Search Results (41,530)

Alkaptonuria (AKU) is a rare metabolic disorder caused by homogentisate 1,2-dioxygenase (HGD) deficiency, leading to homogentisic acid (HGA) accumulation and ochronotic pigment deposition, which drug therapy cannot reverse. The process of pigment formation and deposition is still unclear. This study offers molecular insights into the polymeric structure, with the goal of developing future adjuvant strategies that can inhibit or reverse pigment formation, thereby complementing drug therapy in AKU. HGA polymerisation was examined under physiological, acidic, and alkaline conditions using liquid and solid phase nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR), and polyacrylamide gel electrophoresis. At physiological pH, HGA polymerised slowly, while alkaline catalysis accelerated pigment formation while retaining the HGA aromatic scaffold. During the process, EPR detected a semiquinone radical intermediate, consistent with an oxidative coupling mechanism. Reactivity profiling showed the diphenol ring was essential for polymerisation, while –CH₂COOH modifications did not impair reactivity. Pigments displayed a polydisperse molecular weight range (11–50 kDa) and a strong negative charge. Solid-state NMR has revealed the presence of phenolic ether and biphenyl linkages. Collectively, these identified structural motifs can serve as a foundation for future molecular targeting related to pigment formation. Full article

Introduction: Primary glomerulopathies are immune-driven kidney diseases. IgA nephropathy (IgAN) and membranoproliferative glomerulonephritis (MPGN) are prevalent entities with a risk of chronic progression. Immune checkpoints, such as PD-1/PD-L1, CTLA-4/CD86, and CD200R/CD200, regulate activation and tolerance in T, B, and NK cells, and also exist in soluble forms, reflecting systemic immune balance. Objective: To compare immune checkpoint profiles in IgAN and MPGN versus healthy volunteers (HV) through surface expression, soluble serum levels, and PBMC transcripts, with attention to sex-related differences and diagnostic value assessed by ROC curves. Materials and Methods: Ninety age-matched subjects were studied: IgAN (n = 30), MPGN (n = 30), HV (n = 30). Flow cytometry evaluated checkpoint expression on CD4+/CD8+ T cells, CD19+ B cells, and NK cells. ELISA quantified sPD-1, sPD-L1, sCTLA-4, sCD86, sCD200, sCD200R; PBMC transcript levels were assessed. Group comparisons, sex stratification, and ROC analyses were performed. Results: Lymphocyte distributions were preserved, but IgAN patients showed anemia and impaired renal function, while MPGN patients had greater proteinuria and dyslipidemia. GN patients displayed increased PD-1/PD-L1 and CD200R/CD200, with reduced CTLA-4/CD86, compared to HV. Serum analysis revealed elevated sPD-1, sPD-L1, sCD200, sCD200R and decreased sCTLA-4, sCD86. PBMC transcripts paralleled these trends, with PD-1/PD-L1 mainly increased in MPGN. Sex had minimal impact. ROC analyses showed strong GN vs. HV discrimination by CD19⁺CTLA-4⁺, PD-1/PD-L1, and CD200/CD200R, but limited ability to separate IgAN from MPGN. Conclusions: IgAN and MPGN share a sex-independent checkpoint signature: PD-1/PD-L1 and CD200R/CD200 upregulation with CTLA-4/CD86 downregulation. CD19⁺, CTLA-4⁺, and soluble PD-1/PD-L1/CD200(R) emerge as promising biomarkers requiring further validation. Full article

Understanding how solvents influence the luminescence behavior of Cu(I) complexes is crucial for designing advanced optical sensors. This study reports the synthesis, structures and photophysical investigation of an 8-hydroxyquinoline-functionalized 1H-imidazo[4,5-f][1,10]phenanthroline ligand, ipqH₂, and its four Cu(I) complexes with diphosphine co-ligands. Photoluminescence studies demonstrated distinct solvent-dependent excited-state mechanisms. In DMSO/alcohol mixtures, free ipqH₂ exhibited excited-state proton transfer (ESPT) and enol-keto tautomerization, producing dual emission at about 447 and 560 nm, while the complexes resisted ESPT due to hydrogen bond blocking by PF₆⁻ anions and Cu(I) coordination. In DMSO/H₂O, aggregation-caused quenching (ACQ) and high-energy O–H vibrational quenching dominated, but complexes 1 and 2 showed a significant red-shifted emission (569–574 nm) with high water content due to solvent-stabilized intra-ligand charge transfer and metal-to-ligand charge transfer ((IL+ML)CT) states. In DMSO/DMF, hydrogen bond competition and solvation-shell reorganization led to distinct responses: complexes 1 and 3, with flexible bis[(2-diphenylphosphino)phenyl]ether (POP) ligands, displayed peak splitting and (IL + ML)CT redshift emission (501 ⟶ 530 nm), whereas complexes 2 and 4, with rigid 9,9-dimethyl-4,5-bis(diphenylphosphino)-9H-xanthene (xantphos), showed weaker responses. The flexibility of the diphosphine ligand dictated DMF sensitivity, while the coordination, the hydrogen bonds between PF₆⁻ anions and ipqH₂, and water solubility governed the alcohol/water responses. This work elucidates the multifaceted solvent-responsive mechanisms in Cu(I) complexes, facilitating the design of solvent-discriminative luminescent sensors. Full article

Background: Parkinson’s disease (PD) is a neurodegenerative disorder for which no curative therapies currently exist. Experimental models employing 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) reproduce PD features such as striatal dopaminergic dysfunction and motor deficits. Various MPTP dosing regimens are used to screen drug candidates for PD, but their validity is limited because of the predominant use of young male animals. Sex bias is another issue that is underrepresented in PD research, since females are more susceptible to this pathology. Here, we studied the model of bolus administration of MPTP (30 mg/kg) in aged female mice and assessed its sensitivity to the antioxidants fullerene C₆₀ and fullerenol C₆₀(OH)₂₄, given that oxidative stress is a key contributor to PD. Methods: 12-month-old female C57BL/6 mice received fullerene (0.1 mg/kg/day, via diet) or fullerenol (0.15 mg/kg/day, via drinking water). On day 10, mice were injected with MPTP. We studied tremor, piloerection, and behavior in the pole test, rotarod, pole test, and open field. High-performance liquid chromatography (HPLC) was employed to study dopaminergic neurotransmission, and the expression levels of its molecular regulators and nitric oxide synthase (NOS)-related targets were investigated using RT-PCR in the striatum and cortex. Results: MPTP-challenged mice displayed profound impairment in markers of dopaminergic neurotransmission and cellular distress, and showed disrupted motor behavior and vegetative functions. Antioxidant-treated animals that received a bolus injection of MPTP demonstrated partial preservation of tremor response, dopaminergic parameters, and iNOS and nNOS gene expression, although motor performance in the pole test was only modestly improved. Fullerenol appeared more effective in decreasing MPTP-induced neurochemical changes. Conclusions: The applied MPTP model showed its validity in mimicking PD features and was sensitive to low doses of antioxidants, suggesting its usefulness for screening drugs that target oxidative and nitrosative stress. The neuroprotective effects of fullerene-based compounds suggest their potential utility in the treatment of PD. Full article

Research on Mesoscale Convective Systems (MCSs) in Ecuador has focused on regional studies. However, it lacks a thorough and general examination of their relationship with the nation’s diverse orography and large-scale phenomena. This study conducts a climatological analysis of MCS occurrence throughout Ecuador’s natural regions. We perform this study using Sen’s Slope and the Mann–Kendall test. Teleconnections from the Pacific and Atlantic Oceans are studied through wavelet decomposition between time series and Pacific and Atlantic oceanic indices. The main factors that control MCS formation depend on the region. The Intertropical Convergence Zone (ITCZ) at the large scale affects the entire territory. In western Ecuador, MCS formation is mostly related to the El Niño current and the Chocó Low-Level Jet (CLLJ). The Orinoco Low-Level Jet (OLLJ) and evapotranspiration and nocturnal convection display the largest roles in the east. A progressive intensification of activity from Highlands-North in SON is detected (0.143 MCSs per year). MCSs contribute 26% of total precipitation on average, with regional variations from Coast-South (16.41%) to Amazon-North (44.13%). The research confirms existing knowledge about El Niño’s strong relationship (ρ = 0.7) with MCS occurrence in coastal areas while uncovering new complex patterns. The Trans-Nino Index (TNI) functions as a critical two-sided modulator that conventional analysis methods fail to detect. It produces null correlations over conventional time series of MCS occurrence yet emerges as a primary driver of low-frequency variability in the proposed six natural zones of Ecuador. Wavelet decomposition reveals contrasting TNI responses: Amazon-North shows positive correlation (0.73) while Amazon-South exhibits negative correlation (−0.70) at low frequencies. This affects Walker circulations dynamics over the Pacific Ocean. This research establishes fundamental knowledge about MCSs in Ecuador. It builds on a database with strong methodology as a backbone. The research provides essential information about the factors leading to convection in the country. This will help improve seasonal forecast accuracy and risk management effectiveness. Full article

Antiviral peptides (AVPs) are promising therapeutic candidates, yet the rapid growth of sequence data and the field’s emphasis on predictors have left a gap: the lack of an integrated view linking peptide chemistry with biological context. Here, we map the AVP landscape through interactive data mining using Half-Space Proximal Networks (HSPNs) and Metadata Networks (MNs) in the StarPep toolbox. HSPNs minimize edges and avoid fixed thresholds, reducing computational cost while enabling high-resolution analysis. A threshold-free HSPN resolved eight chemically and biologically distinct communities, while MNs contextualized AVPs by source, function, and target, revealing structural–functional relationships. To capture diversity compactly, we applied centrality-guided scaffold extraction with redundancy removal (90–50% identity), producing four representative subsets suitable for modeling and similarity searches. Alignment-free motif discovery yielded 33 validated motifs, including 10 overlapping with reported AVP signatures and 23 apparently novel. Motifs displayed category-specific enrichment across antimicrobial classes, and sequences carrying multiple motifs (≥4–5) consistently showed higher predicted antiviral probabilities. Beyond computational insights, scaffolds provide representative “entry points” into AVP chemical space, while motifs serve as modular building blocks for rational design. Together, these resources provide an integrated framework that may inform AVP discovery and support scaffold- and motif-guided therapeutic design. Full article

Personnel selection represents a two-sided matching problem in which firms compete for qualified candidates by designing job-offer packages. While traditional models assume fully rational agents, real-world decision-makers often face bounded rationality due to limited information and cognitive constraints. This study develops a matching framework that incorporates bounded rationality through the Quantal Response Equilibrium, where firms and candidates act as probabilistic rather than perfect optimizers under uncertainty. Using Maximum Likelihood Estimation and organizational hiring data, we validate that both sides display bounded rational behavior and that rationality increases as the selection process advances. Building on these findings, we propose a two-stage stochastic optimization approach to determine optimal job-offer packages that balance organizational policies with candidate competencies. The optimization problem is solved using particle swarm optimization, which efficiently explores the solution space under uncertainty. Data analysis reveals that only 23.10% of low-level hiring decisions align with rational choice predictions, compared to 64.32% for high-level positions. In our case study, bounded rationality increases package costs by 26%, while modular compensation packages can reduce costs by up to 25%. These findings highlight the cost implications of bounded rationality, the advantages of flexible offers, and the systematic behavioral differences across job levels. The framework provides theoretical contributions to matching under bounded rationality and offers practical insights to help organizations refine their personnel selection strategies and attract suitable candidates more effectively. Full article

The aim of this study was the evaluation of egg quality between three different farming systems. Eggs collected from intensive (IS), extensive (ES), and dual-purpose systems (DPSs) at three stages of the production cycle (age) were analyzed for both external and internal traits. ISs represent high-input systems while ESs and DPSs represent low-input systems. Both the farming system and age had significant effects on quality characteristics. Eggs from the ES displayed a greater egg weight (64.3 ± 0.20 g) and shell weight (6.6 ± 0.03 g). Eggs from the IS farms displayed a higher Haugh unit score (83.2 ± 0.50), darker colored yolks (12.0 ± 0.06), and a lower incidence of blood spots (0.2 ± 0.05). The age and farming system influenced the fatty acid profile of eggs across farming systems. In particular, DPS eggs showed higher levels of unsaturated (62.2 ± 0.20%) and lower levels of saturated (37.8 ± 0.10%) fatty acids. The effect of age was also significant on the oxidation stability of yolks. The interaction effect (farming system × age) had significant effects on most traits. However, the farming system alone accounted for a greater portion of the variation in most egg quality parameters. Full article

This study presents a paleopathological analysis of individual T4.2 from the archaeological site of the castle of Zorita de los Canes (Guadalajara, Spain). The individual exhibits ultradolichocephaly and was dated between the 13th and 15th centuries. Based on the context, the individual could have been a member of the military–religious Order of Calatrava. Standard bioanthropological and paleopathological methods were applied. The results indicate a male aged between 45 and 49 years with a maximum cranial length and width of 230 mm and 122 mm, respectively. The cranial index (53%) allows him to be classified as ultradolichocephalic. The remains present craniosynostosis at the sagittal, squamosal and sphenofrontal sutures, together with underdevelopment of the skull base width and a dolichognathic mandible with the possible presence of type III prognathism. The left hemimandible and hemimaxilla display a large amount of tartar covering the occlusal, labial and lingual areas of the teeth completely. The right hemimandible and hemimaxilla exhibit almost no tartar, and some teeth were lost in vivo. In addition, two stab wounds—to the external occipital protuberance and to the left temple—as well as a contused injury in the left tibia, can be observed without evidence of bone remodeling. Differential diagnosis indicates a case consistent with Crouzon syndrome. This individual is of particular significance because he was a possibly knight of the Order of Calatrava who presents a syndromic craniosynostosis consistent with Crouzon syndrome and exhibits lesions, which may suggest that he could have died in battle. Full article

Three-dimensional concrete printing (3DCP), an innovative fabrication technique, has emerged as an environmentally friendly digital manufacturing process for using recycled waste materials in the construction industry. The aim of this review paper is to critically evaluate the current state of research on the use of recycled materials such as aggregates and powders in 3DCP, correlating the environmental, economic, and performance parameter effects. This review comprehensively evaluates the potential benefits of incorporating recycled waste materials in 3D printing by critically reviewing the existing peer-reviewed articles through a scientometric review. The resulting bibliometric analysis identified 73 relevant papers published between 2018 and 2024. Through the critical review, five main research categories were identified: recycled materials in 3DCP arising mainly from construction demolition in powder and aggregate forms, which investigates the types of recycled materials used, their extraction methods, morphology and physical and chemical properties. The morphology properties of the materials used displayed high irregularities in terms of shape and percentage of adhered mortar. In the second category, printability and performance, the buildability, rheological properties and the mechanical performance of 3DCP with recycled materials were investigated. Category 3 assessed the latest developments in terms of 3D-printed techniques, including Neural Networks, in predicting performance. Category 4 analysed the environmental and economic impact of 3DCP. The results indicated anisotropic behaviour for the printed samples influencing mechanical performance, with the parallel printing direction showing improved performance. The environmental performance findings indicated higher global warming potential when comparing 3DCP to cast-in situ methods. This impact was reduced by 2.47% when recycled aggregates and binder replacements other than cement were used (fly ash, ground slag, etc.). The photochemical pollution impact of 3DPC was found to be less than that of cast-in situ, 0.16 to 0.18 C2H4-eq. This environmental impact category was further reduced up to 0.10 C2H4-eq following 100% replacement. Lastly, category 5 explored some of the challenges and barriers for the implementation of 3DCP with recycled materials. The findings highlighted the main issues, namely inconsistency in material properties, which can lead to a lack of regulation in the industry. Full article

Seawater intrusion into coastal river systems poses increasing challenges for freshwater availability and estuarine ecosystem integrity, especially under evolving climatic and anthropogenic pressures. This study presents a multidisciplinary investigation of marine intrusion dynamics within the Magra River estuary (Northwest Italy), integrating field monitoring, isotopic tracing (δ¹⁸O; δD), and multivariate statistical modeling. Over an 18-month period, 11 fixed stations were monitored across six seasonal campaigns, yielding a comprehensive dataset of water electrical conductivity (EC) and stable isotope measurements from fresh water to salty water. EC and oxygen isotopic ratios displayed strong spatial and temporal coherence (R² = 0.99), confirming their combined effectiveness in identifying intrusion patterns. The mass-balance model based on δ¹⁸O revealed that marine water fractions exceeded 50% in the lower estuary for up to eight months annually, reaching as far as 8.5 km inland during dry periods. Complementary δD measurements provided additional insight into water origin and fractionation processes, revealing a slight excess relative to the local meteoric water line (LMWL), indicative of evaporative enrichment during anomalously warm periods. Multivariate regression models (PLS, Ridge, LASSO, and Elastic Net) identified river discharge as the primary limiting factor of intrusion, while wind intensity emerged as a key promoting variable, particularly when aligned with the valley axis. Tidal effects were marginal under standard conditions, except during anomalous events such as tidal surges. The results demonstrate that marine intrusion is governed by complex and interacting environmental drivers. Combined isotopic and machine learning approaches can offer high-resolution insights for environmental monitoring, early-warning systems, and adaptive resource management under climate-change scenarios. Full article

In southern white rhinoceroses (Ceratotherium simum simum), pant calls are well-studied contact vocalisations, whereas the function of frequently emitted snorts remains unclear. We conducted playback experiments with 15 rhinoceroses at three European zoos. The first experiment tested responses to conspecific versus heterospecific snorts, comparing pulsed and non-pulsed acoustic structures. The second experiment contrasted conspecific snorts with conspecific pants from males differing in age and faecal testosterone metabolite (fTM) levels. Behavioural responses—including body orientation, approach toward loudspeaker, locomotion, and vocalisations—were analysed. Snorts, regardless of sender species or pulsation, elicited uniformly low-intensity responses, suggesting limited communicative function. In contrast, pants evoked significantly stronger responses depending on sex and group setting. While males showed increased locomotion, females vocalised more, reflecting the species’ social dynamics. Individuals tested alone displayed overall heightened vigilance and vocal activity compared to those tested in pairs, emphasising the role of social context. No evidence was found for discrimination between pant calls differing in fTM levels. Our findings reinforce the communicative relevance of pants in conveying social cues while indicating that snorts may either lack species-specific acoustic markers or not be socially salient. Playback experiments thus appear as valuable tools for assessing acoustic communication in zoo-housed mammals. Full article

Strawberry (Fragaria × ananassa Duch.) is a widely cultivated and economically important fruit crop with increasing consumer demand worldwide. Nowadays, in Uzbekistan, strawberry cultivation surpasses that of many other fruits and vegetables in terms of production volume. However, most genetic studies have focused on a limited set of cultivars, leaving a substantial portion of varietal diversity unexplored. This study aimed to evaluate the genetic variability and heritability among selected strawberry cultivars, as well as correlations between certain valuable agronomic traits, using molecular and statistical approaches. Polymorphism analysis was performed, using 67 gene-specific SSR markers, through PCR, and allele variations were observed in 46.3% of the markers analyzed. Among them, 31 markers displayed polymorphic bands, identifying fifty alleles, with one to four alleles per marker. Phylogenetic analysis was performed using MEGA 11 software, while statistical evaluations included AMOVA (GenAIEx), correlation (OriginPro), and descriptive statistics based on standard agronomic methods. Additionally, the degree of cross-compatibility and pollen viability among the cultivars were studied, and their significance for cultivar hybridization was analyzed. The highest fruit weight was observed in the Cinderella cultivar (26.2 g), and a moderate negative correlation (r = −0.688) was found between fruit number and fruit weight. These findings demonstrate the potential of molecular tools for assessing genetic diversity and provide valuable insights for breeding programs aimed at developing improved strawberry cultivars with desirable agronomic traits. Full article

Aquaculture is an important food sector, which involves the commercial production of fish for consumption. Tilapias (Oreochromis sp.) are hardy and are one of the most commonly produced fishes in the aquaculture industry. Disease outbreaks caused by Streptococcus agalactiae, however, widely affect tilapia farms, resulting in high mortality. Consequently, this may lead to the misuse of antibiotics for the prevention of disease or overuse of antibiotics when used for the treatment of fishes, contributing to antibiotic resistance. In this study, date palm pits, a waste product from the date palm industry, were tested for potential antibacterial activity against S. agalactiae and for their ability to act as an immune enhancer in vitro through the use of the head kidney and serum from healthy adult tilapias. An in vivo study was performed by dividing tilapias into two groups, consisting of infected S. agalactiae and uninfected S. agalactiae. Each group consisted of extract-fed and distilled-water-fed tilapia. Then, the serum, spleen and head kidney were isolated from both groups and tested for their respiratory burst, lysozyme and myeloperoxidase activities. The results from this study indicate that the Raziz methanol extract at a concentration of 1 g/mL inhibited the growth of S. agalactiae, and concentrations of 10 mg/mL, 2 mg/mL and 0.016 mg/mL displayed the highest respiratory burst, lysozyme and myeloperoxidase activities, respectively, in vitro. In the infected group, extract-fed tilapias showed a significant effect on respiratory burst activity and lysozyme activity compared to the distilled-water-fed tilapias, while no significant activity was observed in the uninfected group. In conclusion, the Raziz methanol extract has promising potential to act as an antibacterial agent, and it enhanced the innate immune function during active infection of S. agalactiae. Full article

Staphylococcus aureus is a major pathogen responsible for staphylococcal food poisoning (SFP), with its pathogenicity primarily dependent on staphylococcal enterotoxins (SEs). Among these, staphylococcal enterotoxin A (SEA) is a critical risk factor due to its high toxicity, high detection rate (accounting for 80% of SFP cases), strong thermal stability, and resistance to hydrolysis. Traditional SEA immunoassays, such as enzyme-linked immunosorbent assay (ELISA), are prone to false-positive results caused by nonspecific binding interference from S. aureus surface protein A (SpA). In recent years, nanobodies (single-domain heavy-chain antibodies) have emerged as an ideal alternative to address SpA interference owing to their small molecular weight (15 kDa), high affinity, robust stability, and lack of Fc regions. In this study, based on a previously developed highly specific monoclonal antibody against SEA (mAb-4C6), four anti-SEA nanobodies paired with mAb-4C6 were obtained through two-part (four-round) of biopanning from a naive nanobody phage display library. Among these, SEA-4-20 and SEA-4-31 were selected as optimal candidates and paired with mAb-4C6 to construct double-antibody sandwich ELISAs. The detection limits for SEA were 0.135 ng/mL and 0.137 ng/mL, respectively, with effective elimination of SpA interference. This approach provides a reliable tool for rapid and accurate detection of SEA in food, clinical, and environmental samples. Full article