Search Results (22,978)

Background/Objectives: In this work, a series of six new indazole-benzimidazole hybrids (M1–M6) were designed, synthesized, and fully characterized. The design of these compounds was based on the combination of two pharmacophoric units, indazole and benzimidazole, both known for their broad spectrum of biological activities. Methods: The molecular hybridization strategy was planned to combine these scaffolds through an effective synthetic pathway, using 6-nitroindazole, two 2-mercaptobenzimidazoles, and 1,3- or 1,5-dihaloalkanes as key precursors, affording the desired hybrids in good yields and with enhanced biological activity. Quantum chemical calculations were performed to investigate the structural, electronic, and electrostatic properties of M1–M6 molecules using Density Functional Theory (DFT) at the B3LYP/6-311++G(d,p) level. The antimicrobial activity efficacy of these compounds was assessed in vitro against four Gram-positive bacteria (Staphylococcus aureus, Enterococcus faecalis, Bacillus cereus, and Lactobacillus plantarum), four Gram-negative bacteria (Salmonella enteritidis, Escherichia coli, Campylobacter coli, Campylobacter jejuni), and four fungal strains (Saccharomyces cerevisiae, Candida albicans, Candida tropicalis, and Candida glabrata) using ampicillin and tetracycline as reference standard drugs. Results: Among the series, compound M6 exhibited remarkable antimicrobial activity, with minimum inhibitory concentrations (MIC) of 1.95 µg/mL against S. cerevisiae and C. tropicalis, and 3.90 µg/mL against S. aureus, B. cereus, and S. enteritidis, while the standards Ampicillin (AmB) (MIC ≥ 15.62 µg/mL) and Tetracycline (TET) (MIC ≥ 7.81 µg/mL) exhibited higher MIC values. To gain molecular insights into the compounds, an in silico docking study was performed to determine the interactions of M1–M6 ligands against the antimicrobial target beta-ketoacyl-acyl carrier protein (ACP) synthase III complexed with malonyl-COA (PDB ID: 1HNJ). Molecular modeling data provided valuable information on the structure-activity relationship (SAR) and the binding modes influencing the candidate ligand-protein recognition. Amino acid residues, such as Arg249, located in the solvent-exposed region, were essential for hydrogen bonding with the nitro group of the 6-nitroindazole moiety. Furthermore, polar side chains such as Asn274, Asn247, and His244 participated in interactions mediated by hydrogen bonding with the 5-nitrobenzimidazole moiety of these compound series. Conclusions: The hybridization of indazole and benzimidazole scaffolds produced compounds with promising antimicrobial activity, particularly M6, which demonstrated superior potency compared to standard antibiotics. Computational and docking analyses provided insights into the structure–activity relationships, highlighting these hybrids as potential candidates for antimicrobial drug development. Full article

Recreation, aesthetic appreciation, identity, and spiritual values are among the cultural ecosystem services (CES) produced by long-distance historic and pilgrimage trails. However, it is still difficult to convert these experiential benefits into quantifiable economic flows. This study collected 560 valid responses from an in-field survey conducted along the Via degli Dei (Bologna–Florence). Robust visitor clusters were created using Gower dissimilarities, Partitioning Around Medoids (PAM), silhouette diagnostics, and Factor Analysis for Mixed Data (FAMD). Each cluster was then profiled according to seasonal patterns, information channels, individual-level, per-category expenditures (accommodation, food, transport, services, and equipment), as well as motivations. Four segments are identified—Student Campers (low-budget, peak-summer), Working-Age Male B&B Hikers (short stays, B&B), Young Women on Mixed Lodging (mixed accommodation), and Midlife Comfort-Seekers (higher spend, shoulder-season)—underpinning our spending, seasonality, and managerial implications. Student Campers had the lowest absolute expenditures, while Midlife Comfort-Seekers had the highest (median lodging €180; food €175). The study offers practical levers for route governance (targeted communications, low-impact lodging strategies, shoulder-season promotion) to improve local value capture while reducing environmental pressure by connecting typologies to monetary CES flows. The findings provide a reproducible model for implementing recreational CES on historical-cultural tours. Full article

The limited availability of high-quality ore deposits and the environmental hazards of metallurgical wastes highlight the importance of developing resource-efficient metal recovery technologies. Zinc kiln slag (ZKS), also known as Waelz slag, a by-product material enriched in non-ferrous metals, was processed through oxidative HCl leaching with H₂O₂ as an oxidant. Thermodynamic simulation and laboratory experiments were applied to determine optimal leaching conditions to dissolve copper, zinc, and iron. Optimal leaching efficiency was achieved with consumptions of 0.8 g HCl and 0.1 g H₂O₂ per gram of ZKS, a liquid-to-solid (L/S) ratio of 5 mL/g, a temperature of 70 °C, and a duration of 180 min, which resulted in recoveries of 96.3% Cu, 93.6% Fe, and 76.8% Zn. The solid residue with 43.5 wt.% C is promising for reuse as a reductant material in pyrometallurgical processes. Copper and arsenic were separated from the leachate via cementation with iron powder, achieving recovery rates of 98.9% and 91.2%, respectively. A subsequent two-step iron precipitation produced ferric hydroxide with 52.2 wt.% Fe and low levels of impurities. As a result, the developed novel hydrochloric acid oxidative leaching and metal precipitation route for ZKS recycling provides an efficient and sustainable alternative to conventional treatment methods. Full article

Efficient scheduling of virtual power plants (VPPs) is essential for the integration of distributed energy resources into modern power systems. This study presents a CUDA-accelerated Multiple-Chain Simulated Annealing (MC-SA) algorithm tailored for optimizing VPP scheduling. Traditional Simulated Annealing algorithms are inherently sequential, limiting their scalability for large-scale applications. The proposed MC-SA algorithm mitigates this limitation by executing multiple independent annealing chains concurrently, enhancing the exploration of the solution space and reducing the requisite number of sequential cooling iterations. The algorithm employs a dual-level parallelism strategy: at the prosumer level, individual energy producers and consumers are assessed in parallel; at the algorithmic level, multiple Simulated Annealing chains operate simultaneously. This architecture not only expedites computation but also improves solution accuracy. Experimental evaluations demonstrate that the CUDA-based MC-SA achieves substantial speedups—up to 10× compared to a single-chain baseline implementation while maintaining or enhancing solution quality. Our analysis reveals an empirical power-law relationship between parallel chains and required sequential iterations (iterations ∝ chains${}^{-0.88\pm 0.17}$), demonstrating that using 50 chains reduces the required number of sequential iterations by approximately 10× compared to single-chain SA while maintaining equivalent solution quality. The algorithm demonstrates scalable performance across VPP sizes from 250 to 1000 prosumers, with approximately 50 chains providing the optimal balance between solution quality and computational efficiency for practical applications. Full article

Carotenoid pigments are widely distributed in nature and play a crucial role in protecting organisms from photodynamic damage. However, the characterization of carotenoid production in clinically relevant mycobacteria has been limited due to the low sensitivity of conventional detection methods. We present a descriptive analysis of carotenoid production in seven mycobacterial isolates from the scotochromogenic, photochromogenic, and non-chromogenic groups. To achieve this, we used a combination of High-performance liquid chromatography with diode-array detection (HPLC-DAD) and Ultra-high performance liquid chromatography–mass spectrometry (UHPLC-MS) to detect carotenoids pigments. Mycobacterium tuberculosis (MTB) and Mycobacterium bovis (MB) (non-chromogenic mycobacteria) produced β-carotene when cultured in the absence of light, at levels comparable to those of photochromogenic mycobacteria such as M. marinum (MM) and M. kansasii (MK). The highest levels of carotenoids were found in scotochromogenic species M. avium (MAV) and M. gordonae (MGOR). Conversely, M. abscessus (MABS), a non-chromogenic species in which no β-carotene was detected, served as a negative control for matrix effects. As expected, the use of highly sensitive analytical techniques such as HPLC-DAD and UHPLC-MS significantly enhanced the detection of β-carotene compared to visual pigment assessment. These methods allowed the detection of basal β-carotene levels even in mycobacteria classified as non-chromogenic. The proposed analytical approach provides a robust research tool to understand the effects of different stimulus that may alter the cell physiology in terms of pigment production. Full article

Within the circular economy, repair is increasingly recognised as a crucial yet underexplored strategy that extends product lifespans and reduces waste. Service design offers approaches to support this transition by addressing technical, social, and systemic dimensions. This review aimed to synthesise how service design contributes to repair practices and identify research gaps. Following PRISMA 2020 guidelines, we systematically searched Scopus and Web of Science, applied inclusion criteria focusing on service design and repair within the circular economy, and conducted multi-step screening and snowballing. From 132 initial records, 73 studies were included (journal articles, conference papers, book chapters). Thematic synthesis identified three areas: micro-level interactions between producers, products, and users (e.g., motivations, trust, communication); meso-level tools, frameworks, and platforms enhancing accessibility and efficiency; and macro-level societal transformation through regulations, standards, and communities. Results highlight service design’s potential to foster systemic change by integrating environmental, social, and economic aspects, while also revealing notable research gaps related to the limited engagement of repairers, policymakers, and cross-level collaboration. Compared to previous studies, this review contributes a novel integrated framework linking micro-, meso-, and macro-level dimensions of repair within the circular economy, offering both conceptual insights and actionable directions for practitioners and policymakers. The study is limited by language constraints and the lack of a formal bias evaluation. All reviewed materials are publicly accessible on OSF. This research was conducted without external financial support. Full article

This paper presents an Explainable Artificial Intelligence (XAI) framework for the automated generation of lesson plans aligned with Bloom’s Taxonomy. The proposed system addresses the dual challenges of accurate cognitive classification and pedagogical transparency by integrating a multi-task transformer-based classifier with a taxonomy-conditioned content generation module. Drawing from a locally curated dataset of 3000 annotated lesson objectives, the model predicts both cognitive process levels and knowledge dimensions using attention-enhanced representations, while offering token-level explanations via SHAP to support interpretability. A GPT-based generator leverages these predictions to produce instructional activities and assessments tailored to the taxonomy level, enabling educators to scaffold learning effectively. Empirical evaluations demonstrate strong classification performance (F1-score of 91.8%), high pedagogical alignment in generated content (mean expert rating: 4.43/5), and robust user trust in the system’s explanatory outputs. The framework is designed with a feedback loop for continuous fine-tuning and incorporates an educator-facing interface conceptually developed for practical deployment. This study advances the integration of trustworthy AI into curriculum design by promoting instructional quality and human-in-the-loop explainability within a theoretically grounded implementation. Full article

The “land governance orthodoxy” that has dominated development circles for the past two decades posits that government-issued title deeds are a prerequisite for economic growth in Africa and elsewhere in the Global South. Anything other than formal certification is viewed as inadequate, informal, insecure and inanimate. In this paper, we explore the “institutional pluralism” that characterizes land formalization efforts in rural Tanzania. We find that the multiple (often competing) objectives, procedures, actors, justifications, technologies, and outcomes have produced a crowded and chaotic field of titling initiatives. Despite an investment of around USD 340 million, progress remains painfully slow—at a rate of ~1% per year—such that it will take the rest of this century to reach universal titling. And at what cost? Our study is based on appraisals of policy and project documents and interviews with government officials, donor agencies, project implementers and NGO staff. Discussion of the findings is supported by data from annual budget speeches, national-level statistics and survey data collected by our team from forty Tanzanian villages. We argue that it is time to return to a broader, integrated approach to rural development and recognize that local landholding systems offer high levels of security. Our findings have relevance beyond land formalization to other areas where duplicative efforts implemented in the name of progress might be counterproductive to achieving economic and social development goals. Full article

Background: The immunogenicity of polysaccharide conjugate vaccines is critically influenced by the choice of carrier protein, which promotes a T-cell-dependent immune response mechanism leading to strong antibody production. In this study, the cholera toxin B subunit (CTB), a non-toxic pentameric protein, was evaluated as a novel carrier protein for pneumococcal polysaccharide antigens. Methods: Recombinant CTB was produced in Escherichia coli and purified using scalable chromatographic methods. Pneumococcal polysaccharides from serotypes 7F, 22F, and 33F were chemically activated with CDAP and conjugated to CTB. Results: The resulting glycoconjugates were characterized by SEC-MALS, confirming successful conjugation, high molecular weights, consistent polysaccharide-to-protein ratios, and acceptable endotoxin levels. Immunogenicity was assessed in rabbits following immunization with alum-adjuvanted formulations. Results: Robust IgG responses were elicited by all CTB-based conjugates, with antibody levels found to be comparable to those induced by CRM197 conjugates, demonstrating the potential of CTB as a promising alternative for the next generation of conjugate vaccines. Full article

Background: Prenatal stress affects fetal neurodevelopment and may increase the risk of seizures. This study aimed to analyze the impact of maternal restraint stress during pregnancy on neonatal status epilepticus (SE) in rats. Methods: Pregnant Wistar rats were subjected to restraint stress from gestation days 12 to 20. Offspring were assessed for body weight, size, and corticosterone levels. SE was induced in postnatal day 7 rats using the lithium–pilocarpine model. Neurodegeneration was analyzed using Fluoro-Jade C staining. Results: Maternal restraint stress resulted in reduced weight gain for the mothers and lower body weight and size for their offspring. Stressed neonates exhibited higher levels of serum corticosterone. Male neonates exhibited shorter latency to stage 1 seizures and increased hippocampal neurodegeneration compared with control males, whereas female neonates were largely unaffected. Conclusions: Maternal restraint stress produced only mild, sex-dependent effects on neonatal seizure susceptibility, affecting males but not females, suggesting a limited yet selective influence of prenatal stress on early brain vulnerability. Full article

The global demand for compost, produced through the bioconversion of organic waste into nutrient-rich soil amendments, is increasing due to the adverse environmental, health, and economic impacts of synthetic fertilizers. Compost use offers a cost-effective and sustainable alternative, improving soil fertility and long-term productivity. However, the potential of tobacco waste as a composting substrate remains insufficiently investigated. This study aimed to evaluate the feasibility of utilizing tobacco waste as a composting feedstock and to develop an optimized composting method. Tobacco waste (scrap leaves and midrib stems) was composted with cow manure in earthen pots to promote decomposition and nutrient mineralization, and its performance was compared with compost produced from cow manure and vegetable waste (vegetable leaves). Vermicomposting, which involves the addition of earthworms to conventional compost treatments, was also implemented to enhance composting efficiency and nutrient release. The final composts, both conventional and vermicompost, were analyzed for organic carbon (OC), nitrogen (N), phosphorus (P), potassium (K), sulfur (S), and the maturity duration. Among the three conventional compost variants, the mixture of cow manure and tobacco leaves had the highest nitrogen concentration at 1.45% and the cow manure and tobacco stems had 1.23% as the second best. Cow manure and tobacco stem compost had the highest K content of 1.13%, followed by tobacco leaves (0.99%). Sulfur levels were also found to be higher in the tobacco stem compost compared to the other compost types, with the highest value of 0.56%, followed by tobacco leaves (0.23%). All three vermicompost variants outperformed their conventional counterparts in terms of nutrient concentrations and achieved maturity in shorter durations. The cow manure with tobacco stem mixed vermicompost was notable for its elevated potassium (1.35%) and sulfur (0.89%) contents. The results indicate that vermicomposting offers a faster and more nutrient-enriched composting approach, particularly with tobacco waste. Incorporating tobacco waste into this process has the potential to produce high-quality compost, presenting a sustainable strategy for waste valorization and enhancing soil fertility. Full article

Escherichia coli LS5218 is an attractive host for producing polyhydroxybutyrate. The strain, however, strongly requires heterologous gene expressions like phaC for efficient production. For enhancing the production, the whole gene expressions relating to end product-producing flow should be optimized so that not only heterologous induced-genes but also other relating genes are comprehensively analyzed on the transcription levels, resulting in normally time-consuming mutant-creation. Additionally, the explanation for each transcriptional relationship is likely to follow the relationships on known metabolic pathway map to limit the consideration. This study aimed to infer gene regulatory networks within glycolysis, a central metabolic pathway in LS5218, using machine learning-based causal discovery methods. To construct a directed acyclic graph representing the gene regulatory network, we employed the NOTEARS algorithm (Non-combinatorial Optimization via Trace Exponential and Augmented lagRangian for Structure learning). Using transcription data of 264 time-resolved sampling points, we inferred the gene regulatory network and identified several distal regulatory relationships. Notably, gapA, a key enzyme controlling the transition between the preparatory and rewarding phases in glycolysis, was found to influence pgi, the enzyme at the pathway’s entry point. These findings suggest that inferring such nonlocal regulatory interactions can provide valuable insights for guiding genetic engineering strategies. Full article

Melia azedarach L. (Meliaceae) exhibits potential as a source of bioactive antibacterial compounds. In this study, the effect of solvent polarity on ultrasound-assisted extraction of M. azedarach leaves and twigs was evaluated in relation to their phytochemical composition and antibacterial activity against both non-resistant and multidrug-resistant bacteria. The results showed that solvent polarity significantly affected the extraction yield, with methanol and water producing yields above 10%. The methanol extracts of twigs and leaves exhibited the strongest antibacterial activity, showing greater potency against Escherichia coli than Bacillus subtilis. Consistent with these findings, the methanol extracts inhibited the growth of multidrug-resistant enteropathogenic E. coli K1-1, resulting in inhibition zone diameters of 10.93 mm (leaf) and 7.73 mm (twig). Furthermore, the methanol extract contained the highest levels of phenolic, flavonoid, and hydroxyl-rich compounds, which were associated with its antibacterial properties. In silico analysis further revealed that isofucosterol, meliasenin, and melianone exhibited strong predicted binding affinities to key antibacterial proteins, particularly those involved in multidrug-resistant bacterial mechanisms. Full article

Road transport in the European Union is responsible for approximately 60% of PM10 emissions and 45% of PM2.5 emissions. Acoustic agglomeration is researched to be the most effective after-treatment method to control particle pollution. Recent experimental research suggests that at a frequency of around 20 kHz and a sound pressure level of 140 dB, particles can be agglomerated. The kinetic energy of the particles is influenced by the presence of acoustics, and this enhances the collision efficiency between the particles. These collided fine particles increase in size and can be easily filtered through conventional filters. Additionally, clean burning biofuels produce comparatively fewer particles; hence RME is used for experiments along with its two blends of isopropanol (RME95I5 and RME90I10). The results are then compared to those of standard diesel fuel. With an increase in load, an average reduction of 20% in fine particles is observed along with an increase in large-sized particles. The aggregation of smaller particles is observed in a range of 0–50% in almost all tested conditions. With the increase in isopropanol from 5 to 10%, oxygen content in the fuel increased by 7%, a 1% reduction in carbon and a 2% reduction in C/H ratio is observed which led to a 6 and 9% reduction in particle emissions at 60 Nm and 90 Nm, respectively. At higher loads, D100, RME95I5 and RME90I10 recorded an agglomeration of 10%, 111% and 189%, respectively. Similar results are observed for the tendency for agglomeration at lower loads. Full article

This study addresses the estimation of the common mean for the zero-inflated inverse Gaussian (ZIIG) distributions, a problem not previously explored. The performance of four interval estimation approaches was evaluated: the generalized confidence interval (GCI), parametric bootstrap, Bayesian, and highest posterior density (HPD). Simulation studies under varying sample sizes, zero-inflation probabilities, mean values, and shape parameters revealed notable differences in coverage probability (CP) and average length (AL). For small samples, the GCI and parametric bootstrap approaches often under-covered, particularly in highly skewed or heavily zero-inflated cases. In contrast, Bayesian and HPD intervals generally maintained coverage closer to the nominal 0.95 level, albeit with longer intervals. As sample size increased, all methods approached nominal coverage and produced shorter intervals, improving precision. Overall, the Bayesian and HPD approaches demonstrated strong robustness across conditions, with HPD intervals frequently achieving accurate coverage with shorter lengths. Finally, the proposed approaches were applied to real-world data on road accident fatalities in Thailand. Full article