Search Results (1,343)

Global warming and anthropogenic climate change are projected to expand the geographic distribution and population abundance of ectothermic species and exacerbate the biological invasion of exotic species. DNA methylation, as a reversible epigenetic modification, could provide a putative link between the phenotypic plasticity of invasive species and environmental temperature variations. We assessed and interpreted the epigenetic mechanisms of invasive and indigenous species’ differential tolerance to thermal stress through the invasive species Bemisia tabaci Mediterranean (MED) and the indigenous species Bemisia tabaci AsiaII3. We examine their thermal tolerance following exposure to heat and cold stress. We found that MED exhibits higher thermal resistance than AsiaII3 under heat stress. The fluorescence-labeled methylation-sensitive amplified polymorphism (F-MSAP) results proved that the increased thermal tolerance in MED is closely related to DNA methylation changes, other than genetic variation. Furthermore, the quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analysis of DNA methyltransferases (Dnmts) suggested that increased expression of Dnmt3 regulates the higher thermal tolerance of female MED adults. A mechanism is revealed whereby DNA methylation enhances thermal tolerance in invasive species. Our results show that the Dnmt-mediated regulation mechanism is particularly significant for understanding invasive species’ successful invasion and rapid adaptation under global warming, providing new potential targets for controlling invasive species worldwide. Full article

Background: Statins exhibit pleiotropic anti-inflammatory, antioxidant, and immunomodulatory effects, suggesting their potential in non-cardiovascular conditions. However, evidence supporting their repurposing remains limited, and off-label prescribing policies vary globally. Objective: To systematically review evidence on statin repurposing in oncology and infectious diseases, and to assess Hungarian regulatory practices regarding off-label statin use. Methods: A systematic literature search (PubMed, Web of Science, Scopus, ScienceDirect; 2010–May 2025) was conducted using the terms “drug repositioning” OR “off-label prescription” AND “statin” NOT “cardiovascular,” following PRISMA guidelines. Hungarian off-label usage data from the NNGYK (2008–2025) were also analyzed. Results: Out of 205 publications, 12 met the inclusion criteria—75% were oncology-focused, and 25% focused on infectious diseases. Most were preclinical (58%); only 25% offered strong clinical evidence. Applications included hematologic malignancies, solid tumors, Cryptococcus neoformans, SARS-CoV-2, and dengue virus. Mechanisms involved mevalonate pathway inhibition and modulation of host immune responses. Hungarian data revealed five approved off-label statin uses—three dermatologic and two pediatric metabolic—supported by the literature and requiring post-treatment reporting. Conclusions: While preclinical findings are promising, clinical validation of off-label statin use remains limited. Statins should be continued in cancer patients with cardiovascular indications, but initiation for other purposes should be trial-based. Future directions include biomarker-based personalization, regulatory harmonization, and cost-effectiveness studies. Full article

Due to their nutritional value and sustainability, edible insect-based foods are gaining popularity in Europe. Their use is regulated by EU legislation, which defines authorised species and sets labelling requirements. Molecular tools are being developed to authenticate such products. In this study, yellow mealworm (Tenebrio molitor) larvae authorised for human consumption were fed wheat flour-based diets containing varying proportions of house cricket (Acheta domesticus) flour for 21 days. This was followed by a 48 h starvation period to assess the persistence of insect DNA in the digestive tract. Two novel, species-specific, single-copy markers were designed: ampd gene for the Acheta domesticus and MyD88 gene for the Tenebrio molitor. These were applied using qPCR and ddPCR. Both methods successfully detected cricket DNA in the guts of starved larvae. Linear regression analysis revealed a strong, statistically significant correlation between the proportion of Acheta domesticus flour in the diet and the normalised relative quantity of DNA. ddPCR proved to be more sensitive than qPCR, particularly in the detection of low DNA levels. These results suggest that the presence of DNA from undeclared insect species in edible insects may be indicative of their diet rather than contamination or adulteration. This highlights the importance of contextual interpretation in food authenticity testing. Full article

The generation of memory CD8⁺ T cells is essential for establishing protective T cell immunity against pathogens and cancers. However, the cellular and molecular mechanisms underlying memory CD8⁺ T cell formation remain incompletely understood. Reliance on specific pathogen-free (SPF) models, characterized by restricted microbial exposure, may limit our understanding of physiologically relevant immune memory development. This study reveals that CD1d-restricted NKT cells regulate central memory T cell (TCM) generation exclusively in a microbe-rich (“dirty”) environment. Under non-SPF housing, CD1d⁺/⁻ and Ja18⁺/⁻ mice exhibited enhanced TCM formation compared to NKT-deficient controls (CD1d⁻/⁻/Ja18⁻/⁻), demonstrating that microbial experience is required for NKT-mediated TCM regulation. Mechanistically, CD1d-restricted NKT cells increased IL-15Rα expression on CD4⁺ T cells in CD1d⁺/⁻ mice, potentiating IL-15 trans-presentation and thereby activating the IL-15/pSTAT5/Eomes axis critical for TCM maintenance. Functional validation through adoptive transfer of CFSE-labeled OT-1 memory cells revealed an NKT cell-dependent survival advantage in CD1d⁺/⁻ hosts. This provides direct evidence that microbiota-experienced niches shape immune memory. Collectively, these findings establish CD1d-restricted NKT cells as physiological regulators of TCM generation and suggest their potential utility as vaccine adjuvants to enhance protective immunity. Full article

Infant clothing represents a critical yet overlooked exposure pathway for heavy metals, with significant implications for child health and sustainable consumption. This study investigates cadmium (Cd) and chromium (Cr) contamination in 33 textile samples, integrating in vitro bioaccessibility assays, cytotoxicity analysis, and risk assessment models to evaluate dermal exposure risks. Results reveal that 80% of samples exceeded OEKO-TEX Class I limits for As (mean 1.01 mg/kg), Cd (max 0.25 mg/kg), and Cr (max 4.32 mg/kg), with infant clothing showing unacceptable hazard indices (HI = 1.13) due to Cd (HQ = 1.12). Artificial sweat extraction demonstrated high bioaccessibility for Cr (37.8%) and Ni (28.5%), while keratinocyte exposure triggered oxidative stress (131% ROS increase) and dose-dependent cytotoxicity (22–59% viability reduction). Dark-colored synthetic fabrics exhibited elevated metal loads, linking industrial dye practices to health hazards. These findings underscore systemic gaps in textile safety regulations, particularly for low- and middle-income countries reliant on cost-effective apparel. We propose three policy levers: (1) tightening infant textile standards for Cd/Cr, (2) incentivizing non-toxic dye technologies, and (3) harmonizing global labeling requirements. By bridging toxicological evidence with circular economy principles, this work advances strategies to mitigate heavy metal exposure while supporting Sustainable Development Goals (SDGs) 3 (health), 12 (responsible consumption), and 12.4 (chemical safety). Full article

The priming effect (PE), a microbially mediated process, critically regulates the balance between carbon sequestration and mineralization. This study used soils from different soil depths (0–20 cm, 20–40 cm, and 40–60 cm) under Picea schrenkiana forest in the Tianshan Mountains as the research object. An indoor incubation experiment was conducted by adding three concentrations (1% SOC, 2% SOC, and 3% SOC) of ¹³C-labelled glucose. We applied ¹³C isotope probe-phospholipid fatty acid (PLFA-SIP) technology to investigate the influence of readily labile organic carbon inputs on soil priming effect (PE), microbial community shifts at various depths, and the mechanisms underlying soil PE. The results indicated that the addition of ¹³C-labeled glucose accelerated the mineralization of soil organic carbon (SOC); CO₂ emissions were highest in the 0–20 cm soil layer and decreased trend with increasing soil depth, with significant differences observed across different soil layers (p < 0.05). Soil depth had a positive direct effect on the cumulative priming effect (CPE); however, it showed negative indirect effects through physico-chemical properties and microbial biomass. The CPE of the 0–20 cm soil layer was significantly positively correlated with ¹³C-Gram-positive bacteria, ¹³C-Gram-negative bacteria, and ¹³C-actinomycetes. The CPE of the 20–40 cm and 40–60 cm soil layers exhibited a significant positive correlation with cumulative mineralization (CM) and microbial biomass carbon (MBC). Glucose addition had the largest and most significant positive effect on the CPE. Glucose addition positively affected PLFAs and particularly microbial biomass. This study provides valuable insights into the dynamics of soil carbon pools at varying depths following glucose application, advancing the understanding of forest soil carbon sequestration. Full article

In epithelial cells, nonmuscle myosin-2B (NM2B) shows a cortical localization and is tethered to tight junctions (TJs) and adherens junctions (AJs) by the junctional adaptor proteins cingulin and paracingulin. MDCK cells knock-out (KO) for cingulin show decreased apical membrane cortex stiffness and decreased TJ membrane tortuosity, and the rescue of these phenotypes requires the myosin-binding region of cingulin. Here, we investigated whether NM2B contributes to these phenotypes independently of cingulin by generating and characterizing clonal lines of MDCK cells KO for NM2B. The loss of NM2B resulted in decreased stiffness and increased fluidity of the apical cortex and reduced accumulation of E-cadherin and phalloidin-labeled actin filaments at junctions but had no significant effect on TJ membrane tortuosity. Fluorescence recovery after photobleaching (FRAP) showed that the KO of NM2B increased the dynamics of the TJ scaffold protein ZO-1, correlating with decreased ZO-1 accumulation at TJs. Finally, the KO of NM2B increased cell size in cells grown both in 2D and 3D but did not alter lumen morphogenesis of cysts. These results extend our understanding of the functions of NM2B by describing its role in the regulation of the mechanical properties of the apical membrane cortex and cell size and validate our model about the role of cingulin–NM2B interaction in the regulation of ZO-1 dynamics. Full article

This study aimed to investigate the underlying mechanisms by which dandelion extract inhibits the proliferation of breast cancer MDA-MB-231 cells. Dandelion root and leaf extracts were prepared using a heat reflux method and subjected to solvent gradient extraction to obtain fractions with different polarities. MTT assays revealed that the ethyl acetate fraction exhibited the strongest inhibitory effect on cell proliferation. LC-MS analysis identified 12 potential active compounds, including sesquiterpenes such as Isoalantolactone and Artemisinin, which showed significantly lower toxicity toward normal mammary epithelial MCF-10A cells compared to tumor cells (p < 0.01). Mechanistic studies demonstrated that the extract induced apoptosis in a dose-dependent manner, with an apoptosis rate as high as 85.04%, and significantly arrested the cell cycle at the S and G2/M phases. Label-free quantitative proteomics identified 137 differentially expressed proteins (|FC| > 2, p < 0.05). GO enrichment analysis indicated that these proteins were mainly involved in cell cycle regulation and apoptosis. KEGG pathway analysis revealed that the antitumor effects were primarily mediated through the regulation of PI3K-Akt (hsa04151), JAK-STAT (hsa04630), and PPAR (hsa03320) signaling pathways. Moreover, differential proteins such as PI3K, AKT1S1, SIRT6, JAK1, SCD, STAT3, CASP8, STAT2, STAT6, and PAK1 showed strong correlation with the core components of the EA-2 fraction of dandelion. Molecular docking results demonstrated that these active compounds exhibited strong binding affinities with key target proteins such as PI3K and JAK1 (binding energy < −5.0 kcal/mol). This study elucidates the multi-target, multi-pathway synergistic mechanisms by which dandelion extract inhibits breast cancer, providing a theoretical basis for the development of novel antitumor agents. Full article

Alkaline earth elements have emerged as crucial electronic modifiers for regulating active sites in catalytic systems, yet the influence of metal–support interactions (MSIs) between alkaline earth compounds and active metals remains insufficiently understood. This study systematically investigated Pt nanoparticles supported on alkaline earth carbonates (Pt/MCO₃, M = Mg, Ca, Ba) for low-temperature propylene combustion. The Pt/BaCO₃ catalyst exhibited outstanding performance, achieving complete propylene conversion at 192 °C, significantly lower than Pt/MgCO₃ (247 °C) and Pt/CaCO₃ (282 °C). The enhanced activity stemmed from distinct MSI effects among the supports, with Pt/BaCO₃ showing the poorest electron enrichment and lowest propylene adsorption energy. Through kinetic analyses, ¹⁸O₂ isotope labeling, and comprehensive characterization, the reaction was confirmed to follow the Mars–van Krevelen (MvK) mechanism. Pt/BaCO₃ achieves an optimal balance between propylene and oxygen adsorption, a critical factor underlying its superior activity. Full article

Cryptococcus neoformans is an opportunistic fungal pathogen and causative agent of cryptococcosis and cryptococcal meningitis (CM). Cryptococcal disease accounts for up to 19% of AIDS-related mortalities globally, warranting its label as a pathogen of critical priority by the World Health Organization. Standard treatments for CM rely heavily on high doses of antifungal agents for long periods of time, contributing to the growing issue of antifungal resistance. Moreover, mortality rates for CM are still incredibly high (13–78%). Attempts to create new and effective treatments have been slow due to the complex and diverse set of immune-evasive and survival-enhancing virulence factors that C. neoformans employs. To bolster the development of better clinical tools, deeper study into host–Cryptococcus proteomes is needed to identify clinically relevant proteins, pathways, antigens, and beneficial host response mechanisms. Mass spectrometry-based proteomics approaches serve as invaluable tools for investigating these complex questions. Here, we discuss some of the insights into cryptococcal disease and biology learned using proteomics, including target proteins and pathways regulating Cryptococcus virulence factors, metabolism, and host defense responses. By utilizing proteomics to probe deeper into these protein interaction networks, new clinical tools for detecting, diagnosing, and treating C. neoformans can be developed. Full article

In order to recycle plastic waste back to food contact materials (FCMs), it is necessary to identify hazardous substances in plastic packaging that pose a toxicological risk. Printing inks on plastics are not yet designed to withstand the high heat stress of mechanical recycling processes and therefore require hazard identification. In this study, virgin polypropylene (PP) foils were printed with different types of inks (UV-cured, water-based) and colour shades. Thermal analysis of printed foils and pigments was performed using differential scanning calorimetry (DSC). Samples were then thermally treated below and above measured thermal events at 120 °C, 160 °C, 200 °C or 240 °C for 30 min. Subsequently, migration tests and miniaturised Ames tests were performed. Four out of thirteen printed foils and all three pigments showed positive results for mutagenicity in miniaturised Ames tests after thermal treatment at 240 °C. Additionally, pre-incubation Plate Ames tests (according to OECD 471) were performed on three pigments and one printed foil, yielding two positive results after thermal treatment at 240 °C. These results indicate that certain ink components form hazardous decomposition products when heated up to a temperature of 240 °C. However, further research is needed to gain a better understanding of the chemical processes that occur during high thermal treatment. Full article

Zebrafish (Danio rerio) combine accessible behavioral phenotypes with conserved neurochemical pathways and molecular features of vertebrate brain function, positioning them as a powerful model for investigating early neurodegenerative processes and screening neuroprotective strategies. In this context, integrated behavioral and proteomic analyses provide valuable insights into the initial pathophysiological events shared by conditions such as Parkinson’s disease and related disorders—including mitochondrial dysfunction, oxidative stress, and synaptic impairment—which emerge before overt neuronal loss and offer a crucial window to understand disease progression and evaluate therapeutic candidates prior to irreversible damage. To investigate this early window of dysfunction, zebrafish larvae were exposed to 500 μM 1-methyl-4-phenylpyridinium (MPP⁺) from 1 to 5 days post-fertilization and evaluated through integrated behavioral and label-free proteomic analyses. MPP⁺-treated larvae exhibited hypokinesia, characterized by significantly reduced total distance traveled, fewer movement bursts, prolonged immobility, and a near-complete absence of light-evoked responses—mirroring features of early Parkinsonian-like motor dysfunction. Label-free proteomic profiling revealed 40 differentially expressed proteins related to mitochondrial metabolism, redox regulation, proteasomal activity, and synaptic organization. Enrichment analysis indicated broad molecular alterations, including pathways such as mitochondrial translation and vesicle-mediated transport. A focused subset of Parkinsonism-related proteins—such as DJ-1 (PARK7), succinate dehydrogenase (SDHA), and multiple 26S proteasome subunits—exhibited coordinated dysregulation, as visualized through protein–protein interaction mapping. The upregulation of proteasome components and antioxidant proteins suggests an early-stage stress response, while the downregulation of mitochondrial enzymes and synaptic regulators reflects canonical PD-related neurodegeneration. Together, these findings provide a comprehensive functional and molecular characterization of MPP⁺-induced neurotoxicity in zebrafish larvae, supporting its use as a relevant in vivo system to investigate early-stage Parkinson’s disease mechanisms and shared neurodegenerative pathways, as well as for screening candidate therapeutics in a developmentally responsive context. Full article

Translation initiation site (TIS) prediction in mRNA sequences constitutes an essential component of transcriptome annotation, playing a crucial role in deciphering gene expression and regulation mechanisms. Numerous computational methods have been proposed and achieved acceptable prediction accuracy. In our previous work, we developed NeuroTIS, a novel method for TIS prediction based on a hybrid dependency network combined with a deep learning framework that explicitly models label dependencies both within coding sequences (CDSs) and between CDSs and TISs. However, this method has limitations in fully exploiting the primary structural information within mRNA sequences. First, it only captures label dependency within three neighboring codon labels. Second, it neglects the heterogeneity of negative TISs originating from different reading frames, which exhibit distinct coding features in their vicinity. In this paper, under the framework of NeuroTIS, we propose its enhanced version, NeuroTIS+, which allows for more sophisticated codon label dependency modeling via temporal convolution and homogenous feature building through an adaptive grouping strategy. Tests on transcriptome-wide human and mouse datasets demonstrate that the proposed method yields excellent prediction performance, significantly surpassing the existing state-of-the-art methods. Full article

Insect pests inflict significant agricultural and economic losses on crops globally. Chemical control refers to the use of agrochemicals, such as insecticides, herbicides, and fungicides, to manage pests and diseases. Chemical control is still the prioritized method, as insecticides are highly effective and toxic to insect pests. However, it reduces the quality of the environment, threatens human health, and causes serious 3R (reduce, reuse, and recycle) problems. Current advances in the mining of functional symbiotic bacteria resources provide the potential to assuage the use of insecticides while maintaining an acceptably low level of crop damage. Recent research on insect–microbe symbiosis has uncovered a mechanism labeled “detoxifying symbiosis”, where symbiotic microorganisms increase host insect resistance through the metabolism of toxins. In addition, the physiological compensation effect caused by insect resistance affects the ability of the host to regulate the community composition of symbiotic bacteria. This paper reviews the relationship between symbiotic bacteria, insects, and insecticide resistance, focusing on the effects of insecticide resistance on the composition of symbiotic bacteria and the role of symbiotic bacteria in the formation of resistance. The functional symbiotic bacteria resources and their mechanisms of action need to be further explored in the future so as to provide theoretical support for the development of pest control strategies based on microbial regulation. Full article

Alcohol is a prevalent psychoactive substance and a risk factor for developing injuries and non-communicable diseases, representing a significant health and economic burden. Alcohol involves numerous molecular pathways. Its metabolism is regulated by alcohol dehydrogenases and aldehyde dehydrogenases; it also stimulates cholinergic interneurons, increasing the sensitivity of 5-HT3 receptors, while chronic alcohol consumption alters the mesolimbic dopaminergic system involved in reward processing. The treatment of alcohol use disorder (AUD) is essential to manage complex patients, following an evidence-based approach. The aim of this narrative review is to provide a clear and practical summary to support and assist healthcare professionals in the Italian context. Approved pharmacological treatments for AUD include oral naltrexone and acamprosate, sodium oxybate, disulfiram, and nalmefene. Off-label therapies include baclofen, topiramate, gabapentin, pregabalin, ondansetron, and cytisine. A more informed clinical and practical approach that understands the altered neuronal signaling pathways is essential for offering effective, efficient, appropriate, and safe therapeutic algorithms for complex patients with alcohol use disorder. A comprehensive framework should include integrated treatments with a personalized approach. Full article