Search Results (12,576)

The rising concern over carbon dioxide (CO₂) emissions has led to increased research on its conversion into value-added chemicals. Glycerol carbonate (GC), a versatile and eco-friendly compound, can be synthesized via the catalytic carbonylation of glycerol with CO₂. This study investigates the catalytic performance of three novel mixed metal oxide catalysts, Ti-Al-Mg, Ti-Cr-Mg, and Ti-Fe-Mg, synthesized via co-precipitation. The catalysts were characterized using XRD, SEM, XPS, CO₂-TPD, FTIR, TGA-DTG, and nitrogen adsorption–desorption isotherms. Among the tested systems, Ti-Al-Mg demonstrated the highest surface area, optimal porosity, and a balanced acid–base profile, resulting in superior catalytic activity. Under optimized conditions (175 °C, 10 bar CO₂, 4 h), Ti-Al-Mg achieved a maximum GC yield of 36.1%, outperforming Ti-Cr-Mg and Ti-Fe-Mg. The improved performance was attributed to the synergistic effects of its physicochemical properties, including high magnesium content and lower CO₂ binding energy, which favored CO₂ activation and glycerol conversion while minimizing side reactions. These findings highlight the potential of tailored mixed metal oxide systems for efficient CO₂ immobilization and sustainable glycerol valorization. Full article

A stereoselective and scalable strategy for the synthesis of phosphorus-containing bicyclic and tricyclic compounds from 1-phenylphosphin-2-en-4-one 1-oxide is presented. This activated dienophile, available in both racemic and enantiopure forms, undergoes smooth [4+2] cycloadditions with acyclic and cyclic dienes, affording products with excellent yields and controlled stereochemistry. Notably, the cis/trans-fusion of the cycloadducts (phosphadecalones and phosphahexahydrochrysene) can be selectively controlled by fine-tuning the conditions of microwave-assisted cycloaddition reaction. The influence of temperature, time, and steric effects on cis/trans and endo/exo selectivity was examined in detail. The molecular structure, including the absolute configuration, of eight products has been determined by X-ray crystallography. These analyses further established the endo-selective nature of the cycloaddition, favoring the P=O face of the dienophile. Post-cycloaddition transformations of selected P-stereogenic phosphadecalone, such as isomerization, reduction and deoxygenation, demonstrate the synthetic versatility of the resulting products. Full article

Background/Objectives: Oxidative stress, the Warburg effect, and resistance to apoptosis are key hallmarks driving colorectal tumorigenesis. This study aimed to develop novel multi-target compounds capable of modulating these pathways. Methods: A library of 24 newly synthesized compounds—incorporating annulated thiophene, thiazole, quinazolinone, 2-oxoindoline, and 1,2,3-oxadiazole scaffolds, as well as N-(1-(4-hydroxy-3-methoxyphenyl)-3-oxo-3-(2-(phenylcarbamothioyl)hydrazineyl) prop-1-en-2-yl)benzamide—was evaluated for antioxidant activity (DPPH assay), PDK-1 and LDHA inhibition, cytotoxic effects against LoVo and HCT-116 colon carcinoma cells, with parallel assessment of safety profiles on normal HUVECs. The underlying anticancer mechanism of the most active compound was investigated through analysis of cell cycle distribution, apoptosis induction, intracellular reactive oxygen species levels, mitochondrial membrane potential disruption, and expression levels of apoptosis-related genes. Molecular docking assessed binding interactions within LDHA and PDK-1 active sites. The physicochemical, drug-likeness, and ADMET properties of the multi-bioactive candidates were predicted in silico. Results: Among the synthesized compounds, thiophenes 3b and 3d exhibited superior PDK-1/LDHA and DPPH/LDHA inhibitions along with significant cytotoxic effects on LoVo and HCT-116 cells (IC₅₀ in µM: 190.3/170.2 and 161.0/156.6), respectively, and minimal cytotoxicity toward HUVECs. Molecular docking revealed favorable interactions with key amino acid residues within the LDHA and/or PDK-1 active sites. Compound 3d notably induced G2/M (LoVo) and G1 (HCT-116) arrest and promoted apoptosis via enhancing ROS generation, modulating Bax/Bcl-2 expressions, disrupting mitochondrial membrane potential, and ultimately activating caspses-3. In silico predictions indicated their promising drug-likeness and pharmacokinetics, though high lipophilicity, poor solubility (especially for 3b), and potential toxicity risks were identified as limitations. Conclusions: Thiophenes 3b and 3d emerged as promising multi-target candidates; however, structural optimization is warranted to enhance their solubility, bioavailability, and safety to support further development as lead anti-colon cancer agents. Full article

Glyphosate (GP) and its derivatives are present in almost all environments and suspected to induce acute and chronic kidney injuries. This public health issue is relatively underexplored. We therefore conducted an investigation on rats and tubular HK2 cells cultured for 24 h to determine whether GP’s and Roundup’s^® (RU) potential renal toxicity might be related to mitochondrial respiration impairment and the increased production of hydrogen peroxide (H₂O₂) in both the renal cortex and medulla (involved in filtration and reabsorption, respectively) using a high-resolution oxygraph (Oxygraph-2K, Oroboros instruments). GP alone decreased maximal uncoupled mitochondrial respiration in the medulla (−14.2%, p = 0.02). RU decreased mitochondrial respiratory chain complexes I and I + II and the maximal respiratory capacity both in the renal cortex (−13.5%, p = 0.04; −20.1%, p = 0.009; and −14.7%, p = 0.08, respectively) and in the medulla for OXPHOS I + II (80.82 ± 7.88 vs. 61.03 ± 7.67 pmol/(s·mL), −24.5%, p = 0.003). Similarly, in HK2 cells, the decrease in OXPHOS CI + II was greater after RU (65.87 ± 1.30 vs. 51.82 ± 3.50 pmol/(s·mL), −21.3%, p = 0.04) compared to GP. Increased H₂O₂ production was mainly observed after RU in the medulla (+14.3% in OXPHOS CI + II, p = 0.04) and in HK2 cells (+19% in OXPHOS CI + II, p = 0.02). In conclusion, although the medulla might be more prone to GP-related mitochondrial damage, RU toxicity was greater in both the renal cortex and medulla and in cultured tubular HK2 cells. Enhancing mitochondrial respiration and reducing oxidative stress might favor the prevention of or reduction in such worldwide-used herbicides’ deleterious effects on the kidneys. Full article

This study systematically investigates the effects of repeated Kurome treatment—a physical modification method combining mechanical stirring and oxidative regulation—on the processing characteristics and film properties of Chinese lacquer (urushi). By subjecting raw lacquer to 1–4 cycles of hydration–dehydration (KL1–KL4), the researchers observed a significant increase in viscosity (from 12,688 to 16,468 mPa·s) and a dramatic reduction in curing time (from 74 h to just 3.6 h), driven by deep oxidation of urushiol and quinone-mediated crosslinking, as confirmed by FTIR spectroscopy. The Kurome treatment enabled controlled darkening (L* value decreased from 29.31 to 26.89) while maintaining stable hue and gloss (88.96–90.96 GU), with no adverse effects on abrasion resistance (mass loss of 0.126–0.150 g/100 r) or adhesion (9.58–9.75 MPa). The reduced transparency of the KL3/KL4 films is associated with a densified polymer network, a feature that may benefit protective coatings. Scanning electron microscopy (SEM) analysis confirmed the formation of uniform, defect-free surfaces across all treatment groups. Among them, the KL2 group (viscosity of 14,630 mPa·s, curing time of 9.2 h) exhibited the most favorable balance for industrial applications. This study establishes Kurome technology as a low-carbon, additive-free strategy that enhances the processability of Chinese lacquer while preserving its traditional craftsmanship standards, offering scientific support for its sustainable use in modern coatings and cultural heritage conservation. Full article

Zizania latifolia (Jiaobai) is an economically important aquatic crop characterized by unique gall formation through interaction with the smut fungus Ustilago esculenta. Understanding factors influencing this interaction is crucial for cultivation. This study investigates the non-target effects of the fungicide Fenaminosulf (FM) on Z. latifolia’s growth, physiology, and underlying molecular pathways. We demonstrate that FM exerts striking concentration-dependent effects, revealing its potential as a modulator of plant development and symbiosis. Physiological measurements showed that a moderate FM concentration (1.25 g/L) promoted key vegetative growth parameters, including plant height and leaf length, while maintaining chlorophyll content, suggesting a potential bio-stimulant effect. In contrast, higher FM concentrations (2.5 g/L and 5 g/L) inhibited vegetative growth but significantly enhanced gall formation, particularly at 2.5 g/L, indicating that FM can redirect plant resources or alter susceptibility to favor the fungal interaction under specific conditions. Transcriptomic analysis provided mechanistic insights, revealing extensive gene expression reprogramming, especially under high FM treatment (5 g/L). Key pathways related to plant-pathogen interaction, phenylpropanoid biosynthesis, and hormone signal transduction were significantly modulated. Notably, FM treatment suppressed key immune-related genes, including Xa21 and PBL19, potentially reducing plant resistance and facilitating gall formation. Hormone signaling analysis revealed inhibition of auxin, cytokinin, brassinosteroid, and jasmonic acid metabolism, indicating a comprehensive molecular recalibration of plant developmental processes. The study provides novel insights into the molecular mechanisms by which FM influences Z. latifolia growth and gall formation. The concentration-dependent effects of FM suggest its potential as a strategic tool for agricultural management, offering a nuanced approach to crop development. These findings contribute to understanding plant-chemical interactions and provide valuable directions for optimizing Z. latifolia cultivation strategies. Full article

Football is a low-scoring sport where a single goal can determine a team’s success. Understanding shot effectiveness and goalkeeper performance is crucial for optimizing match success. This study aimed to evaluate the effectiveness of shots and goalkeeper interventions by identifying the most favorable areas on the field and within the goal. An observational notational analysis was conducted on 15,266 on-target shots from five major European leagues (Premier League, LaLiga, Bundesliga, Serie A, Ligue 1) during the 2022/2023 season. Data were extracted from FotMob and analyzed in SPSS using Pearson’s chi-square test (χ²) and adjusted residuals (AR) to determine significant patterns. Field and goal zones were divided based on previous studies, with the penalty area receiving further subdivisions due to its relevance to the analysis. The results indicated that match context, target areas within the goal, field zones, and previously identified high-effectiveness areas significantly influenced shot success (χ² < 0.001). Similarly, a significant association was found between the shooting foot and the side of attack (χ² < 0.001), while the body part used did not significantly affect the outcome (χ² = 0.077). Understanding these patterns helps coaches and players optimize team performance. Future studies should analyze additional seasons to confirm these results. Full article

STAT3 and STAT5 are two related transcription factors involved in normal mammary gland development and function. However, inappropriate activation of either STAT3 or STAT5 has been shown to play a role in breast cancer, where STAT3 is highly associated with aggressive tumors and STAT5 is associated with lower-grade and more differentiated tumors. As transcription factors, STAT3 and STAT5 transcriptionally regulate genes involved in proliferation, migration, and chemoresistance. Furthermore, STAT3 and STAT5 transcriptional activity can be modulated by several known cofactors, where these cofactors can influence how STAT3 and STAT5 interact with DNA and with other proteins, ultimately affecting transcriptional function. Interestingly, STAT3 and STAT5 share a subset of overlapping target genes and can compete for DNA binding of shared binding sites. These STATs have also been shown to have opposing effects on overlapping target gene expression, where gene expression is determined by the STAT protein occupying the promoter. This is particularly interesting since STAT5-driven breast tumors are molecularly distinct from STAT3-driven breast tumors. Furthermore, concurrent activation of STAT3 and STAT5 is associated with more favorable tumor types compared to tumors with activated STAT3 alone, suggesting that the relationship between these two STATs is critical. Developing a better understanding about the roles that STAT3 and STAT5 play in breast cancer will be important for successful treatment in the future. Full article

High-performance flexible sensors capable of direct integration with biological tissues are essential for personalized health monitoring, assistive rehabilitation, and human–machine interaction. However, conventional devices face significant challenges in achieving conformal integration with biological surfaces, along with sufficient biomechanical compatibility and biocompatibility. This research presents an in situ 3D biomanufacturing strategy utilizing Direct Ink Writing (DIW) technology to fabricate functional bioelectronic interfaces directly onto human skin, based on a novel annealing PEDOT:PSS/PVA composite bio-ink. Central to this strategy is the utilization of a novel annealing PEDOT:PSS/PVA composite material, subjected to specialized processing involving freeze-drying and subsequent thermal annealing, which is then formulated into a DIW ink exhibiting excellent printability. Owing to the enhanced network structure resulting from this unique fabrication process, films derived from this composite material exhibit favorable electrical conductivity (ca. 6 S/m in the dry state and 2 S/m when swollen) and excellent mechanical stretchability (maximum strain reaching 170%). The material also demonstrates good adhesion to biological interfaces and high-fidelity printability. Devices fabricated using this material achieved good conformal integration onto a finger joint and demonstrated strain-sensitive, repeatable responses during joint flexion and extension, capable of effectively transducing local strain into real-time electrical resistance signals. This study validates the feasibility of using the DIW biomanufacturing technique with this novel material for the direct on-body fabrication of functional sensors. It offers new material and manufacturing paradigms for developing highly customized and seamlessly integrated bioelectronic devices. Full article

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, highlighting the need for a deeper understanding of the genetic mechanisms driving its development and progression. Identifying genetic mutations that affect key molecular pathways is crucial for advancing CRC diagnosis, prognosis, and treatment. Patient-derived xenograft (PDX) models are essential tools in precision medicine and preclinical research, aiding in the development of personalized therapeutic strategies. In this study, a comparative analysis was conducted on the most frequently mutated genes—APC, TP53, KRAS, BRAF, NRAS, and ERBB2—using data from publicly available databases (n = 7894) and models from University Medicine Rostock (n = 139). The aim of this study was to evaluate the accuracy of these models in reflecting the mutational landscape observed in patient-derived samples, with a focus on both individual mutations and co-occurring mutational patterns. Our comparative analysis demonstrated that while the ranking of individual mutations remained consistent, their overall frequencies were slightly lower in the PDX models. Interestingly, we observed a notably higher prevalence of BRAF mutations in the PDX cohort. When examining co-occurring mutations, TP53 and APC mutations—both individually and in combination with other alterations—were the most frequent in both datasets. While the PDX models showed a greater prevalence of single mutations and a slightly higher proportion of tumors without detectable mutations compared to the public dataset, these findings present valuable insights into CRC’s mutational landscape. The discrepancies highlight important considerations, such as selective engraftment bias favoring more aggressive tumors, differences in sample size between the two cohorts, and potential bottleneck effects during PDX engraftment. Understanding these factors can help refine the use of PDX models in CRC research, enhancing their potential for more accurate and relevant applications in precision oncology. Full article

The construction industry significantly impacts the environment, consuming 50% of natural resources and generating 20% of global greenhouse gas (GHG) emissions. In developing countries, managing construction and demolition (C&D) waste is a growing challenge due to rapid urbanization and inadequate waste management practices. This study employs life cycle assessment and life cycle costing to compare landfill and recycling scenarios for C&D waste using ISO 14040 (Environmental Management—Life Cycle Assessment—Principles and Framework) and ISO 14044 (Environmental Management—Life Cycle Assessment—Requirements and Guidelines). The study’s system boundary encompasses the entire life cycle of C&D waste management, with one ton of C&D waste as the functional unit. The results demonstrated that landfilling C&D waste is harmful due to negative impacts from transportation and landfill emissions. Recycling shows promising potential by significantly reducing environmental impacts and lowering the demand for new raw materials. The recycling scenario substantially decreased GHG emissions, saving 37 kg of CO₂ equivalents per ton of waste. Economically, recycling C&D waste proved more viable, with favorable indicators. Implementing a recycling plant in Lahore could save USD 2.53 per ton in resource costs and mitigate significant environmental impacts. This study recommends that policymakers in developing countries prioritize C&D waste recycling to enhance sustainability and support the transition to a circular economy. The findings provide valuable insights for developing effective waste management strategies, contributing to environmental conservation and economic efficiency. These recommendations guide future initiatives for sustainable C&D waste management, promoting a greener and more resilient urban environment. Furthermore, this study underlines the potential of C&D waste recycling to contribute significantly to achieving Sustainable Development Goals (SDGs), particularly sustainable cities (SDG 11), responsible consumption and production (SDG 12), and climate action (SDG 13). Full article

Background: Brucellosis poses a significant public health challenge, necessitating effective vaccine development. Current vaccines have limitations such as safety concerns and inadequate mucosal immunity. This study aims to develop an FcRn-targeted mucosal Brucella vaccine by fusing the human Fc domain with Brucella’s multi-epitope protein (MEV), proposing a novel approach for human brucellosis prevention. Methods: The study developed a recombinant antigen (h-tFc-MEV) through computational analyses to validate antigenicity, structural stability, solubility, and allergenic potential. Molecular simulations confirmed FcRn binding. The vaccine was delivered orally via chitosan nanoparticles in murine models. Immunization was compared to MEV-only immunization. Post-challenge assessments were conducted to evaluate protection against Brucella colonization. Mechanistic studies investigated dendritic cell activation and antigen presentation. Results: Computational analyses showed that the antigen had favorable properties without allergenic potential. Molecular simulations demonstrated robust FcRn binding. In murine models, oral delivery elicited enhanced systemic immunity with elevated serum IgG titers and amplified CD4+/CD8+ T-cell ratios compared to MEV-only immunization. Mucosal immunity was evidenced by significant IgA upregulation across multiple tracts. Long-term immune memory persisted for six months. Post-challenge assessments revealed markedly reduced Brucella colonization in visceral organs. Mechanistic studies identified FcRn-mediated dendritic cell activation through enhanced MHC-II expression and antigen presentation efficiency. Conclusions: The FcRn-targeted strategy establishes concurrent mucosal and systemic protective immunity against Brucella infection. This novel vaccine candidate shows potential for effective human brucellosis prevention, offering a promising approach to address the limitations of current vaccines. Full article

Alterations in glycolysis play a crucial role in cancer cells, influencing tumor aggressiveness and therapeutic effect, particularly in pancreatic adenocarcinoma (PAAD). However, the specific glycolysis-related genes involved in PAAD progression remain poorly understood. This study established glycolysis-related molecular subtypes with distinct survival outcomes using TCGA datasets. The favorable prognosis subtype exhibited enhanced immune infiltration and an activated tumor microenvironment. A glycolysis prognostic model effectively predicted PAAD survival, correlating with global glycolytic pathways, and AUCell evaluated neutrophil communication networks of models. Functional validation demonstrated that ENO1/PGM2L1 co-expression promoted tumor proliferation, migration, invasion, and glycolytic flux in vitro, while accelerating xenograft growth in vivo. Conversely, their knockdown suppressed malignancy. Our study demonstrated that the glycolytic prognostic risk model serves as a reliable tool for prognosis and prediction of PAAD progression. ENO1 and PGM2L1 emerge as key risk factors promoting the malignant progression of PAAD. Full article

This paper critically analyzes Italy’s strategies to improve energy efficiency in the residential building sector, focusing on social housing. Using a policy-oriented qualitative research design supported by secondary data analysis, the study examines key instruments such as the Superbonus 110% initiative and the National Recovery and Resilience Plan (PNRR). It explores how these measures align with the European Green Deal and address the dual challenges of ecological transition and social equity. Findings reveal that while the Superbonus and PNRR investments significantly boosted energy retrofitting projects and macroeconomic indicators, access to benefits was uneven, favoring higher-income households. The analysis also highlights systemic barriers, such as bureaucratic complexity and initial cost barriers, that limit participation by vulnerable groups, particularly those living in outdated social housing. The paper concludes that future policies must better integrate social inclusion mechanisms, simplified administrative processes, and effectively target energy poverty to maximize environmental and social outcomes. Full article

This paper studies the estimation and detection problems in the mixture of linear regression models with change point. An improved Expectation–Maximization (EM) algorithm is devised specifically for multi-classified mixture data with change points. Under appropriate conditions, the large-sample properties of the estimator are rigorously proven. This improved EM algorithm not only precisely locates the change points but also yields accurate parameter estimates for each class. Additionally, a detector grounded in the score function is proposed to identify the presence of change points in mixture data. The limiting distributions of the test statistics under both the null and alternative hypotheses are systematically derived. Extensive simulation experiments are conducted to assess the effectiveness of the proposed method, and comparative analyses with the conventional EM algorithm are performed. The results clearly demonstrate that the EM algorithm without considering change points exhibits poor performance in classifying data, often resulting in the misclassification or even omission of certain classes. In contrast, the estimation method introduced in this study showcases remarkable accuracy and robustness, with favorable empirical sizes and powers. Full article