In this work, we explore the intrinsic disorder status of the three members of the synuclein family of proteins - α-, β-, and γ-synucleins. We also analyzed the peculiarities of the amino acid sequences and modeled 3D structures of the human synuclein family members to find potential effects of pathological mutations. Furthermore, we conducted a comparative sequence-based analysis of the synuclein proteins from various evolutionary distant species and evaluated their levels of intrinsic disorder using a set of commonly used bioinformatics tools. Next, we conducted a detailed functional disorder analysis of the proteins in the interactomes of the human synuclein family members using various web-based disorder analysis and prediction tools, such as RIDAO, D2P2 and FuzDrop. We identify that the interactome of human α-synuclein has relatively higher levels of intrinsic disorder, as compared to the interactomes of human β- and γ- synucleins. These observations highlight the critical importance of intrinsic disorder of human α-synuclein and its interactors in neuronal processes as compared to other proteins of the synuclein family.

Today, various dietary supplements are taken to improve endurance performance during physical activity. These supplements have proven to be very successful in controlling and balancing various hormone levels and have contributed to the prevention and healing of metabolic disorders and physical injuries. In this study, we sought to investigate the effects of the ACTN3 gene and nutrient supplementation, including beta-alanine, ashwagandha, L-carnitine, and iron, on athletic performance. The ACTN3 gene has been identified as a potential genetic determinant of athletic performance, particularly in activities that require high levels of power and strength. This study investigated the interaction between the ACTN3 gene and supplementation and highlighted the potential for personalized approaches to improve athletic performance. 24 subjects per group, were randomized in a parallel-group design to examine the effects of supplementation on the ACTN3 gene and athletic performance over a 21-day intervention period. Participants in the intervention were divided into four groups of six members each. The same subjects who did not take supplements formed the control group. In addition, the subjects were divided into 4 groups (G1, G2, G3, and G4), each consisting of subgroups of control and a treated. All treated groups (TG1, TG2, TG3, and TG4) received 4 supplements for 21 days, namely S1 (ashwagandha), S2 (iron), S3 (beta-alanine) and S4 (L-carnitine), together with the 4 control groups, i.e. CG1, CG2, CG3 and CG4, who received no supplements during the same period. In particular, this study determines the effect of these 4 supplements on actn3 gene expression, testosterone, cholesterol and BUN levels of the participants. The P-values determined for all parameters showed statistically significant values and the final result showed that all supplements had positive effects on the tested parameters. The result showed a highly significant difference between the intake of supplements before and after the intake of 24 athletes per group on the ACTN3 gene expression level and biochemical indicators.

Cell-to-cell distant mechanical communication has been demonstrated by using in-vitro and in-vivo models. However, the molecular mechanisms underlying long-range cell mechanoresponsive interactions remain to be more elucidated. This study further examined the roles of α-Catenin and Piezo in traction force-induced rapid branch assembly of airway smooth muscle (ASM) cells on Matrigel hydrogel containing type I collagen. Our findings demonstrate that siRNA-mediated downregulation of α-Catenin or chemical inhibition of Piezo activity significantly reduced both cell directional movement and branching assembly. In regarding the role of N-cadherin in regulating branch assembly but not directional migration, our results further confirmed that siRNA downregulation of α-Catenin caused a remarked reduction of focal adhesion formation, as assessed by focal Paxillin and Integrin α5 localization. These observations implied that mechanosensitive α-Catenin was involved in both cell-cell and cell-matrix adhesions. Additionally, Piezo showed partial localization with Paxillin in focal adhesions, which was inhibited by α-Catenin downregulation with siRNA. This provides a plausible clue for Piezo mechanosensing traction force in the hydrogel. Collectively, our findings highlight the significance of α-Catenin in regulating cell-matrix interactions along with possible interpretation for Piezo mechanosensation at focal adhesions during cell-cell distant mechanical communication.

The focus of our study was the changes in the composition of semi-natural dry grasslands in Hungary. Since these valuable habitats were created with the help of humans, their preservation also requires regular treatment. Our mowing experiment aimed to investigate the suppression of the native Calamagrostis epigejos L. Roth. In Hungary, in the Cserhát Mountains, eight permanent plots were mowed twice a year. The vegetation was sampled annually between 2001 and 2011. The effects of mowing were investigated with repeated measures analysis of variance (ANOVA). After 10 years, the C. epigejos cover of the mowed plots decreased significantly, from the initial average of 62.38 to 7.50%. Surprisingly, we also experienced a similar decrease in the control plots. Regular treatment also had a positive effect on the number of species and diversity. Species richness increased continuously in both treatment types, which indicates the combined effect of vegetation succession and treatment. The biomass growth of other Poaceae and Fabaceae species, which are important from a grassland management perspective, was also facilitated by mowing. Our results suggest that long-term in situ experiments and continuous botanical studies are needed to establish a reliable utilization of grasslands.

L-Theanine, a unique non-protein amino acid, is an important bioactive component of green tea. Previous studies have shown that L-theanine has many potent health benefits, such as anti-anxiety effect, regulation of immune response, relaxing neural tension, reducing oxidative damage. However, little is known concerning whether L-theanine can improve the clearance of mitochondrial DNA (mtDNA) damage in organisms. Here, we reported that L-theanine treatment increased ATP production and improved mitochondrial morphology to extend the lifespan of UVC-exposed nematodes. Mechanistic investigations showed that L-theanine treatment enhanced the removal of mtDNA damage and extended lifespan by activating autophagy, mitophagy, mitochondrial dynamics, and mitochondrial unfolded protein response (UPRmt) in UVC-exposed nematodes. In addition, L-theanine treatment also up-regulated the expression of genes related to mitochondrial energy metabolism in UVC-exposed nematodes. Our study provided a theoretical basis for the possibility that tea drinking may prevent mitochondrial related diseases.

Research has shown that the consumption of herbal teas is linked with positive effects on the regulation of postprandial blood glucose level. In this study, a comparative analysis of aqueous and ethanol extractions is performed on four herbal teas (Mallotus, Cyclocarya, Rubus, Vine) to evaluate their phytochemical profiles and functional activities. Investigations of phytochemical contents, antioxidant activities, α-glucosidase inhibitory activities and chemical compositions are carried out through colorimetric analyses and UPLC-Q-Orbitrap HRMS/MS, respectively. Results showed that among the studied herbal teas, Vine exhibited the highest glucose re-gulating abilities under both aqueous and ethanol extractions. Overall, ethanol extracted samples yielded higher phytochemicals content, but the compositions of the phytochemicals varied. Meanwhile, aqueous extracts showed surprisingly strong antioxidant activities and comparable α-glucosidase inhibitory activities with ethanol extracts. Phytochemicals contents presented a positive correlation with antioxidant activities and α-glucosidase inhibitory activities. Nevertheless, antioxidant activities displayed a weak positive correlation with α-glucosidase inhibitory activities. Results from this study provided evidence that aqueous extracts from herbal teas possessed valuable phytochemicals composition for antioxidants and the hyperglycemic populations, and are promising candidates for potential applications as functional ingredients with health promoting effects and as natural additives to boost the nutritional value of herbal food products.

The aim of the work is to study the effect of the 3D printing process on the microstructural and hydrophilic properties of polylactic acid (PLA) samples with various model printing patterns obtained from the black Filament PLA by sequentially applying polymer layers using the FDM (Fused Deposition Modeling) method. X-ray phase analysis revealed partial crystallization of PLA polymer chains in printed samples, which occurs under thermal and mechanical action on the original amorphous PLA filament during 3D printing to varying degrees, depending on the geometry of the pattern and the morphology of its surface. At the same time, IR spectroscopy data indicate the preservation of all intrastructural chemical bonds of polylactide. Measured at the original installation, the values of the wetting edge angles on the surface of the printed samples are in the range φ = 50-60°, which is significantly less than the right angle. This indicates the hydrophilic properties of all samples’ surface. At the same time, the influence of different geometries of model drawings in printed samples was found not only on the morphology of the samples’ surface according to SEM data, but also on its wettability.

Berberis vulgaris (L.) has remarkable ethnopharmacological properties and is widely used in traditional medicine. The present study investigates B. vulgaris stem bark (Berberidis cortex) by extraction with 50% ethanol. The main secondary metabolites were quantified, resulting in a polyphenols content of 17.6780 ± 3.9320 mg Eq Tannic acid / 100 g extract, phenolic acids amount of 3.3886 ± 0.3481 mg Eq Chlorogenic acid / 100 g extract and 78.95 µg/g berberine. The dried hydro-ethanolic extract (BVE) was thoroughly analyzed using Ultra-High Performance Liquid Chromatography coupled with High-Resolution Mass Spectrometry (UHPLC–HRMS/MS) and HPLC and 40 bioactive phenolic constituents were identified. Then, the antioxidant potential of BVE was evaluated using three methods; our results could explain the protective effects of Berberidis cortex EC50FRAP = 0.1398 mg/mL, IC50ABTS = 0.0442 mg/mL, IC50DPPH = 0.2610 mg/mL compared to ascorbic acid (IC50 = 0.0165 mg/mL). Next, the acute toxicity and teratogenicity of BVE and Berberine - Berberine sulfate hydrate (BS) - investigated on Daphnia sp reported significant BS toxicity after 24 h; BVE revealed considerable toxicity after 48 hours and induced embryonic developmental delays. Finally, the anticancer effects of BVE and BS were evaluated on different tumor cell lines after 24 and 48 hours of treatments. The MTS assay evidenced a dose- and time-dependent antiproliferative activity, higher on BS than BVE. The strongest diminution of tumor cell viability was recorded on breast (MDA-MB-231), colon (LoVo) cancer, and OSCC (PE/CA-PJ49) cell lines after 48 h of exposure (IC50 < 100 µg/mL). However, no cytotoxicity was reported on normal epithelial cells (HUVEC) and hepatocellular carcinoma (HT-29) cell lines. Extensive data analysis supports our results, showing a significant correlation between the BVE's concentration, phenolic compounds content, antioxidant activity, exposure time, and the viability rate of various normal cells and cancer cell lines.

Aquaculture is an important source of food for the growing global population. To meet the increasing demand for fish, intensive aquaculture methods are commonly used. However, these methods can lead to stress and disease in fish, which can result in significant economic losses. Gamma-aminobutyric acid (GABA) is a non-protein amino acid that is found in the brain and central nervous system of animals as inhibitory neurotransmitter. It has been shown to have a variety of physiological functions, including stress reduction and immune enhancement. This study investigated the effects of dietary supplementation of GABA on growth, serum biochemistry, innate immunity and disease resistance in juvenile olive flounder (Paralichthys olivaceus) challenged with Edwardsiella tarda under high stocking density. A control diet and three experimental diets were prepared, with 150 mg/kg (GABA150), 200 mg/kg (GABA200), and 250 mg/kg (GABA250) of GABA added to each diet, respectively. The actual GABA content of the experimental diets was analyzed and found to be 63.9 mg/kg (CON), 231.3 mg/kg (GABA150), 291.6 mg/kg (GABA200), and 323.9 mg/kg (GABA250). Each experimental diet was fed to olive flounder with an initial weight of 12.75 g ± 0.3 g in 40 L tanks at two stocking densities: normal density (20 fish/tank) and high density (40 fish/tank). The experiment was conducted in triplicate for each diet and stocking density. The water temperature was maintained at 17.5 ± 1℃ and the salinity at 33 ± 1 ppt. After 8 weeks of feeding trial, growth, feed utilization, whole-body proximate composition, blood analysis, non-specific immune response, and challenge test were performed. There were no significant difference in weight gain and specific growth rate among the GABA concentrations and density × GABA concentration interaction groups. However, the low-density groups showed significantly higher values than the high-density groups (P < 0.05). There was no significant difference in feed efficiency and protein efficiency ratio among all groups. Moreover, there was no significant difference in the whole-body general composition analysis (P > 0.05). In the hematological analysis, there was no significant difference in cortisol in terms of diet and density × GABA concentration interaction, but the high-density experimental group showed a significantly higher value. Blood GABA significantly increased in proportion to the addition amount regardless of the density group (P<0.05). Superoxide dismutase activity in the non-specific immune response showed that the GABA-added experimental group had a significantly higher value than the control group, but there was no significant effect of the density densities or density × GABA concentration interaction (P<0.05). Myeloperoxidase activities in fish fed the GABA200 and GABA250 diets showed significantly higher values, and a density × GABA concentration interaction effect was observed (P<0.05). Lysozyme activity was significantly higher in the GABA150 group than in the CON, GABA200, and GABA250 groups (P < 0.05). After 15 days of challenge test by intraperitoneal injection of Edwardsiella tarda, the cumulative survival rates of the GABA150, GABA200, and GABA250 groups were significantly higher than that of the CON group (P < 0.05). The results suggested that the optimal dietary GABA level for juvenile olive flounder culture is 150 mg/kg, regardless of rearing density, to enhance growth, immune function and disease resistance.

The sexual reproduction of ascomycetes is controlled by the mating-type(MAT) locus. (Pseudo)homothallic reproduction has been hypothesized based on genetic data from Hirsutella sinensis (Genotype #1 of Ophiocordyceps sinensis). In this study, the differential occurrence of the mating-type genes in the MAT1-1 and MAT1-2 idiomorphs, which constitute the genetic control of O. sinensis reproduction, was analyzed in 237 strains and 5 genomes of H. sinensis. The mating-type genes were differentially transcribed in H. sinensis Strain L0106, and the MAT1-2-1 transcript in H. sinensis Strain 1229 was alternatively spliced, with an unspliced intron I containing stop codons; these findings constitute O. sinensis reproduction controls at the transcriptional and coupled transcriptional-translational levels. The occurrence of the mating-type genes and a-/α-pheromone receptor genes differed among the 5 H. sinensis genomes. The differential occurrence and transcription of these genes are inconsistent with self-fertilization under (pseudo)homothallism but suggest self-sterility of H. sinensis, which therefore needs a mating partner to achieve sexual outcrossing under heterothallism or hybridization. Consistent occurrence and transcription of the mating-type genes of both the MAT1-1 and MAT1-2 idiomorphs have been reported in natural and cultivated Cordyceps sinensis, but these findings are insufficient to determine the reproduction mode(s) because of the co-occurrence of >90 fungal species and multiple genomically independent genotypes of O. sinensis. The mutant MAT1-1-1 and α-pheromone receptor transcripts in natural C. sinensis result in the N-terminus or middle-truncated proteins, with changes in hydrophobicity and secondary structures of the proteins, suggesting heterogeneous fungal source(s) of the proteins and hybridization reproduction.

Berberis vulgaris L. (Berberidaceae) is a shrub that has been widely used in European folk medicine as an anti-inflammatory and antimicrobial agent. The purpose of our study was to elucidate the mechanisms of antiproliferative action of the plant’s methanolic root extract (BVR) against colon cancer cells. Cytotoxicity and pro-apoptotic activity were determined in human colon adenocarcinoma cell lines (LS180 and HT-29) and control colon epithelial CCD841 CoN cells. According to the MTT assay, after 48 h of cell exposure, the IC50 values were as follows: 4.3; 46.1 and 50.2 µg/mL for LS180, HT-29, and CCD841 CoN cells, respectively, showing the greater sensitivity of cancer cells to BVR. The Cell Death Detection ELISAPLUS kit demonstrated that BVR induced programmed cell death only against HT-29 cells. RT-qPCR with relative quantification method showed significant changes in the expression of genes related to apoptosis in both colon cancer cell lines. The genes BCL2L1 (126.84-366.66%), BCL2L2 (277.08-330.12%), CASP3 (180.36-261.36%) and CASP9 (158.08-213.46%) had significantly elevated expression, while BCL2 (23.08-52.06%) had reduced expression. Furthermore, in a panel of antioxidant tests, BVR showed positive effects (63.93±0.01, 122.92±0.01, and 220.29±0.02 mg Trolox equivalents (TE)/g in the DPPH•, ABTS•+ and ORAC assays, respectively). In the lipoxygenase (LOX) inhibition test, BVR revealed 62,60±0.87% of enzyme inhibition. The chemical composition of BVR was determined using UHPLC-UV-CAD-MS/MS analysis and confirmed the presence of several known alkaloids, including berberine, as well as other alkaloids and two derivatives of hydroxycinnamic acid (ferulic and sinapic acid hexosides). This is the first such extensive assessment of the biological activity of BVR. The results are very promising and encourage for the use of BVR as a comprehensive chemopreventive agent (anti-inflammatory, antioxidant, and pro-apoptotic) in colorectal cancer.

Existing implants used with Total Knee Arthroplasty (TKA), Total Hip Arthroplasty (THA), and other joint reconstruction treatments, have displayed premature failures and frequent needs for revision surgery in recent years, particularly with young active patients who represent more than 55% of all joint reconstruction patients. Bone cement and stress shielding have been identified as the major reasons for premature joint failures. A breakdown of the cement may happen, and revision surgery may be needed because of the aseptic loosening. The significant mismatch of stiffness properties of patient trabecular bones and metallic implant materials in joint reconstruction surgery results in the stress shielding phenomenon. This could lead to significant bone resorption and increased risk of bone fracture and the aseptic loosening of implants. The present project introduces an approach for development of customized cellular structures to match the mechanical properties and architecture of human trabecular bone. It consists of four modules:1- characterization of geometry, microarchitecture, and stiffness properties of patient’s bones; 2- developing customized lattice structures tailored to mimic properties established in module 1; 3 - integration of developed lattice structure into full scale implant design and manufacturing; 4- implementation of the developed technology for use in implants that would overcome most of the issues related to aseptic loosening phenomenon. The present work aims at fulfilling the objectives of module 2 by exploring new designs of customized lattice structures and texture tailored to mimic closely patients’ bone anisotropic properties and that can incorporate an engineered biological press-fit fixation technique. The effects of various lattice design variables on mechanical performance of the structure are examined through systematic experimental plan using statistical design of experiments technique and analysis of variance method. All tested lattice designs were explored under realistic geometrical, biological, and manufacturing constraints. Of the four design factors examined in this study, strut thickness was found to have the highest percent contribution (41%) regarding the structure stiffness, followed by unit cell type, and cell size. Srut shape was found to have the lowest effect with only 11% contribution. The introduced solution offers lattice structure designs that can be adjusted to match bone stiffness distribution and promote bone ingrowth and hence eliminating the phenomenon of stress shielding while incorporating biological press-fit fixation technique.

Nitrogen fertilization can provide greater nutritional support and mitigate salt stress in the millet crop. The aim of this study was to evaluate the physiological responses and agronomic performance of millet crops subjected to nitrogen fertilization and irrigation water salinity. The study was carried out in a greenhouse, using a completely randomized design in a 5 x 2 factorial scheme, with 4 rep-lications, with five doses of nitrogen (40; 60; 80; 100 and 120 kg ha-1 of N) and two levels of elec-trical conductivity of the irrigation water: 0.3 and 4.0 dS m-1. We concluded that salt stress in-creased leaf sodium levels and had a negative impact on stalk dry mass and panicle dry, leaf gas exchange, mineral element concentrations (K, P and Ca), and water use efficiency. The use of lower salinity water associated with increased nitrogen fertilization provides greater stalk dry mass and panicle dry, photosynthesis, water use efficiency, chlorophyll index, leaf potassium concentration, and biomass production. Salt stress negatively affected transpiration, stomatal conductance, leaf P and Ca levels, and increased leaf sodium levels as nitrogen fertilization increased in millet plants grown under pot conditions. These results can be used to create a strategy to reduce the negative impact of salt stress associated with the nutrition of millet plants, using nitrogen fertilization.

Cervical cancer is caused by a persistent and high-grade infection, caused by the Human Papilloma Virus (HPV), which, when entering cervical cells, alters their physiology and generates serious lesions. HPV 18 - is among those most involved in carcinogenesis in this region, but there are still no drug treatments that cause cure or total remission of lesions caused by HPV. Knowing that L-Asparaginase is an amidohydrolase, which plays a significant role in the pharmaceutical industry, particularly in the treatment of specific cancers, due to its antitumor properties, some studies have demonstrated its cytotoxic effect against cervical cancer cells. However, the commercial version of this enzyme has side effects, such as hypersensitivity, allergic reactions and silent inactivation due to the formation of antibodies. To mitigate these adverse effects, several alternatives have been explored, including the use of L-asparaginase from other microbiological sources, which is the case with the use of the fungus Aspergillus niger, a high producer of L-asparaginase. The study investigated the influence of the type of fermentation, precipitant, purification, characterization and in vitro cytotoxicity of L-asparaginase. The results revealed that semisolid fermentation produced higher enzymatic activity and protein concentration of A. niger. The characterized enzyme showed excellent stability at pH 9.0, temperature of 50ºC, resistance to surfactants and metallic ions, and an increase in enzymatic activity was also noted with the organic solvent ethanol. Furthermore, it exhibited low cytotoxicity in GM and RAW cells, and significant cytotoxicity in HeLa cells. These findings indicate that L-asparaginase derived from Aspergillus niger may be a promising alternative for pharmaceutical production. Its attributes, including stability, activity and low toxicity in healthy cells, suggest that this modified enzyme could overcome challenges associated with antitumor therapy.

Research on titanium oxo complexes (TOCs) are usually focused on their structure and photocatalytic properties. Findings from these investigations spurred our interest in exploring also their potential biological activities. In this study, we focused on the synthesis and structure of a compound with the general formula [Ti8O2(OiPr)20(man)4] (1), which was isolated from the reaction mixture of titanium(IV) isopropoxide with mandelic acid (Hman) in a molar ratio of 4:1. The structure (1) was determined using single-crystal X-ray diffraction, while spectroscopic studies provided insights into its physicochemical properties. To assess the potential practical applications of (1), its microcrystals were incorporated into a polymethyl methacrylate (PMMA) matrix, yielding composite materials of the type PMMA + (1) (2 wt.%, 5 wt.%, 10 wt.%, and 20 wt.%). The next stage of our research involved the antimicrobial activity evaluation of the obtained materials. Investigations carried out demonstrated antimicrobial activity of pure (1) and its composites (PMMA + (1)) against both Gram-positive and Gram-negative strains. Furthermore, MTT tests conducted on the L929 murine fibroblast cell line confirmed the lack of cytotoxicity of these composites. Our study identified (1) as a promising antimicrobial agent, also for producing composite coatings.

Woodland strawberry (Fragaria vesca L.) is an underutilized plant species, appreciated by consumers for its qualitative features. Utilizing technical means of production, such as plant biostimulants, that can increase crop productivity and quality could be highly important in woodland strawberry cultivation. The scope of the present study was to appraise the influence of two biostimulants (Trichoderma atroviride and plant protein hydrolysate) - used either alone or combined - on plant performance and economic profitability of two woodland strawberry genotypes (‘Alpine’ and ‘Regina delle Valli’). Overall, data showed that ‘Alpine’ had the highest productive performances, whereas ‘Regina delle Valli’ revealed the highest fruit qualitative traits. T. atroviride inoculation and V-PH application significantly boosted plant marketable yield (+20.5% for T. atroviride and +12.9% for V-PH), total sugars (+1.9% for Trichoderma and +1.4% for V-PH) and anthocyanins (+14.1% for T. atroviride and +9.8% for V-PH) compared to non-treated plants. Plants supplied with both biostimulants had higher marketable yield (+34.8%), mean fruit weight (+6.0%), fruit dry matter (+13.8%), total sugars (+3.5%), ascorbic acid (+12.7%), flavonoid (+26.3%) and anthocyanins (+29.9%) compared to non-treated plants. Furthermore, our study revealed that the highest fruit polyphenols concentration was recorded in both genotypes treated with the combination of biostimulants and in ‘Regina delle Valli’ sprayed with V-PH, whereas the highest antioxidant activity was found in ‘Regina delle Valli’ fruit when plants were supplied with both biostimulants. Our study pointed out that the application of microbial and non-microbial biostimulants, especially in combination, might be an useful strategy for improving performances of underutilized species and, therefore, encourage its cultivation, valorisation and economic profitability (+10195.3 €/ha when plants were exposed to both biostimulants).

Background: The management of erectile dysfunction (ED) shows several grey zones and new treatments for reduce the percentage of patients who discontinued the treatment are required. Here, we aim to evaluate the role of a natural mixture of named Icarifil (L-Citrulline, L-Carnitine, Eruca vesicaria, Panax ginseng, Tribulus terrestris, Turnera diffusa, Taurine, Vitamin E, Zinc) in the management of patients with ED. Methods: From September 2022 to March 2023, all patients attending 3 urological institutions due to ED were randomized to receive: Icarifil 1 sachet every 24 h (Group 1) or Icarifil 1 sachet + tadalafil 5 mg 1 tablet every 24 h (Group 2) or tadalafil 5 mg 1 tablet daily (Group 3), for 3 months. All patients underwent urologic visit and dedicated questionnaires (IIEF-5, SEP-2, SEP-3) at the enrollment and at the follow-up evaluation (3 months). Patient Reported Outcomes (PROs) at the follow-up evaluation were used. Primary endpoint was the difference in the questionnaires at the follow-up visit when compared with enrollment among the study groups. Results: In the per-protocol analysis, 52 patients in the Group 1, 55 in the Group 2 and 57 in Group 3 have been analyzed. At the follow-up evaluation, IIEF-5 have been improved in all the 3 Groups between enrollment and follow-up evaluation, but a statistically significant difference has been reported between Group 2 (+7.4) versus Group 1 (+4.1) or 3 (+5.1), (p<0.001; p<0.001). Moreover, 47 patients (94.0%) in the Group 2 showed an improvement in the SEP questionnaires, when compared with the baseline, while 29 in the Group 1 (56.9%) and 42 in the Group 3 (82.3%) with a statistically significant difference (p=0.004; p=0.003) among the Groups. The PROs analysis reported a better efficacy and patients’ satisfaction in Group 2 when compared with Group 1 or 3. Conclusions: In conclusion, Icarifil is able to improve penile erectile function in mild–moderate ED and it is able to significantly improve the clinical efficacy of tadalafil 5 mg daily use. Icarifil could be represent an interesting alternative treatment in patients experiencing adverse effects or with contraindications for chronic treatment with PDE5-is.

Industrial hemp (Cannabis sativa L.) is an attractive candidate for sustainable pest management due to its abundance of bioactive compounds with potential pesticidal properties. Solvent choice has a significant impact on the extraction efficiency of bioactive compounds. Deep Eutectic Solvents (DESs) are gaining popularity in extraction because they are safe and environmentally friendly, making them viable alternatives to organic solvents (OSs). This research first compared the extraction efficiency of OSs on the extraction of phytochemicals from the infloresences of two hemp varieties, Citrus and Cherry Dwarf. Inflorescences were extracted using three OSs, ethanol, ethyl acetate, and hexane. The highest level of cannabidiol (CBD; 0.69%) was extracted from Cherry Dwarf using ethanol while the level of delta-9 tetrahydrocannabinol THC (0.19%) was essentially the same in both. Therefore, Cherry Dwarf was selected to compare the extraction efficiency of DESs to the OSs. The DESs were choline chloride/ethylene glycol, citric acid/ethylene glycol, menthol/lauric acid, choline chloride/urea and choline chloride/glycerol. In the targeted analysis, choline chloride/ethylene glycol extracted the highest amount of CBD (0.87%) followed by choline chloride/urea (0.78%). As some DESs outperformed ethanol, the popular solvent for extracting cannabinoids, DESs are viable candidates to replace organic solvents.

Fibrosis is a ubiquitous pathology, and prior studies have indicated that various artemisinin (ART) derivatives (including artesunate (AS), artemether (AM), and dihydroartemisinin (DHA)) can reduce fibrosis in vitro and in vivo. The medicinal plant, Artemisia annua L., is the natural source of ART and is widely used, especially in underdeveloped countries, to treat a variety of diseases including malaria, while A. afra contains no ART but is also antimalarial. Using human dermal fibroblasts (CRL-2097), we compared the effects of A. annua and A. afra tea infusions, ART, AS, AM, DHA, and a liver metabolite of ART, deoxyART (dART), on fibroblast viability and expression of key fibrotic marker genes after 1 and 4 days of treatment. AS, DHA, and Artemisia tea significantly reduced fibroblast viability at 1 and 4 d post-treatment. After 4 d post treatment, AS, DHA, and A. afra tea downregulated ACTA2, and upregulated MMP3, with other genes either being unaffected or differentially affected. ART and AM had no significant effect on either fibroblast viability or fibrotic gene expression. Although A. annua contains ART, it had a significantly greater anti-fibrotic effect than ART alone. Immunofluorescent staining for smooth muscle α-actin (α-SMA) correlated well with transcriptional responses of drug-treated fibroblasts. Together, proliferation, qPCR, and immunofluorescence results show that treatment with ART, AS, DHA, and the two Artemisia teas yield differing responses, including those related to fibrosis, in human dermal fibroblasts.

Yellow eels were sampled by electrofishing in 1979, 1980 and 1981 in Vester Vedsted Baeck, Denmark, stem 6 km, catchment 24 km², with outlet to the North Sea. Yellow eels were aged by burning the otoliths. The eels were not sexed, and they varied from 6.5 to 44 cm in length. The ages varied from 0+ to 10+ year. The annual growth rate ∆ varied from 3.4 cm for 0+ eel to 2.2 cm for 10+ eel with a mean of 3.1 cm. Body mass wet wt. was recalculated to Kcal energy, with an annual growth rate ∆ of 5.33 Kcal. In contrast to body mass, the annual growth rate ∆ in Kcal increased with age. Von Bertalanffy growth trajectory (cm) of length-at-age was calculated and L∞ = 118.4 cm. Annual natural mortality M was estimated, and M was significantly depending on body mass, i.e. high M and low body mass vs. low M at high body mass. The biological production was calculated to 13.5 g wet weight m^-2 year^-1. Total 780 eel stomachs were analyzed, of which 287 (37%) were empty. The weight of food content (2.1% of eel body mass) increased proportional with eel body mass. Chironomid larvae, Ephemeroptera nymph, Simulium larvae and Gammarus pulix were the dominating food taxa, followed by Trichoptera larvae. Size of prey were independent on length of eel.

Cadmium Sulfide nanoparticle (CdS-LA hybrid nanoparticles) was synthesized here by a green approach using the precursor cadmium acetate and sodium sulphide along with the extract of a plant Lathyrus aphaca L. containing the phytochemicals which were responsible for surface modification of nanoparticles. The nanoparticle was used to evaluate their inhibition potential against species of bacteria and fungi. The nanoparticles were characterized by XRD which demonstrates the hexagonal crystal structure. SEM confirms the homogenous surface appearance of the CdS-LA hybrid crystalline structure. EDX analysis confirms surface modification of nanoparticles by phytochemicals. FTIR confirmed the Cd-S linkage laterally with the related functional groups and the presence of metabolites on the surface of nanoparticles. The UV-visible spectroscopy confirmed the peak at the characteristic wavelength range but a slight shift occurred in the peak of the CdS nanoparticles due to the presence of the phytochemicals. This study particularly provides an environment-friendly strategy to synthesize the CdS nanoparticles capped by Lathyrus Aphaca L. extract that are biologically active due to the mediation of the plant extract. CdS-LA hybrid nanoparticles have shown inhibition potential against various species of bacteria and fungi and realize the biological importance of the green synthesis of nanoparticles especially mediated with the plant extract.

Malaria remains an important and challenging infectious disease, and novel antimalarials are required. Benzyl isothiocyanate (BITC), the main breakdown product of benzyl glucosinolate, is present in all parts of Tropaeolum majus L. (T. majus) and has antibacterial and antiparasitic activities. To our knowledge, there is no information on the effects of BITC against malaria. The present study evaluates the antimalarial activity of BITC and T. majus seeds, leaves, and stems aqueous extracts. We used flow cytometry to calculate the growth inhibition (GI) percentage of the extracts and BITC against unsynchronized cultures of chloroquine-susceptible Plasmodium falciparum (P. falciparum) 3D7-GFP strain. Extracts and/or compounds with at least 70% GI were validated by IC50 estimation against P. falciparum 3D7-GFP and Dd2 (chloroquine-resistant strain) unsynchronized cultures by flow cytometry, and the resistance index (RI) was determined. T. majus aqueous extracts showed some antimalarial activity higher in seeds than in leaves or stems. BITC’s GI was comparable to chloroquine’s. BITC’s IC50 was similar in both strains, thus a cross-resistance absence with aminoquinolines was found (RI < 1). BITC presented features that could open new avenues for malaria drug discovery.

Keywords: apoptosis; arbutus unedo L; formaldehyde; hippocampus; oxidative stress

Background and Objectives: Knee osteoarthritis (KOA) is a degenerative disease that is targeting continuously people of different ages, but especially the elderly population, the number of which tends to increase continuously at the global level. Apart from age, excess weight can influence the evolution of the disease, with obesity being associated with a weak inflammation stage, and an imbalance between pro-inflammatory and anti-inflammatory cytokines. The present work aimed to identify specific biomarkers alike ACRP-30, IL-10, TNF-α, and IL-6 in synovial fluid and correlate them with patients’ clinical data. Materials and Methods: 24 subjects with KOA and over 50 years of age are involved in the present study. All patients performed a supine X-ray at the target knee. Ultrasound was performed using an ESAOTE MyLab Omega (ESAOTE Spa, Italy) ultrasound device and a 6-19 MHz linear array transducer. Results: The obtained results highlighted a significant correlation between age and adiponectin level (p=0.0451, r=-0.412). Also, the IL-10 values are lower in cases where the intensity of the pain is more pronounced (p=0.0405, r=-0.421). In addition, analyzing the data by gender, it was observed that in the case of males, stiffness is more related to age (p=0.0079, r=0.7993), compared to women (p=0.0203, r=0.6223). In the case of women, the progression of the disease tends to increase more intensively total WOMAC score’s values (p=0.00031, r=0.8342), compared with men (p=0.0289, r=7013). Regarding interleukins and BMI, significant correlations were observed only in the case of men. Conclusions: A significant correlation between age and adiponectin, and adiponectin and IL-6, suggests that advanced age may contribute to adiponectin reduction. Comparing men with women, it was observed that men's age is more related to rigidity, and IL-6 and IL-10 are directly correlated to BMI and women seem to be more sensitive to pain and stiffness.

The present work was aimed at the chemical characterization and antimicrobial activity of some extracts of aerial parts (essential oils from leaves and inflorescences, and resins from inflorescences) of two legal hemp (Cannabis sativa) varieties, Tisza and Kompolti, grown in Sardinia. Chemical characterization was carried out by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) techniques. The antimicrobial activity of these extracts against a panel of microorganisms was also determined via minimum inhibitory concentration (M.I.C.) determination. While the results showed a minor or negligible antimicrobial activity of the extracts against Gram+ and Candida strains, a good antibacterial activity (especially of resins) was recorded against S. aureus; no substantial differences were detected between of the chemical compositions of the two Cannabis varieties.

Natural products from medicinal plants, either as pure compounds or as standardized extracts, provide unlimited opportunities for new drug leads because of the unmatched availability of chemical diversity. The objects of the study are medicinal plant raw materials Saussurea sordida Kar&Kir and Saussurea alpina DC. collected from South Kazakhstan during the flowering period in the spring-summer months of 2021. The present study was aimed to investigate the toxic effects acute administration of ethanol extracts from plants S. sordida and S. alpina in male Wistar rats. The ethanol extract by subjected to Phytochemical Screening, Fourier transform infrared spec-troscopy (FTIR) analysis. Phytochemical screening of the extract revealed the presence of phenolic compounds. FT-IR spectroscopic analysis revealed various characteristic band values with various functional groups in the formulation extract such as amines, alcohol, phenol, alkane, alkene, and conjugated acid groups. FT-IR analysis of peak values with various functional compounds such as alcohols, phenols, carboxylic acids, aldehydes, amides, amino acids, anhydrides, esters, ketones, unsaturated aliphatic, aromatics, unsaturated heterocycles, amines, nitro compound, alkanes, al-kenes and sugars. Histological examination of organ samples after studying the chronic toxicity of ex-tracts of two plant species (S. sordida . and S. alpina) revealed no pathological changes. The acute toxicity study revealed no lethal effects and behavioral signs of toxicity at the tested doses indicating that LD50 is greater than 2000 mg/kg. These results show low toxicity of on short-term use and liver toxicity on long-term use. This study helps to predict the formula and structure of active molecules which can be used as medicinal drugs. This result also enhances the traditional usage of S. sordida and S. alpina , which possesses a number of bioactive compounds.

This article describes a novel topical composition constituted by gamma-amino butyric acid (GABA) and microbial chondroitin sulfate. This composition, formulated by the author and manufactured in a certified facility in the United States of America, exhibits potential for non-invasive intervention in anxiety management, sleep quality enhancement, and promotion of brain-related functions like meditation and nonlocal consciousness. The core component comprises GABA, a key inhibitory neurotransmitter within the central nervous system, complexed with a suitable carrier molecule, microbial chondroitin sulfate. This complexation aims to enhance transdermal absorption and optimize delivery of GABA to target tissues. The proposed mechanism of action involves modulation of GABAergic signal transduction pathways. Application of the topical composition allows GABA penetration into the skin and potentially deeper tissues, where it interacts with GABA receptors. This interaction leads to mental calmness and relaxation as assessed by electroencephalography. The influence of GABAergic signaling on brain circuits demonstrated in this article, when associated with meditation and nonlocal consciousness, suggests potential for the composition to support these practices. The advantage of such an approach consists in avoiding the potential systemic side effects associated with oral or injectable administration of GABA, anxiolytics or hypnotics. Furthermore, the combination of GABA and microbial chondroitin sulfate may offer synergistic benefits, potentially enhancing the overall biological effects. In conclusion, this article presents a novel topical approach for managing anxiety, enhancing sleep quality, and potentially facilitating meditation and nonlocal consciousness through modulation of GABAergic signaling pathways. While further research is necessary, the potential for a non-invasive and potentially side-effect-free intervention in these areas is promising.

Extensive genome structure variation, such as copy number variations (CNVs) and presence/absence variations, is the basis for the remarkable maize genetic diversity; however, the effect of CNVs on maize herbivory defense remains largely underexplored. Here, we report that the naturally occurring duplication of the maize 9-lipoxygenase gene, ZmLOX5, leads to increased resistance of maize to herbivory by fall armyworms (FAW). Previously, we showed that ZmLOX5-derived oxylipins are required for defense against chewing insect herbivores and identified several inbred lines, including Yu796, that contained duplicated CNVs of ZmLOX5, referred to as Yu796-2×LOX5. To test whether introgression of the Yu796-2×LOX5 locus into the herbivore-susceptible B73 background that contains a single ZmLOX5 gene is a feasible approach to increase resistance, we generated a series of near-isogenic lines that contained either 2, 1 or 0 copies of the Yu796-2×LOX5 locus in the B73 background by six back crosses (BC6). Droplet digital PCR (ddPCR) confirmed the successful introgression of the Yu796-2×LOX5 locus in B73. The resulting B73-2×LOX5 inbred line displayed increased resistance against FAW associated with increased expression of ZmLOX5, increased wound-induced production of its primary oxylipin product, the α-ketol, 9-hydroxy-10-oxo-12(Z),15(Z)-octadecadienoic acid (9,10-KODA), and the downstream defense hormones regulated by this molecule, 12-oxo-phytodienoic acid (12-OPDA) and abscisic acid (ABA). Surprisingly, wound-induced JA-Ile production was not increased in B73-2×LOX5, resulting from the increased JA catabolism. Furthermore, B73-2×LOX5 displayed enhanced drought tolerance likely due to increased ABA and 12-OPDA content. Taken together, this study revealed that the duplicated CNV of ZmLOX5 quantitively contributes to maize antiherbivore defense and presents proof-of-concept evidence that the introgression of naturally occurring duplicated CNVs of a defensive gene into the productive, but susceptible, crop varieties is a feasible breeding approach for enhancing plant resistance to herbivory and tolerance to abiotic stress.

In vitro glucose uptake in yeast cell facilitated by Abelmoschus esculentus L. (okra seed) for management of type 2 diabetes was studied. Plant material was collected, identified, processed, and stored for further use. 80% methanol was employed for extraction and sonicated to release antidiabetic-bioactive component in solution and was filtered, concentrated, freeze-dried, and fractionated using standard techniques. Glucose uptake at an initial concentration of 5mM/L and 10mM/L by the crude extract was consistent to that of the known standard drug while at 25mM/L glucose concentration was equivalent with the crude extract. Also, at 0.625 mg/mL the linear equations, and R2 demonstrations that the crude extract was higher in dose predictability than the standard drug as presented by the equation; y = 35.754x - 57.822, and R² = 0.9502 (95%). The extract-fractions were employed to evaluate the ability of yeast cell line culture to take up glucose from the system through DPPH, FRAP, lipid peroxidation and anti-diabetes effect of extract-fraction assays. Extract-fractions were found to poses antioxidant activity high enough to inhibit stress-related diseases. The extract fractions were active as drug candidates both at low and high concentrations and were better compared with the standard drug and standard antioxidant was comparable. The high bioactive extract fractions require encapsulation with a nanoparticle as a drug candidate for type 2 diabetes patients. And an animal trial of the drug candidate may be necessary to monitor the in vivo performances of the extract fractions and subsequent human volunteered trial.

Pigmented corn is a gramineae food of great biological, cultural and nutritional importance for many Latin American countries, with more than 250 breeds in the American continent. It confers a large number of health benefits due to its diverse and abundant bioactive compounds. In this narrative review we decided to organize the information on the nutrients, bioactive compounds and phytochemicals present in pigmented corn, as well as their effects on human health. Phenolic compounds and anthocyanins are some of the most studied and representative compounds in these grasses, with a wide range of health properties, mainly the reduction of prooxidant molecules. Carotenoids are a group of molecules belonging to the terpenic compounds, present in a large number of pigmented corn breeds, mainly the yellow ones, whose biological activity incorporates a wide spectrum. Bioactive peptides can be found in abundance in corn, having very diverse biological effects that include analgesic, opioid, antihypertensive, etc. activity. Other compounds with biological activity found in pigmented corn are resistant starches, some fatty acids, phytosterols, policosanols, phospholipids, ferulic acid and phlobaphenes, as well as a great variety of vitamins, elements, and fibers. This review aims to disseminate and integrate the existing knowledge on compounds with biological activity in pigmented corn, in order to promote their research, interest and use by scientists, nutrition professionals, physicians, industries and the general population.

Food authorities aim to safeguard our food. This requires sensitive analyses to guarantee detection of both banned and regulated substances at low concentrations. At the same time, broad screening methods are needed to identify new emerging risks. For this purpose effect-based bioassays combined with mass spectrometric analyses offer an advantage. During the regular monitoring of dioxins in agricultural products, a discrepancy was observed between the results of the DR CALUX (Dioxin-Responsive Chemical Activated Luciferase gene Expression) bioassay and the confirmatory gas chromatographic high resolution mass spectrometric (GC-HRMS) analysis in egg and broiler fat samples. The response in the bioassay was high, suggesting a clear exceedance of the maximum limits of dioxins in these samples, yet regulated dioxins or dl-PCBs were not detected by GC/HRMS analysis . Ultimately, a broad screening analysis using GC-HRMS resulted in the identification of 2,3,7,8-tetrabromo-dibenzofuran (2,3,7,8-TBDF) in both egg and broiler fat. To investigate the potential; source of this brominated furan contaminant, different samples were analysed: bedding material, poultry feed, feed additives (choline chloride and L-lysine) and seaweed. The poultry feed and feed additives all contained 2,3,7,8-TBDF. Using a feed to food converter, it became clear that the poultry feed was probably the source of 2,3,7,8-TBDF in broilers and eggs through a feed additive like L-lysine or choline chloride. This study underlines the importance of using a combination of effect based screening assays with sensitive analytical methods to detect potential new and emerging risks.

The present study focuses on the yield, chemical composition, and antioxidant activity of essential oils from the leaves and fruit of wild-grown bay laurel (Laurus nobilis L.) in Montenegro. The chemical composition of isolated essential oils was determined by GC/MS and GC/FID. Antioxidant activity was determined using the DPPH assay. The laurel bay essential oil (LEO) yield was 0.88% in fruits and 2.65% in the leaves. The results obtained from this study indicate that the LEOs obtained from the different plant parts (leaves, fruit) display different compositions. Fifty components were identified in LEO leaves, with 1,8-cineole (39.4%), linalool (13.9%), α-terpinyl acetate (11.2%), sabinene (6.7%), methyl eugenol (5.7%), β-pinene (3.2%), and α-pinene (3.1%) being the most abundant ones. Fifty-five components were isolated in LEO fruits with 1,8-cineole (34.2%), α-pinene (6.6%), sabinene (6.1%), β-bisabolene (5.8%), β-pinene (4.8), α-terpinyl acetate (4.5%), and α-terpineol (4.3%) as the main components. However, this study is the first to present the chemical composition of the LEO fruits from Montenegro. The results indicate that the composition of LEO is similar to recent studies from Balkan and Mediterranean areas. The degree of DPPH radical neutralization increased with the incubation time. The LEO isolated from leaves showed better antioxidant activity (EC50 value of 1.43 mg/mL) in comparison to the LEO isolated from fruits (EC50 value of 3.74 mg/mL) during the incubation time of 120 min. Taken together, this study indicates that the LEO from leaves and fruits possesses significant antioxidant activities (possibly due to the high level of 1,8-cineole) and is an important component in the food and pharmaceutical industries. All plant parts of L. nobilis can be successfully used in LEO extraction and isolation.

Genetic enhancement of grain production and quality is a priority in wheat breeding projects. In this study, we assessed two key agronomic traits - grain protein content (GPC) and thousand kernel weight (TKW) - across 179 Bulgarian contemporary and historic varieties, and landraces in three growing seasons. Significant phenotypic variation existed for both traits among genotypes and seasons, and no discernible difference was evident between the old and modern accessions. To understand the genetic basis of the traits, we conducted a genome-wide association study with MLM using phenotypic data from the crop seasons, best linear unbiased estimators, genotypic data from the 25K Infinium iSelect array, and a Bonferroni-adjusted p-value. As a result, 776 significant quantitative trait nucleotides (QTNs) organized into quantitative trait loci were discovered, including 25 loci associated with GPC, and 35 loci linked to TKW. Additionally, 14 environmentally stable QTNs were identified for TKW. Certain loci on chromosomes 2A, 3A, and 6B favorably in-fluenced GPC, while the locus on chromosome 6D impacted TKW positively. These loci may reflect novel associations to the two traits. Annotations for proteins involved in the remobilization of carbon and nitrogen from vegetative tissues to developing grain during senescence, as well as in the following buildup of resources required for seed germination, have been found for selected pu-tative candidate genes. These include genes coding for 11S globulin seed storage protein, glutamine synthetase, metalloendopeptidase, components of the ubiquitin/proteasome system, sucrose transporter, alpha-amylase, NAC and bZIP transcription factors. Our findings highlight promising genomic regions for targeted breeding programs aimed at improving grain yield and protein content.

Coffee Coffea arabica L. depends on abundantly distributed rainfall and drought impacts their development, fruit production, bean quality, and ultimately, beverage quality. Plant Biotechnology by means of genetic manipulation and plant regeneration by the somatic embryogenic process is an alternative technology to overcome these prob-lems. In the present work we used the molecular approach of the trehalose/trehalase role in plant surviving in extreme drought/salt environments. We used a cassette containing the antisense C. arabica L. trehalase gene under the RD29 promoter from A. thaliana and the NOS terminator to genetically modified an em-bryogenic coffee C. arabica L. cv typica line under osmotic stress supplemented with mannitol (0.3M) and sorbitol (0.3M) containing medium. Drought resistant SE lines were recovered and regenerate plants. Resistant SE lines showed a higher rate of competence to induce secondary SE capacity. A transcrip-tome analysis was performed from high competent SE lines to understand the acquired molecular mechanisms to developed SE. From the up-regulated genes, a PPI network made by STRING v12.0 with high confidence (0.700) revealed the presence of the 10 modules. The cell cycle, chromatin remodeling, somatic embryogenesis, oxidative stress, generic transcription pathway, carbon metabolism, phenylpropanoid biosynthesis, trehalose biosynthesis, proline bio-synthesis and glycerolipid metabolism.

Inositol is a natural carbocyclic sugar that plays an essential role in regulating the vital cellular functions of plants and animals. Current research has explored methyl derivatives of inositol, reporting on their various biological activities, including antitumor, anti-inflammatory, and anti-osteoporosis activities. Our previous study demonstrated that L-quebrachitol, a methyl derivative of inositol, enhances osteoblastogenesis and bone formation; however, its effect on osteoclastogenesis remains unclear. Consequently, we aimed to investigate the effect of L-quebrachitol on the receptor activator of nuclear factor-κB ligand-induced osteoclastogenesis in pre-osteoclastic RAW 264.7 cells. The results revealed that L-quebrachitol suppressed RANK-mediated signalling, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Fos proto-oncogene (cFOS) pathways, at both gene and protein levels. Moreover, the critical transcription factor for osteoclastogenesis, nuclear factor of activated T cells c1 (NFATc1), was downregulated. Inhibition of osteoclast-associated marker genes encoding proteolytic enzymes, such as tartrate-resistant acid phosphatase (TRAP), matrix metallopeptidase 9 (MMP-9), and cathepsin K, led to reduced formation of TRAP-positive multinucleated cells and resorption pits. These findings demonstrate the dose-dependent inhibitory effect of L-quebrachitol on osteoclastogenesis through the modulation of receptor activator of nuclear factor κB (RANK)-mediated signalling pathways. However, further exploration of L-quebrachitol's potential as a therapeutic approach for osteoporosis is warranted.

In descriptive statistics, U -statistics arise naturally in producing minimum-variance unbiased estimators. In 1984, Serfling considered the distribution formed by evaluating the kernel of the U -statistics and proposed generalized L-statistics which includes Hodges-Lehamnn estimator and Bickel-Lehmann spread as special cases. However, the structures of the kernel distributions remain unclear. In 1954, Hodges and Lehmann demonstrated that if X and Y are independently sampled from the same unimodal distribution, X − Y will exhibit symmetrical unimodality with its peak centered at zero. Building upon this foundational work, the current study delves into the structure of the kernel distribution. It is shown that the kth central moment kernel distributions (k > 2) derived from a unimodal distribution exhibit location invariance and is also nearly unimodal with the mode and median close to zero. This article provides an approach to study the general structure of kernel distributions.

Radish (Raphanus sativus L.), a root vegetable belonging to the Brassicaceae family, is considered as one of the representative crops displaying sporophytic self-incompatibility (SSI). The utilization of a self-incompatibility system in F1 breeding can improve the efficiency of cross combinations, leading to a reduction in breeding time and aiding in the development of novel F1 varieties. The successful implementation of this system necessitates the rapid and accurate identification of S haplotypes in parental lines. In this study, we identified a total of 9 S haplotypes among 22 elite radish lines through Sanger sequencing. Subsequently, we obtained sequences for showing 95% similarity to 9 S haplotypes, along with sequences identified by other researchers using BLAST. Following this, multiple sequence alignment (MSA) was conducted to identify SRK and SLG sequence similarities, as well as polymorphisms within the class I, II groups. Subsequently, S haplotype-specific marker sets were developed, targeting polymorphic regions of SRK and SLG alleles. These markers successfully amplified each of 9 S haplotypes. these markers will play a crucial role in the rapid and precise identification of parental S haplotypes in the radish F1 breeding process, proving instrumental in the radish F1 purity test.

Multi-cropping can solve the energy and GHG balance problems, but the emergence, development and productivity of such mixed crops are at risk due to increasing drought periods. For this reason, single maize crops with inter-row mellowing and weed-mulching practices were compared with faba bean, crimson and Persian clover, and alfalfa intercropped maize cultivations. Tests were performed at the Experimental Station of Vytautas Magnus University, Lithuania. Results showed that by the 30% higher energy inputs were calculated in technologies with intercropped crimson, Persian clover, and alfalfa than in monocropped maize. Single maize crops produced by the 23-40% higher biomass yields compare to clover and alfalfa intercropped maize because, due to the drought periods, intercrops weakly sprouted and developed. Lower harvests reduced the energy output by up to 38%, energy efficiency ratio - by up to 2.5 times and net energy - by up to 42%. All tested technologies were environmentally friendly and similar according to the CO2 equivalent. Long-term drought periods during vegetative season due to climate change make us think about the improvement of intercropping technologies. Sowing intercrops at the same time with maize could solve the problem of its germination but highlight the problem of abundant weed spread. Therefore, this takes us to another sphere of agrotechnologies - the effective non-chemical weed control.

Lactobacilli are considered an inexhaustible source of potentially bioactive substances; indeed, several products from their metabolism are known to have immunomodulatory and anti-inflammatory activity. Recently, we demonstrated that cell-free supernatants (CFS) obtained from Lactobacillus (L.) acidophilus, L. plantarum, L. rhamnosus and L. reuteri can impair Candida pathogenic potential in an in vitro model of epithelial vaginal infection. This effect could be ascribed to a direct effect of living lactobacilli on Candida virulence and to the production of metabolites which are able to impair fungal virulence. In the present work, stemming from those data, we deepened our knowledge on the CFS from these 4 lactobacilli by performing a metabolomic analysis to better characterize their composition. By using an untargeted metabolomic approach, we detected consistent differences in the metabolites produced by these four different lactobacilli. Interestingly, L. rhamnosus showed the most peculiar metabolic profile. Specifically, after a hierarchical clustering analysis in positive and negative ionization mode, L. rhamnosus showed a specific area of significant overexpressed metabolites that strongly differed from the same area in other lactobacilli. In this area, inosine was identified among the overexpressed metabolites of L. rhamnosus. This molecule has been described to have antioxidant, anti-inflammatory, anti-infective and neuroprotective properties. The biological significance of its overproduction by L. rhamnosus might be important in its probiotic and/or postbiotic activity.

In the context of sustainable and eco-friendly agriculture, current scientific researches are focusing on plant-based bioproducts to remedy the toxicity caused by chemical fertilizers and pesticides. This study was conducted on cladodes of Opuntia ficus-indicato screen the bioactive molecules and to evaluate the activity againstfungal agentsisolated from tomato fruits. Quantitative analysis of the methanolic extractrevealed its richeness in total polyphenols (86.6 mg GAE/100 g FW), flavonoids (13.4 mg QE/100 g FW), condensed tannins (08.9 mg TAE/100 g FW), and carotenoids(0.9 mg β-CE/100 g FW). DPPH test revealed that the cladodes extract had a high antioxidant potential (0.6 mg/ml). On the other hand, 7 fungal agents were isolated from infected tomato fruits and identifyed asbelonging to the following genera: Rhizoctonia (EC2), Fusarium (EC1 and EC3), Alternaria (EC4), Mucor (EC5), Aspergillus (EC6) and Penicillium (EC7). At a concentration 0.02% of cladodehydro-ethanolic extract, results of the antifungal activity showed aninhibition of mycelial growth up to70% for the isolates ofAlternariaspEC4 (70.91%), Rhizoctonia solaniEC2 (58.49%), Fusarium oxysporiumEC3 (57.63%) and Fusarium solaniEC1 (53.13%). While,inhibitory activities lower than 50% were obtained for fungal isolates MucorspEC6 (31.08%), Aspergillus sp EC5 (35.14%) and Penicillium sp EC7 (28.38%).At 0.04%all thecladode hydro-ethanolic extractwere able to inhibit mycelium growth in more than 50%.Similarly, maximum spore inhibition development were obtained with 0.04 cladode hydro-ethanolicreaching more than 60%. Inhibition percentages of 83.02%, 85.96%, 87.76% and 90.20% were obtained for fungal isolates Fusarium oxysporium EC3, Fusarium solani EC1, Rhizoctonia solani EC2 and Alternaria sp EC4, respectively. All together, the results show that Opuntia ficus-indica extract has potential tobe used effectively as a biopesticide against fungal agents of tomato fruits.

The presence of valuable bioactive compounds in European eel (Anguilla anguilla) skin was studied. For it, proximate and lipid class compositions and analysis of the fatty acid (FA) profile (individual FAs; FA groups, i.e., saturated, monounsaturated, and polyunsaturated; FA ratios, i.e., polyunsaturated/saturated, ω3/ω6) were determined and compared to the composition of the eel muscle. As a result, higher (p&lt;0.05) levels of proteins (271.6 g·kg-1), lipids (38.0 g·kg-1), ash (27.7 g·kg-1) and ω6 FAs were observed in the skin tissue. Contrary, the muscle tissue showed higher (p&lt;0.05) moisture, ω3 FA and ω3/ω6 values. Regarding lipid classes, a higher (p&lt;0.05) proportion of phospholipids (111.1 g·kg-1 lipids), sterols (104.7 g·kg-1 lipids), α-tocopherol (274.0 mg·kg-1 lipids), and free fatty acids (43.6 g·kg-1 lipids) was observed in the skin tissue. No differences (p&gt;0.05) between both tissues could be detected for triacylglycerol and FA group (saturated, monounsaturated, and polyunsaturated) values, as well as for the polyunsaturated/saturated ratio. It is concluded that eel skin, a by-product resulting from commercial processing, can be considered a valuable source to provide the food and pharmaceutical industries with useful value-added constituents such as proteins, lipids, ω3 FAs, phospholipids, and α-tocopherol.

The Rényi entropy functional was optimised for the novel findings of this investigation under various conditions. Their research's findings suggest that the complete spectrum of Lévy stable distributions is covered by generalised t-distributions. Additionally, an exposition was undertaken to prove that the Lévy distribution generalizes Tsallisian distribution, rather than the reverse. The current study is a strong generalization of an existing research work in the literature.

The aim of the study was to determine the effect of the application of different organic matter, UGmax soil conditioner and simplifications in potato cultivation on the content of dry matter, starch, sugars in tubers of the medium-early edible cultivar 'Satina' after harvest and after long-term storage. The highest dry matter (173.4 g kg-1) and starch (124.6 g kg-1 f. m.) content was ob-tained with the simultaneous application of a manure with soil conditioner at 100% mineral fer-tilization. In the case of sugars, the withdrawal of the soil conditioner from the crop proved most beneficial, for total sugars on the stubble intercrop (5.06 g kg-1 f. m.) and for reducing sug-ars (1.99 g kg-1 f. m.) on the straw. Each protection reduction applied resulted in a significant re-duction in starch content. In this regard, the withdrawal of herbicides with simultaneous appli-cation of manure and UGmax proved most beneficial. Long-term storage of tubers caused a sig-nificant reduction in their quality in terms of dry matter and starch content (average by -3.6 and -2.3%, respectively) and an increase in total and reducing sugars (average by 11.8 and 9.6%, re-spectively). The decrease in dry matter and starch content was significantly influenced by the 50% reduction in NPK fertilization applied during the growing season, while the application of soil conditioner with full protection contributed to the increase in reducing sugars after storage at 28.9 pts%. Our research is in line with current trends of used potato cultivation technologies focused mainly on environmental protection, so the results of this study can provide a basis for validation for researchers currently engaged in such evaluation.

In this paper, we first define the concepts of r-fuzzy soft α-open (semi-open and δ-open) sets on fuzzy soft topological spaces based on the article Aygunoglu et al. (Hacet. J. Math. Stat., 43 (2014), 193-208), and the relations of these sets with each other are established. In addition, we introduce the concepts of fuzzy soft δ-closure (δ-interior) operators, and study some properties of them. Also, the concept of r-fuzzy soft δ-connected sets is introduced and studied with help of fuzzy soft δ-closure operators. Thereafter, we define the concepts of fuzzy soft α-continuous (β-continuous, semi-continuous, pre-continuous and δ-continuous) functions, which are weaker forms of fuzzy soft continuity, and some properties of these functions along with their mutual relationships are discussed. Moreover, a decomposition of fuzzy soft α-continuity and a decomposition of fuzzy soft semi-continuity is obtained. Finally, as a weaker form of a fuzzy soft continuity, the concepts of fuzzy soft almost (weakly) continuous functions are defined, and some properties are specified. Additionally, we explore the notion of continuity in a very general setting called, fuzzy soft (L, M, N, O)-continuous functions and a historical justification is introduced.

Providing simultaneously autotrophic and heterotrophic carbon sources is a promising strategy to overcome the limits of autotrophic syngas fermentations. D-xylose and L-arabinose are particularly interesting as they can be obtained by the hydrolysis of lignocellulosic biomass. The individual conversion of varying initial concentrations of these pentoses and D-fructose as reference was studied with C. autoethanogenum in fully-controlled stirred-tank reactors with a continuous syngas supply. All mixotrophic batch processes showed increased biomass and product formation compared to an autotrophic reference process. Simultaneous CO and D-xylose or L-arabinose conversion was observed in contrast to D-fructose. In the mixotrophic batch processes with Larabinose or D-xylose, the simultaneous CO and sugar conversion resulted in high final alcohol to acid ratios of up to 58 g g-1. L-arabinose was superior as a mixotrophic carbon source because biomass and alcohol concentrations (ethanol and 2,3-butanediol) were highest, and significant amounts of meso-2,3-butanediol (>1 g L-1) in addition to D-2,3-butanediol (>2 g L-1) were solely produced with L-arabinose. Furthermore, C. autoethanogenum could not produce meso-2,3 butanediol under purely heterotrophic conditions. The mixotrophic production of meso-2,3-butanediol from Larabinose and syngas, both available from residual lignocellulosic biomass, is very promising for use as a monomer for bio-based polyurethanes or as an antiseptic agent.

The chloroplast is important organelle responsible for photosynthesis and various bio- synthetic functions essential to green plants. However, the regulatory mechanism of chloroplast development remains elusive. Here, we characterized a mutant with defective chloroplasts in rice (Oryza sativa L.) named it albino and lethal 13(osal13), which exhibited a distinct albino phenotype in leaves, eventually leading to seedling lethality. Molecular cloning revealed that OsAL13 encodes a novel protein in rice for which no homologous gene or known conserved domain was found. Analysis of the biological characteristics showed that the RNAi2 leaf was completely albino phenotype, the root and shoot lengths were significantly inhibited compared with wild type. Transmission electron microscopy indicated that RNAi2 were defective in chloroplast development. Overexpression of OsAL13 resulted the photosynthetic rate increase, So the total grain number per panicle also would be significantly increase. Besides, OsAL13 was located in chloroplast and constitutively expressed in various tissues, including green and non-green tissues. In addition, disruption of OsAL13 resulted in altered expression of plastid-encoded polymerases and nuclear-encoded chloroplast genes, OsAL13 also affected hormone levels in plant tissues. Therefore, our results provide new insights into the role of OsAL13 in regulating chloroplast development in rice.

The precise mathematical description of gaze patterns is still an unsettled matter of debate. This can, consequently, affect the analysis of this type of data in its practical applications. In this scope, we show evidence that a Lévy-flight description of eye-gaze trajectories is not only appropriate but its scale invariant properties are remarkably useful to assist in diagnosing children with Attention Deficit and Hyperactivity Disorder (ADHD), alongside with the usual cognitive tests. Using this picture, we find that the distribution of the characteristic exponent of Lévy-flights statistically is different in children with ADHD. Furthermore, we observe that these children deviate from a strategy that is considered optimal for searching processes, in contrast to non-ADHD children. We focus on the case where both eye-tracking data and data from a cognitive test are present and show that the study of gaze patterns in children with ADHD can help in identifying this condition. Since eye-tracking data can be gathered during cognitive tests without needing extra time-consuming specific tasks, we argue that it is in prime position to provide assistance in the arduous task of ADHD diagnosing.

Low efficiency and excessive application of nitrogen (N) fertilizers is a frequent problem in agriculture that impacts the environment. Omeprazole (OMP) has been reported to promote N uptake and assimilation in tomato, basil, and corn. However, information about the effect of omeprazole on N assimilation, recovery and N use efficiency parameters for bean plants is limited. Therefore, the objective of the present study was to determine the effect of foliar application of OMP at 0, 1, 10 and 100 µM on nitrogen assimilation, growth, yield, nitrogen use efficiency parameters and recovery percentage in green bean plants. Green bean plants cv. Strike grown in pots were used. Biomass, yield, nitrate reductase activity, photosynthetic pigments concentration, soluble amino acids and protein concentration, total nitrogen concentration, nitrogen use efficiency parameters and nitrogen recovery were analyzed. The results obtained indicate that the application of OMP at 1 µM increased yield, biomass and promoted N assimilation through higher NR enzyme activity, higher amino acid concentration, higher N use efficiency coefficient and allowed a more efficient nitrogen recovery percentage.

Heat-stressed lactating dairy cattle exhibit unique metabolic symptoms; many of which are undoubtedly involved in heat-induced subfertility. Because of its known systemic effects, we hypothesized that γ-aminobutyric acid (GABA) participates in the regulation of insulin and progesterone during heat stress. Multiparous lactating Holstein cows (n=6) were studied during four experimental periods: 1) thermoneutral (TN; d 1-5), 2) TN + hyperinsulinemic-hypoglycemic clamp (d 6-10), 3) heat stress (HS; d 16-20), and 4) HS + euglycemic clamp (d 21-25). Blood samples were collected once daily via coccygeal venipuncture into heparinized evacuated tubes. Analysis of GABA concentrations from all four treatment periods yielded no differences. In direct comparison to TN concentrations, plasma GABA tended to be decreased during HS (16.57±2.64 vs 13.87±2.28 ng/ml, respectively, P = 0.06). Both milk production and plasma insulin were moderately correlated with plasma GABA (r=0.35, P<0.01; r = -0.32, P<0.01). Plasma progesterone was correlated with plasma GABA concentrations during TN but not HS. These results are the first to indicate that peripheral GABA could be involved in regulating aspects of production and reproduction during heat stress. More research is needed to determine its precise role(s).

Climate warming profoundly affect vegetative growth, flowering phenology and sexual reproduction of plants, therefore the ornamental value of wild flowers. Despite this, the extent and mechanism of the impact remain unclear. Here, we conducted warming experiment for two growing seasons (1.89 ℃ in 2017 and 2.37 ℃ in 2018 increases) with infrared heaters to examine the effects of warming on ornamental value of wild flower I. oxyanthera, endemic to China, in Mount Emei. We fitted generalized linear mixed models (GLMMs) and generalized linear model (GLM) to examine how warming affected plant morphology and floral traits. We evaluated comprehensive ornamental value based on plant morphology and flowering characteristics using Analytic Hierarchy Process (AHP) and disentangled the impact of the two traits on ornamental value using principal component analysis (PCA) and partial least squares structural equation model (PLS-SEM) under the ambient and warming treatments. Warming decreased significantly plant height and crown width, while increased branch number and single leaf area. Warming also decreased vexillum length, corolla tube length, nectar spur length and pedicel length. In addition, warming shortened flowering duration per plant and reduced flower number, while there was no significant effect on flower longevity, flower color at full-bloom stage between the control and warming treatment. Therefore, comprehensive ornamental value under warming was lower than that under the control. Pedicel length, flower color, flower longevity and flowering duration per plant were the main factors of affecting comprehensive ornamental value. PLS-SEM showed that warming had an indirect negative effect on ornamental value via direct negative effects on flowering traits. Collectively, these results indicate that although promoting vegetative growth, short-term warming decreased significantly ornamental value of I. oxyanthera due to warming-caused smaller flowers and shorter flowering duration.

The core pathological event in Parkinson’s disease (PD) is the specific dying of dopamine (DA) neurons of the substantia nigra pars compacta (SNc). Why SNc DA neurons are especially vulnerable and why idiopathic PD has only been found in humans is still puzzling. The two main underlying factors of SNc DA neuron vulnerability appear related to high DA production, namely (i) the toxic effects of cytoplasmic DA metabolism and (ii) continuous cytosolic Ca2+ oscillations in the absence of the Ca2+-buffer protein calbindin. Both factors cause oxidative stress by producing highly reactive quinones and increasing intra-mitochondrial Ca2+ concentrations, respectively. High DA expression in human SNc DA neuron cell bodies is suggested by the abundant presence of the DA-derived pigment neuromelanin, which is not found in such abundance in other species and has been associated with toxicity at higher levels. The oxidative stress created by their DA production system, despite that the SN does not use unusually high amounts of energy, explains why SNc DA neurons are sensitive to various genetic and environmental factors that create mitochondrial damage and thereby promote PD. Aging increases multiple of the risk factors for PD, and, to a large extent, PD is accelerated aging. To prevent PD neurodegeneration, possible approaches that are discussed here are (1) reducing cytoplasmic DA accumulation, (2) blocking cytoplasmic Ca2+ oscillations, and (3) providing bioenergetic support.

Cassava Solid waste (Onggok) is a solid waste from the cassava-based tapioca industry, the starch content in Onggok is still 50-80 wt.% of residual starch, which can be used to produce maltodextrin for foods application. Furthermore, using cassava solid waste is beneficial in terms of the cost of raw materials. The starch content in cassava can be modified through enzymatic hydrolysis using α-amylase and β-amylase enzymes at 80oC and pH 5.5. Enzymatic hydrolysis was done using mixed enzymes that varied the concentration of α-amylase at 0,.1% and the β-amylase enzymes at 0.05, 0.1, and 0.5%. the concentration of cassava waste (Onggok) varied from 4%, 7%, 10%, and 13%. The optimum concentration of α-amylase and β-amylase enzymes are 0.1% and 0.1% respectively at time intervals of 1 minute resulting in a dextrose equivalent (DE) value 0f 5.7. The characteristics of maltodextrin were studied using scanning electron microscopy (SEM) to determine the morphology of the starch structure which had changed due to the enzyme hydrolysis. Simultaneous thermal analysis (STA) was studied to determine the Thermal stability of hydrolysis products. Maltodextrin produced from cassava waste (Onggok) has a DE value < 10, which has the potential to be used in the pharmaceutical industry

The aim of this study was to determine the changes in chemical composition of the fresh red raspberry ‘Willamette’ fruits, caused by the presence of raspberry leaf blotch emaravirus (RLBV). In three experimental orchards of ‘Willamette’ raspberry, fruits were harvested from RLBV‒free and RLBV-infected plants in 2019 and 2020. Fruits were collected at appropriate maturity stages and further analyzed on total phenolics, total anthocyanins, and selected individual phenolics. In all three experimental orchards, the phenolic profiles of infected and uninfected fruit samples were considerably different during both studied years. Nonetheless, the intensity of the modifications varied greatly depending on location and harvest year. Statistical analysis revealed that the influence of RLBV infection on the studied features is undeniable, although the influences of weather conditions and soil composition outweigh the influence of RLBV. Taking into consideration all experimental and statistical data, it can be concluded that raspberry 'Willamette' fruits may be RLBV-tolerant, while sensitivity to environmental conditions and soil composition is emphasized.

Cornelian cherry (Cornus mas L.) fruits, abundant in iridoids and anthocyanins, are natural products with proven beneficial impact on the functions of the cardiovascular system and the liver. The aim of this study is to stipulate and compare whether and to what extent two different doses of resin-purified cornelian cherry extract (10 mg/kg b.w. or 50 mg/kg b.w.) applied in a cholesterol-rich diet rabbit model affect the levels of ATP-binding cassette transporter A1, ATP-binding cassette transporter G1, CCAAT/enhancer binding protein α, sterol regulatory ele-ment-binding protein 1c, fatty acid synthase, endothelial lipase, carnitine palmitoyltransferase 1A, and adiponectin receptor 2 in liver tissue; lipoprotein lipase, visceral adipose tissue-derived serine protease inhibitor, and retinol-binding protein 4 in visceral adipose tissue; resistive index of com-mon carotid arteries and aortas, and histopathological changes in CCAs. Obtained outcomes are referred to the results of our previous works. Moreover, our study, to our knowledge, test the in-fluence of Cornus derivative on CPT1A, AdipoR2, RBP4, LIPG, and vaspin for the first time, with a relevant outcome for the first three. Oral administration of the cornelian cherry extract decreased the SREBP-1c and C/EBPα in both doses. The dose of 10 mg/kg b.w. increased ABCA1 and de-creased FAS, CPT1A, and RBP4, and the dose of 50 mg/kg b.w. enhanced ABCG1 and AdipoR2. Mitigation in atheromatous changes in rabbits’ CCAs was also observed. The beneficial results confirm that cornelian cherry fruit extract may constitute a potentially effective product in the prevention and treatment of obesity-related disorders.

The study aims to evaluate the Quorum Sensing (QS) system inhibition against some Gram-positive and Gram-negative bacteria detected by molecular modeling of R. cathartica L. plant extract. R. cathartica L. methanol extract was evaluated in vitro. The research was carried out for the possible role and mechanism of R. cathartica L. The antibacterial activity of R. cathartica L. seed extract on some Gram-positive and Gram-negative strains was evaluated using culture-based and computational analysis. Gentamicin (CN; 30 µg/ml, Bioanalyse) was used as an antibacterial control of the extract on the production potential of QS-dependent virulence factors on Pseudomonas aeruginosa PAO1 was investigated. Phytochemical analysis resulted in the identification of 23 phenolic phytochemicals. R. cathartica L. extract was observed to have antimicrobial activity against Gram-positive and Gram-negative bacteria at different rates (11.3 mm-16 mm). The inhibitory effect of R. cathartica L. extract on P. aeruginosa PAO1 (elastase 61%, pyocyanin 18%, and biofilm 61%) was recorded moderately. Phytochemical analysis revealed that the main component of the extract is kaempferol. Therefore, the binding potential of kaempferol on QS system receptors was investigated via molecular docking. Computational analysis showed that kaempferol can inhibit the QS system by preventing competitive ligands from connecting to LasR. This study explored the activity and mechanism of action for a new green alternative against resistance. might provide a mechanism for R. cathartica L. seed extract components and thus provide a new avenue for using R. cathartica L. seed extract as a green antibacterial agent.

Brown leaf spot disease caused by Alternaria spp. is among the most common diseases in potato crops. Typical brown spot symptoms were observed in commercial potato-cultivated areas of northern Korea during June 2021–2022. In total, 77 isolates were collected, and based on sequence analysis of the internal transcribed spacer (ITS) region, the collected isolates were identified as Alternaria spp. (83.1%). Phylogenetic analysis revealed that a majority of these isolates clustered within a clade that included A. alternata. Additionally, the ITS region and rpb2 yielded the most informative sequences for the identification of A. alternata. Pathogenicity tests confirmed that the collected pathogens elicited identical symptoms in the field. In the pathogenicity test performed on seven commercial cultivars, the pathogens exhibited strong virulence in both wound and non-wound inoculations. Among the cultivars tested, Arirang-1ho, Arirang-2ho, and Golden Ball were resistant to the pathogens. Furthermore, when testing effective fungicides in vitro, mancozeb and difenoconazole were found to be effective agents for inhibiting mycelial growth. In summary, our findings suggest that A. alternata plays a critical role in leaf disease in potato crop regions and emphasise the necessity for continuous monitoring and management to protect against this disease in South Korea.

Tomato (Solanum lycopersicum L.) is one of the most commercially essential vegetable crops cultivated worldwide. In addition to the nutritional value, tomato is an excellent model for studying climacteric fruits' ripening process. Despite this, the available natural pool of genes that allows expanding phenotypic diversity is limited, and the difficulties of crossing using classical selection methods when stacking traits increase proportionally with each additional feature. Genetic engineering makes it possible to introduce changes in genes of interest without changing the allelic combinations characteristic of successful commercial varieties, to enhance the expression of existing genes, to create and transfer artificial and heterologous genes, and much more. However, this requires understanding the fundamental principles of the molecular interaction. Although the leading candidate genes for these components have been identified, a complete picture of their relationship has yet to be formed. The review summarizes the latest (2017-2023) achievements related to studying the ripening processes of tomato fruits. In this work, an attempt is made to systematize the results of various research and display the interaction pattern of genes regulating the process of tomato fruit ripening.

Wild rocket plants were cultivated in a plastic greenhouse into two independent sectors, one for soil-bound (SbS) cultivation and another equipped for soilless (ScS) cultivation systems. In both SbS and ScS, the crop was subjected to treatments consisting in a high-compared to a low-input fertilization program (HF and LF treatment, respectively). Water use efficiency (WUE) and partial factor productivity (PFP) for nutrients (N, P, K, Ca and Mg for ScS, and N for SbS) were measured. Rocket leaves, separated for cultivation system and fertilization program, collected at different cuts during the growing cycle, were cold stored at 10 °C until 16 d. At each sampling day (at harvest and during the storage), sensory parameters, respiration rate, dry matter, colour, electrolyte leakage, antioxidant activity, total phenols, total chlorophyll and ammonia content were evaluated. In ScS, the PFP for all nutrients supplied as fertilizers showed a significant increase with the LF treatment, with values higher than 30 % for N, K and Ca. As for the postharvest performance, rocket leaves cultivated in ScS showed better qualitative traits than those cultivated in SbS, as suggested by the lower values of ammonia content and electrolyte leakage recorded at the end of storage in samples grown in ScS. Moreover, in ScS, data showed a lower membrane damage in LF than HF rocket leaves. Finally, regarding total chlorophyll content, even if no effect of treatments was recorded in SbS, rocket cultivated in ScS, showed a better retention of this parameter applying LF than HF treatment. In addition to this, a PLS model (R2 = 0.7) able to predict the cultivation system, using as variables total chlorophyll content no-destructively measured, was implemented.

The effect of Amaranthus cruentus L. seed oil (AmO) on collagen biosynthesis and wound healing was studied in cultured human dermal fibroblasts exposed to UVA radiation. It has been found that UVA radiation inhibited collagen biosynthesis, prolidase activity, expression of β1-integrin receptor, phosphorylated ERK1/2 and TGF-β, while increased the expression of p38 kinase. The AmO at 0.05-0.15% counteracted the above effects induced by UVA radiation in fibroblasts. UVA radiation also induced the expression and nuclear translocation of pro-inflammatory NF-κB fac-tor and enhanced the COX-2 expression. AmO effectively suppressed the expression of these pro-inflammatory factors induced by UVA radiation. Expressions of β1 integrin and IGF-I re-ceptors were decreased in the fibroblasts exposed to UVA radiation, while AmO counteracted the effects. Furthermore, AmO stimulated fibroblast’s migration in a wound healing model, thus facilitating the repair process following exposure of fibroblasts to UVA radiation. This data suggest the potential of AmO to counteract UVA-induced skin damage.

Fifteen transgenic shoot clones (TS A-TS O) regenerated from Hypericum perforatum hairy roots were evaluated for growth characteristics, phenylpropanoid, and naphthodianthrone production, as well as non-enzymatic and enzymatic antioxidant status. Transgenic shoots displayed higher biomass production and non-altered phenotype compared to control shoots. Phenylpropanoid production in TS was not related to phenylalanine ammonia lyase activity indicating that alternative enzymes could be involved in the regulation of phenylpropanoid/flavonoid biosynthesis. The positive correlation between phenylpropanoids (phenolic acids, flavonoids, flavan-3-ols, tannins) and non-enzymatic antioxidant assays suggested that these compounds are the main contributors to the redox state and radical scavenging properties of TS clones. More importantly, enhanced naphthodianthrone production (hypericin, pseudohypericin and protopseudohypericin) in TS was associated with the number of leaf dark glands. Concerning the enzymatic antioxidant status of TS, guaiacol peroxidase was shown as the main enzyme that turn down H2O2 levels, while the up-regulation of superoxide dismutase coincided with decreased O2•− production. The efficiency of antioxidant enzymes for O2•− and H2O2 neutralization declined the MDA level and consequently delayed lipid peroxidation in TS clones. Altogether, H. perforatum transgenic shoots could be proposed as a prospective biotechnological system for scale-up production of naphthodianthrones and phenylpropanoids with antioxidant properties.

Transitions from seed to seedling represent a critical developmental step in the life cycle of higher plants, dramatically affecting plant ontogenesis and stress tolerance. The release from dormancy to acquiring the germination ability is defined by a balance of phytohormones, with a substantial contribution of abscisic acid (ABA), which inhibits germination. We studied the embryonic axes of Pisum sativum L. before and after radicle protrusion. Our previous work compared RNA sequencing-based transcriptomics in the embryonic axes isolated before and after radicle protrusion. The current study aims to analyze ABA-dependent gene regulation during the transition of embryonic axes from germination to post-germination stage. First, we determined the levels of abscisates (ABA, phaseic acid, dihydrophaseic acid, and neo-phaseic acid) using the ultra-high-performance liquid chromatography-tandem mass spectrometry. Second, we made a detailed annotation of ABA-associated genes using RNA sequencing-based transcriptome profiling. Finally, we analyzed the DNA methylation pattern in the promoters of the PsABI3, PsABI4, and PsABI5 genes. We showed that changes in the abscisate profile are characterized by the accumulation of ABA catabolites, and the ABA-related gene profile is accompanied by the upregulation of genes controlling the seedling development and the downregulation of genes controlling the water deprivation. The expression of ABI3, ABI4 and ABI5, which encode the crucial transcription factors during late maturation, was downregulated by more than 20-fold, and their promoters exhibited a high level of methylation already at the late germination stage. Thus, although ABA remains important, other regulators seems to be involved in the transition from seed to seedling.

Polysaccharide from Ficus carica L. (FCP) exert multiple biological activities, as a biological macromolecule, the available knowledge about the specific structures and mechanisms of biological activity of purified 'Brunswick' fig polysaccharide is currently limited. In the present study, by chemical purification and characteristics identified via specific instruments, and then the impact of FCP on the immunomodulation activity in vitro and in vivo was examined. Structural char-acteristics showed that the molecular weight of the FCP was determined to be 127.5 kDa, the primary monosaccharides present in the FCP were galacturonic acid (GalA), arabinose (Ara), galactose (Gal), rhamnose (Rha), glucose (Glc), and xylose (Xyl) at a ratio of 0.321:0.287:0.269:0.091:0.013:0.011. Based on the investigation of in vitro immunomodulatory ac-tivity, FCP was found to stimulate the production of NO, TNF-α, and IL-6 and increased the pi-nocytic activity of macrophages. Further analysis revealed that FCP activated macrophages by interacting with toll-like receptor 4 (TLR4). Moreover, the in vivo test results indicate that FCP showed significant increase serum pro-inflammatory factors in immunosuppressed mice. Overall, this study suggests that FCP has the potential to be utilized as a novel immunomodulator in the pharmaceutical and functional food industries.

Wendan (a type of pomelo), as a popular fruit in China, is less known in other countries. Its peel is widely used in food and traditional medicine. Four different origins of Wendan pomelo were selected, and crude extracts were obtained by the Soxhlet extraction method. The composition of Wendan peel was analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS) in positive ion mode. The compounds were identified by searching the Metabolite Link (METLIN), Spectral Database for Organic Compounds (SDBS) and referring to literature reports. A total of 20 compounds were identified among the samples from the four origins, of which 8 compounds were common. The majority of the compounds belonged to the flavonoid and coumarin classes, Meranzin hydrate was identified for the first time in pomelo peel. In vitro antioxidant activity experiments showed that samples from Taizhou, Zhejiang exhibited the highest antioxidant activity in the DPPH, ABTS, and FRAP assays, with values of 0.59 mg/mL, 97.06 μmol TE/g, and 60.62 μmol Fe2+/g, respectively. Samples from Zhangzhou, Fujian showed antioxidant activity second only to the samples from Taizhou, Zhejiang. The sample from Zhangzhou, Fujian Province, showed excellent inhibitory activity in the α-glucosidase inhibition assay (IC50=7.99 mg/mL).

The viability, productivity and survival of higher plants under the adverse factors influence are largely determined by the functional activity of the antioxidant system. The aim of our work was to investigate changes in formation of high-molecular (superoxide dismutase and peroxidase) and low-molecular (phenolics, including flavanols and proanthocyanidins) antioxidants in callus culture of Camellia sinensis under influence of phenolic precursors (L-phenylalanine – 3 mM, trans-cinnamic acid – 1 mM, naringenin – 0.5 mM). According to the data obtained, precursors effect on tea callus cultures did not lead to significant increasing of superoxide dismutase and peroxidase activity in most cases. However, it led to the increased accumulation of the total phenolics content, as well as flavanols and proanthocyanidins contents. For C. sinensis callus cultures, the most promising regulator of phenolic compounds was L-phenylalanine, in the presence of which its content increased almost twice. Thus, the exogenous effect of various precursors is possible to use for the targeted regulation of the certain phenolics classes accumulation in plant cells.

The genetic engineering of plants often relies on the use of antibiotic or herbicide resistance genes for initial selection of primary transgenic events. Nevertheless, the commercial release of genetically modified crops containing any marker gene encounters several challenges stemming from the lack of consumer acceptance. Development of strategies enabled the generation of marker-free transgenic plants is a possible alternative to deal with public concerns over the safety of biotech crops. Leveraging the high in vitro regeneration and transformation capabilities of potato, this study examined the factors associated with the development of transgenic plants without presence of selective substances in medium. To compare the antibiotic-assisted with the antibiotic-free transformation, nodal explants from five highly regenerative potato cultivars were inoculated with the Agrobacterium strain AGL0 carrying the pBIN-mGFP5-ER (35SGFP/nosNPTII) plasmid. The efficiency of transient expression and the formation of chimeric and completely transgenic shoots were assessed through vital GFP observations. Under non selective conditions, the regeneration efficiency of stable non-chimeric transgenic shoots varied from 0.9 (‘Chicago’) to 2.7% (#12-36-42). In order to streamline transformation protocol, a specific timeline for collecting transgenic plantlets was established for each analyzed cultivar. This timeline strategy was implemented to generate transgenic potato plants, which demonstrated the suppression of homologous SteIF4Es family genes as a result of the successful introduction of the marker-free hpRNAi construct.

To follow the growth and development of each tree (N = 1200) Pinus sylvestris L., var. Negorelskaya starting from the seed and continuing at the juvenile (or even generative) stage is the goal of an ambitious project to create a plant passport if possible. Five datasets of replenished empirical (tab-ular and file) and systematic data reflect the early results of a unique ongoing experiment conducted with families moved along a climatic gradient from the collection area (1731 degree days, 722 mm) to the experimental area (2326 degree days; 786 mm). Datasets of morphometric, VIS-spectrometric, and germination seed data, combined with the first results of biometric data (including the Dickson quality index) of seedlings produced from these seeds, will allow scientists in the future to conduct correlation and other statistical analysis, or train a neural network to determine the presence of connections between a seed and a plant. These data contribute to the early non-destructive diag-nosis and grading of seeds according to VIS-spectrometric properties. This dataset structure can complement the FLR-Library. In the future, by tracing seedlings in their early growth (for example, over three growing seasons at the site being restored), it will be possible to determine the degree of intensification of FRM production depending on the initial properties of the seed.

Delivery systems of the biologically active substance such as proanthocyanidins (PCAN) produced through the electrospinning method were designed using a blend of poly(L-lactide-co-glycolide) and poly[(R,S)-3-hydroxybutyrate]. The research involved the structural and thermal characteristics of the developed electrospun three-dimensional fiber matrix, as well as hydrolytic degradation tests performed on them. Additionally, the release profile of PCAN from the electrospun nonwoven was determined using UV–VIS spectroscopy. Approximately 30% of PCAN was released from the tested electrospun nonwoven during the initial 15-20 days of incubation. The chemical structure of water-soluble oligomers that were formed after the hydrolytic degradation of the developed delivery system was identified through electrospray ionization mass spectrometry. Oligomers of lactic acid and OLAGA oligocopolyester, as well as oligo-3-hydroxybutyrate terminated with hydroxyl and carboxyl end groups, were recognized as degradation products released into the water during the incubation time. It was also demonstrated that variations in the degradation rate of individual mat components influenced the degradation pattern, and the number of formed oligomers. The obtained results suggest that the incorporation of proanthocyanidins into the system slowed down the hydrolytic degradation process of the poly(L-lactide-co-glycolide)/poly[(R,S)-3-hydroxybutyrate] three-dimensional fiber matrix. In addition, in vitro cytotoxicity and antimicrobial studies advocate the use of PCAN for biomedical applications with promising antimicrobial activity.

Ipomoea batatas L. (IBL) has gained significant popularity as a complementary therapy or herbal medicine in the treatment of anti-diabetes. The objective of this review is to examine the mechanism of action of flavonoid compounds found in IBL that can activate GLP-1 as an anti-diabetic agent. The review article refers to PRISMA guidelines. The literature search was conducted using electronic databases such as Crossref, Pubmed, Scopus, and Science Direct. The search query was based on specific keywords, including Ipomoea batatas OR sweet potato AND anti-diabetic OR hypoglycemic. A total of 1055 articles were found, but only 32 articles were selected for further review based on inclusion and exclusion criteria. IBL contains various compounds, including phenolic acid, flavonols, flavanols, flavones, and anthocyanins, which exhibit activity against anti-diabetes. Flavonols, flavonols, and flavones belong to a group of flavonoids that possess the ability to form complexes with AlCl3 and Ca2+. Retention of Ca2+ within intracellular L cells, resulting in the release of GLP-1. Flavonols, flavones, and flavone groups have been found to strongly interact with DPP-IV, which inhibits the degradation of GLP-1. This mechanism effectively prolongs the half-life of GLP-1 in the systemic system, thereby contributing to the anti-diabetic activity of IBL

The principal goal of this current study was to isolate a new potential probiotic strain to prepare contamination-free probiotic dahi in a dosage form with desired shelf life. To achieve our target, firstly, probiotic dahi was prepared by a probiotic strain, Lactobacillus acidophilus JB2CON (OM909067) (identified by 16S sequencing) isolated from natural dahi in Dhaka, Bangladesh. The isolate showed five probiotic features by in vitro test and had an antagonistic effect against five different pathogens. More interestingly, it inhibited Escherichia coli (diameter of zone of inhibition = 15.75±0.35) the most. In the time-kill analysis method, E. coli was killed totally within 5.50 hours of fermentation. Finally, the time duration of 14 days was an ideal shelf life, because the probiotic count increased but a slight change in pH did not affect the taste (sourness/acidity) of dahi. The most significant impact of this research is that the probiotic dahi of our experiment might be used as a cheap option for preventing pathogenic Escherichia coli-related foodborne diseases worldwide, especially in underdeveloped countries like Bangladesh.

The therapeutic effectiveness of current neurodegenerative diseases treatments is still under debate because of problems with bioavailability and a range of side effects. Fungi, which are increasingly recognized as sources of natural antioxidants and AChE enzyme inhibitors, may thus serve as potent neuroprotective agents. Previous studies have associated the anti-AChE and antioxidant activities of fungi mostly with polysaccharides and phenolic compounds, while other secondary metabolites such as polyamines (PAs) have been neglected. This study aimed to investigate eight edible and medicinal fungi from Serbia, marking the initial investigation into the neuroprotective capabilities of Postia caesia, Clitocybe odora, Clitopilus prunulus, and Morchella elata. Neuroprotective activity was examined using Ellman assay, while antioxidant capacity was tested by conducting DPPH, NO, ABTS and FRAP tests. PAs levels were determined by HPLC coupled with fluorescent detection. Ganoderma applanatum and Lepista nuda exhibited the most robust anti-AChE (98.05 ± 0.83% and 99.94 ± 3.10%, respectively) and antioxidant activities attributed to the synergistic effects of total protein, total phenolic and PAs levels. Furthermore, P. caesia displayed significant AChE inhibition (88.21 ± 4.76%), primarily linked to elevated SPD (62.98 ± 3.19%) and PUT levels (55.87 ± 3.16%). Our results highlight the need of thorough research to comprehend the intricate relationships between distinct fungus species and AChE inhibition. However, it's important to recognize that more research is required to identify the precise substances causing the reported inhibitory effects.

Irrigation with water containing a variety of microcystins (MCs) may pose potential threat to normal growth of agricultural plants. The mechanism of microcystin-LR (MC-LR) induced phytotoxicity in rice (Oryza sativa L.) at environmental concentrations is still unknown. Rice seedlings were exposed to MC-LR at concentrations of 0.10, 1.0, 10.0 and 50.0 μg·L−1 in hydroponic nutrient solutions for 7, 15, 20, and 34 days in the current study. The absorption and accumulation in leaf and root tissues, as well as a series of key physio-biochemical process changes in leaves of rice at different exposure time points were measured. Results showed that MC-LR could be detected in rice leaves and roots in all exposure groups, however, a significant accumulation trend of MC-LR in plants (BCF > 1) was only found in the lowest group (0.10 μg·L−1). The time-course study revealed a biphasic response of O2•- levels in rice leaves to the exposure of MC-LR, which was more pronounced in higher concentration groups, which could be attributed to the combined effects of antioxidant and detoxification mechanisms in rice. Exposure to 1.0 - 50.0 μg·L−1 MC-LR resulted in significant depletion of GSH and MDA contents in rice leaves at later exposure times. The changes of nitric oxide synthase (NOS) in rice leaves under MC-LR exposure were firstly investigated in the current study. Low MC-LR concentrations promoted NOS activity, whereas high concentrations inhibited NOS activity during the later exposure times, implying that NO may play a role in MC-LR toxicity in rice. Reduced sucrose synthase (SS) activities in rice exposed to MC-LR can reduce the plant's ability to accumulate carbon and thus may be directly related to the reduction in vegetative growth. These findings suggest that even at low concentrations of MC-LR, terrestrial plants' normal physiological status is disrupted, which, when combined with previous findings, helps reveal the mechanism of MC-LR-induced phytotoxicity.

In recent decades, given the important role of gamma-aminobutyric acid (GABA) in human health, scientists have paid great attention to the enrichment of this chemical compound in food using various methods, including microbial fermentation. Moreover, GABA or GABA-rich products have been successfully commercialized as food additives or functional dietary supplements. Several microorganisms can produce GABA, including bacteria, fungi, and yeasts. Among GABA-producing bacteria, lactic acid bacteria (LAB) are commonly used in the production of many fermented foods. Lactiplantibacillus plantarum (previously Lactobacillus plantarum) has a long history of natural occurrence and safe use in a variety of food products. This LAB species provides functional properties to various fermented foods by producing a variety of bioactive compounds, including GABA. The present review aims, after a preliminary excursus on the function and biosynthesis of GABA, to provide an overview on the current uses of microorganisms and in particular of L. plantarum in the production of GABA, with a detailed focus on fermented foods.

Gut colonization by multidrug resistant organisms(MDROs) is a risk factor for bloodstream infections(BSI) in the early phase of Hematopoietic Stem Cell Transplantation(HSCT). We evaluated, in an exploratory study, the impact of Lactobacillus plantarum on modulation of the gut microbiome in HSCT patients colonized by MDROs. Participants were allocated to an intervention group(IG=22) who received capsules of L. plantarum(5x109 CFU) twice a day until the onset of neutropenia and a control group(CG=20). The V4 region of the 16S bacterial rRNA gene in 93 stool samples from a subset of 33 patients was sequenced(IG=20 and CG=13). Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) (PICRUSt2) program was used for prediction of metagenome functions. L. plantarum had an average 86%(±11%) drug-target engagement at 43(±29) days of consumption and it was safe, tolerable and associated with an increase in the abundance of the Lactobacillales(p=0.004). A significant increase of Lactococcus and reduction of Turicibacter(p<0.05) were identified on the second-week of L. plantarum use. Although Enterococcus abundance had a greater rise in the CG (p=0,07), there were no significant differences concerning the gram-negative MDROs. No serious adverse effects was reported in the IG. . We observed greater non-significant pyruvate fermentation to propanoate I (p=0.193) relative abundance in the IG comparing with CG. L. plantarum use was safe and tolerable by HSCT patients. Although it may have impact on Enterococcus abundance and reduction of Turicibacter, it has not showed impact on Gram-Negative MDRO abundance in MDRO gram-negative colonized HSCT patients.

Malignant melanoma is one of the most aggressive and resistant tumor types which is often accompanied by poor prognosis when spread to nearby or distant tissues. Even though an increasing number of second-line therapies are available for cancer patients, the 5-year survival rate of melanoma patients with regional and distant metastases is still rather low. Therefore, there is an urgent need to develop new, highly efficient treatments. Melanocortin-1-receptor (MC1R) is a cell surface receptor for α-MSH. It is responsible for melanogenesis and is shown to be overexpressed on the surface of cancer cells in a subset of melanoma patients. Here, we designed and synthesized α-MSH analogs and conjugated them to daunomycin through oxime linkage. Using our peptide-drug conjugates (Dau-α-MSHs), we performed comparative in vitro and in vivo evaluations to reveal their suitability for tumor targeting. Firstly, the expression level of MC1R was determined in various melanoma cell lines via RT-qPCR. Then, we examined the antiproliferative effect of our Dau-α-MSHs, moreover we determined the cellular uptake profile and intracellular localization of Dau-α-MSHs. The most efficient Dau-α-MSHs were investigated in vivo using a murine xenograft melanoma model. We found that various cell lines show differential expression on the mRNA levels. We also showed that healthy primary cells have lower expression of MC1R compared to tumor cell lines. Moreover, the concentration-dependent cellular uptake profile of Dau-α-MSHs was detected and the compounds exhibited a great antiproliferative effect on melanoma cell lines. We also provided evidence that our novel Dau-α-MSHs can inhibit tumor expansion significantly and are suitable for targeted tumor therapy.

The article aims to find potential biomarker for the detection of tubular damage in pediatric neurogenic bladder (NB) by investigating urinary levels of liver-type fatty acid-binding protein (uL-FABP). This prospective analysis was conducted on two groups: 42 children with NB and 18 healthy children. The uL-FABP concentrations were measured using ELISA methods. The children’s medical charts were analyzed to determine age, sex, anthropometric measurements, activity assessment using Hoffer’s scale and renal function parameters. The results revealed that the uL-FABP/creatinine ratio was higher in the studied group compared with the reference group. A significant positive correlation between uL-FABP and proteinuria was found. Children with a history of vesicoureteral reflux (VUR) tended to have elevated uL-FABP. In conclusion, uL-FABP may be considered a potential tubular damage biomarker in children with NB. Proteinuria and history of VUR may be the factors influencing uL-FABP.

Three new compounds (1, 11 and 12), together with 32 known ones, were isolated from the root bark of Morus alba L. using various chromatographic methods. The structures of the undescribed compounds were elucidated based on 1D, 2D NMR and HRESIMS data analysis, while the known ones were identified by comparison of their spectroscopic data with those reported in the literature. All the isolates were evaluated for their cytotoxic activities against human gastric cancer HGC27 cells by CCK-8 assay. Among them, compounds 5, 8, 10 and 30 exhibited cytotoxic activities on HGC27 cells with IC50 values of 10.24 ± 0.89 μM, 28.94 ± 0.72 μM, 6.08 ± 0.34 μM and 33.76 ± 2.64 μM, respectively. Furthermore, compound 10 was confirmed to reduce proliferation ability, increase apoptosis rate and inhibit cell migration pathway by annexin V/PI double staining experiment, transwell experiment and western blot analysis.

Declining agricultural productivity caused by soil salinization are becoming global dilemmas in recent years. Biofertilizers show great potential as a sustainable and environmentally friendly fertilization strategy for soil improvement, but their effectiveness for saline soil amendment and improving plant growth under saline stress is not well understood. Assess the effectiveness of biofertilizers in improving saline soils and enhancing crop growth under saline stress, as well as investigate its related potential mechanisms. Changes in soil physico-chemical properties, plant physiological parameters and soil microbial communities were analyzed through pot experiments. The results showed that the application of biofertilizer reduced total soluble salts (TSS) in soil by 30.8% and increased the Brassica rapa L. biomass by 8.4 times. Biofertilizer application increased soil organic matter (SOM), total nitrogen (TN) and available phosphorus (AP). Biofertilizer applications also increased the SOD, CAT, chl.a, chl.b, total soluble sugars, and Proline content. Biofertilizers present plant growth promotion and potential pathogenic fungi reduction by increasing the abundance of Bacillus and Planococcus and decreasing the abundance of Mortierella and Aspergillus. Overall, the results of this study demonstrated the excellent efficacy of biofertilizers in improving saline soils, and the application of biofertilizer strategies will greatly promote agricultural production.

Post-stroke depressive disorders (PSD) and post-stroke cognitive impairments (PCI) are frequent consequences of ischemic stroke (IS). The study was focused on exploring possible associations between relative volumes of cortical and limbic brain structures during the acute period of IS, and changes in biochemical indices of hypothalamic-pituitary-adrenal, sympathoadrenal medullary and inflammatory systems, with the development of PSD or PCI after mild or moderate IS. Patients developing PSD later on had significantly smaller relative volumes of the hippocampus, entorhinal cortex, and temporal pole versus patients without depressive symptoms. PCI development was associated with significantly smaller volumes of temporal pole and supramarginal gyrus versus patients without cognitive changes. Multiple logistic regression analysis showed higher likelihood of developing PSD in patients with smaller temporal pole volume (β0=10.9; β=-4.27; p=0.04) and increased salivary α-amylase activity (β0=-3.55; β=2.68e-05; p=0.02,). PCI likelihood was higher in patients with smaller supramarginal gyrus volume (β0=3.41; β=-0.99; p=0.047), smaller temporal pole volume (β0=3.41; β=-3.12; p=0. 06), and increased hair cortisol concentration at admission (index of accumulated stress load within a month before IS; β0=3.41; β=-0.05; p=0.08). The data support the hypothesis suggesting predisposition to PSD and PCI and multi hit scenarios of their pathogenesis with IS providing a final hit.

The CDPK family genes play crucial roles in signal transduction pathways during plant develop-ment and stress response. In this study, we comprehensively analyzed the CDPK family genes in mustard (Brassica juncea L.), resulting in the identification of 101 genes (BjuCDPK1–101) located on chromosomes AA_Chr01 to BB_Chr08. RNA-seq analysis showed that most BjuCDPK genes were predominantly expressed in the root and flower bud, suggesting their organ-specific expression patterns. Furthermore, the expression levels of most BjuCDPK genes were significantly altered by cold stress. The promoter regions of BjuCDPK genes had abundant cis-acting elements related to hormone and stress. The interaction network analysis predicted that BjuCDPK proteins respond to abiotic stress probably via interaction with ABF1, ABF4, and/or DI19. Our findings provide valu-able information for further investigation of the cold stress adaption of mustard via the CDPK signaling pathway.

Nemaline myopathy (NM) is one of the most common forms of congenital myopathy and it is identified by the presence of "nemaline bodies" (rods) in muscle fibers by histopathological exam-ination. The most common forms of NM are caused by mutations in the ACTA1 (Actin Alpha 1) and NEB (Nebulin) genes. Clinical features include hypotonia and muscle weakness. Unfortunate-ly, there is no curative treatment and the pathogenetic mechanisms remains unclear. In this man-uscript, we examined the pathophysiological alterations in NM using dermal fibroblasts derived from patients with mutations in ACTA1 and NEB genes. Patients’ fibroblasts were stained with rhodamine phalloidin to analyze the polymerization of actin filaments by fluorescence microsco-py. We found that patients' fibroblasts showed incorrect actin filament polymerization compared to control fibroblasts. Actin filament polymerization defects was associated with mitochondrial dysfunction. Furthermore, we identified two mitochondrial boosting compounds, linoleic acid (LA) and L-carnitine (LCAR), that improved the formation of actin filaments in mutant fibro-blasts and corrected mitochondrial bioenergetics. Our results indicate that cellular models can be useful to study the pathophysiological mechanisms involved in NM and to find new potential therapies. Furthermore, targeting mitochondrial dysfunction with LA and LCAR can revert the pathological alterations in NM cellular models.

An array of diverse processes and factors have been linked to the pathoetiology and pathophysiology of Parkinson’s disease (PD), including systemic CNS factors. This article reviews some of the many processes and factors linked to the emergence and progression of PD that culminates in the loss of substantia nigra pars compacts (SNpc) in PD patients. It is proposed that SNpc astrocytes may be a key hub, with numerous systemic and CNS factors acting to suppress the astrocyte tryptophan-melatonin pathway, leading to a loss of astrocyte melatonin and lactate for SNpc dopamine neurons. Consequently, dopamine neurons show an increase in α-synuclein, oxidative stress and suboptimal mitochondrial function, partly due to the loss of melatonin induced PTEN-associated kinase (PINK)1/parkin and mitophagy. This leads to an increase in the major histocompatibility (MHC)-1 and the chemoattraction of CD8+ T cells that destroy SNpc dopamine neurons in an ‘autoimmune’/’immune-mediated’ manner. The upstream processes driving the end-point ‘chaos’ of SNpc dopamine neuron loss are proposed to be driven by the suppression of night-time pineal melatonin, gut microbiome derived butyrate and possibly bcl2-associated athanogene (BAG)-1, which all act to suppress the glucocorticoid receptor (GR) translocation to the nucleus in all systemic and CNS cells, thereby potentiating the effects of the rising levels of cortisol over the night and accelerated rise in the course of the cortisol awakening response (CAR). The potentiation of cortisol effects at the GR has consequences for the homeostatic regulation of the diverse array of systemic and CNS microenvironments, as well as a distinct regulation of different immune and glia cells. The morning CAR is classically proposed to ‘prepare the body for the coming day’. However, the differential regulation of the GR over the circadian rhythm at night would indicate that such preparation for the coming day may be powerfully determined by night-time factors and processes. The article integrates this systemic, night-time pathoetiology with the ‘immune-mediated’ processes that ultimately drive SNpc dopamine neuron loss. This has a number of novel future research and treatment implications.

This study aims to clarify the influence of photographic environments under different light sources on image-based SPAD value prediction. Radish leaf patches of 1.5 cm diameter were photographed under halogen or LED light. The input variables for the SPAD value prediction using random forests were RGB values, HSL values, and HSV values. Additionally, the light color temperature (LCT) and illuminance (ILL) were used as the input variables. Model performance was assessed using Pearson’s correlation coefficient (COR), Nash-Sutcliffe efficiency (NSE), and root mean squared error (RMSE). SPAD value prediction resulted in high accuracy in a stable light environment; CORRGB+ILL+LCT and CORHSL+ILL+LCT were 0.929 and 0.922, respectively. Image-based SPAD value prediction was effective under halogen light with a similar color temperature at dusk; CORRGB+ILL and CORHSL+ILL were 0.895 and 0.876, respectively. The HSL value under LED could be used to predict the SPAD value with high accuracy; COR, NSE, and RMSE were 0.972, 0.944, and 2.07, respectively. The partial dependence plots of the H value indicate a change from blue to green with increasing SPAD values. Further studies are required to examine this method under outdoor conditions in spatiotemporally dynamic light environments.

Alzheimer’s disease manifests itself as a complex pathological condition with neuroinflammation, oxidative stress and cholinergic dysfunction being a few of the many pathological changes. Due to the complexity of the disease current therapeutic strategies aim at a multitargeted approach often relying on a combination of sub-stances with versatile and complementary effects. In the present study, unique combination of α-lipoic acid, citicoline, extracts of leaves from olive tree and green tea, Vitamin D3, selenium and an immune supporting complex was tested in a scopolamine-induced dementia in rats. Using behavioral and biochemical methods we assessed the effects of this combination on learning and memory, and elucidated the mechanisms under-lying its effects. Our results showed that as compared to the components, experimental combination was most efficient in improving short- and long-term memory assessed by the step-through method as well as spatial memory, assessed by T-maze and Barnes maze underlying decrease in AChE activity and LPO, in-creases in SOD activity in cortex; activities of catalase and GPx, levels of BDNF and pCREB in the hippocam-pus. No significant histopathological changes or blood parameter changes were detected, making the experi-mental combination an effective and safe candidate in a multitargeted treatment of AD.

The emergence of antimicrobial resistance remains one of the greatest public health concerns. Biofilm formation has been postulated as a mechanism of microbial pathogens to resist antimicrobial agents. Lactic Acid Bacteria (LAB) and their metabolites have been proposed to combat bacterial biofilms, due to their antimicrobial activity. In this vein, the aim of the present study was to investigate the biofilm removal potential of cell-free supernatant (CFS) of five wild-type Lacticaseibacillus rhamnosus LAB strains, isolated from Greek natural products, in comparison to the commercial available L. rhamnosus GG strain, formed by common foodborne pathogens (Salmonella Enteritidis, Salmonella Typhimurium, Escherichia coli, Listeria monocytogenes, and Staphylococcus aureus). Biofilm removal activity of LAB was assessed on two-days mature biofilm using a microtiter plate-based procedure. Both non-neutralized and neutralized CFSs removed biofilms in a concentration-dependent manner. Biofilm removal activity of the non-neutralized CFSs was significantly higher compared to the neutralized CFSs, as expected, ranging 40 – 90% and 10 – 78%, respectively. Biofilm removal efficiency of L. rhamnosus OLXAL-3 was signifanctly higher among the wild-type L. rhamnosus strains tested (20 – 100% v/v). In conclusion, our results suggested the great potential of application of wild-type Lacticaseibacillus rhamnosus strains CFSs as effective natural agents against pathogenic bacterial biofilms.

Utilization of medicine derived from plants has been documented in various traditional systems of medicines throughout the world for different diseases. Therefore, the current research work was carried out to evaluate the phytochemical and biological potential of Ficus carica L ethanolic leaf extract. For this purpose, physicochemical and phytochemical analysis, total phenolic and flavonoids contents was performed. Antioxidant potential was determined by FRAP, DPPH and H2O2 assay. Proteinase inhibition, heat induced hemolysis and BSA denaturation assay was carried out for inflammation. Antiglycation potential was assessed by fructosamine assay, Congo-red assay and estimation of free carbonyl groups. In-vivo antidiabetic, anti-obesity, effect on liver and kidney were investigated by high fat high sugar diet model. FTIR, HPLC and LCMS/MS analysis was performed to find out the compounds. Tablet based formulation was developed using wet granulation method and tested for physicochemical parameters. Results shows that total phenolic and flavonoids content was (333 mg GAE/g) and (123 mg RE/g) respectively, H2O2 assay shows 35.6% free radical inhibition potential, DPPH assay shows (IC50) inhibitory concentration at 0.58 mg/mL, and 88.769 µg/g Fe2SO4 solution FRAP values. Proteinase inhibition assay, Heat induced hemolysis and BSA-denaturation assay shows percentage inhibition of 28 ± 0.01, 55 ± 0.03 and 51.2 ± 0.05 respectively. In Antiglycation activity β-amyloid formation assay shows absorption of 0.017, Fructosamine assay shows inhibition of 19.4±0.06 and free carbonyl group estimation shows inhibition of 17.0±0.03. In in-vivo study FLE at (500 mg/kg) significantly decreased total bilirubin (p ≤ 0.001), decreased (p ≤ 0.05) alanine transferase, aspartate aminotransferase, alkaline phosphatase, decreased blood glucose, triglycerides and total cholesterol (p ≤ 0.01) while HDL (p ≤ 0.01) was significantly increased in comparison to obesity and diabetic-obesity groups. Different functional groups presence was confirmed by FTIR spectrum. HPLC analysis revealed the existence of ferulic acid, rutin, chlorogenic acid, coumarin and thymoquinone and these results are corelated by LC-MS/MS. Pre-compression characterization showed angle of repose (33.04°), bulk density (0.54 g/cm3), tapped density (0.73 g/cm3), compressibility index (35.179 %) and Hausner’s ratio (1.35), while the post-compression characterization showed weight variation 826±4.17 mg, thickness 10.50±0.25 kg/cm2, friability 0.57 %, and disintegration time 8.19 min. From the above results it is concluded that F. carica L. leaves extract has strong antioxidant, antidiabetic and hypolipidemic potential and can be used for an obesity and diabetes treatment.

The α-synucleinopathies are a group of neurodegenerative diseases characterized by the deposition of α-synuclein aggregates (α-syn) in the brain. Currently, there is no suitable tracer to enable a definitive early diagnosis of these diseases. We reported candidates based on 4,4'-disarylbisthiazole (DABTA) scaffold with a high affinity towards α-syn and excellent selectivity over Aβ and tau fibrils. Based on prior in silico studies a focused library of 23 halide-containing and O-methylated DABTAs was prepared. The DABTAs were synthesized via a modified two-step Hantzsch thiazole synthesis, characterized, and used in competitive binding assays against [3H]PiB, and [3H]DCVJ. The DABTAs gave an overall chemical yield of 15 – 71%, with a calculated lipophilicity of 2.5 – 5.7. The ligands demonstrated an excellent affinity to α-syn with both [3H]PiB and [3H]DCVJ: Ki 0.1 – 4.9 nM and up to 20 – 3900-fold selectivity over Aβ and tau fibrils. It could be concluded that in-silico simulation is useful for the rational design of a new generation of DABTAs. Further investigation of the leads in the next step is encouraged: radiolabeling of the ligands with radioisotopes such as fluorine-18 or carbon-11 for in vivo, ex vivo and translational research and for further in vitro experiments on human-derived protein aggregates.

Bacillus subtilis NCD-2 showed a promising biocontrol effect against plant soil-borne diseases, and was developed as a commercial microbial fungicide against cotton verticillium wilt in China. Spores were main ingredient of the fungicide and played the crucial role in biological control of plant diseases. Therefore, the key to reducing the cost of fungicide was to find ways to increase the number of spores of strain NCD-2 during fermentation. In this study, 755 substances were evaluated by Phenotype Microarray technology, and 5 kinds of carbon sources and 1 kind of nitrogen source were found to promote the metabolism of strain NCD-2. Among carbon sources L-arabinose showed strongest ability to promote the bacteria growth and sporulation of strain NCD-2. When L-arabinose was used as a single carbon source, it could increase the bacteria concentration and the sporulation efficiency of strain NCD-2 by 2.04 times and 1.99 times, respectively, compared with D-glucose. Moreover, L-arabinose could significantly decrease the autolysis of strain NCD-2 revealed by microscopy observation. The mechanism for promoting the sporulation by L-arabinose was analysed by RNA-seq sequencing. Results showed that total of 790, 923 and 1270 genes were up-regulated and 639, 850 and 1001 genes were down-regulated under L-arabinose supplies when cultured at 8 h, 12 h and 16 h, respectively. Fourteen differentially expressed genes associated with arabinose transportation and sporulation were selected for qRT-PCR analysis, and the result showed basically consistent expression trend with transcriptome. Notably, genes associated with arabinose metabolism, sporulation, spore resistance to heat and spore coat formation were significantly up-regulated, and genes associated with sporulation-delaying protein were significantly down-regulated under L-arabinose supplies. msmX gene which was involved in arabinose transport in Bacillus genus was deleted, and the mutant decreased the growth and sporulation by 53.71% and 86.46%, respectively, when compared to strain NCD-2 wild type. Complementary of the mutant by importing intact msmX gene could restore the growth and sporulation of the mutant strain. In conclusion, arabinose played an important role in regulating the growth and sporulation of strain NCD-2.

Our previous studies showed that in patients with brain diseases neurotrophic factors in lacrimal fluid (LF) may change more prominently than in blood serum (BS). Since glial cell line-derived neurotrophic factor (GDNF) is involved in control of neuronal networks in epileptic brain, we aimed to assess GDNF levels in LF and BS as well as BDNF, hypothalamic-pituitary-adrenocortical and inflammation indices in BS of patients with focal epilepsy (PWFE), epilepsy and comorbid depression (PWFE+MDD) compared with major depressive disorder (PWMDD) and healthy controls (HC). GDNF levels in BS were similar in patients and HC and higher in PWFE taking valproates. GDNF levels in LF were significantly lower in all patient groups compared to controls, and independent of drugs used. LF and BS GDNF concentrations positively correlated in HC, but not patient groups. BDNF level was lower in BS of patients compared with HC and higher in PWFE+MDD taking valproates. Logistic regression models demonstrated that GDNF decrease in LF may be an important predictor of focal epilepsy. Probability of focal epilepsy can be evaluated using GDNF in LF and BDNF in BS; MDD - GDNF in LF, cortisol and TNF-α in BS; epilepsy with MDD - GDNF in LF, TNF-α and BDNF in BS.

The use of nitrogen fertilizers can be a source of environmental pollution; the use of or-ganomineral fertilizers can become a nutritional source for crops, ensuring sustainability in the production system. Another alternative approach is through the inoculation and co-inoculation of microorganisms. The objective was to evaluate the development, nutrition, and agronomic yield of common bean through fertilization with organomineral formula "FMO" derived from sewage sludge biosolids, combined with Rhizobium tropici inoculation and co-inoculation with Azospirillum brasilense techniques. Three bean cultivars from different commercial groups, Pérola, BRS Esteio, and BRS Pitanga, were tested. They were subjected to organomineral fertilizer application, orga-nomineral fertilizer application combined with seed inoculation with R. tropici and re-inoculation; seed co-inoculation with R. tropici + A. brasilense prior to sowing, and foliar re-inoculation with R. tropici + A. brasilense. Seed inoculation, combined with foliar re-inoculation at the V4 stage, resulted in higher productivity of common bean. The combination of R. tropici with co-inoculation with A. brasilense generally led to increased productivity compared to mineral nitrogen fertilization. The use of organomineral fertilizer alone enabled gains in development, as well as productivity. The Pérola bean cultivar showed better adaptation to the applied treatments.

The α-glucosidase inhibitor is of interest to researchers due to its association with type-II diabetes treatment by suppressing postprandial hyperglycemia. Hesperidin is a major flavonoid in orange fruit with diverse biological properties. This paper evaluates the effects of hesperidin on α-glucosidase through inhibitory kinetics, fluorescence quenching, and molecular docking methods for the first time. The inhibition kinetic analysis showed that hesperidin reversibly inhibited the α-glucosidase activity with an IC50 value of 18.52 M and the inhibition was performed in an uncompetitive type. Fluorescence quenching studies indicated that the intrinsic fluorescence of α-glucosidase was quenched via a static quenching process and only one binding site was present between hesperidin and α-glucosidase. The interaction between them was spontaneous and mainly driven by hydrogen bonds as well as hydrophobic forces. Furthermore, molecular docking results suggested that hesperidin might bond to the entrance or outlet part of the active site of α-glucosidase through a network of five hydrogen bonds formed between hesperidin and the four amino acid residues (Trp709, Arg422, Asn424, and Arg467) of ?-glucosidase and hydrophobic effects. These results provide new insights into the inhibitory mechanisms of hesperidin on α-glucosidase, supporting the potential application of hesperidin-rich orange product as a hypoglycemic functional food.

Zinc, being a part of many proteins and enzymes, plays an important role in the vital processes of the body. Racemic α-lipoic acid (LA) has a wide range of biological activities: antioxidant, antidiabetic, anticancer, and it is also used in diseases such as Parkinson's and Alzheimer's. Nowadays, the synthesis and structural studies of new zinc complexes with biologically active compounds are of great importance for drug discovery. This work shows the studies carried out on the synthesis, structure, identification, also biological activity using in silico methods of a complex compound based on LA and zinc. A complex compound of zinc with LA (ZnLA) was synthesized in the presence of LA and zinc acetate in ethanol. The identification of ZnLA by (FT-IR, XRD and TGA-DTA), also DFT calculations at the B3LYP/def2-TZVPP level of theory was performed. The molecular docking investigation involved docking ZnLA with two different protein receptors such us Glycogen phosphorylase (2GPA) and Kv potassium channel beta subunit (1ZSX) using CB-Dock 2 server and Auto-Dock Vina program to determine the mechanism of action and biological activity. This study reveals potential ligand-protein interactions at the atomic level and suggests that the treatment of diabetes (non-insulin dependent) with ZnLA.

An undescribed diterpene, stellerterpenoid A (1) and two undescribed sesquiterpenoids, stellerterpenoids B and C (2-3), together with six known compounds, were isolated from the roots of Stellera chamaejasme L. Their structures were elucidated by extensive spectroscopic data (1D, 2D NMR, IR, UV and HR-ESI-MS). The absolute configuration of 1-3 were elucidated based on ECD calculation. Among of them, stellerterpenoid A was a rare 13, 14 - seco nortigliane diterpenoid and stellerterpenoid B was a guaiacane type sesquiterpenoid with an unusual 1, 2-diketone moiety. The known stelleraguaianone B (5) exhibited moderate activity to suppress NO production in LPS - simulated macrophages with an IC50 value of 24.76 ± 0.4 μM. None of the compounds showed inhibitory influenza virus and tumor activity.

Self-compacting concrete is essential for vertical structures due to high reinforcement and usage of pumps for transporting the concrete at the working site. SCC is mainly influenced by self-curing for arid areas. To explore the SCC (Self-Compacting Concrete) mixture and condition influencing the self-curing condition were determined using the experimental procedure. Determination of various parameters was done using T50 slump flow, V-funnel, L-box-box, J ring test, compressive strength, splitting tensile strength, and flexural strength test. After the experimental investigation, it shows that if the dose if the dosage of superplasticizer (SNF%) increases, it will improve the concrete mixture's different properties, such as flowability and ability to pass. Higher water-to-cement ratios (w/c) generally result in enhanced flowability and stability. Mixture 9 (SNF 0.35, w/c 0.5) demonstrates favourable results across all parameters, indicating excellent flowability and stability. Mixture 9 (SNF 0.35, w/c 0.5) also shows favourable flowability and stability characteristics. Lower concentrations, such as 0.5%, may have a positive effect up to a certain point but might not provide sustained improvement over the curing period. On the other hand, concentrations of 1% and 2% demonstrated consistent and significant enhancement in strength throughout the 28 days. It is found that the higher concentrations of PEG 4000 may be more effective in improving the material strength.

The mechanical properties of α-chitin and chitosan biocomposite are investigated due to their broad range of potential applications in bioengineering, materials science, and environmental technology. Employing molecular dynamics (MD), and stress-strain analyses, this study comprehensively investigates biopolymers mechanical response and anisotropic mechanical behavior under uniaxial tensile loading conditions in an aqueous environment. Our computational models were validated against existing experimental data, showing high degrees of correspondence. Uniaxial tensile tests revealed that α-chitin exhibits a remarkable ultimate tensile strength (UTS) of 10.07 GPa in the crystalline chain direction (y-axis) at a high strain rate of 0.636, compared to a significantly lower UTS of 2.78 GPa in the perpendicular direction (x-axis) at a lower strain rate of 0.066. The biocomposite nanostructure, encompassing randomly distributed chitosan, reduced stiffness, maintaining remarkable flexibility as α-chitin, with a UTS of 5.03 GPa in the y-axis and 2.34 GPa in the x-axis. Further, the directional elastic modules for α-chitin were calculated as 51.76 GPa and 39.76 GPa in the x and y directions, respectively. In contrast, these values for the α-chitin-chitosan biocomposite were estimated as 31.66 GPa and 26.00 GPa, respectively. The findings provide valuable insights into the distinct mechanical properties of α-chitin and chitosan biocomposite, making a substantial contribution to optimizing these materials for specialized applications.

As research into the relationship between the gut microbiome and health continues to evolve, probiotics are garnering increasing interest among consumers. Fermentation is rec-ognized as an efficacious biotechnology for augmenting the nutritional and functional at-tributes of foods. In this study, the ameliorative effects of Lycium barbarum L. lyophilized powder fermented with Lactobacillus plantarum NXU0011 (LP+Ly) on dextran sodium sul-fate (DSS)-induced ulcerative colitis (UC) in mice were investigated employing immuno-histochemistry, qRT-PCR, macrogenomics, and metabolomics. The results revealed that LP+Ly intervention significantly ameliorated histopathological inflammation in the ulcer-ated colon, diminished the expression of inflammatory markers such as IL-6, P-STAT3, and miR-214, and enhanced the diversity of intestinal flora in the mouse model group. Moreover, there was an increase in abundance of beneficial bacteria, including Lactobacillus, Prevotella, and Akkermansia. Metabolomic analysis indicated that 15 metabolites, including citrulline, D-xylose, and α-ketoisovaleric acid, exhibited significant variations following LP+Ly inter-vention. The metabolic pathways that displayed substantial differences included tryptophan biosynthesis, arginine biosynthesis, and amino sugar and nucleotide sugar metabolism. By modulating arginine biosynthesis, LP+Ly effectively improved the intestinal inflammatory state, thus mitigating the effects of UC.

We describe the development and validation of a HPLC-MS/MS method to assess the pharmacokinetics and tumour distribution of ZST316, an arginine analogue with inhibitory activity towards dimethylarginine dimethylaminohydrolase 1 (DDAH1) and vasculogenic mimicry, and its active metabolite L-257 in a xenograft model of triple negative breast cancer (TNBC). The method proved to be reproducible, precise, and highly accurate for the measurement of both compounds in plasma and tumour tissue following acute and chronic (five days) intraperitoneal administration of ZST316 (30mg/Kg daily) in six-week-old SCID mice inoculated with MDA-MB-231 TNBC cells. ZST316 was detected in tumour tissue and plasma after 1 hour (6.47 and 9.01M, respectively) and 24 hours (0.13 and 0.16M, respectively) following acute administration, without accumulation during chronic treatment. Similarly, the metabolite L-257 was found in tumour tissue and plasma after 1 hour (15.06 and 8.72M, respectively) and 24 hours (0.17 and 0.17M, respectively) following acute administration of ZST316, without accumulation during chronic treatment. The half-live after acute and chronic treatment ranged between 4.4-7.1hrs (plasma) and 4.5-5.0hrs (tumour) for ZST316, and 4.2-5.3hrs (plasma) and 3.6-4.9hrs (tumour) for L-257. The results of our study demonstrate the a) capacity to accurately measure ZST316 and L-257 concentrations in plasma and tumour tissue in mice using the newly developed HPLC-MS/MS method, b) rapid conversion of ZST316 into L-257, c) good intra-tumour penetration of both compounds, and d) lack of accumulation of both ZST316 and L-257 in plasma and tumour tissue during chronic administration. The new HPLC-MS/MS method is useful to investigate the in vivo effects of ZST316 and L-257 on vasculogenic mimicry, tumour mass, and metastatic burden in xenograft models of TNBC.

Composite polymolecular separation membranes were prepared by combining multi-branched ZIF-L with high porosity electrospinning nanofibers PI. Meanwhile, PDA and PEI were introduced into the membrane in order to improve its adhesion. The new membrane is so called “PI@PDA@PEI/ZIF-L-4” composite membrane; compared with PI@PDA@PEI/ZIF-8 composite membrane, the new membrane’s filtration rates for heavy metal ions such as Cd2+, Cr3+ and Pb2+ were increased by 7.0%, 6.6% and 9.3%, respectively. Furthermore, the new membrane has a permeability up to 1,140.0 L·m−2·h−1·bar−1, and were presenting a very stable performances after four repeated uses. The separation mechanism of PI@PDA@PEI/ZIF-L composite membranes was further analyzed in order to provide a base support for producing separation membranes with high barrier rate and high flux.

The genus Fusarium includes several agronomically important and toxin-producing species, that are worldwide distributed and can cause a wide range of diseases. Crown and stalk rots and grain infections are among the most severe symptoms that Fusarium spp. can cause on maize. The disease development usually occurs during germination, but it may also affect the later phases of plant growth. The purpose of this study was to investigate the diversity and the patho-genicity of 41 isolates recovered from symptomatic seedlings collected in Northern Italy, and from seeds with five different geographical origins during 2019 and 2020. The pathogenicity was tested and confirmed on 23 isolates causing rotting on maize seedlings. A multi-locus phylogeny analysis, based on four genomic loci (tef1-α, rpb2, calm and tub2), was performed for 23 repre-sentative isolates. Representative isolates were identified as species belonging to three species complexes (SC). Fusarium verticillioides and F. annulatum in the F. fujikuroi SC. Fusarium commune was identified in the F. nisikadoi SC, and three different lineages were found in the Fusarium ox-ysporum SC. This study reports F. annulatum, and two lineages of the Fusarium oxysporum SC as maize pathogens for the first time in Italy.

Oral cancer ranks sixth among Taiwan's top 10 cancers, and most patients with poor prognosis acquire metastases. The essential fatty acid alpha-linolenic acid (ALA) has been found to diminish many cancer properties. However, the anti-cancer activity of ALA in oral cancer has yet to be determined. Migration and invasion assays confirmed OSCC cells' EMT capabilities, whereas flow cytometry and Western blotting identified the molecular pathways. ALA dramatically reduced cell growth in a concentration dependent manner, according to the findings. Low concentrations of ALA (100 or 200 μM) inhibit colony formation, expression of Twist and EMT-related proteins, expression of MMP2/-9 proteins and enzyme activity, as well as cell migration and invasion. Treatment with high concentrations of ALA (200 or 400 μM) greatly increases JNK phosphorylation and c-jun nuclear accumulation, then upregulates the FasL/caspase8/caspase3 and Bid/cytochrome c/caspase9/caspase3 pathways, leading to cell death. Low concentrations of ALA inhibit SAS and GNM cell migration and invasion by suppressing Twist and downregulating EMT-related proteins, or by decreasing the protein expression and enzyme activity of MMP-2/-9, whereas high concentrations of ALA promote apoptosis by activating the JNK/FasL/caspase 8/caspase 3-extrinsic pathway and the Bid/cytochrome c/caspase 9 pathway. ALA demonstrates potential as a treatment for OSCC patients.

The broad bean plant contains L-DOPA, a compound that is essential for patients with Parkin-son’s disease. However, little has been reported on other broad bean compounds that have bene-ficial effects on health. The objective was to evaluate plants of four Mexican broad bean varieties to determine the content and yield of total phenolic compounds (TPC), total flavonoids (TF), and L-DOPA, as well as to analyze the flavonoid profile and antioxidant (AA) and anti-inflammatory (AANTI) activity in vitro. Broad bean seeds were sown in the field and plants were harvested 20 days after emergence. The analyses were performed with visible UV spectrophotometry and HPLC. The variety José María produced the highest yield of TPC (9.30 g m-2), TF (8.08 g m-2) and L-DOPA (5.64 g m-2) per unit of area. The highest yields per plant were obtained with the Rojita variety: TPC (0.25 g plant-1), TF (0.21 g plant-1) and L-DOPA (0.17 g plant-1). This variety also had the highest antioxidant (CI50= 87.68 µg mL-¹) and anti-inflammatory (CI50= 74.40 mg mL-1) activi-ty, which was attributed to the L-DOPA compounds and to rutin and isoorientins, respectively. The flavonoid profile revealed the presence of rutin and isoorientins, which had not been previ-ously detected in the broad bean plant.