Search Results (7,110)

Recent advancements have been made in the precise prediction of protein structures within the Protein Folding Problem (PFP), particularly in relation to minimizing the energy function to achieve stable and biologically relevant protein structures. This problem is classified as NP-hard within computational theory, necessitating the development of various techniques and algorithms. Bio-inspired algorithms have proven effective in addressing NP-hard challenges in practical applications. This study introduces a novel hybrid algorithm, termed GRSABio, which integrates the strategies of Jumping Spider Algorithm (JSOA) with the Golden Ratio Simulated Annealing (GRSA) for peptide prediction. Furthermore, the GRSABio algorithm incorporates a Convolutional Neural Network for fragment prediction (FCNN), forms an enhanced methodology called GRSABio-FCNN. This integrated framework achieves improved structure refinement based on energy for protein prediction. The proposed enhanced GRSABio-FCNN approach was applied to a dataset of 60 peptides. The Wilcoxon and Friedman statistics test were employed to compare the GRSABio-FCNN results against recent state-of-the-art-approaches. The results of these tests indicate that the GRSABio-FCNN approach is competitive with state-of-the-art methods for peptides up to 50 amino acids in length and surpasses leading PFP algorithms for peptides with up to 30 amino acids. Full article

Isoquercitrin, a monoglucoside form of quercetin, exhibits superior antioxidant, anti-inflammatory, and cardiovascular protective effects in comparison to its precursor, rutin. However, its natural abundance is limited. This study aimed to increase the functional value of Diospyros lotus leaf extract through enzymatic conversion of rutin to isoquercitrin using α-l-rhamnosidase and to evaluate the changes in biological activities after conversion. A sugar-free D. lotus leaf extract was prepared and subjected to enzymatic hydrolysis with α-l-rhamnosidase under optimized conditions (pH 5.5, 55 °C, and 0.6 U/mL). Isoquercitrin production was monitored via high-performance liquid chromatography. Antioxidant and anti-inflammatory activities were assessed using the 2,2-diphenyl-1-picrylhydrazyl radical scavenging and lipoxygenase (LOX) inhibition assays, respectively. The enzymatic reaction resulted in complete conversion of 30 mM rutin into isoquercitrin within 180 min, increasing isoquercitrin content from 9.8 to 39.8 mM. The enzyme-converted extract exhibited significantly enhanced antioxidant activity, with a 48% improvement in IC₅₀ value compared with the untreated extract. Similarly, LOX inhibition increased from 39.2% to 48.3% after enzymatic conversion. Both extracts showed higher inhibition than isoquercitrin alone, indicating synergistic effects of other phytochemicals present in the extract. This study is the first to demonstrate that α-l-rhamnosidase-mediated conversion of rutin to isoquercitrin in D. lotus leaf extract significantly improves its antioxidant and anti-inflammatory activities. The enzymatically enhanced extract shows potential as a functional food or therapeutic ingredient. Full article

The most prevalent growth of Candida cells is based on biofilm development, which causes the intensification of antifungal resistance against a large range of chemicals. Nanoparticles can be synthesized using green methods via various biological extracts and reducing agents to control Candida biofilms. This study aims to compare copper oxide nanoparticles (CuONPs) synthesized through chemical methods and those synthesized using Cinnamomum verum-based green methods against Candida infections and their biofilms isolated from Iraqi patients, with the potential to improve treatment outcomes. The physical and chemical properties of these nanoparticles were characterized using Fourier-transform infrared spectroscopy (FT-IR,) scanning electron microscopy (SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM) and X-ray diffraction (XRD). Four strains of Candida were isolated and characterized from Iraqi patients in Tikrit Hospital and selected based on their ability to form biofilm on polystyrene microplates. The activity of green-synthesized CuONPs using cinnamon extract was compared with both undoped and doped (Fe, Sn) chemically synthesized CuONPs. Four pathogenic Candida strains (Candida glabrata, Candida lusitaniae, Candida albicans, and Candida tropicalis) were isolated from Iraqi patients, demonstrating high biofilm formation capabilities. Chemically and green-synthesized CuONPs from Cinnamomum verum showed comparable significant antiplanktonic and antibiofilm activities against all strains. Doped CuONPs with iron or tin demonstrated lower minimum inhibitory concentration (MIC) values, indicating stronger antibacterial activity, but exhibited weaker anti-adhesive properties compared to other nanoparticles. The antiadhesive activity revealed that C. albicans strain seems to produce the most resistant biofilms while C. glabrata strain seems to be more resistant towards the doped CuONPs. Moreover, C. tropicalis was the most sensitive to all the CuONPs. Remarkably, at a concentration of 100 µg/mL, all CuONPs were effective in eradicating preformed biofilms by 47–66%. The findings suggest that CuONPs could be effective in controlling biofilm formation by Candida species resistant to treatment in healthcare settings. Full article

Wildfires can significantly alter soil physicochemical conditions and microbial communities in forest ecosystems. This study aimed to characterize the culturable soil fungal community and evaluate biological activity in Banco Totumo Bijibana, a protected dry tropical forest in Atlántico, Colombia, affected by a wildfire in 2014. Twenty soil samples were collected for microbiological (10 cm depth) and physicochemical (30 cm) analysis. Basal respiration was measured using Stotzky’s method, nitrogen mineralization via Rawls’ method, and fungal diversity through culture-based identification and colony-forming unit (CFU) counts. Diversity was assessed using Simpson, Shannon–Weaver, and ACE indices. The soils presented low organic matter (0.70%) and nitrogen content (0.035%), with reduced biological activity as indicated by basal respiration (0.12 kg C ha⁻¹ d⁻¹) and mineralized nitrogen (5.61 kg ha⁻¹). Four fungal morphotypes, likely from the genus Aspergillus, were identified. Simpson index indicated moderate dominance, while Shannon–Weaver values reflected low diversity. Correlation analysis showed Aspergillus-3 was positively associated with moisture, whereas Aspergillus-4 correlated negatively with pH and sand content. The species accumulation curve reached an asymptote, suggesting an adequate sampling effort. Although no control site was included, the findings provide a baseline characterization of post-fire soil microbial structure and function in a dry tropical ecosystem. Full article

Recent advancements in data collection technologies, data science, and speech processing have fueled significant interest in the computational analysis of biological sounds. This enhanced analytical capability shows promise for improved understanding and detection of various pathological conditions, extending beyond traditional speech analysis to encompass other forms of acoustic data. A particularly promising and rapidly evolving area is the application of deep learning techniques for the detection and analysis of diverse pathologies, including respiratory, cardiac, and neurological disorders, through sound processing. This paper provides a comprehensive review of the current state-of-the-art in using deep learning for pathology detection via analysis of biological sounds. It highlights key successes achieved in the field, identifies existing challenges and limitations, and discusses potential future research directions. This review aims to serve as a valuable resource for researchers and clinicians working in this interdisciplinary domain. Full article

Chronic kidney disease (CKD) is a heterogeneous condition with various etiologies, including type 2 diabetes mellitus (T2D), hypertension, and autoimmune disorders. Both diabetic CKD (CKD_T2D) and non-diabetic CKD (CKD_nonT2D) share overlapping clinical features, but understanding the molecular mechanisms underlying each subtype and distinguishing diabetic from non-diabetic forms remain poorly defined. To identify differentially expressed genes (DEGs) and enriched biological pathways between CKD_T2D and CKD_nonT2D cohorts, including autoimmune (CKD_nonT2D_AI) and hypertensive (CKD_nonT2D_HT) subtypes, through integrative transcriptomic analysis. Publicly available gene expression datasets from human glomerular and tubulointerstitial kidney tissues were curated and analyzed from GEO and ArrayExpress. Differential expression analysis and Gene Set Enrichment Analysis (GSEA) were conducted to assess cohort-specific molecular signatures. A considerable overlap in DEGs was observed between CKD_T2D and CKD_nonT2D, with CKD_T2D exhibiting more extensive gene expression changes. Hypertensive-CKD shared greater transcriptomic similarity with CKD_T2D than autoimmune-CKD. Key DEGs involved in fibrosis, inflammation, and complement activation—including Tgfb1, Timp1, Cxcl6, and C1qa/B—were differentially regulated in diabetic samples, where GSEA revealed immune pathway enrichment in glomeruli and metabolic pathway enrichment in tubulointerstitium. The transcriptomic landscape of CKD_T2D reveals stronger immune and metabolic dysregulation compared to non-diabetic CKD. These findings suggest divergent pathological mechanisms and support the need for tailored therapeutic approaches. Full article

Background/Objectives: In many parts of the world, pharmacists hold the primary responsibility for providing safe and effective pharmacotherapy. A key aspect is the availability of appropriate medicines for each individual patient. When industrially manufactured medicines are unsuitable or unavailable, pharmacists can prepare tailor-made medicines. While this principle applies globally, practices vary between countries. In the Netherlands, the preparation of medicines in pharmacies is well-established and integrated into routine healthcare. This narrative review explores the role and significance of extemporaneous compounding, pharmacy preparations and related product care in the Netherlands. Methods: Pharmacists involved in pharmacy preparations across various professional sectors, including community and hospital pharmacies, central compounding facilities, academia, and the professional pharmacists’ organisation, provided detailed and expert insights based on the literature and policy documents while also sharing their critical perspectives. Results: We present arguments supporting the need for pharmacy preparations and examine their position and role in community and hospital pharmacies in the Netherlands. Additional topics are discussed, including the regulatory and legal framework, outsourcing, quality assurance, standardisation, education, and international context. Specific pharmacy preparation topics, often with a research component and a strong focus on product care, are highlighted, including paediatric dosage forms, swallowing difficulties and feeding tubes, hospital-at-home care, reconstitution of oncolytic drugs and biologicals, total parenteral nutrition (TPN), advanced therapy medicinal products (ATMPs), radiopharmaceuticals and optical tracers, clinical trial medication, robotisation in reconstitution, and patient-centric solid oral dosage forms. Conclusions: The widespread acceptance of pharmacy preparations in the Netherlands is the result of a unique combination of strict adherence to tailored regulations that ensure quality and safety, and patient-oriented flexibility in design, formulation, and production. This approach is further reinforced by the standardisation of a broad range of formulations and procedures across primary, secondary and tertiary care, as well as by continuous research-driven innovation to develop new medicines, formulations, and production methods. Full article

The gut microbiota plays an essential role in the host’s metabolism. Its composition and structure depend on biological and environmental factors. This work was designed to identify the composition and structure of the wild and captive red grouper (Epinephelus morio) microbiota and make predictions regarding its metabolic functions. Our hypothesis stated that wild and captive individuals would share the most abundant taxonomic groups, forming a core microbiota, and individuals in captivity might have exclusive taxonomic groups. Metagenomic DNA was extracted from the intestinal contents of wild and captive individuals. The 16S rRNA gene was amplified and sequenced using Illumina pair-end technology. QIIME2 pipeline was used for sequence analysis and alpha and beta diversity assessment. PICRUSt was used to infer metabolic functions. Twenty-nine phyla were identified; the most abundant were Pseudomonadota, Bacillota, Fusobacteriota, and Actinomycetota. The dominant genera were Photobacterium, Vibrio, Cetobacterium, and Escherichia-Shigella. The metabolic prediction analysis suggested that the Epinephelus morio gut microbiota is related to food digestion, the immune system, antioxidant enzymes, antibiotic resistance, and vitamin B12 transport. We concluded that the microbiota of E. morio established in captivity is sensitive to environmental changes such as water pollution, which can cause a decrease in diversity. Full article

Titanium alloys are frequently subjected to surface treatments to enhance their biocompatibility and corrosion resistance in biological environments. Plasma electrolytic oxidation (PEO) is an environmentally friendly electrochemical technique capable of forming oxide layers characterized by high corrosion resistance, biocompatibility, and strong adhesion to the substrate. In this study, the PEO process was performed using a low-melting-point ternary eutectic electrolyte composed of Ca(NO₃)₂–NaNO₃–KNO₃ (41–17–42 wt.%) with the addition of ammonium dihydrogen phosphate (ADP). The use of this electrolyte system enables a reduction in the operating temperature from 280 to 160 °C. The effects of applied voltage from 200 to 400V, current frequency from 50 to 1000 Hz, and ADP concentrations of 0.1, 0.5, 1, 2, and 5 wt.% on the growth of titanium oxide composite coatings on a Ti-6Al-4V substrate were investigated. The incorporation of Ca and P was confirmed by phase and chemical composition analysis, while scanning electron microscopy (SEM) revealed a porous surface morphology typical of PEO coatings. Corrosion resistance in Hank’s solution, evaluated via Tafel plot fitting of potentiodynamic polarization curves, demonstrated a substantial improvement in electrochemical performance of the PEO-treated samples. The corrosion current decreased from 552 to 219 nA/cm², and the corrosion potential shifted from −102 to 793 mV vs. the Reference Hydrogen Electrode (RHE) compared to the uncoated alloy. These findings indicate optimal PEO processing parameters for producing composite oxide coatings on Ti-6Al-4V alloy surfaces with enhanced corrosion resistance and potential bioactivity, which are attributed to the incorporation of Ca and P into the coating structure. Full article

This study evaluated the effects of low-dose recombinant human bone morphogenetic protein-2 (rhBMP-2) coating in combination with vacuum plasma treatment on titanium implants, aiming to enhance osseointegration and bone regeneration while minimizing the adverse effects associated with high-dose rhBMP-2. In vitro analyses demonstrated that plasma treatment increased surface energy, promoting cell adhesion and proliferation. Additionally, it facilitated sustained rhBMP-2 release by enhancing protein binding to the implant surface. In vivo experiments using the four-beagle mandibular defect model were conducted with the following four groups: un-treated implants, rhBMP-2–coated implants, plasma-treated implants, and implants treated with both rhBMP-2 and plasma. Micro-computed tomography (micro-CT) and medical CT analyses revealed a significantly greater volume of newly formed bone in the combined treatment group (p < 0.05). Histological evaluation further confirmed superior outcomes in the combined group, showing significantly higher bone-to-implant contact (BIC), new bone area (NBA), and inter-thread bone density (ITBD) compared to the other groups (p < 0.05). These findings indicate that vacuum plasma treatment enhances the biological efficacy of low-dose rhBMP-2, representing a promising strategy to improve implant integration in compromised conditions. Further studies are warranted to determine the optimal clinical dosage. Full article

In this study, a new, patented form of a water-soluble cannabidiol (CBD) complex was synthesised and tested. The formation of the complex is based on the interactions, presumably through hydrogen bonding, between cannabidiol and glucosamine, the latter contributing significantly to the increased hydrophilicity. The complex was characterised by chromatography, thermal analysis, nuclear magnetic resonance, Fourier transform infrared spectroscopy, and permeability tests. This complex has a substantially higher water solubility than normal CBD. Permeability tests indicate that it has almost five times lower permeability through lipophilic membranes and less than half the membrane mass retention of conventional CBD. At the same time, its equilibrium concentration is almost four times higher than that of normal CBD. These results suggest that this new form of CBD is a promising candidate for future biological and clinical studies, as it offers improved bioavailability and biodistribution. Full article

Here, we report the discovery of silica- and sulfur-enriched deposits forming on the seafloor off Zannone Island (western Mediterranean Sea), where hydrothermal activity is ongoing. Our multidisciplinary investigation reveals that these deposits form through the interplay between hydrothermal processes and microbial activity. The deposits result from a dynamic equilibrium involving microbial mediation, sedimentation, and episodic lithification, driven primarily by two mineralization pathways: silica and sulfur precipitation. This study provides new insights into the bio-sedimentary processes shaping authigenic crusts in shallow submarine hydrothermal settings, contributing to a broader understanding of mineralization in marine environments influenced by both geological and biological factors. Full article

Cynara cardunculus L. subsp. cardunculus (Cynara cardunculus L. var. sylvestris (Lam.) Fiori), the wild cardoon, is known for its culinary applications and potential health benefits. Due to this, and given the growing interest in circular economies, deepening our under-standing of the effects of wild cardoon leaf waste on angiogenesis and collagenase activity represents a valuable opportunity to valorise agricultural byproducts as health-promoting ingredients. In this study, the waste product of wild cardoon leaves was extracted to examine its chemical composition and biological activities. Analytical techniques identified several bioactive compounds, including flavonoids, hydroxycinnamic acids such as dicaffeoyl-succinoylquinic acids, and luteolin-7-O-rutinoside. In vivo tests in zebrafish embryos and the chick chorioallantoic membrane demonstrated dose-dependent antiangiogenic effects, particularly enhanced by the complexation with hydroxypropyl-β-cyclodextrin (HP-β-CD). Considering the link between angiogenesis and collagenase, the potential effects of the extract on collagenase activity was investigated. The extract alone inhibited collagenase with an IC₅₀ value comparable to that of the standard inhibitor while its complexed form exhibited a 4.5-fold greater inhibitory activity. A molecular docking study examined the interaction between the main compounds and collagenase. In conclusion, wild cardoon leaves can represent a valuable source of bioactive compounds. This study demonstrated that the complexation of the extract with cyclodextrin determines an increase in its biological activity. Full article

Background/Objectives: The incidence and prevalence of ischemic stroke, a leading cause of death and disability worldwide, are significantly higher in older adults than in younger individuals. Senescence induces a variety of biological changes that influence the pathogenesis of diseases such as ischemic stroke, thereby necessitating age-specific medical treatments. However, the molecular mechanisms underlying age-related differences in ischemic stroke progression remain poorly understood. Methods: We compared the histological and molecular features of ischemic stroke in a photothrombotic mouse model, focusing on 9-week-old (young) and 90-week-old (old) mice. Results: We found that microglial accumulation at the infarct region of the cerebral cortex was significantly lower in old mice than in young ones. This reduction in the microglial response was accompanied by a decrease in the morphological robustness of the astrocytes forming the glial scar. Furthermore, the mRNA expression of proinflammatory cytokines CXCL10, CCL2, and TNF-α, which were upregulated in the infarct region, was considerably higher in the old mice than in the young ones. Cytokine expression was well correlated with the mRNA levels of Toll-like receptor 4 (TLR4), a key regulator of neuroinflammation in old mice, but less correlated with them in young mice. Interestingly, Tlr4 mRNA expression in young mice was negatively correlated with the mRNA expression of the epigenetic regulator HDAC7, whereas this correlation was positive in old mice. Conclusions: These findings suggest that age-dependent changes in epigenetic regulation, such as the interaction between HDAC7 and TLR4, may contribute to the distinct pathological progression of ischemic stroke in older individuals. Full article

In this study, the design and synthesis of a novel series of cinnamic acid and 1,2,4-triazole hybrids were reported, aiming to enhance antioxidant and lipoxygenase inhibitory activities through pharmacophore combination. Cinnamic acid derivatives and 1,2,4-triazoles exhibit a broad spectrum of biological activities; therefore, by synthesizing hybrid molecules, we would like to exploit the beneficial characteristics of each scaffold. The general synthetic procedure comprises three synthetic steps, starting from the reaction of appropriate substituted cinnamic acid with hydrazine monohydrate in acetonitrile with cyclohexane and resulting in the formation of hydrazides. Consequently, the hydrazides reacted with phenylisothiocyanate under microwave irradiation conditions. Then, cyclization proceeded to the 1,2,4-triazole after the addition of NaOH solution and microwave irradiation. All the synthesized derivatives have been studied for their ability (a) to interact with the free radical DPPH, (b) inhibit lipid peroxidation induced by AAPH, and (c) inhibit soybean lipoxygenase. The synthesized derivatives have shown significant antioxidant activity and have been proved to be very good lipoxygenase inhibitors. Compounds 4b and 4g (IC₅₀ = 4.5 μM) are the most potent within the series followed by compound 6a (IC₅₀ = 5.0 μM). All the synthesized derivatives have been subjected to docking studies related to soybean lipoxygenase. Compound 4g exhibited a docking score of −9.2 kcal/mol and formed hydrophobic interactions with Val126, Tyr525, Lys526, Arg533, and Trp772, as well as a π−cation interaction with Lys526. Full article