Search Results (1,865)

Croatian agricultural legislation acknowledges the significance of radionuclides as pollutants in agricultural lands; however, it lacks specific thresholds or reference values for contamination levels, in contrast to other contaminants. This absence highlights the necessity for a comprehensive assessment of radionuclides across various agricultural systems in Croatia. This study investigates the transfer of radionuclides ¹³⁷Cs and ⁴⁰K from soil to agricultural crops throughout Croatia and estimates the consequent annual ingestion dose for the population. The samples collected comprised food crops and animal feed, with corresponding soil samples analyzed to calculate transfer factors. Activity concentrations of ¹³⁷Cs exhibited regional and crop-type variability, reflecting the uneven distribution of fallout and differing soil properties. Transfer factors were found to range from 0.003 to 0.06 for ¹³⁷Cs and from 0.15 to 3.1 for ⁴⁰K, with the highest uptake occurring in kidney beans. The total estimated annual effective ingestion dose was calculated to be a maximum of 0.748 mSv/year for children aged 2–7, predominantly attributable to ⁴⁰K. Given the homeostatic regulation of potassium in the human body, the dose associated with ¹³⁷Cs poses a more significant radiological concern. These findings underscore the need for radionuclide-specific agricultural legislation in Croatia and offer a baseline for recommending reference values and informing future regulations regarding agricultural soil contamination. Full article

Porous materials are characterized by the pore surface area (S) and volume (V) accessible to a confined fluid. For mesoporous materials NMR measurements of diffusion are used to assess the S/V ratio, because at short times, only the diffusivity of molecules in the adsorbed layer is affected by confinement and the fractional population of these molecules is proportional to the S/V ratio. For materials with sub-nanometer pores, this might not be true, as the adsorbed layer can encompass the entire pore volume. Here, using molecular simulations, we explore the role played by S and S/V in determining the dynamical behavior of two carbon-bearing fluids—CO₂ and ethane—confined in sub-nanometer pores of silica. S and V in a silicalite model representing a sub-nanometer porous material are varied by selectively blocking a part of the pore network by immobile methane molecules. Three classes of adsorbents were thus obtained with either all of the straight (labeled ‘S-major’) or zigzag channels (‘Z-major’) remaining open or a mix of a fraction of both types of channel blocked, resulting in half of the total pore volume being blocked (‘Half’). While the adsorption layers from opposite surfaces overlap, encompassing the entire pore volume for all pores except the intersections, the diffusion coefficient is still found to be reduced at high S/V, especially for CO₂, albeit not so strongly as would be expected in the case of wider pores. This is because of the presence of channel intersections that provide a wider pore space with non-overlapping adsorption layers. Full article

This study presents the first investigation into the application of ultrasonic vibration-assisted electrical discharge machining (UV-EDM) using graphite electrodes for external cylindrical surface machining—an essential surface in the production of tablet punches and sheet metal-forming dies. A custom ultrasonic horn was designed and fabricated using 90CrSi material to operate effectively at a resonant frequency of 20 kHz, ensuring stable vibration transmission throughout the machining process. A Box–Behnken experimental design was employed to explore the effects of five process parameters—vibration amplitude (A), pulse-on time (Ton), pulse-off time (Toff), discharge current (Ip), and servo voltage (SV)—on two key performance indicators: material removal rate (MRR) and surface roughness (Ra). The optimization process was conducted in two stages: single-objective analysis to maximize MRR while ensuring Ra < 4 µm, followed by a hybrid multi-objective approach combining NSGA-II and the Analytic Hierarchy Process (AHP). The optimal solution achieved a high MRR of 9.28 g/h while maintaining Ra below the critical surface finish threshold, thus meeting the practical requirements for punch surface quality. The findings confirm the effectiveness of the proposed horn design and hybrid optimization strategy, offering a new direction for enhancing productivity and surface integrity in cylindrical EDM applications using graphite electrodes. Full article

This paper presents a flight control framework based on neural network Model Predictive Control (NN-MPC) to tackle the challenges of acceleration command tracking for supersonic vehicles (SVs) in complex flight environments, addressing the shortcomings of traditional methods in managing nonlinearity, random disturbances, and real-time performance requirements. Initially, a dynamic model is developed through a comprehensive analysis of the vehicle’s dynamic characteristics, incorporating strong cross-coupling effects and disturbance influences. Subsequently, a predictive mechanism is employed to forecast future states and generate virtual control commands, effectively resolving the issue of sluggish responses under rapidly changing commands. Furthermore, the approximation capability of neural networks is leveraged to optimize the control strategy in real time, ensuring that rudder deflection commands adapt to disturbance variations, thus overcoming the robustness limitations inherent in fixed-parameter control approaches. Within the proposed framework, the ultimate uniform bounded stability of the control system is rigorously established using the Lyapunov method. Simulation results demonstrate that the method exhibits exceptional performance under conditions of system state uncertainty and unknown external disturbances, confirming its effectiveness and reliability. Full article

Background/Objectives: Gastrin-releasing peptide receptor (GRPR) is overexpressed in breast cancer and might be used as a theranostics target. The expression of GRPR strongly correlates with estrogen receptor (ER) expression. Visualization of GRPR-expressing breast tumors might help to select the optimal treatment. Developing GRPR-specific probes for SPECT would permit imaging-guided therapy in regions with restricted access to PET facilities. In this first-in-human study, we evaluated the safety, biodistribution, and dosimetry of the [^99mTc]Tc-DB8 GRPR-antagonistic peptide. We also addressed the important issue of finding the optimal injected peptide mass. Methods: Fifteen female patients with ER-positive primary breast cancer were enrolled and divided into three cohorts receiving [^99mTc]Tc-DB8 (corresponding to three distinct doses of 40, 80, or 120 µg DB8) comprising five patients each. Additionally, four patients with ER-negative primary tumors were injected with 80 µg [^99mTc]Tc-DB8. The injected activity was 360 ± 70 MBq. Planar scintigraphy was performed after 2, 4, 6, and 24 h, and SPECT/CT scans followed planar imaging 2, 4, and 6 h after injection. Results: No adverse events were associated with [^99mTc]Tc-DB8 injections. The effective dose was 0.009–0.014 mSv/MBq. Primary tumors and all known lymph node metastases were visualized irrespective of injected peptide mass. The highest uptake in the ER-positive tumors was 2 h after injection of [^99mTc]Tc-DB8 at a 80 µg DB8 dose (SUV_max 5.3 ± 1.2). Injection of [^99mTc]Tc-DB8 with 80 µg DB8 provided significantly (p < 0.01) higher uptake in primary ER-positive breast cancer lesions than injection with 40 µg DB8 (SUV_max 2.0 ± 0.3) or 120 µg (SUV_max 3.2 ± 1.4). Tumor-to-contralateral breast ratio after injection of 80 μg was also significantly (p < 0.01, ANOVA test) higher than ratios after injection of other peptide masses. The uptake in ER-negative lesions was significantly lower (SUV_max 2.0 ± 0.3) than in ER-positive tumors. Conclusions: Imaging using [^99mTc]Tc-DB8 is safe, tolerable, and associated with low absorbed doses. The tumor uptake is dependent on the injected peptide mass. The injection of an optimal mass (80 µg) provides the highest uptake in ER-positive tumors. At optimal dosing, the uptake was significantly higher in ER-positive than in ER-negative lesions. Full article

Structural variations (SVs) represent genomic variations that involve breakage and rejoining of DNA segments. SVs can alter normal gene dosage, lead to rearrangements of genes and regulatory elements within a topologically associated domain, and potentially contribute to physical traits, genomic disorders, or complex traits. Recent advances in sequencing technologies and bioinformatics have greatly improved SV detection and interpretation at unprecedented resolution and scale. Despite these advances, the functional impact of SVs, the underlying SV mechanism(s) contributing to complex traits, and the technical challenges associated with SV detection and annotation remain active areas of research. This review aims to provide an overview of structural variations, their mutagenesis mechanisms, and their detection in the genomics era, focusing on the biological significance, methodologies, and future directions in the field. Full article

The C-terminus of the BoNT/A heavy chain (BoNT/AHC) mediates binding to its receptor, SV2, a critical step for toxicity. Antibody inhibition of this interaction enhances neuronal survival. We previously identified a functional anti-BoNT/AHC nanobody, HM. To extend its in vivo half-life, we designed and prepared two Fc-optimized nanoparticles, HM-Fc5 and HM-Fc6. Structural modeling (homology/docking) of the HM Fv-AHC complex predicted that HM engages key AHC residues (Tyr¹¹⁵⁵, Phe¹¹⁶⁰, Ile¹¹⁶¹, Val¹¹⁸⁴, Asn¹¹⁸⁸, Lys¹¹⁸⁹, Glu¹¹⁹⁰), which overlap with the SV2 binding site. This suggests HM’s protective mechanism involves blocking toxin-receptor binding and cellular entry. HM-Fc5 and HM-Fc6 retained the stability and function of the parental HM antibody while exhibiting prolonged in vivo half-life. These optimized nanobodies offer economical candidates potentially enabling longer dosing intervals, beneficial for prophylaxis or chronic disease treatment. Significance Statement: The purpose of the study is to design and prepare two Fc optimized nanoparticles, HM-Fc5 and HM-Fc6, and predict the key residues involved in the interaction between HMs and AHC. The experimental results showed that HM-Fc5 and HM-Fc6 have the same stability as the parent HM antibody but have a longer half-life in vivo. The key residues Tyr¹¹⁵⁵, Phe¹¹⁶⁰, Ile¹¹⁶¹, Val¹¹⁸⁴, Asn¹¹⁸⁸, Lys¹¹⁸⁹, and Glu¹¹⁹⁰ overlap with the SV2 binding site. Our experimental results indicate that these nanobody candidates are not only more economical and convenient, but may also have longer dosing intervals, providing strong evidence and reference for prolonging the in vivo half-life of nanomaterials. Full article

Sanghuangporus spp. are medicinal fungi with significant therapeutic value, but their taxonomic ambiguity and frequent market adulteration have hindered their standardized utilization. In this study, untargeted metabolomics based on UPLC-Q-TOF-MS was employed to systematically analyze the metabolic profiles of three Sanghuangporus species: Sanghuangporus. sanghuang (SS), Sanghuangporus. vaninii (SV), and Sanghuangporus. baumii (SB). A total of 788 metabolites were identified and classified into 16 categories, among which 97 were common differential metabolites, including bioactive compounds such as flavonoids, polysaccharides, and terpenoids. Multivariate statistical analyses (PCA and OPLS-DA) revealed distinct metabolic patterns among the species. KEGG pathway enrichment analysis showed that the differential metabolites were mainly involved in flavonoid and isoflavonoid biosynthesis. Notably, SV and SB exhibited significantly higher levels of several key bioactive compounds, including Apigenin and D-glucuronolactone, compared to SS. These findings highlight substantial interspecies differences in metabolic composition and pharmacological potential, providing a scientific basis for species authentication, quality control, and medicinal development of Sanghuangporus. Full article

This study evaluated the activity concentrations of radionuclides in honey, bee pollen, bee bread, and propolis from multiple regions in Poland (Europe) to assess the levels of radiological contamination and their implications for public health. Furthermore, the work considers the use of bee products as bioindicators of the state of environmental contamination with radionuclides. The apiaries from which the samples were collected were selected in eight provinces in Poland, and are also complemented by reference data from soil contamination monitoring. Radionuclide measurements included both natural (e.g., ⁴⁰K, ²²⁶Ra) and anthropogenic isotopes (e.g., ¹³⁷Cs). The results show that although the overall activity concentrations were generally low, certain locations exhibited elevated levels of ¹³⁷Cs in bee products, likely reflecting historical deposition in soils. Propolis was best correlated with ¹³⁷Cs deposited in soil compared to the other products studied. The patterns observed substantiate the hypothesis that bee products, predominantly propolis, accurately reflect local radiological conditions, thereby providing a practical and non-intrusive approach to monitoring radionuclide contamination and informing risk management strategies. An assessment of potential health risks indicates that the effective dose is safe and ranges from 0.02 to 10.3 µSv per year, depending on the type of product and consumption. Full article

ABG analysis is the gold standard for assessing acid–base balance, oxygenation, and ventilation in critically ill patients, but it is invasive and associated with patient discomfort and potential complications. Venous blood gas (VBG) analysis offers a less invasive alternative, although its clinical utility remains debated. This review evaluates the current evidence on VBG analysis, exploring its correlation with ABG, clinical applications, and limitations. Studies show a strong correlation between ABG and VBG for pH and a good correlation for bicarbonate and base excess in most cases, while the correlation for pCO₂ remains controversial. Predictably, pO₂ values differ significantly due to oxygen consumption gradients between the arterial and venous blood. VBG analysis is especially valuable for initial assessments, monitoring therapeutic responses, and guiding resuscitation in intensive care settings. It is not merely an alternative to ABG but a complementary tool that can provide unique insights, such as mixed venous oxygen saturation (SvO₂) or indices that require combined ABG and VBG data, like the pCO₂ gap. This review highlights the diagnostic equivalence of VBG in appropriate contexts and advocates for its use when arterial sampling is unnecessary or impractical. Furthermore, VBG analysis could enhance patient care by enabling the timely, less invasive assessment of hemodynamic and metabolic conditions. Future research should focus on refining interpretation algorithms and expanding the clinical applications of VBG to fully realize its potential in critical care practice. Full article

Background: Homocysteine (Hcy) is a sulfur-containing amino acid crucial for various physiological processes, with elevated levels linked to cardiovascular and neurological adverse conditions. Various factors contribute to high Hcy, and past studies of impact factors relied on traditional statistical methods. Recently, machine learning (ML) techniques have greatly improved and are now widely applied in medical research. This study used four ML methods to identify key factors influencing Hcy in healthy elderly Taiwanese men, comparing their accuracy using multiple linear regression (MLR). The study seeks to improve Hcy prediction accuracy and provide insights into relevant impact factors. Methods: A total of 468 healthy elderly men were studied in terms of 33 parameters using four ML methods: random forest (RF), stochastic gradient boosting (SGB), eXtreme gradient boosting (XGBoost), and elastic net (EN). MLR served as a benchmark. Model performance was assessed using SMAPE, RAE, RRSE, and RMSE. Results: All ML methods demonstrated lower prediction errors than MLR, indicating higher accuracy. By averaging the importance scores from the four ML models, C-reactive protein (CRP) emerged as the leading impact factor for Hcy, followed by GPT, WBC, LDH, eGFR, and sport volume (SV). Conclusions: Machine learning methods outperformed MLR in predicting Hcy levels in healthy elderly Taiwanese men. CRP was identified as the most crucial factor, followed by GPT/ALT, WBC, LDH, and eGFR. Full article

Snail and Zeb1 have been suggested as markers for the hybrid/mixed epithelial (E)/mesenchymal (M) state of cancer cells. Such cancer cells co-express E- and M-specific transcripts and possess cancer stem cell properties. M13HS-2/-8 tumor hybrid clones derived from human M13SV1-EGFP-Neo breast epithelial cells and human HS578T-Hyg breast cancer cells exhibited co-expression of Snail and Zeb1. To explore the impact of Snail on stemness/epithelial-to-mesenchymal transition (EMT)-related properties in M13HS-2/-8 tumor hybrid clones, Snail was knocked out (KO) using CRISPR/Cas9. Mammosphere formation, colony formation, Western blot analyses, cell migration, and invasion assays were conducted for the characterization of Snail knockout cells. Interestingly, Snail-KO in M13SV1-EGFP-Neo cells resulted in the up-regulation of vimentin and N-cadherin, suggesting EMT induction, which was associated with a significantly enhanced colony formation capacity. In contrast, EMT marker pattern and colony formation capacities of M13HS-2/-8 Snail-KO tumor hybrid clones remained unchanged. Notably, the mammosphere formation capacities of M13HS-2/-8 Snail-KO tumor hybrid clones were significantly reduced. The migratory behavior of all Snail-KO cells was not altered compared with their wild-type counterparts. In contrast, M13HS-2 hybrids and their M13HS-2 Snail-KO variant exhibited a markedly enhanced invasive capacity. Therefore, Snail plays a role as a mediator of stemness properties rather than mediating EMT. Full article

The number of people requiring palliative care is increasing. This can result in moral and ethical conflicts that may lead to psychological distress and moral injury. (MI). Solutions are needed to counteract career abandonment—supervision (SV) could be one solution. This study examines the extent to which palliative care nurses link MI to their everyday experiences and whether SV can contribute to the identification and prevention of moral distress and MI. In addition, factors that influence the implementation of, participation in, and perception of SV are analyzed. A qualitative study design was chosen for the investigation, consisting of guided interviews, narrative-generating questions with seven participants working in palliative care, and participant observation with audio recording during two supervisions of two palliative care teams with 16 participants in total. The data was analyzed using qualitative content analysis according to Mayring. The results show differences in workload between acute and palliative care wards. Time pressure and hierarchical structures promote distress and MI and are particularly evident on acute wards. The interviewees described specific experiences of MI. In addition, factors were identified that influence participation in SV. The analysis of SV showed that workload is a key cause of moral distress and can have an impact on health. SV can be used for sensitization and exchange. Implementation and acceptance of SV depend on individual and structural factors. In palliative care, signs of moral distress are present and are specifically addressed in SV, which means that SV can be a tool for dealing with stressful situations. Full article

Synthetic biology has fundamentally advanced cell engineering and helped to develop effective therapeutics such as chimeric antigen receptor (CAR)-T cells. For these applications, the detection, localization, and quantification of heterologous fusion proteins assembled from interchangeable building blocks is of high importance. The V5 tag, a 14-residue epitope tag, offers promising characteristics for these applications but has only rarely been used in this context. Thus, we have systematically evaluated the murine anti-V5 tag antibody mu_SV5-Pk1 as well as its humanized version, hu_SV5-Pk1, to analyze cells expressing V5-tagged receptors in samples from various in vitro and in vivo experiments. We found that the V5 tag signal on cells is affected by certain fixation and detachment reagents. Immunohistochemistry (IHC) on formalin-fixed paraffin-embedded (FFPE) mouse tissue samples was performed to sensitively detect cells in tissue. We improved IHC by applying the hu_SV5-Pk1 monoclonal antibody (mAb) to avoid cross-reactivity within and unspecific background signals arising on fixed mouse tissue. Conversely, the absence of unspecific binding by the mu_SV5-Pk1 mAb was evaluated on 46 human normal or cancer tissues. Our findings present a robust toolbox for utilizing the V5 tag and cognate antibodies in synthetic biology applications. Full article

S-nitrosoglutathione (GSNO), a promising S-nitrosothiol, has been recognized for its ability to modulate vascular tone through its vasodilatory, antiplatelet, and antiproliferative effects. However, data on its vasodilatory effects in human vessels remain limited, and its mechanisms of action have yet to be fully elucidated. In this study, we aimed to investigate the vasorelaxant effect of GSNO and its underlying mechanisms, with particular focus on the soluble guanylate cyclase (sGC)/nitric oxide (NO) pathway and potassium channels in isolated human saphenous veins (SVs) obtained from patients undergoing coronary artery bypass grafting (CABG). GSNO (10⁻⁸–10⁻⁴ M) produced concentration-dependent relaxations in SV rings precontracted with phenylephrine. These relaxations were unaffected by NO synthase inhibition with L-NAME (10⁻⁴ M, 30 min) or NO scavenging with PTIO (10⁻⁴ M, 30 min), but were significantly reduced by the sGC inhibitor, ODQ (10⁻⁵ M, 30 min). Inhibition of ATP-sensitive (glibenclamid; 10⁻⁵ M, 30 min.), high-conductance Ca²⁺-activated (charybdotoxin; 10⁻⁷ M, 30 min), small-conductance Ca²⁺-activated (apamin; 10⁻⁶ M, 30 min), or voltage-dependent (4-aminopyridine; 10⁻³ M, 30 min) potassium channels did not alter the maximum relaxant responses to GSNO. Furthermore, pretreatment with GSNO (10⁻⁴ M, 30 min) significantly attenuated both the contractile response and sensitivity to phenylephrine. Collectively, these findings demonstrate that GSNO exerts acute vasorelaxant and modulatory effects in human SV primarily via cGMP-dependent mechanisms, highlighting its potential as a local therapeutic agent for preventing graft spasm in CABG. Full article