as was the effect of DAT using the Global Improvement subscale of the Clinical Global Impression Scale. Non-parametric tests were used to analyse the data. Results: Of 505 aPD patients treated with DATs at both centres between January 2009 and June 2021, we identified in total 30 patients (6%), who either switched DAT (N=24: 7 LCIG-to-STN-DBS, 1 LCIG-to-CSAI, 5 CSAI-to STN-DBS, 8 CSAI-to-LCIG, 1 STN-DBS-to-LCIG, 1 LCIG-to-CSAI-to-STN-DBS, and 1 STN-DBS-to-CSAI-to-LCIG) or combined DATs (N=6: 5 STN-DBS+LCIG and 1 STN-DBS+CSAI-to-STN-DBS+LCIG). In most of these patients, inadequate control of motor symptoms was the main reason for switching or combining DATs, but non-motor reasons (related to the disease and/or DAT) were also identified. Conclusions: Switching between and combining DATs is uncommon, but in some patients brings substantial clinical improvement and should be considered in those who have either inadequate symptom control on DAT treatment or have developed DAT related complications.

To substitute of conventional manure and peat with alternatives sourcing from environmental conservation concerns, several promising alternatives has been attracting scientific parties’ interest, recently. However, among them compost perform the best, mostly and support carbon sequestration and mitigation against climate change. The article describes the made locally produced 70% in volume olive pruning branches compost (COMP) performance in two trials as an organic amendment in pepper production and an olive sapling substrate during 2019-2021 organic management in Turkey. The application of COMP to pepper trial conducted using factorial randomised block design with 4 replications and 6 treatments increased total organic matter and soil organic carbon, significantly (p<0.05) as compared to non-used plots in two locations. The olive sapling trial was conducted using a randomised plot design with 4 replications and 4 treatments. After the 12 months of growth, compost had the largest architecture rooted plants significantly different (p<0.05). Fresh volume (cm³) of COMP used saplings were obtained 35% less than 40% peat treatment, significantly (p<0.05) while 6^th month measurement was found as 40%. It is concluded that to enhance circular economy recycling and composting olive pruning branches is lucrative for the country to reduce external input usage in organic horticultural production.

HU is the Hypergeometrical Universe Theory (HU)[1-8], proposed in 2006, where the Universe is a Lightspeed Expanding Hyperspherical Hypersurface and Gravitation is an absolute-velocity-dependent, epoch-dependent force. Here we introduce the Big Pop Cosmogenesis and show our calculations associated with the Equation of State of the Universe. This article is the first in a series of articles[9-22] supporting the paradigm shift.

Among the first discovered and most prominent cellular oncogenes is MYC, which encodes a bHLH-ZIP transcription factor (Myc) that both activates and suppresses numerous genes involved in proliferation, energy production, metabolism and translation. Myc belongs to a small group of bHLH-ZIP transcriptional regulators (the Myc Network) that includes its obligate heterodimerization partner Max and six “Mxd proteins” (Mxd1-4, Mnt and Mga) each of which heterodimerizes with Max and largely oppose Myc’s functions. More recently, a second group of bHLH-ZIP proteins (the Mlx Network) has emerged. It is comprised of the Myc-like factors ChREBP and MondoA, which, in association with the Max-like member Mlx, regulate smaller and more functionally restricted sets of target genes, some of which are shared with Myc. Opposing ChREBP and MondoA are heterodimers comprised of Mlx and Mxd1, Mxd4 and Mnt, which also structurally and operationally link the two Networks. We discuss here the functions of these “Extended Myc Network” members with particular emphasis on the roles played by Max, Mlx and Mxd proteins in suppressing normal and neoplastic growth. These roles are complex due to the temporally- and tissue-restricted expression of Extended Myc Network proteins in normal cells, their regulation of both common and unique target genes and, in some cases, their functional redundancy.

There are many medicinal plants that have various medicinal properties in their different parts. The medicinal plants are major backbone of pharmaceutical industries. In this article we compare the antioxidants properties from various plants parts (root, stem, leaf, flower and bark) of the most important medicinal plant, Justicia adhatoda L. Various plant parts showed the good amount of antioxidant properties. These results enhance the medicinal properties of this plant due to the presence of good amount of antioxidants; among all the plant parts leaves and flowers showed maximum natural antioxidants, hence the study could be saying that this plant has good efficacy of antioxidants.

The nutraceutical value of pomegranate in the treatment of many neoplastic, cardiovascular, viral, inflammatory, metabolic, microbial, intestinal, reproductive and skin diseases is well-documented and is linked to its richness in phenolic compounds. This study aims to evaluate nutraceutical and genetic diversity of novel pomegranate genotypes (G1-G5) in comparison to leading commercial pomegranate varieties i.e. ‘Wonderful’, ‘Primosole’, ‘Dente di Cavallo’ and ‘Valenciana’. Morphometric measurements were carried out on fruits, accompanied by chemical characterization and the development of four new polymorphic SSR markers involved in the flavonoid pathway. The cultivars displayed a marked variability in the weight and shape of fruits, as well as in the weight of arils and juice yield. The highest level of total phenolic content and antioxidant activity was found in ‘Wonderful’ and G4, while the lowest was in ‘Dente di Cavallo’. Furthermore, the results showed that the pomegranate juice, is an excellent source of minerals, especially potassium, which plays a key role in organ functioning. The new flavonoid-related markers effectively differentiated the cultivars with the same diversity pattern as morpho-chemical characterization, so the SSRs developed in the present study can be used as a rapid tool for the identification of pomegranate cultivars with relevant nutraceutical traits.

Heteromorphic sex chromosomes are rarely found in plants. They were observed only in 47 species from phylogenetically distant families, suggesting that the evolution of sex chromosomes was independent in these species. It was shown that DNA repeat sequences are one of the major factors driving sex chromosomes evolution, and an accumulation or elimination of the repetitive DNA elements are closely linked with the formation of differences in the sex chromosomes. The goal of this study was to characterize the transposon composition in male and female plants of Cannabis sativa L., Humulus lupulus L. and Humulus japonicus Siebold &amp; Zucc. For the first time, the male and female genomes of H. japonicus as well as male genomes of H. lupulus and C. sativa have been sequenced (there were no open data about them). The analysis of genome-wide sequencing data with using Repeatexplorer2 and author’s scripts was carried out. It was shown that accumulation of Ty3-gypsy may be associated with speciation in Cannabaceae family which is the opposite of the theory of speciation throw whole-genome duplication. Moreover, the sex-specific DNA repeat clusters in C. sativa and H. japonicus were found. The analysis also revealed that the concentration of Tekay, Retand and Ikeros repeats in the Y chromosome of C. sativa is lower than in the X chromosome and the Angela concentration is higher in the Y chromosome.

Amino acid efflux and influx transport systems play vital roles in industrial microorganisms’ cell growth and metabolism. However, although biochemically characterized, most amino acid transporters remain unknown at the molecular level in Bacillus licheniformis. This study focuses on the molecular and functional characterizations of three transporters, YdgF, YvbW, and YveA, mainly when catalyzing the cross-membrane flux of L-Aspartate. When growing in the minimal medium with L-Asp as the only carbon and nitrogen source, the growth of strains lacking proteins YdgF, YvbW, and YveA was significantly inhibited compared with wild-type strains, while supplementing the expression of the corresponding proteins in the single-gene knockout strains can alleviate the inhibition to some extent. Upon overexpression, the recombinant proteins mediate the accumulation of L-aspartate to varying degrees. Compared with wild-type strains, the single knockout strains of the three protein genes exhibited reduced absorption of L-aspartate. In addition, this paper focuses on the effects of these three proteins on the absorption of β-alanine, L-glutamate, D-serine, D-alanine, and glycine.

Owing to their extraordinary properties, carbon-based nanomaterials are gaining traction in biomedicine. Green synthesis is the cost-effective method for fabricating carbon-based nanomaterials due to its rapidity, renewable nature, and sustainability. This study emphasis on the graphene oxide (GO) reduction using a simple one-pot technique that does not require the use of toxic reducing agents. This article reports the green synthesis of reduced graphene oxide (RGO) using Hibiscus sabdariffa L. calyxes extract as the natural reducing agent. Additionally, this article also provides analysis RGO using X-ray diffraction (XRD), UV-Visible spectroscopy (UV-Vis), and Raman spectroscopy. XRD result showed that the GO peak at 11o diminished, and a new hump appear at 22o indicating that the GO is fully reduced when it is refluxed for 6 hours, at 100oC with 1:3 ratio of GO:PE. The UV-Vis data indicated absorption peak of GO (237 nm) and RGO (265 nm) at distinct locations. This finding shed new light on the enormous potential of Hibiscus sabdariffa L. calyxes extract for green GO reduction. As a result, this environmentally friendly method can help reduce dependence on chemical materials.

The cork oak (Quercus suber L.), endemic essence of the Mediterranean Basin, is commonly used in traditional pharmacopoeia. The main objective of this work is to enhance the valorization of this plant species through the study of the anticandidosic activity of cork oak bark methalonic extracts in order to develop an efficient natural formulation for Candidiasis treatment.The anticandidosic activity of methanolic extracts of Q. suber bark stemming from decoction, maceration and Soxhlet methods of extraction in was tested on five different Candida albicans strains. Our results showed that all the tested extracts displayed an inhibitive activity, which varies according to the obtained extract and the tested strain. The best anticandidosic potential was observed with extracts obtained with Soxhlet method. The study of the acute toxicity showed that the lethal dose is 1150 mg/kg in mice, which remained moderately toxic according to Hodge and Sterner classification scale. Thus, this extract can be used in phytotherapy without danger in doses that are below 300 mg/kg of corporal weight. Based on these results, we can conclude that Cork oak bark extracts can be used to treat Candida albicans infections.

Alterations in the carnitine shuttle system may be an indication of the presence of cancer. As such, in-depth analyses of this pathway in different malignant tumors could be important for the detec-tion and treatment of this disease. The current study aims to assess the profiles of carnitine and acylcarnitines in gliomas with respect to their grade, the presence of isocitrate dehydrogenase (IDH) mutations, and 1p/19q co-deletion. Brain tumors obtained from 19 patients were sampled on-site using solid-phase microextraction (SPME) immediately following excision. Analytes were desorbed and then analyzed via liquid chromatography-high resolution mass spectrometry. The results showed that SPME enabled the extraction of carnitine and 22 acylcarnitines. An analysis of the correlation factor revealed presence of two separate clusters: short-chain and long chain car-nitine esters. Slightly higher carnitine and acylcarnitine concentrations were observed in the higher malignancy tumor samples (high vs low grade), and in those samples with worse projected clinical outcomes (without vs with IDH mutation; without vs with 1p/19q co-deletion). Thus, the proposed chemical biopsy approach offers a simple solution for on-site sampling that enables sample preservation, thus supporting comprehensive multi-method analyses.

PHLNs (polymeric lipid hybrid nanoparticles) are core–shell nanoparticle structures made up of polymer cores and lipid shells that have properties similar to both polymeric nanoparticles and liposomes. Methotrexate (MTX) loaded PLHNPs containing tween 80, phosphatidylcholine, poly D, L-lactic-co-glycolic acid (PLGA) & glyceryl tripalmitate prepared using solvent injection & homogenization method for glioblastoma treatment option. The MTX loaded PLHNPs optimized by Box–Behnken design to minimize particle size, higher entrapment efficacy, and maximize MTX concentration in the brain at 4h. The particle size, entrapment efficacy, concentration of drug in brain at 4h, zeta potential and AUC(Brain)/AUC(Plasma) ratio were in the range of 173.51-233.37nm, 70.56-86.34%, 6.38-12.38 μg/mL, 25.78-36.31mV & 1.02-5.32. in-vitro drug release studies, cellular internalization of optimized formulation against U-87 MG shows good anticancer effects.

Cannabis Sativa L. has been used for a long time to obtain food, fiber and as a medicinal and psychoactive plant. Today the nutraceutical potential of C. Sativa is being increasingly reappraised; however, C. Sativa roots remain poorly studied, despite citations in the scientific literature. In this direction, we identified and quantified the presence of valuable bioactives (namely β-sitosterol, stigmasterol, campesterol, friedelin and epi-friedelanol) in the root extracts of C. Sativa, a finding which might pave the way to the exploitation of the therapeutic potential of C. Sativa in all its parts. To facilitate roots harvesting and processing, aeroponic (AP) and aeroponic elicited cultures (AEP), have been set up and compared to soil-cultivated plant (SP): interestingly a considerable overgrowth of the plants - particularly of roots - and a significant increase (up to 20 fold in the case of β-sitosterol) in the total content of the above roots’ bioactive molecules have been observed in AP and AEP. In conclusion aeroponics, an easy, standardised, free of contaminant cultivation tecchnique, allows an ease harvesting/processing of roots along with a greater production of their secondary bioactive metabolites which could be utilized in the formulation of health promoting and health care products.

The objective was to analyze the effects of adding anthocyanin delphinidin-3-O-sambubioside and cyanidin-3-O-sambubioside of Hibiscus sabdariffa L. in animal diets. Scientific articles published before 2021 in clinics, pharmacology, nutrition, and animal production were included. The grains/concentrate, metabolic exigency, and caloric stress contribute to increasing the reactive oxygen species (ROS); the excess of ROS unbalance the oxidants and antioxidants. Cyanidin-3-O-sambubioside and delphinidin-3-O-sambubioside have antioxidant, antibacterial, antiviral, and anthelmintic activities. In the rumen, anthocyanin might show interactions and/or synergisms with substrates, microorganisms, and enzymes which could reduce the fiber degradability, but increase the potential methane (CH4) emissions; since anthocyanin interferes in the biohydrogenation of fats, they increase the fat milk and meat quality. Anthocyanins reduce plasma oxidation and deposit in tissues, increasing the milk and meat antioxidant activities. Cyanidin-3-O-sambubioside and delphinidin-3-O-sambubioside act as inhibitors of the angiotensin-converting enzyme (ACEi) and rennin expression which may improve milk yield (there is not enough evidence in ruminants, though). Polyphenols affect the reproductive potential. Sub products of HS contain as many amounts of polyphenols as calyces, and their inclusion in diets would positively affect the average daily gain and fat meat quality. Including HS in ruminant diets can improve the meat and milk quality.

Pteridophytes, represented by ferns and allies, are an important phytogenetic bridge between lower and higher plants (gymnosperms and angiosperms). Ferns have evolved independently of any other species in the plant kingdom being its secondary metabolism a reservoir of phytoconstituents characteristic of this taxon. The study of the possible medicinal uses of Polypodium vulgare L. (Polypodiaceae), PV, has increased particularly when in 2008 the European Medicines Agency published a monograph about the rhizome of this species. Thus, our objective is to provide scientific knowledge on the methanolic extract from the fronds of P. vulgare L., one of the main ferns described in the Prades Mountains, to contribute to the validation of certain traditional uses. Specifically, we have characterized the methanolic extract of PV fronds (PVM) by HPLC-DAD and investigated its potential cytotoxicity, phototoxicity, ROS production and protective effects against oxidative stress by using in vitro methods. Our results show that PVM is not cytotoxic against the different cell lines assessed, but we found potential cytoprotective and cellular repair activity in 3T3 fibroblast cells. This biological activity could be attributed to the high content of polyphenolic compounds; thus, this extract is positioned as a potential candidate for pharmaceutical uses.

This study aimed to identify new drug molecules against Leishmania parasites, leishmaniasis's causal agent, using Pistacia atlantica leaves as source. The evaluation of the anti-leishmania potential against the promastigote form of Leishmania. infantum and Leishmania. major was performed. A new in silico study was accomplished using molecular docking, with Autodock vina program, to find the binding affinity of two important phytochemical compounds from this plant (Masticadienonic acid, 3-Methoxycarpachromene) towards the trypanothione reductase as target drugs, responsible for defence mechanism against oxidative stress and virulence of this parasites. Results: Several concentrations showed a significant decrease in cell viability (P<0.0001), with IC50 values of 0.3 mg/ mL for L. infantum and 0.12 mg/ mL L. major; The molecular docking confirms the significant relationship between Leishmania survival and the inhibition of this crucial enzyme. There were promising and new positive results on binding modes of selected ligands and the trypanothione reductase for the first time. Through this work, we propose 3-Methoxycarpachromene and Masticadienonic acid as anti Trypanosomatidae species drug.

We used atomistic molecular dynamics (MD) simulations to study polyelectrolyte brushes based on anionic α-L-glutamic acid and α-L-aspartic acid grafted on cellulose in the presence of divalent CaCl2 salt at different concentrations. The motivation is the search of the ways to control properties such as sorption capacity and the structural response of the brush to multivalent salts. For this detailed understanding of the role of side chain length, chemical structure and their interplay is required. It was found that in the case of glutamic acid oligomers, the longer side chains facilitate attractive interactions with the cellulose surface, which forces the grafted chains to lie down on the surface. The additional methylene group in the side chain enables side chain rotation enhancing this effect. On the other hand, the shorter and more restricted side chains of aspartic acid oligomers prevent attractive interactions to a large degree and push the grafted chains away from the surface. The difference in side chain length also leads to differences in other properties of the brush in divalent salt solutions. At a low grafting density, the longer side chains of glutamic acid allow the adsorbed cations to be spatially distributed inside the brush resulting in a charge inversion. With an increase in grafting density, the difference in the total charge of the aspartic and glutamine brushes disappears, but new structural features appear. The longer sides allow for ion bridging between the grafted chains and the cellulose surface without a significant change in main chain conformation. This leads to the brush structure being less sensitive to changes in salt concentration.

Cotton is a potential and excellent candidate to balance both agricultural production and reme-diation of mercury-contained soil, as its main production fiber hardly involve into food chains. However, there is known rarely about the tolerance and response to Hg environments in cotton. In this study, The biochemical and physiological damages, in response to mercury (Hg), were investigated in upland cotton seedlings. The results on cottonseeds germination, indicated the germination rate were suppressed by high Hg levels, as the decrease of percentage was more than 10% at 1000 µM Hg. Shoots and roots’ growth were significantly inhibited above 10 µM Hg. The inhibitor rates (IR) in fresh weight were close between shoots and roots, whereas that in dry weight the root growth was more obviously influenced by Hg. In comparison of organs, the growth inhibition ranked as root > leaf > stem. The declining of translocation factor (TF) op-posed the Hg level even as low to 0.05 at 50 µM Hg. The assimilation of cotton plants was af-fected negatively by Hg toxicity, as evidenced from the performances on photosynthesis pig-ments (chlorophyll a and b) and gas exchange (Intercellular CO2 concentration (Ci), CO2 assimila-tion rate (Pn) and stomatal conductance (Gs)). Sick phenotypes on leaf surface included small white zone, shrinking and necrosis. Membrane lipid peroxidation and leakage were Hg dose-dependent as indicated by malondialdehyde (MDA) content and relative conductivity (RC) values in leaves and roots. More than 10 µM Hg damaged antioxidant enzyme system in both leaves and roots (P<0.05). Concludingly, 10 µM Hg post negative consequences to upland cotton plants in growth, physiology and biochemistry, whereas high phytotoxicity and damage ap-peared at more than 50 µM Hg concentration.

This paper addresses a variant of the product for the Dirichlet $L$--functions. We propose a completely detailed proof for the truth of the generalized Riemann conjecture for the Dirichlet $L$--functions, which states that the real part of the nontrivial zeros is $1/2$. The Wang and Hardy--Littlewood theorems are also discussed with removing the need for it. The results are applicable to show the truth of the Goldbach's conjecture.

Crapemyrtle (Lagerstroemia indica L.: Lythraceae) is the most popular summer flowering tree in the U.S. Its total value sold has almost doubled since 1998. Consumers prize crapemyrtles for their beauty and pest resistance. However, current crapemyrtle production and use is being threatened by crapemyrtle bark scale (Acanthococcus lagerstroemiae (Kuwana, 1907)) (CMBS), which has been confirmed in 12 U.S. states after its first sighting in Texas in 2004. Our survey results indicate that producers anticipate a significant decrease in the value of crapemyrtle due to CMBS, in the magnitude of 29.93% and 33.79%, in our 2018 and 2019 surveys respectively. Our findings indicate industry demand for CMBS control. We used a non-parametric test to compare the producers’ responses to several questions regarding CMBS-control, among the different producer categories included in our sample. Incorporated businesses showed the most support, followed by part-nerships, and family/individual operations were the least supportive of science-based CMBS control research. Large businesses predicted a more serious decrease in crapemyrtles’ value as compared to smaller businesses. More businesses with high volume of crapemyrtle-related business considered the benefits of CMBS-control to be higher than its cost, as compared to other businesses. We also used a relative importance index to illustrate the ranking of different attrib-utes of crapemyrtles that producers consider while making decisions about growing/purchasing the plants. Flower color was found to be the most important attribute, followed by disease re-sistance. If the issue of CMBS gets out of control, the industry might need to find potential re-placements to crapemyrtle. The most popular landscape plants that can potentially replace crapemyrtle, in the opinion of producers we surveyed, are vitex (Texas lilac) and magnolia.

Rhes is one of the most interesting proteins regulated by thyroid hormones that, through the inhibition of the striatal cAMP/PKA pathway, acts as a modulator of dopamine neurotransmission. It is expressed at high levels in the dorsal striatum, with a medial-to-lateral expression gradient reflecting that of both dopamine D2 and adenosine A2A receptors. Rhes is also present in the hippocampus, cerebral cortex, olfactory tubercle and bulb, substantia nigra pars compacta (SNc) and ventral tegmental area of the rodent brain. In line with Rhes-dependent regulation of dopaminergic transmission, several data showed that lack of Rhes enhanced cocaine and amphetamine-induced motor stimulation in mice. Previous studies showed that pharmacological depletion of dopamine significantly reduces Rhes mRNA levels in rodents, non-human primates and Parkinson’s disease (PD) patients, suggesting a link between dopaminergic innervation and physiological Rhes mRNA expression. Rhes protein binds to and activates striatal mTORC1, and modulates L-DOPA-induced dyskinesia in PD rodent models. Finally, Rhes is involved in the survival of mouse midbrain dopaminergic neurons of SNc, thus pointing towards a Rhes-dependent modulation of autophagy and mitophagy processes, and encouraging further investigations about mechanisms underlying dysfunctions of the nigrostriatal system.

Plant species are precursors of a wide variety of secondary metabolites that, besides having useful activity for themselves, can also be used by humans for their consumption and economic benefit. Pepper (Capsicum annuum L.) fruit is not only a common food and spice source, but it also stands out for containing high amounts of antioxidants (such as vitamins C and A), polyphenols and capsaicinoids. Particular attention has been paid to capsaicin, whose anti-inflammatory, antiproliferative and analgesic activities, have been proven. Due to the potential interest in pepper metabolites for human use, in this project, we carried out an investigation to identify new bioactive compounds of this crop is carried out. To achieve this, we developed a metabolomic approach, using an HPLC (high-performance liquid chromatography) separative technique coupled to metabolite identification by high resolution mass spectrometry (HRMS). After chromatographic analysis and data processing against metabolic databases, 12 differential bioactive compounds were identified in sweet pepper fruits, including quercetin and its derivatives, L-tryptophan, phytosphingosin, FAD, gingerglycolipid A, tetrahydropentoxylin, blumenol C glucoside, colnelenic acid and capsoside A. The abundance of these metabolites varied depending on the ripening stage of the fruits, either immature green or ripe red. We also studied the variation of these 12 metabolites upon treatment with exogenous nitric oxide (NO), a free radical gas involved in a good number of physiological processes in higher plants such as germination, growth, flowering, senescence, and fruit ripening, among others. Overall, it was found that the content of the analysed metabolites was modulated by the ripening stage and by the presence of NO. The metabolic pattern followed by quercetin and its derivatives, as a consequence of the ripening stage and NO treatment, was also corroborated by transcriptomic analysis of genes involved in the synthesis of these compounds. This opens new research windows on the pepper fruit’s bioactive compounds with nutraceutical potentiality, where biotechnological strategies can be applied for optimizing the level of these beneficial compounds.

The new Post Accelerating Data and Knowledge Online Society, or ‘Padkos’ requires a new model of decision making. This introductory paper proposes a model where decision making and learning are a single symbiotic process, incorporating man and machine, as well as the AADD (ánthrōpos, apparatus, decider, doctrina) diamond model of individual and organizational decision-making and learning processes. The learning is incorporated by using a newly proposed quadruple loop learning model. This model allows for controlled changes of identity, the process of creating and the sense making of new mental models and assumption, and reflections. The model also incorporates the recently proposed model of quantum decision-making, where time collapse of the opted past and the anticipated future (explicitly including its time horizon) into the present play a key role in the process, leveraging decision-making and learning by human as well as Artificial Intelligence (AI) and Machine Learning (ML) algorithms. The paper closes with conclusions.

The aim of the study was to assess the chemical and biochemical composition of heat-treated dates palm fruits (Phoenix dactylifera L.) cultivated in Algeria and stored under Modified Atmosphere Packaging (MAP). In this research, fresh dates palm fruits at harvest (Phoenix dactylifera L.) have been subjected at heat treatment at 55 ± 2°C for 20 min in a ventilated oven. The samples were packed in specific Polyethylene Terephthalate packaging (PET) bags with a thickness of 2.5 μm under MAP condition. The effect of this heat treatment on date fruits quality was investigated during 5 months of storage at room temperature storage (22 ± 1°C of temperature with 75 to 80% of relative humidity (RH), and 10 ± 1°C with 85 to 90% of RH). Chemical and biochemical composition of the samples were studied. Results indicated that during storage the Brix degree, protein, and vitamin C content changed significantly (p&lt;0.05). The major change was observed for lipid values varied from about 0.02 to 0.06% at 10°C, and 0.04 to 0.07% at 22°C for samples not heat-treated unpacked after 5 months of storage, these results represent a highly significant difference (p&lt;0.01). Harvesting at Tamr stage followed by treating the fruits with heat disinfestation packed in MAP, and storing at 10 ± 1°C showed to be a promising method for maintaining dates fruits storage quality.

Increasing genetic diversity in crop plants has been used for chemical mutagenesis. Through the application of various mutagenic agents, over 430 new varieties have been derived as rice mutants (Oryza sativa L.) Chemical mutagens such as ethyl methane sulphonate (EMS), diepoxybutane derivative (DEB), sodium azide, and gamma ray, x-ray, and quick neutron irradiation have been commonly used to induce a large number of functional variations in rice and others crops. Among chemical mutagens, ethyl methane sulfonate (EMS) is the alkylating agent most widely used in plants because it induces nucleotide substitutions to be extremely frequent, as detected in various genomes. In this study, seeds of potential genotype of the popular variety, (Oryza sativa L. Super Basmati variety) were treated with EMS at concentrations of 0.25%, 0.50%, 0.75%, 1% and 1.5%. Various measurements on the M1 generation determined EMS sensitivity. As concentration of applied EMS increased, will decrease in germination, shoot length, root length, plant height, productive tillers, Panicle Length, Total Spikelet, sterile spikelet and fertility under field conditions were observed in M1 generation as compared to the non-treatment control. Emergence, shoot length, root length, plant height, productive tillers, Panicle Length, Total Spikelet, sterile spikelet and fertility also decreased with increases in EMS mutagenesis in an approximately linear fashion. The LD₅₀ values were observed based on growth reduction of seedlings after EMS treatment with 0.25% and 0.50% on the rice variety (Oryza sativa L. spp.).

This study aimed at the investigation of the effect of substrate preheating on residual stress in laser powder bed fusion using a physics-based analytical model. In this study, an analytical model is proposed to predict the residual stress through the calculation of preheating affected temperature profile and thermal stress. The effect of preheating is super-positioned with initial temperature in the modeling of temperature profile using a moving heat source approach; the resultant temperature gradient is then employed to predict the thermal stress from a point body load approach. If the thermal stress exceeds the yield strength of the material, then the residual stress under cyclic heating and cooling will be calculated based on the incremental plasticity and kinematic hardening behavior of metal. IN718 is used as a material example to pursue this investigation. To validate the predicted residual stress, experimental measurements are conducted using X-ray diffraction on IN718 samples manufactured via laser powder bed fusion under different process conditions. Results showed that preheating of the substrate could reduce the residual stress in an additively manufactured part due to the reduction in temperature gradient and resultant shrinkage stresses. However, the excessive preheating could have an opposite impact on residual stress accumulation. Moreover, the results confirm that the proposed model is a valuable tool for the prediction of residual stress- eliminating the costly experiments and time-consuming finite element simulations.

Methods for cost calculation of Laser-based Additive Manufacturing (LAM) have evolved over the last two decades. Starting from a rapid prototyping manufacturing method, cost calculation over time included more than single part production for small series or mixed batches. New machine developments nowadays aim at large scale production and introduce modular machine designs that give LAM factory operators more decision freedom on machine configurations and expansibility. To leverage this new possibilities, LAM costing methods must be adapted to calculate and visualize the economic consequences of different module configurations.In this work a modelling architecture of L-PBF machines using virtual modules is presented. Using principles of the industry 4.0 communication standard OPC UA, a virtual machine is set up, parametrized and connected to the AM digital process chain. Two different views on the cost information are used, optimized for different use cases.First, the product view allows detailed analysis of cost allocation to parts in mixed batches and the layered geometry of the part. Second, the machine view tracks utilization of all machine modules, divided into the states idle, active, off and maintenance. The theoretical Overall Equipment Effectiveness (OEE) is calculated on a module basis, enabling economic analysis and optimization of module composition as well as module improvements and new modular machine constellations. This allows focusing research and development on most valuable improvements. By calculating different scenarios like spare part production, mass production or rapid prototyping, the part portfolio to be manufactured can be considered.

While L-PBF offers advantages in terms of geometrical freedom or lightweight construction, its use is often limited by economic constraints or currently achievable part costs. With an anticipated increase of L-PBF machine productivity during the next years, an increase of the share of material costs and the share of non-productive time for powder layer application process is to be expected. This results in a demand for less expensive powder materials and advanced processing strategies for the short-and medium-term advancement of L-PBF. As one possible approach, the processing of gas- and water atomized stainless steel (316L) powders with different morphology and particle size distribution as well as their impact on L-PBF productivity is investigated. The actual powder applicability in L-PBF systems and the L-PBF processability determines the minimum necessary powder quality. The main focus of the presented work is put on the interaction between powder quality, powder layer properties, part quality and cost-effectiveness of the L-PBF process. To this end, the influence of the gas and water-atomized powder properties (particle size and morphology) during the powder layer application process at highest possible powder recoater speeds and the resulting powder bed properties (powder layer density, powder bed density, powder demixing) and part properties (part density and tensile strength) is investigated.