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Hilab volt system for electrolyte measurement: a portable solution for point-of-care testing
Ammonium sulfate provides an efficient method for isolating small extracellular vesicles from human biofluids
Abstract Small extracellular vesicles (EVs) are nanosized vesicles (< 200 nm) secreted from various tissues, including the central nervous system (CNS), into diverse biofluids. Due to their ability to carry molecular cargo that reflects the physiological state of their parental cells, small EVs represent promising diagnostic carriers for neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). While biofluid-derived small EVs offer a “liquid biopsy” solution, their clinical translation is severely hindered by the limitations of conventional isolation methods, which are often time-consuming, costly, or yield low purity. Building upon the “ExoPRISM” (Exosome Precipitation by Ionic Strength Modulation) framework, we developed and validated an optimized, cost-effective ammonium sulfate (AS)-based pipeline for small EVs isolation. We have refined and established the optimal AS ratio specifically for plasma and further demonstrated its feasibility for isolating small EVs from saliva. Subsequently, we introduced a targeted purification step using glutamate aspartate transporter (GLAST) antibodies to specifically isolate central nervous system (CNS)-derived EVs. This step robustly demonstrated that our AS-based approach preserves small EVs integrity and enables the effective isolation of Astrocyte-Derived Extracellular Vesicles (ADEVs) for downstream applications. Finally, the practical utility of this optimized protocol was validated in a clinical cohort. Our findings highlight the robustness, high efficiency, and significant translational potential of this AS-based method for the early and accurate diagnosis of neurodegenerative diseases. We optimized the AS concentration for small EVs precipitation, ultimately identifying 2.66 M as the optimal working concentration. This method demonstrated remarkable time efficiency, completing the entire isolation process in approximately 90 min. Furthermore, it only requires centrifugation at 12,000 xg, significantly enhancing its practicality in clinical diagnostic scenarios. To expand its potential application scope, we also tested the method’s efficacy on other bodily fluids and found that the concentration of 2.66 M was equally effective in isolating small EVs from saliva. Comparative analyzes against the commercially available ExoQuick kit demonstrated that our AS-based precipitation method achieved comparable efficacy in isolating small EVs from the plasma of AD patients and in purifying ADEVs. Furthermore, comprehensive validation using nanoparticle tracking analysis (NTA), electron microscopy, and detection of canonical small EVs markers (CD63, CD9) confirmed the functional equivalence of the two isolation methods. The cumulative evidence from this study firmly establishes the AS-based small EVs isolation protocol as a viable and robust efficacy comparable to commercially available kits. This method confers three distinct advantages: enhanced temporal efficiency, reduced cost burden, and minimal interference with downstream assays, rendering it highly amenable to clinical implementation. Notably, it enables the effective isolation of small EVs from plasma, a conventional biofluid widely utilized in clinical diagnostics, as well as from saliva. These attributes underscore the method’s potential in advancing the early detection of neurodegenerative disorders. Looking ahead, the versatility of this approach suggests its applicability across a diverse array of biological specimens, thereby facilitating the expansion of small EVs-based diagnostic research and clinical practice.
MOF-inspired porphyrinic single sites as promising platforms for stable immobilization of 2-thiouracil: a DFT study
Dynamic task offloading for sports training monitoring in MEC-assisted smart wearable device systems
Deep learning algorithm for automatic detection of acute ischemic stroke on noncontrast brain CT
Determinants of protein corona adsorption and abundance revealed by interpretable machine learning across nanoparticle systems
Abstract Nanoparticles (NPs) hold significant potential in biotechnology, including molecular sensing, controlled release systems, and therapeutic applications. However, their behavior in biological environments remains difficult to predict because proteins rapidly absorb onto NP surfaces, forming a protein corona (PC) that reshapes their surface properties and determines their biological identity, transport, and cellular interactions. In this study, we developed large-scale deep neural network (DNN) models to predict both protein adsorption (binary classification) and relative protein abundance (regression) on NP surfaces. We utilized a well-curated and comprehensive PC dataset comprising data from 83 peer-reviewed studies, 817 NP–PC samples, and 2,497 proteins, substantially expanding the scale and diversity compared with prior studies. Then, we employed a prevalence-based filtering strategy to mitigate sparsity and batch noise and trained over 200 machine learning models across proteins. The adsorption classification models achieved high discriminative performance (AUC = 0.96), while the abundance models achieved a pooled R² of 0.67 and an average per-protein R 2 of 0.40 on the test set. SHapley Additive exPlanations (SHAP) revealed that adsorption was predominantly governed by NP material class and surface chemistry, whereas abundance was more strongly influenced by experimental handling and kinetic parameters, particularly isolation and incubation time. Incorporation of applicability domain (AD) analysis enabled identification of reliable prediction regions, with in-AD predictions demonstrating higher confidence and reduced error for both tasks. Together, these results demonstrate that our DNN models can identify predictive drivers of PC composition and reveal feature associations consistent with patterns reported in prior mechanistic literature, offering a data-driven reference to inform nanomaterial design for biomedical and environmental applications.
Anti-Candida albicans effect of the new antifungal compound Venetin-1 obtained from earthworms versus amphotericin B
Abstract Candida albicans is a commensal organism that can cause disease in individuals with weakened and compromised immune systems. These fungi are responsible for superficial or invasive infections associated with high mortality. The aim of this study was to compare the activity of the new antifungal compound Venetin-1, obtained from the coelomic fluid of the earthworm Dendrobaena veneta , with the effects of the antibiotic amphotericin B (AmB). Flow cytometry, fluorescence microscopy, scanning electron microscopy, atomic force microscopy, and FTIR spectroscopic methods were used for comparative analysis. Venetin-1 at the highest concentration used (100 µg mL − 1 ) caused a decrease in the OD of C. albicans cultures by more than 60% compared to the control group, and AmB (0.5 µg mL − 1 ) by 80%. Venetin-1 at the highest concentration reduced the viability of fungal cells by 42%, while AmB reduced it by 30%. The present study shows that both Venetin-1 and AmB induced fungal cell necrosis and apoptosis. SEM analysis showed that both compounds caused morphological changes in cells, including the presence of multiple bundles at the cell poles and the formation of unseparated cell chains. Congo red fluorochrome analysis showed that both compounds caused an increase in the fluorescence intensity of the β-glucan layer in the wall. Flow cytometric analysis of the cell wall showed that Venetin-1 caused exposure of the β-glucan and chitin layers in the fungal cells. FTIR analysis confirmed molecular remodelling of the cell wall structure after exposure to both compounds. AFM analysis indicated an increase in the elasticity of the fungal cell wall after treatment with both compounds. Proteomic analysis showed that amphotericin B and Venetin-1 induced distinct proteomic response patterns in C. albicans cells. AmB caused concentration-restricted response detectable at sublethal conditions, whereas Venetin-1 induced a concentration-dependent and progressively expanding proteomic remodelling. The comparison of Venetin-1 and AmB revealed pronounced differences in their electrokinetic behaviour, originating from their distinct chemical structures and modes of interaction with electrolyte ions. Venetin-1 exhibited significantly more negative zeta potential values, particularly in alkaline media and in the presence of Cl⁻ ions, indicating stronger electrostatic stabilisation and higher electrokinetic stability than AmB. Considering its effect on Candida cells and the fact that the Venetin-1 complex has no toxic effect, this compound is a promising candidate for further biomedical research on new antifungal preparations.
Loneliness as a mediator between family separation and life satisfaction among Ukrainian refugee women in Germany
Abstract The Russian invasion of Ukraine has led to one of the largest population displacements in Europe since World War II. Different from other recent refugee flows, Ukrainian refugees are predominantly women, often separated from partners who remained behind. Using data from the “IAB-BiB/FReDA-BAMF-SOEP Survey on Refugees from Ukraine in Germany,” this cross-sectional study examines how separation-related loneliness and integration barriers are associated with life satisfaction among displaced women who arrived in Germany in 2022. Structural equation modeling showed that the association between forced family separation and life satisfaction operated entirely through indirect pathways involving loneliness and integration barriers. Loneliness accounted for the largest share of this indirect association and acted as a key intermediary, being linked to both lower life satisfaction and greater integration challenges, including economic and health concerns and reduced social integration. These results suggest that loneliness may be an important emotional pathway connecting separation to broader integration difficulties and lower well-being, particularly in the early stage of resettlement. Timely measures to address loneliness could help support integration and improve well-being of refugee women affected by separation.
Predictors and outcomes of hepatic decompensation following transarterial locoregional therapy in hepatocellular carcinoma
Genetic landscape of hereditary spastic paraplegias in the Korean population
Abstract Hereditary spastic paraplegia (HSP) is a genetically neurodegenerative disorder with limited epidemiological data in Korea. This study aimed to characterize the genetic landscape of HSP in a large Korean cohort. We analyzed 657 patients with suspected HSP using Sanger sequencing and a targeted next-generation sequencing (NGS) panel covering 54 HSP-related genes. Variants were classified according to American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines, and copy number variations (CNVs) were detected using in-house methods and multiplex ligation-dependent probe amplification. Pathogenic or likely pathogenic variants were identified in 121 patients (18%), with SPAST (83%) and ATL1 (6%) being the most frequently mutated genes. Notably, 5% of SPAST mutations were CNVs, underscoring the importance of CNV detection. Among the identified variants, 23 novel mutations were discovered, primarily in SPAST (19), REEP1 (3), and SACS (1), expanding the mutational spectrum of HSP. The diagnostic yield was higher with NGS (25%) compared to Sanger sequencing (16%), reflecting the panel’s broader gene coverage. This study highlights the predominance of SPAST and ATL1 mutations in Korean HSP patients and emphasizes the utility of targeted NGS panels, particularly for detecting CNVs and novel variants. Despite these advances, the majority of cases remain unresolved, suggesting the need for broader sequencing approaches to uncover additional genetic factors. These findings provide a foundation for improved diagnostic strategies and personalized treatment in HSP.
Knowledge enhanced framework for managing electricity generation and consumption in micro smart grids using Heronian mean MCDM approach
Experimental evaluation of femoral vein grafts and platelet-rich fibrin for reducing epidural fibrosis in a rat laminectomy model
Abstract Epidural fibrosis (EF) refers to the non-physiological scar formation at the site where a surgical incision is made to access the spinal canal. This condition often results in functional disability and pain following spinal surgery and is a common and difficult-to-treat contributor to Failed Back Surgery Syndrome (FBSS). This study aimed to investigate the effectiveness of platelet-rich fibrin (PRF) clots, vein grafts, or a combination of both in reducing epidural fibrosis after laminectomy in rats. One hundred adult Sprague–Dawley male rats, weighing 300 ± 55 g, were equally and randomly assigned into five groups (n = 20): the control, laminectomy, PRF, vein graft, and PRF/vein graft groups. The control group consisted of normal, untouched rats that did not undergo anesthesia, surgical exposure, laminectomy, or sham operation. Lumbar laminectomy was performed at L3–L5 in the laminectomy, PRF, vein graft, and PRF/vein graft groups. On postoperative day 30, outcomes were assessed in two predefined independent subsets within each group. Ten rats per group were used for macroscopic epidural adhesion scoring after surgical-site reopening, whereas the remaining ten rats per group were used for histopathological, morphometric, and qRT-PCR analyses of IL-6 and TGF-β1 expression. Therefore, the effective analytical sample size was n = 10 animals per group for each endpoint category, not n = 20 per group. The primary endpoint was histological epidural fibrosis score at day 30; all other macroscopic, morphometric, inflammatory, and molecular outcomes were secondary endpoints. The EF area was significantly reduced in all treatment groups compared with the laminectomy group. Overall, the vein graft-containing groups showed the strongest reductions in adhesion, scar density, dura mater thickness, and IL-6/TGF-β1 expression. The combined PRF/vein graft treatment was generally more favorable than PRF alone but was often comparable to vein graft alone, indicating that a consistent superiority of the combined approach over vein graft alone was not demonstrated. Vein graft-containing treatments reduced histological and molecular markers of epidural fibrosis in this rat laminectomy model. The combined PRF/vein graft approach showed favorable anti-inflammatory and anti-fibrotic effects, but it was not consistently superior to the vein graft alone across all assessed endpoints. Therefore, the findings should be interpreted as preliminary preclinical evidence supporting further investigation of vein graft-based local barrier strategies rather than direct evidence of a superior combination therapy or a clinically ready approach.
Enhancing multimodal inpatient fall prediction via nursing statement integration within the OMOP common data model
Multifunctional poly(citric acid)-based ionic liquid polymer composite for scale control and emulsion stabilization: structural and interfacial mechanistic evaluation
Joint UAV trajectory and offloading optimization with robust secrecy for intelligent mining
Development and validation of a sensor-integrated smart driving test system for automated, scalable, and objective driver performance evaluation
Resistance of E2F4DN to p38MAPK phosphorylation reduces genotoxic cell death in N2a neuron-like cells
Abstract E2F4 is a transcription factor involved in cellular homeostasis and a substrate of the stress-activated kinase p38 MAPK , which phosphorylates a conserved Thr248/Thr250 motif. A non-phosphorylatable mutant, E2F4DN (Thr248Ala/Thr250Ala), has demonstrated preclinical efficacy in a murine model of Alzheimer’s disease (AD), but its mechanism of action remains unknown. We hypothesized that cell stress-induced phosphorylation disrupts E2F4’s homeostatic function, whereas exogenous E2F4DN restores it. To begin testing this hypothesis, we treated differentiated N2a neuroblastoma cells (N2a neuron-like cells) with camptothecin (CPT) to induce genotoxic stress. CPT activated p38 MAPK within 8 h, leading to phosphorylation of E2F4 at Thr248/Thr250. We then overexpressed E2F4DN or a phosphomimetic variant, E2F4CA (Thr248Glu/Thr250Glu), and assessed apoptosis via procaspase-3 cleavage. The pro-apoptotic factor E2F1 strongly induced caspase-3 activation in this model system. This effect was partially mimicked by E2F4CA, while E2F4DN markedly suppressed it. Notably, E2F4DN, but not E2F4CA, upregulated the antiapoptotic factor Cited2, and knockdown experiments suggest it may contribute to E2F4DN’s protective effect. Overall, these findings indicate that E2F4DN counteracts p38 MAPK -driven neuronal apoptosis and helps preserve neuronal homeostasis, at least in part, through Cited2 upregulation. This provides mechanistic insight into the neuroprotective role of E2F4DN as a potential therapy for AD.
A lightweight deep learning model with channel attention for kidney cell classification from microscopy images
Phytosphingosine disrupts dual-species oral biofilms and attenuates LPS-induced pro-inflammatory responses in human gingival fibroblasts
Abstract Oral biofilms are major etiological factors in dental caries and periodontitis and are often resistant to conventional anti-microbial therapies, particularly in mixed-species communities. Phytosphingosine (PHS), a naturally occurring bioactive sphingolipid, has demonstrated anti-microbial activity against several pathogens; however, its effects on mixed-species oral biofilms and inflammatory responses remain unclear. This study investigated the in vitro anti-microbial, anti-biofilm, and immunomodulatory activities of PHS against Streptococcus mutans and Aggregatibacter actinomycetemcomitans in single- and dual-species biofilms. Confocal laser scanning microscopy revealed a significant reduction in biofilm matrix formation in both single- and dual-species biofilms treated with PHS compared with untreated controls ( P < 0.001). Cytotoxicity analysis demonstrated that cell viability remained above 90% following exposure to 5 µg/ml PHS for 24 h. Furthermore, PHS pretreatment significantly attenuated LPS-induced IL-6 and TNF-α production ( P < 0.001). Collectively, these findings suggest that PHS is a promising dual-function agent with anti-microbial and anti-inflammatory properties and may have potential as an adjunctive therapeutic strategy for biofilm-associated oral diseases.