Search Results (16,291)

Background: Glioblastoma is an aggressive brain tumor that invariably recurs despite treatment, partly due to metabolic adaptations, including altered lipid metabolism. This study investigates plasma lipidomic profiles in patients with glioblastoma to explore their potential as a liquid biopsy for disease monitoring. Methods: Plasma samples were collected from 36 patients with histopathologically confirmed IDH wild-type glioblastoma at four treatment stages: pre-surgery (n = 36), post-surgery (n = 32), pre-radiation (n = 28), and post-radiation (n = 17). Untargeted lipidomics analysis was performed using liquid chromatography-high resolution mass spectrometry (LC-HR-MS/MS). Results: Plasma lipidomic signatures differed significantly across treatment stages. Specifically, the lipidomic profile prior to surgery was statistically distinct from those at subsequent stages, demonstrating an increased compound abundance of numerous lipids that are decreased at subsequent stages, including linoleic acid (fold-change 2.58, p = 4.21 × 10⁻¹¹), behenic acid (fold-change 2.09, p = 9.3 × 10⁻¹⁰), and linolenic acid (fold-change 4.44, p = 5.83 × 10⁻⁶). Random forest modeling could predict pre-surgical samples with 85.7% accuracy. Conclusions: Plasma lipidomics shows promise as a potential liquid biopsy approach for monitoring glioblastoma treatment but future studies will need to examine these findings in larger and well-controlled cohorts. Full article

Few experimental studies have analyzed the wave energy conversion performance and underlying mechanisms of wave-driven profilers in controlled environments. Therefore, building on linear wave theory, Newton–Euler equations, and the working mechanisms of wave-driven profilers, this study has designed a crank mechanism-driven experimental tank facility. A comprehensive dynamic model of a wave-driven profiler has been established, and the impacts of wave height, wave period, and net buoyancy on the wave energy conversion performance of the wave-driven profiler and their underlying mechanisms have been analyzed. The results show that increased wave height enhances the buoy’s heave velocity, improving the dynamic performance of the wave-driven profiler by 441%. However, increased hydrodynamic resistance and mechanical collisions decreased the wave energy conversion efficiency by 57%. Longer wave periods reduce the wave excitation frequency, decreasing the buoy’s heave velocity; this results in a 35% reduction in the dynamic performance of the wave-driven profiler and a 53% decrease in wave energy conversion efficiency. During the descent phase, increased net buoyancy offsets more propulsive force, causing a 26% decrease in the wave-driven profiler’s dynamic performance yet increasing its energy conversion efficiency by 136%. This study provides a theoretical basis for optimizing the performance of similar wave-driven profilers. Full article

One of the tasks of the FutureWings project, funded by the European Commission within the 7th framework, was to numerically validate the mechanical behavior of a wing whose deflections had to be controlled via a suitable distribution of piezoelectric patches. Starting from a reference geometry (a NACA 0012 airfoil), wing profiles were implemented and analyzed using the fluid–structure interaction analysis technique. The wing section was designed with a morphing profile in which both the front and rear parts self-deform via piezoelectric patches that serve actuators glued to the skin of the profile. A Macro Fiber Composite (MFC) was used as the piezoelectric actuator. Aeroelastic analyses were performed at low Mach numbers under the sea-level flight condition. Analysis of the technical solution was based on an examination of the aerodynamic coefficients and polar curves of the profile, as the control voltage of the patches can vary. The results were compared with those available in the literature. As a preliminary step, this work contributes to examining the current technical possibilities of this technology relating to the application of piezoelectric patches as actuators in the field of aerostructures. Full article

Real-world navigation depends on coordinated head–eye behaviour that standard tests of visual function miss. We investigated how visual impairment affects traffic navigation, whether behaviour differs by visual impairment type, and whether this functional grouping better explains performance than WHO categorisation. Using a virtual reality (VR) headset with integrated head and eye tracking, we evaluated detection of moving cars and safe road-crossing opportunities in 40 patients with central, peripheral, or combined visual impairment and 19 controls. Only two patients with a combination of very low visual acuity and severely constricted visual fields failed both visual tasks. Overall, patients identified safe-crossing intervals 1.3–1.5 s later than controls (p ≤ 0.01). Head-eye movement profiles diverged by visual impairment: patients with central impairment showed shorter, more frequent saccades (p < 0.05); patients with peripheral impairment showed exploratory behaviour similar to controls; while patients with combined impairment executed fewer microsaccades (p < 0.05), reduced total macrosaccade amplitude (p < 0.05), and fewer head turns (p < 0.05). Classification by impairment type explained behaviour better than WHO categorisation. These findings challenge acuity/field-based classifications and support integrating functional metrics into risk stratification and targeted rehabilitation, with VR providing a safe, scalable assessment tool. Full article

Functioning as a critical ecotone between terrestrial and aquatic ecosystems, riparian zones exhibit soil enzyme activities that serve as key biomarkers of their nutrient cycling processes. However, despite considerable focus on riparian soil properties, the dynamics and underlying drivers of these enzymatic activities are not yet fully characterized. To this end, soils were systematically sampled across varying widths and depths from three representative riparian zones to quantify the driving forces of physicochemical properties on enzyme activity dynamics. The results showed that the soil enzyme activity was highest in the forest riparian zone and lowest in the farmland riparian zone, with average enzyme activities of 37.95 (μmol·g⁻¹·h⁻¹) and 26.85 (μmol·g⁻¹·h⁻¹), respectively. The width of the riparian zone changes the spatial distribution of soil enzyme activity. The soil enzyme activity is higher in the land edge area far from the river (profile-1) and lower in the water edge area near the river (profile-4), with average enzyme activities of 47.4384 (μmol·g⁻¹·h⁻¹) and 17.0017 (μmol·g⁻¹·h⁻¹), respectively. Moreover, soil water content (SWC) has a strong impact on enzyme activity changes. The increase in soil depth reduces soil enzyme activity, with enzyme activity in the 0–20 cm soil layer being 1.5 times higher than in the 20–50 cm soil layer. Meanwhile, the primary factors influencing changes in soil enzyme activity have gradually shifted from total nitrogen (TN), nitrate nitrogen (NO₃-N), and soil organic carbon (SOC) to the sole control of SOC. Research has shown that human influence strongly interferes with soil enzyme activity in riparian zones. The width of the riparian zone and soil depth serve as key drivers of the spatial distribution of soil enzyme activity by modulating soil environmental factors. The patterns revealed in this study indicate that maintaining appropriate riparian zone width and reducing anthropogenic disturbances can enhance nutrient cycling dynamics at the micro-scale by increasing soil enzyme activity. This process is crucial for strengthening the riparian zone’s macro-level ecosystem services, particularly by effectively enhancing its capacity to sequester and transform nutrients like nitrogen and phosphorus from agricultural nonpoint sources, thereby safeguarding downstream water quality. Consequently, soil enzyme activity serves as a key indicator, providing essential scientific basis for assessing riparian health and guiding ecological restoration efforts. Full article

Background/Objectives: CDH1 gene is widely studied, as pathogenic variants are involved in diffuse gastric cancers and lobular breast cancers. CDH1 genotype contributes to the management of clinical practice recommendations for cancer prevention. We proposed a qualitative and quantitative description of CDH1 alternative splicing profile on lymphoblastoid cell lines (LCLs). The aim of this description was to allow a comprehensive interpretation of the effect of variants of uncertain significance (VUS) on CDH1 splicing. Methods: We studied, using RNAseq, the splicing profile of 22 LCLs (untreated and treated with puromycin) with no pathogenic variant on CDH1 and evaluated the effect on CDH1 splicing of four VUS. Results: We highlighted a total of eleven alternative splicing events including four junctions starting from intron 2, defining novel isoforms of CDH1. We also identified an isoform causing the skip of exon 11 and leading to a disruption of the reading frame with high levels of expression on negative CDH1 control LCLs, confirmed by ddPCR. Splicing RNAseq results for CDH1 VUS: c.1008+1G>A and c.1936+5G>A showed complex splicing patterns but allowed their classification as pathogenic. We studied CDH1 VUS exon 4 to exon 11 duplication with RNA analysis combined with Bionano optical genome mapping. Depending on alternative splicing of proximal and distal exons 11 within the duplication, we identified four distinct transcripts, leading to truncated proteins, classifying the duplication as pathogenic. Conclusions:CDH1 has a complex alternative splicing profile characterized by a dynamic splicing of intron 2 making CDH1 a good candidate for a study using long-read RNAseq. Full article

Currently, safe alternatives with very low toxicity and good antimicrobial activity are being sought to replace chemical compounds that can be harmful to animal and human health. For this reason, this study evaluated the safety and biofunctional microbiocidal potential of an extract composed of thymol and eucalyptol. Toxicity tests showed low toxicity in both chickens (2000 mg/kg bw) and Artemia salina (EC₅₀ = 2003 mg/L) and Daphnia magna (EC₅₀ = 87 mg/L), indicating a safe usage profile. Oxidative stress biomarkers (nitrite and MDA) and antioxidant enzymes (SOD and catalase) improved in treated chickens at 20 days of age. The hematological and biochemical parameters of the treated birds showed normal values similar to those of the control group chickens, with better protein levels and lower AST levels. Histology of the kidney, intestine, and liver showed no changes in any group, confirming the absence of systemic adverse effects. At the molecular level, an improvement in the expression of tight junction proteins (claudin and occludin) was observed, suggesting a strengthening of the intestinal barrier integrity. Finally, the extract demonstrated an antimicrobial effect (E. coli, C. perfringens, Salmonella sp. and Pseudomonas sp.) comparable to that of organic acids commonly used as food preservatives, positioning it as a promising alternative in applications. Full article

B-cell acute lymphoblastic leukemia (B-ALL) is characterized by the abnormal proliferation of B-lineage lymphocytes in the bone marrow (BM). The roles of immune cells within the BM microenvironment remain incompletely understood. Single-cell RNA sequencing (scRNA-seq) provides the potential for groundbreaking insights into the pathogenesis of B-ALL. In this study, scRNA-seq was conducted on BM samples from 17 B-ALL patients (B-ALL cohorts) and 13 healthy controls (HCs). Bioinformatics analyses, including clustering, differential expression, pathway analysis, and gene set variation analysis, systematically identified immune cell types and assessed T-cell prognostic and metabolic heterogeneity. A metabolic-feature-based machine learning model was developed for B-ALL subtyping. Furthermore, T-cell–monocyte interactions, transcription factor (TF) activity, and drug enrichment analyses were performed to identify therapeutic targets. The results indicated significant increases in Pro-B cells, alongside decreases in B cells, NK cells, monocytes, and plasmacytoid dendritic cells (pDCs) among B-ALL patients, suggesting immune dysfunction. Clinical prognosis correlated significantly with the distribution of T-cell subsets. Metabolic heterogeneity categorized patients into four distinct groups (A–D), all exhibiting enhanced major histocompatibility class I (MHC-I)-mediated intercellular communication. The metabolic-based machine learning model achieved precise classification of B-ALL groups. Analysis of TF activity underscored the critical roles of MYC, STAT3, and TCF7 within the B-ALL immunometabolic network. Drug targeting studies revealed that dorlimomab aritox and palbociclib specifically target dysregulation in ribosomal and CDK4/6 pathways, offering novel therapeutic avenues. This study elucidates immunometabolic dysregulation in B-ALL, characterized by altered cellular composition, metabolic disturbances, and abnormal cellular interactions. Key TFs were identified, and targeted drug profiles were established, demonstrating the significant clinical potential of integrating immunological mechanisms with metabolic regulation for the treatment of B-ALL. Full article

Background: Peri-implantitis is an inflammatory condition caused by bacterial plaque and several factors like diabetes, smoking, titanium bio-tribocorrosion, implant–abutment micromovements, occlusal overload, cement remnants, and poor oral hygiene, resulting in bone resorption. The aim of this review was to evaluate the relationship between titanium metal particles and the development of peri-implantitis, specifically the characterisation of the inflammatory response regarding cytokine profile, immune cell infiltration, and transcription factors up-regulated in the peri-implant sites. Methods: A systematic review was conducted following the PRISMA guidelines, from January 2004 to January 2025, in three databases: PubMed, Web of Science, and Wiley Library. The inclusion criteria included in vivo human studies and in vitro studies with a focus on bio-tribocorrosion of titanium particles in peri-implant tissues, and their immunological and cellular implications. Quality assessment of in vivo transversal and case–control studies used Joanna Briggs Institute Critical Appraisal Tools, and, for in vitro studies, the modified CONSORT checklist. Results: A total of 27 studies were included, 20 in vitro and 7 in vivo. Titanium particles induced the secretion of IL-1β, IL-6, and TNF-α by peri-implant cells, activation of the NLRP3 inflammasome, and RANKL/OPG bone resorption, further stimulating an exacerbated inflammatory response, LPS independent. There was a significant increase in IL-33, an alarmin, possibly associated with implant–pillar micromovements. IL-8 production by gingival stromal cells and fibroblasts, and downregulation of CCR7 can explain an altered leukocyte migration and the mixture of M1/M2 macrophage populations in peri-implantitis. Conclusions: Titanium particle bio-tribocorrosion stimulates a chronic inflammatory response impacting immune cell composition and cytokine secretion in peri-implant tissue, leading, ultimately, to osteolysis. Modulation of the immune response may contribute to the development of therapeutic strategies and the prevention of implant failure. Full article

Kombucha is a functional beverage with growing popularity due to its health-promoting properties. This study aimed to evaluate the impact of herbal infusions on the quality of green tea-based kombucha. Four variants were prepared: a control (K1) and three experimental samples combining 70% green tea with 30% (v/v) Mentha spicata (K2), Hibiscus sabdariffa (K3), or Clitoria ternatea (K4). Fermentation lasted four days at 24 ± 1 °C. Physicochemical parameters, polyphenol profile (HPLC), microbiological safety, and sensory quality were assessed using QDA and electronic tongue analysis. K3 showed the highest polyphenol content (291 mg/L), especially catechins. K4 achieved the highest overall sensory quality due to its fruity aroma, balanced sweet-sour taste, and favorable microbiological profile. K2 had the lowest caffeine content (114 mg/L) and a distinct minty flavor. All samples were microbiologically safe. Herbal additives influenced fermentative microbiota: K3 had fewer acetic acid bacteria, while K4 had the highest lactic acid bacteria count. Electronic tongue analysis confirmed sensory panel results and revealed distinct taste profiles among the variants. Herbal infusions significantly enhance the nutritional and sensory properties of kombucha. Their use offers a promising strategy for developing functional beverages with tailored characteristics. Full article

Didelphis aurita is a widely distributed neotropical marsupial frequently found in peri-urban environments and known to harbor various pathogens, including hemoparasites of the genus Hepatozoon. However, the systemic physiological responses of naturally infected individuals remain poorly understood. This study aimed to characterize the serum proteomic profile of Didelphis aurita naturally infected with Hepatozoon sp., providing insights into host–parasite interactions and potential biomarkers of infection. Serum samples were analyzed using liquid chromatography–tandem mass spectrometry (LC-MS/MS), followed by functional annotation based on Gene Ontology and KEGG pathway enrichment. A total of 67 proteins were identified, 33 of which were exclusive to infected animals. The most abundant proteins included albumin, hemoglobin subunits, and venom metalloproteinase inhibitors (DM43 and DM64). Functional enrichment revealed significant involvement in complement and coagulation cascades, protease inhibition, antioxidant defense, and extracellular vesicle localization. Key proteins such as fibrinogen, plasminogen, antithrombin, SERPIN family members, vitronectin, and fibronectin suggest an integrated host response involving hemostasis, inflammation control, and tissue remodeling. This is the first report of the serum proteome of Didelphis aurita naturally infected with Hepatozoon sp. Despite the absence of protein validation, the findings provide novel insights into marsupial immunophysiology and offer a foundation for future biomarker research and ecoimmunological surveillance in synanthropic species. Full article

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults. This review explains the connections between the genesis and progression of GBM and particular cellular tumorigenic mechanisms, such as angiogenesis, invasion, migration, growth factor overexpression, genetic instability, and apoptotic disorders, as well as possible therapeutic targets that help predict the course of the disease. Glioblastoma multiforme (GBM) diagnosis relies heavily on histopathological features, molecular markers, extracellular vesicles, neuroimaging, and biofluid-based glial tumor identification. In order to improve miRNA stability and stop the proliferation of cancer cells, nanoparticles, magnetic nanoparticles, contrast agents, gold nanoparticles, and nanoprobes are being created for use in cancer treatments, neuroimaging, and biopsy. Targeted nanoparticles can boost the strength of an MRI signal by about 28–50% when compared to healthy tissue or controls in a preclinical model like mouse lymph node metastasis. Combining the investigation of CNAs and noncoding RNAs with deep learning-driven global profiling of genes, proteins, RNAs, miRNAs, and metabolites presents exciting opportunities for creating new diagnostic markers for malignancies of the central nervous system. Artificial intelligence (AI) advances precision medicine and cancer treatment by enabling the real-time analysis of complex biological and clinical data through wearable sensors and nanosensors; optimizing drug dosages, nanomaterial design, and treatment plans; and accelerating the development of nanomedicine through high-throughput testing and predictive modeling. Full article

Background: Degenerative, metabolic and oncologic diseases are scarcely amenable to the complete reconstruction of tissue structure and functionalities using common therapeutic modalities. On the nanoscale, extracellular vesicles (EVs) and nanoparticles (NPs) have emerged as attractive candidates in regenerative and personalised medicine. However, EV transfection is hindered by its heterogeneity and low yield, while NPs suffer from cytotoxicity, immunogenicity, and long-term safety issues. Scope of Review: This review synthesises data from over 180 studies as part of a narrative synthesis, critically evaluating the disease-specific utility, mechanistic insights, and translational obstacles. The focus is laid on comparative cytotoxicity profiles, the capacities of hybrid EV–NP systems to circumvent mutual shortcomings, and the increasing impact of artificial intelligence (AI) on predictive modelling, as well as toxicity appraisal and manufacturing. Key Insights: EVs have inherent biocompatibility, immune evasive and organotropic signalling functions; NPs present structural flexibility, adjustable physicochemical properties, and industrial scalability. Common molecular pathways for NP toxicity, such as ROS production, MAPK and JAK/STAT activation, autophagy, and apoptosis, are significant biomarkers for regulatory platforms. Nanotechnological and biomimetic nanocarriers incorporate biological tropism with engineering control to enhance therapeutic efficacy, as well as their translational potential. AI approaches can support rational drug design, promote reproducibility across laboratories, and meet safe-by-design requirements. Conclusions: The intersection of EVs, NPs and AI signifies a turning point in regenerative nanomedicine. To advance this field, there is a need for convergence on experimental protocols, the adoption of mechanistic biomarkers, and regulatory alignment to ensure reproducibility and clinical competence. If realised, these endeavours will not only transition nanoscale medicament design from experimental constructs into reliable and patient-specific tools for clinical trials, but we also have the strong expectation that they could revolutionise future treatments of challenging human disorders. Full article

Breast milk is a major source of probiotics, particularly lactic acid bacteria (LAB), which are known to regulate the intestinal microbial community and exert antibacterial effects. However, little is known about the preventive effects of feline milk-derived LAB against Salmonella infection in vivo. In this study, a strain of Pediococcus acidilactici (M22) was isolated from feline milk and evaluated for its protective potential in C57BL/6 mice challenged with Salmonella Typhimurium SL1344 (VNP20009). Following oral administration of M22, mice were infected with S. Typhimurium, and protective efficacy was assessed through body weight changes, bacterial loads in tissues, histopathological examination of the colon, oxidative stress markers, cytokine profiles, and 16S rRNA gene sequencing of cecal microbiota. The results showed that pretreatment with M22 significantly reduced bacterial loads in the liver, spleen, and cecum compared with controls. M22 administration enhanced antioxidant capacity, alleviated infection-induced inflammation, and preserved intestinal barrier integrity by restoring villus morphology and upregulating tight junction proteins (ZO-1 and occludin). Microbiota analysis further revealed that M22 enriched short-chain fatty acid-producing beneficial taxa (e.g., lactic acid bacteria) while suppressing pro-inflammatory genera. Collectively, these findings provide scientific evidence that feline milk-derived P. acidilactici M22 is a safe and effective probiotic candidate. By enhancing gut health and host resistance to infection, M22 offers a promising strategy to improve companion animal health, reduce reliance on antibiotics, and mitigate zoonotic transmission of pathogens. Full article

Background: Recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF) are significant challenges in reproductive medicine. For both, embryonic aneuploidy is the leading etiological factor. Preimplantation genetic testing for aneuploidy (PGT-A) via trophectoderm biopsy is the current standard for embryo selection. However, it is limited by its invasiveness, potential for embryo damage, and diagnostic errors due to mosaicism. Rationale/Objectives: This review critically evaluates the emerging role of noninvasive PGT (niPGT). NiPGT analyzes cell-free DNA from spent blastocyst culture media, thus, it is a potential alternative for managing RPL and RIF. Hence, the primary objective is to determine whether current evidence supports niPGT as a reliable replacement for conventional biopsy-based PGT-A in these high-risk populations. Outcomes: The analysis reveals that niPGT offers significant theoretical advantages. These include complete non-invasiveness, enhanced embryo preservation, and high patient acceptability. However, its clinical application is hampered by substantial limitations. Key amongst them is the inconsistent and often suboptimal diagnostic accuracy (sensitivity 70–85%, specificity 88–92%) compared to biopsy. Other significant factors include the high rates of amplification failure (10–50%), vulnerability to maternal DNA contamination, as well as low DNA yield. Crucially, there is a definitive lack of robust, prospective randomized controlled trial (RCT) data demonstrating improved live birth rates or reduced miscarriage rates specifically in RPL and RIF cohorts. As such, niPGT is not yet ready to be a standalone clinical adoption in RPL and RIF cases. However, it may serve as a valuable adjunct for rescue scenarios following biopsy failure or for ethical reasons. Wider Implications: The integration of niPGT with artificial intelligence, time-lapse imaging, and multi-omics profiling underlies a promising future. However, its transition from a predominantly research tool to a clinical standard necessitates various critical undertakings. These include rigorous multicenter RCTs, standardizing international protocol, and tailoring validation for the RPL and RIF subgroups. This review highlights the need for cautious optimism, positing that evidence-based integration, rather than premature adoption, is essential to realizing niPGT’s full potential without compromising patient care in these complex fertility scenarios. Full article