Search Results (773)

Background: Screening for presymptomatic type 1 diabetes (T1D) reduces the risk of diabetic ketoacidosis (DKA) and allows for early intervention with disease-modifying therapies. Despite the rising incidence of T1D in Bulgaria, screening initiatives remain limited. This pilot study aims to evaluate the feasibility of selective T1D screening in high-risk children and identify potential clinical associations with islet autoimmunity. Methods: The study targeted a recruitment of 250 children aged 0–18 years (200 with a relative with T1D and 50 without). Screening for islet autoantibodies (AABs), including glutamic acid decarboxylase (GADA), insulin (IAA), insulinoma-associated-2 (IA-2A), zinc transporter-8 (ZnT8A), and islet cell cytoplasmic autoantibodies (ICAs), was performed via chemiluminescence immunoassay (CLIA). Participants testing positive for one or more AABs were scheduled for longitudinal immunological and metabolic follow-up to evaluate the persistence of autoimmunity and disease progression. Results: Between October 2024 and February 2026, the pilot study recruited 210 participants (84% of the 250 target), including 160 children with a relative (target 200) and 50 without a family history of T1D (target 50). Within the high-risk group, seven children (4.4%) tested positive for a single autoantibody (3 GADA, 2 ZnT8A, 1 IA-2A, and 1 IAA), while no autoantibodies were detected in the group without a relative. No cases of multiple autoantibody positivity or stage 3 T1D were identified in either group. Furthermore, no statistically significant associations were observed between autoantibody positivity and secondary factors, including breastfeeding, allergic status, a high-glycemic diet, frequent illness, and personal history of autoimmune disease. Conclusions: The findings validate the feasibility of selective T1D screening in Bulgaria, driven by high public interest and successful recruitment across both high-risk and general population cohorts. While this exploratory study found no significant clinical correlations, it establishes a vital roadmap for larger, longitudinal research. Ultimately, this pilot framework provides a scalable model for implementing standardized early detection to reduce the burden of T1D on the national healthcare system. Full article

Type 1 diabetes (T1D) is an autoimmune disease characterized by T-cell-mediated destruction of pancreatic β-cells. Antigen-specific peptide immunotherapy represents a promising strategy to restore immune tolerance. Reliable identification of relevant T-cell epitopes requires accurate prediction of peptide binding to disease-associated major histocompatibility complex (MHC) molecules. In this study, we developed and validated artificial intelligence (AI)-driven machine learning (ML) predictive models for peptides binding to the NOD mouse-specific MHC class I molecules H-2D^b and H-2K^d and the class II molecule I-A^g7. Balanced datasets of experimentally validated binders and non-binders were compiled, divided into training and test sets, and used to construct position-specific logo models and supervised ML classifiers based on z-scale physicochemical descriptors. External validation demonstrated moderate predictive performance for the logo models (ROC AUC 0.685–0.738), whereas AI models, including Random Forest, Support Vector Machine, and Gradient Boosting, achieved substantially improved discrimination (ROC AUC 0.888–0.906). The validated models were applied to the major T1D autoantigens glutamic acid decarboxylase 65, insulin-1, insulin-2 and zinc transporter 8 and predicted multiple binders, with some overlapping with previously reported immunodominant regions. Selected binders were prioritized for further synthesis and in vivo immunogenicity testing in NOD mice. Full article

Urban soils along transportation routes are subjected to intense anthropogenic pressure, altering their physicochemical properties and promoting the accumulation of potentially toxic metals (PTM). This study aimed to assess soil contamination levels and evaluate the bioindicative potential of Acer negundo L. growing in urban green areas exposed to varying traffic intensities. Topsoil and leaf samples were collected from eight sites representing different levels of anthropogenic disturbance. Soil granulometric composition, pH, organic carbon content, selected nutrients, and concentrations of PTM (Cu, Pb, Zn, Ni, Co, Mn, Cd, Hg, Fe) were determined, and contamination was evaluated using pollution indices (Igeo, EF, CF, Er). The soils ranged from moderately acidic to slightly alkaline (pH_KCl 5.85–7.66). Elevated concentrations of Zn (1078 ± 3.07 mg kg⁻¹), Pb (401.4 ± 2.51 mg kg⁻¹), Mn (1816 ± 3.3 mg kg⁻¹), and Cd (10.8 ± 2.06 mg kg⁻¹) were recorded at most sites, frequently exceeding permissible limits for urban green areas (Zn: 500; Pb: 200; Mn: 240 and Cd: 2 mg kg⁻¹). Correlation analyses revealed that zinc and cadmium are the two predominantly traffic-related origins. Pollution indices indicated moderate to very high enrichment, particularly for Cu and, locally, for Cd and Zn, while cadmium posed the highest potential ecological risk. The differences in the order of element abundance between the soil and plant tissues indicated a selective enrichment in plant leaves, with a preference for Fe, Zn, Mn, Cu and Pb. A strong positive correlation between soil and leaf cadmium concentrations indicates its high bioavailability and efficient transfer to plant tissues. These results demonstrate that Acer negundo is a valuable bioindicator of urban soil contamination, particularly for cadmium and zinc, and highlight the significant impact of road traffic on urban soil quality. Full article

Colorectal cancer (CRC) persists as a significant public health burden due to its high morbidity and mortality rates worldwide, yet the molecular events that govern its initiation and progression remain incompletely understood. We recently conducted microRNA (miRNA) profiling and identified multiple dysregulated miRNAs in CRC compared to adjacent normal tissue. Among those, miR-138-5p emerged as a potential tumor suppressor due to its marked downregulation in CRC tissue; however, the stage-specific expression of this miRNA during CRC progression and underlying molecular mechanisms remains to be unraveled. In this study, we performed differential expression profiling of healthy colon, adenomatous polyp (AP), and CRC tissues based on public datasets, revealing significant downregulation of miR-138-5p in CRC compared to controls, but not during the AP stage, suggesting a role in later stages of malignant progression. Forced expression of miR-138-5p in HCT116 and HT-29 CRC models suppressed clonogenic survival, proliferation, and migration while inducing cell death. Additionally, miR-138-5p significantly inhibited tumor formation under three-dimensional culture settings, reinforcing its tumor-suppressive function in a physiologically relevant context. Transcriptomic profiling of miR-138-5p-overexpressing CRC models revealed widespread changes in the pathways related to zinc ion binding, cilium morphogenesis, smoothened signaling, and nuclear transport. Integrated computational and experimental analyses identified 41 potential gene targets, among which TCF3, UBE2C, EIF4EBP1, LYPLA1, and CD44 were validated as potential miR-138-5p-regulated genes. Collectively, these findings establish miR-138-5p as a stage-specific tumor suppressor in CRC, acting through coordinated regulation of oncogenic networks across multiple pathways. Downregulation of miR-138-5p appears to be a late oncogenic event, conferring proliferative, survival, and invasive advantages to tumor cells. Restoration of miR-138-5p or therapeutic targeting of its downstream effectors may represent promising avenues for CRC therapeutic intervention. Full article

Background/Objectives: Trace metal homeostasis is regulated by nutritional status and is crucial for maintaining redox balance, vascular function, and neuroinflammation. Dysregulation of systemic copper (Cu) metabolism, especially an elevated level of non-ceruloplasmin-bound copper (NCC), has been linked to oxidative stress and early cognitive decline. However, the nutritional and molecular pathways that connect Cu imbalance to mild cognitive impairment (MCI) are not well understood. Methods: We compared the serum Cu and zinc levels of individuals with normal cognition (NC; n = 116) and MCI (n = 184). An exploratory serum proteomic analysis using pooled samples was conducted to investigate patterns related to Cu dysregulation. We identified proteins using pattern correlation analysis and then performed a protein–protein interaction analysis using STRING and functional annotation and biological and Kyoto Encyclopedia of Genes and Genomes pathways. Results: The individuals with MCI had higher NCC levels than those with NC, indicating disrupted Cu metabolism influenced by nutrition and metabolism. The proteomic analysis revealed changes in proteins related to lipid transport, metal balance, and inflammation, including transthyretin, transferrin, apolipoprotein A-I, alpha-1 antitrypsin, antithrombin III, and alpha-2-macroglobulin, which respond to oxidative stress and vascular injury. Conclusions: In this cross-sectional analysis of baseline data, NCC levels were associated with cognitive status and specific circulating proteomic profiles. These findings suggest a potential relationship between copper-related biomarkers and mild cognitive impairment; however, longitudinal studies are required to clarify temporal relationships and potential mechanistic pathways. Full article

Indium Tin Oxide (ITO) is one of the most widely used ohmic materials for fabricating ohmic layers in thin-film solar cells. ITO thin layers have reached almost the maximum theoretical conductivity and the lowest practical resistivity. Along with indium’s toxic environmental impact and the high cost of materials, these are the reasons why new materials for efficient, cheaper thin-film transparent ohmic layers are being examined. One of those materials is copper-doped zinc oxide (ZnO:Cu). In this paper, we present a new approach to copper-doped zinc oxide fabrication methods, based on the modern authorial Physical Vapor Co-Deposition technique, which involves optimizing Cu concentration to fine-tune crystal structure, optical band gap, and electrical properties, creating n-type TCOs essential for efficient charge transport in next-generation thin films perovskite solar cells. Full article

Carbon-based bifunctional oxygen electrocatalysts with rationally designed architectures are essential for high-performance rechargeable zinc–air batteries (ZABs), yet the concurrent optimization of catalytic activity, durability, and mass transport remains challenging. Herein, hierarchical ZnCo carbon nanofibers/carbon nanotubes (CNFs@CNTs) are fabricated via single-nozzle electrospinning followed by melamine-assisted pyrolysis under a ZnCl₂-regulated atmosphere. During thermal treatment, Co species embedded within carbon nanofibers catalyze in situ carbon nanotube growth, while ZnCl₂ vapor modulates the carbonization process and surface chemistry, collectively generating a hierarchical CNFs@CNTs architecture with high surface area and abundant exposed active sites. As a result, ZnCo CNFs@CNTs exhibit outstanding bifunctional ORR/OER activity, surpassing Zn-free and Co-free counterparts. Combined structural and electrochemical analyses reveal that the synergistic interaction between Co active centers and Zn-assisted carbon structural regulation enhances reaction kinetics and long-term stability. When implemented as air electrodes in rechargeable ZABs, ZnCo CNFs@CNTs deliver high power density, reduced charge–discharge polarization, and excellent cycling durability, demonstrating strong practical applicability. This work presents an effective strategy for constructing hierarchical CNFs@CNTs composites via electrospinning and dual-component thermal regulation, offering new insights into the design of high-efficiency bifunctional air electrodes for advanced ZABs. Full article

The commercialization of lithium metal batteries is hindered by critical challenges such as uncontrollable lithium dendrite growth and interfacial instability. Constructing functional nanocoatings on separator surfaces represents an effective strategy to address these issues. In this study, a uniform aluminum-doped zinc oxide (AZO) modification layer was deposited on the separator via magnetron sputtering to enhance the electrochemical performance and safety of lithium metal batteries. The AZO layer combines the functions of a physical barrier and an interfacial regulator. On one hand, it effectively suppresses lithium dendrite penetration through the separator. On the other hand, its surface properties facilitate uniform lithium-ion transport and reduce the deposition overpotential. Experimental results demonstrate that the symmetric cells employing AZO-modified separators exhibit significantly reduced and stable lithium deposition overpotentials. In full cells assembled with a nickel cobalt aluminum (NCA) cathode, the system demonstrates higher specific capacity and notably extended cycle life compared to cells using unmodified polyethylene (PE) separators. This work proposes a practical strategy based on AZO-modified separators, offering a promising pathway toward the development of next-generation lithium metal batteries with high energy density and improved safety. Full article

Cadmium (Cd) contamination of agricultural soils poses a serious threat to crop productivity and food safety due to its high mobility, bioaccumulation potential, and toxicity. This study investigated the effects of increasing Cd levels on growth performance, physiological responses, Cd partitioning, mineral nutrient disruption, and Cd accumulation in four Brassicaceae crops (cress, watercress, broccoli, and white cabbage). Plants were grown in plastic pots filled with 4 kg of soil under controlled greenhouse conditions and exposed to five different Cd concentrations (0, 5, 10, 20, and 50 mg kg⁻¹). Cd exposure significantly affected growth and physiological responses in a species-dependent manner. Compared to the control, shoot dry weight decreased by up to 66.4% in broccoli and 51.7% in cress at the highest Cd level, while white cabbage exhibited comparatively greater tolerance. Oxidative stress indicators showed contrasting patterns, with hydrogen peroxide (H₂O₂) increasing by up to 8.8-fold, whereas proline and membrane permeability (MP) responses varied among species. Photosynthetic pigments declined in cress but increased in broccoli under high Cd conditions, suggesting differential adaptive strategies. Cd accumulated predominantly in roots; however, root retention capacity declined at elevated Cd concentrations (20–50 mg kg⁻¹ soil), leading to greater Cd translocation to shoots. Elevated translocation factors and shoot Cd distribution demonstrated that physiological tolerance did not necessarily limit Cd accumulation in edible tissues. Cd stress also induced notable imbalances in essential mineral nutrients, particularly potassium (K), calcium (Ca), and zinc (Zn), reflecting strong Cd–nutrient interactions at uptake and transport levels. These nutrient disruptions not only exacerbated physiological stress responses but also reduced the nutritional quality of plant tissues. Notably, species maintaining relatively stable growth under moderate Cd exposure still accumulated substantial Cd concentrations in shoots, highlighting a critical disconnect between agronomic performance and food safety. In conclusion, the findings demonstrate that Brassicaceae crops exhibit contrasting strategies in response to Cd stress, with significant implications for Cd entry into the food chain. The study emphasizes the importance of integrating physiological assessment with metal partitioning and nutrient balance analyses when evaluating crop suitability for cultivation in Cd-contaminated soils and for mitigating potential risks to human health. Full article

Cholestasis in children is characterized by impaired bile flow that disrupts hepatic metabolism, nutrient homeostasis, and effects trace element balance. This narrative review summarizes current evidence on the metabolism, biological functions, and clinical implications of key trace elements—zinc, selenium, copper, and manganese—in pediatric cholestatic liver disease. The liver regulates trace element absorption, intracellular trafficking, storage, and biliary excretion; cholestasis alters these processes, leading to deficiencies or toxic accumulation. Zinc and selenium deficiencies are common and contribute to impaired growth, immune dysfunction, oxidative stress, and delayed hepatic regeneration. Conversely, reduced biliary excretion promotes copper and manganese accumulation, potentially exacerbating liver injury and causing manganese-related neurotoxicity. Recent advances in understanding metal-specific hepatic transporters and trafficking pathways have provided mechanistic insight into these alterations. Management strategies emphasize individualized supplementation, monitoring during enteral and parenteral nutrition, and prevention of deficiency and toxicity. Precision-based nutritional approaches may improve outcomes in pediatric cholestatic liver disease. Full article

The influence of three different types of microplastics (PE, PET, and PS) on soil physicochemical properties is the main scope of the present investigation. To this end, a pot experiment has been conducted, incorporating each kind of microplastic (MP) in two different soil samples in equal portions. The soils were typical of Mediterranean areas, moderately contaminated with Pb and Zn. Furthermore, two different plants, Nicotiana tabacum L. (Burley cv.) and Cannabis sativa L. (Fedora cv.), were planted to study the influence of a multi-contaminated soil environment on plant growth, along with their ability to absorb metals in their tissues. The addition of microplastics caused stronger reactions in slightly acidic soil, where the bioavailability of zinc and lead increased by 5–20% compared to alkaline soil rich in CaCO₃. Plant-to-soil indices have been calculated to monitor the plant’s capacity to transfer metals from the soil environment to plant tissues. PE induced the strongest and most consistent responses, increasing Zn and Pb bioavailability and systematically enhancing total concentration factors (TC), bioaccumulation factors (BAF), and translocation factors (TF) by up to 20%, particularly in acid soil, while PET reduced the mobility of metals on the surface while enhancing vertical transport, and PS caused moderate but stable changes. Plant responses were cultivar-dependent. Plant biomass increased by approximately 7–15% in Cannabis sativa L. (cv. Fedora 17), while Nicotiana tabacum L. (cv. Burley) showed greater sensitivity to the presence of microplastics. Even low MP inputs can subtly but persistently modify soil structure, metal dynamics, and soil–plant transfer processes without increasing total metal loads, highlighting the importance of soil chemistry and polymer type in assessing the environmental risk of microplastics for sustainable agroecosystems. Full article

Irrigation with pig slurry has been employed to discharge large volumes of slurry and to recover resources. However, using swine wastewater for agricultural irrigation may cause the accumulation of heavy metals in soil and their potential leaching to groundwater. Wastewater treatment plants (WWTPs) are crucial to mitigate heavy metal contents in swine wastewater through physical, chemical, and biological processes. This study tracked the fate of eight heavy metals in industrial swine farms: arsenic (As), cadmium (Cd), copper (Cu), chromium (Cr), lead (Pb), mercury (Hg), nickel (Ni), and zinc (Zn). Zn reported the highest removal (82 to 99%) in all WWTPs and Cu the lowest (−5 to 97%). Cu (0.59–1.64 mg L⁻¹) and Zn (0.35–1.14 mg L⁻¹) were the metals reported in all samples for the target treatment stages (influent, after biodigester, and effluent). Comparing the heavy metal concentration in the effluents, Cu and Zn reached the highest concentrations in all WWTPs. As, Cd, and Pb reported values under the practical quantification limit. In groundwater, Cr reported the highest average concentration in farm GP19 for upstream (0.006 mg L⁻¹) and for downstream (0.032 mg L⁻¹) in GP1. In irrigated soil the Cu and Zn reported the highest concentrations in all farms, showing an enrichment compared to natural soil, indicating that wastewater is the main source of these metals in soil in the farm areas. Although all metals met the Mexican and international regulations, total suspended solids (TSSs) and chemical oxygen demand (COD) for effluent were above the reference limits (TSS ≤ 24 mg L⁻¹ and COD ≤ 72 mg L⁻¹) more than ten and four times, respectively, for all WWTPs evaluated. These two parameters were positively related and significantly correlated (p < 0.05) with the presence of metals in the different water fractions, implying possible transport of metals in solids. Cd, Pb, and As, were never reported in treated wastewater and groundwater, but Cr and Hg were. This may be related to external activities such as agriculture for Cr. The enrichment of metals in irrigated soils can be related to the metal presence in groundwater due to leaching because of the karstic soil in the area. Full article

Proteins can be methylated at either of the two N atoms of the imidazole ring of histidine, yielding 1-methylhistidine (or pi-methylhistidine) or 3-methylhistidine (tau-methylhistidine). While protein histidine methylation in mammals was discovered more than 50 years ago, the first histidine methyltransferases were identified only recently. So far, four different human protein histidine methyltransferases have been uncovered, and one of these is METTL9, which is responsible for introducing 1-methylhistidine in a number of proteins. The minimal sequence motif that is required, though not always sufficient, for METTL9-mediated methylation is His-X-His (HxH), where X is preferentially a small uncharged residue. Many METTL9 substrates are methylated at stretches of alternating histidines, i.e., several adjoining HxH motifs, such as HxHxH. Histidines are frequently involved in binding metal ions, such as zinc. Accordingly, it has been shown for several sequences targeted by METTL9, for example, in the immunomodulatory and antibacterial protein S100A9 and the zinc transporter SLC39A7, that histidine methylation diminishes zinc binding and thereby modulates protein function. In this review, we present a detailed account of METTL9-mediated histidine methylation, regarding its discovery, biochemical mechanism, structural features, and biological significance. Full article

Cd-doped ZnS thin films (0–6 at.%) were deposited by SILAR and assessed as buffer layers for thin-film solar cells. XRD shows a single zinc-blende phase, with a small lattice expansion after Cd incorporation. As the Cd content increases, transmittance decreases and the direct band gap narrows, pushing absorption further into the visible. DFT with mBJ reproduces this redshift and attributes it to Cd-related states near the band edges. Hall measurements indicate stronger n-type transport at higher Cd levels, with lower resistivity, higher mobility, and a larger electron concentration. Overall, about 6% Cd provides a workable balance between transparency, absorption, and conductivity, making ZnS:Cd a suitable buffer-layer candidate. Full article

Cadmium (Cd) is a highly toxic heavy metal that severely impairs plant growth and poses ecological and health risks. Chrysanthemum indicum (L.), a dominant species in Cd-contaminated regions, represents a valuable germplasm for phytoremediation. In this study, we cloned and characterized CiWRKY50, a WRKY transcription factor containing a conserved WRKY domain and C2H2-type zinc finger. CiWRKY50 was localized to the nucleus but lacked intrinsic transcriptional activation activity. Overexpression of CiWRKY50 in Arabidopsis thaliana and C. indicum significantly enhanced Cd tolerance, as shown by reduced root Cd accumulation, improved transport efficiency, lower ROS and MDA levels, and increased chlorophyll, proline, and soluble protein contents. Antioxidant enzyme activities and Cd-chelating compounds (GSH, NPT, PCs) were also upregulated. Furthermore, combined Cd and ABA treatments promoted Cd sequestration in roots and activated ABA-responsive genes (CiABF1, CiABF2, CiABF4), alleviating shoot toxicity. These findings indicate that CiWRKY50 enhances Cd tolerance in association with enhanced ABA-mediated signaling and redox homeostasis, providing new insights for breeding Cd-resistant plants and improving phytoremediation strategies. Full article