Search Results (125,048)

NME6 belongs to the family of nucleoside diphosphate kinase enzymes, whose major role is to transfer the terminal phosphate from NTPs, mostly ATP, to other (d)NDPs via a high-energy intermediate. Beside this basic enzymatic activity, the family, comprising 10 genes/proteins in humans, executes a number of diverse biochemical/biological functions in the cell. A few previous studies have reported that NME6 resides in the mitochondria and influences oxidative phosphorylation while interacting with RCC1L, a GTPase involved in mitochondrial ribosome assembly and translation. Considering the multifunctional role of NME family members, the goal of the present study was to assess the influence of the overexpression or silencing of NME6 on fundamental cellular events of MDA-MB-231T metastatic breast cancer cells. Using flow cytometry, Western blotting, and a wound-healing assay, we demonstrated that the overexpression of NME6 reduces cell migration and alters the expression of EMT (epithelial–mesenchymal transition) markers. In addition, NME6 overexpression influences cell cycle distribution exclusively upon DNA damage and impacts the MAPK/ERK signaling pathway, while it has no effect on apoptosis. To conclude, our results demonstrate that NME6 is involved in different cellular processes, providing a solid basis for future, more precise investigations of its role. Full article

For the research on real-time accurate testing technology for the explosion point spatial coordinate of munitions, its currently commonly used methods such as acoustic–electric detection or high-speed imaging are limited by the field conditions, response rate, cost, and other factors. In this paper, a method of spatial coordinate testing for the explosion point based on a 2D PSD (position-sensitive detector) intersection is proposed, which has the advantages of a faster response, better real-time performance, and a lower cost. Firstly, a mathematical model of the spatial coordinate testing system was constructed, and an error propagation model for structural parameters was developed. The influence of the position of the optical axes’ intersection as well as the azimuth angle and pitch angle on the test accuracy of the system was simulated and analyzed, thus obtaining the distribution and variation trend of the overall error propagation coefficient of the system. Finally, experiments were designed to obtain the test error of the system for validation. The results show that the system test accuracy is high when the azimuth angle is 20°–50°, the overall error propagation coefficient does not exceed 48.80, and the average test error is 56.17 mm. When the pitch angle is −2.5°–2.5°, the system has a higher test accuracy, with the overall error propagation coefficient not exceeding 44.82, and the average test error is 41.87 mm. The test accuracy of the system is higher when the position of the optical axes’ intersection is chosen to make sure that explosion points fall in the region of the negative half-axis of the $Z_w$-axis of the world coordinate system, with an overall error propagation coefficient of less than 44.78 and an average test error of 73.38 mm. It is shown that a reasonable selection of system structure parameters can significantly improve the system test accuracy and optimize the system deployment mode under the long-distance field conditions so as to improve the deployment efficiency. Full article

The development of new turbomachinery designs requires numerous time-consuming and computationally intensive computational fluid dynamics (CFD) calculations. However, most of the generated high spatial resolution data remain unused at later development steps. That is also the case with automated optimization processes that use only a few integral values to determine objectives and constraints. To make further use of this vast amount of CFD data a data-driven AI model based on the Transformer architecture is developed and trained using the available CFD data. The presented method subsequently provides a fast approximation of the 3D flow for new designs. In this paper, the structure of the developed AI model is presented and the approximation quality is analyzed using a complex, state-of-the-art compressor test case. It is shown that the AI model can reproduce many characteristics of the 3D flow of new designs, and performance measures such as efficiency can be derived from these flow predictions. In addition, the complex test case revealed that greater design variation reduces the AI approximation quality which can lead to undesirable exploratory behavior in an optimization setup. Overall, the test case has shown promising results and has provided hints for further improvements to the AI model. Full article

Skin inflammation associated with chronic diseases involves a direct role of keratinocytes in its immunopathogenesis, triggering a cascade of immune responses. Despite this, highly targeted treatments remain elusive, highlighting the need for more specific therapeutic strategies. In this study, nanocapsules containing quinizarin (QZ/NC) were developed and evaluated in an in vitro model of keratinocyte-mediated inflammation, incorporating the action of photodynamic therapy (PDT) and analyzing permeation in a 3D skin model. Comprehensive physicochemical, stability, cytotoxicity, and permeation analyses of the nanomaterials were conducted. The nanocapsules demonstrated desirable physicochemical properties, remained stable throughout the analysis period, and exhibited no spectroscopic alterations. Cytotoxicity tests revealed no toxicity at the lowest concentrations of QZ/NC. Permeation and cellular uptake studies confirmed QZ/NC permeation in 3D skin models, along with intracellular incorporation and internalization of the drug, thereby enhancing its efficacy in drug delivery. The developed model for inducing the inflammatory process in vitro yielded promising results, particularly when the synthesized nanomaterial was combined with PDT, showing a reduction in cytokine levels. These findings suggest a potential new therapeutic approach for treating inflammatory skin diseases. Full article

Interior design is considered and practiced as a visual discipline in architecture. The environment and buildings are appreciated through visual representations. We explored how sensory interactions shape a genuine multisensory experience with visual stimulation as a primary focus in architecture and interior design. It is important to consider different factors that contribute to visual stimulation when designing spaces. Visual stimulation is experienced differently, depending on the observer, and it is important to understand how children perceive stimuli. Therefore, we determined the visual factors captured by children. The embedded design method was used for qualitative mapping of visual factors and 3D animation creation for visualization. Eye-tracking experiments were conducted to examine the factors that captured the attention of children. Children were attracted to moving objects such as videos, followed by images on walls, playgrounds, windows, and furniture. Fostering positive distraction is important in designing spaces for children. Full article

Owing to medical historian Erwin H. Ackerknecht’s (1906–1988) pioneering study “Medicine at the Paris Hospital, 1794–1848” (1967), the year 1794 is seen as the decisive separation date on which the development and reorganization of the Parisian clinical school—as a broad movement and a system of medical education and clinical practice—distanced it from the traditions of the 18th century. This precise dating is based on the “Rapport et projet de décret sur l’établissement d’une École centrale de Santé à Paris” (1794) by the French clinician and naturalist Antoine-François Fourcroy (1755–1809), which appeared five years after the French Revolution. Fourcroy was asked by the Conseil d’État to submit a detailed report in which he was obliged to comment on the existing health situation and the state of medical care and research. His report thereby ventured so far as to request the continued dissolution of all medical faculties in France, as these institutions were seen as counter-revolutionary hotbeds in the wider educational landscape of the Grande Nation. Fourcroy’s recommendations were implemented a short time later; he had recommended that medical training should be established again in the traditional locations of Paris, Montpellier, and Strasbourg in France yet in the different settings of so-called health schools, Écoles de Santé. In this article, I look at the corresponding training and care structures after the French Revolution, as well as some of the specific reasons which led to the complete suspension of teaching in academic medicine at the time. In the more recent research literature, Ackerknecht’s view has undergone some modifications, whereby the fixation on the date 1794 has been challenged since the French traditions of the royalistic period have hardly been considered. Furthermore, it has been argued that the reorganization of medicine during the time of the Empire remained largely based on knowledge structures derived from the previous 18th century. In order to keep the complex scientific, institutional, and socio-economic conditions of the context of Parisian Academic Medicine aligned, I first explore some developments up to the time of the French Revolution (1789), before assessing the implications of the reform of knowledge structures and curricular programs instigated since the 1790s, as these remain relevant to medical history in the 19th century. Full article

Rice bran, which is abundant in dietary fiber and phytochemicals, provides multiple health benefits. Nonetheless, its effects on neuroinflammation and gut microbiota in postmenopausal conditions are still not well understood. This study investigated the effects of rice bran and/or tea seed oil supplementation in d-galactose-injected ovariectomized (OVX) old mice fed a fructose drink. The combination of d-galactose injection, ovariectomy, and fructose drink administration creates a comprehensive model that simulates aging in females under multiple metabolic stressors, including oxidative stress, estrogen deficiency, and high-sugar diets, and allows the study of their combined impact on metabolic disorders and related diseases. Eight-week-old and 6–8-month-old female C57BL/6 mice were used. The mice were divided into six groups: a sham + young mice, a sham + old mice, an OVX + soybean oil, an OVX + soybean oil with rice bran, an OVX + tea seed oil (TO), and an OVX + TO with rice bran diet group. The OVX groups were subcutaneously injected with d-galactose (100 mg/kg/day) and received a 15% (v/v) fructose drink. The rice bran and tea seed oil supplementation formed 10% of the diet (w/w). The results showed that the rice bran with TO diet increased the number of short-chain fatty acid (SCFA)-producing Clostridia and reduced the number of endotoxin-producing Tannerellaceae, which mitigated imbalances in the gut–liver–brain axis. Rice bran supplementation reduced the relative weight of the liver, levels of hepatic triglycerides and total cholesterol; aspartate transaminase and alanine aminotransferase activity; brain levels of proinflammatory cytokines, including interleukin-1β and tumor necrosis factor-α; and plasma 8-hydroxy-2-deoxyguanosine. This study concludes that rice bran inhibits hepatic fat accumulation, which mitigates peripheral metaflammation and oxidative damage and reduces neuroinflammation in the brain. Full article

Background/Objectives: The accurate quantification of ground-glass opacities (GGOs) and consolidation volumes has prognostic value in COVID-19 patients. Nevertheless, the accurate manual quantification of the corresponding volumes remains a time-consuming task. Deep learning (DL) has demonstrated good performance in the segmentation of normal lung parenchyma and COVID-19 pneumonia. We introduce a Human-in-the-Loop (HITL) strategy for the segmentation of normal lung parenchyma and COVID-19 pneumonia that is both time efficient and quality effective. Furthermore, we propose a Gaussian Mixture Model (GMM) to classify GGO and consolidation based on a probabilistic characterization and case-sensitive thresholds. Methods: A total of 65 Computed Tomography (CT) scans from 64 patients, acquired between March 2020 and June 2021, were randomly selected. We pretrained a 3D-UNet with an international dataset and implemented a HITL strategy to refine the local dataset with delineations by teams of medical interns, radiology residents, and radiologists. Following each HITL cycle, 3D-UNet was re-trained until the Dice Similarity Coefficients (DSCs) reached the quality criteria set by radiologists (DSC = 0.95/0.8 for the normal lung parenchyma/COVID-19 pneumonia). For the probabilistic characterization, a Gaussian Mixture Model (GMM) was fitted to the Hounsfield Units (HUs) of voxels from the CT scans of patients with COVID-19 pneumonia on the assumption that two distinct populations were superimposed: one for GGO and one for consolidation. Results: Manual delineation of the normal lung parenchyma and COVID-19 pneumonia was performed by seven teams on 65 CT scans from 64 patients (56 ± 16 years old (μ ± σ), 46 males, 62 with reported symptoms). Automated lung/COVID-19 pneumonia segmentation with a DSC > 0.96/0.81 was achieved after three HITL cycles. The HITL strategy improved the DSC by 0.2 and 0.5 for the normal lung parenchyma and COVID-19 pneumonia segmentation, respectively. The distribution of the patient-specific thresholds derived from the GMM yielded a mean of −528.4 ± 99.5 HU (μ ± σ), which is below most of the reported fixed HU thresholds. Conclusions: The HITL strategy allowed for fast and effective annotations, thereby enhancing the quality of segmentation for a local CT dataset. Probabilistic characterization of COVID-19 pneumonia by the GMM enabled patient-specific segmentation of GGO and consolidation. The combination of both approaches is essential to gain confidence in DL approaches in our local environment. The patient-specific probabilistic approach, when combined with the automatic quantification of COVID-19 imaging findings, enhances the understanding of GGO and consolidation during the course of the disease, with the potential to improve the accuracy of clinical predictions. Full article

In post-rift basins, the thickness center, fine-grained deposit center, and subsidence center rarely converge. Clearing the three centers with the thickest center is difficult. In the Huangyan district of Xihu Sag, the East China Sea Shelf Basin, an Oligocene post-rift basin beneath major potential igneous provinces, has inconsistent thickness and composition. Analysis of core samples, drilling, and 3D seismic data corroborated this finding. This means that the formation thickness center does not match the lithology center, which indicates water depth. Gravity and magnetic measurements in the studied region show that significant magmatic activity is responsible for the difference between the center of thickness and the fine-grained deposit. Thermal sinking must be restored to fix this. Therefore, we propose (1) recreating the early Oligocene residual geomorphology in Huangyan using 3D seismic data. (2) Software computing quantitative subsidence. (3) Paleogeomorphology is verified by normal and trace element paleowater depths. (4) Reconstruct the paleogeomorphology and analyze how volcanic activity affected them and the three centers in the basin formed after tectonic plates separated. A shallow water delta and thermal subsidence show that magmatic activity is persistent in the north. With less thermal subsidence and deeper water, the southern area features a shallow lake sedimentary system. The thickness and fine-grained deposition centers were in the north and south, respectively. Geophysical and geological methods were used to reproduce the post-rift paleogeomorphology shaped by magmatic processes. Full article

Based on social interdependence and social constructivism theories, the authors of this study examined the effects of a cooperative learning (CL) pedagogical model on the engagement and outcomes of undergraduate students in an Ethiopian university’s classrooms. We did this by using a quasi-experimental post-test control group design. The study participants included undergraduate students enrolled in the courses “Risk Management and Insurance” (n = 99) and “Foundation Engineering I” (n = 94). The control groups received regular lecture-based teaching, while the experimental group received CL instruction over two weeks in six to eight sessions. The results from the Management sample, which demonstrated that the CL intervention group reported significantly higher learning outcomes and more engagement than the control groups, are sufficient evidence for the study to validate the hypothesis. The effect sizes were moderate and ranged from 0.52 to 0.78 Cohen’s d. In the Engineering course, the results demonstrate the smallest difference between the mean scores reported by the CL group and those of the regular lecture group, with the CL group showing slightly higher student engagement and outcomes across the three categories assessed. The Engineering sample’s results, however, did not show any significant differences between the CL and control groups. This study provides evidence that course reform utilizing a CL pedagogical design could improve student engagement and learning outcomes as compared to the regular lecture-based method. By incorporating CL pedagogies, higher educators and institutions can create more engaging and effective learning environments for students. Full article

Pancreatic ductal adenocarcinoma (PDAC) is a significant cause of cancer-associated mortality, with a rising global incidence. A paucity of strong predictive risk factors mean screening programmes are difficult to implement. Historically, a lack of identifiable and actionable driver mutations, coupled with a relatively immunosuppressed tumour microenvironment, has led to a reliance on cytotoxic chemotherapy. The NAPOLI-3 trial has reported data supporting consideration of NALIRIFOX as a new first-line standard of care. Kirsten Rat Sarcoma Virus (KRAS) G12D mutations are present in >90% of all PDAC’s; exciting breakthroughs in small molecule inhibitors targeting KRAS G12D may open new modalities of treatment, and therapies targeting multiple KRAS mutations are also in early clinical trials. Although immunotherapy strategies to date have been disappointing, combination with chemotherapy and/or small molecule inhibitors hold promise and warrant further exploration. Full article

Background/Objectives: This study evaluated the clinical outcomes of selective retina therapy (SRT) for treating central serous chorioretinopathy. A fundus image-based titration method was used for laser irradiation. Methods: This retrospective cohort study included 29 eyes (29 patients) that underwent SRT for CSC. Both the pulse energy and number of micropulses were adjusted according to the fundus image. Mean best-corrected visual acuity (BCVA), central foveal thickness (CFT), and subretinal fluid (SRF) height were measured 1, 2, 3, 4, and 6 months after SRT. Mean deviation (MD) was measured using microperimetry at 3 and 6 months post-treatment. Results: At 6 months after SRT treatment, SRF was completely resolved in 89.7% of cases (26/29 eyes). The mean Snellen BCVA significantly improved from 0.34 ± 0.31 logMAR (logarithm of the minimum angle of resolution) (20/40) at baseline to 0.24 ± 0.24 logMAR (20/32) at 6 months (p = 0.009). The 0.1 improvement in mean BCVA is equivalent to a 5-letter gain on the ETDRS chart. The mean CFT decreased significantly from 309.31 ± 81.6 μm at baseline to 211.07 ± 50.21 μm at 6 months (p < 0.001). The mean SRF height also decreased significantly from 138.36 ± 56.78 μm at baseline to 23.75 ± 61.19 μm at 6 months (p < 0.001). The mean MD was improved from −1.56 ± 1.47 dB at baseline to −1.03 ± 2.43 dB at 6 months (p = 0.07) after treatment. Conclusions: SRT using fundus image-based titration can yield favorable functional and anatomical outcomes in the treatment of CSC. Full article

This study systematically investigated the effects of tea polyphenols on methane (CH₄) production and the rumen epithelial cell transport capability in cattle using both in vitro and animal experiments, employing multi-omics techniques. The in vitro results demonstrated that, compared to the control group, tea polyphenols significantly reduced CH₄ production and the acetate/propionate ratio (p < 0.05). Tea polyphenols reduced CH₄ production by inhibiting the relative abundance of unclassified_d_Archaea methanogens and the protozoa Pseudoentodinium and g__Balantioides. The animal experiments showed that tea polyphenols significantly increased the concentrations of T-AOC and GSH-PX in bovine blood (p < 0.05). In addition, microbial groups such as Rikenellaceae_RC9_gut_group, Ruminococcaceae_NK4A214_group, and Butyrivibrio_2 were significantly enriched in the ruminal fluid of the tea polyphenol group (p < 0.05). The proteomic results indicated significant upregulation of proteins such as COIII, S100A8, FABP1, SLC2A8, and SLC29A1 (p < 0.05) and downregulation of proteins including HBB, RAB4A, RBP4, LOC107131172, HBA, and ZFYVE19 (p < 0.05), with FABP1 showing a positive correlation with propionate concentration, and RAB4A had a negative correlation (p < 0.05). Overall, tea polyphenols modulate the microbial composition within the rumen, inhibiting CH₄ production and enhancing the host’s rumen epithelial cell transport capacity for volatile fatty acids. Full article

Dextro-transposition of the great arteries (D-TGA) is a critical congenital heart defect that can impact neurodevelopment due to cerebral perfusion and oxygenation disorders followed by alterations in synaptogenesis, gyrification, sulcation, and the microstructure. Brain injuries can occur both pre-operatively and postoperatively, especially white matter injuries, neuronal loss, and stroke. Materials and Methods: In a retrospective study conducted at a tertiary center between 2016 and 2023, we investigated the early effects of Prostaglandin E1 (PGE1) administration and balloon atrial septostomy (BAS) on cerebral blood flow and oxygenation in inborn neonates with D-TGA. Cerebral Doppler Ultrasound in the anterior cerebral artery (ACA) was performed to assess the resistive index (RI), Peak Systolic Velocity (PSV), and End-Diastolic Velocity (EVD) before PGE1, before the BAS procedure, and 24 h after birth. Cerebral regional saturations of oxygen (crSO₂) and cerebral fractional tissue oxygen extraction (cFTOE) were evaluated. D-TGA patients were divided into the PGE1 group and the PGE1 + BAS group. Age-matched healthy controls were used for comparison. Results: All 83 D-TGA newborns received PGE1 within two hours after delivery, of whom 46 (55.42%) underwent BAS. In addition, 77 newborns composed the control group. PGE1 administration increased crSO₂ from 47% to 50% in the PGE1 group, but lower than in controls at 24 h of life, while cFTOE remained elevated. The RI increased 24 h after delivery (0.718 vs. 0.769; p = 0.000002) due to decreased EDV (10.71 vs. 8.74; p < 0.0001) following PGE1 treatment. The BAS procedure resulted in a significant increase in crSO₂ from 42% to 51% at 24 h of life in the PGE1 + BAS group. Doppler parameters exhibited a similar trend as observed in the PGE1 group. Conclusions: PGE1 treatment and BAS are lifesaving interventions that may improve cerebral perfusion and oxygenation in newborns with D-TGA during the transition period, as reflected by increasing SpO₂ and crSO₂. Full article

Topological materials with well-defined surfaces and edges have become a prominent research topic. As topological insulators, MnBi₂Te₄ thin films, with their unique surfaces, exhibit exceptional electron transport properties and good applicability in low-noise, high-sensitivity photoelectric detection. This paper reports a straightforward, efficient, and cost-effective thermal evaporation method for preparing quantum MnBi₂Te₄ thin films, along with an investigation into their photoelectric detection performance. These films can be used to fabricate array devices, with the resulting photodetectors achieving a response current of 97 mA W⁻¹ at room temperature and a response speed of <1 ms. Moreover, they demonstrate stability in the air for >30 d, with the photoelectric performance degrading by <15%. Our research introduces a new application for topological materials in photoelectric detection and establishes a strong foundation for the design and development of high-performance photodetectors in the future. Full article