Search Results (587)

The clinical efficacy of chemotherapy against rapidly proliferating cells stimulates both the development of new agents and the reassessment of established drugs. Spectroscopic methods (UV, FT-IR, and ¹H NMR) were applied to characterize prospidium chloride and related substances. The FT-IR spectrum of prospidium chloride, arising from vibrational transitions within the alkyl fragments of the dispirotripiperazinium cation, is reported with band assignments. Electronic transitions between molecular orbitals are analyzed using quantum–mechanical selection rules (Laporte and spin selection rules). The n→σ* transition (ΔS = 0) corresponds to the absorption maximum at λmax = 282 ± 0.40 nm (ε = 3.89 ± 0.08 L·mol⁻¹·cm⁻¹). A ¹H NMR spectrum (700 MHz) was used to assign chemical shifts δ (ppm), J-coupling constants (Hz), and gauche conformational features of prospidium chloride and its dihydroxy and epoxy impurities. Quantitative ¹H NMR (qNMR) was applied to determine the content of the active pharmaceutical ingredient and related substances. The methods provide complementary structural information for the characterization of prospidium chloride. Full article

Multi-system integration (e.g., high-speed rail, intercity rail, suburban rail, and metro) in regional rail transit has become an important strategy for enhancing regional travel quality. Nevertheless, optimizing line plans for such integrated networks remains a challenging task. Existing approaches are typically limited to dual-system integration and rely on pre-specified line pools, while often overlooking rolling stock heterogeneity. These limitations inevitably constrain the flexibility of stopping patterns and hinder the achievement of global cost optimality for the entire system. To address these challenges, this study proposes a comprehensive optimization framework for multi-system line plans. First, a hierarchical decoupling of the multi-system physical network is performed to identify candidate train service routes. Second, a deeply coupled network consisting of train service and passenger travel is developed. Subsequently, a multi-commodity flow model is established, incorporating critical constraints such as flexible stopping rules, rolling stock-system compatibility, and connecting line capacities. This framework integrates decisions regarding flow distribution, frequency, route design, stop patterns, and rolling stock assignment. Validated via a real-world case study using Gurobi, the results indicate that the through operation mode reduces operator costs by 20.4% and passenger costs by 6.5% compared to independent operations. This research offers a quantitative tool for developing coordinated plans that improve operator efficiency and passenger experience. Full article

The aim of our study was to evaluate the effect of dietary cobalt chloride (CoCl₂) supplementation on diarrhea, growth performance, and intestinal development in post-weaning piglets. Twenty-six piglets weaned at 21 days of age (d 21) with similar body weights were randomly assigned to three treatments: a control group (n = 10), a low-dose CoCl₂ group (1 mg/kg of diet; n = 8) and a high dose CoCl₂ group (2 mg/kg of diet, n = 8). Piglets were housed individually and fed the experimental diets for 28 days, with a dietary transition at day 15. During the early post-weaning period (d0 to d14), dietary CoCl₂ supplementation was associated with favorable trends in growth performance parameters, including ADG (average daily gain: linear, 0.05 < p < 0.1) and gain to feed ratio (linear, p < 0.05), as well as reduced fecal scores (Linear, p < 0.05). However, during the later post-weaning period (d15 to d28), increasing dietary CoCl₂ levels were unfavorable trends in feed intake (Linear, p < 0.05) and ADG (Linear, 0.05 < p < 0.1). At the intestinal level, CoCl₂ supplementation was associated with dose-related changes in intestinal morphology, epithelial cell differentiation, and luminal pH. Alterations were observed in duodenal crypt depth (CD) and ileal villus height (VH), and duodenal VH/CD (Linear, p < 0.05), without significant effects on ileal epithelial proliferation and apoptosis (p > 0.1). Changes in the numbers of goblet cells in villi (Quadratic, p < 0.05) and crypt (Linear, p < 0.05), and enteroendocrine cells (Quadratic, p < 0.05) in crypt exhibited dose-dependent trends. In addition, with the increase in the CoCl₂ concentration, the expressions of genes related to nutrient transporters (DMT1, GLUT2, and SGLT1) and metabolism (HIF-1α, FBP1, and FBP2), as well as those related to the NOTCH signaling pathway (LGR5, ATOH1, HES1, and NOTCH2), showed a linear decrease (Liner, p < 0.05). This was the case except for LDHA and DLL4 (Liner, p < 0.05). The expression of the former was the lowest in the high-dose group, while that of the latter was the lowest in the low-dose group. In vitro, CoCl₂ exposure was associated with reduced organoid budding rates (Quadratic, p < 0.01), the budding numbers (Linear, p < 0.05) per organoid, and altered gene expression of SGLT1 and CHGA (Linear, p < 0.05). In summary, dietary supplementation with CoCl₂ exhibited dose- and time-dependent trends in weaned piglets. CoCl₂ supplementation during the early post-weaning period (two weeks after weaning) was associated with favorable trends in growth performance and diarrhea, whereas prolonged supplementation (4 weeks after weaning) or higher dietary level (2 mg/kg of diet) were associated with unfavorable trends in growth performance and intestinal development. These findings suggest that CoCl₂ may have potential as a short-term (two weeks after weaning), low-level (below 2 mg/kg diet) nutritional supplement, while caution is warranted regarding long-term supplementation or higher dietary inclusion levels. Full article

To address the safety and efficiency challenges in planning emergency evacuation routes for personnel in complex environments, this study proposes an integrated and improved ant colony optimization (ACO) with a genetic algorithm (GA). First, an emergency evacuation route planning model for subway incidents is constructed by optimizing evacuation time, route risk, and the passenger panic index. Then, the ant colony algorithm is enhanced by assigning pheromones to each objective and optimizing the state transition probabilities, which helps avoid premature convergence on local optima. Simultaneously, a GA is employed to conduct a global search and generate an initial population, which serves as the initial pheromone for the ACO. This approach achieves the integration of ACO and GA, enabling them to synergistically leverage the advantages of global and local search. Finally, an evacuation simulation was conducted using a specific subway station as an example, and the results were compared with those of traditional algorithms. The results indicate that the proposed algorithm can find the optimal solution for all evacuation routes and significantly improve convergence speed and global search capabilities. In simulations across different hazard development stages, the proposed integrated method outperforms basic ACO and SSA by accounting for evacuation time, safety, and crowd panic to yield optimal routes. Full article

Against the backdrop of urban renewal, the transformation and functional enhancement of Existing Urban Industrial Areas (EUIAs) play a crucial role. Focusing on the rational development of underground space in EUIAs, this study explores forecasting methods for the development demand of such underground space, aiming to alleviate the contradiction between the protection of industrial heritage and intensive land use in EUIAs. This paper systematically sorts out the forecasting methods for the scale demand of underground space. Firstly, through a literature review, two major categories of factors influencing underground space demand—driving factors and conditional factors—are summarized, and an indicator system consisting of 23 indicators is constructed. On this basis, the modified Delphi method is employed to screen 7 dominant indicators, including the protection value of industrial heritage, the spatial distribution of industrial heritage, existing underground space, development functions, rail transit, spatial location, and surrounding supporting facilities. Based on the matrix of industrial heritage protection levels and land use nature, the development potential of underground space is evaluated, and a demand level correction model is introduced. Demand intensity is quantified through expert experience-based assignment with reference to typical domestic cases, thereby establishing a demand forecasting model for the underground space scale in EUIAs. Finally, the model is applied to the Saint-Gobain Industrial Area. Through the analysis of its industrial heritage value assessment, land use planning, and location characteristics, the areas with demand for underground space are delineated and their levels are corrected, forecasting a total underground space demand of 224,600–454,600 m². The research results provide a theoretical basis and methodological support for the underground space planning of EUIAs, and offer references for the development practice of similar regions. Full article

In the current context of the energy transition, the reuse of offshore oil and gas (O&G) structures that have reached the end of their operational life presents new engineering challenges. Many projects aim to adapt existing facilities for a range of alternative uses. This paper outlines guidelines for identifying the most suitable conversion options aligned with the goals of the ongoing energy transition, focusing on the Italian offshore area. The study promotes the reuse—instead of partial or full removal—of existing offshore platforms originally built for the exploitation of hydrocarbon reservoirs. From an engineering perspective, the project describes the development of guidelines based on an innovative methodology to identify new uses for both offshore oil and gas platforms and the depleted reservoirs, with a focus on safety and environmental impact. The guidelines identify the most suitable and effective conversion option for the platform–reservoir system under consideration. To ensure a realistic approach, the developed methodology allows one to identify the preferable conversion option even when some piece of information is missing or incomplete, as often happens in the early stages of a feasibility study. The screening process provides an associated level of uncertainty related to the degree of data incompleteness. The outcome is a complete evaluation procedure divided into five phases: definition of criteria; assignment of an importance scale to determine how critical each criterion is; connection of indices and weights to each criterion; and analysis of the relationships between them. The guidelines are implemented in a software tool that supports and simplifies the decision-making process. The results are very promising. The developed methodology and the related guidelines applied to a case study have proven to be an effective decision-support for analysts. The study shows that it is possible to identify the most suitable conversion option from a technical, engineering, and operational point of view while also considering its environmental impact and safety implications. Full article

Interim periods between peak and off-peak operations in urban rail transit networks often suffer from mismatched headways across lines, which increases passenger transfer waiting and operating costs. This paper proposes a passenger-oriented timetable synchronization method for network-wide interim period train service. In this study, based on the AFC data, passengers are assigned to the shortest travel time paths, and passenger transfer flows are linked to connecting train pairs by consideration of the maximum acceptable waiting time. As a result, the transfer waiting time is accurately calculated by matching passengers’ platform arrival times with the departures of feasible connecting trains. A mixed integer nonlinear programming model then jointly optimizes departure headways at each line’s first station, arrival and departure times at transfer stations, subject to safety headways and time bounds. The objective minimizes total cost, combining transfer waiting time cost and train operating cost (depreciation and distance-related cost). A simulated-annealing-based genetic algorithm (SA-GA) is designed to solve the NP-hard problem. A case study on the Nanjing rail transit network from 6:30 to 7:30 reduces total cost by 6.88%, including 3.77% lower transfer waiting time cost and 14.49% lower operating cost, and shows stable results under typical transfer demand fluctuations. Full article

Characterizing tight reservoirs is challenging due to the complex pore structure and strong heterogeneity at various scales. Current digital rock physics often struggles to reconcile high-resolution imaging with representative sample sizes, and 3D digital cores are frequently used primarily as visualization tools rather than predictive, computable platforms. Thus, a clear methodological gap persists: high-resolution models typically lack macroscopic geological features, while existing 3D digital models are seldom leveraged for quantitative, predictive analysis. This study, based on a full-diameter core sample of a single lithology (gray-black shale), aims to bridge this gap by developing an integrated workflow to construct a high-fidelity, computable 3D model that connects the micro–nano to the macroscopic scale. The core was scanned using high-resolution X-ray computed tomography (CT) at 0.4 μm resolution. The raw CT images were processed through a dedicated pipeline to mitigate artifacts and noise, followed by segmentation using Otsu’s algorithm and region-growing techniques in Avizo 9.0 to isolate minerals, pores, and the matrix. The segmented model was converted into an unstructured tetrahedral finite element mesh within ANSYS 2024 Workbench, with quality control (aspect ratio ≤ 3; skewness ≤ 0.4), enabling mechanical property assignment and simulation. The digital core model was rigorously validated against physical laboratory measurements, showing excellent agreement with relative errors below 5% for key properties, including porosity (4.52% vs. 4.615%), permeability (0.0186 mD vs. 0.0192 mD), and elastic modulus (38.2 GPa vs. 39.5 GPa). Pore network analysis quantified the poor connectivity of the tight reservoir, revealing an average coordination number of 2.8 and a pore throat radius distribution of 0.05–0.32 μm. The presented workflow successfully creates a quantitatively validated “digital twin” of a full-diameter core. It provides a tangible solution to the scale-representativeness trade-off and transitions digital core analysis from a visualization tool to a computable platform for predicting key reservoir properties, such as permeability and elastic modulus, through numerical simulation, offering a robust technical means for the accurate evaluation of tight reservoirs. Full article

Background/Objectives: Falls represent a major health concern for stroke survivors, necessitating effective risk assessment tools. This study proposes the Instrumented Fall Risk Assessment (IFRA) scale, a novel screening tool derived from Instrumented Timed Up and Go (ITUG) test data, designed to capture mobility measures often missed by traditional scales. Methods: We employed a two-step machine learning approach to develop the IFRA scale: first, identifying predictive mobility features from ITUG data and, second, creating a stratification strategy to classify patients into low-, medium-, or high-fall-risk categories. This study included 142 participants, who were divided into training (including synthetic cases), validation, and testing sets (comprising 22 non-fallers and 10 fallers). IFRA’s performance was compared against traditional clinical scales (e.g., standard TUG and Mini-BESTest) using Fisher’s Exact test. Results: Machine learning analysis identified specific features as key predictors, namely vertical and medio-lateral acceleration, and angular velocity during walking and sit-to-walk transitions. IFRA demonstrated a statistically significant association with fall status (Fisher’s Exact test p = 0.004) and was the only scale to assign more than half of the actual fallers to the high-risk category, outperforming the comparative clinical scales in this dataset. Conclusions: This proof-of-concept study demonstrates IFRA’s potential as an automated, complementary approach for fall risk stratification in post-stroke patients. While IFRA shows promising discriminative capability, particularly for identifying high-risk individuals, these preliminary findings require validation in larger cohorts before clinical implementation. Full article

Transitioning from theoretical learning to practical application remains a significant challenge for students in medical and veterinary science education, particularly in the context of medical imaging and ultrasound interpretation. Traditional lecture-based methods offer limited support for developing the spatial reasoning and technical skills required for ultrasound pregnancy diagnosis. This study evaluates the effectiveness of an interactive mixed reality (MR) training tool, Ewe Scan, delivered through the Apple Vision Pro, compared to traditional lecture-based instruction. Forty-two undergraduate students were randomly assigned to either a lecture-trained or MR-trained group and assessed immediately after training and again after six weeks. Results showed that MR-trained students significantly outperformed their lecture-trained peers in both immediate comprehension and retention over time, particularly in ultrasound interpretation skills. The MR-trained group also reported higher levels of engagement, confidence, and satisfaction with their training experience. These findings suggest that MR-based learning enhances educational outcomes by improving spatial understanding, increasing active engagement, and supporting knowledge retention. Integrating MR simulations into ultrasound education offers a scalable, ethical, and effective alternative to traditional training methods, contributing to advancements in medical imagery education. Full article

This paper addresses the highly important and timely issue of the energy transition, a topic of particular relevance within the European Union (EU), which has long been a global leader in pursuing climate neutrality. The article proposes a novel framework for monitoring energy transition progress and its temporal dynamics across the EU countries, adopting a decade-long analytical horizon. The research employs the Dynamic Energy Transition Assessment (DETA) method, which is structured around five key pillars of the energy transition: (1) decarbonization and the shift toward clean energy; (2) energy security and system resilience; (3) energy justice, health impacts, and affordability; (4) energy efficiency and energy management; (5) development, innovation, and modernization of energy infrastructure. Applying this method enabled the study to meet its central objective: evaluating the level of development of these pillars, analyzing the balance among them, and examining both the direction and speed of changes over time. This dynamic approach integrates three core components of transformation processes, state, quality (coherence), and pace of change, offering an innovative combination of structural and temporal perspectives. The originality of this framework lies in its ability to capture the multidimensional and evolving nature of the energy transition. The study is based on 19 indicators, with indicator weights determined through Entropy and Criteria Importance Through Intercriteria Correlation (CRITIC) analytical methods, while pillar weights were assigned using the AHP method in alignment with EU strategic priorities. The findings reveal substantial variation and dynamism in the implementation of energy transition processes across the EU countries. Denmark, Sweden, Germany, France, Portugal, and Spain demonstrate the highest performance in terms of both quality and dynamism, whereas Malta, Cyprus, and Luxembourg perform the weakest. The proposed methodology and the resulting assessment of the level, quality, and dynamics of transformation processes offer broad practical applications. In particular, they can support the monitoring of progress toward EU climate and energy policy goals and inform management and decision-making aimed at achieving a resilient, sustainable, and equitable energy transition. Full article

In this paper, characteristic ultraviolet absorption spectra are presented for benzene and chlorobenzene in transparent hexagonal water–ice solutions at temperatures between 273 K and 78 K. In addition, the liquid solution spectra at 292 K have also been included. The two lowest symmetry-forbidden transitions from the ground state (¹A_1g) to the first excited level of symmetry (B_2u), denoted as ¹B_2u ← ¹A_1g, and the transition from the ground state to the second excited level of symmetry (¹B_1u), denoted as ¹B_1u ← ¹A_1g, of benzene are recorded. The two lowest transitions of chlorobenzene from the ground state (¹A₁) to the first excited level of symmetry (¹B₂), denoted as ¹B₂ ← ¹A₁, and the transition from the ground state to the second excited level of symmetry (¹A₁) denoted as, ¹A₁ ← ¹A₁, are also studied. The bands are obtained for slowly cooled transparent water–ice solutions. Such ice samples, that were frozen from liquid water and cooled, show gradual changes in the spectra. Our study shows the spectra at eight temperatures, separating the spectra in different regions based on the range for the bands from ground state to the first and second excited states of benzene and chlorobenzene, observing changes in the integrated absorbances as a function of the temperature. For the spectra recorded at 78 K, the peak absorbances as a function of the wavelength are presented and tentatively assigned. Peak assignments are based on the known literature of benzene and chlorobenzene. The temperature range of our study covers some of the average temperatures that have been found in the icy moons of Saturn and the polar regions of Earth. Full article

Background: Dictyostelium discoideum is widely used in developmental and evolutionary biology due to its ability to transition from a single cell to a multicellular organism in response to starvation. While transcriptome information across its life cycle is widely available, only early-stage data exist at the proteome level. This study characterizes and compares the proteomes of D. discoideum cells at the vegetative, aggregation, mound, culmination and fruiting body stages. Methods: Samples were collected from cells developing synchronously on nitrocellulose filters. Proteins were extracted and digested with trypsin, and peptides were analyzed by liquid chromatography–tandem mass spectrometry. Data were processed using Proteome Discoverer™ for protein identification and label-free quantification. Results: A total of 4502 proteins were identified, of which 1848 (41%) were present across all stages. Pairwise comparisons between adjacent stages revealed clear transitions, the largest ones occurring between the culmination and fruiting body and between the fruiting body and vegetative stage, involving 29% and 52% of proteins, respectively. Hierarchical clustering assigned proteins to one of nine clusters, each displaying a distinct pattern of abundances across the life cycle. Conclusions: This study presents the first complete developmental proteomic time series for D. discoideum, revealing changes that contribute to multicellularity, cellular differentiation and morphogenesis. Full article

Background/Objectives: Obesity-associated hyperleptinemia has been linked to breast cancer (BC) progression via mechanisms that remain incompletely understood. This study explores the role of leptin and its receptor (LEPR) in facilitating BC cell proliferation, migration, epithelial–mesenchymal transition (EMT), and STAT3 signaling pathway activation. Methods: We analyzed gene expression and survival data from TCGA BRCA dataset. MCF-7 and MDA-MB-231 BC cells were exposed to leptin at 10 ng/mL (lean-associated levels) and 100 ng/mL (elevated levels linked to obesity). MTT assays, colony formation tests, wound-healing and tumor spheroid dissemination experiments evaluated cell proliferation and migration. Immunofluorescence and Western blot analysis assessed changes in EMT markers and cytoskeletal alterations, while Western blotting and qPCR assessed STAT3 and NCOA1 expression and activation levels. Results: Elevated LEPR expression was linked with unfavorable prognosis in BC patients. Higher doses of leptin (100 ng/mL) significantly enhanced cellular proliferation rates and migratory capabilities, in both cell lines, and promoted EMT characteristics marked by downregulated E-cadherin and cytoskeleton structural changes. Whereas heightened JAK2/STAT3 signaling correlated with elevated leptin dosages, STAT3 inhibition using AG490 reversed leptin-induced migration while reinstating E-cadherin levels to baseline. Furthermore, leptin upregulated NCOA1, an essential STAT3 coactivator, facilitating increased expression of Cyclin D1 and VEGF target genes. Clinical positive relationships were seen between LEP/LEPR expressions and NCOA1 levels and between NCOA1 and various gene signatures related to STAT3/P-STAT3 within BC specimens. Conclusions: Obesity-associated hyperleptinemia enhances aggressiveness in BC through a mechanism involving LEPR-mediated activation pathways encompassing NCOA1/STAT3, which drive proliferation, migration, and EMT. This assigns a potential therapeutic utility for obesity-related advancements found within BC pathology. Full article

Across plants, the PEBP gene family is reported to regulate storage organ formation, developmental plasticity, and floral transitioning. However, its evolutionary dynamics and functional diversification within Allium species remain poorly understood. In this study, we performed genomic and transcriptomic analyses of the PEBP gene family across three economically important Allium species, including Allium fistulosum (bunching onion), Allium sativum (garlic), and Allium cepa (onion), identifying 19, 17, and 21 PEBP genes, respectively. The genes were assigned into five subfamilies (FT-like, TFL1-like, MFT-like, BFT-like, and PEBP-like), with MFT-like members being the most abundant. Structural analysis revealed strong conservation of key motifs (e.g., GxHR and DPDxP) across species, while substantial variation in intron–exon organization suggested subfunctionalization. Collinearity analysis indicated that segmental duplication primarily drove PEBP gene expansion in garlic and onion, whereas tandem duplication was absent in bunching onion. Promoter analysis showed enrichment of light- and hormone-related cis-regulatory elements, implicating their involvement in environmental and hormonal regulation. Expression profiling demonstrated clear tissue specificity, with AsPEBP11/13/14/16/19 exhibiting significantly higher expression in normal flowers than in abnormal ones, suggesting key roles in floral morphogenesis. Together, these findings will prove useful for future breeding programs aimed at improving reproductive development and fertility in Allium species. Full article